Heart Failure

Updated August 30, 2021

The SGLT2 inhibitor empagliflozin achieved in EMPEROR-Preserved what no other agent could previously do: unequivocally cut the incidence of cardiovascular death or hospitalization in patients with heart failure and preserved ejection fraction (HFpEF).

MDedge News

Treatment with empagliflozin (Jardiance) led to a significant 21% relative reduction in the rate of cardiovascular death or hospitalization for heart failure (HHF), compared with placebo, among 5,988 randomized patients with HFpEF during a median 26 months of follow-up, proving that patients with HFpEF finally have a treatment that gives them clinically meaningful benefit, and paving the way to an abrupt change in management of these patients, experts said.

“This is the first trial to show unequivocal benefits of any drug on major heart failure outcomes in patients with HFpEF,” Stefan D. Anker, MD, PhD, declared at the virtual annual congress of the European Society of Cardiology.

The 21% relative reduction, which reflected a cut in the absolute rate of the trial’s primary composite endpoint of 3.3% compared with placebo, was driven mainly by a significant 27% relative reduction in the incidence of HHF (P < .001). Empagliflozin treatment, on top of standard therapy for patients with HFpEF, also resulted in a nonsignificant 9% relative risk reduction in the incidence of cardiovascular death, but it had no discernible impact on the rate of death from any cause, said Dr. Anker, professor of cardiology at Charité Medical University in Berlin.

Concurrently with his talk at the meeting, the results were published online in the New England Journal of Medicine.
 

Practice will change ‘quickly’

“This will definitely change our practice, and quite quickly,” said Carlos Aguiar, MD, chair of the Advanced Heart Failure and Heart Transplantation Unit at Hospital Santa Cruz in Carnaxide, Portugal, who was not involved in the study.

Transition to routine use of empagliflozin in patients with HFpEF should be swift because it has already become a mainstay of treatment for patients with heart failure with reduced ejection fraction (HFrEF) based on evidence for empagliflozin in EMPEROR-Reduced. A second sodium-glucose cotransporter 2 (SGLT2 ) inhibitor, dapagliflozin (Farxiga), is also an option for treating HFrEF based on results in the DAPA-HF trial, and the DELIVER trial, still in progress, is testing dapagliflozin as a HFpEF treatment in about 6,000 patients, with results expected in 2022.

About half of the patients in EMPEROR-Preserved had diabetes, and the treatment effects on HFpEF were similar regardless of patients’ diabetes status. Empagliflozin, like other members of the SGLT2 inhibitor class, boosts urinary excretion of glucose and received initial regulatory approval as an agent for glycemic control in patients with type 2 diabetes. Empagliflozin also has U.S.-approved marketing indications for treating patients with HFrEF whether or not they also have diabetes, and for reducing cardiovascular death in patients with type 2 diabetes and cardiovascular disease.

“We already use this drug class in cardiovascular medicine and to treat patients with type 2 diabetes, and we have been eager to find a treatment for patients with HFpEF. This is something that will be really significant,” said Dr. Aguiar.

Heart failure clinicians have “become familiar prescribing” SGLT2 inhibitors following approval of HFrEF indications for some of these agents, noted Mary Norine Walsh, MD, a heart failure specialist with Ascension Medical Group in Indianapolis. The new results “are good news because there have been so few options” for patients with HFpEF, she said in an interview.

EMPEROR-Preserved “is the first phase 3 clinical trial that exclusively enrolled patients with heart failure and an ejection fraction of more than 40% to meet its primary outcome,” and the results “represent a major win against a medical condition that had previously proven formidable,” Mark H. Drazner, MD, said in an editorial that accompanied the published results.

The trial’s findings “should contribute to a change in clinical practice given the paucity of therapeutic options available for patients with HFpEF,” wrote Dr. Drazner, a heart failure specialist who is professor and clinical chief of cardiology at UT Southwestern Medical Center in Dallas.

Theresa A, McDonagh, MD, MBChB, who chaired the panel that just released revised guidelines from the European Society of Cardiology for managing patients with heart failure, predicted that empagliflozin treatment for patients with HFpEF will soon show up in guidelines. It will likely receive a “should be considered” ranking despite being a single study because of the impressive size of the treatment effect and lack of well-supported alternative treatments, she commented as a discussant of the trial during its presentation at the congress. If the DELIVER trial with dapagliflozin shows a similar effect, the recommendation would likely become even stronger, added Dr. McDonagh, a heart failure specialist and professor of cardiology at King’s College, London.

More women enrolled than ever before

EMPEROR-Preserved enrolled adults with chronic HFpEF in New York Heart Association functional class II-IV and a left ventricular ejection fraction greater than 40% starting in 2017 at more than 600 sites in more than 20 countries worldwide including the United States. As background therapy, more than 80% of patients received treatment with either an ACE inhibitor or angiotensin receptor blocker (in some instances in the form of sacubitril/valsartan), more than 80% were on a beta-blocker, and about a third were taking a mineralocorticoid receptor antagonist, making them “very well treated HFpEF patients,” Dr. Anker said.

One of the most notable features of enrollment was that 45% of participants were women, giving this trial the highest inclusion of women compared with all prior studies in patients with HFpEF or with HFrEF, said Dr. Walsh. “HFpEF is very prevalent in woman,” she noted, and having this high participation rate of women in the study increases its relevance to these patients. “It’s important to be able to tell women that patients like you were in the study so we can more easily apply the lessons from the trial to you. That can’t be stressed enough,” she said.

The primary outcome occurred in 415 (13.8%) of the 2,997 patients in the empagliflozin group and in 511 (17.1%) of 2,991 patients who received placebo (hazard ratio, 0.79; 95% confidence interval, 0.69-0.90; P < .001).

The study showed a safety profile consistent with prior experience with empagliflozin, Dr. Anker added.

Pooling EMPEROR-Preserved with EMPEROR-Reduced

The investigators who ran EMPEROR-Preserved designed the trial to closely parallel the EMPEROR-Reduced trial in patients with HFrEF, and they included a prespecified analysis (EMPEROR-Pooled) that combined the more than 9,700 patients in the two studies. This showed a consistent and robust benefit from empagliflozin for reducing HHF across a wide spectrum of patients with heart failure, ranging from patients with left ventricular ejection fractions of less than 25% to patients with ejection fractions as high as 64%. However, the analysis also showed that patients with ejection fractions of 65% or greater received no discernible benefit from empagliflozin, Milton Packer, MD, reported in a separate talk at the congress.

MDedge News

“The findings demonstrate the benefits of empagliflozin across a broad range of patients with heart failure who have ejection fractions of less than 60%-65%,” said Dr. Packer, a researcher at Baylor University Medical Center in Dallas.

This apparent attenuation of an effect at higher ejection fractions “has been observed in other HFpEF trials, most recently in the PARAGON-HF trial” of sacubitril/valsartan (Entresto), he noted. Additional analyses led by Dr. Packer showed that in patients with ejection fractions below 65% the HHF benefit from empagliflozin consistently surpassed the benefit seen with sacubitril/valsartan in PARAGON-HF. But he recommended using both drugs in patients with HFpEF and an ejection fraction up to about 60%.

“If I had a patient with HFpEF I would use both drugs as well as beta-blockers and mineralocorticoid receptor antagonists,” he said during a press briefing.

Another finding from analysis of the EMPEROR-Reduced and EMPEROR-Preserved trials together was that patients with reduced ejection fractions showed a significant 49% relative reduction in the incidence of serious renal outcomes, but this effect was completely blunted in EMPEROR-Preserved.

“Ejection fraction influences the effects of empagliflozin on major renal outcomes,” concluded Dr. Packer in a report on this analysis published simultaneously with the main EMPEROR-Preserved findings (N Engl J Med. 2021 Aug 27. doi: 10.1056/NEJMc2112411). “These data from the EMPEROR trials are unique. We have no comparable data” from any of the other reported studies of SGLT2 inhibitors,” he said.

EMPEROR-Preserved was sponsored by Boehringer Ingelheim and by Eli Lilly, the two companies that jointly market empagliflozin (Jardiance). Dr. Anker has received personal fees from Boehringer Ingelheim and from several other companies, and he has received grants and personal fees from Abbott Vascular and Vifor. Dr. Packer has received consulting fees from Boehringer Ingelheim and from numerous other companies. Dr. McDonagh has has recent financial relationships with AstraZeneca, Cprpus, Novartis, Pfizer, and Vifor. Dr. Aguiar and Dr. Walsh had no disclosures.

[email protected]

Updated August 30, 2021

The SGLT2 inhibitor empagliflozin achieved in EMPEROR-Preserved what no other agent could previously do: unequivocally cut the incidence of cardiovascular death or hospitalization in patients with heart failure and preserved ejection fraction (HFpEF).

MDedge News

Treatment with empagliflozin (Jardiance) led to a significant 21% relative reduction in the rate of cardiovascular death or hospitalization for heart failure (HHF), compared with placebo, among 5,988 randomized patients with HFpEF during a median 26 months of follow-up, proving that patients with HFpEF finally have a treatment that gives them clinically meaningful benefit, and paving the way to an abrupt change in management of these patients, experts said.

“This is the first trial to show unequivocal benefits of any drug on major heart failure outcomes in patients with HFpEF,” Stefan D. Anker, MD, PhD, declared at the virtual annual congress of the European Society of Cardiology.

The 21% relative reduction, which reflected a cut in the absolute rate of the trial’s primary composite endpoint of 3.3% compared with placebo, was driven mainly by a significant 27% relative reduction in the incidence of HHF (P < .001). Empagliflozin treatment, on top of standard therapy for patients with HFpEF, also resulted in a nonsignificant 9% relative risk reduction in the incidence of cardiovascular death, but it had no discernible impact on the rate of death from any cause, said Dr. Anker, professor of cardiology at Charité Medical University in Berlin.

Concurrently with his talk at the meeting, the results were published online in the New England Journal of Medicine.
 

Practice will change ‘quickly’

“This will definitely change our practice, and quite quickly,” said Carlos Aguiar, MD, chair of the Advanced Heart Failure and Heart Transplantation Unit at Hospital Santa Cruz in Carnaxide, Portugal, who was not involved in the study.

Transition to routine use of empagliflozin in patients with HFpEF should be swift because it has already become a mainstay of treatment for patients with heart failure with reduced ejection fraction (HFrEF) based on evidence for empagliflozin in EMPEROR-Reduced. A second sodium-glucose cotransporter 2 (SGLT2 ) inhibitor, dapagliflozin (Farxiga), is also an option for treating HFrEF based on results in the DAPA-HF trial, and the DELIVER trial, still in progress, is testing dapagliflozin as a HFpEF treatment in about 6,000 patients, with results expected in 2022.

About half of the patients in EMPEROR-Preserved had diabetes, and the treatment effects on HFpEF were similar regardless of patients’ diabetes status. Empagliflozin, like other members of the SGLT2 inhibitor class, boosts urinary excretion of glucose and received initial regulatory approval as an agent for glycemic control in patients with type 2 diabetes. Empagliflozin also has U.S.-approved marketing indications for treating patients with HFrEF whether or not they also have diabetes, and for reducing cardiovascular death in patients with type 2 diabetes and cardiovascular disease.

“We already use this drug class in cardiovascular medicine and to treat patients with type 2 diabetes, and we have been eager to find a treatment for patients with HFpEF. This is something that will be really significant,” said Dr. Aguiar.

Heart failure clinicians have “become familiar prescribing” SGLT2 inhibitors following approval of HFrEF indications for some of these agents, noted Mary Norine Walsh, MD, a heart failure specialist with Ascension Medical Group in Indianapolis. The new results “are good news because there have been so few options” for patients with HFpEF, she said in an interview.

EMPEROR-Preserved “is the first phase 3 clinical trial that exclusively enrolled patients with heart failure and an ejection fraction of more than 40% to meet its primary outcome,” and the results “represent a major win against a medical condition that had previously proven formidable,” Mark H. Drazner, MD, said in an editorial that accompanied the published results.

The trial’s findings “should contribute to a change in clinical practice given the paucity of therapeutic options available for patients with HFpEF,” wrote Dr. Drazner, a heart failure specialist who is professor and clinical chief of cardiology at UT Southwestern Medical Center in Dallas.

Theresa A, McDonagh, MD, MBChB, who chaired the panel that just released revised guidelines from the European Society of Cardiology for managing patients with heart failure, predicted that empagliflozin treatment for patients with HFpEF will soon show up in guidelines. It will likely receive a “should be considered” ranking despite being a single study because of the impressive size of the treatment effect and lack of well-supported alternative treatments, she commented as a discussant of the trial during its presentation at the congress. If the DELIVER trial with dapagliflozin shows a similar effect, the recommendation would likely become even stronger, added Dr. McDonagh, a heart failure specialist and professor of cardiology at King’s College, London.

More women enrolled than ever before

EMPEROR-Preserved enrolled adults with chronic HFpEF in New York Heart Association functional class II-IV and a left ventricular ejection fraction greater than 40% starting in 2017 at more than 600 sites in more than 20 countries worldwide including the United States. As background therapy, more than 80% of patients received treatment with either an ACE inhibitor or angiotensin receptor blocker (in some instances in the form of sacubitril/valsartan), more than 80% were on a beta-blocker, and about a third were taking a mineralocorticoid receptor antagonist, making them “very well treated HFpEF patients,” Dr. Anker said.

One of the most notable features of enrollment was that 45% of participants were women, giving this trial the highest inclusion of women compared with all prior studies in patients with HFpEF or with HFrEF, said Dr. Walsh. “HFpEF is very prevalent in woman,” she noted, and having this high participation rate of women in the study increases its relevance to these patients. “It’s important to be able to tell women that patients like you were in the study so we can more easily apply the lessons from the trial to you. That can’t be stressed enough,” she said.

The primary outcome occurred in 415 (13.8%) of the 2,997 patients in the empagliflozin group and in 511 (17.1%) of 2,991 patients who received placebo (hazard ratio, 0.79; 95% confidence interval, 0.69-0.90; P < .001).

The study showed a safety profile consistent with prior experience with empagliflozin, Dr. Anker added.

Pooling EMPEROR-Preserved with EMPEROR-Reduced

The investigators who ran EMPEROR-Preserved designed the trial to closely parallel the EMPEROR-Reduced trial in patients with HFrEF, and they included a prespecified analysis (EMPEROR-Pooled) that combined the more than 9,700 patients in the two studies. This showed a consistent and robust benefit from empagliflozin for reducing HHF across a wide spectrum of patients with heart failure, ranging from patients with left ventricular ejection fractions of less than 25% to patients with ejection fractions as high as 64%. However, the analysis also showed that patients with ejection fractions of 65% or greater received no discernible benefit from empagliflozin, Milton Packer, MD, reported in a separate talk at the congress.

MDedge News

“The findings demonstrate the benefits of empagliflozin across a broad range of patients with heart failure who have ejection fractions of less than 60%-65%,” said Dr. Packer, a researcher at Baylor University Medical Center in Dallas.

This apparent attenuation of an effect at higher ejection fractions “has been observed in other HFpEF trials, most recently in the PARAGON-HF trial” of sacubitril/valsartan (Entresto), he noted. Additional analyses led by Dr. Packer showed that in patients with ejection fractions below 65% the HHF benefit from empagliflozin consistently surpassed the benefit seen with sacubitril/valsartan in PARAGON-HF. But he recommended using both drugs in patients with HFpEF and an ejection fraction up to about 60%.

“If I had a patient with HFpEF I would use both drugs as well as beta-blockers and mineralocorticoid receptor antagonists,” he said during a press briefing.

Another finding from analysis of the EMPEROR-Reduced and EMPEROR-Preserved trials together was that patients with reduced ejection fractions showed a significant 49% relative reduction in the incidence of serious renal outcomes, but this effect was completely blunted in EMPEROR-Preserved.

“Ejection fraction influences the effects of empagliflozin on major renal outcomes,” concluded Dr. Packer in a report on this analysis published simultaneously with the main EMPEROR-Preserved findings (N Engl J Med. 2021 Aug 27. doi: 10.1056/NEJMc2112411). “These data from the EMPEROR trials are unique. We have no comparable data” from any of the other reported studies of SGLT2 inhibitors,” he said.

EMPEROR-Preserved was sponsored by Boehringer Ingelheim and by Eli Lilly, the two companies that jointly market empagliflozin (Jardiance). Dr. Anker has received personal fees from Boehringer Ingelheim and from several other companies, and he has received grants and personal fees from Abbott Vascular and Vifor. Dr. Packer has received consulting fees from Boehringer Ingelheim and from numerous other companies. Dr. McDonagh has has recent financial relationships with AstraZeneca, Cprpus, Novartis, Pfizer, and Vifor. Dr. Aguiar and Dr. Walsh had no disclosures.

[email protected]

Updated August 30, 2021

The SGLT2 inhibitor empagliflozin achieved in EMPEROR-Preserved what no other agent could previously do: unequivocally cut the incidence of cardiovascular death or hospitalization in patients with heart failure and preserved ejection fraction (HFpEF).

MDedge News

Treatment with empagliflozin (Jardiance) led to a significant 21% relative reduction in the rate of cardiovascular death or hospitalization for heart failure (HHF), compared with placebo, among 5,988 randomized patients with HFpEF during a median 26 months of follow-up, proving that patients with HFpEF finally have a treatment that gives them clinically meaningful benefit, and paving the way to an abrupt change in management of these patients, experts said.

“This is the first trial to show unequivocal benefits of any drug on major heart failure outcomes in patients with HFpEF,” Stefan D. Anker, MD, PhD, declared at the virtual annual congress of the European Society of Cardiology.

The 21% relative reduction, which reflected a cut in the absolute rate of the trial’s primary composite endpoint of 3.3% compared with placebo, was driven mainly by a significant 27% relative reduction in the incidence of HHF (P < .001). Empagliflozin treatment, on top of standard therapy for patients with HFpEF, also resulted in a nonsignificant 9% relative risk reduction in the incidence of cardiovascular death, but it had no discernible impact on the rate of death from any cause, said Dr. Anker, professor of cardiology at Charité Medical University in Berlin.

Concurrently with his talk at the meeting, the results were published online in the New England Journal of Medicine.
 

Practice will change ‘quickly’

“This will definitely change our practice, and quite quickly,” said Carlos Aguiar, MD, chair of the Advanced Heart Failure and Heart Transplantation Unit at Hospital Santa Cruz in Carnaxide, Portugal, who was not involved in the study.

Transition to routine use of empagliflozin in patients with HFpEF should be swift because it has already become a mainstay of treatment for patients with heart failure with reduced ejection fraction (HFrEF) based on evidence for empagliflozin in EMPEROR-Reduced. A second sodium-glucose cotransporter 2 (SGLT2 ) inhibitor, dapagliflozin (Farxiga), is also an option for treating HFrEF based on results in the DAPA-HF trial, and the DELIVER trial, still in progress, is testing dapagliflozin as a HFpEF treatment in about 6,000 patients, with results expected in 2022.

About half of the patients in EMPEROR-Preserved had diabetes, and the treatment effects on HFpEF were similar regardless of patients’ diabetes status. Empagliflozin, like other members of the SGLT2 inhibitor class, boosts urinary excretion of glucose and received initial regulatory approval as an agent for glycemic control in patients with type 2 diabetes. Empagliflozin also has U.S.-approved marketing indications for treating patients with HFrEF whether or not they also have diabetes, and for reducing cardiovascular death in patients with type 2 diabetes and cardiovascular disease.

“We already use this drug class in cardiovascular medicine and to treat patients with type 2 diabetes, and we have been eager to find a treatment for patients with HFpEF. This is something that will be really significant,” said Dr. Aguiar.

Heart failure clinicians have “become familiar prescribing” SGLT2 inhibitors following approval of HFrEF indications for some of these agents, noted Mary Norine Walsh, MD, a heart failure specialist with Ascension Medical Group in Indianapolis. The new results “are good news because there have been so few options” for patients with HFpEF, she said in an interview.

EMPEROR-Preserved “is the first phase 3 clinical trial that exclusively enrolled patients with heart failure and an ejection fraction of more than 40% to meet its primary outcome,” and the results “represent a major win against a medical condition that had previously proven formidable,” Mark H. Drazner, MD, said in an editorial that accompanied the published results.

The trial’s findings “should contribute to a change in clinical practice given the paucity of therapeutic options available for patients with HFpEF,” wrote Dr. Drazner, a heart failure specialist who is professor and clinical chief of cardiology at UT Southwestern Medical Center in Dallas.

Theresa A, McDonagh, MD, MBChB, who chaired the panel that just released revised guidelines from the European Society of Cardiology for managing patients with heart failure, predicted that empagliflozin treatment for patients with HFpEF will soon show up in guidelines. It will likely receive a “should be considered” ranking despite being a single study because of the impressive size of the treatment effect and lack of well-supported alternative treatments, she commented as a discussant of the trial during its presentation at the congress. If the DELIVER trial with dapagliflozin shows a similar effect, the recommendation would likely become even stronger, added Dr. McDonagh, a heart failure specialist and professor of cardiology at King’s College, London.

More women enrolled than ever before

EMPEROR-Preserved enrolled adults with chronic HFpEF in New York Heart Association functional class II-IV and a left ventricular ejection fraction greater than 40% starting in 2017 at more than 600 sites in more than 20 countries worldwide including the United States. As background therapy, more than 80% of patients received treatment with either an ACE inhibitor or angiotensin receptor blocker (in some instances in the form of sacubitril/valsartan), more than 80% were on a beta-blocker, and about a third were taking a mineralocorticoid receptor antagonist, making them “very well treated HFpEF patients,” Dr. Anker said.

One of the most notable features of enrollment was that 45% of participants were women, giving this trial the highest inclusion of women compared with all prior studies in patients with HFpEF or with HFrEF, said Dr. Walsh. “HFpEF is very prevalent in woman,” she noted, and having this high participation rate of women in the study increases its relevance to these patients. “It’s important to be able to tell women that patients like you were in the study so we can more easily apply the lessons from the trial to you. That can’t be stressed enough,” she said.

The primary outcome occurred in 415 (13.8%) of the 2,997 patients in the empagliflozin group and in 511 (17.1%) of 2,991 patients who received placebo (hazard ratio, 0.79; 95% confidence interval, 0.69-0.90; P < .001).

The study showed a safety profile consistent with prior experience with empagliflozin, Dr. Anker added.

Pooling EMPEROR-Preserved with EMPEROR-Reduced

The investigators who ran EMPEROR-Preserved designed the trial to closely parallel the EMPEROR-Reduced trial in patients with HFrEF, and they included a prespecified analysis (EMPEROR-Pooled) that combined the more than 9,700 patients in the two studies. This showed a consistent and robust benefit from empagliflozin for reducing HHF across a wide spectrum of patients with heart failure, ranging from patients with left ventricular ejection fractions of less than 25% to patients with ejection fractions as high as 64%. However, the analysis also showed that patients with ejection fractions of 65% or greater received no discernible benefit from empagliflozin, Milton Packer, MD, reported in a separate talk at the congress.

MDedge News

“The findings demonstrate the benefits of empagliflozin across a broad range of patients with heart failure who have ejection fractions of less than 60%-65%,” said Dr. Packer, a researcher at Baylor University Medical Center in Dallas.

This apparent attenuation of an effect at higher ejection fractions “has been observed in other HFpEF trials, most recently in the PARAGON-HF trial” of sacubitril/valsartan (Entresto), he noted. Additional analyses led by Dr. Packer showed that in patients with ejection fractions below 65% the HHF benefit from empagliflozin consistently surpassed the benefit seen with sacubitril/valsartan in PARAGON-HF. But he recommended using both drugs in patients with HFpEF and an ejection fraction up to about 60%.

“If I had a patient with HFpEF I would use both drugs as well as beta-blockers and mineralocorticoid receptor antagonists,” he said during a press briefing.

Another finding from analysis of the EMPEROR-Reduced and EMPEROR-Preserved trials together was that patients with reduced ejection fractions showed a significant 49% relative reduction in the incidence of serious renal outcomes, but this effect was completely blunted in EMPEROR-Preserved.

“Ejection fraction influences the effects of empagliflozin on major renal outcomes,” concluded Dr. Packer in a report on this analysis published simultaneously with the main EMPEROR-Preserved findings (N Engl J Med. 2021 Aug 27. doi: 10.1056/NEJMc2112411). “These data from the EMPEROR trials are unique. We have no comparable data” from any of the other reported studies of SGLT2 inhibitors,” he said.

EMPEROR-Preserved was sponsored by Boehringer Ingelheim and by Eli Lilly, the two companies that jointly market empagliflozin (Jardiance). Dr. Anker has received personal fees from Boehringer Ingelheim and from several other companies, and he has received grants and personal fees from Abbott Vascular and Vifor. Dr. Packer has received consulting fees from Boehringer Ingelheim and from numerous other companies. Dr. McDonagh has has recent financial relationships with AstraZeneca, Cprpus, Novartis, Pfizer, and Vifor. Dr. Aguiar and Dr. Walsh had no disclosures.

[email protected]

There will be so much more to the annual congress of the European Society of Cardiology, which begins Aug. 27 with an all-virtual format, than detailed primary results of EMPEROR-Preserved, a trial that could mark a turning point for heart failure (HF) medical therapy.

Also among the featured Hot Line and Late-Breaking Science sessions are – along with many other studies – explorations of arrhythmia management (ablation or guided by loop recorder); secondary prevention, including by vaccination; oral anticoagulation, notably after transcatheter valve procedures; and colchicine or thrombosis prophylaxis in hospitalized patients with COVID-19.

There will even be a head-to-head comparison of two long-familiar left atrial appendage (LAA) occluders, and a population-based, randomized trial of sodium restriction through wide-scale use of a potassium-based salt substitute.

The congress will also introduce four guideline documents at sessions throughout the Congress, one on each day. They cover new and modified recommendations for heart failure; pacing, including cardiac resynchronization therapy (CRT); cardiovascular (CV) disease prevention; and, with cosponsorship from the European Association for Cardio-Thoracic Surgery, valvular heart disease.
 

The virtues of virtual

That next year’s Congress is slated for Aug. 27-30 in Barcelona should be welcome news for anyone whose “what if” curiosity about all-virtual conferences has already been satisfied. But with experience comes wisdom, as the medical societies have learned that online scientific meetings have some winning qualities that may be worth keeping, as least for a while.

“I think there is no doubt that the digital format will continue, for several reasons. One is that this pandemic is not over,” ESC Congress program committee chair Stephan Windecker, MD, Bern (Switzerland) University Hospital, , told this news organization. “As long as it is not over, the digital format is here to stay.”

But it also appears that people who haven’t been able to attend the congress in person are keen to log in and engage online, Dr. Windecker said. The 2020 all-virtual conference drew a much younger pool of registrants, on average, than did the live conferences before the pandemic.

“I think that’s an indication of people that may be in training, in early stages of their career, or they don’t have the support from departments or from their practice, or other financial means.” But they are able to participate via computer, tablet, or smartphone, he said.

“Another advantage is that the recorded content can be replayed at the convenience of whoever wants to consume it at a later point in time,” he added. “Those are just some examples why the digital format is likely to stay,” on its own or in a new age of hybrid meetings.  
 

New and updated guidelines

Leading off the guideline series is the document on diagnosis and treatment of acute and chronic HF, which leveraged the past few busy years of HF clinical trials to arrive at a number of new recommendations and strengthened level-of-evidence ratings. It covers both drug and device therapy of HF with reduced ejection fraction (HFrEF) and acute decompensated HF, and tweaks and further enshrines the concept of HF with mildly reduced ejection fraction (HFmrEF).

Several updated recommendations for both long-used and novel medications, notably the sodium-glucose cotransporter 2 inhibitors, will be included because of the recently appreciated evidence-based impact in HFrEF, Dr. Windecker noted.

“I think it will be particularly interesting to look for the SGLT2 inhibitors as not a completely new class of drugs, but certainly one where there has been a lot of new evidence, to look at how those drugs will be integrated in the overall care pathway.”

A top-line preview of the new HF guideline limited to drug therapy, presented at July’s Heart Failure Association of the European Society of Cardiology (ESC-HFA), provided a simple answer to a common question in the new, bountiful age of HFrEF medications: Which meds, initiated in what order?

As it happens, the new recommendation for first-line HFrEF drug therapy is not a silver bullet, but a shotgun – prompt initiation of at least four meds, one from each of four drug classes: renin-angiotensin system inhibitors, beta-blockers, mineralocorticoid receptor antagonists (MRA), and SGLT2 inhibitors. Each class, as described in the document, is to be started as soon as safely feasible, in a sequence deemed appropriate for each individual patient.
 

Spotlight on EMPEROR-Preserved

The world already knows that the trial, which tested the SGLT2 inhibitor empagliflozin (Jardiance, Boehringer Ingelheim/Eli Lilly) on top of standard therapy, “met” its primary endpoint in almost 6,000 patients with HF with preserved ejection fraction (HFpEF), who included some with HFmrEF by more contemporary definitions.

That means patients in EMPEROR-Preserved assigned to take empagliflozin showed significantly fewer events that made up the study’s primary endpoint, a composite of CV death or HF hospitalization. It appears to be the first clearly significant overall medical therapy benefit for a clinical primary endpoint in a major randomized HFpEF drug trial.

And that, pending fuller presentation of trial results at the Congress on Aug. 27, could be a huge deal for the half of HF patients with left ventricular ejection fractions (LVEF) higher than the HFrEF range.

Those early top-line results weren’t a decisive bombshell for a field now filled with hope for a practice-changing empagliflozin outcome in EMPEROR-Preserved, which isn’t a certainty. They were more like the “boom” of a mortar launching a rocket of fireworks that may explode into a chrysanthemum or green comet or, sometimes, turn out to be no more than a dud. The promise of the early cursory results critically depends on further details.

“Provided there is a compelling benefit, this is what everyone has been waiting for in this condition for decades,” Mikhail N. Kosiborod, MD, director of cardiometabolic research at Saint Luke’s Mid-America Heart Institute, Kansas City, Mo., said.

“Already knowing that the trial met the primary endpoint is obviously very intriguing and encouraging,” he added. “But there are things we don’t know, such as: What is the magnitude of benefit? And whether that benefit, whatever the magnitude, is driven by reductions in both heart failure hospitalizations and cardiovascular death, or only one of the two.”

For example: “If we see an impressive benefit for reduction of hospitalizations, but not a significant reduction in death, that would still be a huge advance. That’s because, to date, we don’t have any drug for HFpEF that has convincingly demonstrated a compelling reduction in heart failure hospitalization or improvement in symptoms, function, or quality of life,” observed Dr. Kosiborod, who wasn’t part of EMPEROR-Preserved.

There have been “suggestions” from HFrEF trials that empagliflozin and dapagliflozin (Farxiga, AstraZeneca) “have very comparable effects on at least the endpoint of cardiovascular death or hospitalization for heart failure,” he said. “So, my expectation would be that whatever is observed in EMPEROR-Preserved is likely a class effect, as well.”

Following EMPEROR-Preserved on the agenda is EMPEROR-Pooled, a patient-level combined analysis of the EMPEROR series of trials that spans the range of HF, regardless of ejection fraction or diabetes status, primarily exploring the effects of empagliflozin on renal function.
 

Other offerings, Friday, Aug. 27

Scheduled immediately after EMPEROR-Preserved is a presentation on the SMART-MI trial, which should clarify whether management guided by continuous ambulatory monitoring is effective in patients considered at especially high arrhythmic risk. Entry called for recent myocardial infarction and an LVEF of 36%-50% with evidence of cardiac autonomic dysfunction.

The trial randomly assigned 400 such patients to be or not be implanted with a Reveal LINQ (Medtronic) loop recorder and followed them for up to 18 months, primarily for detection of potentially serious arrhythmic events. Endpoints that involved mortality, hospitalization or other clinical events were secondary.

In a time slot preceding both SMART-MI and EMPEROR-Preserved, the GUIDE-HF trial is following a projected 3,600 patients with HF implanted with a CardioMEMS HF System (Abbott) pulmonary artery (PA) pressure sensor to explore the its value for guiding management.

The trial’s three cohorts, followed for at least 12 months, include randomized sensor-monitored and control groups of patients with New York Heart Association class 2-4 symptoms, as well as a third observational set of patients in NYHA class 3. That’s the indication for which the CardioMEMS monitor gained approval in the United States in 2014 based on the 2011 CHAMPION trial, and which fared just as well in the 2017 CHAMPION Post-Approval Study.

The Friday Hot Lines also include Dal-GenE, which has entered about 6,000 patients with recent MI to test the once-abandoned cholesterol ester transfer protein (CETP) inhibitor dalcetrapib (DalCor) for any secondary-prevention benefits when used selectively. The trial’s hook: All its patients are confirmed to have the AA genotype of the rs1967309 variant in the ADCY9 gene, which has been associated with a pronounced clinical response to CETP inhibition.

Saturday, Aug. 28

The direct oral anticoagulants (DOACs) have largely replaced vitamin K antagonists in patients with nonvalvular atrial fibrillation (AFib). But whether DOACs are similarly preferable in the growing world population of people who have undergone transcatheter aortic valve replacement (TAVR or TAVI), an issue explored with variable results in the ATLANTIS and GALILEO trials, is far from settled.

The ENVISAGE-TAVI AF trial explored the question for the factor X inhibitor edoxaban (Savaysa, Lixiana, Daiichi-Sankyo) in 1,400 patients with AFib and a transfemoral TAVR in the previous 5 days, who were randomly assigned to the DOAC or standard management along with discretionary antiplatelet therapy. They’ve been followed for up to 3 years for a composite endpoint of clinical events – including death, MI, and stroke – and for major bleeding.

The day will also feature MASTER DAPT, a comparison of two dual-antiplatelet therapy (DAPT) regimens in an estimated 4,300 patients considered to be high-risk for bleeding who had received the sirolimus-eluting Ultimaster (Terumo) coronary stent, which has a bioresorbable polymer coating.

Investigators have randomly assigned patients to receive either very-short-duration DAPT, for about a month after stenting, followed by a P2Y12 inhibitor alone for up to a year after the procedure; or a more conventional regimen of a P2Y12 inhibitor for 6-12 months with aspirin maintained for a total of 12 months.

Later that day, investigators from the FIGARO-DKD trial will present their results based on 7,437 patients with type 2 diabetes and chronic kidney disease (CKD), a much fuller version than the top-line findings announced by sponsor Bayer 3 months ago.

Those top-line results suggested that patients assigned to receive the nonsteroidal nonselective mineralocorticoid receptor antagonist (MRA) finerenone (Kerendia) on top of standard care benefited with a drop in risk for the primary endpoint of CV death or nonfatal CV events.

Finerenone was recently approved in the United States for treating patients with both type 2 diabetes and CKD based on the published FIDELIO-DKD trial, which had seen less CKD progression and fewer CV events in such patients who took the novel MRA.

Although similar in design to FIGARO-DKD, FIDELIO-DKD had entered fewer patients with early-stage diabetic kidney disease (DKD). That led researchers to pool the two trials’ populations to create a cohort that spans the spectrum of DKD severity. An analysis of the pooled cohort, dubbed FIDELITY, is on the schedule after FIGARO-DKD.

After FIDELITY is the prospective APAF-CRT trial that is following a projected 1,830 patients with permanent, symptomatic AFib and a recent hospitalization for AFib or HF and who were not good candidates for standard ablation. They were assigned to receive either atrioventricular junctional ablation followed by CRT, with or without a defibrillation, on top of optimal meds – a so-called “ablate-and-pace” strategy – or an implantable cardioverter defibrillator with rate-control drug therapy.

The new analysis represents the trial’s second phase in which mortality was followed for 4 years as the primary endpoint, in contrast to the previously reported initial phase that followed the first 102 patients for 2 years for the composite primary endpoint of death, worsening HF, and HF hospitalization. The first phase had halted enrollment before reaching its planned target of 280 patients after an interim analysis showed a significant benefit for ablate and pace. 

Next up: DECAAF 2, a randomized assessment of whether catheter ablation for AFib guided by delayed gadolinium enhancement on MRI, a proxy for scar tissue, can be more effective than standard AFib ablation by pulmonary vein isolation alone. An estimated 900 patients with persistent AFib who had never before undergone ablation for the arrhythmia were randomly assigned to one strategy or the other and followed for AFib recurrence over 18 months.
 

Sunday, Aug. 29

The TOMAHAWK trial aimed to clarify the optimal timing of invasive coronary angiography for resuscitated patients with non–ST-segment elevation out-of-hospital cardiac arrest, a broad population in a setting for which there is little randomized-trial guidance. Investigators randomly assigned 558 such patients to undergo immediate invasive angiography or to direct intensive care unit admission for initial standard care with discretionary delayed angiography. Patients were followed for all-cause mortality, with other clinical events and neurologic outcomes as secondary endpoints.

Next on the schedule, the RIPCORD-2 trial randomly assigned 1,100 patients with stable known or suspected coronary artery disease (CAD) to undergo conventional angiography alone or with added direct pressure-wire measurement of fractional flow reserve to guide management decisions. Primary outcomes include health care costs and patient-reported quality of life at 1 year.

Slated for later that day, the Asymptomatic Carotid Surgery Trial-2 (ACST-2) has entered an estimated 3600 patients with a substantial carotid artery narrowing not associated with symptoms but for which either carotid endarterectomy (CEA) or carotid artery stenting (CAS) was considered anatomically feasible. There also must have been “substantial uncertainty” regarding the optimal procedure choice.

The trial, conducted in 40 countries primarily in Europe and North America and launched in 2008, randomly assigned the patients to undergo either CEA or CAS, in both cases with appropriate medical therapy, and followed them for periprocedural events and up to 10 years for strokes and stroke-related events.

The LOOP study, which is to directly follow ACST-2, has explored whether screening for AFib using the Medtronic Reveal LINQ monitor in older patients with non-AFib stroke risk factors – with oral anticoagulation prescribed for those who test positive – can lower their risk for stroke or systemic embolism. It randomly assigned 6,000 such patients to care guided by the loop recorder or to standard care.

On a somewhat larger scale, the Salt Substitute and Stroke Study (SSaSS) randomly assigned a total of 20,996 people in about 600 villages across northern China and Tibet to sodium-restriction intervention and control groups by village. All participants had a history of stroke or were aged at least 60 years with uncontrolled hypertension.

As described by the trial’s online portal, participants in villages assigned to the intervention group were given a supply of a low-sodium, potassium-supplementing salt substitute to replace their own salt supplies, along with education on the health benefits of sodium restriction. Participants in control villages continued their normal diets and, at the trial’s beginning, received “advice to reduce their salt intake.” All were required to own a telephone.

Clinical events, including strokes and hospitalizations throughout a 5-year follow-up, were tracked by phone calls made to all participants every 6 months and were documented at follow-up home visits.

Sunday is also to feature a Late-Breaking Trials session with a focus on COVID-19, which leads off with COLCOVID, a test of colchicine in patients hospitalized for suspected SARS-CoV-2 infection and in acute respiratory distress.

The 1,279 participants in Argentina were randomly assigned to receive or not receive the potent anti-inflammatory agent on top of antivirals and other standard management and followed for death or new need for mechanical ventilation. A successful outcome would contrast with the RECOVERY trial, which terminated a colchicine group of patients hospitalized with COVID-19 because of a lack of efficacy earlier this year.

COLCOVID is to be followed by the MICHELLE trial of rivaroxaban (Xarelto, Bayer/Janssen) prophylaxis, compared with no preventive oral anticoagulant, in 320 patients who, when hospitalized with COVID-19, had been on parenteral anticoagulants because of an elevated risk for venous thromboembolism. The trial, conducted in Brazil, called for postdischarge rivaroxaban at a once-daily dosage of 10 mg for about 1 month.

The session also includes a presentation called “Insights into the Effects of the COVID-19 Pandemic: Comprehensive Analysis from the GUIDE-HF Trial,” the primary outcomes of which will be reported on the first day of the Congress.

Following is a presentation on the PREPARE-IT study of icosapent ethyl (Vascepa, Amarin), given at high dosages intended to be anti-inflammatory, compared with placebo, in an estimated 4,000 adults. The trial has two groups: A prevention group of adults living and circulating in the community; and a treatment group of patients aged at least 40 years with confirmed symptomatic SARS-CoV-2 infection for whom the need for hospitalization isn’t clear.
 

Monday, Aug. 30

The final day of the Congress features a trial called Influenza Vaccination after Myocardial Infarction (IAMI), which has tested the secondary preventive effect of influenza vaccination by randomly assigning 2,571 patients to receive a standard vaccine or a saline placebo injection on one occasion.

Entry to the international trial called for a diagnosis of MI with or without ST-segment elevation, or stable CAD and age at least 75 years with other risk factors. The patients were followed for death, MI, stent thrombosis, and a slew of secondary endpoints over 12 months.

Monday offerings continue later in a time block leading off with the STEP trial, which has randomly assigned an estimated 8,000 patients at 40 centers in China who are 60 to 80 years of age with a systolic blood pressure of 140 to <190 mm Hg to be on standard guideline-based therapy or an intensive drug-management strategy.

The systolic BP goals are 130 to <150 mm Hg for standard care and 110 to <130 mm Hg for the intensive regimen. The composite primary endpoint includes death and clinical events related to acute coronary syndromes, HF, revascularization, and stroke.

Following on heels of STEP, the Amulet IDE trial – the first major randomized comparison of two transcatheter LAA closure devices – entered 1,878 patients with nonvalvular AFib who were considered high-risk for bleeding and stroke or systemic embolism.

They were randomly assigned in the noninferiority trial to receive either the AMPLATZER Amulet (Abbott Medical Devices) or the WATCHMAN (Boston Scientific) closure devices and were followed for safety and efficacy for up to 5 years.

Both LAA closure devices, intended to make patients with AFib less reliant on oral anticoagulation, are now available on both sides of the Atlantic – as well as many other countries – after the Amulet’s United States market approval on Aug. 16, based largely on the Amulet IDE trial.

Rounding out the final Hot Line set is one of the latest efforts to show the efficacy and safety of a very short DAPT period after coronary stenting in patients with acute coronary syndromes, the STOPDAPT-2 ACS trial.

The study assigned 3,008 patients in Japan to receive aspirin and clopidogrel for either 1 month or 1 year after implantation with an everolimus-eluting cobalt-chromium stent and followed them for up to 5 years for a composite of MI, CV death, stent thrombosis, stroke, and bleeding.

The trial follows the published STOPDAPT-2 trial that showed superiority for the 1-month DAPT regimen in a predominantly stable-CAD population treated with the same kind of stent.
 

Program structure and format

A total of 15 online channels are to be available in the morning, European time, their schedules running in parallel. Presentations often are prerecorded, but also include live sessions at 8:00 a.m. Central time and 12 p.m. CET (2:00 a.m. and 6:00 a.m. Eastern time) to liven up the channel offerings, Dr. Windecker observed, and to make them more immediate and potentially interactive.

Many of the parallel channels are devoted throughout the Congress to particular silos of cardiology; for example, arrhythmias and device therapy is on channel 3; CAD and acute care is on 5; HF is on 6; and preventive cardiology is on 9.

Other channels swing across different topics from day to day, such as channel 1, which covers COVID-19 topics on the first and third day of the meeting, “advances in science” on day 2, and “digital health, public health, health economics” on day 4.

The focus each day, starting at 2:00 p.m. CET (8:00 a.m. ET) and continuing into the evening in Europe, shifts over to the Prime Time live program, which features the Hot Line and guideline presentations and many of the live abstract presentations.

Dr. Kosiborod, not a researcher with the EMPEROR trials, is chair of the Dapagliflozin in Preserved Ejection Fraction Heart Failure ( PRESERVED-HF ) trial, which is scheduled for presentation at the September 2021 Heart Failure Society of American meeting.

A version of this article first appeared on Medscape.com.

There will be so much more to the annual congress of the European Society of Cardiology, which begins Aug. 27 with an all-virtual format, than detailed primary results of EMPEROR-Preserved, a trial that could mark a turning point for heart failure (HF) medical therapy.

Also among the featured Hot Line and Late-Breaking Science sessions are – along with many other studies – explorations of arrhythmia management (ablation or guided by loop recorder); secondary prevention, including by vaccination; oral anticoagulation, notably after transcatheter valve procedures; and colchicine or thrombosis prophylaxis in hospitalized patients with COVID-19.

There will even be a head-to-head comparison of two long-familiar left atrial appendage (LAA) occluders, and a population-based, randomized trial of sodium restriction through wide-scale use of a potassium-based salt substitute.

The congress will also introduce four guideline documents at sessions throughout the Congress, one on each day. They cover new and modified recommendations for heart failure; pacing, including cardiac resynchronization therapy (CRT); cardiovascular (CV) disease prevention; and, with cosponsorship from the European Association for Cardio-Thoracic Surgery, valvular heart disease.
 

The virtues of virtual

That next year’s Congress is slated for Aug. 27-30 in Barcelona should be welcome news for anyone whose “what if” curiosity about all-virtual conferences has already been satisfied. But with experience comes wisdom, as the medical societies have learned that online scientific meetings have some winning qualities that may be worth keeping, as least for a while.

“I think there is no doubt that the digital format will continue, for several reasons. One is that this pandemic is not over,” ESC Congress program committee chair Stephan Windecker, MD, Bern (Switzerland) University Hospital, , told this news organization. “As long as it is not over, the digital format is here to stay.”

But it also appears that people who haven’t been able to attend the congress in person are keen to log in and engage online, Dr. Windecker said. The 2020 all-virtual conference drew a much younger pool of registrants, on average, than did the live conferences before the pandemic.

“I think that’s an indication of people that may be in training, in early stages of their career, or they don’t have the support from departments or from their practice, or other financial means.” But they are able to participate via computer, tablet, or smartphone, he said.

“Another advantage is that the recorded content can be replayed at the convenience of whoever wants to consume it at a later point in time,” he added. “Those are just some examples why the digital format is likely to stay,” on its own or in a new age of hybrid meetings.  
 

New and updated guidelines

Leading off the guideline series is the document on diagnosis and treatment of acute and chronic HF, which leveraged the past few busy years of HF clinical trials to arrive at a number of new recommendations and strengthened level-of-evidence ratings. It covers both drug and device therapy of HF with reduced ejection fraction (HFrEF) and acute decompensated HF, and tweaks and further enshrines the concept of HF with mildly reduced ejection fraction (HFmrEF).

Several updated recommendations for both long-used and novel medications, notably the sodium-glucose cotransporter 2 inhibitors, will be included because of the recently appreciated evidence-based impact in HFrEF, Dr. Windecker noted.

“I think it will be particularly interesting to look for the SGLT2 inhibitors as not a completely new class of drugs, but certainly one where there has been a lot of new evidence, to look at how those drugs will be integrated in the overall care pathway.”

A top-line preview of the new HF guideline limited to drug therapy, presented at July’s Heart Failure Association of the European Society of Cardiology (ESC-HFA), provided a simple answer to a common question in the new, bountiful age of HFrEF medications: Which meds, initiated in what order?

As it happens, the new recommendation for first-line HFrEF drug therapy is not a silver bullet, but a shotgun – prompt initiation of at least four meds, one from each of four drug classes: renin-angiotensin system inhibitors, beta-blockers, mineralocorticoid receptor antagonists (MRA), and SGLT2 inhibitors. Each class, as described in the document, is to be started as soon as safely feasible, in a sequence deemed appropriate for each individual patient.
 

Spotlight on EMPEROR-Preserved

The world already knows that the trial, which tested the SGLT2 inhibitor empagliflozin (Jardiance, Boehringer Ingelheim/Eli Lilly) on top of standard therapy, “met” its primary endpoint in almost 6,000 patients with HF with preserved ejection fraction (HFpEF), who included some with HFmrEF by more contemporary definitions.

That means patients in EMPEROR-Preserved assigned to take empagliflozin showed significantly fewer events that made up the study’s primary endpoint, a composite of CV death or HF hospitalization. It appears to be the first clearly significant overall medical therapy benefit for a clinical primary endpoint in a major randomized HFpEF drug trial.

And that, pending fuller presentation of trial results at the Congress on Aug. 27, could be a huge deal for the half of HF patients with left ventricular ejection fractions (LVEF) higher than the HFrEF range.

Those early top-line results weren’t a decisive bombshell for a field now filled with hope for a practice-changing empagliflozin outcome in EMPEROR-Preserved, which isn’t a certainty. They were more like the “boom” of a mortar launching a rocket of fireworks that may explode into a chrysanthemum or green comet or, sometimes, turn out to be no more than a dud. The promise of the early cursory results critically depends on further details.

“Provided there is a compelling benefit, this is what everyone has been waiting for in this condition for decades,” Mikhail N. Kosiborod, MD, director of cardiometabolic research at Saint Luke’s Mid-America Heart Institute, Kansas City, Mo., said.

“Already knowing that the trial met the primary endpoint is obviously very intriguing and encouraging,” he added. “But there are things we don’t know, such as: What is the magnitude of benefit? And whether that benefit, whatever the magnitude, is driven by reductions in both heart failure hospitalizations and cardiovascular death, or only one of the two.”

For example: “If we see an impressive benefit for reduction of hospitalizations, but not a significant reduction in death, that would still be a huge advance. That’s because, to date, we don’t have any drug for HFpEF that has convincingly demonstrated a compelling reduction in heart failure hospitalization or improvement in symptoms, function, or quality of life,” observed Dr. Kosiborod, who wasn’t part of EMPEROR-Preserved.

There have been “suggestions” from HFrEF trials that empagliflozin and dapagliflozin (Farxiga, AstraZeneca) “have very comparable effects on at least the endpoint of cardiovascular death or hospitalization for heart failure,” he said. “So, my expectation would be that whatever is observed in EMPEROR-Preserved is likely a class effect, as well.”

Following EMPEROR-Preserved on the agenda is EMPEROR-Pooled, a patient-level combined analysis of the EMPEROR series of trials that spans the range of HF, regardless of ejection fraction or diabetes status, primarily exploring the effects of empagliflozin on renal function.
 

Other offerings, Friday, Aug. 27

Scheduled immediately after EMPEROR-Preserved is a presentation on the SMART-MI trial, which should clarify whether management guided by continuous ambulatory monitoring is effective in patients considered at especially high arrhythmic risk. Entry called for recent myocardial infarction and an LVEF of 36%-50% with evidence of cardiac autonomic dysfunction.

The trial randomly assigned 400 such patients to be or not be implanted with a Reveal LINQ (Medtronic) loop recorder and followed them for up to 18 months, primarily for detection of potentially serious arrhythmic events. Endpoints that involved mortality, hospitalization or other clinical events were secondary.

In a time slot preceding both SMART-MI and EMPEROR-Preserved, the GUIDE-HF trial is following a projected 3,600 patients with HF implanted with a CardioMEMS HF System (Abbott) pulmonary artery (PA) pressure sensor to explore the its value for guiding management.

The trial’s three cohorts, followed for at least 12 months, include randomized sensor-monitored and control groups of patients with New York Heart Association class 2-4 symptoms, as well as a third observational set of patients in NYHA class 3. That’s the indication for which the CardioMEMS monitor gained approval in the United States in 2014 based on the 2011 CHAMPION trial, and which fared just as well in the 2017 CHAMPION Post-Approval Study.

The Friday Hot Lines also include Dal-GenE, which has entered about 6,000 patients with recent MI to test the once-abandoned cholesterol ester transfer protein (CETP) inhibitor dalcetrapib (DalCor) for any secondary-prevention benefits when used selectively. The trial’s hook: All its patients are confirmed to have the AA genotype of the rs1967309 variant in the ADCY9 gene, which has been associated with a pronounced clinical response to CETP inhibition.

Saturday, Aug. 28

The direct oral anticoagulants (DOACs) have largely replaced vitamin K antagonists in patients with nonvalvular atrial fibrillation (AFib). But whether DOACs are similarly preferable in the growing world population of people who have undergone transcatheter aortic valve replacement (TAVR or TAVI), an issue explored with variable results in the ATLANTIS and GALILEO trials, is far from settled.

The ENVISAGE-TAVI AF trial explored the question for the factor X inhibitor edoxaban (Savaysa, Lixiana, Daiichi-Sankyo) in 1,400 patients with AFib and a transfemoral TAVR in the previous 5 days, who were randomly assigned to the DOAC or standard management along with discretionary antiplatelet therapy. They’ve been followed for up to 3 years for a composite endpoint of clinical events – including death, MI, and stroke – and for major bleeding.

The day will also feature MASTER DAPT, a comparison of two dual-antiplatelet therapy (DAPT) regimens in an estimated 4,300 patients considered to be high-risk for bleeding who had received the sirolimus-eluting Ultimaster (Terumo) coronary stent, which has a bioresorbable polymer coating.

Investigators have randomly assigned patients to receive either very-short-duration DAPT, for about a month after stenting, followed by a P2Y12 inhibitor alone for up to a year after the procedure; or a more conventional regimen of a P2Y12 inhibitor for 6-12 months with aspirin maintained for a total of 12 months.

Later that day, investigators from the FIGARO-DKD trial will present their results based on 7,437 patients with type 2 diabetes and chronic kidney disease (CKD), a much fuller version than the top-line findings announced by sponsor Bayer 3 months ago.

Those top-line results suggested that patients assigned to receive the nonsteroidal nonselective mineralocorticoid receptor antagonist (MRA) finerenone (Kerendia) on top of standard care benefited with a drop in risk for the primary endpoint of CV death or nonfatal CV events.

Finerenone was recently approved in the United States for treating patients with both type 2 diabetes and CKD based on the published FIDELIO-DKD trial, which had seen less CKD progression and fewer CV events in such patients who took the novel MRA.

Although similar in design to FIGARO-DKD, FIDELIO-DKD had entered fewer patients with early-stage diabetic kidney disease (DKD). That led researchers to pool the two trials’ populations to create a cohort that spans the spectrum of DKD severity. An analysis of the pooled cohort, dubbed FIDELITY, is on the schedule after FIGARO-DKD.

After FIDELITY is the prospective APAF-CRT trial that is following a projected 1,830 patients with permanent, symptomatic AFib and a recent hospitalization for AFib or HF and who were not good candidates for standard ablation. They were assigned to receive either atrioventricular junctional ablation followed by CRT, with or without a defibrillation, on top of optimal meds – a so-called “ablate-and-pace” strategy – or an implantable cardioverter defibrillator with rate-control drug therapy.

The new analysis represents the trial’s second phase in which mortality was followed for 4 years as the primary endpoint, in contrast to the previously reported initial phase that followed the first 102 patients for 2 years for the composite primary endpoint of death, worsening HF, and HF hospitalization. The first phase had halted enrollment before reaching its planned target of 280 patients after an interim analysis showed a significant benefit for ablate and pace. 

Next up: DECAAF 2, a randomized assessment of whether catheter ablation for AFib guided by delayed gadolinium enhancement on MRI, a proxy for scar tissue, can be more effective than standard AFib ablation by pulmonary vein isolation alone. An estimated 900 patients with persistent AFib who had never before undergone ablation for the arrhythmia were randomly assigned to one strategy or the other and followed for AFib recurrence over 18 months.
 

Sunday, Aug. 29

The TOMAHAWK trial aimed to clarify the optimal timing of invasive coronary angiography for resuscitated patients with non–ST-segment elevation out-of-hospital cardiac arrest, a broad population in a setting for which there is little randomized-trial guidance. Investigators randomly assigned 558 such patients to undergo immediate invasive angiography or to direct intensive care unit admission for initial standard care with discretionary delayed angiography. Patients were followed for all-cause mortality, with other clinical events and neurologic outcomes as secondary endpoints.

Next on the schedule, the RIPCORD-2 trial randomly assigned 1,100 patients with stable known or suspected coronary artery disease (CAD) to undergo conventional angiography alone or with added direct pressure-wire measurement of fractional flow reserve to guide management decisions. Primary outcomes include health care costs and patient-reported quality of life at 1 year.

Slated for later that day, the Asymptomatic Carotid Surgery Trial-2 (ACST-2) has entered an estimated 3600 patients with a substantial carotid artery narrowing not associated with symptoms but for which either carotid endarterectomy (CEA) or carotid artery stenting (CAS) was considered anatomically feasible. There also must have been “substantial uncertainty” regarding the optimal procedure choice.

The trial, conducted in 40 countries primarily in Europe and North America and launched in 2008, randomly assigned the patients to undergo either CEA or CAS, in both cases with appropriate medical therapy, and followed them for periprocedural events and up to 10 years for strokes and stroke-related events.

The LOOP study, which is to directly follow ACST-2, has explored whether screening for AFib using the Medtronic Reveal LINQ monitor in older patients with non-AFib stroke risk factors – with oral anticoagulation prescribed for those who test positive – can lower their risk for stroke or systemic embolism. It randomly assigned 6,000 such patients to care guided by the loop recorder or to standard care.

On a somewhat larger scale, the Salt Substitute and Stroke Study (SSaSS) randomly assigned a total of 20,996 people in about 600 villages across northern China and Tibet to sodium-restriction intervention and control groups by village. All participants had a history of stroke or were aged at least 60 years with uncontrolled hypertension.

As described by the trial’s online portal, participants in villages assigned to the intervention group were given a supply of a low-sodium, potassium-supplementing salt substitute to replace their own salt supplies, along with education on the health benefits of sodium restriction. Participants in control villages continued their normal diets and, at the trial’s beginning, received “advice to reduce their salt intake.” All were required to own a telephone.

Clinical events, including strokes and hospitalizations throughout a 5-year follow-up, were tracked by phone calls made to all participants every 6 months and were documented at follow-up home visits.

Sunday is also to feature a Late-Breaking Trials session with a focus on COVID-19, which leads off with COLCOVID, a test of colchicine in patients hospitalized for suspected SARS-CoV-2 infection and in acute respiratory distress.

The 1,279 participants in Argentina were randomly assigned to receive or not receive the potent anti-inflammatory agent on top of antivirals and other standard management and followed for death or new need for mechanical ventilation. A successful outcome would contrast with the RECOVERY trial, which terminated a colchicine group of patients hospitalized with COVID-19 because of a lack of efficacy earlier this year.

COLCOVID is to be followed by the MICHELLE trial of rivaroxaban (Xarelto, Bayer/Janssen) prophylaxis, compared with no preventive oral anticoagulant, in 320 patients who, when hospitalized with COVID-19, had been on parenteral anticoagulants because of an elevated risk for venous thromboembolism. The trial, conducted in Brazil, called for postdischarge rivaroxaban at a once-daily dosage of 10 mg for about 1 month.

The session also includes a presentation called “Insights into the Effects of the COVID-19 Pandemic: Comprehensive Analysis from the GUIDE-HF Trial,” the primary outcomes of which will be reported on the first day of the Congress.

Following is a presentation on the PREPARE-IT study of icosapent ethyl (Vascepa, Amarin), given at high dosages intended to be anti-inflammatory, compared with placebo, in an estimated 4,000 adults. The trial has two groups: A prevention group of adults living and circulating in the community; and a treatment group of patients aged at least 40 years with confirmed symptomatic SARS-CoV-2 infection for whom the need for hospitalization isn’t clear.
 

Monday, Aug. 30

The final day of the Congress features a trial called Influenza Vaccination after Myocardial Infarction (IAMI), which has tested the secondary preventive effect of influenza vaccination by randomly assigning 2,571 patients to receive a standard vaccine or a saline placebo injection on one occasion.

Entry to the international trial called for a diagnosis of MI with or without ST-segment elevation, or stable CAD and age at least 75 years with other risk factors. The patients were followed for death, MI, stent thrombosis, and a slew of secondary endpoints over 12 months.

Monday offerings continue later in a time block leading off with the STEP trial, which has randomly assigned an estimated 8,000 patients at 40 centers in China who are 60 to 80 years of age with a systolic blood pressure of 140 to <190 mm Hg to be on standard guideline-based therapy or an intensive drug-management strategy.

The systolic BP goals are 130 to <150 mm Hg for standard care and 110 to <130 mm Hg for the intensive regimen. The composite primary endpoint includes death and clinical events related to acute coronary syndromes, HF, revascularization, and stroke.

Following on heels of STEP, the Amulet IDE trial – the first major randomized comparison of two transcatheter LAA closure devices – entered 1,878 patients with nonvalvular AFib who were considered high-risk for bleeding and stroke or systemic embolism.

They were randomly assigned in the noninferiority trial to receive either the AMPLATZER Amulet (Abbott Medical Devices) or the WATCHMAN (Boston Scientific) closure devices and were followed for safety and efficacy for up to 5 years.

Both LAA closure devices, intended to make patients with AFib less reliant on oral anticoagulation, are now available on both sides of the Atlantic – as well as many other countries – after the Amulet’s United States market approval on Aug. 16, based largely on the Amulet IDE trial.

Rounding out the final Hot Line set is one of the latest efforts to show the efficacy and safety of a very short DAPT period after coronary stenting in patients with acute coronary syndromes, the STOPDAPT-2 ACS trial.

The study assigned 3,008 patients in Japan to receive aspirin and clopidogrel for either 1 month or 1 year after implantation with an everolimus-eluting cobalt-chromium stent and followed them for up to 5 years for a composite of MI, CV death, stent thrombosis, stroke, and bleeding.

The trial follows the published STOPDAPT-2 trial that showed superiority for the 1-month DAPT regimen in a predominantly stable-CAD population treated with the same kind of stent.
 

Program structure and format

A total of 15 online channels are to be available in the morning, European time, their schedules running in parallel. Presentations often are prerecorded, but also include live sessions at 8:00 a.m. Central time and 12 p.m. CET (2:00 a.m. and 6:00 a.m. Eastern time) to liven up the channel offerings, Dr. Windecker observed, and to make them more immediate and potentially interactive.

Many of the parallel channels are devoted throughout the Congress to particular silos of cardiology; for example, arrhythmias and device therapy is on channel 3; CAD and acute care is on 5; HF is on 6; and preventive cardiology is on 9.

Other channels swing across different topics from day to day, such as channel 1, which covers COVID-19 topics on the first and third day of the meeting, “advances in science” on day 2, and “digital health, public health, health economics” on day 4.

The focus each day, starting at 2:00 p.m. CET (8:00 a.m. ET) and continuing into the evening in Europe, shifts over to the Prime Time live program, which features the Hot Line and guideline presentations and many of the live abstract presentations.

Dr. Kosiborod, not a researcher with the EMPEROR trials, is chair of the Dapagliflozin in Preserved Ejection Fraction Heart Failure ( PRESERVED-HF ) trial, which is scheduled for presentation at the September 2021 Heart Failure Society of American meeting.

A version of this article first appeared on Medscape.com.

There will be so much more to the annual congress of the European Society of Cardiology, which begins Aug. 27 with an all-virtual format, than detailed primary results of EMPEROR-Preserved, a trial that could mark a turning point for heart failure (HF) medical therapy.

Also among the featured Hot Line and Late-Breaking Science sessions are – along with many other studies – explorations of arrhythmia management (ablation or guided by loop recorder); secondary prevention, including by vaccination; oral anticoagulation, notably after transcatheter valve procedures; and colchicine or thrombosis prophylaxis in hospitalized patients with COVID-19.

There will even be a head-to-head comparison of two long-familiar left atrial appendage (LAA) occluders, and a population-based, randomized trial of sodium restriction through wide-scale use of a potassium-based salt substitute.

The congress will also introduce four guideline documents at sessions throughout the Congress, one on each day. They cover new and modified recommendations for heart failure; pacing, including cardiac resynchronization therapy (CRT); cardiovascular (CV) disease prevention; and, with cosponsorship from the European Association for Cardio-Thoracic Surgery, valvular heart disease.
 

The virtues of virtual

That next year’s Congress is slated for Aug. 27-30 in Barcelona should be welcome news for anyone whose “what if” curiosity about all-virtual conferences has already been satisfied. But with experience comes wisdom, as the medical societies have learned that online scientific meetings have some winning qualities that may be worth keeping, as least for a while.

“I think there is no doubt that the digital format will continue, for several reasons. One is that this pandemic is not over,” ESC Congress program committee chair Stephan Windecker, MD, Bern (Switzerland) University Hospital, , told this news organization. “As long as it is not over, the digital format is here to stay.”

But it also appears that people who haven’t been able to attend the congress in person are keen to log in and engage online, Dr. Windecker said. The 2020 all-virtual conference drew a much younger pool of registrants, on average, than did the live conferences before the pandemic.

“I think that’s an indication of people that may be in training, in early stages of their career, or they don’t have the support from departments or from their practice, or other financial means.” But they are able to participate via computer, tablet, or smartphone, he said.

“Another advantage is that the recorded content can be replayed at the convenience of whoever wants to consume it at a later point in time,” he added. “Those are just some examples why the digital format is likely to stay,” on its own or in a new age of hybrid meetings.  
 

New and updated guidelines

Leading off the guideline series is the document on diagnosis and treatment of acute and chronic HF, which leveraged the past few busy years of HF clinical trials to arrive at a number of new recommendations and strengthened level-of-evidence ratings. It covers both drug and device therapy of HF with reduced ejection fraction (HFrEF) and acute decompensated HF, and tweaks and further enshrines the concept of HF with mildly reduced ejection fraction (HFmrEF).

Several updated recommendations for both long-used and novel medications, notably the sodium-glucose cotransporter 2 inhibitors, will be included because of the recently appreciated evidence-based impact in HFrEF, Dr. Windecker noted.

“I think it will be particularly interesting to look for the SGLT2 inhibitors as not a completely new class of drugs, but certainly one where there has been a lot of new evidence, to look at how those drugs will be integrated in the overall care pathway.”

A top-line preview of the new HF guideline limited to drug therapy, presented at July’s Heart Failure Association of the European Society of Cardiology (ESC-HFA), provided a simple answer to a common question in the new, bountiful age of HFrEF medications: Which meds, initiated in what order?

As it happens, the new recommendation for first-line HFrEF drug therapy is not a silver bullet, but a shotgun – prompt initiation of at least four meds, one from each of four drug classes: renin-angiotensin system inhibitors, beta-blockers, mineralocorticoid receptor antagonists (MRA), and SGLT2 inhibitors. Each class, as described in the document, is to be started as soon as safely feasible, in a sequence deemed appropriate for each individual patient.
 

Spotlight on EMPEROR-Preserved

The world already knows that the trial, which tested the SGLT2 inhibitor empagliflozin (Jardiance, Boehringer Ingelheim/Eli Lilly) on top of standard therapy, “met” its primary endpoint in almost 6,000 patients with HF with preserved ejection fraction (HFpEF), who included some with HFmrEF by more contemporary definitions.

That means patients in EMPEROR-Preserved assigned to take empagliflozin showed significantly fewer events that made up the study’s primary endpoint, a composite of CV death or HF hospitalization. It appears to be the first clearly significant overall medical therapy benefit for a clinical primary endpoint in a major randomized HFpEF drug trial.

And that, pending fuller presentation of trial results at the Congress on Aug. 27, could be a huge deal for the half of HF patients with left ventricular ejection fractions (LVEF) higher than the HFrEF range.

Those early top-line results weren’t a decisive bombshell for a field now filled with hope for a practice-changing empagliflozin outcome in EMPEROR-Preserved, which isn’t a certainty. They were more like the “boom” of a mortar launching a rocket of fireworks that may explode into a chrysanthemum or green comet or, sometimes, turn out to be no more than a dud. The promise of the early cursory results critically depends on further details.

“Provided there is a compelling benefit, this is what everyone has been waiting for in this condition for decades,” Mikhail N. Kosiborod, MD, director of cardiometabolic research at Saint Luke’s Mid-America Heart Institute, Kansas City, Mo., said.

“Already knowing that the trial met the primary endpoint is obviously very intriguing and encouraging,” he added. “But there are things we don’t know, such as: What is the magnitude of benefit? And whether that benefit, whatever the magnitude, is driven by reductions in both heart failure hospitalizations and cardiovascular death, or only one of the two.”

For example: “If we see an impressive benefit for reduction of hospitalizations, but not a significant reduction in death, that would still be a huge advance. That’s because, to date, we don’t have any drug for HFpEF that has convincingly demonstrated a compelling reduction in heart failure hospitalization or improvement in symptoms, function, or quality of life,” observed Dr. Kosiborod, who wasn’t part of EMPEROR-Preserved.

There have been “suggestions” from HFrEF trials that empagliflozin and dapagliflozin (Farxiga, AstraZeneca) “have very comparable effects on at least the endpoint of cardiovascular death or hospitalization for heart failure,” he said. “So, my expectation would be that whatever is observed in EMPEROR-Preserved is likely a class effect, as well.”

Following EMPEROR-Preserved on the agenda is EMPEROR-Pooled, a patient-level combined analysis of the EMPEROR series of trials that spans the range of HF, regardless of ejection fraction or diabetes status, primarily exploring the effects of empagliflozin on renal function.
 

Other offerings, Friday, Aug. 27

Scheduled immediately after EMPEROR-Preserved is a presentation on the SMART-MI trial, which should clarify whether management guided by continuous ambulatory monitoring is effective in patients considered at especially high arrhythmic risk. Entry called for recent myocardial infarction and an LVEF of 36%-50% with evidence of cardiac autonomic dysfunction.

The trial randomly assigned 400 such patients to be or not be implanted with a Reveal LINQ (Medtronic) loop recorder and followed them for up to 18 months, primarily for detection of potentially serious arrhythmic events. Endpoints that involved mortality, hospitalization or other clinical events were secondary.

In a time slot preceding both SMART-MI and EMPEROR-Preserved, the GUIDE-HF trial is following a projected 3,600 patients with HF implanted with a CardioMEMS HF System (Abbott) pulmonary artery (PA) pressure sensor to explore the its value for guiding management.

The trial’s three cohorts, followed for at least 12 months, include randomized sensor-monitored and control groups of patients with New York Heart Association class 2-4 symptoms, as well as a third observational set of patients in NYHA class 3. That’s the indication for which the CardioMEMS monitor gained approval in the United States in 2014 based on the 2011 CHAMPION trial, and which fared just as well in the 2017 CHAMPION Post-Approval Study.

The Friday Hot Lines also include Dal-GenE, which has entered about 6,000 patients with recent MI to test the once-abandoned cholesterol ester transfer protein (CETP) inhibitor dalcetrapib (DalCor) for any secondary-prevention benefits when used selectively. The trial’s hook: All its patients are confirmed to have the AA genotype of the rs1967309 variant in the ADCY9 gene, which has been associated with a pronounced clinical response to CETP inhibition.

Saturday, Aug. 28

The direct oral anticoagulants (DOACs) have largely replaced vitamin K antagonists in patients with nonvalvular atrial fibrillation (AFib). But whether DOACs are similarly preferable in the growing world population of people who have undergone transcatheter aortic valve replacement (TAVR or TAVI), an issue explored with variable results in the ATLANTIS and GALILEO trials, is far from settled.

The ENVISAGE-TAVI AF trial explored the question for the factor X inhibitor edoxaban (Savaysa, Lixiana, Daiichi-Sankyo) in 1,400 patients with AFib and a transfemoral TAVR in the previous 5 days, who were randomly assigned to the DOAC or standard management along with discretionary antiplatelet therapy. They’ve been followed for up to 3 years for a composite endpoint of clinical events – including death, MI, and stroke – and for major bleeding.

The day will also feature MASTER DAPT, a comparison of two dual-antiplatelet therapy (DAPT) regimens in an estimated 4,300 patients considered to be high-risk for bleeding who had received the sirolimus-eluting Ultimaster (Terumo) coronary stent, which has a bioresorbable polymer coating.

Investigators have randomly assigned patients to receive either very-short-duration DAPT, for about a month after stenting, followed by a P2Y12 inhibitor alone for up to a year after the procedure; or a more conventional regimen of a P2Y12 inhibitor for 6-12 months with aspirin maintained for a total of 12 months.

Later that day, investigators from the FIGARO-DKD trial will present their results based on 7,437 patients with type 2 diabetes and chronic kidney disease (CKD), a much fuller version than the top-line findings announced by sponsor Bayer 3 months ago.

Those top-line results suggested that patients assigned to receive the nonsteroidal nonselective mineralocorticoid receptor antagonist (MRA) finerenone (Kerendia) on top of standard care benefited with a drop in risk for the primary endpoint of CV death or nonfatal CV events.

Finerenone was recently approved in the United States for treating patients with both type 2 diabetes and CKD based on the published FIDELIO-DKD trial, which had seen less CKD progression and fewer CV events in such patients who took the novel MRA.

Although similar in design to FIGARO-DKD, FIDELIO-DKD had entered fewer patients with early-stage diabetic kidney disease (DKD). That led researchers to pool the two trials’ populations to create a cohort that spans the spectrum of DKD severity. An analysis of the pooled cohort, dubbed FIDELITY, is on the schedule after FIGARO-DKD.

After FIDELITY is the prospective APAF-CRT trial that is following a projected 1,830 patients with permanent, symptomatic AFib and a recent hospitalization for AFib or HF and who were not good candidates for standard ablation. They were assigned to receive either atrioventricular junctional ablation followed by CRT, with or without a defibrillation, on top of optimal meds – a so-called “ablate-and-pace” strategy – or an implantable cardioverter defibrillator with rate-control drug therapy.

The new analysis represents the trial’s second phase in which mortality was followed for 4 years as the primary endpoint, in contrast to the previously reported initial phase that followed the first 102 patients for 2 years for the composite primary endpoint of death, worsening HF, and HF hospitalization. The first phase had halted enrollment before reaching its planned target of 280 patients after an interim analysis showed a significant benefit for ablate and pace. 

Next up: DECAAF 2, a randomized assessment of whether catheter ablation for AFib guided by delayed gadolinium enhancement on MRI, a proxy for scar tissue, can be more effective than standard AFib ablation by pulmonary vein isolation alone. An estimated 900 patients with persistent AFib who had never before undergone ablation for the arrhythmia were randomly assigned to one strategy or the other and followed for AFib recurrence over 18 months.
 

Sunday, Aug. 29

The TOMAHAWK trial aimed to clarify the optimal timing of invasive coronary angiography for resuscitated patients with non–ST-segment elevation out-of-hospital cardiac arrest, a broad population in a setting for which there is little randomized-trial guidance. Investigators randomly assigned 558 such patients to undergo immediate invasive angiography or to direct intensive care unit admission for initial standard care with discretionary delayed angiography. Patients were followed for all-cause mortality, with other clinical events and neurologic outcomes as secondary endpoints.

Next on the schedule, the RIPCORD-2 trial randomly assigned 1,100 patients with stable known or suspected coronary artery disease (CAD) to undergo conventional angiography alone or with added direct pressure-wire measurement of fractional flow reserve to guide management decisions. Primary outcomes include health care costs and patient-reported quality of life at 1 year.

Slated for later that day, the Asymptomatic Carotid Surgery Trial-2 (ACST-2) has entered an estimated 3600 patients with a substantial carotid artery narrowing not associated with symptoms but for which either carotid endarterectomy (CEA) or carotid artery stenting (CAS) was considered anatomically feasible. There also must have been “substantial uncertainty” regarding the optimal procedure choice.

The trial, conducted in 40 countries primarily in Europe and North America and launched in 2008, randomly assigned the patients to undergo either CEA or CAS, in both cases with appropriate medical therapy, and followed them for periprocedural events and up to 10 years for strokes and stroke-related events.

The LOOP study, which is to directly follow ACST-2, has explored whether screening for AFib using the Medtronic Reveal LINQ monitor in older patients with non-AFib stroke risk factors – with oral anticoagulation prescribed for those who test positive – can lower their risk for stroke or systemic embolism. It randomly assigned 6,000 such patients to care guided by the loop recorder or to standard care.

On a somewhat larger scale, the Salt Substitute and Stroke Study (SSaSS) randomly assigned a total of 20,996 people in about 600 villages across northern China and Tibet to sodium-restriction intervention and control groups by village. All participants had a history of stroke or were aged at least 60 years with uncontrolled hypertension.

As described by the trial’s online portal, participants in villages assigned to the intervention group were given a supply of a low-sodium, potassium-supplementing salt substitute to replace their own salt supplies, along with education on the health benefits of sodium restriction. Participants in control villages continued their normal diets and, at the trial’s beginning, received “advice to reduce their salt intake.” All were required to own a telephone.

Clinical events, including strokes and hospitalizations throughout a 5-year follow-up, were tracked by phone calls made to all participants every 6 months and were documented at follow-up home visits.

Sunday is also to feature a Late-Breaking Trials session with a focus on COVID-19, which leads off with COLCOVID, a test of colchicine in patients hospitalized for suspected SARS-CoV-2 infection and in acute respiratory distress.

The 1,279 participants in Argentina were randomly assigned to receive or not receive the potent anti-inflammatory agent on top of antivirals and other standard management and followed for death or new need for mechanical ventilation. A successful outcome would contrast with the RECOVERY trial, which terminated a colchicine group of patients hospitalized with COVID-19 because of a lack of efficacy earlier this year.

COLCOVID is to be followed by the MICHELLE trial of rivaroxaban (Xarelto, Bayer/Janssen) prophylaxis, compared with no preventive oral anticoagulant, in 320 patients who, when hospitalized with COVID-19, had been on parenteral anticoagulants because of an elevated risk for venous thromboembolism. The trial, conducted in Brazil, called for postdischarge rivaroxaban at a once-daily dosage of 10 mg for about 1 month.

The session also includes a presentation called “Insights into the Effects of the COVID-19 Pandemic: Comprehensive Analysis from the GUIDE-HF Trial,” the primary outcomes of which will be reported on the first day of the Congress.

Following is a presentation on the PREPARE-IT study of icosapent ethyl (Vascepa, Amarin), given at high dosages intended to be anti-inflammatory, compared with placebo, in an estimated 4,000 adults. The trial has two groups: A prevention group of adults living and circulating in the community; and a treatment group of patients aged at least 40 years with confirmed symptomatic SARS-CoV-2 infection for whom the need for hospitalization isn’t clear.
 

Monday, Aug. 30

The final day of the Congress features a trial called Influenza Vaccination after Myocardial Infarction (IAMI), which has tested the secondary preventive effect of influenza vaccination by randomly assigning 2,571 patients to receive a standard vaccine or a saline placebo injection on one occasion.

Entry to the international trial called for a diagnosis of MI with or without ST-segment elevation, or stable CAD and age at least 75 years with other risk factors. The patients were followed for death, MI, stent thrombosis, and a slew of secondary endpoints over 12 months.

Monday offerings continue later in a time block leading off with the STEP trial, which has randomly assigned an estimated 8,000 patients at 40 centers in China who are 60 to 80 years of age with a systolic blood pressure of 140 to <190 mm Hg to be on standard guideline-based therapy or an intensive drug-management strategy.

The systolic BP goals are 130 to <150 mm Hg for standard care and 110 to <130 mm Hg for the intensive regimen. The composite primary endpoint includes death and clinical events related to acute coronary syndromes, HF, revascularization, and stroke.

Following on heels of STEP, the Amulet IDE trial – the first major randomized comparison of two transcatheter LAA closure devices – entered 1,878 patients with nonvalvular AFib who were considered high-risk for bleeding and stroke or systemic embolism.

They were randomly assigned in the noninferiority trial to receive either the AMPLATZER Amulet (Abbott Medical Devices) or the WATCHMAN (Boston Scientific) closure devices and were followed for safety and efficacy for up to 5 years.

Both LAA closure devices, intended to make patients with AFib less reliant on oral anticoagulation, are now available on both sides of the Atlantic – as well as many other countries – after the Amulet’s United States market approval on Aug. 16, based largely on the Amulet IDE trial.

Rounding out the final Hot Line set is one of the latest efforts to show the efficacy and safety of a very short DAPT period after coronary stenting in patients with acute coronary syndromes, the STOPDAPT-2 ACS trial.

The study assigned 3,008 patients in Japan to receive aspirin and clopidogrel for either 1 month or 1 year after implantation with an everolimus-eluting cobalt-chromium stent and followed them for up to 5 years for a composite of MI, CV death, stent thrombosis, stroke, and bleeding.

The trial follows the published STOPDAPT-2 trial that showed superiority for the 1-month DAPT regimen in a predominantly stable-CAD population treated with the same kind of stent.
 

Program structure and format

A total of 15 online channels are to be available in the morning, European time, their schedules running in parallel. Presentations often are prerecorded, but also include live sessions at 8:00 a.m. Central time and 12 p.m. CET (2:00 a.m. and 6:00 a.m. Eastern time) to liven up the channel offerings, Dr. Windecker observed, and to make them more immediate and potentially interactive.

Many of the parallel channels are devoted throughout the Congress to particular silos of cardiology; for example, arrhythmias and device therapy is on channel 3; CAD and acute care is on 5; HF is on 6; and preventive cardiology is on 9.

Other channels swing across different topics from day to day, such as channel 1, which covers COVID-19 topics on the first and third day of the meeting, “advances in science” on day 2, and “digital health, public health, health economics” on day 4.

The focus each day, starting at 2:00 p.m. CET (8:00 a.m. ET) and continuing into the evening in Europe, shifts over to the Prime Time live program, which features the Hot Line and guideline presentations and many of the live abstract presentations.

Dr. Kosiborod, not a researcher with the EMPEROR trials, is chair of the Dapagliflozin in Preserved Ejection Fraction Heart Failure ( PRESERVED-HF ) trial, which is scheduled for presentation at the September 2021 Heart Failure Society of American meeting.

A version of this article first appeared on Medscape.com.

U.S. prescribing data from 160,000 adults with type 2 diabetes and diabetic kidney disease showed a notable uptick in new prescriptions for sodium-glucose cotransporter 2 inhibitors and less dramatic gains for glucagonlike peptide–1 receptor agonists during 2019 and continuing into early 2020, compared with prior years, with usage levels of both classes during the first quarter of 2020 rivaling those of more traditional agents including metformin and insulin.

During the first 3 months of 2020, initiation of a SGLT2 inhibitor constituted 13% of all new starts of an antidiabetes drug among adults with type 2 diabetes and diabetic kidney disease (DKD). This compared with initiation rates during the same early 2020 period of 17% for GLP-1 receptor agonists, 19% for metformin, 16% for sulfonylureas, 15% for insulins, 14% for thiazolidinediones, and 6% for dipeptidyl peptidase–4 inhibitors, the seven drug classes examined in a study published in Diabetes Care.

Early 2020 was the first time that starts of a GLP-1 receptor agonist ranked second (behind only metformin) among these seven drug classes in the studied U.S. population, and early 2020 also marked an unprecedentedly high start rate for SGLT2 inhibitors that nearly tripled the roughly 5% rate in place as recently as 2018.
 

Rises are ‘what we expected’

The recent rise of SGLT2 inhibitors and GLP-1 receptor agonists in these patients “was what we expected,” given the evidence for both classes in slowing progression of DKD, said Julie M. Paik, MD, senior author on the study and a nephrologist and pharmacoepidemiologist at Brigham and Women’s Hospital in Boston.

“We’ve seen other beneficial drugs slow on the uptake, so it’s not surprising to see it here, and I’m optimistic” about further increases going forward, she said in an interview.

Both drug classes “were originally marketed as diabetes drugs,” and it is only since 2019, with the publication of trials showing dramatic renal benefits from canagliflozin (Invokana) in CREDENCE, and from dapagliflozin (Farxiga) in DAPA-CKD in 2020 that the evidence became truly compelling for SGLT2 inhibitors. This evidence also led to new renal-protection indications approved by the Food and Drug Administration for canagliflozin and for dapagliflozin, noted Dr. Paik.

Evidence for renal protection also emerged in 2017 for the GLP-1 receptor agonist liraglutide (Victoza) in the LEADER trial, and for dulaglutide (Trulicity) in the AWARD-7 trial, although neither drug has received a renal indication in its labeling.

By 2020, guidelines for managing patients with type 2 diabetes and chronic kidney disease from the influential Kidney Disease: Improving Global Outcomes organization had identified agents from the SGLT2 inhibitor class as top-tier options, along with metformin, for treating these patients, with agents from the GLP-1 receptor agonist class as the top third class to add in patients who require additional glycemic control.

Additional analyses Dr. Paik and associates ran showed how this played out in terms of which specialists prescribed these drugs during the full period studied beginning in 2013. Throughout this roughly 7-year span, about 70% of the prescriptions written for either SGLT2 inhibitors or for GLP-1 receptor agonists were from internal medicine physicians, followed by about 20% written by endocrinologists. Prescriptions from nephrologists, as well as from cardiologists, have hovered at about 5% each, but seem poised to start rising based on the recently added indications and newer treatment recommendations.

“It’s good to see the recent uptick in use since 2019,” Katherine R. Tuttle, MD, commented in an interview. It’s a positive development for U.S. public health, “but we need to do more to disseminate and implement these life-, kidney-, and heart-saving therapies.”

Future use could approach 80% of DKD patients

Dr. Tuttle estimated that “target” levels of use for SGLT2 inhibitors and for GLP-1 receptor agonists “could reasonably approach 80%” for patients with type 2 diabetes and diabetic kidney disease.

“We will likely move to combination therapy” with simultaneous use of agents from both classes in a targeted way using “precision phenotyping based on clinical characteristics, and eventually perhaps by biomarkers, kidney biopsies, or both.” Combined treatment with both an SGLT2 inhibitor and a GLP-1 receptor agonist may be especially suited to patients with type 2 diabetes, atherosclerotic cardiovascular disease, low estimated glomerular filtration rate, and need for better glycemic control and weight loss, a profile that is “pretty typical” in real-world practice, said Dr. Tuttle, a nephrologist and endocrinologist and executive director for research at Providence Healthcare in Spokane, Wash.
 

Study included patients with commercial or Medicare Advantage coverage

The study used information in an Optum database that included patients enrolled in either commercial or in Medicare Advantage health insurance plans from 2013 to the first quarter of 2020. This included 160,489 adults with type 2 diabetes and DKD who started during that period at least one agent from any of the seven included drug classes.

This focus may have biased the findings because, overall, U.S. coverage of the relatively expensive agents from the SGLT2 inhibitor and GLP-1 receptor agonist classes has often been problematic.

“There are issues of cost, coverage, and access” using these medications, as well as limited data on cost-effectiveness, Dr. Paik acknowledged. Additional issues that have helped generate prescribing lags include concerns about possible adverse effects, low familiarity by providers with these drugs early on, and limited trial experience using them in older patients. The process of clinicians growing more comfortable prescribing these new agents has depended on their “working through the evidence,” she explained.

The FDA’s approval in July 2021 of finerenone (Kerendia) for treating patients with type 2 diabetes and chronic kidney disease threw yet another new variable into the prescribing mix for these patients.

“SGLT2 inhibitors are here to stay as a new standard of care for patients with diabetic kidney disease, but combination with finerenone might be especially useful for patients with diabetic kidney disease and heart failure,” Dr. Tuttle suggested. A new generation of clinical trials will likely soon launch to test these combinations, she predicted.

Dr. Paik had no disclosures. Dr. Tuttle has been a consultant to AstraZeneca, Bayer, Boehringer Ingelheim, Gilead, Goldfinch Bio, Eli Lilly, and Novo Nordisk.

[email protected]

U.S. prescribing data from 160,000 adults with type 2 diabetes and diabetic kidney disease showed a notable uptick in new prescriptions for sodium-glucose cotransporter 2 inhibitors and less dramatic gains for glucagonlike peptide–1 receptor agonists during 2019 and continuing into early 2020, compared with prior years, with usage levels of both classes during the first quarter of 2020 rivaling those of more traditional agents including metformin and insulin.

During the first 3 months of 2020, initiation of a SGLT2 inhibitor constituted 13% of all new starts of an antidiabetes drug among adults with type 2 diabetes and diabetic kidney disease (DKD). This compared with initiation rates during the same early 2020 period of 17% for GLP-1 receptor agonists, 19% for metformin, 16% for sulfonylureas, 15% for insulins, 14% for thiazolidinediones, and 6% for dipeptidyl peptidase–4 inhibitors, the seven drug classes examined in a study published in Diabetes Care.

Early 2020 was the first time that starts of a GLP-1 receptor agonist ranked second (behind only metformin) among these seven drug classes in the studied U.S. population, and early 2020 also marked an unprecedentedly high start rate for SGLT2 inhibitors that nearly tripled the roughly 5% rate in place as recently as 2018.
 

Rises are ‘what we expected’

The recent rise of SGLT2 inhibitors and GLP-1 receptor agonists in these patients “was what we expected,” given the evidence for both classes in slowing progression of DKD, said Julie M. Paik, MD, senior author on the study and a nephrologist and pharmacoepidemiologist at Brigham and Women’s Hospital in Boston.

“We’ve seen other beneficial drugs slow on the uptake, so it’s not surprising to see it here, and I’m optimistic” about further increases going forward, she said in an interview.

Both drug classes “were originally marketed as diabetes drugs,” and it is only since 2019, with the publication of trials showing dramatic renal benefits from canagliflozin (Invokana) in CREDENCE, and from dapagliflozin (Farxiga) in DAPA-CKD in 2020 that the evidence became truly compelling for SGLT2 inhibitors. This evidence also led to new renal-protection indications approved by the Food and Drug Administration for canagliflozin and for dapagliflozin, noted Dr. Paik.

Evidence for renal protection also emerged in 2017 for the GLP-1 receptor agonist liraglutide (Victoza) in the LEADER trial, and for dulaglutide (Trulicity) in the AWARD-7 trial, although neither drug has received a renal indication in its labeling.

By 2020, guidelines for managing patients with type 2 diabetes and chronic kidney disease from the influential Kidney Disease: Improving Global Outcomes organization had identified agents from the SGLT2 inhibitor class as top-tier options, along with metformin, for treating these patients, with agents from the GLP-1 receptor agonist class as the top third class to add in patients who require additional glycemic control.

Additional analyses Dr. Paik and associates ran showed how this played out in terms of which specialists prescribed these drugs during the full period studied beginning in 2013. Throughout this roughly 7-year span, about 70% of the prescriptions written for either SGLT2 inhibitors or for GLP-1 receptor agonists were from internal medicine physicians, followed by about 20% written by endocrinologists. Prescriptions from nephrologists, as well as from cardiologists, have hovered at about 5% each, but seem poised to start rising based on the recently added indications and newer treatment recommendations.

“It’s good to see the recent uptick in use since 2019,” Katherine R. Tuttle, MD, commented in an interview. It’s a positive development for U.S. public health, “but we need to do more to disseminate and implement these life-, kidney-, and heart-saving therapies.”

Future use could approach 80% of DKD patients

Dr. Tuttle estimated that “target” levels of use for SGLT2 inhibitors and for GLP-1 receptor agonists “could reasonably approach 80%” for patients with type 2 diabetes and diabetic kidney disease.

“We will likely move to combination therapy” with simultaneous use of agents from both classes in a targeted way using “precision phenotyping based on clinical characteristics, and eventually perhaps by biomarkers, kidney biopsies, or both.” Combined treatment with both an SGLT2 inhibitor and a GLP-1 receptor agonist may be especially suited to patients with type 2 diabetes, atherosclerotic cardiovascular disease, low estimated glomerular filtration rate, and need for better glycemic control and weight loss, a profile that is “pretty typical” in real-world practice, said Dr. Tuttle, a nephrologist and endocrinologist and executive director for research at Providence Healthcare in Spokane, Wash.
 

Study included patients with commercial or Medicare Advantage coverage

The study used information in an Optum database that included patients enrolled in either commercial or in Medicare Advantage health insurance plans from 2013 to the first quarter of 2020. This included 160,489 adults with type 2 diabetes and DKD who started during that period at least one agent from any of the seven included drug classes.

This focus may have biased the findings because, overall, U.S. coverage of the relatively expensive agents from the SGLT2 inhibitor and GLP-1 receptor agonist classes has often been problematic.

“There are issues of cost, coverage, and access” using these medications, as well as limited data on cost-effectiveness, Dr. Paik acknowledged. Additional issues that have helped generate prescribing lags include concerns about possible adverse effects, low familiarity by providers with these drugs early on, and limited trial experience using them in older patients. The process of clinicians growing more comfortable prescribing these new agents has depended on their “working through the evidence,” she explained.

The FDA’s approval in July 2021 of finerenone (Kerendia) for treating patients with type 2 diabetes and chronic kidney disease threw yet another new variable into the prescribing mix for these patients.

“SGLT2 inhibitors are here to stay as a new standard of care for patients with diabetic kidney disease, but combination with finerenone might be especially useful for patients with diabetic kidney disease and heart failure,” Dr. Tuttle suggested. A new generation of clinical trials will likely soon launch to test these combinations, she predicted.

Dr. Paik had no disclosures. Dr. Tuttle has been a consultant to AstraZeneca, Bayer, Boehringer Ingelheim, Gilead, Goldfinch Bio, Eli Lilly, and Novo Nordisk.

[email protected]

U.S. prescribing data from 160,000 adults with type 2 diabetes and diabetic kidney disease showed a notable uptick in new prescriptions for sodium-glucose cotransporter 2 inhibitors and less dramatic gains for glucagonlike peptide–1 receptor agonists during 2019 and continuing into early 2020, compared with prior years, with usage levels of both classes during the first quarter of 2020 rivaling those of more traditional agents including metformin and insulin.

During the first 3 months of 2020, initiation of a SGLT2 inhibitor constituted 13% of all new starts of an antidiabetes drug among adults with type 2 diabetes and diabetic kidney disease (DKD). This compared with initiation rates during the same early 2020 period of 17% for GLP-1 receptor agonists, 19% for metformin, 16% for sulfonylureas, 15% for insulins, 14% for thiazolidinediones, and 6% for dipeptidyl peptidase–4 inhibitors, the seven drug classes examined in a study published in Diabetes Care.

Early 2020 was the first time that starts of a GLP-1 receptor agonist ranked second (behind only metformin) among these seven drug classes in the studied U.S. population, and early 2020 also marked an unprecedentedly high start rate for SGLT2 inhibitors that nearly tripled the roughly 5% rate in place as recently as 2018.
 

Rises are ‘what we expected’

The recent rise of SGLT2 inhibitors and GLP-1 receptor agonists in these patients “was what we expected,” given the evidence for both classes in slowing progression of DKD, said Julie M. Paik, MD, senior author on the study and a nephrologist and pharmacoepidemiologist at Brigham and Women’s Hospital in Boston.

“We’ve seen other beneficial drugs slow on the uptake, so it’s not surprising to see it here, and I’m optimistic” about further increases going forward, she said in an interview.

Both drug classes “were originally marketed as diabetes drugs,” and it is only since 2019, with the publication of trials showing dramatic renal benefits from canagliflozin (Invokana) in CREDENCE, and from dapagliflozin (Farxiga) in DAPA-CKD in 2020 that the evidence became truly compelling for SGLT2 inhibitors. This evidence also led to new renal-protection indications approved by the Food and Drug Administration for canagliflozin and for dapagliflozin, noted Dr. Paik.

Evidence for renal protection also emerged in 2017 for the GLP-1 receptor agonist liraglutide (Victoza) in the LEADER trial, and for dulaglutide (Trulicity) in the AWARD-7 trial, although neither drug has received a renal indication in its labeling.

By 2020, guidelines for managing patients with type 2 diabetes and chronic kidney disease from the influential Kidney Disease: Improving Global Outcomes organization had identified agents from the SGLT2 inhibitor class as top-tier options, along with metformin, for treating these patients, with agents from the GLP-1 receptor agonist class as the top third class to add in patients who require additional glycemic control.

Additional analyses Dr. Paik and associates ran showed how this played out in terms of which specialists prescribed these drugs during the full period studied beginning in 2013. Throughout this roughly 7-year span, about 70% of the prescriptions written for either SGLT2 inhibitors or for GLP-1 receptor agonists were from internal medicine physicians, followed by about 20% written by endocrinologists. Prescriptions from nephrologists, as well as from cardiologists, have hovered at about 5% each, but seem poised to start rising based on the recently added indications and newer treatment recommendations.

“It’s good to see the recent uptick in use since 2019,” Katherine R. Tuttle, MD, commented in an interview. It’s a positive development for U.S. public health, “but we need to do more to disseminate and implement these life-, kidney-, and heart-saving therapies.”

Future use could approach 80% of DKD patients

Dr. Tuttle estimated that “target” levels of use for SGLT2 inhibitors and for GLP-1 receptor agonists “could reasonably approach 80%” for patients with type 2 diabetes and diabetic kidney disease.

“We will likely move to combination therapy” with simultaneous use of agents from both classes in a targeted way using “precision phenotyping based on clinical characteristics, and eventually perhaps by biomarkers, kidney biopsies, or both.” Combined treatment with both an SGLT2 inhibitor and a GLP-1 receptor agonist may be especially suited to patients with type 2 diabetes, atherosclerotic cardiovascular disease, low estimated glomerular filtration rate, and need for better glycemic control and weight loss, a profile that is “pretty typical” in real-world practice, said Dr. Tuttle, a nephrologist and endocrinologist and executive director for research at Providence Healthcare in Spokane, Wash.
 

Study included patients with commercial or Medicare Advantage coverage

The study used information in an Optum database that included patients enrolled in either commercial or in Medicare Advantage health insurance plans from 2013 to the first quarter of 2020. This included 160,489 adults with type 2 diabetes and DKD who started during that period at least one agent from any of the seven included drug classes.

This focus may have biased the findings because, overall, U.S. coverage of the relatively expensive agents from the SGLT2 inhibitor and GLP-1 receptor agonist classes has often been problematic.

“There are issues of cost, coverage, and access” using these medications, as well as limited data on cost-effectiveness, Dr. Paik acknowledged. Additional issues that have helped generate prescribing lags include concerns about possible adverse effects, low familiarity by providers with these drugs early on, and limited trial experience using them in older patients. The process of clinicians growing more comfortable prescribing these new agents has depended on their “working through the evidence,” she explained.

The FDA’s approval in July 2021 of finerenone (Kerendia) for treating patients with type 2 diabetes and chronic kidney disease threw yet another new variable into the prescribing mix for these patients.

“SGLT2 inhibitors are here to stay as a new standard of care for patients with diabetic kidney disease, but combination with finerenone might be especially useful for patients with diabetic kidney disease and heart failure,” Dr. Tuttle suggested. A new generation of clinical trials will likely soon launch to test these combinations, she predicted.

Dr. Paik had no disclosures. Dr. Tuttle has been a consultant to AstraZeneca, Bayer, Boehringer Ingelheim, Gilead, Goldfinch Bio, Eli Lilly, and Novo Nordisk.

[email protected]

The U.S. Food and Drug Administration approved empagliflozin (Jardiance) as a treatment for adults with heart failure with reduced ejection fraction (HFrEF) regardless of whether patients have diabetes on Aug. 18, making it the second agent from the sodium-glucose transporter 2 inhibitor class to received this indication.

Empagliflozin first received FDA marketing approval in 2014 for improving glycemic control in patients with type 2 diabetes, and in 2016 the agency added a second indication of reducing cardiovascular death in patients with type 2 diabetes and cardiovascular disease. The newly granted indication for patients with HFrEF without regard to glycemic status was for reducing the risk for cardiovascular death and hospitalization for heart failure, according to a statement from Boehringer Ingelheim and Lilly, the two companies that together market empagliflozin.

The statement also said that the approval allowed for empagliflozin treatment in patients with HFrEF and an estimated glomerular filtration rate (eGFR) as low as 20 mL/min per 1.73 m², in contrast to its indication for improving glycemic control in patients with type 2 diabetes that limits use to patients with an eGFR of at least 30 mL per 1.73 m².


EMPEROR-Reduced results drive approval

The FDA based its decision on results from the EMPEROR-Reduced study, first reported in August 2020, that showed treatment of patients with HFrEF with empagliflozin on top of standard therapy for a median of 16 months cut the incidence of cardiovascular death or hospitalization for worsening heart failure by 25% relative to placebo, and by an absolute 5.3%, compared with placebo-treated patients.

Patients enrolled in EMPEROR-Reduced had chronic heart failure in New York Heart Association functional class II-IV and with a left ventricular ejection fraction of 40% or less, the standard ejection fraction criterion for defining HFrEF. Half the enrolled patients had diabetes, and analysis showed no heterogeneity in the primary outcome response based on diabetes status at enrollment.


Empagliflozin joins dapagliflozin for treating HFrEF

Dapagliflozin (Farxiga) was the first agent from the SGLT2 inhibitor class to receive an FDA indication, in 2020, for treating patients with HFrEF regardless of their diabetes status, a decision based on results from the DAPA-HF trial. Results from DAPA-HF showed that treatment with dapagliflozin in patients with HFrEF for a median of 18 months led to a 26% relative reduction in the incidence of cardiovascular death or worsening heart failure and a 4.9% absolute reduction, compared with placebo when added to standard treatment. DAPA-HF enrolled patients using similar criteria to EMPEROR-Reduced, and 42% of enrolled patients had diabetes with no heterogeneity in the primary outcome related to baseline diabetes status.

Subsequent to the report of results from the EMPEROR-Reduced trial nearly a year ago, heart failure experts declared that treatment with an agent from the SGLT2 inhibitor class had become a “new pillar of foundational therapy for HFrEF,” and they urged rapid initiation of an SGLT2 inhibitor (along with other appropriate medications) at the time of initial diagnosis of HFrEF.

[email protected]

The U.S. Food and Drug Administration approved empagliflozin (Jardiance) as a treatment for adults with heart failure with reduced ejection fraction (HFrEF) regardless of whether patients have diabetes on Aug. 18, making it the second agent from the sodium-glucose transporter 2 inhibitor class to received this indication.

Empagliflozin first received FDA marketing approval in 2014 for improving glycemic control in patients with type 2 diabetes, and in 2016 the agency added a second indication of reducing cardiovascular death in patients with type 2 diabetes and cardiovascular disease. The newly granted indication for patients with HFrEF without regard to glycemic status was for reducing the risk for cardiovascular death and hospitalization for heart failure, according to a statement from Boehringer Ingelheim and Lilly, the two companies that together market empagliflozin.

The statement also said that the approval allowed for empagliflozin treatment in patients with HFrEF and an estimated glomerular filtration rate (eGFR) as low as 20 mL/min per 1.73 m², in contrast to its indication for improving glycemic control in patients with type 2 diabetes that limits use to patients with an eGFR of at least 30 mL per 1.73 m².


EMPEROR-Reduced results drive approval

The FDA based its decision on results from the EMPEROR-Reduced study, first reported in August 2020, that showed treatment of patients with HFrEF with empagliflozin on top of standard therapy for a median of 16 months cut the incidence of cardiovascular death or hospitalization for worsening heart failure by 25% relative to placebo, and by an absolute 5.3%, compared with placebo-treated patients.

Patients enrolled in EMPEROR-Reduced had chronic heart failure in New York Heart Association functional class II-IV and with a left ventricular ejection fraction of 40% or less, the standard ejection fraction criterion for defining HFrEF. Half the enrolled patients had diabetes, and analysis showed no heterogeneity in the primary outcome response based on diabetes status at enrollment.


Empagliflozin joins dapagliflozin for treating HFrEF

Dapagliflozin (Farxiga) was the first agent from the SGLT2 inhibitor class to receive an FDA indication, in 2020, for treating patients with HFrEF regardless of their diabetes status, a decision based on results from the DAPA-HF trial. Results from DAPA-HF showed that treatment with dapagliflozin in patients with HFrEF for a median of 18 months led to a 26% relative reduction in the incidence of cardiovascular death or worsening heart failure and a 4.9% absolute reduction, compared with placebo when added to standard treatment. DAPA-HF enrolled patients using similar criteria to EMPEROR-Reduced, and 42% of enrolled patients had diabetes with no heterogeneity in the primary outcome related to baseline diabetes status.

Subsequent to the report of results from the EMPEROR-Reduced trial nearly a year ago, heart failure experts declared that treatment with an agent from the SGLT2 inhibitor class had become a “new pillar of foundational therapy for HFrEF,” and they urged rapid initiation of an SGLT2 inhibitor (along with other appropriate medications) at the time of initial diagnosis of HFrEF.

[email protected]

The U.S. Food and Drug Administration approved empagliflozin (Jardiance) as a treatment for adults with heart failure with reduced ejection fraction (HFrEF) regardless of whether patients have diabetes on Aug. 18, making it the second agent from the sodium-glucose transporter 2 inhibitor class to received this indication.

Empagliflozin first received FDA marketing approval in 2014 for improving glycemic control in patients with type 2 diabetes, and in 2016 the agency added a second indication of reducing cardiovascular death in patients with type 2 diabetes and cardiovascular disease. The newly granted indication for patients with HFrEF without regard to glycemic status was for reducing the risk for cardiovascular death and hospitalization for heart failure, according to a statement from Boehringer Ingelheim and Lilly, the two companies that together market empagliflozin.

The statement also said that the approval allowed for empagliflozin treatment in patients with HFrEF and an estimated glomerular filtration rate (eGFR) as low as 20 mL/min per 1.73 m², in contrast to its indication for improving glycemic control in patients with type 2 diabetes that limits use to patients with an eGFR of at least 30 mL per 1.73 m².


EMPEROR-Reduced results drive approval

The FDA based its decision on results from the EMPEROR-Reduced study, first reported in August 2020, that showed treatment of patients with HFrEF with empagliflozin on top of standard therapy for a median of 16 months cut the incidence of cardiovascular death or hospitalization for worsening heart failure by 25% relative to placebo, and by an absolute 5.3%, compared with placebo-treated patients.

Patients enrolled in EMPEROR-Reduced had chronic heart failure in New York Heart Association functional class II-IV and with a left ventricular ejection fraction of 40% or less, the standard ejection fraction criterion for defining HFrEF. Half the enrolled patients had diabetes, and analysis showed no heterogeneity in the primary outcome response based on diabetes status at enrollment.


Empagliflozin joins dapagliflozin for treating HFrEF

Dapagliflozin (Farxiga) was the first agent from the SGLT2 inhibitor class to receive an FDA indication, in 2020, for treating patients with HFrEF regardless of their diabetes status, a decision based on results from the DAPA-HF trial. Results from DAPA-HF showed that treatment with dapagliflozin in patients with HFrEF for a median of 18 months led to a 26% relative reduction in the incidence of cardiovascular death or worsening heart failure and a 4.9% absolute reduction, compared with placebo when added to standard treatment. DAPA-HF enrolled patients using similar criteria to EMPEROR-Reduced, and 42% of enrolled patients had diabetes with no heterogeneity in the primary outcome related to baseline diabetes status.

Subsequent to the report of results from the EMPEROR-Reduced trial nearly a year ago, heart failure experts declared that treatment with an agent from the SGLT2 inhibitor class had become a “new pillar of foundational therapy for HFrEF,” and they urged rapid initiation of an SGLT2 inhibitor (along with other appropriate medications) at the time of initial diagnosis of HFrEF.

[email protected]

About one in six patients with heart failure in the United States are skipping doctors’ appointments, not taking their medications as directed, or forgoing some other type of care, and their recalcitrance actually ends up costing the health care system 20%-30% more per patient.

That’s according to a cross-sectional study using data from a large public database reported in JACC: Heart Failure on Aug. 11.

The investigators pooled data on 2,050 patients with HF enrolled in the Medical Expenditure Panel Survey, a public database sponsored by the Agency for Healthcare Research and Quality, from 2004 to 2015. Some 339 of those HF patients were classified in the forgone or delayed (F/D) care group. This is the first study to describe the cost impact of missed care in heart failure, lead author Alexander Thomas, MD, and colleagues wrote.

“I think we make a pretty strong case linking forgone care to higher cost,” Dr. Thomas said in an interview. “Obviously this is a prospective study, so causality is not made based on this study, but there’s a strong association, it appears.” He acknowledged that prospective studies would need to confirm these findings, but added, “I think even this is enough to give us cause to look at the somewhat granular reasons as to why patients are forgoing care.”

Average annual total costs for adults who skipped care were $8,027 higher than for those heart failure patients who kept up with their regimen (P = .02). However, for people 65 and older, the cost differential was even higher: $10,581 (P = .02), which translates into a 50% premium over average costs for compliant elderly patients, noted Dr. Thomas, a cardiovascular medicine fellow at Yale University, New Haven, Conn.

In the nonelderly F/D group, average per-patient costs were $27,000 annually; in the elderly, it was a little over $30,000.

However, nonelderly patients were more likely to forgo care. While 16% of all patients in the study were considered F/D, 27% of nonelderly patients were classified as such vs. 10% of the elderly.
 

Elderly forgoing care drives cost

But, Dr. Thomas said, elderly patients forgoing care drive higher costs because they’re more fragile, have more comorbidities and more advanced heart failure, and tend to decompensate more quickly. “For them, missing one appointment or missing some medications is not nearly as well tolerated as it is in the younger population,” he said. In these elderly patients, inpatient costs accounted for 75% of the increased expense, Dr. Thomas added.

Reasons for forgoing care range from the obvious, such as cost or insurance issues – 191 individuals cited the former, 69 the latter – to more granular reasons, such as transportation issues or lack of time.

The study also found a number of demographic features that were associated with forgone or delayed care: non-Hispanic Black race; lack of insurance; low-income; and worse cardiovascular risk factor profiles.

The study’s call to action is for further research and policy changes aimed at better understanding barriers to care and improving access. “It’s a really great driver for policy interventions to attack this problem and to have the financial backing also to put money and resources into fixing this problem – which is probably not only going to decrease costs and allow more cost-effective care, but lead to better outcomes in this population as well,” Dr. Thomas said.

The sentiment for policy changes was echoed in an accompanying editorial by Khadijah Breathett, MD, MS, a heart failure/transplant cardiologist at the Sarver Heart Center, University of Arizona, Tucson. But she also noted the study exposed insufficiencies with Medicare. In an interview, she expanded on that. 

“Our system is failing this population,” she said of the elderly with heart failure who have forgone care. “I think that’s because of the complexity of our system: One person’s Medicare is different from another’s. There are multiple parts to Medicare that provide different forms of care – hospital care, prescription care, and so forth – and everyone does not necessarily have the same parts.” Also, many Medicare beneficiaries are still working, and “they’re still trying to figure out how to make ends meet,” Dr. Breathett added.

The study also showed that the pre-Medicare population requires the attention of policymakers. “How do we help the younger population so that they don’t develop the comorbidities that worsen their quality of life and contribute to rising hospital costs?” Dr. Breathett said.

Dr. Thomas had no financial relationships to disclose. Dr. Breathett has received grants from the National Heart, Lung, and Blood Institute.

About one in six patients with heart failure in the United States are skipping doctors’ appointments, not taking their medications as directed, or forgoing some other type of care, and their recalcitrance actually ends up costing the health care system 20%-30% more per patient.

That’s according to a cross-sectional study using data from a large public database reported in JACC: Heart Failure on Aug. 11.

The investigators pooled data on 2,050 patients with HF enrolled in the Medical Expenditure Panel Survey, a public database sponsored by the Agency for Healthcare Research and Quality, from 2004 to 2015. Some 339 of those HF patients were classified in the forgone or delayed (F/D) care group. This is the first study to describe the cost impact of missed care in heart failure, lead author Alexander Thomas, MD, and colleagues wrote.

“I think we make a pretty strong case linking forgone care to higher cost,” Dr. Thomas said in an interview. “Obviously this is a prospective study, so causality is not made based on this study, but there’s a strong association, it appears.” He acknowledged that prospective studies would need to confirm these findings, but added, “I think even this is enough to give us cause to look at the somewhat granular reasons as to why patients are forgoing care.”

Average annual total costs for adults who skipped care were $8,027 higher than for those heart failure patients who kept up with their regimen (P = .02). However, for people 65 and older, the cost differential was even higher: $10,581 (P = .02), which translates into a 50% premium over average costs for compliant elderly patients, noted Dr. Thomas, a cardiovascular medicine fellow at Yale University, New Haven, Conn.

In the nonelderly F/D group, average per-patient costs were $27,000 annually; in the elderly, it was a little over $30,000.

However, nonelderly patients were more likely to forgo care. While 16% of all patients in the study were considered F/D, 27% of nonelderly patients were classified as such vs. 10% of the elderly.
 

Elderly forgoing care drives cost

But, Dr. Thomas said, elderly patients forgoing care drive higher costs because they’re more fragile, have more comorbidities and more advanced heart failure, and tend to decompensate more quickly. “For them, missing one appointment or missing some medications is not nearly as well tolerated as it is in the younger population,” he said. In these elderly patients, inpatient costs accounted for 75% of the increased expense, Dr. Thomas added.

Reasons for forgoing care range from the obvious, such as cost or insurance issues – 191 individuals cited the former, 69 the latter – to more granular reasons, such as transportation issues or lack of time.

The study also found a number of demographic features that were associated with forgone or delayed care: non-Hispanic Black race; lack of insurance; low-income; and worse cardiovascular risk factor profiles.

The study’s call to action is for further research and policy changes aimed at better understanding barriers to care and improving access. “It’s a really great driver for policy interventions to attack this problem and to have the financial backing also to put money and resources into fixing this problem – which is probably not only going to decrease costs and allow more cost-effective care, but lead to better outcomes in this population as well,” Dr. Thomas said.

The sentiment for policy changes was echoed in an accompanying editorial by Khadijah Breathett, MD, MS, a heart failure/transplant cardiologist at the Sarver Heart Center, University of Arizona, Tucson. But she also noted the study exposed insufficiencies with Medicare. In an interview, she expanded on that. 

“Our system is failing this population,” she said of the elderly with heart failure who have forgone care. “I think that’s because of the complexity of our system: One person’s Medicare is different from another’s. There are multiple parts to Medicare that provide different forms of care – hospital care, prescription care, and so forth – and everyone does not necessarily have the same parts.” Also, many Medicare beneficiaries are still working, and “they’re still trying to figure out how to make ends meet,” Dr. Breathett added.

The study also showed that the pre-Medicare population requires the attention of policymakers. “How do we help the younger population so that they don’t develop the comorbidities that worsen their quality of life and contribute to rising hospital costs?” Dr. Breathett said.

Dr. Thomas had no financial relationships to disclose. Dr. Breathett has received grants from the National Heart, Lung, and Blood Institute.

About one in six patients with heart failure in the United States are skipping doctors’ appointments, not taking their medications as directed, or forgoing some other type of care, and their recalcitrance actually ends up costing the health care system 20%-30% more per patient.

That’s according to a cross-sectional study using data from a large public database reported in JACC: Heart Failure on Aug. 11.

The investigators pooled data on 2,050 patients with HF enrolled in the Medical Expenditure Panel Survey, a public database sponsored by the Agency for Healthcare Research and Quality, from 2004 to 2015. Some 339 of those HF patients were classified in the forgone or delayed (F/D) care group. This is the first study to describe the cost impact of missed care in heart failure, lead author Alexander Thomas, MD, and colleagues wrote.

“I think we make a pretty strong case linking forgone care to higher cost,” Dr. Thomas said in an interview. “Obviously this is a prospective study, so causality is not made based on this study, but there’s a strong association, it appears.” He acknowledged that prospective studies would need to confirm these findings, but added, “I think even this is enough to give us cause to look at the somewhat granular reasons as to why patients are forgoing care.”

Average annual total costs for adults who skipped care were $8,027 higher than for those heart failure patients who kept up with their regimen (P = .02). However, for people 65 and older, the cost differential was even higher: $10,581 (P = .02), which translates into a 50% premium over average costs for compliant elderly patients, noted Dr. Thomas, a cardiovascular medicine fellow at Yale University, New Haven, Conn.

In the nonelderly F/D group, average per-patient costs were $27,000 annually; in the elderly, it was a little over $30,000.

However, nonelderly patients were more likely to forgo care. While 16% of all patients in the study were considered F/D, 27% of nonelderly patients were classified as such vs. 10% of the elderly.
 

Elderly forgoing care drives cost

But, Dr. Thomas said, elderly patients forgoing care drive higher costs because they’re more fragile, have more comorbidities and more advanced heart failure, and tend to decompensate more quickly. “For them, missing one appointment or missing some medications is not nearly as well tolerated as it is in the younger population,” he said. In these elderly patients, inpatient costs accounted for 75% of the increased expense, Dr. Thomas added.

Reasons for forgoing care range from the obvious, such as cost or insurance issues – 191 individuals cited the former, 69 the latter – to more granular reasons, such as transportation issues or lack of time.

The study also found a number of demographic features that were associated with forgone or delayed care: non-Hispanic Black race; lack of insurance; low-income; and worse cardiovascular risk factor profiles.

The study’s call to action is for further research and policy changes aimed at better understanding barriers to care and improving access. “It’s a really great driver for policy interventions to attack this problem and to have the financial backing also to put money and resources into fixing this problem – which is probably not only going to decrease costs and allow more cost-effective care, but lead to better outcomes in this population as well,” Dr. Thomas said.

The sentiment for policy changes was echoed in an accompanying editorial by Khadijah Breathett, MD, MS, a heart failure/transplant cardiologist at the Sarver Heart Center, University of Arizona, Tucson. But she also noted the study exposed insufficiencies with Medicare. In an interview, she expanded on that. 

“Our system is failing this population,” she said of the elderly with heart failure who have forgone care. “I think that’s because of the complexity of our system: One person’s Medicare is different from another’s. There are multiple parts to Medicare that provide different forms of care – hospital care, prescription care, and so forth – and everyone does not necessarily have the same parts.” Also, many Medicare beneficiaries are still working, and “they’re still trying to figure out how to make ends meet,” Dr. Breathett added.

The study also showed that the pre-Medicare population requires the attention of policymakers. “How do we help the younger population so that they don’t develop the comorbidities that worsen their quality of life and contribute to rising hospital costs?” Dr. Breathett said.

Dr. Thomas had no financial relationships to disclose. Dr. Breathett has received grants from the National Heart, Lung, and Blood Institute.

In April, a group of more than a dozen cardiologists at St. Louis Heart and Vascular (SLHV) lost their privileges at SSM Health, an eight-hospital system in St. Louis.

The physicians did not lose their privileges because of a clinical failure. Rather, it was because of SSM’s decision to enter into an exclusive contract with another set of cardiologists.

“The current situation is economically untenable for us,” said Harvey Serota, MD, founder and medical director of SLHV. “This is an existential threat to the practice.”

Because of the exclusive contract, many of SLHV’s patients are now being redirected to SSM-contracted cardiologists. Volume for the group’s new $15 million catheterization lab has plummeted. SLHV is suing SSM to restore its privileges, claiming lack of due process, restraint of trade, interference with its business, and breach of contract.

Losing privileges because a hospital seeks to increase their profits is becoming all too familiar for many independent specialists in fields such as cardiology, orthopedic surgery, and urology, as the hospitals that hosted them become their competitors and forge exclusive contracts with opposing groups.

What can these doctors do if they’re shut out? File a lawsuit, as SLHV has done? Demand a hearing before the medical staff and try to resolve the problem? Or simply give up their privileges and move on?

Unfortunately, none of these approaches offer a quick or certain solution, and each comes with risks.

Generally, courts have upheld hospitals’ use of exclusive contracts, which is also known as economic credentialing, says Barry F. Rosen, a health law attorney at Gordon Feinblatt, in Baltimore.

“Courts have long recognized exclusive contracts, and challenges by excluded doctors usually fail,” he says.

However, Mr. Rosen can cite several examples in which excluded doctors launched legal challenges that prevailed, owing to nuances in the law. The legal field in this area is tangled, and it varies by state.
 

Can hospitals make exclusive deals?

Hospitals have long used exclusive contracts for hospital-based specialists – anesthesiologists, radiologists, pathologists, emergency physicians, and hospitalists. They say that restricting patients to one group of anesthesiologists or radiologists enhances operational efficiency and that these contracts do not disrupt patients, because patients have no ties to hospital-based physicians. Such contracts are often more profitable for the hospital because of the negotiated rates.

Exclusive contracts in other specialties, however, are less accepted because they involve markedly different strategies and have different effects. In such cases, the hospital is no longer simply enhancing operational efficiency but is competing with physicians on staff, and the arrangement can disrupt the care of patients of the excluded doctors.

In the courts, these concerns might form the basis of an antitrust action or a claim of tortious interference with physicians’ ability to provide care for their patients, but neither claim is easy to win, Mr. Rosen says.

In antitrust cases, “the issue is not whether the excluded doctor was injured but whether the action harmed competition,” Mr. Rosen says. “Will the exclusion lead to higher prices?”

In the case of interference with patient care, “you will always find interference by one entity in the affairs of another,” he says, “but tortious interference applies to situations where something nefarious is going on, such as the other side was out to destroy your business and create a monopoly.”

Hospitals may try to restrict the privileges of physicians who invest in competing facilities such as cath labs and ambulatory surgery centers (ASCs), says Gregory Mertz, managing director of Physician Strategies Group, a consultancy in Virginia Beach.

“However, any revenge that a hospital might take against the doctors who started an ASC would usually not be publicly admitted,” Mr. Mertz says. “Revenge would be exacted in subtle ways.”

In the St. Louis situation, SSM did not cite SLHV’s cath lab as a reason for its exclusive contract. SSM stated in court documents that the decision was based on the recommendations of an expert panel. Furthermore, SSM said the board created the panel in response to a state report that cited the limited experience of some SLHV cardiologists in treating a rare type of heart attack.

Mr. Mertz says the board’s interest in the state’s concern and then its forming the special panel lent a great deal of legitimacy to SSM’s decision to start an exclusive contract. “SSM can show evidence that the board’s decision was based on a clinical matter and not on trying to squeeze out the cardiologists,” he says.

In SLHV’s defense, Dr. Serota says the practice offered to stop taking calls for the type of heart attack that was cited, but the hospital did not respond to its offer. He says SSM should have consulted the hospital’s medical staff to address the state’s concern and to create the exclusive contract, because these decisions involved clinical issues that the medical staff understands better than the board.

The law, however, does not require a hospital board to consult with its medical staff, says Alice G. Gosfield, a health care attorney in Philadelphia. “The board has ultimate legal control of everything in the hospital,” she says. However, the board often delegates certain functions to the medical staff in the hospital bylaws, and depending on the wording of the bylaws, it is still possible that the board violated the bylaws, Ms. Gosfield adds.
 

Can excluded physicians get peer review?

Can the hospital medical staff help restore the privileges of excluded physicians? Don’t these physicians have the right to peer review – a hearing before the medical staff?

Indeed, the Joint Commission, which accredits hospitals, states that the hospital must have “mechanisms, including a fair hearing and appeal process, for addressing adverse decisions for existing medical staff members and other individuals holding clinical privileges for renewal, revocation, or revision of clinical privileges.”

However, excluded physicians may not have a right to a hearing if they have not been fully stripped of privileges. SSM discontinued adult cardiology privileges for SLHV doctors but retained some doctors’ internal medicine privileges. Dr. Serota says internal medicine privileges are useless to cardiologists, but because the doctors’ privileges had not been fully removed, they cannot ask for a hearing.

More fundamentally, exclusive contracts are not a good fit for peer review. Mr. Rosen says the hearings were designed to review the physicians’ clinical competence or behavior, but excluded physicians do not have these problems. About all the hearing could focus on is the hospital’s policy, which the board would not want to allow. To avoid this, “the hospital might rule out a hearing as contrary to the intent of the bylaws,” Mr. Rosen says.

Furthermore, even if peer review goes forward, “what the medical staff decides is only advisory, and the hospital board makes the final decision,” Mr. Rosen says. He notes that the doctor could challenge the decision in court, but the hospital might still prevail.
 

Excluded physicians sometimes prevail

Although it is rare for excluded physicians to win a lawsuit against their hospital, it does happen, says Michael R. Callahan, health lawyer at Katten Muchin Rosenman, in Chicago.

Mr. Callahan cites a 2010 decision by the Arkansas Supreme Court that stopped the state’s largest health system from denying physicians’ privileges. Among other things, the hospital was found to have tortiously interfered with the physicians’ contracts with patients.

In a 2007 decision, a West Virginia court ruled that hospitals that have a mission to serve the public cannot exclude physicians for nonquality issues. In addition, some states, such as Texas, limit the economic factors that can be considered when credentialing decisions are made. Other states, such as Ohio, give hospitals a great deal of leeway to alter credentialing.

Dr. Serota is optimistic about his Missouri lawsuit. Although the judge in the case did not immediately grant SLHV’s request for restoration of privileges while the case proceeds, she did grant expedited discovery – allowing SLHV to obtain documents from SSM that could strengthen the doctors’ case – and she agreed to a hearing on SLHV’s request for a temporary restoration of privileges.

Ms. Gosfield says Dr. Serota’s optimism seems justified, but she adds that such cases cost a lot of money and that they may still not be winnable.

Often plaintiffs can settle lawsuits before they go to trial, but Mr. Callahan says hospitals are loath to restore privileges in a settlement because they don’t want to undermine an exclusivity deal. “The exclusive group expects a certain volume, which can’t be reached if the competing doctors are allowed back in,” he says.
 

Many physicians don’t challenge the exclusion

Quite often, excluded doctors decide not to challenge the decision. For example, Dr. Serota says groups of orthopedic surgeons and urologists have decided not to challenge similar decisions by SSM. “They wanted to move on,” he says.

Mr. Callahan says many excluded doctors also don’t even ask for a hearing. “They expect that the hospital’s decision will be upheld,” he says.

This was the case for Devendra K. Amin, MD, an independent cardiologist in Easton, Pa. Dr. Amin has not had any hospital privileges since July 2020. Even though he is board certified in interventional cardiology, which involves catheterization, Dr. Amin says he cannot perform these procedures because they can only be performed in a hospital in the area.

In the 1990s, Dr. Amin says, he had invasive cardiology privileges at five hospitals, but then those hospitals consolidated, and the remaining ones started constricting his privileges. First he could no longer work in the emergency department, then he could no longer read echocardiograms and interpret stress test results, because that work was assigned exclusively to employed doctors, he says.

Then the one remaining hospital announced that privileges would only be available to physicians by invitation, and he was not invited. Dr. Amin says he could have regained general cardiology privileges if he had accepted employment at the hospital, but he did not want to do this. A recruiter and the head of the cardiology section at the hospital even took him out to dinner 2 years ago to discuss employment, but there was a stipulation that the hospital would not agree to.

“I wanted to get back my interventional privileges back,” Dr. Amin says, “but they told me that would not be possible because they had an exclusive contract with a group.”

Dr. Amin says that now, he can only work as a general cardiologist with reduced volume. He says primary care physicians in the local hospital systems only refer to cardiologists within their systems. “When these patients do come to me, it is only because they specifically requested to see me,” Dr. Amin says.

He does not want to challenge the decisions regarding privileging. “Look, I am 68 years old,” Dr. Amin says. “I’m not retiring yet, but I don’t want to get into a battle with a hospital that has very deep pockets. I’m not a confrontational person to begin with, and I don’t want to spend the next 10 years of my life in litigation.”
 

Diverging expectations

The law on exclusive contracts does not provide easy answers for excluded doctors, and often it defies physicians’ conception of their own role in the hospital.

Many physicians expect the hospital to be a haven where they can do their work without being cut out by a competitor. This view is reinforced by organizations such as the American Medical Association.

The AMA Council on Medical Service states that privileges “can only be abridged upon recommendation of the medical staff and only for reason related to professional competence, adherence to standards of care, and other parameters agreed to by the medical staff.”

But the courts don’t tend to agree with that position. “Hospitals have a fiduciary duty to protect their own financial interests,” Mr. Callahan says. “This may involve anything that furthers the hospital’s mission to provide high-quality health care services to its patient community.”

At the same time, however, there are plenty of instances in which courts have ruled that exclusive contracts had gone too far. But usually it takes a lawyer experienced in these cases to know what those exceptions are.

A version of this article first appeared on Medscape.com.

In April, a group of more than a dozen cardiologists at St. Louis Heart and Vascular (SLHV) lost their privileges at SSM Health, an eight-hospital system in St. Louis.

The physicians did not lose their privileges because of a clinical failure. Rather, it was because of SSM’s decision to enter into an exclusive contract with another set of cardiologists.

“The current situation is economically untenable for us,” said Harvey Serota, MD, founder and medical director of SLHV. “This is an existential threat to the practice.”

Because of the exclusive contract, many of SLHV’s patients are now being redirected to SSM-contracted cardiologists. Volume for the group’s new $15 million catheterization lab has plummeted. SLHV is suing SSM to restore its privileges, claiming lack of due process, restraint of trade, interference with its business, and breach of contract.

Losing privileges because a hospital seeks to increase their profits is becoming all too familiar for many independent specialists in fields such as cardiology, orthopedic surgery, and urology, as the hospitals that hosted them become their competitors and forge exclusive contracts with opposing groups.

What can these doctors do if they’re shut out? File a lawsuit, as SLHV has done? Demand a hearing before the medical staff and try to resolve the problem? Or simply give up their privileges and move on?

Unfortunately, none of these approaches offer a quick or certain solution, and each comes with risks.

Generally, courts have upheld hospitals’ use of exclusive contracts, which is also known as economic credentialing, says Barry F. Rosen, a health law attorney at Gordon Feinblatt, in Baltimore.

“Courts have long recognized exclusive contracts, and challenges by excluded doctors usually fail,” he says.

However, Mr. Rosen can cite several examples in which excluded doctors launched legal challenges that prevailed, owing to nuances in the law. The legal field in this area is tangled, and it varies by state.
 

Can hospitals make exclusive deals?

Hospitals have long used exclusive contracts for hospital-based specialists – anesthesiologists, radiologists, pathologists, emergency physicians, and hospitalists. They say that restricting patients to one group of anesthesiologists or radiologists enhances operational efficiency and that these contracts do not disrupt patients, because patients have no ties to hospital-based physicians. Such contracts are often more profitable for the hospital because of the negotiated rates.

Exclusive contracts in other specialties, however, are less accepted because they involve markedly different strategies and have different effects. In such cases, the hospital is no longer simply enhancing operational efficiency but is competing with physicians on staff, and the arrangement can disrupt the care of patients of the excluded doctors.

In the courts, these concerns might form the basis of an antitrust action or a claim of tortious interference with physicians’ ability to provide care for their patients, but neither claim is easy to win, Mr. Rosen says.

In antitrust cases, “the issue is not whether the excluded doctor was injured but whether the action harmed competition,” Mr. Rosen says. “Will the exclusion lead to higher prices?”

In the case of interference with patient care, “you will always find interference by one entity in the affairs of another,” he says, “but tortious interference applies to situations where something nefarious is going on, such as the other side was out to destroy your business and create a monopoly.”

Hospitals may try to restrict the privileges of physicians who invest in competing facilities such as cath labs and ambulatory surgery centers (ASCs), says Gregory Mertz, managing director of Physician Strategies Group, a consultancy in Virginia Beach.

“However, any revenge that a hospital might take against the doctors who started an ASC would usually not be publicly admitted,” Mr. Mertz says. “Revenge would be exacted in subtle ways.”

In the St. Louis situation, SSM did not cite SLHV’s cath lab as a reason for its exclusive contract. SSM stated in court documents that the decision was based on the recommendations of an expert panel. Furthermore, SSM said the board created the panel in response to a state report that cited the limited experience of some SLHV cardiologists in treating a rare type of heart attack.

Mr. Mertz says the board’s interest in the state’s concern and then its forming the special panel lent a great deal of legitimacy to SSM’s decision to start an exclusive contract. “SSM can show evidence that the board’s decision was based on a clinical matter and not on trying to squeeze out the cardiologists,” he says.

In SLHV’s defense, Dr. Serota says the practice offered to stop taking calls for the type of heart attack that was cited, but the hospital did not respond to its offer. He says SSM should have consulted the hospital’s medical staff to address the state’s concern and to create the exclusive contract, because these decisions involved clinical issues that the medical staff understands better than the board.

The law, however, does not require a hospital board to consult with its medical staff, says Alice G. Gosfield, a health care attorney in Philadelphia. “The board has ultimate legal control of everything in the hospital,” she says. However, the board often delegates certain functions to the medical staff in the hospital bylaws, and depending on the wording of the bylaws, it is still possible that the board violated the bylaws, Ms. Gosfield adds.
 

Can excluded physicians get peer review?

Can the hospital medical staff help restore the privileges of excluded physicians? Don’t these physicians have the right to peer review – a hearing before the medical staff?

Indeed, the Joint Commission, which accredits hospitals, states that the hospital must have “mechanisms, including a fair hearing and appeal process, for addressing adverse decisions for existing medical staff members and other individuals holding clinical privileges for renewal, revocation, or revision of clinical privileges.”

However, excluded physicians may not have a right to a hearing if they have not been fully stripped of privileges. SSM discontinued adult cardiology privileges for SLHV doctors but retained some doctors’ internal medicine privileges. Dr. Serota says internal medicine privileges are useless to cardiologists, but because the doctors’ privileges had not been fully removed, they cannot ask for a hearing.

More fundamentally, exclusive contracts are not a good fit for peer review. Mr. Rosen says the hearings were designed to review the physicians’ clinical competence or behavior, but excluded physicians do not have these problems. About all the hearing could focus on is the hospital’s policy, which the board would not want to allow. To avoid this, “the hospital might rule out a hearing as contrary to the intent of the bylaws,” Mr. Rosen says.

Furthermore, even if peer review goes forward, “what the medical staff decides is only advisory, and the hospital board makes the final decision,” Mr. Rosen says. He notes that the doctor could challenge the decision in court, but the hospital might still prevail.
 

Excluded physicians sometimes prevail

Although it is rare for excluded physicians to win a lawsuit against their hospital, it does happen, says Michael R. Callahan, health lawyer at Katten Muchin Rosenman, in Chicago.

Mr. Callahan cites a 2010 decision by the Arkansas Supreme Court that stopped the state’s largest health system from denying physicians’ privileges. Among other things, the hospital was found to have tortiously interfered with the physicians’ contracts with patients.

In a 2007 decision, a West Virginia court ruled that hospitals that have a mission to serve the public cannot exclude physicians for nonquality issues. In addition, some states, such as Texas, limit the economic factors that can be considered when credentialing decisions are made. Other states, such as Ohio, give hospitals a great deal of leeway to alter credentialing.

Dr. Serota is optimistic about his Missouri lawsuit. Although the judge in the case did not immediately grant SLHV’s request for restoration of privileges while the case proceeds, she did grant expedited discovery – allowing SLHV to obtain documents from SSM that could strengthen the doctors’ case – and she agreed to a hearing on SLHV’s request for a temporary restoration of privileges.

Ms. Gosfield says Dr. Serota’s optimism seems justified, but she adds that such cases cost a lot of money and that they may still not be winnable.

Often plaintiffs can settle lawsuits before they go to trial, but Mr. Callahan says hospitals are loath to restore privileges in a settlement because they don’t want to undermine an exclusivity deal. “The exclusive group expects a certain volume, which can’t be reached if the competing doctors are allowed back in,” he says.
 

Many physicians don’t challenge the exclusion

Quite often, excluded doctors decide not to challenge the decision. For example, Dr. Serota says groups of orthopedic surgeons and urologists have decided not to challenge similar decisions by SSM. “They wanted to move on,” he says.

Mr. Callahan says many excluded doctors also don’t even ask for a hearing. “They expect that the hospital’s decision will be upheld,” he says.

This was the case for Devendra K. Amin, MD, an independent cardiologist in Easton, Pa. Dr. Amin has not had any hospital privileges since July 2020. Even though he is board certified in interventional cardiology, which involves catheterization, Dr. Amin says he cannot perform these procedures because they can only be performed in a hospital in the area.

In the 1990s, Dr. Amin says, he had invasive cardiology privileges at five hospitals, but then those hospitals consolidated, and the remaining ones started constricting his privileges. First he could no longer work in the emergency department, then he could no longer read echocardiograms and interpret stress test results, because that work was assigned exclusively to employed doctors, he says.

Then the one remaining hospital announced that privileges would only be available to physicians by invitation, and he was not invited. Dr. Amin says he could have regained general cardiology privileges if he had accepted employment at the hospital, but he did not want to do this. A recruiter and the head of the cardiology section at the hospital even took him out to dinner 2 years ago to discuss employment, but there was a stipulation that the hospital would not agree to.

“I wanted to get back my interventional privileges back,” Dr. Amin says, “but they told me that would not be possible because they had an exclusive contract with a group.”

Dr. Amin says that now, he can only work as a general cardiologist with reduced volume. He says primary care physicians in the local hospital systems only refer to cardiologists within their systems. “When these patients do come to me, it is only because they specifically requested to see me,” Dr. Amin says.

He does not want to challenge the decisions regarding privileging. “Look, I am 68 years old,” Dr. Amin says. “I’m not retiring yet, but I don’t want to get into a battle with a hospital that has very deep pockets. I’m not a confrontational person to begin with, and I don’t want to spend the next 10 years of my life in litigation.”
 

Diverging expectations

The law on exclusive contracts does not provide easy answers for excluded doctors, and often it defies physicians’ conception of their own role in the hospital.

Many physicians expect the hospital to be a haven where they can do their work without being cut out by a competitor. This view is reinforced by organizations such as the American Medical Association.

The AMA Council on Medical Service states that privileges “can only be abridged upon recommendation of the medical staff and only for reason related to professional competence, adherence to standards of care, and other parameters agreed to by the medical staff.”

But the courts don’t tend to agree with that position. “Hospitals have a fiduciary duty to protect their own financial interests,” Mr. Callahan says. “This may involve anything that furthers the hospital’s mission to provide high-quality health care services to its patient community.”

At the same time, however, there are plenty of instances in which courts have ruled that exclusive contracts had gone too far. But usually it takes a lawyer experienced in these cases to know what those exceptions are.

A version of this article first appeared on Medscape.com.

In April, a group of more than a dozen cardiologists at St. Louis Heart and Vascular (SLHV) lost their privileges at SSM Health, an eight-hospital system in St. Louis.

The physicians did not lose their privileges because of a clinical failure. Rather, it was because of SSM’s decision to enter into an exclusive contract with another set of cardiologists.

“The current situation is economically untenable for us,” said Harvey Serota, MD, founder and medical director of SLHV. “This is an existential threat to the practice.”

Because of the exclusive contract, many of SLHV’s patients are now being redirected to SSM-contracted cardiologists. Volume for the group’s new $15 million catheterization lab has plummeted. SLHV is suing SSM to restore its privileges, claiming lack of due process, restraint of trade, interference with its business, and breach of contract.

Losing privileges because a hospital seeks to increase their profits is becoming all too familiar for many independent specialists in fields such as cardiology, orthopedic surgery, and urology, as the hospitals that hosted them become their competitors and forge exclusive contracts with opposing groups.

What can these doctors do if they’re shut out? File a lawsuit, as SLHV has done? Demand a hearing before the medical staff and try to resolve the problem? Or simply give up their privileges and move on?

Unfortunately, none of these approaches offer a quick or certain solution, and each comes with risks.

Generally, courts have upheld hospitals’ use of exclusive contracts, which is also known as economic credentialing, says Barry F. Rosen, a health law attorney at Gordon Feinblatt, in Baltimore.

“Courts have long recognized exclusive contracts, and challenges by excluded doctors usually fail,” he says.

However, Mr. Rosen can cite several examples in which excluded doctors launched legal challenges that prevailed, owing to nuances in the law. The legal field in this area is tangled, and it varies by state.
 

Can hospitals make exclusive deals?

Hospitals have long used exclusive contracts for hospital-based specialists – anesthesiologists, radiologists, pathologists, emergency physicians, and hospitalists. They say that restricting patients to one group of anesthesiologists or radiologists enhances operational efficiency and that these contracts do not disrupt patients, because patients have no ties to hospital-based physicians. Such contracts are often more profitable for the hospital because of the negotiated rates.

Exclusive contracts in other specialties, however, are less accepted because they involve markedly different strategies and have different effects. In such cases, the hospital is no longer simply enhancing operational efficiency but is competing with physicians on staff, and the arrangement can disrupt the care of patients of the excluded doctors.

In the courts, these concerns might form the basis of an antitrust action or a claim of tortious interference with physicians’ ability to provide care for their patients, but neither claim is easy to win, Mr. Rosen says.

In antitrust cases, “the issue is not whether the excluded doctor was injured but whether the action harmed competition,” Mr. Rosen says. “Will the exclusion lead to higher prices?”

In the case of interference with patient care, “you will always find interference by one entity in the affairs of another,” he says, “but tortious interference applies to situations where something nefarious is going on, such as the other side was out to destroy your business and create a monopoly.”

Hospitals may try to restrict the privileges of physicians who invest in competing facilities such as cath labs and ambulatory surgery centers (ASCs), says Gregory Mertz, managing director of Physician Strategies Group, a consultancy in Virginia Beach.

“However, any revenge that a hospital might take against the doctors who started an ASC would usually not be publicly admitted,” Mr. Mertz says. “Revenge would be exacted in subtle ways.”

In the St. Louis situation, SSM did not cite SLHV’s cath lab as a reason for its exclusive contract. SSM stated in court documents that the decision was based on the recommendations of an expert panel. Furthermore, SSM said the board created the panel in response to a state report that cited the limited experience of some SLHV cardiologists in treating a rare type of heart attack.

Mr. Mertz says the board’s interest in the state’s concern and then its forming the special panel lent a great deal of legitimacy to SSM’s decision to start an exclusive contract. “SSM can show evidence that the board’s decision was based on a clinical matter and not on trying to squeeze out the cardiologists,” he says.

In SLHV’s defense, Dr. Serota says the practice offered to stop taking calls for the type of heart attack that was cited, but the hospital did not respond to its offer. He says SSM should have consulted the hospital’s medical staff to address the state’s concern and to create the exclusive contract, because these decisions involved clinical issues that the medical staff understands better than the board.

The law, however, does not require a hospital board to consult with its medical staff, says Alice G. Gosfield, a health care attorney in Philadelphia. “The board has ultimate legal control of everything in the hospital,” she says. However, the board often delegates certain functions to the medical staff in the hospital bylaws, and depending on the wording of the bylaws, it is still possible that the board violated the bylaws, Ms. Gosfield adds.
 

Can excluded physicians get peer review?

Can the hospital medical staff help restore the privileges of excluded physicians? Don’t these physicians have the right to peer review – a hearing before the medical staff?

Indeed, the Joint Commission, which accredits hospitals, states that the hospital must have “mechanisms, including a fair hearing and appeal process, for addressing adverse decisions for existing medical staff members and other individuals holding clinical privileges for renewal, revocation, or revision of clinical privileges.”

However, excluded physicians may not have a right to a hearing if they have not been fully stripped of privileges. SSM discontinued adult cardiology privileges for SLHV doctors but retained some doctors’ internal medicine privileges. Dr. Serota says internal medicine privileges are useless to cardiologists, but because the doctors’ privileges had not been fully removed, they cannot ask for a hearing.

More fundamentally, exclusive contracts are not a good fit for peer review. Mr. Rosen says the hearings were designed to review the physicians’ clinical competence or behavior, but excluded physicians do not have these problems. About all the hearing could focus on is the hospital’s policy, which the board would not want to allow. To avoid this, “the hospital might rule out a hearing as contrary to the intent of the bylaws,” Mr. Rosen says.

Furthermore, even if peer review goes forward, “what the medical staff decides is only advisory, and the hospital board makes the final decision,” Mr. Rosen says. He notes that the doctor could challenge the decision in court, but the hospital might still prevail.
 

Excluded physicians sometimes prevail

Although it is rare for excluded physicians to win a lawsuit against their hospital, it does happen, says Michael R. Callahan, health lawyer at Katten Muchin Rosenman, in Chicago.

Mr. Callahan cites a 2010 decision by the Arkansas Supreme Court that stopped the state’s largest health system from denying physicians’ privileges. Among other things, the hospital was found to have tortiously interfered with the physicians’ contracts with patients.

In a 2007 decision, a West Virginia court ruled that hospitals that have a mission to serve the public cannot exclude physicians for nonquality issues. In addition, some states, such as Texas, limit the economic factors that can be considered when credentialing decisions are made. Other states, such as Ohio, give hospitals a great deal of leeway to alter credentialing.

Dr. Serota is optimistic about his Missouri lawsuit. Although the judge in the case did not immediately grant SLHV’s request for restoration of privileges while the case proceeds, she did grant expedited discovery – allowing SLHV to obtain documents from SSM that could strengthen the doctors’ case – and she agreed to a hearing on SLHV’s request for a temporary restoration of privileges.

Ms. Gosfield says Dr. Serota’s optimism seems justified, but she adds that such cases cost a lot of money and that they may still not be winnable.

Often plaintiffs can settle lawsuits before they go to trial, but Mr. Callahan says hospitals are loath to restore privileges in a settlement because they don’t want to undermine an exclusivity deal. “The exclusive group expects a certain volume, which can’t be reached if the competing doctors are allowed back in,” he says.
 

Many physicians don’t challenge the exclusion

Quite often, excluded doctors decide not to challenge the decision. For example, Dr. Serota says groups of orthopedic surgeons and urologists have decided not to challenge similar decisions by SSM. “They wanted to move on,” he says.

Mr. Callahan says many excluded doctors also don’t even ask for a hearing. “They expect that the hospital’s decision will be upheld,” he says.

This was the case for Devendra K. Amin, MD, an independent cardiologist in Easton, Pa. Dr. Amin has not had any hospital privileges since July 2020. Even though he is board certified in interventional cardiology, which involves catheterization, Dr. Amin says he cannot perform these procedures because they can only be performed in a hospital in the area.

In the 1990s, Dr. Amin says, he had invasive cardiology privileges at five hospitals, but then those hospitals consolidated, and the remaining ones started constricting his privileges. First he could no longer work in the emergency department, then he could no longer read echocardiograms and interpret stress test results, because that work was assigned exclusively to employed doctors, he says.

Then the one remaining hospital announced that privileges would only be available to physicians by invitation, and he was not invited. Dr. Amin says he could have regained general cardiology privileges if he had accepted employment at the hospital, but he did not want to do this. A recruiter and the head of the cardiology section at the hospital even took him out to dinner 2 years ago to discuss employment, but there was a stipulation that the hospital would not agree to.

“I wanted to get back my interventional privileges back,” Dr. Amin says, “but they told me that would not be possible because they had an exclusive contract with a group.”

Dr. Amin says that now, he can only work as a general cardiologist with reduced volume. He says primary care physicians in the local hospital systems only refer to cardiologists within their systems. “When these patients do come to me, it is only because they specifically requested to see me,” Dr. Amin says.

He does not want to challenge the decisions regarding privileging. “Look, I am 68 years old,” Dr. Amin says. “I’m not retiring yet, but I don’t want to get into a battle with a hospital that has very deep pockets. I’m not a confrontational person to begin with, and I don’t want to spend the next 10 years of my life in litigation.”
 

Diverging expectations

The law on exclusive contracts does not provide easy answers for excluded doctors, and often it defies physicians’ conception of their own role in the hospital.

Many physicians expect the hospital to be a haven where they can do their work without being cut out by a competitor. This view is reinforced by organizations such as the American Medical Association.

The AMA Council on Medical Service states that privileges “can only be abridged upon recommendation of the medical staff and only for reason related to professional competence, adherence to standards of care, and other parameters agreed to by the medical staff.”

But the courts don’t tend to agree with that position. “Hospitals have a fiduciary duty to protect their own financial interests,” Mr. Callahan says. “This may involve anything that furthers the hospital’s mission to provide high-quality health care services to its patient community.”

At the same time, however, there are plenty of instances in which courts have ruled that exclusive contracts had gone too far. But usually it takes a lawyer experienced in these cases to know what those exceptions are.

A version of this article first appeared on Medscape.com.

Cardiologist Samirkumar J. Shah, MD, was sentenced to 78 months in prison after his conviction on two counts of federal health care fraud involving more than $13 million.

Instants/Getty Images

As part of his sentence, Dr. Shah, 58, of Fox Chapel, Pa., must pay $1.7 million in restitution and other penalties and undergo 3 years of supervised release after prison.

“Dr. Shah risked the health of his patients so he could make millions of dollars through unnecessary procedures, and lied and fabricated records for years to perpetuate his fraud scheme,” acting U.S. Attorney Stephen R. Kaufman said in an Aug. 5 statement from the Department of Justice.

As previously reported, Dr. Shah was convicted June 14, 2019, of submitting fraudulent claims to private and federal insurance programs between 2008 and 2013 for external counterpulsation (ECP) therapy, a lower limb compression treatment approved for patients with coronary artery disease and refractory angina.

Dr. Shah, however, advertised ECP as the “fountain of youth,” claimed it made patients “younger and smarter,” and offered the treatment for conditions such as obesity, hypertension, hypotension, diabetes, and erectile dysfunction.

Patients were required to undergo diagnostic ultrasounds as a precautionary measure prior to starting ECP, but witness testimony established that Dr. Shah did not review any of the imaging before approving new patients for ECP, placing his patients at risk for serious injury or even death, the DOJ stated.

The evidence also showed that Dr. Shah double-billed insurers, routinely submitted fabricated patient files, and made false statements concerning his practice, patient population, recording keeping, and compliance with coverage guidelines, the government said.

During the scheme, Dr. Shah submitted ECP-related claims for Medicare Part B, UPMC Health Plan, Highmark Blue Cross Blue Shield, and Gateway Health Plan beneficiaries totalling more than $13 million and received reimbursement payments in excess of $3.5 million.

“Rather than upholding the oath he swore and providing care for patients who trusted him, this defendant misled patients and drained critical Medicaid funds from families who needed it,” said Attorney General Josh Shapiro. “We will not let anyone put their patients’ lives at risk for a profit.”

“Today’s sentence holds Mr. Shah accountable for his appalling actions,” said FBI Pittsburgh Special Agent in Charge Mike Nordwall. “Mr. Shah used his position as a doctor to illegally profit from a health care program paid for by taxpayers. Fraud of this magnitude will not be tolerated.”

Dr. Shah has been in custody since July 15, 2021, after skipping out on his original July 14 sentencing date. The Tribune-Review reported that Dr. Shah filed a last-minute request for a continuance, claiming he had an adverse reaction to the Pfizer COVID-19 vaccination and was advised by his doctor that he needed “strict bedrest for at least 6 weeks.”

Dr. Shah reportedly turned himself after presiding U.S. District Judge David S. Cercone denied the motion and issued an arrest warrant.

A version of this article first appeared on Medscape.com.

Cardiologist Samirkumar J. Shah, MD, was sentenced to 78 months in prison after his conviction on two counts of federal health care fraud involving more than $13 million.

Instants/Getty Images

As part of his sentence, Dr. Shah, 58, of Fox Chapel, Pa., must pay $1.7 million in restitution and other penalties and undergo 3 years of supervised release after prison.

“Dr. Shah risked the health of his patients so he could make millions of dollars through unnecessary procedures, and lied and fabricated records for years to perpetuate his fraud scheme,” acting U.S. Attorney Stephen R. Kaufman said in an Aug. 5 statement from the Department of Justice.

As previously reported, Dr. Shah was convicted June 14, 2019, of submitting fraudulent claims to private and federal insurance programs between 2008 and 2013 for external counterpulsation (ECP) therapy, a lower limb compression treatment approved for patients with coronary artery disease and refractory angina.

Dr. Shah, however, advertised ECP as the “fountain of youth,” claimed it made patients “younger and smarter,” and offered the treatment for conditions such as obesity, hypertension, hypotension, diabetes, and erectile dysfunction.

Patients were required to undergo diagnostic ultrasounds as a precautionary measure prior to starting ECP, but witness testimony established that Dr. Shah did not review any of the imaging before approving new patients for ECP, placing his patients at risk for serious injury or even death, the DOJ stated.

The evidence also showed that Dr. Shah double-billed insurers, routinely submitted fabricated patient files, and made false statements concerning his practice, patient population, recording keeping, and compliance with coverage guidelines, the government said.

During the scheme, Dr. Shah submitted ECP-related claims for Medicare Part B, UPMC Health Plan, Highmark Blue Cross Blue Shield, and Gateway Health Plan beneficiaries totalling more than $13 million and received reimbursement payments in excess of $3.5 million.

“Rather than upholding the oath he swore and providing care for patients who trusted him, this defendant misled patients and drained critical Medicaid funds from families who needed it,” said Attorney General Josh Shapiro. “We will not let anyone put their patients’ lives at risk for a profit.”

“Today’s sentence holds Mr. Shah accountable for his appalling actions,” said FBI Pittsburgh Special Agent in Charge Mike Nordwall. “Mr. Shah used his position as a doctor to illegally profit from a health care program paid for by taxpayers. Fraud of this magnitude will not be tolerated.”

Dr. Shah has been in custody since July 15, 2021, after skipping out on his original July 14 sentencing date. The Tribune-Review reported that Dr. Shah filed a last-minute request for a continuance, claiming he had an adverse reaction to the Pfizer COVID-19 vaccination and was advised by his doctor that he needed “strict bedrest for at least 6 weeks.”

Dr. Shah reportedly turned himself after presiding U.S. District Judge David S. Cercone denied the motion and issued an arrest warrant.

A version of this article first appeared on Medscape.com.

Cardiologist Samirkumar J. Shah, MD, was sentenced to 78 months in prison after his conviction on two counts of federal health care fraud involving more than $13 million.

Instants/Getty Images

As part of his sentence, Dr. Shah, 58, of Fox Chapel, Pa., must pay $1.7 million in restitution and other penalties and undergo 3 years of supervised release after prison.

“Dr. Shah risked the health of his patients so he could make millions of dollars through unnecessary procedures, and lied and fabricated records for years to perpetuate his fraud scheme,” acting U.S. Attorney Stephen R. Kaufman said in an Aug. 5 statement from the Department of Justice.

As previously reported, Dr. Shah was convicted June 14, 2019, of submitting fraudulent claims to private and federal insurance programs between 2008 and 2013 for external counterpulsation (ECP) therapy, a lower limb compression treatment approved for patients with coronary artery disease and refractory angina.

Dr. Shah, however, advertised ECP as the “fountain of youth,” claimed it made patients “younger and smarter,” and offered the treatment for conditions such as obesity, hypertension, hypotension, diabetes, and erectile dysfunction.

Patients were required to undergo diagnostic ultrasounds as a precautionary measure prior to starting ECP, but witness testimony established that Dr. Shah did not review any of the imaging before approving new patients for ECP, placing his patients at risk for serious injury or even death, the DOJ stated.

The evidence also showed that Dr. Shah double-billed insurers, routinely submitted fabricated patient files, and made false statements concerning his practice, patient population, recording keeping, and compliance with coverage guidelines, the government said.

During the scheme, Dr. Shah submitted ECP-related claims for Medicare Part B, UPMC Health Plan, Highmark Blue Cross Blue Shield, and Gateway Health Plan beneficiaries totalling more than $13 million and received reimbursement payments in excess of $3.5 million.

“Rather than upholding the oath he swore and providing care for patients who trusted him, this defendant misled patients and drained critical Medicaid funds from families who needed it,” said Attorney General Josh Shapiro. “We will not let anyone put their patients’ lives at risk for a profit.”

“Today’s sentence holds Mr. Shah accountable for his appalling actions,” said FBI Pittsburgh Special Agent in Charge Mike Nordwall. “Mr. Shah used his position as a doctor to illegally profit from a health care program paid for by taxpayers. Fraud of this magnitude will not be tolerated.”

Dr. Shah has been in custody since July 15, 2021, after skipping out on his original July 14 sentencing date. The Tribune-Review reported that Dr. Shah filed a last-minute request for a continuance, claiming he had an adverse reaction to the Pfizer COVID-19 vaccination and was advised by his doctor that he needed “strict bedrest for at least 6 weeks.”

Dr. Shah reportedly turned himself after presiding U.S. District Judge David S. Cercone denied the motion and issued an arrest warrant.

A version of this article first appeared on Medscape.com.

A retracted study on the safety of blood pressure medications in patients with COVID-19 continues to be cited nearly a year later, new research shows.

Floaria Bicher/iStock/Getty Images Plus

The study in question, published on May 1, 2020, in the New England Journal of Medicine, showed no increased risk for in-hospital death with the use of ACE inhibitors or angiotensin-receptor blockers (ARBs) in hospitalized patients with COVID-19.

Concerns about the veracity of the Surgisphere database used for the study, however, led to a June 4 retraction and to the June 13 retraction of a second study, published in the Lancet, that focused on hydroxychloroquine as a COVID-19 treatment.

Although the Surgisphere scandal caused a global reckoning of COVID-19 scientific studies, the new analysis identified 652 citations of the NEJM article as of May 31.

More than a third of the citations occurred in the first 2 months after the retraction, 54% were at least 3 months later, and 2.8% at least 6 months later. In May, 11 months after the article was retracted, it was cited 21 times, senior author Emily G. McDonald, MD, MSc, McGill University, Montreal, and colleagues reported in a research letter in JAMA Internal Medicine.

“In early May and June there were already more than 200 citations in one of the world’s leading scientific journals, so I do believe it was a highly influential article early on and had an impact on different types of studies or research taking place,” she said in an interview.

Dr. McDonald said she’s also “certain that it impacted patient care,” observing that when there are no guidelines available on how to manage patients, physicians will turn to the most recent evidence in the most reputable journals.

“In the case of ACE [inhibitors] and ARBs, although the study was based on fraudulent data, we were lucky that the overall message was in the end probably correct, but that might not have been the case for another study or dataset,” she said.

Early in the pandemic, concerns existed that ACE inhibitors and ARBs could be harmful, increasing the expression of ACE2 receptors, which the SARS-CoV-2 virus uses to gain entry into cells. The first randomized trial to examine the issue, BRACE CORONA, showed no clinical benefit to interrupting use of the agents in hospitalized patients. An observational study suggested ACE inhibitors may even be protective.

Of two high-profile retractions, McDonald said they chose to bypass the hydroxychloroquine study, which had an eye-popping Altmetric attention score of 23,084, compared with 3,727 for the NEJM paper, because it may have been cited for “other” reasons. “We wanted to focus less on the politics and more on the problem of retracted work.”

The team found that researchers across the globe were citing the retracted ACE/ARB paper (18.7% in the United States, 8.1% in Italy, and 44% other countries). Most citations were used to support a statement in the main text of a study, but in nearly 3% of cases, the data were incorporated into new analyses.

Just 17.6% of the studies cited or noted the retraction. “For sure, that was surprising to us. We suspected it, but our study confirmed it,” Dr. McDonald said.

Although retracted articles can be identified by a watermark or line of text, in some cases that can be easily missed, she noted. What’s more, not all citation software points out when a study has been retracted, a fate shared by the copyediting process.

“There are a lot of mechanisms in place and, in general, what’s happening is rare but there isn’t a perfect automated system solution to absolutely prevent this from happening,” she said. “It’s still subject to human error.”

The findings also have to be taken in the context of a rapidly emerging pandemic and the unprecedented torrent of scientific papers released over the past year.

“That might have contributed to why this happened, but the takeaway message is that this can happen despite our best efforts, and we need to challenge ourselves to come up with a system solution to prevent this from happening in the future,” Dr. McDonald said. “Current mechanisms are probably capturing 95% of it, but we need to do better.”

Limitations of the present analysis are that it was limited to the single retracted study; used only a single search engine, Google Scholar, to identify the citing works; and that additional citations may have been missed, the authors noted.

McDonald and coauthor Todd C. Lee, MD, report being signatories on a public letter calling for the retraction of the Surgisphere papers. Dr. Lee also reported receiving research support from Fonds De Recherche du Quebec-Sante during the conduct of the study.

A version of this article first appeared on Medscape.com.

A retracted study on the safety of blood pressure medications in patients with COVID-19 continues to be cited nearly a year later, new research shows.

Floaria Bicher/iStock/Getty Images Plus

The study in question, published on May 1, 2020, in the New England Journal of Medicine, showed no increased risk for in-hospital death with the use of ACE inhibitors or angiotensin-receptor blockers (ARBs) in hospitalized patients with COVID-19.

Concerns about the veracity of the Surgisphere database used for the study, however, led to a June 4 retraction and to the June 13 retraction of a second study, published in the Lancet, that focused on hydroxychloroquine as a COVID-19 treatment.

Although the Surgisphere scandal caused a global reckoning of COVID-19 scientific studies, the new analysis identified 652 citations of the NEJM article as of May 31.

More than a third of the citations occurred in the first 2 months after the retraction, 54% were at least 3 months later, and 2.8% at least 6 months later. In May, 11 months after the article was retracted, it was cited 21 times, senior author Emily G. McDonald, MD, MSc, McGill University, Montreal, and colleagues reported in a research letter in JAMA Internal Medicine.

“In early May and June there were already more than 200 citations in one of the world’s leading scientific journals, so I do believe it was a highly influential article early on and had an impact on different types of studies or research taking place,” she said in an interview.

Dr. McDonald said she’s also “certain that it impacted patient care,” observing that when there are no guidelines available on how to manage patients, physicians will turn to the most recent evidence in the most reputable journals.

“In the case of ACE [inhibitors] and ARBs, although the study was based on fraudulent data, we were lucky that the overall message was in the end probably correct, but that might not have been the case for another study or dataset,” she said.

Early in the pandemic, concerns existed that ACE inhibitors and ARBs could be harmful, increasing the expression of ACE2 receptors, which the SARS-CoV-2 virus uses to gain entry into cells. The first randomized trial to examine the issue, BRACE CORONA, showed no clinical benefit to interrupting use of the agents in hospitalized patients. An observational study suggested ACE inhibitors may even be protective.

Of two high-profile retractions, McDonald said they chose to bypass the hydroxychloroquine study, which had an eye-popping Altmetric attention score of 23,084, compared with 3,727 for the NEJM paper, because it may have been cited for “other” reasons. “We wanted to focus less on the politics and more on the problem of retracted work.”

The team found that researchers across the globe were citing the retracted ACE/ARB paper (18.7% in the United States, 8.1% in Italy, and 44% other countries). Most citations were used to support a statement in the main text of a study, but in nearly 3% of cases, the data were incorporated into new analyses.

Just 17.6% of the studies cited or noted the retraction. “For sure, that was surprising to us. We suspected it, but our study confirmed it,” Dr. McDonald said.

Although retracted articles can be identified by a watermark or line of text, in some cases that can be easily missed, she noted. What’s more, not all citation software points out when a study has been retracted, a fate shared by the copyediting process.

“There are a lot of mechanisms in place and, in general, what’s happening is rare but there isn’t a perfect automated system solution to absolutely prevent this from happening,” she said. “It’s still subject to human error.”

The findings also have to be taken in the context of a rapidly emerging pandemic and the unprecedented torrent of scientific papers released over the past year.

“That might have contributed to why this happened, but the takeaway message is that this can happen despite our best efforts, and we need to challenge ourselves to come up with a system solution to prevent this from happening in the future,” Dr. McDonald said. “Current mechanisms are probably capturing 95% of it, but we need to do better.”

Limitations of the present analysis are that it was limited to the single retracted study; used only a single search engine, Google Scholar, to identify the citing works; and that additional citations may have been missed, the authors noted.

McDonald and coauthor Todd C. Lee, MD, report being signatories on a public letter calling for the retraction of the Surgisphere papers. Dr. Lee also reported receiving research support from Fonds De Recherche du Quebec-Sante during the conduct of the study.

A version of this article first appeared on Medscape.com.

A retracted study on the safety of blood pressure medications in patients with COVID-19 continues to be cited nearly a year later, new research shows.

Floaria Bicher/iStock/Getty Images Plus

The study in question, published on May 1, 2020, in the New England Journal of Medicine, showed no increased risk for in-hospital death with the use of ACE inhibitors or angiotensin-receptor blockers (ARBs) in hospitalized patients with COVID-19.

Concerns about the veracity of the Surgisphere database used for the study, however, led to a June 4 retraction and to the June 13 retraction of a second study, published in the Lancet, that focused on hydroxychloroquine as a COVID-19 treatment.

Although the Surgisphere scandal caused a global reckoning of COVID-19 scientific studies, the new analysis identified 652 citations of the NEJM article as of May 31.

More than a third of the citations occurred in the first 2 months after the retraction, 54% were at least 3 months later, and 2.8% at least 6 months later. In May, 11 months after the article was retracted, it was cited 21 times, senior author Emily G. McDonald, MD, MSc, McGill University, Montreal, and colleagues reported in a research letter in JAMA Internal Medicine.

“In early May and June there were already more than 200 citations in one of the world’s leading scientific journals, so I do believe it was a highly influential article early on and had an impact on different types of studies or research taking place,” she said in an interview.

Dr. McDonald said she’s also “certain that it impacted patient care,” observing that when there are no guidelines available on how to manage patients, physicians will turn to the most recent evidence in the most reputable journals.

“In the case of ACE [inhibitors] and ARBs, although the study was based on fraudulent data, we were lucky that the overall message was in the end probably correct, but that might not have been the case for another study or dataset,” she said.

Early in the pandemic, concerns existed that ACE inhibitors and ARBs could be harmful, increasing the expression of ACE2 receptors, which the SARS-CoV-2 virus uses to gain entry into cells. The first randomized trial to examine the issue, BRACE CORONA, showed no clinical benefit to interrupting use of the agents in hospitalized patients. An observational study suggested ACE inhibitors may even be protective.

Of two high-profile retractions, McDonald said they chose to bypass the hydroxychloroquine study, which had an eye-popping Altmetric attention score of 23,084, compared with 3,727 for the NEJM paper, because it may have been cited for “other” reasons. “We wanted to focus less on the politics and more on the problem of retracted work.”

The team found that researchers across the globe were citing the retracted ACE/ARB paper (18.7% in the United States, 8.1% in Italy, and 44% other countries). Most citations were used to support a statement in the main text of a study, but in nearly 3% of cases, the data were incorporated into new analyses.

Just 17.6% of the studies cited or noted the retraction. “For sure, that was surprising to us. We suspected it, but our study confirmed it,” Dr. McDonald said.

Although retracted articles can be identified by a watermark or line of text, in some cases that can be easily missed, she noted. What’s more, not all citation software points out when a study has been retracted, a fate shared by the copyediting process.

“There are a lot of mechanisms in place and, in general, what’s happening is rare but there isn’t a perfect automated system solution to absolutely prevent this from happening,” she said. “It’s still subject to human error.”

The findings also have to be taken in the context of a rapidly emerging pandemic and the unprecedented torrent of scientific papers released over the past year.

“That might have contributed to why this happened, but the takeaway message is that this can happen despite our best efforts, and we need to challenge ourselves to come up with a system solution to prevent this from happening in the future,” Dr. McDonald said. “Current mechanisms are probably capturing 95% of it, but we need to do better.”

Limitations of the present analysis are that it was limited to the single retracted study; used only a single search engine, Google Scholar, to identify the citing works; and that additional citations may have been missed, the authors noted.

McDonald and coauthor Todd C. Lee, MD, report being signatories on a public letter calling for the retraction of the Surgisphere papers. Dr. Lee also reported receiving research support from Fonds De Recherche du Quebec-Sante during the conduct of the study.

A version of this article first appeared on Medscape.com.

While cases of pericarditis or myocarditis temporally linked to COVID-19 vaccination remain rare, they may happen more often than reported, according to a large review of electronic medical records (EMRs).

peterschreiber_media/iStock/Getty Images

They also appear to represent two “distinct syndromes,” George Diaz, MD, Providence Regional Medical Center Everett (Washington), said in an interview.

Myocarditis typically occurs soon after vaccination in younger patients and mostly after the second dose, while pericarditis occurs later in older patients, after the first or second dose.

Dr. Diaz and colleagues reported their analysis in a research letter published online August 4 in JAMA.

They reviewed the records of 2,000,287 people who received at least one COVID-19 vaccination at 40 hospitals in Washington, Oregon, Montana, and California that are part of the Providence health care system and use the same EMRs.

The median age of the cohort was 57 years and 59% were women.

A little more than three quarters (77%) received more than one dose; most received the mRNA vaccines made by Pfizer (53%) and Moderna (44%); 3% received the Johnson & Johnson vaccine.

The records showed that 20 people had vaccine-related myocarditis (1.0 per 100,000) and 37 had pericarditis (1.8 per 100,000).

A recent report, based on data from the Centers for Disease Control and Prevention’s Vaccine Adverse Events Reporting System, suggested an incidence of myocarditis of about 4.8 cases per 1 million following receipt of mRNA COVID-19 vaccine.

The new study shows a “similar pattern, although at higher incidence, suggesting vaccine adverse event underreporting. In addition, pericarditis may be more common than myocarditis among older patients,” the study team wrote.

“Our study resulted in higher numbers of cases probably because we searched the EMR, and VAERS requires doctors to report suspected cases voluntarily,” Dr. Diaz said in an interview.

Also, in the governments’ statistics, pericarditis and myocarditis were “lumped together,” he noted.
 

Myocarditis cases

The 20 myocarditis cases occurred a median of 3.5 days after vaccination (11 after the Moderna vaccine and 9 after the Pfizer vaccine), 15 of the patients (75%) were men, and the median age was 36 years.

Four individuals (20%) developed myocarditis symptoms after the first vaccination and 16 (80%) after the second dose. Nineteen of the patients (95%) were admitted to the hospital and all were discharged after a median of 2 days.

None of the 20 patients were readmitted or died. Two received a second vaccination after onset of myocarditis; neither had worsening of symptoms. At last available follow-up (median, 23.5 days after symptom onset), 13 patients (65%) had a resolution of their myocarditis symptoms and seven (35%) were improving.
 

Pericarditis cases

The 37 pericarditis cases occurred a median of 20 days after the most recent COVID-19 vaccination: 23 (62%) with Pfizer, 12 (32%) with Moderna, and 2 (5%) with the J&J vaccine. Fifteen developed pericarditis after the first vaccine dose (41%) and 22 (59%) after the second.

Twenty-seven (73%) of the cases occurred in men; the median age was 59 years.

Thirteen patients (35%) were admitted to the hospital, none to intensive care. The median hospital stay was 1 day. Seven patients with pericarditis received a second vaccination. No patient died.

At last available follow-up (median, 28 days), 7 patients (19%) had resolved symptoms and 23 (62%) were improving.

The researchers also calculate that the average monthly number of cases of myocarditis or myopericarditis during the prevaccine period of January 2019 through January 2021 was 16.9 (95% confidence interval, 15.3-18.6) compared with 27.3 (95% CI, 22.4-32.9) during the vaccine period of February through May 2021 (P < .001).

The mean numbers of pericarditis cases during the same periods were 49.1 (95% CI, 46.4-51.9) and 78.8 (95% CI, 70.3-87.9), respectively (P < .001).

The authors say limitations of their analysis include potential missed cases outside care settings and missed diagnoses of myocarditis or pericarditis, which would underestimate the incidence, as well as inaccurate EMR vaccination information.

“Temporal association does not prove causation, although the short span between vaccination and myocarditis onset and the elevated incidence of myocarditis and pericarditis in the study hospitals lend support to a possible relationship,” they wrote.

In late June, the Food and Drug Administration added a warning to the fact sheets accompanying the Pfizer and Moderna mRNA COVID-19 vaccines, flagging the rare risk of heart inflammation after their use.  

Dr. Diaz cautioned that myocarditis and pericarditis events remain “a rare occurrence” after COVID-19 vaccination.

“When discussing vaccination with patients, [health care providers] can advise them that patients generally recover in the rare event they get pericarditis or myocarditis and no deaths were found, and that the vaccines are safe and effective,” Dr. Diaz said.

The study had no specific funding. Dr. Diaz reported receipt of clinical trial research support from Gilead Sciences, Regeneron, Roche, Boehringer Ingelheim, and Edesa Biotech and scientific advisory board membership for Safeology.

A version of this article first appeared on Medscape.com.

While cases of pericarditis or myocarditis temporally linked to COVID-19 vaccination remain rare, they may happen more often than reported, according to a large review of electronic medical records (EMRs).

peterschreiber_media/iStock/Getty Images

They also appear to represent two “distinct syndromes,” George Diaz, MD, Providence Regional Medical Center Everett (Washington), said in an interview.

Myocarditis typically occurs soon after vaccination in younger patients and mostly after the second dose, while pericarditis occurs later in older patients, after the first or second dose.

Dr. Diaz and colleagues reported their analysis in a research letter published online August 4 in JAMA.

They reviewed the records of 2,000,287 people who received at least one COVID-19 vaccination at 40 hospitals in Washington, Oregon, Montana, and California that are part of the Providence health care system and use the same EMRs.

The median age of the cohort was 57 years and 59% were women.

A little more than three quarters (77%) received more than one dose; most received the mRNA vaccines made by Pfizer (53%) and Moderna (44%); 3% received the Johnson & Johnson vaccine.

The records showed that 20 people had vaccine-related myocarditis (1.0 per 100,000) and 37 had pericarditis (1.8 per 100,000).

A recent report, based on data from the Centers for Disease Control and Prevention’s Vaccine Adverse Events Reporting System, suggested an incidence of myocarditis of about 4.8 cases per 1 million following receipt of mRNA COVID-19 vaccine.

The new study shows a “similar pattern, although at higher incidence, suggesting vaccine adverse event underreporting. In addition, pericarditis may be more common than myocarditis among older patients,” the study team wrote.

“Our study resulted in higher numbers of cases probably because we searched the EMR, and VAERS requires doctors to report suspected cases voluntarily,” Dr. Diaz said in an interview.

Also, in the governments’ statistics, pericarditis and myocarditis were “lumped together,” he noted.
 

Myocarditis cases

The 20 myocarditis cases occurred a median of 3.5 days after vaccination (11 after the Moderna vaccine and 9 after the Pfizer vaccine), 15 of the patients (75%) were men, and the median age was 36 years.

Four individuals (20%) developed myocarditis symptoms after the first vaccination and 16 (80%) after the second dose. Nineteen of the patients (95%) were admitted to the hospital and all were discharged after a median of 2 days.

None of the 20 patients were readmitted or died. Two received a second vaccination after onset of myocarditis; neither had worsening of symptoms. At last available follow-up (median, 23.5 days after symptom onset), 13 patients (65%) had a resolution of their myocarditis symptoms and seven (35%) were improving.
 

Pericarditis cases

The 37 pericarditis cases occurred a median of 20 days after the most recent COVID-19 vaccination: 23 (62%) with Pfizer, 12 (32%) with Moderna, and 2 (5%) with the J&J vaccine. Fifteen developed pericarditis after the first vaccine dose (41%) and 22 (59%) after the second.

Twenty-seven (73%) of the cases occurred in men; the median age was 59 years.

Thirteen patients (35%) were admitted to the hospital, none to intensive care. The median hospital stay was 1 day. Seven patients with pericarditis received a second vaccination. No patient died.

At last available follow-up (median, 28 days), 7 patients (19%) had resolved symptoms and 23 (62%) were improving.

The researchers also calculate that the average monthly number of cases of myocarditis or myopericarditis during the prevaccine period of January 2019 through January 2021 was 16.9 (95% confidence interval, 15.3-18.6) compared with 27.3 (95% CI, 22.4-32.9) during the vaccine period of February through May 2021 (P < .001).

The mean numbers of pericarditis cases during the same periods were 49.1 (95% CI, 46.4-51.9) and 78.8 (95% CI, 70.3-87.9), respectively (P < .001).

The authors say limitations of their analysis include potential missed cases outside care settings and missed diagnoses of myocarditis or pericarditis, which would underestimate the incidence, as well as inaccurate EMR vaccination information.

“Temporal association does not prove causation, although the short span between vaccination and myocarditis onset and the elevated incidence of myocarditis and pericarditis in the study hospitals lend support to a possible relationship,” they wrote.

In late June, the Food and Drug Administration added a warning to the fact sheets accompanying the Pfizer and Moderna mRNA COVID-19 vaccines, flagging the rare risk of heart inflammation after their use.  

Dr. Diaz cautioned that myocarditis and pericarditis events remain “a rare occurrence” after COVID-19 vaccination.

“When discussing vaccination with patients, [health care providers] can advise them that patients generally recover in the rare event they get pericarditis or myocarditis and no deaths were found, and that the vaccines are safe and effective,” Dr. Diaz said.

The study had no specific funding. Dr. Diaz reported receipt of clinical trial research support from Gilead Sciences, Regeneron, Roche, Boehringer Ingelheim, and Edesa Biotech and scientific advisory board membership for Safeology.

A version of this article first appeared on Medscape.com.

While cases of pericarditis or myocarditis temporally linked to COVID-19 vaccination remain rare, they may happen more often than reported, according to a large review of electronic medical records (EMRs).

peterschreiber_media/iStock/Getty Images

They also appear to represent two “distinct syndromes,” George Diaz, MD, Providence Regional Medical Center Everett (Washington), said in an interview.

Myocarditis typically occurs soon after vaccination in younger patients and mostly after the second dose, while pericarditis occurs later in older patients, after the first or second dose.

Dr. Diaz and colleagues reported their analysis in a research letter published online August 4 in JAMA.

They reviewed the records of 2,000,287 people who received at least one COVID-19 vaccination at 40 hospitals in Washington, Oregon, Montana, and California that are part of the Providence health care system and use the same EMRs.

The median age of the cohort was 57 years and 59% were women.

A little more than three quarters (77%) received more than one dose; most received the mRNA vaccines made by Pfizer (53%) and Moderna (44%); 3% received the Johnson & Johnson vaccine.

The records showed that 20 people had vaccine-related myocarditis (1.0 per 100,000) and 37 had pericarditis (1.8 per 100,000).

A recent report, based on data from the Centers for Disease Control and Prevention’s Vaccine Adverse Events Reporting System, suggested an incidence of myocarditis of about 4.8 cases per 1 million following receipt of mRNA COVID-19 vaccine.

The new study shows a “similar pattern, although at higher incidence, suggesting vaccine adverse event underreporting. In addition, pericarditis may be more common than myocarditis among older patients,” the study team wrote.

“Our study resulted in higher numbers of cases probably because we searched the EMR, and VAERS requires doctors to report suspected cases voluntarily,” Dr. Diaz said in an interview.

Also, in the governments’ statistics, pericarditis and myocarditis were “lumped together,” he noted.
 

Myocarditis cases

The 20 myocarditis cases occurred a median of 3.5 days after vaccination (11 after the Moderna vaccine and 9 after the Pfizer vaccine), 15 of the patients (75%) were men, and the median age was 36 years.

Four individuals (20%) developed myocarditis symptoms after the first vaccination and 16 (80%) after the second dose. Nineteen of the patients (95%) were admitted to the hospital and all were discharged after a median of 2 days.

None of the 20 patients were readmitted or died. Two received a second vaccination after onset of myocarditis; neither had worsening of symptoms. At last available follow-up (median, 23.5 days after symptom onset), 13 patients (65%) had a resolution of their myocarditis symptoms and seven (35%) were improving.
 

Pericarditis cases

The 37 pericarditis cases occurred a median of 20 days after the most recent COVID-19 vaccination: 23 (62%) with Pfizer, 12 (32%) with Moderna, and 2 (5%) with the J&J vaccine. Fifteen developed pericarditis after the first vaccine dose (41%) and 22 (59%) after the second.

Twenty-seven (73%) of the cases occurred in men; the median age was 59 years.

Thirteen patients (35%) were admitted to the hospital, none to intensive care. The median hospital stay was 1 day. Seven patients with pericarditis received a second vaccination. No patient died.

At last available follow-up (median, 28 days), 7 patients (19%) had resolved symptoms and 23 (62%) were improving.

The researchers also calculate that the average monthly number of cases of myocarditis or myopericarditis during the prevaccine period of January 2019 through January 2021 was 16.9 (95% confidence interval, 15.3-18.6) compared with 27.3 (95% CI, 22.4-32.9) during the vaccine period of February through May 2021 (P < .001).

The mean numbers of pericarditis cases during the same periods were 49.1 (95% CI, 46.4-51.9) and 78.8 (95% CI, 70.3-87.9), respectively (P < .001).

The authors say limitations of their analysis include potential missed cases outside care settings and missed diagnoses of myocarditis or pericarditis, which would underestimate the incidence, as well as inaccurate EMR vaccination information.

“Temporal association does not prove causation, although the short span between vaccination and myocarditis onset and the elevated incidence of myocarditis and pericarditis in the study hospitals lend support to a possible relationship,” they wrote.

In late June, the Food and Drug Administration added a warning to the fact sheets accompanying the Pfizer and Moderna mRNA COVID-19 vaccines, flagging the rare risk of heart inflammation after their use.  

Dr. Diaz cautioned that myocarditis and pericarditis events remain “a rare occurrence” after COVID-19 vaccination.

“When discussing vaccination with patients, [health care providers] can advise them that patients generally recover in the rare event they get pericarditis or myocarditis and no deaths were found, and that the vaccines are safe and effective,” Dr. Diaz said.

The study had no specific funding. Dr. Diaz reported receipt of clinical trial research support from Gilead Sciences, Regeneron, Roche, Boehringer Ingelheim, and Edesa Biotech and scientific advisory board membership for Safeology.

A version of this article first appeared on Medscape.com.

John Winkler II was dying of heart failure when doctors came to his hospital bedside, offering a chance to prolong his life. The HeartWare Ventricular Assist Device, or HVAD, could be implanted in Winkler’s chest until a transplant was possible. The heart pump came with disclaimers of risk, but Winkler wanted to fight for time. He was only 46 and had a loving wife and four children, and his second grandchild was on the way.

So, in August 2014, Winkler had surgery to implant the device. A golf-ball–sized rotor was attached to his left ventricle to pump blood through a tube and into his aorta. A cable threading out of a small incision in his waist connected to a battery-powered controller strapped to his body. If something went wrong, an alarm as loud as a fire drill would sound.

Winkler returned home weeks later and, as he regained his strength, became hopeful about the future. He started making plans to visit colleges with his daughter, and was able to host his parents and new grandchild for Christmas. “He was doing so much better,” his wife, Tina Winkler, said. “We thought he was coasting until he got his transplant.”

What John Winkler didn’t know: Months before his implant, the Food and Drug Administration put HeartWare on notice for not properly monitoring or repairing HVAD defects, such as faulty batteries and short circuits caused by static electricity, that had killed patients. The agency issued a warning letter, one of its most serious citations. It demanded fixes within 15 days, but took no decisive action as problems persisted.

Ten days after Christmas of 2014, Winkler’s two teenage children heard the HVAD’s piercing alarm and ran upstairs. They found their father collapsed on his bedroom floor, completely unresponsive. Kelly, 17, dropped to his side and tried to copy how people on television did CPR. She told her brother to call 911, and over the device’s siren did her best to hear instructions from the operator.

When paramedics arrived and assessed her father, one made a passing comment that has haunted Kelly ever since: “Well, his toes are already cold.” He died 2 days later. Medtronic, the company that acquired HeartWare in 2016, settled a lawsuit by the family last year, admitting no fault. Tina Winkler believes her children blamed themselves for their father’s death. “Those two kids have never been the same,” she said. “I think they feel like they didn’t do things they needed to do.”

But it was the FDA that failed to protect Winkler and thousands of other patients whose survival depended on the HVAD, a ProPublica investigation found.

As HeartWare and Medtronic failed inspection after inspection and reports of device-related deaths piled up, the FDA relied on the device makers to fix the problems voluntarily rather than compelling them to do so.

The HVAD was implanted into more than 19,000 patients, the majority of whom got it after the FDA found in 2014 that the device didn’t meet federal standards. By the end of last year, the agency had received more than 3,000 reports of patient deaths that may have been caused or contributed to by the device.

Among them were reports of deaths the company linked to serious device problems: a patient who vomited blood as a family member struggled to restart a defective HVAD; a patient who bled out internally and died after implant surgery because a tube attached to the pump tore open; a patient whose heart tissue was left charred after an HVAD short-circuited and voltage surged through the pump.

The ineffective regulatory oversight of the HVAD is emblematic of larger, more systemic weaknesses.

For decades, the FDA and its Center for Devices and Radiological Health have been responsible for ensuring that high-risk medical devices are safe and effective. Yet they rely mostly on manufacturers to identify and correct problems. The agency says it can seize products, order injunctions against companies, or issue fines, but it rarely does so, preferring instead for companies to make fixes voluntarily.

When federal investigators found repeated manufacturing issues with the HVAD for years, the FDA didn’t penalize the company, even as the company issued 15 serious recalls of the device starting in 2014, the most of any single high-risk device in the FDA’s database. Thousands of patients with recalled models needed to have external HVAD parts replaced or take extra caution while handling their devices and monitor them for signs of malfunctions that could cause injury or death.

Meanwhile, the processes to inform the public through formal FDA notices and messages to health care providers repeatedly failed and left patients in the dark about known problems with the HVAD.

“Patients have no idea, and they rely on the FDA to ensure the safety and effectiveness of high-risk devices,” said Dr. Rita Redberg, a cardiologist at the University of California, San Francisco, who studies medical device regulation. “How can you not take action on a warning letter with these serious issues with very sick patients?”

In response to ProPublica’s findings, the FDA said it had been closely monitoring issues with the HVAD. It said that after Medtronic acquired HeartWare in 2016, it met with the company more than 100 times to ensure problems were being fixed and to review safety concerns related to the heart pump. The agency also said it initiated formal reviews of new device modifications and continually tracked whether the HVAD had a “reasonable assurance of safety and effectiveness.”

“Our decisions that we made along the way have always been patient focused,” said Dr. William Maisel, director of product evaluation and quality at the FDA’s device division. He added that more than 80% of companies fix their problems by the time the FDA reinspects.

That did not happen with the HVAD. In 2016 and 2018, inspectors found that issues detailed in the 2014 warning letter remained unresolved. Medtronic told the FDA last year that it had fixed the problems, but, before the agency could verify the claim, inspections were paused because of the coronavirus pandemic.

In June, Medtronic stopped HVAD sales and implants. The company conceded that a competing device was safer after a new study showed the HVAD had higher rates of death and neurological injury. Medtronic also cited a 12-year-old problem with its devices not restarting if they disconnect from power, leaving patients’ hearts without support.

Medtronic declined to make Geoffrey Martha, CEO, or Nnamdi Njoku, president of mechanical heart support, available for interviews. In an email, a spokesperson said, “There is nothing more important to Medtronic than the safety and well-being of patients.”

The email continued: “Medtronic takes this matter very seriously and, over the past five years, we have worked closely with FDA and engaged external experts to resolve the issues noted in the warning letter. FDA is aware of the steps Medtronic has taken to address the underlying concerns.”

The company said it will have a support system in place for the 4,000 patients worldwide and 2,000 in the United States who still rely on the HVAD. Medtronic will station 20 specialists across the globe to help with device maintenance and patient education. A centralized engineering team will provide technical support and troubleshooting for patients and medical staff. Medtronic said it will offer financial assistance if insurance doesn’t fully cover the surgery to replace a device with a competing product, but only if a doctor decides it’s medically necessary.

Patients with HVADs have little choice but to hope the devices keep working: The surgery to remove HVADs is so risky that both Medtronic and the FDA advise against it. The device is meant to be left in place until its wearer gets a heart transplant. Or dies.
 

Warning signs

In late 2012, HeartWare, then an independent company headquartered in Massachusetts, won FDA approval to sell a new device that could keep heart failure patients alive and mobile while awaiting a transplant.

A competing device, the HeartMate, was already gaining attention, with high-profile patients like former Vice President Dick Cheney, a heart attack survivor who eventually got a transplant after using the device for 20 months.

The HVAD offered a smaller option that could even be used in children, and it led to a string of publicized successes. A fitness model was able to return to the gym. A 13-year-old with heart defects could attend school again. Medtronic’s YouTube page features 16 interviews with grateful patients and families.

The patients who received HVADs had already been in grave peril. They had advanced heart failure, serious enough to need blood pumped out of their hearts artificially. Most patients were older than 50, but there were also younger patients with heart defects or other cardiac conditions. The device provided help but brought its own risks. Implanting it required invasive open-heart surgery, and clots could develop inside the pump, which, in the worst cases, led to deadly strokes.

The device also came with a steep price tag. Each HVAD cost about $80,000, and, even though HeartWare never made a profit as an independent company, in 2015 device sales brought in $276 million in revenue.

For many severe heart failure patients, the opportunity to survive longer and return to normal life made the device worth the risks and cost.

But patients were unaware the FDA started finding manufacturing issues at HeartWare’s Miami Lakes, Florida, plant as early as 2011, when the device was still seeking approval.

Among the findings, a federal inspector expressed concerns that engineering staff “were not completely reviewing documents before approving them” and found one employee assigned to monitoring device quality had missed several required monthly trainings. HeartWare leadership promised quick corrective action, according to FDA documents.

Then, in 2014, the FDA found more serious lapses, detailed in federal inspection reports.

For example, HeartWare knew of 119 instances in which batteries failed unexpectedly, which could leave the pump powerless, stopping support for the patient’s heart. But the company didn’t test the batteries in inventory for defects, or the batteries of current patients, even though one person’s death had already been linked to battery failure.

The company also received complaints that static electricity could short-circuit its devices. It learned of at least 27 such cases between 2010 and 2013, including four that resulted in serious injuries and two that led to death. HVAD patients would need to avoid contact with certain household objects like televisions or vacuum cleaners — anything that could create strong static electricity. HeartWare added warnings to the patient manual and redesigned its shield to protect the device controller, but the FDA found that the company didn’t replace shields for devices already being used by current patients or produced and sitting in inventory.

Continuing quality control concerns led to the FDA warning letter in June 2014. The document labeled the HVAD as “adulterated,” meaning the device did not meet federal manufacturing standards. The agency gave HeartWare 15 days to correct the problems or face regulatory action.

Still, investment analysts who followed HeartWare believed the warning posed little risk to the company’s business prospects. One described it as being “as benign as possible.”

The 15-day deadline passed, and the FDA never penalized the company.

The agency told ProPublica it had provided additional time because HeartWare was a relatively new manufacturer and the HVAD was a complicated device. It also said it avoided punitive action to make sure patients with severe heart failure had access to this treatment option. “We’re talking about the sickest of the sick patients who really have very few alternatives,” Maisel, the head of device quality, said.

But the HeartMate, the competing device, was available and already being used by the majority of patients. When Medtronic stopped HVAD sales, both companies said the HeartMate could fill the gap.

Inspectors continued to find problems at HeartWare facilities in 2015, 2016, 2017 and 2018. In the most recent report in 2018, inspectors identified seven separate violations at the HVAD plant, including three previously cited in the 2014 warning letter. The company was still mishandling newly discovered defects like pins connecting the controller to a power source that could bend and become unusable, and controllers built with incompatible parts that could chemically react and “attack” the plastic exterior.

Again, the inspection report said the company “promised to correct” the issues.

“What penalty is there for noncompliance? There isn’t one,” said Madris Kinard, a former public health analyst with the FDA and the CEO of Device Events, a software company that analyzes FDA device data. “There’s nothing the FDA is doing that penalizes, in any true sense of the matter, the manufacturer.”

By the time sales were halted last month, the HVAD had become the subject of 15 company-initiated “Class I” recalls for dangerous device problems that could cause injury or death.

One recall came with a warning sent to health care providers in December that said pumps were failing to start up properly. The pattern of malfunctions was almost as old as the device itself, the company later admitted when it halted device sales in June. But even recent patients were completely unaware of the problem.
 

“A no-brainer”

When children asked Latoya Johnson Keelen about the cable that came out of her side and connected to a controller on her hip, she told them she was Iron Woman.

For a while, she felt invulnerable with the HVAD on her heart.

Johnson Keelen, who lives in the Atlanta suburbs, learned she needed the device after delivering her fourth child, Isaiah, in early 2018. Doctors diagnosed her with postpartum cardiomyopathy, a rare and mysterious form of heart failure that afflicts mothers during pregnancy or after birth. Black mothers in the South have among the highest rates of the illness. Some mothers quickly regain heart function, some only partially recuperate and others never recover.

Tests showed that Johnson Keelen, then 42, was suddenly in end-stage heart failure.

Her body’s immune response at the time was too strong for her to receive a heart transplant. Doctors gave her two choices: an HVAD or end-of-life hospice care.

“It became a no-brainer,” she said. “I just had a baby. I just gave birth. I’m not ready to plan for a funeral.”

Johnson Keelen, a woman of faith, believed God would heal her, either through a medical advancement or a miracle. She thought the HVAD was the answer.

Living with a life-sustaining medical device was difficult at first for the fiercely independent mother. She had to leave her job as a public health communications specialist, ask her older sons to change her bandages and lean heavily on her new husband, only a year into their marriage.

But, for about three years, she found comfort in the soft humming of the HVAD’s spinning rotor at night. It served as a lullaby for her new baby when he lay on her chest.

She said she was never told about the manufacturing problems the FDA repeatedly found at HeartWare’s facilities or about device recalls, including one sent to patients in December 2020. The notice said the device sometimes wouldn’t restart properly, which had led to two patient deaths at that point. It warned that current patients should always keep at least one power source, a battery or an AC or DC adapter, connected at all times to avoid the need for a restart.

Two months after that notice, Johnson Keelen was getting her kids ready for school when the HVAD’s low-battery alarm blared. She had unplugged the battery to replace it without realizing her wall adapter was disconnected.

Once before, Johnson Keelen had simply plugged the charger back into the outlet and her device restarted. But this time it wouldn’t.

As an emergency alarm sounded, she called the ventricular-assist team assigned to her case, and a specialist directed her to switch out the device controller.

Nothing changed, and panic crept into the voice on the phone.

An ambulance took Johnson Keelen to a hospital where medical staff used several backup controllers to try to start the pump.

Still nothing.

Doctors and nurses tried to keep calm, but Johnson Keelen could see fear and shock on their faces. Without the HVAD, her only options were a transplant or a completely new pump.

Doctors scurried to locate a donor heart and airlifted her for an emergency transplant. But while running tests, the medical team was stunned to find that Johnson Keelen’s miracle had occurred: Her heart was once again pumping blood on its own.

She had a new choice. She could avoid the risks of transplant rejection and open heart surgery during the pandemic by leaving the device on her functioning heart, while cutting the wires, removing the external components and sealing the pump.

She chose to trust her newly functioning heart, and leave the decommissioned HVAD inside her.

Three months later, when Medtronic said it was stopping HeartWare sales and implants, its announcement cited the problem with pumps not restarting among the reasons.
 

Company-led oversight

If evidence suggests a medical device may be linked to a serious patient injury or death, hospitals and other health care facilities must submit a report to the manufacturer and the FDA. Device companies must also submit reports if they learn independently of any incidents.

By the end of 2020, roughly 3,000 death reports and 20,000 injury reports related to the HVAD had been filed with the FDA.

Any details that could identify patients, like their age or gender, are removed from the publicly available reports. Most only have limited details about circumstances surrounding deaths or injuries. But it’s clear from the reports on the HVAD that some of these outcomes could be linked to problems previously identified by FDA inspectors.

Doctors attempted CPR for two hours after an electrostatic shock short-circuited one patient’s device in 2014, a few months after the FDA inspection that year. An autopsy revealed voltage had caused “deep charring” of the tissue inside the patient’s chest.

Friends found another patient dead in the kitchen, with groceries still on the counter, in 2018 after their device, which did not have the recommended static shield, short-circuited.

Last year, paramedics found a patient with the device disconnected from power. They struggled to restart the device, but it wouldn’t plug back into the power source because the connector pins were bent. The patient would die at the hospital.

In most cases, the FDA turned to the company to investigate whether a malfunction caused or contributed to the incidents.

But the FDA has long known HeartWare and Medtronic could not be relied on to properly submit HVAD incident reports.

In 2014, the FDA cited HeartWare because in at least 10 cases, there were no documents showing the company attempted to investigate.

In 2016, the agency wrote another citation when the company was late in reporting more than 200 cases, some more than a year past their 30-day reporting deadlines, and failed to report malfunctions that occurred during clinical trials.

The FDA told ProPublica the agency increased its monitoring of HVAD reports, and Medtronic hired new employees to submit timely reports. But by 2018, its backlog had only grown, with 677 late case filings. Again, the FDA did nothing beyond telling the company to fix the problem and further increasing its monitoring.

In an email, Medtronic said it “has robust systems in place to monitor the safety of all of our products, including the HVAD device.”

The email said, “When any potential safety issues are identified, those issues are thoroughly investigated and relevant information is shared with regulators and healthcare providers.” The company didn’t respond to the pattern of late reports and incomplete investigations identified in FDA inspections.

Maisel, the director of FDA device evaluation and quality, once criticized asking companies to investigate their own devices. In 2008, as a practicing cardiologist, he testified to the U.S. House oversight committee about his concerns.

“In the majority of cases, FDA relies on industry to identify, correct and report the problems,” he said. “But there is obviously an inherent financial conflict of interest for the manufacturers, sometimes measured in billions of dollars.”

Maisel has since had a change of heart. When asked about his 2008 testimony, he told ProPublica that he now believes the regulatory system “generally serves patients well” and “most companies are well intentioned.”

HeartWare’s track record of questionable investigations was glaring in John Winkler II’s case.

A report submitted by HeartWare that matches the dates and details of Winkler’s case shows the company decided there was “no indication of any device malfunctions.” It told the FDA that the device couldn’t be removed from the body because the hospital said his family declined an autopsy. HeartWare added that the evidence of the device’s role in Winkler’s death was inconclusive.

Yet little of this appears to be true. Documents reviewed by ProPublica show an autopsy of the heart and lungs was performed a day after the death. Tina Winkler said she was told the pump was removed from her husband’s body and was available for inspection.

A year after John Winkler’s death, HeartWare recalled 18,000 potentially faulty batteries produced between 2013 and 2015. Tina Winkler came across the notice online and found her husband’s battery serial numbers on the list. The company never contacted her about it or any further investigation, she said.
 

Rewards, not penalties

As deaths and recalls mounted, HeartWare and Medtronic touted additional FDA approval to treat more patients and their attempts to develop new cutting-edge devices.

With the company on notice under the 2014 warning letter, HeartWare geared up to begin human trials on a smaller heart pump, called the MVAD or Miniaturized Ventricular Assist Device. It would be powered by a new algorithm to more efficiently pump blood. Industry analysts predicted robust sales.

In July 2015, implantations were set to begin on a select group of 60 patients in Europe and Australia. But they were abruptly stopped less than two months later after only 11 implants. Patients experienced numerous adverse events, including major bleeding, infection and device malfunction, according to published data.

HeartWare’s stock price plummeted from about $85 to $35 by October 2015. The next year, Medtronic bought HeartWare for $1.1 billion, replacing much of the company’s leadership shortly after.

Some former HeartWare investors filed a class action lawsuit in January 2016 alleging deception in the development of the MVAD.

According to the accounts of six anonymous former employees in the lawsuit, the details mirror the scandal surrounding Theranos, the former blood test company charged with fraud for raising more than $700 million by allegedly lying about its technology.

Where Theranos made empty promises of a test that only needed a few drops of blood, the suit alleges HeartWare promoted a life-sustaining medical device that former employees said had many problems and actually worsened blood flow, increasing clotting risks.

“Nothing really worked right,” one former HeartWare manager said in the lawsuit, citing “improper alarms, improper touch screen performance, gibberish on display screens — just so many alerts and problems.”

Leadership proceeded with human testing anyway, the suit alleges.

Months later, at an investor conference, HeartWare leadership acknowledged the pump and algorithm led to multiple adverse events. For two patients in particular, the algorithm would direct the pump to speed up so fast that it would try to suck up more blood than was available inside the heart for prolonged periods of time.

HeartWare and Medtronic settled the investor suit for $54.5 million in 2018, admitting no fault.

None of the allegations slowed the FDA as it gave Medtronic additional approval and support for its heart pump technologies.

In September 2017, the agency approved the HVAD as “destination therapy” for patients who were not heart transplant candidates and would rely on the device for the rest of their lives.

“We’re really excited about our HVAD destination therapy approval,” a Medtronic executive said on an investor earnings call. “That’s a real game changer for us in that market.”

Two years later, Medtronic announced it was developing a fully implantable version of the HVAD that would no longer need a cable coming through the waist to connect to power.

Even though issues with the HeartWare device had been unresolved for five years at that point, the FDA accepted the pitch into its new fast-track approval process for high-risk devices.

“Slipped Through The Cracks”

After Johnson Keelen’s pump failed in February, she found a news story about the recall notice sent to medical providers two months prior.

It said the company had identified a problem with pump restarts that could cause heart attacks or serious patient harm. Nineteen patients had been seriously injured so far, and two people had died. The recall warned that patients should be careful to avoid disconnecting the device’s power sources.

“I kept seeing Medtronic on record saying they notified patients,” Johnson Keelen said. “Who did they contact? No one told me.”

Her doctor later told her she must have “slipped through the cracks,” she said.

The current system for informing patients of new safety concerns with high-risk devices relies on a communication chain that can easily break. The device company contacts the FDA and health care providers that work with device patients. The FDA typically issues a public notice, while health professionals contact their patients.

But the agency admits most patients don’t know to look for formal FDA postings. And, experts say, the medical system can lose track of who needs to be notified, especially if a patient moves or switches primary care physicians.

Tina Winkler still wonders why she was never told about FDA-known safety issues with the HVAD. She said her husband’s medical team “had to teach me how to clean his wound, how to change his batteries and what to do if alarms go off. And they never mentioned any of this.”

She said, “If we had all the facts, there’s no way he would have gotten that device implanted in his heart.”

When FDA inspectors find serious safety issues with a medical device, inspection reports are not posted online or sent to patients. The public can obtain reports through a Freedom of Information Act request, but the agency’s records department has said new requests can be stuck behind a year-long backlog.

Patients can find warning letters online in a searchable database of thousands of letters from different FDA divisions, including the center for devices. But HeartWare’s 2014 letter is no longer available for public review because the website purges letters older than five years.

There are also few documents available in state courts about faulty products, because of restrictions on lawsuits related to medical devices. The restrictions date back to a 2008 Supreme Court decision in a case against Medtronic. The court found that U.S. law bars patients and their survivors from suing device makers in state court, essentially because their products go through such a rigorous FDA approval process.

Two recent patient lawsuits against HeartWare and Medtronic, including one filed by Tina Winkler, were moved from state court to federal court. In both cases, Medtronic filed to dismiss the cases because of the U.S. law that protects device companies. Medtronic and the families reached private settlements soon after.

Winkler and an attorney for the other family said they could not comment on their settlements.

Johnson Keelen, with a decommissioned HVAD still attached to her heart, wonders what that means for her and other patients’ chances of recourse.

“Why isn’t anyone now stepping up for the patient?” she asked. “They are now liable for taking care of us because we relied on them.”
 

“Run its course”

Deserae Cain, 33, is one of the 4,000 patients still relying on a HeartWare device.

She was implanted with the heart pump in late 2017, after suddenly being diagnosed with heart failure. Scans showed her heart was three times normal size. It took time for her to come to terms with needing a life-sustaining device — not long before her diagnosis, she had been going on five-mile runs. In the four years since, though, Cain has built a life around the HVAD with her fiance in their Dayton, Ohio, home.

They know the device can malfunction. In 2019, the pump failed for almost an hour as doctors at a nearby hospital struggled to restart it. Cain just tried to stay calm, knowing anxiety could threaten her unsupported weak heart. Months later, she needed an emergency experimental procedure to clear out blood clots developed within her HVAD.

Then, in 2020, Cain developed a widespread infection. Doctors told her she needed surgery to clean out and replace the pump.

Cain asked her medical team if she could switch to the alternative HeartMate device, which other patients told her presented fewer problems, she said. Doctors said the HVAD was better suited for her smaller frame.

But her new pump had problems soon after the surgery.

The device’s suction alarms, which alert when the pump is trying to pull in more blood than is available within the heart, sounded multiple times a day, for hours at a time, she said. Baffled by the issue for months, her medical team eventually turned off that specific alarm.

Soon after, her ventricular-assist specialist called her about a patient’s death linked to the belt that holds the device controller, she said. The belt had ripped and the equipment had fallen, yanking on the cable that connected the controller to the pump. Cain replaced her belt but it quickly frayed and had to be replaced again within six weeks.

Then, in June, she found out about Medtronic’s decision to stop sales and implants. Cain received a letter from her hospital mentioning a Medtronic support program, but it provided few specifics.

Cain wondered if things would be any different than before. Anxious about her future, she asked: “Are they just going to let it run its course until there is none of us left?”

This article first appeared on Propublica.

John Winkler II was dying of heart failure when doctors came to his hospital bedside, offering a chance to prolong his life. The HeartWare Ventricular Assist Device, or HVAD, could be implanted in Winkler’s chest until a transplant was possible. The heart pump came with disclaimers of risk, but Winkler wanted to fight for time. He was only 46 and had a loving wife and four children, and his second grandchild was on the way.

So, in August 2014, Winkler had surgery to implant the device. A golf-ball–sized rotor was attached to his left ventricle to pump blood through a tube and into his aorta. A cable threading out of a small incision in his waist connected to a battery-powered controller strapped to his body. If something went wrong, an alarm as loud as a fire drill would sound.

Winkler returned home weeks later and, as he regained his strength, became hopeful about the future. He started making plans to visit colleges with his daughter, and was able to host his parents and new grandchild for Christmas. “He was doing so much better,” his wife, Tina Winkler, said. “We thought he was coasting until he got his transplant.”

What John Winkler didn’t know: Months before his implant, the Food and Drug Administration put HeartWare on notice for not properly monitoring or repairing HVAD defects, such as faulty batteries and short circuits caused by static electricity, that had killed patients. The agency issued a warning letter, one of its most serious citations. It demanded fixes within 15 days, but took no decisive action as problems persisted.

Ten days after Christmas of 2014, Winkler’s two teenage children heard the HVAD’s piercing alarm and ran upstairs. They found their father collapsed on his bedroom floor, completely unresponsive. Kelly, 17, dropped to his side and tried to copy how people on television did CPR. She told her brother to call 911, and over the device’s siren did her best to hear instructions from the operator.

When paramedics arrived and assessed her father, one made a passing comment that has haunted Kelly ever since: “Well, his toes are already cold.” He died 2 days later. Medtronic, the company that acquired HeartWare in 2016, settled a lawsuit by the family last year, admitting no fault. Tina Winkler believes her children blamed themselves for their father’s death. “Those two kids have never been the same,” she said. “I think they feel like they didn’t do things they needed to do.”

But it was the FDA that failed to protect Winkler and thousands of other patients whose survival depended on the HVAD, a ProPublica investigation found.

As HeartWare and Medtronic failed inspection after inspection and reports of device-related deaths piled up, the FDA relied on the device makers to fix the problems voluntarily rather than compelling them to do so.

The HVAD was implanted into more than 19,000 patients, the majority of whom got it after the FDA found in 2014 that the device didn’t meet federal standards. By the end of last year, the agency had received more than 3,000 reports of patient deaths that may have been caused or contributed to by the device.

Among them were reports of deaths the company linked to serious device problems: a patient who vomited blood as a family member struggled to restart a defective HVAD; a patient who bled out internally and died after implant surgery because a tube attached to the pump tore open; a patient whose heart tissue was left charred after an HVAD short-circuited and voltage surged through the pump.

The ineffective regulatory oversight of the HVAD is emblematic of larger, more systemic weaknesses.

For decades, the FDA and its Center for Devices and Radiological Health have been responsible for ensuring that high-risk medical devices are safe and effective. Yet they rely mostly on manufacturers to identify and correct problems. The agency says it can seize products, order injunctions against companies, or issue fines, but it rarely does so, preferring instead for companies to make fixes voluntarily.

When federal investigators found repeated manufacturing issues with the HVAD for years, the FDA didn’t penalize the company, even as the company issued 15 serious recalls of the device starting in 2014, the most of any single high-risk device in the FDA’s database. Thousands of patients with recalled models needed to have external HVAD parts replaced or take extra caution while handling their devices and monitor them for signs of malfunctions that could cause injury or death.

Meanwhile, the processes to inform the public through formal FDA notices and messages to health care providers repeatedly failed and left patients in the dark about known problems with the HVAD.

“Patients have no idea, and they rely on the FDA to ensure the safety and effectiveness of high-risk devices,” said Dr. Rita Redberg, a cardiologist at the University of California, San Francisco, who studies medical device regulation. “How can you not take action on a warning letter with these serious issues with very sick patients?”

In response to ProPublica’s findings, the FDA said it had been closely monitoring issues with the HVAD. It said that after Medtronic acquired HeartWare in 2016, it met with the company more than 100 times to ensure problems were being fixed and to review safety concerns related to the heart pump. The agency also said it initiated formal reviews of new device modifications and continually tracked whether the HVAD had a “reasonable assurance of safety and effectiveness.”

“Our decisions that we made along the way have always been patient focused,” said Dr. William Maisel, director of product evaluation and quality at the FDA’s device division. He added that more than 80% of companies fix their problems by the time the FDA reinspects.

That did not happen with the HVAD. In 2016 and 2018, inspectors found that issues detailed in the 2014 warning letter remained unresolved. Medtronic told the FDA last year that it had fixed the problems, but, before the agency could verify the claim, inspections were paused because of the coronavirus pandemic.

In June, Medtronic stopped HVAD sales and implants. The company conceded that a competing device was safer after a new study showed the HVAD had higher rates of death and neurological injury. Medtronic also cited a 12-year-old problem with its devices not restarting if they disconnect from power, leaving patients’ hearts without support.

Medtronic declined to make Geoffrey Martha, CEO, or Nnamdi Njoku, president of mechanical heart support, available for interviews. In an email, a spokesperson said, “There is nothing more important to Medtronic than the safety and well-being of patients.”

The email continued: “Medtronic takes this matter very seriously and, over the past five years, we have worked closely with FDA and engaged external experts to resolve the issues noted in the warning letter. FDA is aware of the steps Medtronic has taken to address the underlying concerns.”

The company said it will have a support system in place for the 4,000 patients worldwide and 2,000 in the United States who still rely on the HVAD. Medtronic will station 20 specialists across the globe to help with device maintenance and patient education. A centralized engineering team will provide technical support and troubleshooting for patients and medical staff. Medtronic said it will offer financial assistance if insurance doesn’t fully cover the surgery to replace a device with a competing product, but only if a doctor decides it’s medically necessary.

Patients with HVADs have little choice but to hope the devices keep working: The surgery to remove HVADs is so risky that both Medtronic and the FDA advise against it. The device is meant to be left in place until its wearer gets a heart transplant. Or dies.
 

Warning signs

In late 2012, HeartWare, then an independent company headquartered in Massachusetts, won FDA approval to sell a new device that could keep heart failure patients alive and mobile while awaiting a transplant.

A competing device, the HeartMate, was already gaining attention, with high-profile patients like former Vice President Dick Cheney, a heart attack survivor who eventually got a transplant after using the device for 20 months.

The HVAD offered a smaller option that could even be used in children, and it led to a string of publicized successes. A fitness model was able to return to the gym. A 13-year-old with heart defects could attend school again. Medtronic’s YouTube page features 16 interviews with grateful patients and families.

The patients who received HVADs had already been in grave peril. They had advanced heart failure, serious enough to need blood pumped out of their hearts artificially. Most patients were older than 50, but there were also younger patients with heart defects or other cardiac conditions. The device provided help but brought its own risks. Implanting it required invasive open-heart surgery, and clots could develop inside the pump, which, in the worst cases, led to deadly strokes.

The device also came with a steep price tag. Each HVAD cost about $80,000, and, even though HeartWare never made a profit as an independent company, in 2015 device sales brought in $276 million in revenue.

For many severe heart failure patients, the opportunity to survive longer and return to normal life made the device worth the risks and cost.

But patients were unaware the FDA started finding manufacturing issues at HeartWare’s Miami Lakes, Florida, plant as early as 2011, when the device was still seeking approval.

Among the findings, a federal inspector expressed concerns that engineering staff “were not completely reviewing documents before approving them” and found one employee assigned to monitoring device quality had missed several required monthly trainings. HeartWare leadership promised quick corrective action, according to FDA documents.

Then, in 2014, the FDA found more serious lapses, detailed in federal inspection reports.

For example, HeartWare knew of 119 instances in which batteries failed unexpectedly, which could leave the pump powerless, stopping support for the patient’s heart. But the company didn’t test the batteries in inventory for defects, or the batteries of current patients, even though one person’s death had already been linked to battery failure.

The company also received complaints that static electricity could short-circuit its devices. It learned of at least 27 such cases between 2010 and 2013, including four that resulted in serious injuries and two that led to death. HVAD patients would need to avoid contact with certain household objects like televisions or vacuum cleaners — anything that could create strong static electricity. HeartWare added warnings to the patient manual and redesigned its shield to protect the device controller, but the FDA found that the company didn’t replace shields for devices already being used by current patients or produced and sitting in inventory.

Continuing quality control concerns led to the FDA warning letter in June 2014. The document labeled the HVAD as “adulterated,” meaning the device did not meet federal manufacturing standards. The agency gave HeartWare 15 days to correct the problems or face regulatory action.

Still, investment analysts who followed HeartWare believed the warning posed little risk to the company’s business prospects. One described it as being “as benign as possible.”

The 15-day deadline passed, and the FDA never penalized the company.

The agency told ProPublica it had provided additional time because HeartWare was a relatively new manufacturer and the HVAD was a complicated device. It also said it avoided punitive action to make sure patients with severe heart failure had access to this treatment option. “We’re talking about the sickest of the sick patients who really have very few alternatives,” Maisel, the head of device quality, said.

But the HeartMate, the competing device, was available and already being used by the majority of patients. When Medtronic stopped HVAD sales, both companies said the HeartMate could fill the gap.

Inspectors continued to find problems at HeartWare facilities in 2015, 2016, 2017 and 2018. In the most recent report in 2018, inspectors identified seven separate violations at the HVAD plant, including three previously cited in the 2014 warning letter. The company was still mishandling newly discovered defects like pins connecting the controller to a power source that could bend and become unusable, and controllers built with incompatible parts that could chemically react and “attack” the plastic exterior.

Again, the inspection report said the company “promised to correct” the issues.

“What penalty is there for noncompliance? There isn’t one,” said Madris Kinard, a former public health analyst with the FDA and the CEO of Device Events, a software company that analyzes FDA device data. “There’s nothing the FDA is doing that penalizes, in any true sense of the matter, the manufacturer.”

By the time sales were halted last month, the HVAD had become the subject of 15 company-initiated “Class I” recalls for dangerous device problems that could cause injury or death.

One recall came with a warning sent to health care providers in December that said pumps were failing to start up properly. The pattern of malfunctions was almost as old as the device itself, the company later admitted when it halted device sales in June. But even recent patients were completely unaware of the problem.
 

“A no-brainer”

When children asked Latoya Johnson Keelen about the cable that came out of her side and connected to a controller on her hip, she told them she was Iron Woman.

For a while, she felt invulnerable with the HVAD on her heart.

Johnson Keelen, who lives in the Atlanta suburbs, learned she needed the device after delivering her fourth child, Isaiah, in early 2018. Doctors diagnosed her with postpartum cardiomyopathy, a rare and mysterious form of heart failure that afflicts mothers during pregnancy or after birth. Black mothers in the South have among the highest rates of the illness. Some mothers quickly regain heart function, some only partially recuperate and others never recover.

Tests showed that Johnson Keelen, then 42, was suddenly in end-stage heart failure.

Her body’s immune response at the time was too strong for her to receive a heart transplant. Doctors gave her two choices: an HVAD or end-of-life hospice care.

“It became a no-brainer,” she said. “I just had a baby. I just gave birth. I’m not ready to plan for a funeral.”

Johnson Keelen, a woman of faith, believed God would heal her, either through a medical advancement or a miracle. She thought the HVAD was the answer.

Living with a life-sustaining medical device was difficult at first for the fiercely independent mother. She had to leave her job as a public health communications specialist, ask her older sons to change her bandages and lean heavily on her new husband, only a year into their marriage.

But, for about three years, she found comfort in the soft humming of the HVAD’s spinning rotor at night. It served as a lullaby for her new baby when he lay on her chest.

She said she was never told about the manufacturing problems the FDA repeatedly found at HeartWare’s facilities or about device recalls, including one sent to patients in December 2020. The notice said the device sometimes wouldn’t restart properly, which had led to two patient deaths at that point. It warned that current patients should always keep at least one power source, a battery or an AC or DC adapter, connected at all times to avoid the need for a restart.

Two months after that notice, Johnson Keelen was getting her kids ready for school when the HVAD’s low-battery alarm blared. She had unplugged the battery to replace it without realizing her wall adapter was disconnected.

Once before, Johnson Keelen had simply plugged the charger back into the outlet and her device restarted. But this time it wouldn’t.

As an emergency alarm sounded, she called the ventricular-assist team assigned to her case, and a specialist directed her to switch out the device controller.

Nothing changed, and panic crept into the voice on the phone.

An ambulance took Johnson Keelen to a hospital where medical staff used several backup controllers to try to start the pump.

Still nothing.

Doctors and nurses tried to keep calm, but Johnson Keelen could see fear and shock on their faces. Without the HVAD, her only options were a transplant or a completely new pump.

Doctors scurried to locate a donor heart and airlifted her for an emergency transplant. But while running tests, the medical team was stunned to find that Johnson Keelen’s miracle had occurred: Her heart was once again pumping blood on its own.

She had a new choice. She could avoid the risks of transplant rejection and open heart surgery during the pandemic by leaving the device on her functioning heart, while cutting the wires, removing the external components and sealing the pump.

She chose to trust her newly functioning heart, and leave the decommissioned HVAD inside her.

Three months later, when Medtronic said it was stopping HeartWare sales and implants, its announcement cited the problem with pumps not restarting among the reasons.
 

Company-led oversight

If evidence suggests a medical device may be linked to a serious patient injury or death, hospitals and other health care facilities must submit a report to the manufacturer and the FDA. Device companies must also submit reports if they learn independently of any incidents.

By the end of 2020, roughly 3,000 death reports and 20,000 injury reports related to the HVAD had been filed with the FDA.

Any details that could identify patients, like their age or gender, are removed from the publicly available reports. Most only have limited details about circumstances surrounding deaths or injuries. But it’s clear from the reports on the HVAD that some of these outcomes could be linked to problems previously identified by FDA inspectors.

Doctors attempted CPR for two hours after an electrostatic shock short-circuited one patient’s device in 2014, a few months after the FDA inspection that year. An autopsy revealed voltage had caused “deep charring” of the tissue inside the patient’s chest.

Friends found another patient dead in the kitchen, with groceries still on the counter, in 2018 after their device, which did not have the recommended static shield, short-circuited.

Last year, paramedics found a patient with the device disconnected from power. They struggled to restart the device, but it wouldn’t plug back into the power source because the connector pins were bent. The patient would die at the hospital.

In most cases, the FDA turned to the company to investigate whether a malfunction caused or contributed to the incidents.

But the FDA has long known HeartWare and Medtronic could not be relied on to properly submit HVAD incident reports.

In 2014, the FDA cited HeartWare because in at least 10 cases, there were no documents showing the company attempted to investigate.

In 2016, the agency wrote another citation when the company was late in reporting more than 200 cases, some more than a year past their 30-day reporting deadlines, and failed to report malfunctions that occurred during clinical trials.

The FDA told ProPublica the agency increased its monitoring of HVAD reports, and Medtronic hired new employees to submit timely reports. But by 2018, its backlog had only grown, with 677 late case filings. Again, the FDA did nothing beyond telling the company to fix the problem and further increasing its monitoring.

In an email, Medtronic said it “has robust systems in place to monitor the safety of all of our products, including the HVAD device.”

The email said, “When any potential safety issues are identified, those issues are thoroughly investigated and relevant information is shared with regulators and healthcare providers.” The company didn’t respond to the pattern of late reports and incomplete investigations identified in FDA inspections.

Maisel, the director of FDA device evaluation and quality, once criticized asking companies to investigate their own devices. In 2008, as a practicing cardiologist, he testified to the U.S. House oversight committee about his concerns.

“In the majority of cases, FDA relies on industry to identify, correct and report the problems,” he said. “But there is obviously an inherent financial conflict of interest for the manufacturers, sometimes measured in billions of dollars.”

Maisel has since had a change of heart. When asked about his 2008 testimony, he told ProPublica that he now believes the regulatory system “generally serves patients well” and “most companies are well intentioned.”

HeartWare’s track record of questionable investigations was glaring in John Winkler II’s case.

A report submitted by HeartWare that matches the dates and details of Winkler’s case shows the company decided there was “no indication of any device malfunctions.” It told the FDA that the device couldn’t be removed from the body because the hospital said his family declined an autopsy. HeartWare added that the evidence of the device’s role in Winkler’s death was inconclusive.

Yet little of this appears to be true. Documents reviewed by ProPublica show an autopsy of the heart and lungs was performed a day after the death. Tina Winkler said she was told the pump was removed from her husband’s body and was available for inspection.

A year after John Winkler’s death, HeartWare recalled 18,000 potentially faulty batteries produced between 2013 and 2015. Tina Winkler came across the notice online and found her husband’s battery serial numbers on the list. The company never contacted her about it or any further investigation, she said.
 

Rewards, not penalties

As deaths and recalls mounted, HeartWare and Medtronic touted additional FDA approval to treat more patients and their attempts to develop new cutting-edge devices.

With the company on notice under the 2014 warning letter, HeartWare geared up to begin human trials on a smaller heart pump, called the MVAD or Miniaturized Ventricular Assist Device. It would be powered by a new algorithm to more efficiently pump blood. Industry analysts predicted robust sales.

In July 2015, implantations were set to begin on a select group of 60 patients in Europe and Australia. But they were abruptly stopped less than two months later after only 11 implants. Patients experienced numerous adverse events, including major bleeding, infection and device malfunction, according to published data.

HeartWare’s stock price plummeted from about $85 to $35 by October 2015. The next year, Medtronic bought HeartWare for $1.1 billion, replacing much of the company’s leadership shortly after.

Some former HeartWare investors filed a class action lawsuit in January 2016 alleging deception in the development of the MVAD.

According to the accounts of six anonymous former employees in the lawsuit, the details mirror the scandal surrounding Theranos, the former blood test company charged with fraud for raising more than $700 million by allegedly lying about its technology.

Where Theranos made empty promises of a test that only needed a few drops of blood, the suit alleges HeartWare promoted a life-sustaining medical device that former employees said had many problems and actually worsened blood flow, increasing clotting risks.

“Nothing really worked right,” one former HeartWare manager said in the lawsuit, citing “improper alarms, improper touch screen performance, gibberish on display screens — just so many alerts and problems.”

Leadership proceeded with human testing anyway, the suit alleges.

Months later, at an investor conference, HeartWare leadership acknowledged the pump and algorithm led to multiple adverse events. For two patients in particular, the algorithm would direct the pump to speed up so fast that it would try to suck up more blood than was available inside the heart for prolonged periods of time.

HeartWare and Medtronic settled the investor suit for $54.5 million in 2018, admitting no fault.

None of the allegations slowed the FDA as it gave Medtronic additional approval and support for its heart pump technologies.

In September 2017, the agency approved the HVAD as “destination therapy” for patients who were not heart transplant candidates and would rely on the device for the rest of their lives.

“We’re really excited about our HVAD destination therapy approval,” a Medtronic executive said on an investor earnings call. “That’s a real game changer for us in that market.”

Two years later, Medtronic announced it was developing a fully implantable version of the HVAD that would no longer need a cable coming through the waist to connect to power.

Even though issues with the HeartWare device had been unresolved for five years at that point, the FDA accepted the pitch into its new fast-track approval process for high-risk devices.

“Slipped Through The Cracks”

After Johnson Keelen’s pump failed in February, she found a news story about the recall notice sent to medical providers two months prior.

It said the company had identified a problem with pump restarts that could cause heart attacks or serious patient harm. Nineteen patients had been seriously injured so far, and two people had died. The recall warned that patients should be careful to avoid disconnecting the device’s power sources.

“I kept seeing Medtronic on record saying they notified patients,” Johnson Keelen said. “Who did they contact? No one told me.”

Her doctor later told her she must have “slipped through the cracks,” she said.

The current system for informing patients of new safety concerns with high-risk devices relies on a communication chain that can easily break. The device company contacts the FDA and health care providers that work with device patients. The FDA typically issues a public notice, while health professionals contact their patients.

But the agency admits most patients don’t know to look for formal FDA postings. And, experts say, the medical system can lose track of who needs to be notified, especially if a patient moves or switches primary care physicians.

Tina Winkler still wonders why she was never told about FDA-known safety issues with the HVAD. She said her husband’s medical team “had to teach me how to clean his wound, how to change his batteries and what to do if alarms go off. And they never mentioned any of this.”

She said, “If we had all the facts, there’s no way he would have gotten that device implanted in his heart.”

When FDA inspectors find serious safety issues with a medical device, inspection reports are not posted online or sent to patients. The public can obtain reports through a Freedom of Information Act request, but the agency’s records department has said new requests can be stuck behind a year-long backlog.

Patients can find warning letters online in a searchable database of thousands of letters from different FDA divisions, including the center for devices. But HeartWare’s 2014 letter is no longer available for public review because the website purges letters older than five years.

There are also few documents available in state courts about faulty products, because of restrictions on lawsuits related to medical devices. The restrictions date back to a 2008 Supreme Court decision in a case against Medtronic. The court found that U.S. law bars patients and their survivors from suing device makers in state court, essentially because their products go through such a rigorous FDA approval process.

Two recent patient lawsuits against HeartWare and Medtronic, including one filed by Tina Winkler, were moved from state court to federal court. In both cases, Medtronic filed to dismiss the cases because of the U.S. law that protects device companies. Medtronic and the families reached private settlements soon after.

Winkler and an attorney for the other family said they could not comment on their settlements.

Johnson Keelen, with a decommissioned HVAD still attached to her heart, wonders what that means for her and other patients’ chances of recourse.

“Why isn’t anyone now stepping up for the patient?” she asked. “They are now liable for taking care of us because we relied on them.”
 

“Run its course”

Deserae Cain, 33, is one of the 4,000 patients still relying on a HeartWare device.

She was implanted with the heart pump in late 2017, after suddenly being diagnosed with heart failure. Scans showed her heart was three times normal size. It took time for her to come to terms with needing a life-sustaining device — not long before her diagnosis, she had been going on five-mile runs. In the four years since, though, Cain has built a life around the HVAD with her fiance in their Dayton, Ohio, home.

They know the device can malfunction. In 2019, the pump failed for almost an hour as doctors at a nearby hospital struggled to restart it. Cain just tried to stay calm, knowing anxiety could threaten her unsupported weak heart. Months later, she needed an emergency experimental procedure to clear out blood clots developed within her HVAD.

Then, in 2020, Cain developed a widespread infection. Doctors told her she needed surgery to clean out and replace the pump.

Cain asked her medical team if she could switch to the alternative HeartMate device, which other patients told her presented fewer problems, she said. Doctors said the HVAD was better suited for her smaller frame.

But her new pump had problems soon after the surgery.

The device’s suction alarms, which alert when the pump is trying to pull in more blood than is available within the heart, sounded multiple times a day, for hours at a time, she said. Baffled by the issue for months, her medical team eventually turned off that specific alarm.

Soon after, her ventricular-assist specialist called her about a patient’s death linked to the belt that holds the device controller, she said. The belt had ripped and the equipment had fallen, yanking on the cable that connected the controller to the pump. Cain replaced her belt but it quickly frayed and had to be replaced again within six weeks.

Then, in June, she found out about Medtronic’s decision to stop sales and implants. Cain received a letter from her hospital mentioning a Medtronic support program, but it provided few specifics.

Cain wondered if things would be any different than before. Anxious about her future, she asked: “Are they just going to let it run its course until there is none of us left?”

This article first appeared on Propublica.

John Winkler II was dying of heart failure when doctors came to his hospital bedside, offering a chance to prolong his life. The HeartWare Ventricular Assist Device, or HVAD, could be implanted in Winkler’s chest until a transplant was possible. The heart pump came with disclaimers of risk, but Winkler wanted to fight for time. He was only 46 and had a loving wife and four children, and his second grandchild was on the way.

So, in August 2014, Winkler had surgery to implant the device. A golf-ball–sized rotor was attached to his left ventricle to pump blood through a tube and into his aorta. A cable threading out of a small incision in his waist connected to a battery-powered controller strapped to his body. If something went wrong, an alarm as loud as a fire drill would sound.

Winkler returned home weeks later and, as he regained his strength, became hopeful about the future. He started making plans to visit colleges with his daughter, and was able to host his parents and new grandchild for Christmas. “He was doing so much better,” his wife, Tina Winkler, said. “We thought he was coasting until he got his transplant.”

What John Winkler didn’t know: Months before his implant, the Food and Drug Administration put HeartWare on notice for not properly monitoring or repairing HVAD defects, such as faulty batteries and short circuits caused by static electricity, that had killed patients. The agency issued a warning letter, one of its most serious citations. It demanded fixes within 15 days, but took no decisive action as problems persisted.

Ten days after Christmas of 2014, Winkler’s two teenage children heard the HVAD’s piercing alarm and ran upstairs. They found their father collapsed on his bedroom floor, completely unresponsive. Kelly, 17, dropped to his side and tried to copy how people on television did CPR. She told her brother to call 911, and over the device’s siren did her best to hear instructions from the operator.

When paramedics arrived and assessed her father, one made a passing comment that has haunted Kelly ever since: “Well, his toes are already cold.” He died 2 days later. Medtronic, the company that acquired HeartWare in 2016, settled a lawsuit by the family last year, admitting no fault. Tina Winkler believes her children blamed themselves for their father’s death. “Those two kids have never been the same,” she said. “I think they feel like they didn’t do things they needed to do.”

But it was the FDA that failed to protect Winkler and thousands of other patients whose survival depended on the HVAD, a ProPublica investigation found.

As HeartWare and Medtronic failed inspection after inspection and reports of device-related deaths piled up, the FDA relied on the device makers to fix the problems voluntarily rather than compelling them to do so.

The HVAD was implanted into more than 19,000 patients, the majority of whom got it after the FDA found in 2014 that the device didn’t meet federal standards. By the end of last year, the agency had received more than 3,000 reports of patient deaths that may have been caused or contributed to by the device.

Among them were reports of deaths the company linked to serious device problems: a patient who vomited blood as a family member struggled to restart a defective HVAD; a patient who bled out internally and died after implant surgery because a tube attached to the pump tore open; a patient whose heart tissue was left charred after an HVAD short-circuited and voltage surged through the pump.

The ineffective regulatory oversight of the HVAD is emblematic of larger, more systemic weaknesses.

For decades, the FDA and its Center for Devices and Radiological Health have been responsible for ensuring that high-risk medical devices are safe and effective. Yet they rely mostly on manufacturers to identify and correct problems. The agency says it can seize products, order injunctions against companies, or issue fines, but it rarely does so, preferring instead for companies to make fixes voluntarily.

When federal investigators found repeated manufacturing issues with the HVAD for years, the FDA didn’t penalize the company, even as the company issued 15 serious recalls of the device starting in 2014, the most of any single high-risk device in the FDA’s database. Thousands of patients with recalled models needed to have external HVAD parts replaced or take extra caution while handling their devices and monitor them for signs of malfunctions that could cause injury or death.

Meanwhile, the processes to inform the public through formal FDA notices and messages to health care providers repeatedly failed and left patients in the dark about known problems with the HVAD.

“Patients have no idea, and they rely on the FDA to ensure the safety and effectiveness of high-risk devices,” said Dr. Rita Redberg, a cardiologist at the University of California, San Francisco, who studies medical device regulation. “How can you not take action on a warning letter with these serious issues with very sick patients?”

In response to ProPublica’s findings, the FDA said it had been closely monitoring issues with the HVAD. It said that after Medtronic acquired HeartWare in 2016, it met with the company more than 100 times to ensure problems were being fixed and to review safety concerns related to the heart pump. The agency also said it initiated formal reviews of new device modifications and continually tracked whether the HVAD had a “reasonable assurance of safety and effectiveness.”

“Our decisions that we made along the way have always been patient focused,” said Dr. William Maisel, director of product evaluation and quality at the FDA’s device division. He added that more than 80% of companies fix their problems by the time the FDA reinspects.

That did not happen with the HVAD. In 2016 and 2018, inspectors found that issues detailed in the 2014 warning letter remained unresolved. Medtronic told the FDA last year that it had fixed the problems, but, before the agency could verify the claim, inspections were paused because of the coronavirus pandemic.

In June, Medtronic stopped HVAD sales and implants. The company conceded that a competing device was safer after a new study showed the HVAD had higher rates of death and neurological injury. Medtronic also cited a 12-year-old problem with its devices not restarting if they disconnect from power, leaving patients’ hearts without support.

Medtronic declined to make Geoffrey Martha, CEO, or Nnamdi Njoku, president of mechanical heart support, available for interviews. In an email, a spokesperson said, “There is nothing more important to Medtronic than the safety and well-being of patients.”

The email continued: “Medtronic takes this matter very seriously and, over the past five years, we have worked closely with FDA and engaged external experts to resolve the issues noted in the warning letter. FDA is aware of the steps Medtronic has taken to address the underlying concerns.”

The company said it will have a support system in place for the 4,000 patients worldwide and 2,000 in the United States who still rely on the HVAD. Medtronic will station 20 specialists across the globe to help with device maintenance and patient education. A centralized engineering team will provide technical support and troubleshooting for patients and medical staff. Medtronic said it will offer financial assistance if insurance doesn’t fully cover the surgery to replace a device with a competing product, but only if a doctor decides it’s medically necessary.

Patients with HVADs have little choice but to hope the devices keep working: The surgery to remove HVADs is so risky that both Medtronic and the FDA advise against it. The device is meant to be left in place until its wearer gets a heart transplant. Or dies.
 

Warning signs

In late 2012, HeartWare, then an independent company headquartered in Massachusetts, won FDA approval to sell a new device that could keep heart failure patients alive and mobile while awaiting a transplant.

A competing device, the HeartMate, was already gaining attention, with high-profile patients like former Vice President Dick Cheney, a heart attack survivor who eventually got a transplant after using the device for 20 months.

The HVAD offered a smaller option that could even be used in children, and it led to a string of publicized successes. A fitness model was able to return to the gym. A 13-year-old with heart defects could attend school again. Medtronic’s YouTube page features 16 interviews with grateful patients and families.

The patients who received HVADs had already been in grave peril. They had advanced heart failure, serious enough to need blood pumped out of their hearts artificially. Most patients were older than 50, but there were also younger patients with heart defects or other cardiac conditions. The device provided help but brought its own risks. Implanting it required invasive open-heart surgery, and clots could develop inside the pump, which, in the worst cases, led to deadly strokes.

The device also came with a steep price tag. Each HVAD cost about $80,000, and, even though HeartWare never made a profit as an independent company, in 2015 device sales brought in $276 million in revenue.

For many severe heart failure patients, the opportunity to survive longer and return to normal life made the device worth the risks and cost.

But patients were unaware the FDA started finding manufacturing issues at HeartWare’s Miami Lakes, Florida, plant as early as 2011, when the device was still seeking approval.

Among the findings, a federal inspector expressed concerns that engineering staff “were not completely reviewing documents before approving them” and found one employee assigned to monitoring device quality had missed several required monthly trainings. HeartWare leadership promised quick corrective action, according to FDA documents.

Then, in 2014, the FDA found more serious lapses, detailed in federal inspection reports.

For example, HeartWare knew of 119 instances in which batteries failed unexpectedly, which could leave the pump powerless, stopping support for the patient’s heart. But the company didn’t test the batteries in inventory for defects, or the batteries of current patients, even though one person’s death had already been linked to battery failure.

The company also received complaints that static electricity could short-circuit its devices. It learned of at least 27 such cases between 2010 and 2013, including four that resulted in serious injuries and two that led to death. HVAD patients would need to avoid contact with certain household objects like televisions or vacuum cleaners — anything that could create strong static electricity. HeartWare added warnings to the patient manual and redesigned its shield to protect the device controller, but the FDA found that the company didn’t replace shields for devices already being used by current patients or produced and sitting in inventory.

Continuing quality control concerns led to the FDA warning letter in June 2014. The document labeled the HVAD as “adulterated,” meaning the device did not meet federal manufacturing standards. The agency gave HeartWare 15 days to correct the problems or face regulatory action.

Still, investment analysts who followed HeartWare believed the warning posed little risk to the company’s business prospects. One described it as being “as benign as possible.”

The 15-day deadline passed, and the FDA never penalized the company.

The agency told ProPublica it had provided additional time because HeartWare was a relatively new manufacturer and the HVAD was a complicated device. It also said it avoided punitive action to make sure patients with severe heart failure had access to this treatment option. “We’re talking about the sickest of the sick patients who really have very few alternatives,” Maisel, the head of device quality, said.

But the HeartMate, the competing device, was available and already being used by the majority of patients. When Medtronic stopped HVAD sales, both companies said the HeartMate could fill the gap.

Inspectors continued to find problems at HeartWare facilities in 2015, 2016, 2017 and 2018. In the most recent report in 2018, inspectors identified seven separate violations at the HVAD plant, including three previously cited in the 2014 warning letter. The company was still mishandling newly discovered defects like pins connecting the controller to a power source that could bend and become unusable, and controllers built with incompatible parts that could chemically react and “attack” the plastic exterior.

Again, the inspection report said the company “promised to correct” the issues.

“What penalty is there for noncompliance? There isn’t one,” said Madris Kinard, a former public health analyst with the FDA and the CEO of Device Events, a software company that analyzes FDA device data. “There’s nothing the FDA is doing that penalizes, in any true sense of the matter, the manufacturer.”

By the time sales were halted last month, the HVAD had become the subject of 15 company-initiated “Class I” recalls for dangerous device problems that could cause injury or death.

One recall came with a warning sent to health care providers in December that said pumps were failing to start up properly. The pattern of malfunctions was almost as old as the device itself, the company later admitted when it halted device sales in June. But even recent patients were completely unaware of the problem.
 

“A no-brainer”

When children asked Latoya Johnson Keelen about the cable that came out of her side and connected to a controller on her hip, she told them she was Iron Woman.

For a while, she felt invulnerable with the HVAD on her heart.

Johnson Keelen, who lives in the Atlanta suburbs, learned she needed the device after delivering her fourth child, Isaiah, in early 2018. Doctors diagnosed her with postpartum cardiomyopathy, a rare and mysterious form of heart failure that afflicts mothers during pregnancy or after birth. Black mothers in the South have among the highest rates of the illness. Some mothers quickly regain heart function, some only partially recuperate and others never recover.

Tests showed that Johnson Keelen, then 42, was suddenly in end-stage heart failure.

Her body’s immune response at the time was too strong for her to receive a heart transplant. Doctors gave her two choices: an HVAD or end-of-life hospice care.

“It became a no-brainer,” she said. “I just had a baby. I just gave birth. I’m not ready to plan for a funeral.”

Johnson Keelen, a woman of faith, believed God would heal her, either through a medical advancement or a miracle. She thought the HVAD was the answer.

Living with a life-sustaining medical device was difficult at first for the fiercely independent mother. She had to leave her job as a public health communications specialist, ask her older sons to change her bandages and lean heavily on her new husband, only a year into their marriage.

But, for about three years, she found comfort in the soft humming of the HVAD’s spinning rotor at night. It served as a lullaby for her new baby when he lay on her chest.

She said she was never told about the manufacturing problems the FDA repeatedly found at HeartWare’s facilities or about device recalls, including one sent to patients in December 2020. The notice said the device sometimes wouldn’t restart properly, which had led to two patient deaths at that point. It warned that current patients should always keep at least one power source, a battery or an AC or DC adapter, connected at all times to avoid the need for a restart.

Two months after that notice, Johnson Keelen was getting her kids ready for school when the HVAD’s low-battery alarm blared. She had unplugged the battery to replace it without realizing her wall adapter was disconnected.

Once before, Johnson Keelen had simply plugged the charger back into the outlet and her device restarted. But this time it wouldn’t.

As an emergency alarm sounded, she called the ventricular-assist team assigned to her case, and a specialist directed her to switch out the device controller.

Nothing changed, and panic crept into the voice on the phone.

An ambulance took Johnson Keelen to a hospital where medical staff used several backup controllers to try to start the pump.

Still nothing.

Doctors and nurses tried to keep calm, but Johnson Keelen could see fear and shock on their faces. Without the HVAD, her only options were a transplant or a completely new pump.

Doctors scurried to locate a donor heart and airlifted her for an emergency transplant. But while running tests, the medical team was stunned to find that Johnson Keelen’s miracle had occurred: Her heart was once again pumping blood on its own.

She had a new choice. She could avoid the risks of transplant rejection and open heart surgery during the pandemic by leaving the device on her functioning heart, while cutting the wires, removing the external components and sealing the pump.

She chose to trust her newly functioning heart, and leave the decommissioned HVAD inside her.

Three months later, when Medtronic said it was stopping HeartWare sales and implants, its announcement cited the problem with pumps not restarting among the reasons.
 

Company-led oversight

If evidence suggests a medical device may be linked to a serious patient injury or death, hospitals and other health care facilities must submit a report to the manufacturer and the FDA. Device companies must also submit reports if they learn independently of any incidents.

By the end of 2020, roughly 3,000 death reports and 20,000 injury reports related to the HVAD had been filed with the FDA.

Any details that could identify patients, like their age or gender, are removed from the publicly available reports. Most only have limited details about circumstances surrounding deaths or injuries. But it’s clear from the reports on the HVAD that some of these outcomes could be linked to problems previously identified by FDA inspectors.

Doctors attempted CPR for two hours after an electrostatic shock short-circuited one patient’s device in 2014, a few months after the FDA inspection that year. An autopsy revealed voltage had caused “deep charring” of the tissue inside the patient’s chest.

Friends found another patient dead in the kitchen, with groceries still on the counter, in 2018 after their device, which did not have the recommended static shield, short-circuited.

Last year, paramedics found a patient with the device disconnected from power. They struggled to restart the device, but it wouldn’t plug back into the power source because the connector pins were bent. The patient would die at the hospital.

In most cases, the FDA turned to the company to investigate whether a malfunction caused or contributed to the incidents.

But the FDA has long known HeartWare and Medtronic could not be relied on to properly submit HVAD incident reports.

In 2014, the FDA cited HeartWare because in at least 10 cases, there were no documents showing the company attempted to investigate.

In 2016, the agency wrote another citation when the company was late in reporting more than 200 cases, some more than a year past their 30-day reporting deadlines, and failed to report malfunctions that occurred during clinical trials.

The FDA told ProPublica the agency increased its monitoring of HVAD reports, and Medtronic hired new employees to submit timely reports. But by 2018, its backlog had only grown, with 677 late case filings. Again, the FDA did nothing beyond telling the company to fix the problem and further increasing its monitoring.

In an email, Medtronic said it “has robust systems in place to monitor the safety of all of our products, including the HVAD device.”

The email said, “When any potential safety issues are identified, those issues are thoroughly investigated and relevant information is shared with regulators and healthcare providers.” The company didn’t respond to the pattern of late reports and incomplete investigations identified in FDA inspections.

Maisel, the director of FDA device evaluation and quality, once criticized asking companies to investigate their own devices. In 2008, as a practicing cardiologist, he testified to the U.S. House oversight committee about his concerns.

“In the majority of cases, FDA relies on industry to identify, correct and report the problems,” he said. “But there is obviously an inherent financial conflict of interest for the manufacturers, sometimes measured in billions of dollars.”

Maisel has since had a change of heart. When asked about his 2008 testimony, he told ProPublica that he now believes the regulatory system “generally serves patients well” and “most companies are well intentioned.”

HeartWare’s track record of questionable investigations was glaring in John Winkler II’s case.

A report submitted by HeartWare that matches the dates and details of Winkler’s case shows the company decided there was “no indication of any device malfunctions.” It told the FDA that the device couldn’t be removed from the body because the hospital said his family declined an autopsy. HeartWare added that the evidence of the device’s role in Winkler’s death was inconclusive.

Yet little of this appears to be true. Documents reviewed by ProPublica show an autopsy of the heart and lungs was performed a day after the death. Tina Winkler said she was told the pump was removed from her husband’s body and was available for inspection.

A year after John Winkler’s death, HeartWare recalled 18,000 potentially faulty batteries produced between 2013 and 2015. Tina Winkler came across the notice online and found her husband’s battery serial numbers on the list. The company never contacted her about it or any further investigation, she said.
 

Rewards, not penalties

As deaths and recalls mounted, HeartWare and Medtronic touted additional FDA approval to treat more patients and their attempts to develop new cutting-edge devices.

With the company on notice under the 2014 warning letter, HeartWare geared up to begin human trials on a smaller heart pump, called the MVAD or Miniaturized Ventricular Assist Device. It would be powered by a new algorithm to more efficiently pump blood. Industry analysts predicted robust sales.

In July 2015, implantations were set to begin on a select group of 60 patients in Europe and Australia. But they were abruptly stopped less than two months later after only 11 implants. Patients experienced numerous adverse events, including major bleeding, infection and device malfunction, according to published data.

HeartWare’s stock price plummeted from about $85 to $35 by October 2015. The next year, Medtronic bought HeartWare for $1.1 billion, replacing much of the company’s leadership shortly after.

Some former HeartWare investors filed a class action lawsuit in January 2016 alleging deception in the development of the MVAD.

According to the accounts of six anonymous former employees in the lawsuit, the details mirror the scandal surrounding Theranos, the former blood test company charged with fraud for raising more than $700 million by allegedly lying about its technology.

Where Theranos made empty promises of a test that only needed a few drops of blood, the suit alleges HeartWare promoted a life-sustaining medical device that former employees said had many problems and actually worsened blood flow, increasing clotting risks.

“Nothing really worked right,” one former HeartWare manager said in the lawsuit, citing “improper alarms, improper touch screen performance, gibberish on display screens — just so many alerts and problems.”

Leadership proceeded with human testing anyway, the suit alleges.

Months later, at an investor conference, HeartWare leadership acknowledged the pump and algorithm led to multiple adverse events. For two patients in particular, the algorithm would direct the pump to speed up so fast that it would try to suck up more blood than was available inside the heart for prolonged periods of time.

HeartWare and Medtronic settled the investor suit for $54.5 million in 2018, admitting no fault.

None of the allegations slowed the FDA as it gave Medtronic additional approval and support for its heart pump technologies.

In September 2017, the agency approved the HVAD as “destination therapy” for patients who were not heart transplant candidates and would rely on the device for the rest of their lives.

“We’re really excited about our HVAD destination therapy approval,” a Medtronic executive said on an investor earnings call. “That’s a real game changer for us in that market.”

Two years later, Medtronic announced it was developing a fully implantable version of the HVAD that would no longer need a cable coming through the waist to connect to power.

Even though issues with the HeartWare device had been unresolved for five years at that point, the FDA accepted the pitch into its new fast-track approval process for high-risk devices.

“Slipped Through The Cracks”

After Johnson Keelen’s pump failed in February, she found a news story about the recall notice sent to medical providers two months prior.

It said the company had identified a problem with pump restarts that could cause heart attacks or serious patient harm. Nineteen patients had been seriously injured so far, and two people had died. The recall warned that patients should be careful to avoid disconnecting the device’s power sources.

“I kept seeing Medtronic on record saying they notified patients,” Johnson Keelen said. “Who did they contact? No one told me.”

Her doctor later told her she must have “slipped through the cracks,” she said.

The current system for informing patients of new safety concerns with high-risk devices relies on a communication chain that can easily break. The device company contacts the FDA and health care providers that work with device patients. The FDA typically issues a public notice, while health professionals contact their patients.

But the agency admits most patients don’t know to look for formal FDA postings. And, experts say, the medical system can lose track of who needs to be notified, especially if a patient moves or switches primary care physicians.

Tina Winkler still wonders why she was never told about FDA-known safety issues with the HVAD. She said her husband’s medical team “had to teach me how to clean his wound, how to change his batteries and what to do if alarms go off. And they never mentioned any of this.”

She said, “If we had all the facts, there’s no way he would have gotten that device implanted in his heart.”

When FDA inspectors find serious safety issues with a medical device, inspection reports are not posted online or sent to patients. The public can obtain reports through a Freedom of Information Act request, but the agency’s records department has said new requests can be stuck behind a year-long backlog.

Patients can find warning letters online in a searchable database of thousands of letters from different FDA divisions, including the center for devices. But HeartWare’s 2014 letter is no longer available for public review because the website purges letters older than five years.

There are also few documents available in state courts about faulty products, because of restrictions on lawsuits related to medical devices. The restrictions date back to a 2008 Supreme Court decision in a case against Medtronic. The court found that U.S. law bars patients and their survivors from suing device makers in state court, essentially because their products go through such a rigorous FDA approval process.

Two recent patient lawsuits against HeartWare and Medtronic, including one filed by Tina Winkler, were moved from state court to federal court. In both cases, Medtronic filed to dismiss the cases because of the U.S. law that protects device companies. Medtronic and the families reached private settlements soon after.

Winkler and an attorney for the other family said they could not comment on their settlements.

Johnson Keelen, with a decommissioned HVAD still attached to her heart, wonders what that means for her and other patients’ chances of recourse.

“Why isn’t anyone now stepping up for the patient?” she asked. “They are now liable for taking care of us because we relied on them.”
 

“Run its course”

Deserae Cain, 33, is one of the 4,000 patients still relying on a HeartWare device.

She was implanted with the heart pump in late 2017, after suddenly being diagnosed with heart failure. Scans showed her heart was three times normal size. It took time for her to come to terms with needing a life-sustaining device — not long before her diagnosis, she had been going on five-mile runs. In the four years since, though, Cain has built a life around the HVAD with her fiance in their Dayton, Ohio, home.

They know the device can malfunction. In 2019, the pump failed for almost an hour as doctors at a nearby hospital struggled to restart it. Cain just tried to stay calm, knowing anxiety could threaten her unsupported weak heart. Months later, she needed an emergency experimental procedure to clear out blood clots developed within her HVAD.

Then, in 2020, Cain developed a widespread infection. Doctors told her she needed surgery to clean out and replace the pump.

Cain asked her medical team if she could switch to the alternative HeartMate device, which other patients told her presented fewer problems, she said. Doctors said the HVAD was better suited for her smaller frame.

But her new pump had problems soon after the surgery.

The device’s suction alarms, which alert when the pump is trying to pull in more blood than is available within the heart, sounded multiple times a day, for hours at a time, she said. Baffled by the issue for months, her medical team eventually turned off that specific alarm.

Soon after, her ventricular-assist specialist called her about a patient’s death linked to the belt that holds the device controller, she said. The belt had ripped and the equipment had fallen, yanking on the cable that connected the controller to the pump. Cain replaced her belt but it quickly frayed and had to be replaced again within six weeks.

Then, in June, she found out about Medtronic’s decision to stop sales and implants. Cain received a letter from her hospital mentioning a Medtronic support program, but it provided few specifics.

Cain wondered if things would be any different than before. Anxious about her future, she asked: “Are they just going to let it run its course until there is none of us left?”

This article first appeared on Propublica.