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Add AFib to noncardiac surgery risk evaluation: New support
Practice has gone back and forth on whether atrial fibrillation (AFib) should be considered in the preoperative cardiovascular risk (CV) evaluation of patients slated for noncardiac surgery, and the Revised Cardiac Risk Index (RCRI), currently widely used as an assessment tool, doesn’t include the arrhythmia.
But consideration of preexisting AFib along with the RCRI predicted 30-day mortality more sharply than the RCRI alone in an analysis of data covering several million patients slated for such procedures.
Indeed, AFib emerged as a significant, independent risk factor for a number of bad postoperative outcomes. Mortality within a month of the procedure climbed about 30% for patients with AFib before the noncardiac surgery. Their 30-day risks for stroke and for heart failure hospitalization went up similarly.
The addition of AFib to the RCRI significantly improved its ability to discriminate 30-day postoperative risk levels regardless of age, sex, and type of noncardiac surgery, Amgad Mentias, MD, Cleveland Clinic, told this news organization. And “it was able to correctly up-classify patients to high risk, if AFib was there, and it was able to down-classify some patients to lower risk if it wasn’t there.”
“I think [the findings] are convincing evidence that atrial fib should at least be part of the thought process for the surgical team and the medical team taking care of the patient,” said Dr. Mentias, who is senior author on the study published in the Journal of the American College of Cardiology, with lead author Sameer Prasada, MD, also of the Cleveland Clinic.
The results “call for incorporating AFib as a risk factor in perioperative risk scores for cardiovascular morbidity and mortality,” the published report states.
Supraventricular arrhythmias had been part of the Goldman Risk Index once widely used preoperatively to assess cardiac risk before practice adopted the RCRI in the past decade, observe Anne B. Curtis, MD, and Sai Krishna C. Korada, MD, University at Buffalo, New York, in an accompanying editorial.
The current findings “demonstrate improved prediction of adverse postsurgical outcomes” from supplementing the RCRI with AFib, they write. Given associations between preexisting AFib and serious cardiac events, “it is time to ‘re-revise’ the RCRI and acknowledge the importance of AFib in predicting adverse outcomes” after noncardiac surgery.
The new findings, however, aren’t all straightforward. In one result that remains a bit of a head-scratcher, postoperative risk of myocardial infarction (MI) in patients with preexisting AFib went in the opposite direction of risk for death and other CV outcomes, falling by almost 20%.
That is “hard to explain with the available data,” the report states, but “the use of anticoagulation, whether oral or parenteral (as a bridge therapy in the perioperative period), is a plausible explanation” given the frequent role of thrombosis in triggering MIs.
Consistent with such a mechanism, the group argues, the MI risk reduction was seen primarily among patients with AFib and a CHA2DS2-VASc score of 2 or higher – that is, those at highest risk for stroke and therefore most likely to be on oral anticoagulation. The MI risk reduction wasn’t seen in such patients with a CHA2DS2-VASc score of 0 or 1.
“I think that’s part of the explanation, that anticoagulation can reduce risk of MI. But it’s not the whole explanation,” Dr. Mentias said in an interview. If it were the sole mechanism, he said, then the same oral anticoagulation that protected against MI should have also cut the postoperative stroke risk. Yet that risk climbed 40% among patients with preexisting AFib.
The analysis started with 8.6 million Medicare patients with planned noncardiac surgery, seen from 2015 to 2019, of whom 16.4% had preexisting AFib. Propensity matching for demographics, urgency and type of surgery, CHA2DS2-VASc score, and RCRI index created two cohorts for comparison: 1.13 million patients with and 1.92 million without preexisting AFib.
Preexisting AFib was associated with a higher 30-day risk for death from any cause, the primary endpoint being 8.3% versus 5.8% for those without such AFib (P < .001), for an odds ratio of 1.31 (95% confidence interval, 1.30-1.32).
Corresponding 30-day ORs for other events, all significant at P < .001, were:
- 1.31 (95% CI, 1.30-1.33) for heart failure
- 1.40 (95% CI, 1.37-1.43) for stroke
- 1.59 (95% CI, 1.43-1.75) for systemic embolism
- 1.14 (95% CI, 1.13-1.16) for major bleeding
- 0.81 (95% CI, 0.79-0.82) for MI
Those with preexisting AFib also had longer hospitalizations at a median 5 days, compared with 4 days for those without such AFib (P < .001).
The study has the limitations of most any retrospective cohort analysis. Other limitations, the report notes, include lack of information on any antiarrhythmic meds given during hospitalization or type of AFib.
For example, AFib that is permanent – compared with paroxysmal or persistent – may be associated with more atrial fibrosis, greater atrial dilatation, “and probably higher pressures inside the heart,” Dr. Mentias observed.
“That’s not always the case, but that’s the notion. So presumably people with persistent or permanent atrial fib would have more advanced heart disease, and that could imply more risk. But we did not have that kind of data.”
Dr. Mentias and Dr. Prasada report no relevant financial relationships; disclosures for the other authors are in the report. Dr. Curtis discloses serving on advisory boards for Abbott, Janssen Pharmaceuticals, Sanofi, and Milestone Pharmaceuticals; receiving honoraria for speaking from Medtronic and Zoll; and serving on a data-monitoring board for Medtronic. Dr. Korada reports he has no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Practice has gone back and forth on whether atrial fibrillation (AFib) should be considered in the preoperative cardiovascular risk (CV) evaluation of patients slated for noncardiac surgery, and the Revised Cardiac Risk Index (RCRI), currently widely used as an assessment tool, doesn’t include the arrhythmia.
But consideration of preexisting AFib along with the RCRI predicted 30-day mortality more sharply than the RCRI alone in an analysis of data covering several million patients slated for such procedures.
Indeed, AFib emerged as a significant, independent risk factor for a number of bad postoperative outcomes. Mortality within a month of the procedure climbed about 30% for patients with AFib before the noncardiac surgery. Their 30-day risks for stroke and for heart failure hospitalization went up similarly.
The addition of AFib to the RCRI significantly improved its ability to discriminate 30-day postoperative risk levels regardless of age, sex, and type of noncardiac surgery, Amgad Mentias, MD, Cleveland Clinic, told this news organization. And “it was able to correctly up-classify patients to high risk, if AFib was there, and it was able to down-classify some patients to lower risk if it wasn’t there.”
“I think [the findings] are convincing evidence that atrial fib should at least be part of the thought process for the surgical team and the medical team taking care of the patient,” said Dr. Mentias, who is senior author on the study published in the Journal of the American College of Cardiology, with lead author Sameer Prasada, MD, also of the Cleveland Clinic.
The results “call for incorporating AFib as a risk factor in perioperative risk scores for cardiovascular morbidity and mortality,” the published report states.
Supraventricular arrhythmias had been part of the Goldman Risk Index once widely used preoperatively to assess cardiac risk before practice adopted the RCRI in the past decade, observe Anne B. Curtis, MD, and Sai Krishna C. Korada, MD, University at Buffalo, New York, in an accompanying editorial.
The current findings “demonstrate improved prediction of adverse postsurgical outcomes” from supplementing the RCRI with AFib, they write. Given associations between preexisting AFib and serious cardiac events, “it is time to ‘re-revise’ the RCRI and acknowledge the importance of AFib in predicting adverse outcomes” after noncardiac surgery.
The new findings, however, aren’t all straightforward. In one result that remains a bit of a head-scratcher, postoperative risk of myocardial infarction (MI) in patients with preexisting AFib went in the opposite direction of risk for death and other CV outcomes, falling by almost 20%.
That is “hard to explain with the available data,” the report states, but “the use of anticoagulation, whether oral or parenteral (as a bridge therapy in the perioperative period), is a plausible explanation” given the frequent role of thrombosis in triggering MIs.
Consistent with such a mechanism, the group argues, the MI risk reduction was seen primarily among patients with AFib and a CHA2DS2-VASc score of 2 or higher – that is, those at highest risk for stroke and therefore most likely to be on oral anticoagulation. The MI risk reduction wasn’t seen in such patients with a CHA2DS2-VASc score of 0 or 1.
“I think that’s part of the explanation, that anticoagulation can reduce risk of MI. But it’s not the whole explanation,” Dr. Mentias said in an interview. If it were the sole mechanism, he said, then the same oral anticoagulation that protected against MI should have also cut the postoperative stroke risk. Yet that risk climbed 40% among patients with preexisting AFib.
The analysis started with 8.6 million Medicare patients with planned noncardiac surgery, seen from 2015 to 2019, of whom 16.4% had preexisting AFib. Propensity matching for demographics, urgency and type of surgery, CHA2DS2-VASc score, and RCRI index created two cohorts for comparison: 1.13 million patients with and 1.92 million without preexisting AFib.
Preexisting AFib was associated with a higher 30-day risk for death from any cause, the primary endpoint being 8.3% versus 5.8% for those without such AFib (P < .001), for an odds ratio of 1.31 (95% confidence interval, 1.30-1.32).
Corresponding 30-day ORs for other events, all significant at P < .001, were:
- 1.31 (95% CI, 1.30-1.33) for heart failure
- 1.40 (95% CI, 1.37-1.43) for stroke
- 1.59 (95% CI, 1.43-1.75) for systemic embolism
- 1.14 (95% CI, 1.13-1.16) for major bleeding
- 0.81 (95% CI, 0.79-0.82) for MI
Those with preexisting AFib also had longer hospitalizations at a median 5 days, compared with 4 days for those without such AFib (P < .001).
The study has the limitations of most any retrospective cohort analysis. Other limitations, the report notes, include lack of information on any antiarrhythmic meds given during hospitalization or type of AFib.
For example, AFib that is permanent – compared with paroxysmal or persistent – may be associated with more atrial fibrosis, greater atrial dilatation, “and probably higher pressures inside the heart,” Dr. Mentias observed.
“That’s not always the case, but that’s the notion. So presumably people with persistent or permanent atrial fib would have more advanced heart disease, and that could imply more risk. But we did not have that kind of data.”
Dr. Mentias and Dr. Prasada report no relevant financial relationships; disclosures for the other authors are in the report. Dr. Curtis discloses serving on advisory boards for Abbott, Janssen Pharmaceuticals, Sanofi, and Milestone Pharmaceuticals; receiving honoraria for speaking from Medtronic and Zoll; and serving on a data-monitoring board for Medtronic. Dr. Korada reports he has no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Practice has gone back and forth on whether atrial fibrillation (AFib) should be considered in the preoperative cardiovascular risk (CV) evaluation of patients slated for noncardiac surgery, and the Revised Cardiac Risk Index (RCRI), currently widely used as an assessment tool, doesn’t include the arrhythmia.
But consideration of preexisting AFib along with the RCRI predicted 30-day mortality more sharply than the RCRI alone in an analysis of data covering several million patients slated for such procedures.
Indeed, AFib emerged as a significant, independent risk factor for a number of bad postoperative outcomes. Mortality within a month of the procedure climbed about 30% for patients with AFib before the noncardiac surgery. Their 30-day risks for stroke and for heart failure hospitalization went up similarly.
The addition of AFib to the RCRI significantly improved its ability to discriminate 30-day postoperative risk levels regardless of age, sex, and type of noncardiac surgery, Amgad Mentias, MD, Cleveland Clinic, told this news organization. And “it was able to correctly up-classify patients to high risk, if AFib was there, and it was able to down-classify some patients to lower risk if it wasn’t there.”
“I think [the findings] are convincing evidence that atrial fib should at least be part of the thought process for the surgical team and the medical team taking care of the patient,” said Dr. Mentias, who is senior author on the study published in the Journal of the American College of Cardiology, with lead author Sameer Prasada, MD, also of the Cleveland Clinic.
The results “call for incorporating AFib as a risk factor in perioperative risk scores for cardiovascular morbidity and mortality,” the published report states.
Supraventricular arrhythmias had been part of the Goldman Risk Index once widely used preoperatively to assess cardiac risk before practice adopted the RCRI in the past decade, observe Anne B. Curtis, MD, and Sai Krishna C. Korada, MD, University at Buffalo, New York, in an accompanying editorial.
The current findings “demonstrate improved prediction of adverse postsurgical outcomes” from supplementing the RCRI with AFib, they write. Given associations between preexisting AFib and serious cardiac events, “it is time to ‘re-revise’ the RCRI and acknowledge the importance of AFib in predicting adverse outcomes” after noncardiac surgery.
The new findings, however, aren’t all straightforward. In one result that remains a bit of a head-scratcher, postoperative risk of myocardial infarction (MI) in patients with preexisting AFib went in the opposite direction of risk for death and other CV outcomes, falling by almost 20%.
That is “hard to explain with the available data,” the report states, but “the use of anticoagulation, whether oral or parenteral (as a bridge therapy in the perioperative period), is a plausible explanation” given the frequent role of thrombosis in triggering MIs.
Consistent with such a mechanism, the group argues, the MI risk reduction was seen primarily among patients with AFib and a CHA2DS2-VASc score of 2 or higher – that is, those at highest risk for stroke and therefore most likely to be on oral anticoagulation. The MI risk reduction wasn’t seen in such patients with a CHA2DS2-VASc score of 0 or 1.
“I think that’s part of the explanation, that anticoagulation can reduce risk of MI. But it’s not the whole explanation,” Dr. Mentias said in an interview. If it were the sole mechanism, he said, then the same oral anticoagulation that protected against MI should have also cut the postoperative stroke risk. Yet that risk climbed 40% among patients with preexisting AFib.
The analysis started with 8.6 million Medicare patients with planned noncardiac surgery, seen from 2015 to 2019, of whom 16.4% had preexisting AFib. Propensity matching for demographics, urgency and type of surgery, CHA2DS2-VASc score, and RCRI index created two cohorts for comparison: 1.13 million patients with and 1.92 million without preexisting AFib.
Preexisting AFib was associated with a higher 30-day risk for death from any cause, the primary endpoint being 8.3% versus 5.8% for those without such AFib (P < .001), for an odds ratio of 1.31 (95% confidence interval, 1.30-1.32).
Corresponding 30-day ORs for other events, all significant at P < .001, were:
- 1.31 (95% CI, 1.30-1.33) for heart failure
- 1.40 (95% CI, 1.37-1.43) for stroke
- 1.59 (95% CI, 1.43-1.75) for systemic embolism
- 1.14 (95% CI, 1.13-1.16) for major bleeding
- 0.81 (95% CI, 0.79-0.82) for MI
Those with preexisting AFib also had longer hospitalizations at a median 5 days, compared with 4 days for those without such AFib (P < .001).
The study has the limitations of most any retrospective cohort analysis. Other limitations, the report notes, include lack of information on any antiarrhythmic meds given during hospitalization or type of AFib.
For example, AFib that is permanent – compared with paroxysmal or persistent – may be associated with more atrial fibrosis, greater atrial dilatation, “and probably higher pressures inside the heart,” Dr. Mentias observed.
“That’s not always the case, but that’s the notion. So presumably people with persistent or permanent atrial fib would have more advanced heart disease, and that could imply more risk. But we did not have that kind of data.”
Dr. Mentias and Dr. Prasada report no relevant financial relationships; disclosures for the other authors are in the report. Dr. Curtis discloses serving on advisory boards for Abbott, Janssen Pharmaceuticals, Sanofi, and Milestone Pharmaceuticals; receiving honoraria for speaking from Medtronic and Zoll; and serving on a data-monitoring board for Medtronic. Dr. Korada reports he has no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Meta-analysis points to safety of acetylcholine coronary testing
Provocation testing with intracoronary acetylcholine is safe, particularly among Western patients, suggests a large systematic review that underscores the importance of functional coronary angiography to diagnose epicardial or microvascular spasm.
The results, derived from more than 12,000 patients in 16 studies, showed a 0.5% risk of major complications, defined as death, ventricular tachycardia/ventricular fibrillation, myocardial infarction, and shock requiring resuscitation.
Ventricular tachycardia/fibrillation were the most common events and mainly reported from two Japanese studies. There were no deaths.
Exploratory subgroup analyses revealed significantly fewer major complications in Western populations (0.0%; P for heterogeneity = .938), compared with Asian populations (2.3%; P for heterogeneity < .001).
The pooled positive vasospasm rate was also lower in Western versus Asian studies (37.9% vs. 50.7%; P for between-group heterogeneity = .010), as reported by the Microvascular Network in the Journal of the American College of Cardiology.
“If you look at the data between Asian studies versus others, mainly European or U.S. studies, primarily in Caucasian populations, it’s like zero percent history of major complications. So, it sounds extremely safe to do this testing in Caucasian populations,” Yuhei Kobayashi, MD, NewYork-Presbyterian Brooklyn Methodist Hospital, Weill Cornell Medicine, said.
Safety will need to be assessed in African Americans and other racial/ethnic groups, but “it makes us think we should end up testing more in the United States,” he told this news organization.
Intracoronary acetylcholine testing is daily practice in Japan but is limited in the United States and Europe to a few specialized centers due to safety concerns. Three deaths were reported in 1980 with intravenous ergonovine testing, whereas the safety of acetylcholine protocols has been studied largely in single-center retrospective studies, typically in Asian populations.
Growing recognition of myocardial infarction with nonobstructive coronary arteries (MINOCA) and ischemia with no obstructive coronary arteries (INOCA), however, is changing the landscape. In recent U.S. and European guidelines, intracoronary acetylcholine testing is indicated as a class 2a recommendation in MINOCA/INOCA.
“More and more institutions in Europe and the United States are starting to do acetylcholine testing, because now we know that chest pain isn’t necessarily coming from the blocked arteries,” Dr. Kobayashi said. “There are functional abnormalities, including coronary spasm, and if we diagnose it, we have appropriate medical regimens for this kind of disease.”
First safety meta-analysis
The present review and meta-analysis included 12,585 participants in 16 studies through November 2021. Of these, 63% were conducted in Western countries, and most were prospective studies published over the past decade in patients with MINOCA or INOCA.
Ten studies used the contemporary diagnostic criteria for epicardial spasm of at least 90% reduction in coronary diameter. Acetylcholine was administered into the left coronary artery at up to 100 mcg and 200 mcg in seven and six studies, respectively, and was used in the other three studies to assess endothelial function with a slower infusion of up to 36.4 mcg.
Major complications were significantly higher in studies following the contemporary diagnostic cutoff than in those using a lower cutoff of at least 75% diameter reduction (1.0% vs. 0.0%; P for between-group heterogeneity < .001).
The incidence of major complications was 0.2% with the slower infusion of up to 36.4 mcg, 0.8% with a maximum dose of 100 mcg, and 0.3% with a maximum dose of 200 mcg. The positive vasospasm rate was similar with the latter two protocols, at 46.3% and 41.4%, respectively.
Minor complications occurred in 3.3% of patients but were not detailed. They can include paroxysmal atrial fibrillation, ventricular ectopic beats, transient hypotension, and bradycardia requiring intervention.
As with major complications, minor complications were lower in studies using noncontemporary versus contemporary diagnostic cutoffs for epicardial spasm (1.8% vs. 4.7%) and in Western versus Asian populations (2.6% vs. 9.4%). Minor complications were similar between protocols with maximum doses of 100 mcg and 200 mcg (3.6% vs. 3.8%).
Dr. Kobayashi suggested that several factors may explain the racial differences, including previously reported smooth muscle hyperresponsiveness to provocation stimuli in Japanese patients and the inclusion of a wide range of patients in Japanese studies, such as those with obstructive coronary disease.
Japanese studies also used sequential acetylcholine injection into both the right and left coronaries, a faster injection speed of 20 seconds, and upfront placement of a temporary pacing catheter in case of acetylcholine-induced bradycardia, particularly with right coronary injection.
Although the protocol is largely settled in Japan, he said, provocation protocols need to be standardized because “depending on the country and depending on the institution, people are doing totally different things.”
A big step forward
Commenting on the study, C. Noel Bairey Merz, MD, from Cedars Sinai, Los Angeles, said it has “widespread relevance” because half of all coronary angiograms done invasively in the United States for suspected ischemia find no obstructive coronary disease. Left untreated, however, MINOCA has a 2.5% annual event rate, and a quarter of that is death.
“This is a big step forward with likely equal opportunity to improve women and men’s ischemic heart disease,” she said.
On the other hand, all studies were conducted at centers of excellence, so safety will need to be carefully watched as testing rolls out to more community care, Dr. Merz said. “And it always needs to be underscored that this is done by an interventional cardiologist because they’re familiar with wires that can dissect arteries, and they’re familiar with minor complications that could turn into major, if someone didn’t act appropriately.”
Dr. Merz also called for unifying protocols and the need to raise awareness within the general cardiology community to ask interventionalists for acetylcholine spasm testing. Randomized controlled data from within the WISE study and the CorMica study showed that diagnostic certainty leads to greater therapeutic certainty. “You do a much better job about who and how to treat,” she said.
There are also three ongoing randomized controlled trials – WARRIOR, MINOCA-BAT, and iCorMica – in the INOCA and MINOCA populations testing different treatment strategies for hard clinical outcomes like death and myocardial infarction.
“So in addition to this publication being guideline-forming for diagnosis, we anticipate in the next several years to have clinical trial evidence about therapeutics, again, for formulation of class 1 guidelines,” Dr. Merz said.
John Beltrame, BMBS, PhD, University of Adelaide, Australia, said the meta-analysis shows that intracoronary acetylcholine spasm testing is safe and should prompt greater adoption of invasive functional angiography.
Interventionalists are quite happy to do fractional flow reserve using intravenous adenosine to assess coronary microvascular dysfunction, he said, and “what we think is that functional angiography should test both – both the spasm as well as the microvasculature – and that will give us a clear direction because the treatments are slightly different when you’re treating the large arteries as compared to the microscopic arteries. It’s an important thing.”
Dr. Beltrame and colleagues further detail the benefits of comprehensive invasive functional angiography over structural angiography in a related editorial.
He also noted that the Coronary Vasomotion Disorders International Study Group published international diagnostic criteria for microvascular angina and that several protocols for acetylcholine spasm testing are in the works, including one from Australia. Australian investigators are also organizing an accreditation program for those performing the test.
“The protocol itself is relatively straightforward, but it’s not merely picking up a manual and following the instructions,” Dr. Beltrame said. “Just the same as when you train someone in angioplasty, you don’t just go out and do it. You need to develop some experience in it and so should be proctored.”
Dr. Kobayashi reported consulting agreements with Abbott Vascular. Coauthor disclosures are listed in the paper. Dr. Beltrame and colleagues have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Provocation testing with intracoronary acetylcholine is safe, particularly among Western patients, suggests a large systematic review that underscores the importance of functional coronary angiography to diagnose epicardial or microvascular spasm.
The results, derived from more than 12,000 patients in 16 studies, showed a 0.5% risk of major complications, defined as death, ventricular tachycardia/ventricular fibrillation, myocardial infarction, and shock requiring resuscitation.
Ventricular tachycardia/fibrillation were the most common events and mainly reported from two Japanese studies. There were no deaths.
Exploratory subgroup analyses revealed significantly fewer major complications in Western populations (0.0%; P for heterogeneity = .938), compared with Asian populations (2.3%; P for heterogeneity < .001).
The pooled positive vasospasm rate was also lower in Western versus Asian studies (37.9% vs. 50.7%; P for between-group heterogeneity = .010), as reported by the Microvascular Network in the Journal of the American College of Cardiology.
“If you look at the data between Asian studies versus others, mainly European or U.S. studies, primarily in Caucasian populations, it’s like zero percent history of major complications. So, it sounds extremely safe to do this testing in Caucasian populations,” Yuhei Kobayashi, MD, NewYork-Presbyterian Brooklyn Methodist Hospital, Weill Cornell Medicine, said.
Safety will need to be assessed in African Americans and other racial/ethnic groups, but “it makes us think we should end up testing more in the United States,” he told this news organization.
Intracoronary acetylcholine testing is daily practice in Japan but is limited in the United States and Europe to a few specialized centers due to safety concerns. Three deaths were reported in 1980 with intravenous ergonovine testing, whereas the safety of acetylcholine protocols has been studied largely in single-center retrospective studies, typically in Asian populations.
Growing recognition of myocardial infarction with nonobstructive coronary arteries (MINOCA) and ischemia with no obstructive coronary arteries (INOCA), however, is changing the landscape. In recent U.S. and European guidelines, intracoronary acetylcholine testing is indicated as a class 2a recommendation in MINOCA/INOCA.
“More and more institutions in Europe and the United States are starting to do acetylcholine testing, because now we know that chest pain isn’t necessarily coming from the blocked arteries,” Dr. Kobayashi said. “There are functional abnormalities, including coronary spasm, and if we diagnose it, we have appropriate medical regimens for this kind of disease.”
First safety meta-analysis
The present review and meta-analysis included 12,585 participants in 16 studies through November 2021. Of these, 63% were conducted in Western countries, and most were prospective studies published over the past decade in patients with MINOCA or INOCA.
Ten studies used the contemporary diagnostic criteria for epicardial spasm of at least 90% reduction in coronary diameter. Acetylcholine was administered into the left coronary artery at up to 100 mcg and 200 mcg in seven and six studies, respectively, and was used in the other three studies to assess endothelial function with a slower infusion of up to 36.4 mcg.
Major complications were significantly higher in studies following the contemporary diagnostic cutoff than in those using a lower cutoff of at least 75% diameter reduction (1.0% vs. 0.0%; P for between-group heterogeneity < .001).
The incidence of major complications was 0.2% with the slower infusion of up to 36.4 mcg, 0.8% with a maximum dose of 100 mcg, and 0.3% with a maximum dose of 200 mcg. The positive vasospasm rate was similar with the latter two protocols, at 46.3% and 41.4%, respectively.
Minor complications occurred in 3.3% of patients but were not detailed. They can include paroxysmal atrial fibrillation, ventricular ectopic beats, transient hypotension, and bradycardia requiring intervention.
As with major complications, minor complications were lower in studies using noncontemporary versus contemporary diagnostic cutoffs for epicardial spasm (1.8% vs. 4.7%) and in Western versus Asian populations (2.6% vs. 9.4%). Minor complications were similar between protocols with maximum doses of 100 mcg and 200 mcg (3.6% vs. 3.8%).
Dr. Kobayashi suggested that several factors may explain the racial differences, including previously reported smooth muscle hyperresponsiveness to provocation stimuli in Japanese patients and the inclusion of a wide range of patients in Japanese studies, such as those with obstructive coronary disease.
Japanese studies also used sequential acetylcholine injection into both the right and left coronaries, a faster injection speed of 20 seconds, and upfront placement of a temporary pacing catheter in case of acetylcholine-induced bradycardia, particularly with right coronary injection.
Although the protocol is largely settled in Japan, he said, provocation protocols need to be standardized because “depending on the country and depending on the institution, people are doing totally different things.”
A big step forward
Commenting on the study, C. Noel Bairey Merz, MD, from Cedars Sinai, Los Angeles, said it has “widespread relevance” because half of all coronary angiograms done invasively in the United States for suspected ischemia find no obstructive coronary disease. Left untreated, however, MINOCA has a 2.5% annual event rate, and a quarter of that is death.
“This is a big step forward with likely equal opportunity to improve women and men’s ischemic heart disease,” she said.
On the other hand, all studies were conducted at centers of excellence, so safety will need to be carefully watched as testing rolls out to more community care, Dr. Merz said. “And it always needs to be underscored that this is done by an interventional cardiologist because they’re familiar with wires that can dissect arteries, and they’re familiar with minor complications that could turn into major, if someone didn’t act appropriately.”
Dr. Merz also called for unifying protocols and the need to raise awareness within the general cardiology community to ask interventionalists for acetylcholine spasm testing. Randomized controlled data from within the WISE study and the CorMica study showed that diagnostic certainty leads to greater therapeutic certainty. “You do a much better job about who and how to treat,” she said.
There are also three ongoing randomized controlled trials – WARRIOR, MINOCA-BAT, and iCorMica – in the INOCA and MINOCA populations testing different treatment strategies for hard clinical outcomes like death and myocardial infarction.
“So in addition to this publication being guideline-forming for diagnosis, we anticipate in the next several years to have clinical trial evidence about therapeutics, again, for formulation of class 1 guidelines,” Dr. Merz said.
John Beltrame, BMBS, PhD, University of Adelaide, Australia, said the meta-analysis shows that intracoronary acetylcholine spasm testing is safe and should prompt greater adoption of invasive functional angiography.
Interventionalists are quite happy to do fractional flow reserve using intravenous adenosine to assess coronary microvascular dysfunction, he said, and “what we think is that functional angiography should test both – both the spasm as well as the microvasculature – and that will give us a clear direction because the treatments are slightly different when you’re treating the large arteries as compared to the microscopic arteries. It’s an important thing.”
Dr. Beltrame and colleagues further detail the benefits of comprehensive invasive functional angiography over structural angiography in a related editorial.
He also noted that the Coronary Vasomotion Disorders International Study Group published international diagnostic criteria for microvascular angina and that several protocols for acetylcholine spasm testing are in the works, including one from Australia. Australian investigators are also organizing an accreditation program for those performing the test.
“The protocol itself is relatively straightforward, but it’s not merely picking up a manual and following the instructions,” Dr. Beltrame said. “Just the same as when you train someone in angioplasty, you don’t just go out and do it. You need to develop some experience in it and so should be proctored.”
Dr. Kobayashi reported consulting agreements with Abbott Vascular. Coauthor disclosures are listed in the paper. Dr. Beltrame and colleagues have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Provocation testing with intracoronary acetylcholine is safe, particularly among Western patients, suggests a large systematic review that underscores the importance of functional coronary angiography to diagnose epicardial or microvascular spasm.
The results, derived from more than 12,000 patients in 16 studies, showed a 0.5% risk of major complications, defined as death, ventricular tachycardia/ventricular fibrillation, myocardial infarction, and shock requiring resuscitation.
Ventricular tachycardia/fibrillation were the most common events and mainly reported from two Japanese studies. There were no deaths.
Exploratory subgroup analyses revealed significantly fewer major complications in Western populations (0.0%; P for heterogeneity = .938), compared with Asian populations (2.3%; P for heterogeneity < .001).
The pooled positive vasospasm rate was also lower in Western versus Asian studies (37.9% vs. 50.7%; P for between-group heterogeneity = .010), as reported by the Microvascular Network in the Journal of the American College of Cardiology.
“If you look at the data between Asian studies versus others, mainly European or U.S. studies, primarily in Caucasian populations, it’s like zero percent history of major complications. So, it sounds extremely safe to do this testing in Caucasian populations,” Yuhei Kobayashi, MD, NewYork-Presbyterian Brooklyn Methodist Hospital, Weill Cornell Medicine, said.
Safety will need to be assessed in African Americans and other racial/ethnic groups, but “it makes us think we should end up testing more in the United States,” he told this news organization.
Intracoronary acetylcholine testing is daily practice in Japan but is limited in the United States and Europe to a few specialized centers due to safety concerns. Three deaths were reported in 1980 with intravenous ergonovine testing, whereas the safety of acetylcholine protocols has been studied largely in single-center retrospective studies, typically in Asian populations.
Growing recognition of myocardial infarction with nonobstructive coronary arteries (MINOCA) and ischemia with no obstructive coronary arteries (INOCA), however, is changing the landscape. In recent U.S. and European guidelines, intracoronary acetylcholine testing is indicated as a class 2a recommendation in MINOCA/INOCA.
“More and more institutions in Europe and the United States are starting to do acetylcholine testing, because now we know that chest pain isn’t necessarily coming from the blocked arteries,” Dr. Kobayashi said. “There are functional abnormalities, including coronary spasm, and if we diagnose it, we have appropriate medical regimens for this kind of disease.”
First safety meta-analysis
The present review and meta-analysis included 12,585 participants in 16 studies through November 2021. Of these, 63% were conducted in Western countries, and most were prospective studies published over the past decade in patients with MINOCA or INOCA.
Ten studies used the contemporary diagnostic criteria for epicardial spasm of at least 90% reduction in coronary diameter. Acetylcholine was administered into the left coronary artery at up to 100 mcg and 200 mcg in seven and six studies, respectively, and was used in the other three studies to assess endothelial function with a slower infusion of up to 36.4 mcg.
Major complications were significantly higher in studies following the contemporary diagnostic cutoff than in those using a lower cutoff of at least 75% diameter reduction (1.0% vs. 0.0%; P for between-group heterogeneity < .001).
The incidence of major complications was 0.2% with the slower infusion of up to 36.4 mcg, 0.8% with a maximum dose of 100 mcg, and 0.3% with a maximum dose of 200 mcg. The positive vasospasm rate was similar with the latter two protocols, at 46.3% and 41.4%, respectively.
Minor complications occurred in 3.3% of patients but were not detailed. They can include paroxysmal atrial fibrillation, ventricular ectopic beats, transient hypotension, and bradycardia requiring intervention.
As with major complications, minor complications were lower in studies using noncontemporary versus contemporary diagnostic cutoffs for epicardial spasm (1.8% vs. 4.7%) and in Western versus Asian populations (2.6% vs. 9.4%). Minor complications were similar between protocols with maximum doses of 100 mcg and 200 mcg (3.6% vs. 3.8%).
Dr. Kobayashi suggested that several factors may explain the racial differences, including previously reported smooth muscle hyperresponsiveness to provocation stimuli in Japanese patients and the inclusion of a wide range of patients in Japanese studies, such as those with obstructive coronary disease.
Japanese studies also used sequential acetylcholine injection into both the right and left coronaries, a faster injection speed of 20 seconds, and upfront placement of a temporary pacing catheter in case of acetylcholine-induced bradycardia, particularly with right coronary injection.
Although the protocol is largely settled in Japan, he said, provocation protocols need to be standardized because “depending on the country and depending on the institution, people are doing totally different things.”
A big step forward
Commenting on the study, C. Noel Bairey Merz, MD, from Cedars Sinai, Los Angeles, said it has “widespread relevance” because half of all coronary angiograms done invasively in the United States for suspected ischemia find no obstructive coronary disease. Left untreated, however, MINOCA has a 2.5% annual event rate, and a quarter of that is death.
“This is a big step forward with likely equal opportunity to improve women and men’s ischemic heart disease,” she said.
On the other hand, all studies were conducted at centers of excellence, so safety will need to be carefully watched as testing rolls out to more community care, Dr. Merz said. “And it always needs to be underscored that this is done by an interventional cardiologist because they’re familiar with wires that can dissect arteries, and they’re familiar with minor complications that could turn into major, if someone didn’t act appropriately.”
Dr. Merz also called for unifying protocols and the need to raise awareness within the general cardiology community to ask interventionalists for acetylcholine spasm testing. Randomized controlled data from within the WISE study and the CorMica study showed that diagnostic certainty leads to greater therapeutic certainty. “You do a much better job about who and how to treat,” she said.
There are also three ongoing randomized controlled trials – WARRIOR, MINOCA-BAT, and iCorMica – in the INOCA and MINOCA populations testing different treatment strategies for hard clinical outcomes like death and myocardial infarction.
“So in addition to this publication being guideline-forming for diagnosis, we anticipate in the next several years to have clinical trial evidence about therapeutics, again, for formulation of class 1 guidelines,” Dr. Merz said.
John Beltrame, BMBS, PhD, University of Adelaide, Australia, said the meta-analysis shows that intracoronary acetylcholine spasm testing is safe and should prompt greater adoption of invasive functional angiography.
Interventionalists are quite happy to do fractional flow reserve using intravenous adenosine to assess coronary microvascular dysfunction, he said, and “what we think is that functional angiography should test both – both the spasm as well as the microvasculature – and that will give us a clear direction because the treatments are slightly different when you’re treating the large arteries as compared to the microscopic arteries. It’s an important thing.”
Dr. Beltrame and colleagues further detail the benefits of comprehensive invasive functional angiography over structural angiography in a related editorial.
He also noted that the Coronary Vasomotion Disorders International Study Group published international diagnostic criteria for microvascular angina and that several protocols for acetylcholine spasm testing are in the works, including one from Australia. Australian investigators are also organizing an accreditation program for those performing the test.
“The protocol itself is relatively straightforward, but it’s not merely picking up a manual and following the instructions,” Dr. Beltrame said. “Just the same as when you train someone in angioplasty, you don’t just go out and do it. You need to develop some experience in it and so should be proctored.”
Dr. Kobayashi reported consulting agreements with Abbott Vascular. Coauthor disclosures are listed in the paper. Dr. Beltrame and colleagues have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Cause of death in pig heart recipient: New clues
The underlying cause of David Bennett’s death on March 8, two months after he received the heart of a genetically altered pig, remains unknown and is only slightly less mysterious for what can likely be ruled out, suggests a progress report on the case from the director of the cardiac xenotransplantation program where the pioneering surgery took place.
Mr. Bennett died in “diastolic heart failure,” reported Muhammad M. Mohiuddin, MBBS, University of Maryland School of Medicine, Baltimore, “but the mechanism is still under investigation.”
Although the immediate cause could have been single or multiple, evidence so far does not point to immune rejection nor does it support a role for a recently proposed suspect, infection by porcine cytomegalovirus (PCMV), Dr. Mohiuddin observed in front of a standing-room-only audience June 6 at the American Transplant Congress (ATC) in Boston. The congress is a joint meeting of the American Society of Transplant Surgeons (ASTS) and the American Society of Transplantation (AST).
Rocky clinical course
Early characterizations of the patient’s death focused more on his diminished, end-stage clinical condition at the time of the surgery than on immune rejection or other direct effects of the xenograft or on the first-of-its-kind procedure itself.
The 57-year-old Mr. Bennett had presented to the University of Maryland team with nonischemic cardiomyopathy, on multiple inotropes, and requiring an intra-aortic balloon pump, Dr. Mohiuddin said in his ATC presentation. The patient had suffered multiple arrests and resuscitations, and by the time of surgery had been hospitalized for almost 2 months, including 40 days on veno-arterial extracorporeal membrane oxygenation (ECMO).
The transplant procedure itself went as planned until removal of the aortic cross clamp, which triggered a type-A aortic dissection. “We put a graft in the ascending aorta and a stent in the descending aorta. Even after 2 days, we found the dissection extending to the renal artery, so we had to go back and also put a stent in the renal artery,” Dr. Mohiuddin said.
Mr. Bennett also underwent two exploratory laparotomies in the first 10 days after transplantation, after CT imaging revealed signs of possible bowel inflammation and ischemia.
Further, he had to fight back a series of infections that led to major changes to his experimental drug regimen, which included immunosuppressants methylprednisolone and mycophenolate mofetil (MMF), the investigational anti-CD40 antibody KPL-404 (Kiniksa Pharmaceuticals), and the anti-inflammatories etanercept (Enbrel) and tocilizumab (Actemra).
One episode of sepsis, in particular, forced temporary withdrawal of MMF and a reduction in methylprednisolone dosage. It’s unknown whether the 30-day MMF suspension played a role in Mr. Bennett’s ultimate clinical deterioration and death, but it’s “highly possible,” Dr. Mohiuddin said in an interview.
Realistically, Mr. Bennett’s death was likely “multifactorial,” Dr. Mohiuddin said. He was in such poor clinical condition going into the procedure, and afterward confronted so many clinical challenges, that “it’s very difficult to say that one thing caused it.”
That hasn’t lessened speculation that the patient’s heart failed secondary to immunologic rejection or PCMV infection, either in Mr. Bennett or the donor pig.
A role for PCMV?
Weeks after Mr. Bennett’s death, as previously reported, his surgeon announced at a public forum that PCMV had been identified in the transplanted heart and in tissues of the donor pig. Mr. Bennett’s circulation showed traces of the viral DNA but not of the virus itself.
The presence of PCMV in transplanted porcine hearts is a well-recognized potential hazard in animal models but is considered avoidable with proper screening. In Mr. Bennett’s case, preoperative screening of the pig donor missed signs of the virus.
Still, PCMV could potentially have contributed to Mr. Bennett’s death, acknowledged Bartley P. Griffith, MD, University of Maryland School of Medicine, who had announced the PCMV finding in an AST-sponsored April 20 webcast.
Preclinical evidence does suggest that PCMV can harm a xenograft organ, observed David H. Sachs, MD, Columbia University Medical Center, New York, from the audience during the comment period after Dr. Mohiuddin’s presentation.
“Each species has a CMV, and they’re quite species-specific,” observed the renowned surgeon and xenotransplantation immunologist. “We showed almost 10 years ago that if PCMV was in a pig kidney, it led to a much shortened survival of the pig kidney in a baboon. There was never any evidence, however, that the CMV infected the baboon or any baboon cells.”
Dr. Sachs asked Dr. Mohiuddin for confirmation that Mr. Bennett displayed no more than DNAemia, circulating cell-free PCMV DNA presumably shed from the porcine heart, but no sign of the virus itself outside of the heart’s porcine cells.
Cell-free DNA had shown up in Mr. Bennett’s circulation about 20 days after the surgery, with concentrations rising until at least day 50. Post-hoc polymerase chain reaction (PCR) testing disclosed PCMV only in the pig’s spleen and porcine cells of the transplanted heart, Dr. Mohiuddin noted.
“We have not found any evidence that the patient was infected by PCMV,” nor was there evidence of any disease related to PCMV, Dr. Mohiuddin replied.
Nor of ongoing rejection
Mr. Bennett’s new heart passed a critical test in the first post-implantation hours by avoiding acute rejection, a potentially disastrous outcome that three of the pig’s 10 gene edits had been designed to prevent.
Although chronic immune rejection was always a concern despite Mr. Bennett’s novel immunosuppressant regimen, myocardial biopsy on postoperative days 34, 50, and 56 and necropsy showed “no signs of typical xenograft rejection,” Dr. Mohiuddin said at the ATC presentation. But “there’s a chance of atypical rejection which we were not accustomed to.”
By day 50, his diastolic function showed echocardiographic signs of deterioration, and “we started seeing interstitial edema with some extravasation of red blood cells, which we thought would resolve over a period of time,” he said. Eventually, however, “we saw that turn into fibroblasts and scar tissue.”
Mr. Bennett once again went on veno-arterial ECMO but died 10 days later. Once they had seen histologic evidence of fibrosis, Dr. Mohiuddin told this news organization, the team believed the myocardial injury was irreversible. “That was the reason we gave up on recovery.”
Mr. Bennett’s xenotransplantation journey has taught the field a lot, he said. “By no means was this a failure; we consider this a huge success. You can do all the experiments in animal models, but you won’t find out the true mechanism of rejection unless you do these kinds of human experiments.”
Looking ahead to clinical trials
Research involving humans is always subject to vagaries of human nature, including degree of adherence to prescribed therapy and – in xenotransplantation – precautions in place to mitigate any risks to public health. Such risks theoretically include transfer of porcine viruses or other pathogens to the patient and subsequent release into the general population.
Looking ahead to the possibility of clinical trials after this successful xenotransplantation experience, transplant nephrologist and epidemiologist Peter P. Reese, MD, PhD, University of Pennsylvania, Philadelphia, raised the potentially controversial issue in discussion following Dr. Mohiuddin’s presentation.
It’s known that Mr. Bennett had been repeatedly turned down for a conventional allograft transplant primarily because of his history of treatment noncompliance. Should such a record, Dr. Reese asked, be a relative contraindication to enrollment in any future xenotransplantation trials? Or does the field need a standardized gauge of a patient’s readiness, once discharged, to adhere not only to all medications – including those that fight infection – but also with rules established for public safety, such as routine contact reporting?
“It makes me wonder about choosing a noncompliant patient for these trials,” Dr. Reese said. “If we discharge a patient from the hospital who is at risk for a zoonotic infection that could spread if they basically refuse to cooperate with us or with public health authorities, it really could have negative consequences for the reputation of the field.”
Dr. Mohiuddin agreed such concerns are valid. Mr. Bennett “and all his immediate contacts” signed consent forms acknowledging their willingness to be followed should he be discharged. Mr. Bennett himself “signed a consent to inform us if he has any other intimate contact with someone,” he said in an interview.
“But those are only on paper.” Had Mr. Bennett survived to be discharged, Dr. Mohuiddin said, “no one knows how he would have behaved.”
Dr. Mohiuddin said the research staff had prepared to monitor Mr. Bennett at his home if that’s what it took. “We were ready to follow him as long as we could. There was a surveillance plan in place.”
A version of this article first appeared on Medscape.com.
The underlying cause of David Bennett’s death on March 8, two months after he received the heart of a genetically altered pig, remains unknown and is only slightly less mysterious for what can likely be ruled out, suggests a progress report on the case from the director of the cardiac xenotransplantation program where the pioneering surgery took place.
Mr. Bennett died in “diastolic heart failure,” reported Muhammad M. Mohiuddin, MBBS, University of Maryland School of Medicine, Baltimore, “but the mechanism is still under investigation.”
Although the immediate cause could have been single or multiple, evidence so far does not point to immune rejection nor does it support a role for a recently proposed suspect, infection by porcine cytomegalovirus (PCMV), Dr. Mohiuddin observed in front of a standing-room-only audience June 6 at the American Transplant Congress (ATC) in Boston. The congress is a joint meeting of the American Society of Transplant Surgeons (ASTS) and the American Society of Transplantation (AST).
Rocky clinical course
Early characterizations of the patient’s death focused more on his diminished, end-stage clinical condition at the time of the surgery than on immune rejection or other direct effects of the xenograft or on the first-of-its-kind procedure itself.
The 57-year-old Mr. Bennett had presented to the University of Maryland team with nonischemic cardiomyopathy, on multiple inotropes, and requiring an intra-aortic balloon pump, Dr. Mohiuddin said in his ATC presentation. The patient had suffered multiple arrests and resuscitations, and by the time of surgery had been hospitalized for almost 2 months, including 40 days on veno-arterial extracorporeal membrane oxygenation (ECMO).
The transplant procedure itself went as planned until removal of the aortic cross clamp, which triggered a type-A aortic dissection. “We put a graft in the ascending aorta and a stent in the descending aorta. Even after 2 days, we found the dissection extending to the renal artery, so we had to go back and also put a stent in the renal artery,” Dr. Mohiuddin said.
Mr. Bennett also underwent two exploratory laparotomies in the first 10 days after transplantation, after CT imaging revealed signs of possible bowel inflammation and ischemia.
Further, he had to fight back a series of infections that led to major changes to his experimental drug regimen, which included immunosuppressants methylprednisolone and mycophenolate mofetil (MMF), the investigational anti-CD40 antibody KPL-404 (Kiniksa Pharmaceuticals), and the anti-inflammatories etanercept (Enbrel) and tocilizumab (Actemra).
One episode of sepsis, in particular, forced temporary withdrawal of MMF and a reduction in methylprednisolone dosage. It’s unknown whether the 30-day MMF suspension played a role in Mr. Bennett’s ultimate clinical deterioration and death, but it’s “highly possible,” Dr. Mohiuddin said in an interview.
Realistically, Mr. Bennett’s death was likely “multifactorial,” Dr. Mohiuddin said. He was in such poor clinical condition going into the procedure, and afterward confronted so many clinical challenges, that “it’s very difficult to say that one thing caused it.”
That hasn’t lessened speculation that the patient’s heart failed secondary to immunologic rejection or PCMV infection, either in Mr. Bennett or the donor pig.
A role for PCMV?
Weeks after Mr. Bennett’s death, as previously reported, his surgeon announced at a public forum that PCMV had been identified in the transplanted heart and in tissues of the donor pig. Mr. Bennett’s circulation showed traces of the viral DNA but not of the virus itself.
The presence of PCMV in transplanted porcine hearts is a well-recognized potential hazard in animal models but is considered avoidable with proper screening. In Mr. Bennett’s case, preoperative screening of the pig donor missed signs of the virus.
Still, PCMV could potentially have contributed to Mr. Bennett’s death, acknowledged Bartley P. Griffith, MD, University of Maryland School of Medicine, who had announced the PCMV finding in an AST-sponsored April 20 webcast.
Preclinical evidence does suggest that PCMV can harm a xenograft organ, observed David H. Sachs, MD, Columbia University Medical Center, New York, from the audience during the comment period after Dr. Mohiuddin’s presentation.
“Each species has a CMV, and they’re quite species-specific,” observed the renowned surgeon and xenotransplantation immunologist. “We showed almost 10 years ago that if PCMV was in a pig kidney, it led to a much shortened survival of the pig kidney in a baboon. There was never any evidence, however, that the CMV infected the baboon or any baboon cells.”
Dr. Sachs asked Dr. Mohiuddin for confirmation that Mr. Bennett displayed no more than DNAemia, circulating cell-free PCMV DNA presumably shed from the porcine heart, but no sign of the virus itself outside of the heart’s porcine cells.
Cell-free DNA had shown up in Mr. Bennett’s circulation about 20 days after the surgery, with concentrations rising until at least day 50. Post-hoc polymerase chain reaction (PCR) testing disclosed PCMV only in the pig’s spleen and porcine cells of the transplanted heart, Dr. Mohiuddin noted.
“We have not found any evidence that the patient was infected by PCMV,” nor was there evidence of any disease related to PCMV, Dr. Mohiuddin replied.
Nor of ongoing rejection
Mr. Bennett’s new heart passed a critical test in the first post-implantation hours by avoiding acute rejection, a potentially disastrous outcome that three of the pig’s 10 gene edits had been designed to prevent.
Although chronic immune rejection was always a concern despite Mr. Bennett’s novel immunosuppressant regimen, myocardial biopsy on postoperative days 34, 50, and 56 and necropsy showed “no signs of typical xenograft rejection,” Dr. Mohiuddin said at the ATC presentation. But “there’s a chance of atypical rejection which we were not accustomed to.”
By day 50, his diastolic function showed echocardiographic signs of deterioration, and “we started seeing interstitial edema with some extravasation of red blood cells, which we thought would resolve over a period of time,” he said. Eventually, however, “we saw that turn into fibroblasts and scar tissue.”
Mr. Bennett once again went on veno-arterial ECMO but died 10 days later. Once they had seen histologic evidence of fibrosis, Dr. Mohiuddin told this news organization, the team believed the myocardial injury was irreversible. “That was the reason we gave up on recovery.”
Mr. Bennett’s xenotransplantation journey has taught the field a lot, he said. “By no means was this a failure; we consider this a huge success. You can do all the experiments in animal models, but you won’t find out the true mechanism of rejection unless you do these kinds of human experiments.”
Looking ahead to clinical trials
Research involving humans is always subject to vagaries of human nature, including degree of adherence to prescribed therapy and – in xenotransplantation – precautions in place to mitigate any risks to public health. Such risks theoretically include transfer of porcine viruses or other pathogens to the patient and subsequent release into the general population.
Looking ahead to the possibility of clinical trials after this successful xenotransplantation experience, transplant nephrologist and epidemiologist Peter P. Reese, MD, PhD, University of Pennsylvania, Philadelphia, raised the potentially controversial issue in discussion following Dr. Mohiuddin’s presentation.
It’s known that Mr. Bennett had been repeatedly turned down for a conventional allograft transplant primarily because of his history of treatment noncompliance. Should such a record, Dr. Reese asked, be a relative contraindication to enrollment in any future xenotransplantation trials? Or does the field need a standardized gauge of a patient’s readiness, once discharged, to adhere not only to all medications – including those that fight infection – but also with rules established for public safety, such as routine contact reporting?
“It makes me wonder about choosing a noncompliant patient for these trials,” Dr. Reese said. “If we discharge a patient from the hospital who is at risk for a zoonotic infection that could spread if they basically refuse to cooperate with us or with public health authorities, it really could have negative consequences for the reputation of the field.”
Dr. Mohiuddin agreed such concerns are valid. Mr. Bennett “and all his immediate contacts” signed consent forms acknowledging their willingness to be followed should he be discharged. Mr. Bennett himself “signed a consent to inform us if he has any other intimate contact with someone,” he said in an interview.
“But those are only on paper.” Had Mr. Bennett survived to be discharged, Dr. Mohuiddin said, “no one knows how he would have behaved.”
Dr. Mohiuddin said the research staff had prepared to monitor Mr. Bennett at his home if that’s what it took. “We were ready to follow him as long as we could. There was a surveillance plan in place.”
A version of this article first appeared on Medscape.com.
The underlying cause of David Bennett’s death on March 8, two months after he received the heart of a genetically altered pig, remains unknown and is only slightly less mysterious for what can likely be ruled out, suggests a progress report on the case from the director of the cardiac xenotransplantation program where the pioneering surgery took place.
Mr. Bennett died in “diastolic heart failure,” reported Muhammad M. Mohiuddin, MBBS, University of Maryland School of Medicine, Baltimore, “but the mechanism is still under investigation.”
Although the immediate cause could have been single or multiple, evidence so far does not point to immune rejection nor does it support a role for a recently proposed suspect, infection by porcine cytomegalovirus (PCMV), Dr. Mohiuddin observed in front of a standing-room-only audience June 6 at the American Transplant Congress (ATC) in Boston. The congress is a joint meeting of the American Society of Transplant Surgeons (ASTS) and the American Society of Transplantation (AST).
Rocky clinical course
Early characterizations of the patient’s death focused more on his diminished, end-stage clinical condition at the time of the surgery than on immune rejection or other direct effects of the xenograft or on the first-of-its-kind procedure itself.
The 57-year-old Mr. Bennett had presented to the University of Maryland team with nonischemic cardiomyopathy, on multiple inotropes, and requiring an intra-aortic balloon pump, Dr. Mohiuddin said in his ATC presentation. The patient had suffered multiple arrests and resuscitations, and by the time of surgery had been hospitalized for almost 2 months, including 40 days on veno-arterial extracorporeal membrane oxygenation (ECMO).
The transplant procedure itself went as planned until removal of the aortic cross clamp, which triggered a type-A aortic dissection. “We put a graft in the ascending aorta and a stent in the descending aorta. Even after 2 days, we found the dissection extending to the renal artery, so we had to go back and also put a stent in the renal artery,” Dr. Mohiuddin said.
Mr. Bennett also underwent two exploratory laparotomies in the first 10 days after transplantation, after CT imaging revealed signs of possible bowel inflammation and ischemia.
Further, he had to fight back a series of infections that led to major changes to his experimental drug regimen, which included immunosuppressants methylprednisolone and mycophenolate mofetil (MMF), the investigational anti-CD40 antibody KPL-404 (Kiniksa Pharmaceuticals), and the anti-inflammatories etanercept (Enbrel) and tocilizumab (Actemra).
One episode of sepsis, in particular, forced temporary withdrawal of MMF and a reduction in methylprednisolone dosage. It’s unknown whether the 30-day MMF suspension played a role in Mr. Bennett’s ultimate clinical deterioration and death, but it’s “highly possible,” Dr. Mohiuddin said in an interview.
Realistically, Mr. Bennett’s death was likely “multifactorial,” Dr. Mohiuddin said. He was in such poor clinical condition going into the procedure, and afterward confronted so many clinical challenges, that “it’s very difficult to say that one thing caused it.”
That hasn’t lessened speculation that the patient’s heart failed secondary to immunologic rejection or PCMV infection, either in Mr. Bennett or the donor pig.
A role for PCMV?
Weeks after Mr. Bennett’s death, as previously reported, his surgeon announced at a public forum that PCMV had been identified in the transplanted heart and in tissues of the donor pig. Mr. Bennett’s circulation showed traces of the viral DNA but not of the virus itself.
The presence of PCMV in transplanted porcine hearts is a well-recognized potential hazard in animal models but is considered avoidable with proper screening. In Mr. Bennett’s case, preoperative screening of the pig donor missed signs of the virus.
Still, PCMV could potentially have contributed to Mr. Bennett’s death, acknowledged Bartley P. Griffith, MD, University of Maryland School of Medicine, who had announced the PCMV finding in an AST-sponsored April 20 webcast.
Preclinical evidence does suggest that PCMV can harm a xenograft organ, observed David H. Sachs, MD, Columbia University Medical Center, New York, from the audience during the comment period after Dr. Mohiuddin’s presentation.
“Each species has a CMV, and they’re quite species-specific,” observed the renowned surgeon and xenotransplantation immunologist. “We showed almost 10 years ago that if PCMV was in a pig kidney, it led to a much shortened survival of the pig kidney in a baboon. There was never any evidence, however, that the CMV infected the baboon or any baboon cells.”
Dr. Sachs asked Dr. Mohiuddin for confirmation that Mr. Bennett displayed no more than DNAemia, circulating cell-free PCMV DNA presumably shed from the porcine heart, but no sign of the virus itself outside of the heart’s porcine cells.
Cell-free DNA had shown up in Mr. Bennett’s circulation about 20 days after the surgery, with concentrations rising until at least day 50. Post-hoc polymerase chain reaction (PCR) testing disclosed PCMV only in the pig’s spleen and porcine cells of the transplanted heart, Dr. Mohiuddin noted.
“We have not found any evidence that the patient was infected by PCMV,” nor was there evidence of any disease related to PCMV, Dr. Mohiuddin replied.
Nor of ongoing rejection
Mr. Bennett’s new heart passed a critical test in the first post-implantation hours by avoiding acute rejection, a potentially disastrous outcome that three of the pig’s 10 gene edits had been designed to prevent.
Although chronic immune rejection was always a concern despite Mr. Bennett’s novel immunosuppressant regimen, myocardial biopsy on postoperative days 34, 50, and 56 and necropsy showed “no signs of typical xenograft rejection,” Dr. Mohiuddin said at the ATC presentation. But “there’s a chance of atypical rejection which we were not accustomed to.”
By day 50, his diastolic function showed echocardiographic signs of deterioration, and “we started seeing interstitial edema with some extravasation of red blood cells, which we thought would resolve over a period of time,” he said. Eventually, however, “we saw that turn into fibroblasts and scar tissue.”
Mr. Bennett once again went on veno-arterial ECMO but died 10 days later. Once they had seen histologic evidence of fibrosis, Dr. Mohiuddin told this news organization, the team believed the myocardial injury was irreversible. “That was the reason we gave up on recovery.”
Mr. Bennett’s xenotransplantation journey has taught the field a lot, he said. “By no means was this a failure; we consider this a huge success. You can do all the experiments in animal models, but you won’t find out the true mechanism of rejection unless you do these kinds of human experiments.”
Looking ahead to clinical trials
Research involving humans is always subject to vagaries of human nature, including degree of adherence to prescribed therapy and – in xenotransplantation – precautions in place to mitigate any risks to public health. Such risks theoretically include transfer of porcine viruses or other pathogens to the patient and subsequent release into the general population.
Looking ahead to the possibility of clinical trials after this successful xenotransplantation experience, transplant nephrologist and epidemiologist Peter P. Reese, MD, PhD, University of Pennsylvania, Philadelphia, raised the potentially controversial issue in discussion following Dr. Mohiuddin’s presentation.
It’s known that Mr. Bennett had been repeatedly turned down for a conventional allograft transplant primarily because of his history of treatment noncompliance. Should such a record, Dr. Reese asked, be a relative contraindication to enrollment in any future xenotransplantation trials? Or does the field need a standardized gauge of a patient’s readiness, once discharged, to adhere not only to all medications – including those that fight infection – but also with rules established for public safety, such as routine contact reporting?
“It makes me wonder about choosing a noncompliant patient for these trials,” Dr. Reese said. “If we discharge a patient from the hospital who is at risk for a zoonotic infection that could spread if they basically refuse to cooperate with us or with public health authorities, it really could have negative consequences for the reputation of the field.”
Dr. Mohiuddin agreed such concerns are valid. Mr. Bennett “and all his immediate contacts” signed consent forms acknowledging their willingness to be followed should he be discharged. Mr. Bennett himself “signed a consent to inform us if he has any other intimate contact with someone,” he said in an interview.
“But those are only on paper.” Had Mr. Bennett survived to be discharged, Dr. Mohuiddin said, “no one knows how he would have behaved.”
Dr. Mohiuddin said the research staff had prepared to monitor Mr. Bennett at his home if that’s what it took. “We were ready to follow him as long as we could. There was a surveillance plan in place.”
A version of this article first appeared on Medscape.com.
Emergency angiography for cardiac arrest without ST elevation?
Patients successfully resuscitated after an out-of-hospital cardiac arrest who did not have ST-segment elevation on their electrocardiogram did not benefit from emergency coronary angiography in a new randomized clinical trial.
In the EMERGE trial, a strategy of emergency coronary angiography was not found to be better than a strategy of delayed coronary angiography with respect to the 180-day survival rate with no or minimal neurologic sequelae.
The authors note that, although the study was underpowered, the results are consistent with previously published studies and do not support routine emergency coronary angiography in survivors of out-of-hospital cardiac arrest without ST elevation.
But senior author, Christian Spaulding, MD, PhD, European Hospital Georges Pompidou, Paris, believes some such patients may still benefit from emergency angiography.
“Most patients who have been resuscitated after out of hospital cardiac arrest will have neurological damage, which will be the primary cause of death,” Dr. Spaulding told this news organization. “It will not make any difference to these patients if they have a coronary lesion treated. So, going forward, I think we need to look for patients who are likely not to have a high degree of neurological damage and who could still benefit from early angiography.”
The EMERGE study was published online in JAMA Cardiology.
In patients who have suffered an out-of-hospital cardiac arrest with no obvious noncardiac cause such as trauma, it is believed that the cardiac arrest is caused by coronary occlusions, and emergency angiography may be able to improve survival in these patients, Dr. Spaulding explained.
In about one-third of such patients, the ECG before hospitalization shows ST elevation, and in this group, there is a high probability (around 70%-80%) that there is going to be a coronary occlusion, so these patients are usually taken directly to emergency angiography.
But, in the other two-thirds of patients, there is no ST elevation on the ECG, and in these patients the chances of finding a coronary occlusion are lower (around 25%-35%).
The EMERGE trial was conducted in this latter group without ST elevation.
For the study, which was conducted in 22 French centers, 279 such patients (mean age, 64 years) were randomized to either emergency or delayed (48-96 hours) coronary angiography. The mean time delay between randomization and coronary angiography was 0.6 hours in the emergency group and 55.1 hours in the delayed group.
The primary outcome was the 180-day survival rate with minimal neurological damage, defined as Cerebral Performance Category of 2 or less. This occurred in 34.1% of the emergency angiography group and 30.7% of the delayed angiography group (hazard ratio, 0.87; 95% confidence interval, 0.65-1.15; P = .32).
There was also no difference in the overall survival rate at 180 days (36.2% vs. 33.3%; HR, 0.86; P = .31) and in secondary outcomes between the two groups.
Dr. Spaulding noted that three other randomized trials in a similar patient population have all shown similar results, with no difference in survival found between patients who have emergency coronary angiography as soon as they are admitted to hospital and those in whom angiography was not performed until a couple of days later.
However, several registry studies in a total of more than 6,000 patients have suggested a benefit of immediate angiography in these patients. “So, there is some disconnect here,” he said.
Dr. Spaulding believes the reason for this disconnect may be that the registry studies may have included patients with less neurological damage so more likely to survive and to benefit from having coronary lesions treated promptly.
“Paramedics sometimes make a judgment on which patients may have minimal neurological damage, and this may affect the choice of hospital a patient is taken to, and then the emergency department doctor may again assess whether a patient should go for immediate angiography or not. So, patients in these registry studies who received emergency angiography were likely already preselected to some extent,” he suggested.
In contrast, the randomized trials have accepted all patients, so there were probably more with neurological damage. “In our trial, almost 70% of patients were in asystole. These are the ones who [are] the most likely to have neurological damage,” he pointed out.
“Because there was such a striking difference in the registry studies, I think there is a group of patients [who] will benefit from immediate emergency coronary angiography, but we have to work out how to select these patients,” he commented.
Dr. Spaulding noted that a recent registry study published in JACC: Cardiovascular Interventions used a score known as MIRACLE2, (which takes into account various factors including age of patient and type of rhythm on ECG) and the degree of cardiogenic shock on arrival at hospital as measured by the SCAI shock score to define a potential cohort of patients at low risk for neurologic injury who benefit most from immediate coronary angiography.
“In my practice at present, I would advise the emergency team that a young patient who had had resuscitation started quickly, had been defibrillated early, and got to hospital quickly should go for an immediate coronary angiogram. It can’t do any harm, and there may be a benefit in such patients,” Dr. Spaulding added.The EMERGE study was supported in part by Assistance Publique–Hôpitaux de Paris and the French Ministry of Health, through the national Programme Hospitalier de Recherche Clinique. Dr. Spaulding reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Patients successfully resuscitated after an out-of-hospital cardiac arrest who did not have ST-segment elevation on their electrocardiogram did not benefit from emergency coronary angiography in a new randomized clinical trial.
In the EMERGE trial, a strategy of emergency coronary angiography was not found to be better than a strategy of delayed coronary angiography with respect to the 180-day survival rate with no or minimal neurologic sequelae.
The authors note that, although the study was underpowered, the results are consistent with previously published studies and do not support routine emergency coronary angiography in survivors of out-of-hospital cardiac arrest without ST elevation.
But senior author, Christian Spaulding, MD, PhD, European Hospital Georges Pompidou, Paris, believes some such patients may still benefit from emergency angiography.
“Most patients who have been resuscitated after out of hospital cardiac arrest will have neurological damage, which will be the primary cause of death,” Dr. Spaulding told this news organization. “It will not make any difference to these patients if they have a coronary lesion treated. So, going forward, I think we need to look for patients who are likely not to have a high degree of neurological damage and who could still benefit from early angiography.”
The EMERGE study was published online in JAMA Cardiology.
In patients who have suffered an out-of-hospital cardiac arrest with no obvious noncardiac cause such as trauma, it is believed that the cardiac arrest is caused by coronary occlusions, and emergency angiography may be able to improve survival in these patients, Dr. Spaulding explained.
In about one-third of such patients, the ECG before hospitalization shows ST elevation, and in this group, there is a high probability (around 70%-80%) that there is going to be a coronary occlusion, so these patients are usually taken directly to emergency angiography.
But, in the other two-thirds of patients, there is no ST elevation on the ECG, and in these patients the chances of finding a coronary occlusion are lower (around 25%-35%).
The EMERGE trial was conducted in this latter group without ST elevation.
For the study, which was conducted in 22 French centers, 279 such patients (mean age, 64 years) were randomized to either emergency or delayed (48-96 hours) coronary angiography. The mean time delay between randomization and coronary angiography was 0.6 hours in the emergency group and 55.1 hours in the delayed group.
The primary outcome was the 180-day survival rate with minimal neurological damage, defined as Cerebral Performance Category of 2 or less. This occurred in 34.1% of the emergency angiography group and 30.7% of the delayed angiography group (hazard ratio, 0.87; 95% confidence interval, 0.65-1.15; P = .32).
There was also no difference in the overall survival rate at 180 days (36.2% vs. 33.3%; HR, 0.86; P = .31) and in secondary outcomes between the two groups.
Dr. Spaulding noted that three other randomized trials in a similar patient population have all shown similar results, with no difference in survival found between patients who have emergency coronary angiography as soon as they are admitted to hospital and those in whom angiography was not performed until a couple of days later.
However, several registry studies in a total of more than 6,000 patients have suggested a benefit of immediate angiography in these patients. “So, there is some disconnect here,” he said.
Dr. Spaulding believes the reason for this disconnect may be that the registry studies may have included patients with less neurological damage so more likely to survive and to benefit from having coronary lesions treated promptly.
“Paramedics sometimes make a judgment on which patients may have minimal neurological damage, and this may affect the choice of hospital a patient is taken to, and then the emergency department doctor may again assess whether a patient should go for immediate angiography or not. So, patients in these registry studies who received emergency angiography were likely already preselected to some extent,” he suggested.
In contrast, the randomized trials have accepted all patients, so there were probably more with neurological damage. “In our trial, almost 70% of patients were in asystole. These are the ones who [are] the most likely to have neurological damage,” he pointed out.
“Because there was such a striking difference in the registry studies, I think there is a group of patients [who] will benefit from immediate emergency coronary angiography, but we have to work out how to select these patients,” he commented.
Dr. Spaulding noted that a recent registry study published in JACC: Cardiovascular Interventions used a score known as MIRACLE2, (which takes into account various factors including age of patient and type of rhythm on ECG) and the degree of cardiogenic shock on arrival at hospital as measured by the SCAI shock score to define a potential cohort of patients at low risk for neurologic injury who benefit most from immediate coronary angiography.
“In my practice at present, I would advise the emergency team that a young patient who had had resuscitation started quickly, had been defibrillated early, and got to hospital quickly should go for an immediate coronary angiogram. It can’t do any harm, and there may be a benefit in such patients,” Dr. Spaulding added.The EMERGE study was supported in part by Assistance Publique–Hôpitaux de Paris and the French Ministry of Health, through the national Programme Hospitalier de Recherche Clinique. Dr. Spaulding reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Patients successfully resuscitated after an out-of-hospital cardiac arrest who did not have ST-segment elevation on their electrocardiogram did not benefit from emergency coronary angiography in a new randomized clinical trial.
In the EMERGE trial, a strategy of emergency coronary angiography was not found to be better than a strategy of delayed coronary angiography with respect to the 180-day survival rate with no or minimal neurologic sequelae.
The authors note that, although the study was underpowered, the results are consistent with previously published studies and do not support routine emergency coronary angiography in survivors of out-of-hospital cardiac arrest without ST elevation.
But senior author, Christian Spaulding, MD, PhD, European Hospital Georges Pompidou, Paris, believes some such patients may still benefit from emergency angiography.
“Most patients who have been resuscitated after out of hospital cardiac arrest will have neurological damage, which will be the primary cause of death,” Dr. Spaulding told this news organization. “It will not make any difference to these patients if they have a coronary lesion treated. So, going forward, I think we need to look for patients who are likely not to have a high degree of neurological damage and who could still benefit from early angiography.”
The EMERGE study was published online in JAMA Cardiology.
In patients who have suffered an out-of-hospital cardiac arrest with no obvious noncardiac cause such as trauma, it is believed that the cardiac arrest is caused by coronary occlusions, and emergency angiography may be able to improve survival in these patients, Dr. Spaulding explained.
In about one-third of such patients, the ECG before hospitalization shows ST elevation, and in this group, there is a high probability (around 70%-80%) that there is going to be a coronary occlusion, so these patients are usually taken directly to emergency angiography.
But, in the other two-thirds of patients, there is no ST elevation on the ECG, and in these patients the chances of finding a coronary occlusion are lower (around 25%-35%).
The EMERGE trial was conducted in this latter group without ST elevation.
For the study, which was conducted in 22 French centers, 279 such patients (mean age, 64 years) were randomized to either emergency or delayed (48-96 hours) coronary angiography. The mean time delay between randomization and coronary angiography was 0.6 hours in the emergency group and 55.1 hours in the delayed group.
The primary outcome was the 180-day survival rate with minimal neurological damage, defined as Cerebral Performance Category of 2 or less. This occurred in 34.1% of the emergency angiography group and 30.7% of the delayed angiography group (hazard ratio, 0.87; 95% confidence interval, 0.65-1.15; P = .32).
There was also no difference in the overall survival rate at 180 days (36.2% vs. 33.3%; HR, 0.86; P = .31) and in secondary outcomes between the two groups.
Dr. Spaulding noted that three other randomized trials in a similar patient population have all shown similar results, with no difference in survival found between patients who have emergency coronary angiography as soon as they are admitted to hospital and those in whom angiography was not performed until a couple of days later.
However, several registry studies in a total of more than 6,000 patients have suggested a benefit of immediate angiography in these patients. “So, there is some disconnect here,” he said.
Dr. Spaulding believes the reason for this disconnect may be that the registry studies may have included patients with less neurological damage so more likely to survive and to benefit from having coronary lesions treated promptly.
“Paramedics sometimes make a judgment on which patients may have minimal neurological damage, and this may affect the choice of hospital a patient is taken to, and then the emergency department doctor may again assess whether a patient should go for immediate angiography or not. So, patients in these registry studies who received emergency angiography were likely already preselected to some extent,” he suggested.
In contrast, the randomized trials have accepted all patients, so there were probably more with neurological damage. “In our trial, almost 70% of patients were in asystole. These are the ones who [are] the most likely to have neurological damage,” he pointed out.
“Because there was such a striking difference in the registry studies, I think there is a group of patients [who] will benefit from immediate emergency coronary angiography, but we have to work out how to select these patients,” he commented.
Dr. Spaulding noted that a recent registry study published in JACC: Cardiovascular Interventions used a score known as MIRACLE2, (which takes into account various factors including age of patient and type of rhythm on ECG) and the degree of cardiogenic shock on arrival at hospital as measured by the SCAI shock score to define a potential cohort of patients at low risk for neurologic injury who benefit most from immediate coronary angiography.
“In my practice at present, I would advise the emergency team that a young patient who had had resuscitation started quickly, had been defibrillated early, and got to hospital quickly should go for an immediate coronary angiogram. It can’t do any harm, and there may be a benefit in such patients,” Dr. Spaulding added.The EMERGE study was supported in part by Assistance Publique–Hôpitaux de Paris and the French Ministry of Health, through the national Programme Hospitalier de Recherche Clinique. Dr. Spaulding reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
New guideline for in-hospital care of diabetes says use CGMs
Goal-directed glycemic management – which may include new technologies for glucose monitoring – for non–critically ill hospitalized patients who have diabetes or newly recognized hyperglycemia can improve outcomes, according to a new practice guideline from the Endocrine Society.
Even though roughly 35% of hospitalized patients have diabetes or newly discovered hyperglycemia, there is “wide variability in glycemic management in clinical practice,” writing panel chair Mary Korytkowski, MD, from the University of Pittsburgh, said at the annual meeting of the Endocrine Society. “These patients get admitted to every patient service in the hospital, meaning that every clinical service will encounter this group of patients, and their glycemic management can have a major effect on their outcomes. Both short term and long term.”
This guideline provides strategies “to achieve previously recommended glycemic goals while also reducing the risk for hypoglycemia, and this includes inpatient use of insulin pump therapy or continuous glucose monitoring [CGM] devices, among others,” she said.
It also includes “recommendations for preoperative glycemic goals as well as when the use of correctional insulin – well known as sliding scale insulin – may be appropriate” and when it is not.
The document, which replaces a 2012 guideline, was published online in the Journal of Clinical Endocrinology & Metabolism.
A multidisciplinary panel developed the document over the last 3 years to answer 10 clinical practice questions related to management of non–critically ill hospitalized patients with diabetes or newly discovered hyperglycemia.
Use of CGM devices in hospital
The first recommendation is: “In adults with insulin-treated diabetes hospitalized for noncritical illness who are at high risk of hypoglycemia, we suggest the use of real-time [CGM] with confirmatory bedside point-of-care blood glucose monitoring for adjustments in insulin dosing rather than point-of-care blood glucose rather than testing alone in hospital settings where resources and training are available.” (Conditional recommendation. Low certainty of evidence).
“We were actually very careful in terms of looking at the data” for use of CGMs, Dr. Korytkowski said in an interview.
Although CGMs are approved by the Food and Drug Administration in the outpatient setting, and that’s becoming the standard of care there, they are not yet approved for in-hospital use.
However, the FDA granted an emergency allowance for use of CGMs in hospitals during the COVID-19 pandemic.
That was “when everyone was scrambling for what to do,” Dr. Korytkowski noted. “There was a shortage of personal protective equipment and a real interest in trying to limit the amount of exposure of healthcare personnel in some of these really critically ill patients for whom intravenous insulin therapy was used to control their glucose level.”
On March 1, the FDA granted Breakthrough Devices Designation for Dexcom CGM use in the hospital setting.
The new guideline suggests CGM be used to detect trends in glycemic management, with insulin dosing decisions made with point-of-care glucose measure (the standard of care).
To implement CGM for glycemic management in hospitals, Dr. Korytkowski said, would require “extensive staff and nursing education to have people with expertise available to provide support to nursing personnel who are both placing these devices, changing these devices, looking at trends, and then knowing when to remove them for certain procedures such as MRI or radiologic procedures.”
“We know that not all hospitals may be readily available to use these devices,” she said. “It is an area of active research. But the use of these devices during the pandemic, in both critical care and non–critical care setting has really provided us with a lot of information that was used to formulate this suggestion in the guideline.”
The document addresses the following areas: CGM, continuous subcutaneous insulin infusion pump therapy, inpatient diabetes education, prespecified preoperative glycemic targets, use of neutral protamine Hagedorn insulin for glucocorticoid or enteral nutrition-associated hyperglycemia, noninsulin therapies, preoperative carbohydrate-containing oral fluids, carbohydrate counting for prandial (mealtime) insulin dosing, and correctional and scheduled (basal or basal bolus) insulin therapies.
Nine key recommendations
Dr. Korytkowski identified nine key recommendations:
- CGM systems can help guide glycemic management with reduced risk for hypoglycemia.
- Patients experiencing glucocorticoid- or enteral nutrition–associated hyperglycemia require scheduled insulin therapy to address anticipated glucose excursions.
- Selected patients using insulin pump therapy prior to a hospital admission can continue to use these devices in the hospital if they have the mental and physical capacity to do so with knowledgeable hospital personnel.
- Diabetes self-management education provided to hospitalized patients can promote improved glycemic control following discharge with reductions in the risk for hospital readmission. “We know that is recommended for patients in the outpatient setting but often they do not get this,” she said. “We were able to observe that this can also impact long-term outcomes “
- Patients with diabetes scheduled for elective surgery may have improved postoperative outcomes when preoperative hemoglobin A1c is 8% or less and preoperative blood glucose is less than 180 mg/dL. “This recommendation answers the question: ‘Where should glycemic goals be for people who are undergoing surgery?’ ”
- Providing preoperative carbohydrate-containing beverages to patients with known diabetes is not recommended.
- Patients with newly recognized hyperglycemia or well-managed diabetes on noninsulin therapy may be treated with correctional insulin alone as initial therapy at hospital admission.
- Some noninsulin diabetes therapies can be used in combination with correction insulin for patients with type 2 diabetes who have mild hyperglycemia.
- Correctional insulin – “otherwise known as sliding-scale insulin” – can be used as initial therapy for patients with newly recognized hyperglycemia or type 2 diabetes treated with noninsulin therapy prior to hospital admission.
- Scheduled insulin therapy is preferred for patients experiencing persistent blood glucose values greater than 180 mg/dL and is recommended for patients using insulin therapy prior to admission.
The guideline writers’ hopes
“We hope that this guideline will resolve debates” about appropriate preoperative glycemic management and when sliding-scale insulin can be used and should not be used, said Dr. Korytkowski.
The authors also hope that “it will stimulate research funding for this very important aspect of diabetes care, and that hospitals will recognize the importance of having access to knowledgeable diabetes care and education specialists who can provide staff education regarding inpatient glycemic management, provide oversight for patients using insulin pump therapy or CGM devices, and empower hospital nurses to provide diabetes [self-management] education prior to patient discharge.”
Claire Pegg, the patient representative on the panel, hopes “that this guideline serves as the beginning of a conversation that will allow inpatient caregivers to provide individualized care to patients – some of whom may be self-sufficient with their glycemic management and others who need additional assistance.”
Development of the guideline was funded by the Endocrine Society. Dr. Korytkowski has reported no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
Goal-directed glycemic management – which may include new technologies for glucose monitoring – for non–critically ill hospitalized patients who have diabetes or newly recognized hyperglycemia can improve outcomes, according to a new practice guideline from the Endocrine Society.
Even though roughly 35% of hospitalized patients have diabetes or newly discovered hyperglycemia, there is “wide variability in glycemic management in clinical practice,” writing panel chair Mary Korytkowski, MD, from the University of Pittsburgh, said at the annual meeting of the Endocrine Society. “These patients get admitted to every patient service in the hospital, meaning that every clinical service will encounter this group of patients, and their glycemic management can have a major effect on their outcomes. Both short term and long term.”
This guideline provides strategies “to achieve previously recommended glycemic goals while also reducing the risk for hypoglycemia, and this includes inpatient use of insulin pump therapy or continuous glucose monitoring [CGM] devices, among others,” she said.
It also includes “recommendations for preoperative glycemic goals as well as when the use of correctional insulin – well known as sliding scale insulin – may be appropriate” and when it is not.
The document, which replaces a 2012 guideline, was published online in the Journal of Clinical Endocrinology & Metabolism.
A multidisciplinary panel developed the document over the last 3 years to answer 10 clinical practice questions related to management of non–critically ill hospitalized patients with diabetes or newly discovered hyperglycemia.
Use of CGM devices in hospital
The first recommendation is: “In adults with insulin-treated diabetes hospitalized for noncritical illness who are at high risk of hypoglycemia, we suggest the use of real-time [CGM] with confirmatory bedside point-of-care blood glucose monitoring for adjustments in insulin dosing rather than point-of-care blood glucose rather than testing alone in hospital settings where resources and training are available.” (Conditional recommendation. Low certainty of evidence).
“We were actually very careful in terms of looking at the data” for use of CGMs, Dr. Korytkowski said in an interview.
Although CGMs are approved by the Food and Drug Administration in the outpatient setting, and that’s becoming the standard of care there, they are not yet approved for in-hospital use.
However, the FDA granted an emergency allowance for use of CGMs in hospitals during the COVID-19 pandemic.
That was “when everyone was scrambling for what to do,” Dr. Korytkowski noted. “There was a shortage of personal protective equipment and a real interest in trying to limit the amount of exposure of healthcare personnel in some of these really critically ill patients for whom intravenous insulin therapy was used to control their glucose level.”
On March 1, the FDA granted Breakthrough Devices Designation for Dexcom CGM use in the hospital setting.
The new guideline suggests CGM be used to detect trends in glycemic management, with insulin dosing decisions made with point-of-care glucose measure (the standard of care).
To implement CGM for glycemic management in hospitals, Dr. Korytkowski said, would require “extensive staff and nursing education to have people with expertise available to provide support to nursing personnel who are both placing these devices, changing these devices, looking at trends, and then knowing when to remove them for certain procedures such as MRI or radiologic procedures.”
“We know that not all hospitals may be readily available to use these devices,” she said. “It is an area of active research. But the use of these devices during the pandemic, in both critical care and non–critical care setting has really provided us with a lot of information that was used to formulate this suggestion in the guideline.”
The document addresses the following areas: CGM, continuous subcutaneous insulin infusion pump therapy, inpatient diabetes education, prespecified preoperative glycemic targets, use of neutral protamine Hagedorn insulin for glucocorticoid or enteral nutrition-associated hyperglycemia, noninsulin therapies, preoperative carbohydrate-containing oral fluids, carbohydrate counting for prandial (mealtime) insulin dosing, and correctional and scheduled (basal or basal bolus) insulin therapies.
Nine key recommendations
Dr. Korytkowski identified nine key recommendations:
- CGM systems can help guide glycemic management with reduced risk for hypoglycemia.
- Patients experiencing glucocorticoid- or enteral nutrition–associated hyperglycemia require scheduled insulin therapy to address anticipated glucose excursions.
- Selected patients using insulin pump therapy prior to a hospital admission can continue to use these devices in the hospital if they have the mental and physical capacity to do so with knowledgeable hospital personnel.
- Diabetes self-management education provided to hospitalized patients can promote improved glycemic control following discharge with reductions in the risk for hospital readmission. “We know that is recommended for patients in the outpatient setting but often they do not get this,” she said. “We were able to observe that this can also impact long-term outcomes “
- Patients with diabetes scheduled for elective surgery may have improved postoperative outcomes when preoperative hemoglobin A1c is 8% or less and preoperative blood glucose is less than 180 mg/dL. “This recommendation answers the question: ‘Where should glycemic goals be for people who are undergoing surgery?’ ”
- Providing preoperative carbohydrate-containing beverages to patients with known diabetes is not recommended.
- Patients with newly recognized hyperglycemia or well-managed diabetes on noninsulin therapy may be treated with correctional insulin alone as initial therapy at hospital admission.
- Some noninsulin diabetes therapies can be used in combination with correction insulin for patients with type 2 diabetes who have mild hyperglycemia.
- Correctional insulin – “otherwise known as sliding-scale insulin” – can be used as initial therapy for patients with newly recognized hyperglycemia or type 2 diabetes treated with noninsulin therapy prior to hospital admission.
- Scheduled insulin therapy is preferred for patients experiencing persistent blood glucose values greater than 180 mg/dL and is recommended for patients using insulin therapy prior to admission.
The guideline writers’ hopes
“We hope that this guideline will resolve debates” about appropriate preoperative glycemic management and when sliding-scale insulin can be used and should not be used, said Dr. Korytkowski.
The authors also hope that “it will stimulate research funding for this very important aspect of diabetes care, and that hospitals will recognize the importance of having access to knowledgeable diabetes care and education specialists who can provide staff education regarding inpatient glycemic management, provide oversight for patients using insulin pump therapy or CGM devices, and empower hospital nurses to provide diabetes [self-management] education prior to patient discharge.”
Claire Pegg, the patient representative on the panel, hopes “that this guideline serves as the beginning of a conversation that will allow inpatient caregivers to provide individualized care to patients – some of whom may be self-sufficient with their glycemic management and others who need additional assistance.”
Development of the guideline was funded by the Endocrine Society. Dr. Korytkowski has reported no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
Goal-directed glycemic management – which may include new technologies for glucose monitoring – for non–critically ill hospitalized patients who have diabetes or newly recognized hyperglycemia can improve outcomes, according to a new practice guideline from the Endocrine Society.
Even though roughly 35% of hospitalized patients have diabetes or newly discovered hyperglycemia, there is “wide variability in glycemic management in clinical practice,” writing panel chair Mary Korytkowski, MD, from the University of Pittsburgh, said at the annual meeting of the Endocrine Society. “These patients get admitted to every patient service in the hospital, meaning that every clinical service will encounter this group of patients, and their glycemic management can have a major effect on their outcomes. Both short term and long term.”
This guideline provides strategies “to achieve previously recommended glycemic goals while also reducing the risk for hypoglycemia, and this includes inpatient use of insulin pump therapy or continuous glucose monitoring [CGM] devices, among others,” she said.
It also includes “recommendations for preoperative glycemic goals as well as when the use of correctional insulin – well known as sliding scale insulin – may be appropriate” and when it is not.
The document, which replaces a 2012 guideline, was published online in the Journal of Clinical Endocrinology & Metabolism.
A multidisciplinary panel developed the document over the last 3 years to answer 10 clinical practice questions related to management of non–critically ill hospitalized patients with diabetes or newly discovered hyperglycemia.
Use of CGM devices in hospital
The first recommendation is: “In adults with insulin-treated diabetes hospitalized for noncritical illness who are at high risk of hypoglycemia, we suggest the use of real-time [CGM] with confirmatory bedside point-of-care blood glucose monitoring for adjustments in insulin dosing rather than point-of-care blood glucose rather than testing alone in hospital settings where resources and training are available.” (Conditional recommendation. Low certainty of evidence).
“We were actually very careful in terms of looking at the data” for use of CGMs, Dr. Korytkowski said in an interview.
Although CGMs are approved by the Food and Drug Administration in the outpatient setting, and that’s becoming the standard of care there, they are not yet approved for in-hospital use.
However, the FDA granted an emergency allowance for use of CGMs in hospitals during the COVID-19 pandemic.
That was “when everyone was scrambling for what to do,” Dr. Korytkowski noted. “There was a shortage of personal protective equipment and a real interest in trying to limit the amount of exposure of healthcare personnel in some of these really critically ill patients for whom intravenous insulin therapy was used to control their glucose level.”
On March 1, the FDA granted Breakthrough Devices Designation for Dexcom CGM use in the hospital setting.
The new guideline suggests CGM be used to detect trends in glycemic management, with insulin dosing decisions made with point-of-care glucose measure (the standard of care).
To implement CGM for glycemic management in hospitals, Dr. Korytkowski said, would require “extensive staff and nursing education to have people with expertise available to provide support to nursing personnel who are both placing these devices, changing these devices, looking at trends, and then knowing when to remove them for certain procedures such as MRI or radiologic procedures.”
“We know that not all hospitals may be readily available to use these devices,” she said. “It is an area of active research. But the use of these devices during the pandemic, in both critical care and non–critical care setting has really provided us with a lot of information that was used to formulate this suggestion in the guideline.”
The document addresses the following areas: CGM, continuous subcutaneous insulin infusion pump therapy, inpatient diabetes education, prespecified preoperative glycemic targets, use of neutral protamine Hagedorn insulin for glucocorticoid or enteral nutrition-associated hyperglycemia, noninsulin therapies, preoperative carbohydrate-containing oral fluids, carbohydrate counting for prandial (mealtime) insulin dosing, and correctional and scheduled (basal or basal bolus) insulin therapies.
Nine key recommendations
Dr. Korytkowski identified nine key recommendations:
- CGM systems can help guide glycemic management with reduced risk for hypoglycemia.
- Patients experiencing glucocorticoid- or enteral nutrition–associated hyperglycemia require scheduled insulin therapy to address anticipated glucose excursions.
- Selected patients using insulin pump therapy prior to a hospital admission can continue to use these devices in the hospital if they have the mental and physical capacity to do so with knowledgeable hospital personnel.
- Diabetes self-management education provided to hospitalized patients can promote improved glycemic control following discharge with reductions in the risk for hospital readmission. “We know that is recommended for patients in the outpatient setting but often they do not get this,” she said. “We were able to observe that this can also impact long-term outcomes “
- Patients with diabetes scheduled for elective surgery may have improved postoperative outcomes when preoperative hemoglobin A1c is 8% or less and preoperative blood glucose is less than 180 mg/dL. “This recommendation answers the question: ‘Where should glycemic goals be for people who are undergoing surgery?’ ”
- Providing preoperative carbohydrate-containing beverages to patients with known diabetes is not recommended.
- Patients with newly recognized hyperglycemia or well-managed diabetes on noninsulin therapy may be treated with correctional insulin alone as initial therapy at hospital admission.
- Some noninsulin diabetes therapies can be used in combination with correction insulin for patients with type 2 diabetes who have mild hyperglycemia.
- Correctional insulin – “otherwise known as sliding-scale insulin” – can be used as initial therapy for patients with newly recognized hyperglycemia or type 2 diabetes treated with noninsulin therapy prior to hospital admission.
- Scheduled insulin therapy is preferred for patients experiencing persistent blood glucose values greater than 180 mg/dL and is recommended for patients using insulin therapy prior to admission.
The guideline writers’ hopes
“We hope that this guideline will resolve debates” about appropriate preoperative glycemic management and when sliding-scale insulin can be used and should not be used, said Dr. Korytkowski.
The authors also hope that “it will stimulate research funding for this very important aspect of diabetes care, and that hospitals will recognize the importance of having access to knowledgeable diabetes care and education specialists who can provide staff education regarding inpatient glycemic management, provide oversight for patients using insulin pump therapy or CGM devices, and empower hospital nurses to provide diabetes [self-management] education prior to patient discharge.”
Claire Pegg, the patient representative on the panel, hopes “that this guideline serves as the beginning of a conversation that will allow inpatient caregivers to provide individualized care to patients – some of whom may be self-sufficient with their glycemic management and others who need additional assistance.”
Development of the guideline was funded by the Endocrine Society. Dr. Korytkowski has reported no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
FROM ENDO 2022
Harmony pulmonary valve update: Regurgitation resolved 1 year out
The 1-year results of the Harmony transcatheter pulmonary valve to treat severe pulmonary regurgitation have shown a high rate of eliminating or reducing the degree of symptoms as well as freedom from endocarditis, sustained ventricular tachycardia, and the need for further interventions.
“Simply put, the good news is no endocarditis,” said Daniel S. Levi, MD, in presenting results from three different studies with 108 patients who received three different iterations of the device at the Society for Cardiovascular Angiography & Interventions annual scientific sessions.
“Endocarditis has been an issue for us in the pulmonary position; we have yet to have an endocarditis in these patients in 1 year,” he stressed.
The studies evaluated three different versions of the Harmony valve: TPV22 (42 patients), the first version with a 22-mm diameter; the Clinical TPV25 (17 patients), the first iteration of a 25 mm–wide device that has since been discontinued; and the modified TPV25 (45 patients), the second version of the 25-mm valve. The three studies are the early feasibility study of the TPV22, the continued-access study of the TPV22 and the mTPV25, and the pivotal study that included all three versions.
At baseline, 89% of patients had severe and 11% had moderate pulmonary regurgitation (PR). At 1 year, 92% had none or trace PR, 3% had mild PR, and 4% moderate disease.
Dr. Levi said the device “speaks for itself” in the results he presented. They include no deaths, no heart attacks, and no pulmonary thromboembolism. Other key outcomes include:
- One major stent fracture in one of the early feasibility study patients at 1-month follow-up.
- Four explants, with two in the discontinued cTPV25 and two with the TPV22 in the early-feasibility study.
- Four reinterventions, two with the discontinued cTPV25 and two valve-in-valve procedures with the mTPV25 in the continued-access study, one with stent placement in the right ventricular outflow tract.
Dr. Levi and coinvestigators also performed a breakdown of 1-year outcomes – freedom from PR, stenosis, and interventions – by device: 95.1% for TPV22; 89.7% for mTPV25; and 73.3% for the discontinued cTPV25.
Although the valve is indicated for adolescents and adults, most of the patients in the three studies were adults, with an average weight of 165 pounds (75 kg) who have had PR for decades, said Dr. Levi, an interventional pediatric cardiologist at the University of California, Los Angeles. “With a device like this we are hopefully shifting to treating that a little bit earlier, but fortunately we don’t usually need to treat it before puberty.” The 25-mm TPV gives “a really nice landing zone” for future valve placement. “The goal is to keep patients out of the operating room for at least a few decades if not their whole lives,” he said.
Dr. Levi said the Harmony investigators will follow outcomes with the 22- and modified 25-mm Harmony valves, both of which remain commercially available, out to 10 years.
The study represents the first collective cohort evaluating the Harmony device across the early feasibility, continued access and pivotal studies, said Brian Morray, MD. “It’s important that people understand that evolution and how that impacts the way we look at outcomes, because when you aggregate the data, particularly for the TPV25, some of the procedural outcomes and the adverse events are no longer really reflective in the current time frame.”
These Harmony results “represent another big step in the evolution of interventional cardiology and will be up there with development of the Melody valve and the utility and the use of the Sapien valve in the pulmonary position,” said Dr. Morray, an associate professor of pediatrics at the University of Washington, Seattle, and an interventional cardiologist at Seattle Children’s Hospital.
Dr. Levi disclosed he is a consultant to Medtronic and Edwards Lifesciences. Dr. Morray disclosed he is a clinical proctor for Abbott and a consultant to Medtronic, but not for the Harmony device.
The 1-year results of the Harmony transcatheter pulmonary valve to treat severe pulmonary regurgitation have shown a high rate of eliminating or reducing the degree of symptoms as well as freedom from endocarditis, sustained ventricular tachycardia, and the need for further interventions.
“Simply put, the good news is no endocarditis,” said Daniel S. Levi, MD, in presenting results from three different studies with 108 patients who received three different iterations of the device at the Society for Cardiovascular Angiography & Interventions annual scientific sessions.
“Endocarditis has been an issue for us in the pulmonary position; we have yet to have an endocarditis in these patients in 1 year,” he stressed.
The studies evaluated three different versions of the Harmony valve: TPV22 (42 patients), the first version with a 22-mm diameter; the Clinical TPV25 (17 patients), the first iteration of a 25 mm–wide device that has since been discontinued; and the modified TPV25 (45 patients), the second version of the 25-mm valve. The three studies are the early feasibility study of the TPV22, the continued-access study of the TPV22 and the mTPV25, and the pivotal study that included all three versions.
At baseline, 89% of patients had severe and 11% had moderate pulmonary regurgitation (PR). At 1 year, 92% had none or trace PR, 3% had mild PR, and 4% moderate disease.
Dr. Levi said the device “speaks for itself” in the results he presented. They include no deaths, no heart attacks, and no pulmonary thromboembolism. Other key outcomes include:
- One major stent fracture in one of the early feasibility study patients at 1-month follow-up.
- Four explants, with two in the discontinued cTPV25 and two with the TPV22 in the early-feasibility study.
- Four reinterventions, two with the discontinued cTPV25 and two valve-in-valve procedures with the mTPV25 in the continued-access study, one with stent placement in the right ventricular outflow tract.
Dr. Levi and coinvestigators also performed a breakdown of 1-year outcomes – freedom from PR, stenosis, and interventions – by device: 95.1% for TPV22; 89.7% for mTPV25; and 73.3% for the discontinued cTPV25.
Although the valve is indicated for adolescents and adults, most of the patients in the three studies were adults, with an average weight of 165 pounds (75 kg) who have had PR for decades, said Dr. Levi, an interventional pediatric cardiologist at the University of California, Los Angeles. “With a device like this we are hopefully shifting to treating that a little bit earlier, but fortunately we don’t usually need to treat it before puberty.” The 25-mm TPV gives “a really nice landing zone” for future valve placement. “The goal is to keep patients out of the operating room for at least a few decades if not their whole lives,” he said.
Dr. Levi said the Harmony investigators will follow outcomes with the 22- and modified 25-mm Harmony valves, both of which remain commercially available, out to 10 years.
The study represents the first collective cohort evaluating the Harmony device across the early feasibility, continued access and pivotal studies, said Brian Morray, MD. “It’s important that people understand that evolution and how that impacts the way we look at outcomes, because when you aggregate the data, particularly for the TPV25, some of the procedural outcomes and the adverse events are no longer really reflective in the current time frame.”
These Harmony results “represent another big step in the evolution of interventional cardiology and will be up there with development of the Melody valve and the utility and the use of the Sapien valve in the pulmonary position,” said Dr. Morray, an associate professor of pediatrics at the University of Washington, Seattle, and an interventional cardiologist at Seattle Children’s Hospital.
Dr. Levi disclosed he is a consultant to Medtronic and Edwards Lifesciences. Dr. Morray disclosed he is a clinical proctor for Abbott and a consultant to Medtronic, but not for the Harmony device.
The 1-year results of the Harmony transcatheter pulmonary valve to treat severe pulmonary regurgitation have shown a high rate of eliminating or reducing the degree of symptoms as well as freedom from endocarditis, sustained ventricular tachycardia, and the need for further interventions.
“Simply put, the good news is no endocarditis,” said Daniel S. Levi, MD, in presenting results from three different studies with 108 patients who received three different iterations of the device at the Society for Cardiovascular Angiography & Interventions annual scientific sessions.
“Endocarditis has been an issue for us in the pulmonary position; we have yet to have an endocarditis in these patients in 1 year,” he stressed.
The studies evaluated three different versions of the Harmony valve: TPV22 (42 patients), the first version with a 22-mm diameter; the Clinical TPV25 (17 patients), the first iteration of a 25 mm–wide device that has since been discontinued; and the modified TPV25 (45 patients), the second version of the 25-mm valve. The three studies are the early feasibility study of the TPV22, the continued-access study of the TPV22 and the mTPV25, and the pivotal study that included all three versions.
At baseline, 89% of patients had severe and 11% had moderate pulmonary regurgitation (PR). At 1 year, 92% had none or trace PR, 3% had mild PR, and 4% moderate disease.
Dr. Levi said the device “speaks for itself” in the results he presented. They include no deaths, no heart attacks, and no pulmonary thromboembolism. Other key outcomes include:
- One major stent fracture in one of the early feasibility study patients at 1-month follow-up.
- Four explants, with two in the discontinued cTPV25 and two with the TPV22 in the early-feasibility study.
- Four reinterventions, two with the discontinued cTPV25 and two valve-in-valve procedures with the mTPV25 in the continued-access study, one with stent placement in the right ventricular outflow tract.
Dr. Levi and coinvestigators also performed a breakdown of 1-year outcomes – freedom from PR, stenosis, and interventions – by device: 95.1% for TPV22; 89.7% for mTPV25; and 73.3% for the discontinued cTPV25.
Although the valve is indicated for adolescents and adults, most of the patients in the three studies were adults, with an average weight of 165 pounds (75 kg) who have had PR for decades, said Dr. Levi, an interventional pediatric cardiologist at the University of California, Los Angeles. “With a device like this we are hopefully shifting to treating that a little bit earlier, but fortunately we don’t usually need to treat it before puberty.” The 25-mm TPV gives “a really nice landing zone” for future valve placement. “The goal is to keep patients out of the operating room for at least a few decades if not their whole lives,” he said.
Dr. Levi said the Harmony investigators will follow outcomes with the 22- and modified 25-mm Harmony valves, both of which remain commercially available, out to 10 years.
The study represents the first collective cohort evaluating the Harmony device across the early feasibility, continued access and pivotal studies, said Brian Morray, MD. “It’s important that people understand that evolution and how that impacts the way we look at outcomes, because when you aggregate the data, particularly for the TPV25, some of the procedural outcomes and the adverse events are no longer really reflective in the current time frame.”
These Harmony results “represent another big step in the evolution of interventional cardiology and will be up there with development of the Melody valve and the utility and the use of the Sapien valve in the pulmonary position,” said Dr. Morray, an associate professor of pediatrics at the University of Washington, Seattle, and an interventional cardiologist at Seattle Children’s Hospital.
Dr. Levi disclosed he is a consultant to Medtronic and Edwards Lifesciences. Dr. Morray disclosed he is a clinical proctor for Abbott and a consultant to Medtronic, but not for the Harmony device.
FROM SCAI 2022
Data concerns mount despite ISCHEMIA substudy correction
A long-standing request to clarify data irregularities in a 2021 ISCHEMIA substudy resulted in the publication of one correction, with a second correction in the works.
Further, the lone cardiac surgeon on the ISCHEMIA trial steering committee, T. Bruce Ferguson, MD, has resigned from the committee, citing a series of factors, including an inability to reconcile data in the substudy and two additional ISCHEMIA papers currently under review.
As previously reported, cardiac surgeons Faisal Bakaeen, MD, and Joseph Sabik III, MD, notified the journal Circulation in March that the Dr. Reynolds et al. substudy had inconsistencies between data in the main paper and supplemental tables detailing patients’ coronary artery disease (CAD) and ischemia severity.
The substudy found that CAD severity, classified using the modified Duke Prognostic Index score, predicted 4-year mortality and myocardial infarction in the landmark trial.
Circulation published a correction for the substudy on May 20, explaining that a “formatting error” resulted in data being incorrectly presented in two supplemental tables. It does not mention the surgeons’ letter to the editor, which can be found by clicking the “Q” icon below the paper.
Dr. Bakaeen, from the Cleveland Clinic, and Dr. Sabik, from University Hospitals Cleveland Medical Center, told this news organization that they submitted a second letter to editor on May 23 stating that “significant discrepancies” persist.
For example, 7.2% of participants (179/2,475) had moderate stenosis in one coronary vessel in the corrected Reynolds paper (Supplemental Tables I and II) versus 23.3% (697/2,986) in the primary ISCHEMIA manuscript published in the New England Journal of Medicine (Table S5).
The number of patients with left main ≥ 50% stenosis is, surprisingly, identical in both manuscripts, at 40, they said, despite the denominator dropping from 3,845 participants in the primary study to 2,475 participants with an evaluable modified Duke Prognostic Index score in the substudy.
The number of participants with previous coronary artery bypass surgery (CABG) is also hard to reconcile between manuscripts and, importantly, the substudy doesn’t distinguish between lesions bypassed with patent grafts and unbypassed grafts or those with occluded grafts.
“The fact that the authors are working on a second correction is appreciated, but with such numerous inconsistencies, at some point you reach the conclusion that an independent review of the data is the right thing to do for such a high-profile study that received over $100 million of National Institutes of Health support,” Dr. Bakaeen said. “No one should be satisfied or happy if there is any shadow of doubt here regarding the accuracy of the data.”
Speaking to this news organization prior to the first correction, lead substudy author Harmony Reynolds, MD, NYU Langone Health, detailed in depth how the formatting glitch inadvertently upgraded the number of diseased vessels and lesion severity in two supplemental tables.
She noted, as does the correction, that the data were correctly reported in the main manuscript tables and figures and in the remainder of the supplement.
Dr. Reynolds also said they’re in the process of preparing the data for “public sharing soon,” including the Duke Prognostic score at all levels. Dr. Reynolds had not responded by the time of this publication to a request for further details or a timeline.
The surgeons’ first letter to the editor was rejected because it was submitted outside the journal’s 6-week window for letters and was posted as a public comment April 18 via the research platform, Remarq.
Dr. Bakaeen said they were told their second letter was rejected because of Circulation’s “long standing policy” not to publish letters to the editor regarding manuscript corrections but that a correction is being issued.
Circulation editor-in-chief Joseph A. Hill, MD, PhD, UT Southwestern Medical Center, Dallas, said via email that the journal will update its online policies to more clearly state its requirements for publication and that it has been fully transparent with Dr. Bakaeen and Dr. Sabik regarding where it is in the current process.
He confirmed the surgeons were told June 1 that “after additional review, the authors have determined that whereas there are no errors, an additional minor correction is warranted to clarify the description of the study population and sample size. This correction will be published soon.”
Dr. Hill thanked Dr. Bakaeen and Dr. Sabik for bringing the matter to their attention and said, “It is also important to note that both updates to the Dr. Reynolds et al. paper are published as corrections. However, the results and conclusions of the paper remain unchanged.”
The bigger issue
Importantly, the recent AHA/ACC/SCAI coronary revascularization guidelines used ISCHEMIA data to support downgrading the CABG recommendation from class 1 to class 2B in 3-vessel CAD with normal left ventricular function and from class 1 to 2a in 3-vessel CAD with mild to moderate left ventricular dysfunction.
The trial reported no significant benefit with an initial invasive strategy over medical therapy in stable patients with moderate or severe CAD. European guidelines, however, give CABG a class I recommendation for severe three- or two-vessel disease with proximal left anterior descending (LAD) involvement.
Dr. Sabik and Dr. Bakaeen say patients with severe three- or two-vessel disease with proximal LAD involvement were underrepresented in the randomized trials cited by the guidelines but are the typical CABG patients in modern-day practice.
“That is why it is important to determine the severity of CAD accurately and definitively in ISCHEMIA,” Dr. Bakaeen said. “But the more we look at the data, the more errors we encounter.”
Two U.S. surgical groups that were part of the writing process withdrew support for the revascularization guidelines, as did several international surgical societies, citing the data used to support the changes as well as the makeup of the writing committee.
Dr. Ferguson, now with the medical device manufacturer Perfusio, said he resigned from the ISCHEMIA steering committee on May 8 after being unable to accurately reconcile the ISCHEMIA surgical subset data with the Reynolds substudy and two other ISCHEMIA papers on the CABG subset. At least one of those papers, he noted, was being hurriedly pushed through the review process to counter concerns raised by surgeons regarding interpretation of ISCHEMIA.
“This is the first time in my lengthy career in medicine where a level of political agendaism was actually driving the truck,” he said. “It was appalling to me, and I would have said that if I was an interventional cardiologist looking at the results.”
ISCHEMIA results have also been touted as representing state-of-the-art care around the world, but that didn’t appear to be the case for the surgical subset where, for example, China and India performed most CABGs off pump, and globally there was considerable variation in how surgeons approached surgical revascularization strategies, Dr. Ferguson said. “Whether this variability might impact the guideline discussion and these papers coming out remains to be determined.”
He noted that the study protocol allowed for the ISCHEMIA investigators to evaluate whether the variability in the surgical subset influenced the results by comparing the data to that in the Society of Thoracic Surgeons registry, but this option was never acted upon despite being brought to their attention.
“Something political between 2020 and 2022 has crept into the ISCHEMIA trial mindset gestalt, and I don’t like it,” Dr. Ferguson said. “And this can have enormous consequences.”
Asked whether their letters to Circulation are being used to undermine confidence in the ISCHEMIA findings, Dr. Sabik replied, “It is not about undermining ISCHEMIA, but understanding how applicable ISCHEMIA is to patients having CABG today. Understanding the severity of the CAD in patients enrolled in ISCHEMIA is, therefore, necessary.”
“The authors and Circulation have admitted to errors,” he said. “We want to be sure we understand how severe the errors are.”
“This is just about accuracy in a manuscript that may affect patient treatment and therefore patient lives. We want to make sure it is correct,” Dr. Sabik added.
A version of this article first appeared on Medscape.com.
A long-standing request to clarify data irregularities in a 2021 ISCHEMIA substudy resulted in the publication of one correction, with a second correction in the works.
Further, the lone cardiac surgeon on the ISCHEMIA trial steering committee, T. Bruce Ferguson, MD, has resigned from the committee, citing a series of factors, including an inability to reconcile data in the substudy and two additional ISCHEMIA papers currently under review.
As previously reported, cardiac surgeons Faisal Bakaeen, MD, and Joseph Sabik III, MD, notified the journal Circulation in March that the Dr. Reynolds et al. substudy had inconsistencies between data in the main paper and supplemental tables detailing patients’ coronary artery disease (CAD) and ischemia severity.
The substudy found that CAD severity, classified using the modified Duke Prognostic Index score, predicted 4-year mortality and myocardial infarction in the landmark trial.
Circulation published a correction for the substudy on May 20, explaining that a “formatting error” resulted in data being incorrectly presented in two supplemental tables. It does not mention the surgeons’ letter to the editor, which can be found by clicking the “Q” icon below the paper.
Dr. Bakaeen, from the Cleveland Clinic, and Dr. Sabik, from University Hospitals Cleveland Medical Center, told this news organization that they submitted a second letter to editor on May 23 stating that “significant discrepancies” persist.
For example, 7.2% of participants (179/2,475) had moderate stenosis in one coronary vessel in the corrected Reynolds paper (Supplemental Tables I and II) versus 23.3% (697/2,986) in the primary ISCHEMIA manuscript published in the New England Journal of Medicine (Table S5).
The number of patients with left main ≥ 50% stenosis is, surprisingly, identical in both manuscripts, at 40, they said, despite the denominator dropping from 3,845 participants in the primary study to 2,475 participants with an evaluable modified Duke Prognostic Index score in the substudy.
The number of participants with previous coronary artery bypass surgery (CABG) is also hard to reconcile between manuscripts and, importantly, the substudy doesn’t distinguish between lesions bypassed with patent grafts and unbypassed grafts or those with occluded grafts.
“The fact that the authors are working on a second correction is appreciated, but with such numerous inconsistencies, at some point you reach the conclusion that an independent review of the data is the right thing to do for such a high-profile study that received over $100 million of National Institutes of Health support,” Dr. Bakaeen said. “No one should be satisfied or happy if there is any shadow of doubt here regarding the accuracy of the data.”
Speaking to this news organization prior to the first correction, lead substudy author Harmony Reynolds, MD, NYU Langone Health, detailed in depth how the formatting glitch inadvertently upgraded the number of diseased vessels and lesion severity in two supplemental tables.
She noted, as does the correction, that the data were correctly reported in the main manuscript tables and figures and in the remainder of the supplement.
Dr. Reynolds also said they’re in the process of preparing the data for “public sharing soon,” including the Duke Prognostic score at all levels. Dr. Reynolds had not responded by the time of this publication to a request for further details or a timeline.
The surgeons’ first letter to the editor was rejected because it was submitted outside the journal’s 6-week window for letters and was posted as a public comment April 18 via the research platform, Remarq.
Dr. Bakaeen said they were told their second letter was rejected because of Circulation’s “long standing policy” not to publish letters to the editor regarding manuscript corrections but that a correction is being issued.
Circulation editor-in-chief Joseph A. Hill, MD, PhD, UT Southwestern Medical Center, Dallas, said via email that the journal will update its online policies to more clearly state its requirements for publication and that it has been fully transparent with Dr. Bakaeen and Dr. Sabik regarding where it is in the current process.
He confirmed the surgeons were told June 1 that “after additional review, the authors have determined that whereas there are no errors, an additional minor correction is warranted to clarify the description of the study population and sample size. This correction will be published soon.”
Dr. Hill thanked Dr. Bakaeen and Dr. Sabik for bringing the matter to their attention and said, “It is also important to note that both updates to the Dr. Reynolds et al. paper are published as corrections. However, the results and conclusions of the paper remain unchanged.”
The bigger issue
Importantly, the recent AHA/ACC/SCAI coronary revascularization guidelines used ISCHEMIA data to support downgrading the CABG recommendation from class 1 to class 2B in 3-vessel CAD with normal left ventricular function and from class 1 to 2a in 3-vessel CAD with mild to moderate left ventricular dysfunction.
The trial reported no significant benefit with an initial invasive strategy over medical therapy in stable patients with moderate or severe CAD. European guidelines, however, give CABG a class I recommendation for severe three- or two-vessel disease with proximal left anterior descending (LAD) involvement.
Dr. Sabik and Dr. Bakaeen say patients with severe three- or two-vessel disease with proximal LAD involvement were underrepresented in the randomized trials cited by the guidelines but are the typical CABG patients in modern-day practice.
“That is why it is important to determine the severity of CAD accurately and definitively in ISCHEMIA,” Dr. Bakaeen said. “But the more we look at the data, the more errors we encounter.”
Two U.S. surgical groups that were part of the writing process withdrew support for the revascularization guidelines, as did several international surgical societies, citing the data used to support the changes as well as the makeup of the writing committee.
Dr. Ferguson, now with the medical device manufacturer Perfusio, said he resigned from the ISCHEMIA steering committee on May 8 after being unable to accurately reconcile the ISCHEMIA surgical subset data with the Reynolds substudy and two other ISCHEMIA papers on the CABG subset. At least one of those papers, he noted, was being hurriedly pushed through the review process to counter concerns raised by surgeons regarding interpretation of ISCHEMIA.
“This is the first time in my lengthy career in medicine where a level of political agendaism was actually driving the truck,” he said. “It was appalling to me, and I would have said that if I was an interventional cardiologist looking at the results.”
ISCHEMIA results have also been touted as representing state-of-the-art care around the world, but that didn’t appear to be the case for the surgical subset where, for example, China and India performed most CABGs off pump, and globally there was considerable variation in how surgeons approached surgical revascularization strategies, Dr. Ferguson said. “Whether this variability might impact the guideline discussion and these papers coming out remains to be determined.”
He noted that the study protocol allowed for the ISCHEMIA investigators to evaluate whether the variability in the surgical subset influenced the results by comparing the data to that in the Society of Thoracic Surgeons registry, but this option was never acted upon despite being brought to their attention.
“Something political between 2020 and 2022 has crept into the ISCHEMIA trial mindset gestalt, and I don’t like it,” Dr. Ferguson said. “And this can have enormous consequences.”
Asked whether their letters to Circulation are being used to undermine confidence in the ISCHEMIA findings, Dr. Sabik replied, “It is not about undermining ISCHEMIA, but understanding how applicable ISCHEMIA is to patients having CABG today. Understanding the severity of the CAD in patients enrolled in ISCHEMIA is, therefore, necessary.”
“The authors and Circulation have admitted to errors,” he said. “We want to be sure we understand how severe the errors are.”
“This is just about accuracy in a manuscript that may affect patient treatment and therefore patient lives. We want to make sure it is correct,” Dr. Sabik added.
A version of this article first appeared on Medscape.com.
A long-standing request to clarify data irregularities in a 2021 ISCHEMIA substudy resulted in the publication of one correction, with a second correction in the works.
Further, the lone cardiac surgeon on the ISCHEMIA trial steering committee, T. Bruce Ferguson, MD, has resigned from the committee, citing a series of factors, including an inability to reconcile data in the substudy and two additional ISCHEMIA papers currently under review.
As previously reported, cardiac surgeons Faisal Bakaeen, MD, and Joseph Sabik III, MD, notified the journal Circulation in March that the Dr. Reynolds et al. substudy had inconsistencies between data in the main paper and supplemental tables detailing patients’ coronary artery disease (CAD) and ischemia severity.
The substudy found that CAD severity, classified using the modified Duke Prognostic Index score, predicted 4-year mortality and myocardial infarction in the landmark trial.
Circulation published a correction for the substudy on May 20, explaining that a “formatting error” resulted in data being incorrectly presented in two supplemental tables. It does not mention the surgeons’ letter to the editor, which can be found by clicking the “Q” icon below the paper.
Dr. Bakaeen, from the Cleveland Clinic, and Dr. Sabik, from University Hospitals Cleveland Medical Center, told this news organization that they submitted a second letter to editor on May 23 stating that “significant discrepancies” persist.
For example, 7.2% of participants (179/2,475) had moderate stenosis in one coronary vessel in the corrected Reynolds paper (Supplemental Tables I and II) versus 23.3% (697/2,986) in the primary ISCHEMIA manuscript published in the New England Journal of Medicine (Table S5).
The number of patients with left main ≥ 50% stenosis is, surprisingly, identical in both manuscripts, at 40, they said, despite the denominator dropping from 3,845 participants in the primary study to 2,475 participants with an evaluable modified Duke Prognostic Index score in the substudy.
The number of participants with previous coronary artery bypass surgery (CABG) is also hard to reconcile between manuscripts and, importantly, the substudy doesn’t distinguish between lesions bypassed with patent grafts and unbypassed grafts or those with occluded grafts.
“The fact that the authors are working on a second correction is appreciated, but with such numerous inconsistencies, at some point you reach the conclusion that an independent review of the data is the right thing to do for such a high-profile study that received over $100 million of National Institutes of Health support,” Dr. Bakaeen said. “No one should be satisfied or happy if there is any shadow of doubt here regarding the accuracy of the data.”
Speaking to this news organization prior to the first correction, lead substudy author Harmony Reynolds, MD, NYU Langone Health, detailed in depth how the formatting glitch inadvertently upgraded the number of diseased vessels and lesion severity in two supplemental tables.
She noted, as does the correction, that the data were correctly reported in the main manuscript tables and figures and in the remainder of the supplement.
Dr. Reynolds also said they’re in the process of preparing the data for “public sharing soon,” including the Duke Prognostic score at all levels. Dr. Reynolds had not responded by the time of this publication to a request for further details or a timeline.
The surgeons’ first letter to the editor was rejected because it was submitted outside the journal’s 6-week window for letters and was posted as a public comment April 18 via the research platform, Remarq.
Dr. Bakaeen said they were told their second letter was rejected because of Circulation’s “long standing policy” not to publish letters to the editor regarding manuscript corrections but that a correction is being issued.
Circulation editor-in-chief Joseph A. Hill, MD, PhD, UT Southwestern Medical Center, Dallas, said via email that the journal will update its online policies to more clearly state its requirements for publication and that it has been fully transparent with Dr. Bakaeen and Dr. Sabik regarding where it is in the current process.
He confirmed the surgeons were told June 1 that “after additional review, the authors have determined that whereas there are no errors, an additional minor correction is warranted to clarify the description of the study population and sample size. This correction will be published soon.”
Dr. Hill thanked Dr. Bakaeen and Dr. Sabik for bringing the matter to their attention and said, “It is also important to note that both updates to the Dr. Reynolds et al. paper are published as corrections. However, the results and conclusions of the paper remain unchanged.”
The bigger issue
Importantly, the recent AHA/ACC/SCAI coronary revascularization guidelines used ISCHEMIA data to support downgrading the CABG recommendation from class 1 to class 2B in 3-vessel CAD with normal left ventricular function and from class 1 to 2a in 3-vessel CAD with mild to moderate left ventricular dysfunction.
The trial reported no significant benefit with an initial invasive strategy over medical therapy in stable patients with moderate or severe CAD. European guidelines, however, give CABG a class I recommendation for severe three- or two-vessel disease with proximal left anterior descending (LAD) involvement.
Dr. Sabik and Dr. Bakaeen say patients with severe three- or two-vessel disease with proximal LAD involvement were underrepresented in the randomized trials cited by the guidelines but are the typical CABG patients in modern-day practice.
“That is why it is important to determine the severity of CAD accurately and definitively in ISCHEMIA,” Dr. Bakaeen said. “But the more we look at the data, the more errors we encounter.”
Two U.S. surgical groups that were part of the writing process withdrew support for the revascularization guidelines, as did several international surgical societies, citing the data used to support the changes as well as the makeup of the writing committee.
Dr. Ferguson, now with the medical device manufacturer Perfusio, said he resigned from the ISCHEMIA steering committee on May 8 after being unable to accurately reconcile the ISCHEMIA surgical subset data with the Reynolds substudy and two other ISCHEMIA papers on the CABG subset. At least one of those papers, he noted, was being hurriedly pushed through the review process to counter concerns raised by surgeons regarding interpretation of ISCHEMIA.
“This is the first time in my lengthy career in medicine where a level of political agendaism was actually driving the truck,” he said. “It was appalling to me, and I would have said that if I was an interventional cardiologist looking at the results.”
ISCHEMIA results have also been touted as representing state-of-the-art care around the world, but that didn’t appear to be the case for the surgical subset where, for example, China and India performed most CABGs off pump, and globally there was considerable variation in how surgeons approached surgical revascularization strategies, Dr. Ferguson said. “Whether this variability might impact the guideline discussion and these papers coming out remains to be determined.”
He noted that the study protocol allowed for the ISCHEMIA investigators to evaluate whether the variability in the surgical subset influenced the results by comparing the data to that in the Society of Thoracic Surgeons registry, but this option was never acted upon despite being brought to their attention.
“Something political between 2020 and 2022 has crept into the ISCHEMIA trial mindset gestalt, and I don’t like it,” Dr. Ferguson said. “And this can have enormous consequences.”
Asked whether their letters to Circulation are being used to undermine confidence in the ISCHEMIA findings, Dr. Sabik replied, “It is not about undermining ISCHEMIA, but understanding how applicable ISCHEMIA is to patients having CABG today. Understanding the severity of the CAD in patients enrolled in ISCHEMIA is, therefore, necessary.”
“The authors and Circulation have admitted to errors,” he said. “We want to be sure we understand how severe the errors are.”
“This is just about accuracy in a manuscript that may affect patient treatment and therefore patient lives. We want to make sure it is correct,” Dr. Sabik added.
A version of this article first appeared on Medscape.com.
CTO PCI success rates rising, with blip during COVID-19, registry shows
Technical and procedural success rates for chronic total occlusion percutaneous coronary intervention (CTO PCI) have increased steadily over the past 6 years, with rates of in-hospital major adverse cardiac events (MACE) declining to the 2%-or-lower range in that time.
“CTO PCI technical and procedural success rates are high and continue to increase over time,” Spyridon Kostantinis, MD said in presenting updated results from the international PROGRESS-CTO registry at the Society for Cardiovascular Angiography & Interventions annual scientific sessions.
“The overall success rate increased from 81.6% in 2018 to 88.1% in 2021,” he added. The overall incidence of in-hospital MACE in that time was “an acceptable” 2.1% without significant changes over that period.
The analysis examined clinical, angiographic and procedural outcomes of 10,249 CTO PCIs performed on 10,019 patients from 63 centers in nine countries during 2016-2021. PROGRESS-CTO stands for Prospective Global Registry for the Study of Chronic Total Occlusion Intervention.
The target CTOs were highly complex, he said, with an average J-CTO (multicenter CTO registry in Japan) score of 2.4 ± 1.3 and PROGRESS-CTO score of 1.3 ± 1. The most common CTO target vessel was the right coronary artery (53%), followed by the left anterior descending artery (26%) and the circumflex artery (19%).
The registry also tracked how characteristics of the CTO PCI procedures themselves changed over time. “The septal and the epicardial collaterals were the most common collaterals used for retrograde crossing, with a decreasing trend for epicardial collaterals over time,” said Dr. Kostantinis, a research fellow at the Minneapolis Heart Institute.
Septal collateral use varied between 64% and 69% of cases from 2016 to 2021, but the share of epicardial collaterals declined from 35% to 22% in that time.
“Over time, the range of antegrade wiring as the final successfully crossing strategy increased from 46% in 2016 to 61% in 2021, with a decrease in antegrade dissection and re-entry (ADR) and no change in the retrograde approach,” Dr. Kostantinis said. The percentage of procedures using ADR as the final crossing strategy declined from 18% in 2016 to 12% in 2021, with the rate of retrograde crossings peaking at 21% in 2016 but leveling off to 18% or 19% in the subsequent years.
“An increasing use in the efficiency of antegrade wiring may reflect an improvement in guidewire retrograde crossing as well as the increasing operator expertise,” Dr. Kostantinis said.
The study also found that contrast volume, air kerma radiation dose, fluoroscopy time, and procedure time declined steadily over time. “The potential explanations for these are using new x-ray systems as well as the use of intravascular imaging,” Dr. Kostantinis said.
In 2020, the rates of technical and procedural success, as well as the number of overall procedures, declined from 2019, while MACE rates ticked upward that year, probably because of the COVID-19 pandemic, Dr. Kostantinis said.
“It is true that we noticed a rise in MACE rate from 1.6% in 2019 to 2.7% in 2020, but in 2021 that decreased again to 1.7%,” he said in an interview. “Another potential explanation is the higher angiographic complexity of CTOs treated during that year (2020) that resulted in more adverse events.”
Previous results from the PROGRESS-CTO registry reported the difference in MACE between 2019 and 2020 was significant (P = .01). “So, yes, the difference between those 2 years is significant,” Dr. Kostantinis said. However, he noted, the overall trend was not significant, with a P value of .194.
The risk profile of CTO PCI has improved “slowly” over time, said Kirk N. Garratt, MD, but “it’s not yet were it needs to be.”
He added, “Undoubtedly we’ve learned that, without any question, one method for minimizing the risk is to concentrate these cases in the hands of those that do many of them.” As the number of procedures fell – an “embedded” pandemic impact –“I worry that it’s inevitable that complication rates will tick up a bit,” said Dr. Garratt, director of the Center for Heart and Vascular Health at Christiana Care in Newark, Del.
By the same token, he added, this situation with regard to CTOs “parallels what’s happening elsewhere in interventional medicine and medicine broadly; numbers are increasing and we’re busy again. In most domains we’re not as busy as we had been prepandemic, and time will allow us to catch up.”
PROGRESS-CTO has received funding from the Joseph F. and Mary M. Fleischhacker Foundation and the Abbott Northwestern Hospital Foundation Innovation Grant.
Dr. Kostantinis has no disclosures. Dr. Garratt is an advisory board member for Abbott.
Technical and procedural success rates for chronic total occlusion percutaneous coronary intervention (CTO PCI) have increased steadily over the past 6 years, with rates of in-hospital major adverse cardiac events (MACE) declining to the 2%-or-lower range in that time.
“CTO PCI technical and procedural success rates are high and continue to increase over time,” Spyridon Kostantinis, MD said in presenting updated results from the international PROGRESS-CTO registry at the Society for Cardiovascular Angiography & Interventions annual scientific sessions.
“The overall success rate increased from 81.6% in 2018 to 88.1% in 2021,” he added. The overall incidence of in-hospital MACE in that time was “an acceptable” 2.1% without significant changes over that period.
The analysis examined clinical, angiographic and procedural outcomes of 10,249 CTO PCIs performed on 10,019 patients from 63 centers in nine countries during 2016-2021. PROGRESS-CTO stands for Prospective Global Registry for the Study of Chronic Total Occlusion Intervention.
The target CTOs were highly complex, he said, with an average J-CTO (multicenter CTO registry in Japan) score of 2.4 ± 1.3 and PROGRESS-CTO score of 1.3 ± 1. The most common CTO target vessel was the right coronary artery (53%), followed by the left anterior descending artery (26%) and the circumflex artery (19%).
The registry also tracked how characteristics of the CTO PCI procedures themselves changed over time. “The septal and the epicardial collaterals were the most common collaterals used for retrograde crossing, with a decreasing trend for epicardial collaterals over time,” said Dr. Kostantinis, a research fellow at the Minneapolis Heart Institute.
Septal collateral use varied between 64% and 69% of cases from 2016 to 2021, but the share of epicardial collaterals declined from 35% to 22% in that time.
“Over time, the range of antegrade wiring as the final successfully crossing strategy increased from 46% in 2016 to 61% in 2021, with a decrease in antegrade dissection and re-entry (ADR) and no change in the retrograde approach,” Dr. Kostantinis said. The percentage of procedures using ADR as the final crossing strategy declined from 18% in 2016 to 12% in 2021, with the rate of retrograde crossings peaking at 21% in 2016 but leveling off to 18% or 19% in the subsequent years.
“An increasing use in the efficiency of antegrade wiring may reflect an improvement in guidewire retrograde crossing as well as the increasing operator expertise,” Dr. Kostantinis said.
The study also found that contrast volume, air kerma radiation dose, fluoroscopy time, and procedure time declined steadily over time. “The potential explanations for these are using new x-ray systems as well as the use of intravascular imaging,” Dr. Kostantinis said.
In 2020, the rates of technical and procedural success, as well as the number of overall procedures, declined from 2019, while MACE rates ticked upward that year, probably because of the COVID-19 pandemic, Dr. Kostantinis said.
“It is true that we noticed a rise in MACE rate from 1.6% in 2019 to 2.7% in 2020, but in 2021 that decreased again to 1.7%,” he said in an interview. “Another potential explanation is the higher angiographic complexity of CTOs treated during that year (2020) that resulted in more adverse events.”
Previous results from the PROGRESS-CTO registry reported the difference in MACE between 2019 and 2020 was significant (P = .01). “So, yes, the difference between those 2 years is significant,” Dr. Kostantinis said. However, he noted, the overall trend was not significant, with a P value of .194.
The risk profile of CTO PCI has improved “slowly” over time, said Kirk N. Garratt, MD, but “it’s not yet were it needs to be.”
He added, “Undoubtedly we’ve learned that, without any question, one method for minimizing the risk is to concentrate these cases in the hands of those that do many of them.” As the number of procedures fell – an “embedded” pandemic impact –“I worry that it’s inevitable that complication rates will tick up a bit,” said Dr. Garratt, director of the Center for Heart and Vascular Health at Christiana Care in Newark, Del.
By the same token, he added, this situation with regard to CTOs “parallels what’s happening elsewhere in interventional medicine and medicine broadly; numbers are increasing and we’re busy again. In most domains we’re not as busy as we had been prepandemic, and time will allow us to catch up.”
PROGRESS-CTO has received funding from the Joseph F. and Mary M. Fleischhacker Foundation and the Abbott Northwestern Hospital Foundation Innovation Grant.
Dr. Kostantinis has no disclosures. Dr. Garratt is an advisory board member for Abbott.
Technical and procedural success rates for chronic total occlusion percutaneous coronary intervention (CTO PCI) have increased steadily over the past 6 years, with rates of in-hospital major adverse cardiac events (MACE) declining to the 2%-or-lower range in that time.
“CTO PCI technical and procedural success rates are high and continue to increase over time,” Spyridon Kostantinis, MD said in presenting updated results from the international PROGRESS-CTO registry at the Society for Cardiovascular Angiography & Interventions annual scientific sessions.
“The overall success rate increased from 81.6% in 2018 to 88.1% in 2021,” he added. The overall incidence of in-hospital MACE in that time was “an acceptable” 2.1% without significant changes over that period.
The analysis examined clinical, angiographic and procedural outcomes of 10,249 CTO PCIs performed on 10,019 patients from 63 centers in nine countries during 2016-2021. PROGRESS-CTO stands for Prospective Global Registry for the Study of Chronic Total Occlusion Intervention.
The target CTOs were highly complex, he said, with an average J-CTO (multicenter CTO registry in Japan) score of 2.4 ± 1.3 and PROGRESS-CTO score of 1.3 ± 1. The most common CTO target vessel was the right coronary artery (53%), followed by the left anterior descending artery (26%) and the circumflex artery (19%).
The registry also tracked how characteristics of the CTO PCI procedures themselves changed over time. “The septal and the epicardial collaterals were the most common collaterals used for retrograde crossing, with a decreasing trend for epicardial collaterals over time,” said Dr. Kostantinis, a research fellow at the Minneapolis Heart Institute.
Septal collateral use varied between 64% and 69% of cases from 2016 to 2021, but the share of epicardial collaterals declined from 35% to 22% in that time.
“Over time, the range of antegrade wiring as the final successfully crossing strategy increased from 46% in 2016 to 61% in 2021, with a decrease in antegrade dissection and re-entry (ADR) and no change in the retrograde approach,” Dr. Kostantinis said. The percentage of procedures using ADR as the final crossing strategy declined from 18% in 2016 to 12% in 2021, with the rate of retrograde crossings peaking at 21% in 2016 but leveling off to 18% or 19% in the subsequent years.
“An increasing use in the efficiency of antegrade wiring may reflect an improvement in guidewire retrograde crossing as well as the increasing operator expertise,” Dr. Kostantinis said.
The study also found that contrast volume, air kerma radiation dose, fluoroscopy time, and procedure time declined steadily over time. “The potential explanations for these are using new x-ray systems as well as the use of intravascular imaging,” Dr. Kostantinis said.
In 2020, the rates of technical and procedural success, as well as the number of overall procedures, declined from 2019, while MACE rates ticked upward that year, probably because of the COVID-19 pandemic, Dr. Kostantinis said.
“It is true that we noticed a rise in MACE rate from 1.6% in 2019 to 2.7% in 2020, but in 2021 that decreased again to 1.7%,” he said in an interview. “Another potential explanation is the higher angiographic complexity of CTOs treated during that year (2020) that resulted in more adverse events.”
Previous results from the PROGRESS-CTO registry reported the difference in MACE between 2019 and 2020 was significant (P = .01). “So, yes, the difference between those 2 years is significant,” Dr. Kostantinis said. However, he noted, the overall trend was not significant, with a P value of .194.
The risk profile of CTO PCI has improved “slowly” over time, said Kirk N. Garratt, MD, but “it’s not yet were it needs to be.”
He added, “Undoubtedly we’ve learned that, without any question, one method for minimizing the risk is to concentrate these cases in the hands of those that do many of them.” As the number of procedures fell – an “embedded” pandemic impact –“I worry that it’s inevitable that complication rates will tick up a bit,” said Dr. Garratt, director of the Center for Heart and Vascular Health at Christiana Care in Newark, Del.
By the same token, he added, this situation with regard to CTOs “parallels what’s happening elsewhere in interventional medicine and medicine broadly; numbers are increasing and we’re busy again. In most domains we’re not as busy as we had been prepandemic, and time will allow us to catch up.”
PROGRESS-CTO has received funding from the Joseph F. and Mary M. Fleischhacker Foundation and the Abbott Northwestern Hospital Foundation Innovation Grant.
Dr. Kostantinis has no disclosures. Dr. Garratt is an advisory board member for Abbott.
FROM SCAI 2022
Hand outcomes similar with distal or proximal radial cardiac cath
The first randomized controlled study comparing the use of the emerging distal radial artery access to the traditional proximal access for cardiac catheterization has found no significant differences in postprocedure hand function and other secondary outcomes a month afterward, along with similar rates of bleeding and gaining successful RA access at the time of the procedure.
Karim Al-Azizi, MD, reported results of the single-center, Distal vs. Proximal Radial Artery (DIPRA) study at the Society for Cardiovascular Angiography and Interventions annual scientific sessions. DIPRA randomized 300 patients on a 1:1 basis to cardiac catheterization via either the distal or proximal RAs (dRA or pRA). The trial was conducted at the Baylor Scott & White Health The Heart Hospital–Plano in Richardson, Texas, where Dr. Al-Azizi is an interventional cardiologist and structural heart disease specialist.
“Distal radial artery access is a safe strategy for access for cardiovascular patients with a low complication rate,” Dr. Al-Azizi said. “Similarly, the success with distal vs. radial artery access was noted in the study: No significant bleeding or hematomas were noted in the dRA cohort.”
In an interview, Dr. Al-Azizi added, “Our study is the first of its kind and the first to evaluate the true hand function post distal/radial.”
He explained the rationale for the study. “One of the biggest criticisms that came up a few years ago when distal access was being developed and started gaining some momentum is the fact that it is yet unknown what would be the effect on hand function given the proximity to the fingers, proximity to the nerve, and despite that RA occlusion rates were lower.”
The final DIPRA analysis included 254 patients who completed their 30-day follow-up, 128 of whom were randomized to dRA access, 126 to pRA access. Demographics and procedural characteristics were balanced between both arms. The latter included similarities in sheath size used (6-French in 99.3% of both arms) and type of procedure (35.9% in the dRA and 32.9% in pRA arms had percutaneous coronary angioplasty).
To evaluate the primary outcome of hand function in the catheterization hand, the study used a composite of the Quick Disabilities of Arm, Shoulder, and Hand (DASH) questionnaire, hand-grip test, and thumb/forefinger pinch test. The composite score changed –.4 and .1 in the dRA and pRA arms, respectively (P = .07), which didn’t reach statistical significance, Dr. Al-Azizi said.
Outcomes at the time of intervention were similar. Successful RA access failed in six dRA patients, who were converted to pRA, and in two pRA patients. Overall rates for successful RA access were 96.7% in the distal arm and 98% in the proximal arm (P = .72). Bleeding rates were 0% and 1.4% in the respective arms (P = .25).
Dr. Al-Azizi said that he and his coinvestigators are collecting 1-year outcomes data that they will present next year.
The DIPRA findings “provide reassurance that hand function is not compromised regardless of access site,” Sunil V. Rao, MD, moderator of the session where Dr. Al-Azizi reported the results, said in an interview.
“Prior studies indicated no difference in hand function between radial and femoral access, and now these data indicate no difference between distal radial and proximal radial access.” Dr. Rao, the incoming SCAI president, is a professor at Duke University Medical Center in Durham, N.C., and cardiology section chief at Durham Veterans Affairs Medical Center.
“We do need more patient-reported outcomes in percutaneous coronary intervention studies. The DIPRA study is a great example of this,” Dr. Rao added. “The DIPRA study adds to the body of literature indicating that access site choice is an important aspect of the PCI procedure. With meticulous procedural technique, patients can have an excellent outcome from PCI procedures.”
Dr. Al-Azizi disclosed consulting for Edwards Lifesciences and Phillips. Dr. Rao has no disclosures.
The first randomized controlled study comparing the use of the emerging distal radial artery access to the traditional proximal access for cardiac catheterization has found no significant differences in postprocedure hand function and other secondary outcomes a month afterward, along with similar rates of bleeding and gaining successful RA access at the time of the procedure.
Karim Al-Azizi, MD, reported results of the single-center, Distal vs. Proximal Radial Artery (DIPRA) study at the Society for Cardiovascular Angiography and Interventions annual scientific sessions. DIPRA randomized 300 patients on a 1:1 basis to cardiac catheterization via either the distal or proximal RAs (dRA or pRA). The trial was conducted at the Baylor Scott & White Health The Heart Hospital–Plano in Richardson, Texas, where Dr. Al-Azizi is an interventional cardiologist and structural heart disease specialist.
“Distal radial artery access is a safe strategy for access for cardiovascular patients with a low complication rate,” Dr. Al-Azizi said. “Similarly, the success with distal vs. radial artery access was noted in the study: No significant bleeding or hematomas were noted in the dRA cohort.”
In an interview, Dr. Al-Azizi added, “Our study is the first of its kind and the first to evaluate the true hand function post distal/radial.”
He explained the rationale for the study. “One of the biggest criticisms that came up a few years ago when distal access was being developed and started gaining some momentum is the fact that it is yet unknown what would be the effect on hand function given the proximity to the fingers, proximity to the nerve, and despite that RA occlusion rates were lower.”
The final DIPRA analysis included 254 patients who completed their 30-day follow-up, 128 of whom were randomized to dRA access, 126 to pRA access. Demographics and procedural characteristics were balanced between both arms. The latter included similarities in sheath size used (6-French in 99.3% of both arms) and type of procedure (35.9% in the dRA and 32.9% in pRA arms had percutaneous coronary angioplasty).
To evaluate the primary outcome of hand function in the catheterization hand, the study used a composite of the Quick Disabilities of Arm, Shoulder, and Hand (DASH) questionnaire, hand-grip test, and thumb/forefinger pinch test. The composite score changed –.4 and .1 in the dRA and pRA arms, respectively (P = .07), which didn’t reach statistical significance, Dr. Al-Azizi said.
Outcomes at the time of intervention were similar. Successful RA access failed in six dRA patients, who were converted to pRA, and in two pRA patients. Overall rates for successful RA access were 96.7% in the distal arm and 98% in the proximal arm (P = .72). Bleeding rates were 0% and 1.4% in the respective arms (P = .25).
Dr. Al-Azizi said that he and his coinvestigators are collecting 1-year outcomes data that they will present next year.
The DIPRA findings “provide reassurance that hand function is not compromised regardless of access site,” Sunil V. Rao, MD, moderator of the session where Dr. Al-Azizi reported the results, said in an interview.
“Prior studies indicated no difference in hand function between radial and femoral access, and now these data indicate no difference between distal radial and proximal radial access.” Dr. Rao, the incoming SCAI president, is a professor at Duke University Medical Center in Durham, N.C., and cardiology section chief at Durham Veterans Affairs Medical Center.
“We do need more patient-reported outcomes in percutaneous coronary intervention studies. The DIPRA study is a great example of this,” Dr. Rao added. “The DIPRA study adds to the body of literature indicating that access site choice is an important aspect of the PCI procedure. With meticulous procedural technique, patients can have an excellent outcome from PCI procedures.”
Dr. Al-Azizi disclosed consulting for Edwards Lifesciences and Phillips. Dr. Rao has no disclosures.
The first randomized controlled study comparing the use of the emerging distal radial artery access to the traditional proximal access for cardiac catheterization has found no significant differences in postprocedure hand function and other secondary outcomes a month afterward, along with similar rates of bleeding and gaining successful RA access at the time of the procedure.
Karim Al-Azizi, MD, reported results of the single-center, Distal vs. Proximal Radial Artery (DIPRA) study at the Society for Cardiovascular Angiography and Interventions annual scientific sessions. DIPRA randomized 300 patients on a 1:1 basis to cardiac catheterization via either the distal or proximal RAs (dRA or pRA). The trial was conducted at the Baylor Scott & White Health The Heart Hospital–Plano in Richardson, Texas, where Dr. Al-Azizi is an interventional cardiologist and structural heart disease specialist.
“Distal radial artery access is a safe strategy for access for cardiovascular patients with a low complication rate,” Dr. Al-Azizi said. “Similarly, the success with distal vs. radial artery access was noted in the study: No significant bleeding or hematomas were noted in the dRA cohort.”
In an interview, Dr. Al-Azizi added, “Our study is the first of its kind and the first to evaluate the true hand function post distal/radial.”
He explained the rationale for the study. “One of the biggest criticisms that came up a few years ago when distal access was being developed and started gaining some momentum is the fact that it is yet unknown what would be the effect on hand function given the proximity to the fingers, proximity to the nerve, and despite that RA occlusion rates were lower.”
The final DIPRA analysis included 254 patients who completed their 30-day follow-up, 128 of whom were randomized to dRA access, 126 to pRA access. Demographics and procedural characteristics were balanced between both arms. The latter included similarities in sheath size used (6-French in 99.3% of both arms) and type of procedure (35.9% in the dRA and 32.9% in pRA arms had percutaneous coronary angioplasty).
To evaluate the primary outcome of hand function in the catheterization hand, the study used a composite of the Quick Disabilities of Arm, Shoulder, and Hand (DASH) questionnaire, hand-grip test, and thumb/forefinger pinch test. The composite score changed –.4 and .1 in the dRA and pRA arms, respectively (P = .07), which didn’t reach statistical significance, Dr. Al-Azizi said.
Outcomes at the time of intervention were similar. Successful RA access failed in six dRA patients, who were converted to pRA, and in two pRA patients. Overall rates for successful RA access were 96.7% in the distal arm and 98% in the proximal arm (P = .72). Bleeding rates were 0% and 1.4% in the respective arms (P = .25).
Dr. Al-Azizi said that he and his coinvestigators are collecting 1-year outcomes data that they will present next year.
The DIPRA findings “provide reassurance that hand function is not compromised regardless of access site,” Sunil V. Rao, MD, moderator of the session where Dr. Al-Azizi reported the results, said in an interview.
“Prior studies indicated no difference in hand function between radial and femoral access, and now these data indicate no difference between distal radial and proximal radial access.” Dr. Rao, the incoming SCAI president, is a professor at Duke University Medical Center in Durham, N.C., and cardiology section chief at Durham Veterans Affairs Medical Center.
“We do need more patient-reported outcomes in percutaneous coronary intervention studies. The DIPRA study is a great example of this,” Dr. Rao added. “The DIPRA study adds to the body of literature indicating that access site choice is an important aspect of the PCI procedure. With meticulous procedural technique, patients can have an excellent outcome from PCI procedures.”
Dr. Al-Azizi disclosed consulting for Edwards Lifesciences and Phillips. Dr. Rao has no disclosures.
FROM SCAI 2022
Path to parenthood in cardiology training fraught with obstacles
The first international survey of parental benefits and policies among cardiovascular training programs shows wide variability among institutions.
Although a majority of cardiology fellows became parents during training, the survey found that family benefits and policies were not uniformly available and that knowledge about the existence of such policies was low across all institutions.
The findings are published in the Journal of the American College of Cardiology.
Such variability highlights disparities in real-world experiences, say Estefania Oliveros, MD, Temple University Hospital, Philadelphia, and colleagues.
“There are no policies to protect cardiology trainees when they become parents that are uniform across the United States or even internationally, even though, according to our survey, 61.7% become parents during training,” Dr. Oliveros told this news organization.
Dr. Oliveros said she wanted to learn more about the status of institutional practices surrounding pregnant trainees during cardiovascular fellowship, not only in the U.S., but internationally: “I wanted to study this because of my own experience.”
“I was probably the first pregnant trainee at my institution, and there were no specific policies in place, so I had to find out on my own what to do about radiation safety, where I would breastfeed, schedule changes, how that would impact my graduation time, things like that,” Dr. Oliveros said. “It would be nice if you had the resources and your institution could accommodate your needs, instead of every time you have a pregnant person on your staff, you have to reinvent the wheel.”
Dr. Oliveros and colleagues conducted an online survey during August 2020-October 2020 that was distributed via social media. Responses were made anonymous to encourage unbiased feedback.
Among the 417 completed responses, 47 (11.3%) were from training program directors, 146 (35%) from current or former pregnant trainees, and 224 (53.7%) from current or former trainees who were not pregnant during cardiology training. Two-thirds of the respondents (67.1%) were parents.
Most survey respondents said they became pregnant during the third year of general cardiology (29.1%), followed by the first year of general cardiology (26.3%), and the second year of general cardiology (23.5%).
Only 13 of the 47 training program directors (27.7%) received guidance or training on how to accommodate pregnant trainees during fellowship.
Additionally, 26% of the trainees reported their institution had readily available breastfeeding and pumping policies, 39% responded that their institution had no such policies, and 34.9% said they did not know.
Nearly one-half of the programs offered rearrangement of schedules because of radiation concerns, 27.5% did not.
The amount of parental leave varied greatly worldwide. For Europe, Central and South America, Africa, and Australia, the average parental leave was more than 4 months; for Canada, it was more than 3 months; for the United States, it was 1 to 2 months; and for Asia, it was 3 to 4 weeks.
“There is no uniformity, no policies for things like breastfeeding or places where you can pump. None of that is installed, even though by law we’re supposed to have these things,” Dr. Oliveros said.
In all countries, paternity leave was uncommon (2.6% of respondents), even though 48.5% of the programs had paternity leave.
“I would like to see associations, program directors, even trainees helping each other in finding ways to accommodate parents to promote wellness and assure that trainees can have both good training and life balance,” she added.
In an accompanying editorial, Ileana L. Piña, MD, MPH, Thomas Jefferson Institute, Philadelphia, writes: “Enough has been said about our need for a greater percentage of women cardiologists. There is no need to further debate that fact. However, it is puzzling that despite > 50% of medical students being women, the cardiology specialty is fraught with recent survey reports of hostility in the workplace, concerns of long hours, exposure to radiation, and poor work-life balance that can compel trainees to choose delaying pregnancy or taking unpaid leave, which will, in turn, delay training. Therefore, it is not surprising that only 14.9% of cardiologist specialists and 21.9% of cardiology fellows are women.”
Dr. Piña notes that while the authors understand that it’s difficult to change national policies, they issue a “call to action” for organizations and program directors to demonstrate leadership by developing fair and balanced decisions regarding parental policies.
“Those decisions are so impactful that they can change career trajectories for the better or worse ... the current status is unacceptable and must change for the benefit of all trainees, their families, and the program directors. The problem is too important and pervasive,” she adds.
Dr. Piña concludes: “Perhaps if the women who are the subjects of, and often the unwitting party to, administrative decisions about their lives, choices, and welfare were invited to contribute to the changes, we would finally see an increase in the number of women in cardiology careers. After all, aren’t we about diversity and belonging?”
“We need to normalize pregnancy and parental leave across the globe,” Laxmi S. Mehta, MD, Ohio State University Weiner Medical Center, Columbus, said in an interview.
As previously reported, Dr. Mehta recently led a study that surveyed 323 women cardiologists who were working while they were pregnant. Her study found that 75% of these women experienced discriminatory maternity leave practices, some of which were likely violations of the federal Family and Medical Leave Act.
“If we want more women to pursue a career in cardiology, then employers and health systems need to adequately support parenthood, including allowing people to spend uninterrupted time with their newborns without the fear of discrimination, retaliation, or financial burden,” Dr. Mehta said.
Limitations of the study are the small sample size, potential for bias associated with social media distribution, and the fact that 75% of respondents were women, Dr. Oliveros and colleagues write.
Dr. Oliveros, Dr. Piña, and Dr. Mehta report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The first international survey of parental benefits and policies among cardiovascular training programs shows wide variability among institutions.
Although a majority of cardiology fellows became parents during training, the survey found that family benefits and policies were not uniformly available and that knowledge about the existence of such policies was low across all institutions.
The findings are published in the Journal of the American College of Cardiology.
Such variability highlights disparities in real-world experiences, say Estefania Oliveros, MD, Temple University Hospital, Philadelphia, and colleagues.
“There are no policies to protect cardiology trainees when they become parents that are uniform across the United States or even internationally, even though, according to our survey, 61.7% become parents during training,” Dr. Oliveros told this news organization.
Dr. Oliveros said she wanted to learn more about the status of institutional practices surrounding pregnant trainees during cardiovascular fellowship, not only in the U.S., but internationally: “I wanted to study this because of my own experience.”
“I was probably the first pregnant trainee at my institution, and there were no specific policies in place, so I had to find out on my own what to do about radiation safety, where I would breastfeed, schedule changes, how that would impact my graduation time, things like that,” Dr. Oliveros said. “It would be nice if you had the resources and your institution could accommodate your needs, instead of every time you have a pregnant person on your staff, you have to reinvent the wheel.”
Dr. Oliveros and colleagues conducted an online survey during August 2020-October 2020 that was distributed via social media. Responses were made anonymous to encourage unbiased feedback.
Among the 417 completed responses, 47 (11.3%) were from training program directors, 146 (35%) from current or former pregnant trainees, and 224 (53.7%) from current or former trainees who were not pregnant during cardiology training. Two-thirds of the respondents (67.1%) were parents.
Most survey respondents said they became pregnant during the third year of general cardiology (29.1%), followed by the first year of general cardiology (26.3%), and the second year of general cardiology (23.5%).
Only 13 of the 47 training program directors (27.7%) received guidance or training on how to accommodate pregnant trainees during fellowship.
Additionally, 26% of the trainees reported their institution had readily available breastfeeding and pumping policies, 39% responded that their institution had no such policies, and 34.9% said they did not know.
Nearly one-half of the programs offered rearrangement of schedules because of radiation concerns, 27.5% did not.
The amount of parental leave varied greatly worldwide. For Europe, Central and South America, Africa, and Australia, the average parental leave was more than 4 months; for Canada, it was more than 3 months; for the United States, it was 1 to 2 months; and for Asia, it was 3 to 4 weeks.
“There is no uniformity, no policies for things like breastfeeding or places where you can pump. None of that is installed, even though by law we’re supposed to have these things,” Dr. Oliveros said.
In all countries, paternity leave was uncommon (2.6% of respondents), even though 48.5% of the programs had paternity leave.
“I would like to see associations, program directors, even trainees helping each other in finding ways to accommodate parents to promote wellness and assure that trainees can have both good training and life balance,” she added.
In an accompanying editorial, Ileana L. Piña, MD, MPH, Thomas Jefferson Institute, Philadelphia, writes: “Enough has been said about our need for a greater percentage of women cardiologists. There is no need to further debate that fact. However, it is puzzling that despite > 50% of medical students being women, the cardiology specialty is fraught with recent survey reports of hostility in the workplace, concerns of long hours, exposure to radiation, and poor work-life balance that can compel trainees to choose delaying pregnancy or taking unpaid leave, which will, in turn, delay training. Therefore, it is not surprising that only 14.9% of cardiologist specialists and 21.9% of cardiology fellows are women.”
Dr. Piña notes that while the authors understand that it’s difficult to change national policies, they issue a “call to action” for organizations and program directors to demonstrate leadership by developing fair and balanced decisions regarding parental policies.
“Those decisions are so impactful that they can change career trajectories for the better or worse ... the current status is unacceptable and must change for the benefit of all trainees, their families, and the program directors. The problem is too important and pervasive,” she adds.
Dr. Piña concludes: “Perhaps if the women who are the subjects of, and often the unwitting party to, administrative decisions about their lives, choices, and welfare were invited to contribute to the changes, we would finally see an increase in the number of women in cardiology careers. After all, aren’t we about diversity and belonging?”
“We need to normalize pregnancy and parental leave across the globe,” Laxmi S. Mehta, MD, Ohio State University Weiner Medical Center, Columbus, said in an interview.
As previously reported, Dr. Mehta recently led a study that surveyed 323 women cardiologists who were working while they were pregnant. Her study found that 75% of these women experienced discriminatory maternity leave practices, some of which were likely violations of the federal Family and Medical Leave Act.
“If we want more women to pursue a career in cardiology, then employers and health systems need to adequately support parenthood, including allowing people to spend uninterrupted time with their newborns without the fear of discrimination, retaliation, or financial burden,” Dr. Mehta said.
Limitations of the study are the small sample size, potential for bias associated with social media distribution, and the fact that 75% of respondents were women, Dr. Oliveros and colleagues write.
Dr. Oliveros, Dr. Piña, and Dr. Mehta report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The first international survey of parental benefits and policies among cardiovascular training programs shows wide variability among institutions.
Although a majority of cardiology fellows became parents during training, the survey found that family benefits and policies were not uniformly available and that knowledge about the existence of such policies was low across all institutions.
The findings are published in the Journal of the American College of Cardiology.
Such variability highlights disparities in real-world experiences, say Estefania Oliveros, MD, Temple University Hospital, Philadelphia, and colleagues.
“There are no policies to protect cardiology trainees when they become parents that are uniform across the United States or even internationally, even though, according to our survey, 61.7% become parents during training,” Dr. Oliveros told this news organization.
Dr. Oliveros said she wanted to learn more about the status of institutional practices surrounding pregnant trainees during cardiovascular fellowship, not only in the U.S., but internationally: “I wanted to study this because of my own experience.”
“I was probably the first pregnant trainee at my institution, and there were no specific policies in place, so I had to find out on my own what to do about radiation safety, where I would breastfeed, schedule changes, how that would impact my graduation time, things like that,” Dr. Oliveros said. “It would be nice if you had the resources and your institution could accommodate your needs, instead of every time you have a pregnant person on your staff, you have to reinvent the wheel.”
Dr. Oliveros and colleagues conducted an online survey during August 2020-October 2020 that was distributed via social media. Responses were made anonymous to encourage unbiased feedback.
Among the 417 completed responses, 47 (11.3%) were from training program directors, 146 (35%) from current or former pregnant trainees, and 224 (53.7%) from current or former trainees who were not pregnant during cardiology training. Two-thirds of the respondents (67.1%) were parents.
Most survey respondents said they became pregnant during the third year of general cardiology (29.1%), followed by the first year of general cardiology (26.3%), and the second year of general cardiology (23.5%).
Only 13 of the 47 training program directors (27.7%) received guidance or training on how to accommodate pregnant trainees during fellowship.
Additionally, 26% of the trainees reported their institution had readily available breastfeeding and pumping policies, 39% responded that their institution had no such policies, and 34.9% said they did not know.
Nearly one-half of the programs offered rearrangement of schedules because of radiation concerns, 27.5% did not.
The amount of parental leave varied greatly worldwide. For Europe, Central and South America, Africa, and Australia, the average parental leave was more than 4 months; for Canada, it was more than 3 months; for the United States, it was 1 to 2 months; and for Asia, it was 3 to 4 weeks.
“There is no uniformity, no policies for things like breastfeeding or places where you can pump. None of that is installed, even though by law we’re supposed to have these things,” Dr. Oliveros said.
In all countries, paternity leave was uncommon (2.6% of respondents), even though 48.5% of the programs had paternity leave.
“I would like to see associations, program directors, even trainees helping each other in finding ways to accommodate parents to promote wellness and assure that trainees can have both good training and life balance,” she added.
In an accompanying editorial, Ileana L. Piña, MD, MPH, Thomas Jefferson Institute, Philadelphia, writes: “Enough has been said about our need for a greater percentage of women cardiologists. There is no need to further debate that fact. However, it is puzzling that despite > 50% of medical students being women, the cardiology specialty is fraught with recent survey reports of hostility in the workplace, concerns of long hours, exposure to radiation, and poor work-life balance that can compel trainees to choose delaying pregnancy or taking unpaid leave, which will, in turn, delay training. Therefore, it is not surprising that only 14.9% of cardiologist specialists and 21.9% of cardiology fellows are women.”
Dr. Piña notes that while the authors understand that it’s difficult to change national policies, they issue a “call to action” for organizations and program directors to demonstrate leadership by developing fair and balanced decisions regarding parental policies.
“Those decisions are so impactful that they can change career trajectories for the better or worse ... the current status is unacceptable and must change for the benefit of all trainees, their families, and the program directors. The problem is too important and pervasive,” she adds.
Dr. Piña concludes: “Perhaps if the women who are the subjects of, and often the unwitting party to, administrative decisions about their lives, choices, and welfare were invited to contribute to the changes, we would finally see an increase in the number of women in cardiology careers. After all, aren’t we about diversity and belonging?”
“We need to normalize pregnancy and parental leave across the globe,” Laxmi S. Mehta, MD, Ohio State University Weiner Medical Center, Columbus, said in an interview.
As previously reported, Dr. Mehta recently led a study that surveyed 323 women cardiologists who were working while they were pregnant. Her study found that 75% of these women experienced discriminatory maternity leave practices, some of which were likely violations of the federal Family and Medical Leave Act.
“If we want more women to pursue a career in cardiology, then employers and health systems need to adequately support parenthood, including allowing people to spend uninterrupted time with their newborns without the fear of discrimination, retaliation, or financial burden,” Dr. Mehta said.
Limitations of the study are the small sample size, potential for bias associated with social media distribution, and the fact that 75% of respondents were women, Dr. Oliveros and colleagues write.
Dr. Oliveros, Dr. Piña, and Dr. Mehta report no relevant financial relationships.
A version of this article first appeared on Medscape.com.