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Many hydroxychloroquine COVID-19 prophylaxis trials lack ECG screening
Many planned randomized trials to test the efficacy of hydroxychloroquine or related drugs for preventing COVID-19 infection have, as of the end of April 2020, failed to include ECG assessment to either exclude people at the highest risk for possibly developing a life-threatening cardiac arrhythmia or to flag people who achieve a dangerous QTc interval on treatment, according to an analysis of the posted designs of several dozen studies.
Hydroxychloroquine, the related agent chloroquine, and azithromycin have all recently received attention as potentially effective but unproven agents for both reducing the severity and duration of established COVID-19 infection as well as possibly preventing or mitigating an incident infection. As of April 30, 155 randomized, control trials listed on a major index for pending and in-progress trials, clinicaltrials.gov, had designs that intended to randomized an overall total of more than 85,000 healthy people to receive hydroxychloroquine or chloroquine, in some cases in combination with azithromycin, to test their efficacy and safety for COVID-19 prophylaxis, Michael H. Gollob, MD, said in an article posted by the Journal of the American College of Cardiology (2020 May 11. doi: 10.1016/j.jacc.2020.05.008).
The problem is that all three agents are documented to potentially produce lengthening of the corrected QT interval (QTc), and if this happens in a person who starts treatment with a QTc on the high end, the incremental prolongation from drug treatment could push their heart rhythm into a range where their risk for a life-threatening arrhythmia becomes substantial, said Dr. Gollob, a cardiac arrhythmia researcher at Toronto General Hospital and the University of Toronto. As a consequence, he recommended excluding from these prophylaxis trials anyone with a resting QTc at baseline assessment of greater than 450 msec, as well as discontinuing treatment from anyone who develops a resting QTc of more than 480 ms while on treatment.
“Though this may seem like a conservative value for subject withdrawal from a study, this is a prudent QTc cut-off, particularly when the severity of the adverse event, sudden death, may be worse than the study endpoint” of reduced incidence of COVID-19 infection, he wrote in his opinion piece.
“We cannot provide an accurate number for elevated risk” faced by people whose QTc climbs above these thresholds, “but we know that events will occur, which is why most trials that involve QT-prolonging drugs typically have an ECG exclusion criterion of QTc greater than 450 msec,” Dr. Gollob said in an interview.
His analysis of the 155 planned randomized prophylaxis trials on clinicaltrials.gov that he examined in detail had enrollment goals that would translate into more than 85,000 uninfected people who would receive hydroxychloroquine or chloroquine plus, in come cases, azithromycin. Only six relatively small studies from among these 155 included a plan for ECG screening and monitoring in its design, he noted. “It is reasonable to estimate that among the 80,000 patients randomized to a QT-prolonging drug [without ECG screening or monitoring] there will certainly be arrhythmic events.” If some of these people were to then die from a drug-induced arrhythmic event that could have been prevented by ECG screening or monitoring, it would be a “tragedy,” Dr. Gollob said.
“It is not only inexplicable, but also inexcusable that clinical investigators would dare to include healthy individuals in a clinical trial involving QT-prolonging medications without bothering to screen their electrocardiogram,” commented Sami Viskin, MD, an electrophysiologist at Tel Aviv Sourasky Medical Center. “The fact that we needed Dr. Gollob to ring this alarm is, itself, shocking,” he said in an interview.
“ECG screening is a good option to minimize the risk. You don’t eliminate the risk, but you can minimize it,” commented Arthur Wilde, MD, a cardiac electrophysiologist and professor of medicine at the Academic Medical Center in Amsterdam. Both Dr. Viskin and Dr. Wilde agreed with the QTc interval thresholds Dr. Gollob recommended using for excluding or discontinuing study participants.
In his commentary, Dr. Gollob estimated that if 85,000 otherwise healthy adults were randomized to received a drug that can increase the QTc interval, as many as about 3,400 people (4%) in the group could statistically be expected to have an especially high vulnerability to QT prolongation because of genetic variants they might carry that collectively have roughly this prevalence. In some people of African heritage, the prevalence of genetic risk for excessive QTc lengthening can be even higher, approaching about 10%, noted Dr. Wilde.
Dr. Gollob hoped the concerns he raised will prompt the organizers of many of these studies to revise their design, and he said he already knew of one study based in Toronto that recently added an ECG-monitoring strategy in response to the concerns he raised. He expressed optimism that more studies will follow.
“It’s a real issue to have these trials designed without ECG exclusions or monitoring. I’m glad that Dr. Gollob sent this warning, because he is right. ECG monitoring during treatment is important so you can stop the treatment in time,” Dr. Wilde said. Dr. Wilde also noted that many, if not most, of the studies listed on clinicaltrials.gov may not actually launch.
In April, representatives from several cardiology societies coauthored a document of considerations when using hydroxychloroquine, chloroquine, or azithromycin to treat patients with a diagnosed COVID-19 infection, and highlighted a QTc interval of 500 msec or greater as flagging patients who should no longer receive these drugs (J Am Coll Cardiol. 2020 Apr 10. doi: 10.1016/j.jacc.2020.04.016). For patients who do not yet have COVID-19 disease and the goal from treatment is prevention the potential efficacy of these drugs is reasonable to explore, but “does not exclude the need to minimize risk to research participants, especially when enrolling healthy subjects,” Dr. Gollob said.
Dr. Gollob, Dr. Viskin, and Dr. Wilde had no relevant financial disclosures.
Many planned randomized trials to test the efficacy of hydroxychloroquine or related drugs for preventing COVID-19 infection have, as of the end of April 2020, failed to include ECG assessment to either exclude people at the highest risk for possibly developing a life-threatening cardiac arrhythmia or to flag people who achieve a dangerous QTc interval on treatment, according to an analysis of the posted designs of several dozen studies.
Hydroxychloroquine, the related agent chloroquine, and azithromycin have all recently received attention as potentially effective but unproven agents for both reducing the severity and duration of established COVID-19 infection as well as possibly preventing or mitigating an incident infection. As of April 30, 155 randomized, control trials listed on a major index for pending and in-progress trials, clinicaltrials.gov, had designs that intended to randomized an overall total of more than 85,000 healthy people to receive hydroxychloroquine or chloroquine, in some cases in combination with azithromycin, to test their efficacy and safety for COVID-19 prophylaxis, Michael H. Gollob, MD, said in an article posted by the Journal of the American College of Cardiology (2020 May 11. doi: 10.1016/j.jacc.2020.05.008).
The problem is that all three agents are documented to potentially produce lengthening of the corrected QT interval (QTc), and if this happens in a person who starts treatment with a QTc on the high end, the incremental prolongation from drug treatment could push their heart rhythm into a range where their risk for a life-threatening arrhythmia becomes substantial, said Dr. Gollob, a cardiac arrhythmia researcher at Toronto General Hospital and the University of Toronto. As a consequence, he recommended excluding from these prophylaxis trials anyone with a resting QTc at baseline assessment of greater than 450 msec, as well as discontinuing treatment from anyone who develops a resting QTc of more than 480 ms while on treatment.
“Though this may seem like a conservative value for subject withdrawal from a study, this is a prudent QTc cut-off, particularly when the severity of the adverse event, sudden death, may be worse than the study endpoint” of reduced incidence of COVID-19 infection, he wrote in his opinion piece.
“We cannot provide an accurate number for elevated risk” faced by people whose QTc climbs above these thresholds, “but we know that events will occur, which is why most trials that involve QT-prolonging drugs typically have an ECG exclusion criterion of QTc greater than 450 msec,” Dr. Gollob said in an interview.
His analysis of the 155 planned randomized prophylaxis trials on clinicaltrials.gov that he examined in detail had enrollment goals that would translate into more than 85,000 uninfected people who would receive hydroxychloroquine or chloroquine plus, in come cases, azithromycin. Only six relatively small studies from among these 155 included a plan for ECG screening and monitoring in its design, he noted. “It is reasonable to estimate that among the 80,000 patients randomized to a QT-prolonging drug [without ECG screening or monitoring] there will certainly be arrhythmic events.” If some of these people were to then die from a drug-induced arrhythmic event that could have been prevented by ECG screening or monitoring, it would be a “tragedy,” Dr. Gollob said.
“It is not only inexplicable, but also inexcusable that clinical investigators would dare to include healthy individuals in a clinical trial involving QT-prolonging medications without bothering to screen their electrocardiogram,” commented Sami Viskin, MD, an electrophysiologist at Tel Aviv Sourasky Medical Center. “The fact that we needed Dr. Gollob to ring this alarm is, itself, shocking,” he said in an interview.
“ECG screening is a good option to minimize the risk. You don’t eliminate the risk, but you can minimize it,” commented Arthur Wilde, MD, a cardiac electrophysiologist and professor of medicine at the Academic Medical Center in Amsterdam. Both Dr. Viskin and Dr. Wilde agreed with the QTc interval thresholds Dr. Gollob recommended using for excluding or discontinuing study participants.
In his commentary, Dr. Gollob estimated that if 85,000 otherwise healthy adults were randomized to received a drug that can increase the QTc interval, as many as about 3,400 people (4%) in the group could statistically be expected to have an especially high vulnerability to QT prolongation because of genetic variants they might carry that collectively have roughly this prevalence. In some people of African heritage, the prevalence of genetic risk for excessive QTc lengthening can be even higher, approaching about 10%, noted Dr. Wilde.
Dr. Gollob hoped the concerns he raised will prompt the organizers of many of these studies to revise their design, and he said he already knew of one study based in Toronto that recently added an ECG-monitoring strategy in response to the concerns he raised. He expressed optimism that more studies will follow.
“It’s a real issue to have these trials designed without ECG exclusions or monitoring. I’m glad that Dr. Gollob sent this warning, because he is right. ECG monitoring during treatment is important so you can stop the treatment in time,” Dr. Wilde said. Dr. Wilde also noted that many, if not most, of the studies listed on clinicaltrials.gov may not actually launch.
In April, representatives from several cardiology societies coauthored a document of considerations when using hydroxychloroquine, chloroquine, or azithromycin to treat patients with a diagnosed COVID-19 infection, and highlighted a QTc interval of 500 msec or greater as flagging patients who should no longer receive these drugs (J Am Coll Cardiol. 2020 Apr 10. doi: 10.1016/j.jacc.2020.04.016). For patients who do not yet have COVID-19 disease and the goal from treatment is prevention the potential efficacy of these drugs is reasonable to explore, but “does not exclude the need to minimize risk to research participants, especially when enrolling healthy subjects,” Dr. Gollob said.
Dr. Gollob, Dr. Viskin, and Dr. Wilde had no relevant financial disclosures.
Many planned randomized trials to test the efficacy of hydroxychloroquine or related drugs for preventing COVID-19 infection have, as of the end of April 2020, failed to include ECG assessment to either exclude people at the highest risk for possibly developing a life-threatening cardiac arrhythmia or to flag people who achieve a dangerous QTc interval on treatment, according to an analysis of the posted designs of several dozen studies.
Hydroxychloroquine, the related agent chloroquine, and azithromycin have all recently received attention as potentially effective but unproven agents for both reducing the severity and duration of established COVID-19 infection as well as possibly preventing or mitigating an incident infection. As of April 30, 155 randomized, control trials listed on a major index for pending and in-progress trials, clinicaltrials.gov, had designs that intended to randomized an overall total of more than 85,000 healthy people to receive hydroxychloroquine or chloroquine, in some cases in combination with azithromycin, to test their efficacy and safety for COVID-19 prophylaxis, Michael H. Gollob, MD, said in an article posted by the Journal of the American College of Cardiology (2020 May 11. doi: 10.1016/j.jacc.2020.05.008).
The problem is that all three agents are documented to potentially produce lengthening of the corrected QT interval (QTc), and if this happens in a person who starts treatment with a QTc on the high end, the incremental prolongation from drug treatment could push their heart rhythm into a range where their risk for a life-threatening arrhythmia becomes substantial, said Dr. Gollob, a cardiac arrhythmia researcher at Toronto General Hospital and the University of Toronto. As a consequence, he recommended excluding from these prophylaxis trials anyone with a resting QTc at baseline assessment of greater than 450 msec, as well as discontinuing treatment from anyone who develops a resting QTc of more than 480 ms while on treatment.
“Though this may seem like a conservative value for subject withdrawal from a study, this is a prudent QTc cut-off, particularly when the severity of the adverse event, sudden death, may be worse than the study endpoint” of reduced incidence of COVID-19 infection, he wrote in his opinion piece.
“We cannot provide an accurate number for elevated risk” faced by people whose QTc climbs above these thresholds, “but we know that events will occur, which is why most trials that involve QT-prolonging drugs typically have an ECG exclusion criterion of QTc greater than 450 msec,” Dr. Gollob said in an interview.
His analysis of the 155 planned randomized prophylaxis trials on clinicaltrials.gov that he examined in detail had enrollment goals that would translate into more than 85,000 uninfected people who would receive hydroxychloroquine or chloroquine plus, in come cases, azithromycin. Only six relatively small studies from among these 155 included a plan for ECG screening and monitoring in its design, he noted. “It is reasonable to estimate that among the 80,000 patients randomized to a QT-prolonging drug [without ECG screening or monitoring] there will certainly be arrhythmic events.” If some of these people were to then die from a drug-induced arrhythmic event that could have been prevented by ECG screening or monitoring, it would be a “tragedy,” Dr. Gollob said.
“It is not only inexplicable, but also inexcusable that clinical investigators would dare to include healthy individuals in a clinical trial involving QT-prolonging medications without bothering to screen their electrocardiogram,” commented Sami Viskin, MD, an electrophysiologist at Tel Aviv Sourasky Medical Center. “The fact that we needed Dr. Gollob to ring this alarm is, itself, shocking,” he said in an interview.
“ECG screening is a good option to minimize the risk. You don’t eliminate the risk, but you can minimize it,” commented Arthur Wilde, MD, a cardiac electrophysiologist and professor of medicine at the Academic Medical Center in Amsterdam. Both Dr. Viskin and Dr. Wilde agreed with the QTc interval thresholds Dr. Gollob recommended using for excluding or discontinuing study participants.
In his commentary, Dr. Gollob estimated that if 85,000 otherwise healthy adults were randomized to received a drug that can increase the QTc interval, as many as about 3,400 people (4%) in the group could statistically be expected to have an especially high vulnerability to QT prolongation because of genetic variants they might carry that collectively have roughly this prevalence. In some people of African heritage, the prevalence of genetic risk for excessive QTc lengthening can be even higher, approaching about 10%, noted Dr. Wilde.
Dr. Gollob hoped the concerns he raised will prompt the organizers of many of these studies to revise their design, and he said he already knew of one study based in Toronto that recently added an ECG-monitoring strategy in response to the concerns he raised. He expressed optimism that more studies will follow.
“It’s a real issue to have these trials designed without ECG exclusions or monitoring. I’m glad that Dr. Gollob sent this warning, because he is right. ECG monitoring during treatment is important so you can stop the treatment in time,” Dr. Wilde said. Dr. Wilde also noted that many, if not most, of the studies listed on clinicaltrials.gov may not actually launch.
In April, representatives from several cardiology societies coauthored a document of considerations when using hydroxychloroquine, chloroquine, or azithromycin to treat patients with a diagnosed COVID-19 infection, and highlighted a QTc interval of 500 msec or greater as flagging patients who should no longer receive these drugs (J Am Coll Cardiol. 2020 Apr 10. doi: 10.1016/j.jacc.2020.04.016). For patients who do not yet have COVID-19 disease and the goal from treatment is prevention the potential efficacy of these drugs is reasonable to explore, but “does not exclude the need to minimize risk to research participants, especially when enrolling healthy subjects,” Dr. Gollob said.
Dr. Gollob, Dr. Viskin, and Dr. Wilde had no relevant financial disclosures.
REPORTING FROM JACC
S-ICD ‘noninferior’ to transvenous-lead ICD in head-to-head PRAETORIAN trial
by turning in a “noninferior” performance when it was compared with transvenous-lead devices in a first-of-its-kind head-to-head study.
Patients implanted with the subcutaneous-lead S-ICD (Boston Scientific) defibrillator showed a 4-year risk for inappropriate shocks or device-related complications similar to that seen with standard transvenous-lead implantable cardioverter defibrillators (ICD) in a randomized comparison.
At the same time, the S-ICD did its job by showing a highly significant three-fourths reduction in risk for lead-related complications, compared with ICDs with standard leads, in the trial with more than 800 patients, called PRAETORIAN.
The study population represented a mix of patients seen in “real-world” practice who have an ICD indication, of whom about two-thirds had ischemic cardiomyopathy, said Reinoud Knops, MD, PhD, Academic Medical Center, Hilversum, the Netherlands. About 80% received the devices for primary prevention.
Knops, the trial’s principal investigator, presented the results online May 8 as one of the Heart Rhythm Society 2020 Scientific Sessions virtual presentations.
“I think the PRAETORIAN trial has really shown now, in a conventional ICD population – the real-world patients that we treat with ICD therapy, the single-chamber ICD cohort – that the S-ICD is a really good alternative option,” he said to reporters during a media briefing.
“The main conclusion is that the S-ICD should be considered in all patients who need an ICD who do not have a pacing indication,” Knops said.
This latter part is critical, because the S-ICD does not provide pacing therapy, including antitachycardia pacing (ATP) and cardiac resynchronization therapy (CRT), and the trial did not enter patients considered likely to benefit from it. For example, it excluded anyone with bradycardia or treatment-refractory monomorphic ventricular tachycardia (VT) and patients considered appropriate for CRT.
In fact, there are a lot reasons clinicians might prefer a transvenous-lead ICD over the S-ICD, observed Anne B. Curtis, MD, University at Buffalo, State University of New York, who is not associated with PRAETORIAN.
A transvenous-lead system might be preferred in older patients, those with heart failure, and those with a lot of comorbidities. “A lot of these patients already have cardiomyopathies, so they’re more likely to develop atrial fibrillation or a need for CRT,” conditions that might make a transvenous-lead system the better choice, Curtis told theheart.org | Medscape Cardiology.
“For a lot of patients, you’re always thinking that you may have a need for that kind of therapy.”
In contrast, younger patients who perhaps have survived cardiac arrest and probably don’t have heart failure, and so may be less likely to benefit from pacing therapy, Curtis said, “are the kind of patient who you would probably lean very strongly toward for an S-ICD rather than a transvenous ICD.”
Remaining patients, those who might be considered candidates for either kind of device, are actually “a fairly limited subset,” she said.
The trial randomized 849 patients in Europe and the United States, from March 2011 to January 2017, who had a class I or IIa indication for an ICD but no bradycardia or need for CRT or ATP, to be implanted with an S-ICD or a transvenous-lead ICD.
The rates of the primary end point, a composite of device-related complications and inappropriate shocks at a median follow-up of 4 years, were comparable, at 15.1% in the S-ICD group and 15.7% for those with transvenous-lead ICDs.
The incidence of device-related complications numerically favored the S-ICD group, and the incidence of inappropriate shocks numerically favored the transvenous-lead group, but neither difference reached significance.
Knops said the PRAETORIAN researchers are seeking addition funding to extend the follow-up to 8 years. “We will get more insight into the durability of the S-ICD when we follow these patients longer,” he told theheart.org | Medscape Cardiology.
The investigator-initiated trial received support from Boston Scientific. Knops discloses receiving consultancy fees and research grants from Abbott, Boston Scientific, Medtronic, and Cairdac, and holding stock options from AtaCor Medical.
This article first appeared on Medscape.com.
by turning in a “noninferior” performance when it was compared with transvenous-lead devices in a first-of-its-kind head-to-head study.
Patients implanted with the subcutaneous-lead S-ICD (Boston Scientific) defibrillator showed a 4-year risk for inappropriate shocks or device-related complications similar to that seen with standard transvenous-lead implantable cardioverter defibrillators (ICD) in a randomized comparison.
At the same time, the S-ICD did its job by showing a highly significant three-fourths reduction in risk for lead-related complications, compared with ICDs with standard leads, in the trial with more than 800 patients, called PRAETORIAN.
The study population represented a mix of patients seen in “real-world” practice who have an ICD indication, of whom about two-thirds had ischemic cardiomyopathy, said Reinoud Knops, MD, PhD, Academic Medical Center, Hilversum, the Netherlands. About 80% received the devices for primary prevention.
Knops, the trial’s principal investigator, presented the results online May 8 as one of the Heart Rhythm Society 2020 Scientific Sessions virtual presentations.
“I think the PRAETORIAN trial has really shown now, in a conventional ICD population – the real-world patients that we treat with ICD therapy, the single-chamber ICD cohort – that the S-ICD is a really good alternative option,” he said to reporters during a media briefing.
“The main conclusion is that the S-ICD should be considered in all patients who need an ICD who do not have a pacing indication,” Knops said.
This latter part is critical, because the S-ICD does not provide pacing therapy, including antitachycardia pacing (ATP) and cardiac resynchronization therapy (CRT), and the trial did not enter patients considered likely to benefit from it. For example, it excluded anyone with bradycardia or treatment-refractory monomorphic ventricular tachycardia (VT) and patients considered appropriate for CRT.
In fact, there are a lot reasons clinicians might prefer a transvenous-lead ICD over the S-ICD, observed Anne B. Curtis, MD, University at Buffalo, State University of New York, who is not associated with PRAETORIAN.
A transvenous-lead system might be preferred in older patients, those with heart failure, and those with a lot of comorbidities. “A lot of these patients already have cardiomyopathies, so they’re more likely to develop atrial fibrillation or a need for CRT,” conditions that might make a transvenous-lead system the better choice, Curtis told theheart.org | Medscape Cardiology.
“For a lot of patients, you’re always thinking that you may have a need for that kind of therapy.”
In contrast, younger patients who perhaps have survived cardiac arrest and probably don’t have heart failure, and so may be less likely to benefit from pacing therapy, Curtis said, “are the kind of patient who you would probably lean very strongly toward for an S-ICD rather than a transvenous ICD.”
Remaining patients, those who might be considered candidates for either kind of device, are actually “a fairly limited subset,” she said.
The trial randomized 849 patients in Europe and the United States, from March 2011 to January 2017, who had a class I or IIa indication for an ICD but no bradycardia or need for CRT or ATP, to be implanted with an S-ICD or a transvenous-lead ICD.
The rates of the primary end point, a composite of device-related complications and inappropriate shocks at a median follow-up of 4 years, were comparable, at 15.1% in the S-ICD group and 15.7% for those with transvenous-lead ICDs.
The incidence of device-related complications numerically favored the S-ICD group, and the incidence of inappropriate shocks numerically favored the transvenous-lead group, but neither difference reached significance.
Knops said the PRAETORIAN researchers are seeking addition funding to extend the follow-up to 8 years. “We will get more insight into the durability of the S-ICD when we follow these patients longer,” he told theheart.org | Medscape Cardiology.
The investigator-initiated trial received support from Boston Scientific. Knops discloses receiving consultancy fees and research grants from Abbott, Boston Scientific, Medtronic, and Cairdac, and holding stock options from AtaCor Medical.
This article first appeared on Medscape.com.
by turning in a “noninferior” performance when it was compared with transvenous-lead devices in a first-of-its-kind head-to-head study.
Patients implanted with the subcutaneous-lead S-ICD (Boston Scientific) defibrillator showed a 4-year risk for inappropriate shocks or device-related complications similar to that seen with standard transvenous-lead implantable cardioverter defibrillators (ICD) in a randomized comparison.
At the same time, the S-ICD did its job by showing a highly significant three-fourths reduction in risk for lead-related complications, compared with ICDs with standard leads, in the trial with more than 800 patients, called PRAETORIAN.
The study population represented a mix of patients seen in “real-world” practice who have an ICD indication, of whom about two-thirds had ischemic cardiomyopathy, said Reinoud Knops, MD, PhD, Academic Medical Center, Hilversum, the Netherlands. About 80% received the devices for primary prevention.
Knops, the trial’s principal investigator, presented the results online May 8 as one of the Heart Rhythm Society 2020 Scientific Sessions virtual presentations.
“I think the PRAETORIAN trial has really shown now, in a conventional ICD population – the real-world patients that we treat with ICD therapy, the single-chamber ICD cohort – that the S-ICD is a really good alternative option,” he said to reporters during a media briefing.
“The main conclusion is that the S-ICD should be considered in all patients who need an ICD who do not have a pacing indication,” Knops said.
This latter part is critical, because the S-ICD does not provide pacing therapy, including antitachycardia pacing (ATP) and cardiac resynchronization therapy (CRT), and the trial did not enter patients considered likely to benefit from it. For example, it excluded anyone with bradycardia or treatment-refractory monomorphic ventricular tachycardia (VT) and patients considered appropriate for CRT.
In fact, there are a lot reasons clinicians might prefer a transvenous-lead ICD over the S-ICD, observed Anne B. Curtis, MD, University at Buffalo, State University of New York, who is not associated with PRAETORIAN.
A transvenous-lead system might be preferred in older patients, those with heart failure, and those with a lot of comorbidities. “A lot of these patients already have cardiomyopathies, so they’re more likely to develop atrial fibrillation or a need for CRT,” conditions that might make a transvenous-lead system the better choice, Curtis told theheart.org | Medscape Cardiology.
“For a lot of patients, you’re always thinking that you may have a need for that kind of therapy.”
In contrast, younger patients who perhaps have survived cardiac arrest and probably don’t have heart failure, and so may be less likely to benefit from pacing therapy, Curtis said, “are the kind of patient who you would probably lean very strongly toward for an S-ICD rather than a transvenous ICD.”
Remaining patients, those who might be considered candidates for either kind of device, are actually “a fairly limited subset,” she said.
The trial randomized 849 patients in Europe and the United States, from March 2011 to January 2017, who had a class I or IIa indication for an ICD but no bradycardia or need for CRT or ATP, to be implanted with an S-ICD or a transvenous-lead ICD.
The rates of the primary end point, a composite of device-related complications and inappropriate shocks at a median follow-up of 4 years, were comparable, at 15.1% in the S-ICD group and 15.7% for those with transvenous-lead ICDs.
The incidence of device-related complications numerically favored the S-ICD group, and the incidence of inappropriate shocks numerically favored the transvenous-lead group, but neither difference reached significance.
Knops said the PRAETORIAN researchers are seeking addition funding to extend the follow-up to 8 years. “We will get more insight into the durability of the S-ICD when we follow these patients longer,” he told theheart.org | Medscape Cardiology.
The investigator-initiated trial received support from Boston Scientific. Knops discloses receiving consultancy fees and research grants from Abbott, Boston Scientific, Medtronic, and Cairdac, and holding stock options from AtaCor Medical.
This article first appeared on Medscape.com.
Silent brain infarcts found in 3% of AFib patients, tied to cognitive decline
Patients with atrial fibrillation, even those on oral anticoagulant therapy, developed clinically silent brain infarctions at a striking rate of close to 3% per year, according to results from SWISS-AF, a prospective of study of 1,227 Swiss patients followed with serial MR brain scans over a 2 year period.
The results also showed that these brain infarctions – which occurred in 68 (5.5%) of the atrial fibrillation (AFib) patients, including 58 (85%) who did not have any strokes or transient ischemic attacks during follow-up – appeared to represent enough pathology to link with a small but statistically significant decline in three separate cognitive measures, compared with patients who did not develop brain infarctions during follow-up.
“Cognitive decline may go unrecognized for a long time in clinical practice because usually no one tests for it,” plus “the absolute declines were small and probably not appreciable” in the everyday behavior of affected patients, David Conen, MD, said at the annual scientific sessions of the Heart Rhythm Society, held online because of COVID-19. But “we were surprised to see a significant change after just 2 years. We expect much larger effects to develop over time,” he said during a press briefing.
Another key finding was that roughly half the patients had large cortical or noncortical infarcts, which usually have a thromboembolic cause, but the other half had small noncortical infarcts that likely have a different etiology involving the microvasculature. Causes for those small infarcts might include localized atherosclerotic disease or amyloidosis, proposed Dr. Conen, a cardiologist at McMaster University, Hamilton, Ont.
This finding also suggests that, as a consequence, anticoagulation alone may not be enough to prevent this brain damage in Afib patients. “It calls for a more comprehensive approach to prevention,” with attention to atherosclerotic cardiovascular disease risk factors in AFib patients, including interventions that address hypertension, diabetes, hyperlipidemia, and smoking cessation. “Anticoagulation in AFib patients is critical, but it also is not enough,” Dr. Conen said.
These data “are very important. The two pillars for taking care of AFib patients have traditionally been to manage the patient’s stroke risk and to treat symptoms. Dr. Conen’s data suggest that simply starting anticoagulation is not sufficient, and it stresses the importance of continued management of hypertension, diabetes, and other medical and social issues,” commented Fred Kusumoto, MD, director of heart rhythm services at the Mayo Clinic in Jacksonville, Fla.
“The risk factors associated with the development of cardiovascular disease are similar to those associated with the development of AFib and heart failure. It is important to understand the importance of managing hypertension, diabetes, and obesity; encouraging exercise and a healthy diet; and stopping smoking in all AFib patients as well as in the general population. Many clinicians have not emphasized the importance of continually addressing these behaviors,” Dr. Kusumoto said in an interview.
The SWISS-AF (Swiss Atrial Fibrillation Cohort) study enrolled 2,415 AFib patients at 14 Swiss centers during 2014-2017, and obtained both a baseline brain MR scan and baseline cognitive-test results for 1,737 patients (J Am Coll Cardiol. 2019 Mar;73[9]:989-99). Patients retook the cognitive tests annually, and 1,227 had a second MR brain scan after 2 years in the study, the cohort that supplied the data Dr. Conen presented. At baseline, these patients averaged 71 years of age, just over a quarter were women, and 90% were on an oral anticoagulant, with 84% on an oral anticoagulant at 2-year follow-up. Treatment split roughly equally between direct-acting oral anticoagulants and vitamin K antagonists like warfarin.
Among the 68 patients with evidence for an incident brain infarct after 2 years, 59 (87%) were on treatment with an OAC, and 51 (75%) who were both on treatment with a direct-acting oral anticoagulant and developed their brain infarct without also having a stroke or transient ischemic attack, which Dr. Conen called a “silent event.” The cognitive tests that showed statistically significant declines after 2 years in the patients with silent brain infarcts compared with those without a new infarct were the Trail Making Test parts A and B, and the animal-naming verbal fluency test. The two other tests applied were the Montreal Cognitive Assessment and the Digital Symbol Substitution Test.
Results from several prior studies also indicated a relationship between AFib and cognitive decline, but SWISS-AF is “the largest study to rigorously examine the incidence of silent brain infarcts in AFib patients,” commented Christine M. Albert, MD, chair of cardiology at the Smidt Heart Institute of Cedars-Sinai Medical Center in Los Angeles. “Silent infarcts could be the cause, at least in part, for the cognitive decline and dementia associated with AFib,” she noted. But divining the therapeutic implications of the finding will require further investigation that looks at factors such as the impact of anticoagulant type, other treatment that addresses AFib such as ablation and rate control, the duration and type of AFib, and the prevalence of hypertension and other stroke risk factors, she said as a designated discussant for Dr. Conen’s report.
SWISS-AF received no commercial funding. Dr. Conen has been a speaker on behalf of Servier. Dr. Kusumoto had no disclosures. Dr. Albert has been a consultant to Roche Diagnostics and has received research funding from Abbott, Roche Diagnostics, and St. Jude Medical.
Patients with atrial fibrillation, even those on oral anticoagulant therapy, developed clinically silent brain infarctions at a striking rate of close to 3% per year, according to results from SWISS-AF, a prospective of study of 1,227 Swiss patients followed with serial MR brain scans over a 2 year period.
The results also showed that these brain infarctions – which occurred in 68 (5.5%) of the atrial fibrillation (AFib) patients, including 58 (85%) who did not have any strokes or transient ischemic attacks during follow-up – appeared to represent enough pathology to link with a small but statistically significant decline in three separate cognitive measures, compared with patients who did not develop brain infarctions during follow-up.
“Cognitive decline may go unrecognized for a long time in clinical practice because usually no one tests for it,” plus “the absolute declines were small and probably not appreciable” in the everyday behavior of affected patients, David Conen, MD, said at the annual scientific sessions of the Heart Rhythm Society, held online because of COVID-19. But “we were surprised to see a significant change after just 2 years. We expect much larger effects to develop over time,” he said during a press briefing.
Another key finding was that roughly half the patients had large cortical or noncortical infarcts, which usually have a thromboembolic cause, but the other half had small noncortical infarcts that likely have a different etiology involving the microvasculature. Causes for those small infarcts might include localized atherosclerotic disease or amyloidosis, proposed Dr. Conen, a cardiologist at McMaster University, Hamilton, Ont.
This finding also suggests that, as a consequence, anticoagulation alone may not be enough to prevent this brain damage in Afib patients. “It calls for a more comprehensive approach to prevention,” with attention to atherosclerotic cardiovascular disease risk factors in AFib patients, including interventions that address hypertension, diabetes, hyperlipidemia, and smoking cessation. “Anticoagulation in AFib patients is critical, but it also is not enough,” Dr. Conen said.
These data “are very important. The two pillars for taking care of AFib patients have traditionally been to manage the patient’s stroke risk and to treat symptoms. Dr. Conen’s data suggest that simply starting anticoagulation is not sufficient, and it stresses the importance of continued management of hypertension, diabetes, and other medical and social issues,” commented Fred Kusumoto, MD, director of heart rhythm services at the Mayo Clinic in Jacksonville, Fla.
“The risk factors associated with the development of cardiovascular disease are similar to those associated with the development of AFib and heart failure. It is important to understand the importance of managing hypertension, diabetes, and obesity; encouraging exercise and a healthy diet; and stopping smoking in all AFib patients as well as in the general population. Many clinicians have not emphasized the importance of continually addressing these behaviors,” Dr. Kusumoto said in an interview.
The SWISS-AF (Swiss Atrial Fibrillation Cohort) study enrolled 2,415 AFib patients at 14 Swiss centers during 2014-2017, and obtained both a baseline brain MR scan and baseline cognitive-test results for 1,737 patients (J Am Coll Cardiol. 2019 Mar;73[9]:989-99). Patients retook the cognitive tests annually, and 1,227 had a second MR brain scan after 2 years in the study, the cohort that supplied the data Dr. Conen presented. At baseline, these patients averaged 71 years of age, just over a quarter were women, and 90% were on an oral anticoagulant, with 84% on an oral anticoagulant at 2-year follow-up. Treatment split roughly equally between direct-acting oral anticoagulants and vitamin K antagonists like warfarin.
Among the 68 patients with evidence for an incident brain infarct after 2 years, 59 (87%) were on treatment with an OAC, and 51 (75%) who were both on treatment with a direct-acting oral anticoagulant and developed their brain infarct without also having a stroke or transient ischemic attack, which Dr. Conen called a “silent event.” The cognitive tests that showed statistically significant declines after 2 years in the patients with silent brain infarcts compared with those without a new infarct were the Trail Making Test parts A and B, and the animal-naming verbal fluency test. The two other tests applied were the Montreal Cognitive Assessment and the Digital Symbol Substitution Test.
Results from several prior studies also indicated a relationship between AFib and cognitive decline, but SWISS-AF is “the largest study to rigorously examine the incidence of silent brain infarcts in AFib patients,” commented Christine M. Albert, MD, chair of cardiology at the Smidt Heart Institute of Cedars-Sinai Medical Center in Los Angeles. “Silent infarcts could be the cause, at least in part, for the cognitive decline and dementia associated with AFib,” she noted. But divining the therapeutic implications of the finding will require further investigation that looks at factors such as the impact of anticoagulant type, other treatment that addresses AFib such as ablation and rate control, the duration and type of AFib, and the prevalence of hypertension and other stroke risk factors, she said as a designated discussant for Dr. Conen’s report.
SWISS-AF received no commercial funding. Dr. Conen has been a speaker on behalf of Servier. Dr. Kusumoto had no disclosures. Dr. Albert has been a consultant to Roche Diagnostics and has received research funding from Abbott, Roche Diagnostics, and St. Jude Medical.
Patients with atrial fibrillation, even those on oral anticoagulant therapy, developed clinically silent brain infarctions at a striking rate of close to 3% per year, according to results from SWISS-AF, a prospective of study of 1,227 Swiss patients followed with serial MR brain scans over a 2 year period.
The results also showed that these brain infarctions – which occurred in 68 (5.5%) of the atrial fibrillation (AFib) patients, including 58 (85%) who did not have any strokes or transient ischemic attacks during follow-up – appeared to represent enough pathology to link with a small but statistically significant decline in three separate cognitive measures, compared with patients who did not develop brain infarctions during follow-up.
“Cognitive decline may go unrecognized for a long time in clinical practice because usually no one tests for it,” plus “the absolute declines were small and probably not appreciable” in the everyday behavior of affected patients, David Conen, MD, said at the annual scientific sessions of the Heart Rhythm Society, held online because of COVID-19. But “we were surprised to see a significant change after just 2 years. We expect much larger effects to develop over time,” he said during a press briefing.
Another key finding was that roughly half the patients had large cortical or noncortical infarcts, which usually have a thromboembolic cause, but the other half had small noncortical infarcts that likely have a different etiology involving the microvasculature. Causes for those small infarcts might include localized atherosclerotic disease or amyloidosis, proposed Dr. Conen, a cardiologist at McMaster University, Hamilton, Ont.
This finding also suggests that, as a consequence, anticoagulation alone may not be enough to prevent this brain damage in Afib patients. “It calls for a more comprehensive approach to prevention,” with attention to atherosclerotic cardiovascular disease risk factors in AFib patients, including interventions that address hypertension, diabetes, hyperlipidemia, and smoking cessation. “Anticoagulation in AFib patients is critical, but it also is not enough,” Dr. Conen said.
These data “are very important. The two pillars for taking care of AFib patients have traditionally been to manage the patient’s stroke risk and to treat symptoms. Dr. Conen’s data suggest that simply starting anticoagulation is not sufficient, and it stresses the importance of continued management of hypertension, diabetes, and other medical and social issues,” commented Fred Kusumoto, MD, director of heart rhythm services at the Mayo Clinic in Jacksonville, Fla.
“The risk factors associated with the development of cardiovascular disease are similar to those associated with the development of AFib and heart failure. It is important to understand the importance of managing hypertension, diabetes, and obesity; encouraging exercise and a healthy diet; and stopping smoking in all AFib patients as well as in the general population. Many clinicians have not emphasized the importance of continually addressing these behaviors,” Dr. Kusumoto said in an interview.
The SWISS-AF (Swiss Atrial Fibrillation Cohort) study enrolled 2,415 AFib patients at 14 Swiss centers during 2014-2017, and obtained both a baseline brain MR scan and baseline cognitive-test results for 1,737 patients (J Am Coll Cardiol. 2019 Mar;73[9]:989-99). Patients retook the cognitive tests annually, and 1,227 had a second MR brain scan after 2 years in the study, the cohort that supplied the data Dr. Conen presented. At baseline, these patients averaged 71 years of age, just over a quarter were women, and 90% were on an oral anticoagulant, with 84% on an oral anticoagulant at 2-year follow-up. Treatment split roughly equally between direct-acting oral anticoagulants and vitamin K antagonists like warfarin.
Among the 68 patients with evidence for an incident brain infarct after 2 years, 59 (87%) were on treatment with an OAC, and 51 (75%) who were both on treatment with a direct-acting oral anticoagulant and developed their brain infarct without also having a stroke or transient ischemic attack, which Dr. Conen called a “silent event.” The cognitive tests that showed statistically significant declines after 2 years in the patients with silent brain infarcts compared with those without a new infarct were the Trail Making Test parts A and B, and the animal-naming verbal fluency test. The two other tests applied were the Montreal Cognitive Assessment and the Digital Symbol Substitution Test.
Results from several prior studies also indicated a relationship between AFib and cognitive decline, but SWISS-AF is “the largest study to rigorously examine the incidence of silent brain infarcts in AFib patients,” commented Christine M. Albert, MD, chair of cardiology at the Smidt Heart Institute of Cedars-Sinai Medical Center in Los Angeles. “Silent infarcts could be the cause, at least in part, for the cognitive decline and dementia associated with AFib,” she noted. But divining the therapeutic implications of the finding will require further investigation that looks at factors such as the impact of anticoagulant type, other treatment that addresses AFib such as ablation and rate control, the duration and type of AFib, and the prevalence of hypertension and other stroke risk factors, she said as a designated discussant for Dr. Conen’s report.
SWISS-AF received no commercial funding. Dr. Conen has been a speaker on behalf of Servier. Dr. Kusumoto had no disclosures. Dr. Albert has been a consultant to Roche Diagnostics and has received research funding from Abbott, Roche Diagnostics, and St. Jude Medical.
FROM HEART RHYTHM 2020
UNTOUCHED: Inappropriate shocks cut by subcutaneous ICD improvements
Patients with an indication for an implantable cardiac defibrillator for primary prevention of sudden cardiac death and a sharply reduced left ventricular ejection fraction of 35% or less safely received treatment from a refined, subcutaneous device that produced one of the lowest rates of inappropriate cardiac shocks ever seen in a reported ICD study, in a single-arm trial with 1,111 patients followed for 18 months.
The results showed “high efficacy and safety with contemporary devices and programming” despite being “the ‘sickest’ cohort studied to date” for use of a subcutaneous ICD (S-ICD), Michael R. Gold, MD, said at the annual scientific sessions of the Heart Rhythm Society, held online because of COVID-19. The 3.1% 1-year rate of patients who received at least one inappropriate shock was “the lowest reported for the S-ICD, and lower than in many transvenous ICD device studies,” and was also “the lowest 1-year rate reported to date for a multicenter ICD trial,” said Dr. Gold, a cardiac electrophysiologist and professor of medicine at the Medical University of South Carolina, Charleston. The upshot is that these data may help convince clinicians to be more liberal about offering a S-ICD device to patients with left ventricular function in this low range who need an ICD and do not need pacing.
The study’s primary endpoint was the rate of freedom from inappropriate shocks during 18 months of follow-up, which happened in 95.9% of patients and was highly statistically significant for meeting the prespecified performance goal of 91.6% that had been set using “standard Food and Drug Administration benchmarks,” with particular reliance on the performance shown in the MADIT-RIT trial (N Engl J Med. 2012 Dec 13;367[24]:2275-83).
S-ICDs maintain ‘niche’ status despite advantages
The S-ICD first received Food and Drug Administration clearance for U.S. use in 2012, but despite not requiring placement of a transvenous lead and thus eliminating the possibility for lead complications and deterioration, it so far has had very modest penetration into American practice. Recently, roughly 4% of U.S. patients who’ve received an ICD have had a subcutaneous model placed, relegating the S-ICD to “niche device” status, noted Andrea M. Russo, MD, director of electrophysiology and arrhythmia services at Cooper University Health Care in Camden, N.J. A major limitation of S-ICD devices is that they cannot provide chronic pacing and so aren’t an option for the many patients who also need this function in addition to protection from life-threatening ventricular arrhythmias.
“We have had a bias for whom we place an S-ICD,” explained Dr. Gold. “They have mostly been used in younger patients with less heart disease,” but when used in the current study cohort with markedly depressed heart function, the results showed that “we didn’t appear to harm patients in any way,” including no episodes of syncope because of an arrhythmia. Compared with other S-ICD studies, the patients in the new study, UNTOUCHED, had “lower ejection fractions, more heart failure diagnoses, and a higher rate of ischemic etiology.”
The tested S-ICD device appears to have safety and efficacy that is “just as good, and perhaps better” than many ICDs that use transvenous leads, “which was very surprising to us,” said Dr. Gold during a press briefing. “I think it will change practice” for ICD placement in patients who do not need pacing. “We found the device works even in the sickest patients.”
“This was a classic ICD population, with a low ejection fraction, and the results showed that the device performed well,” commented Dr. Russo, who served on the steering committee for the study. “I agree that the results will help” increase use of this device, but she added that other factors in addition to concerns about the inappropriate shock rate and the lack of most pacing functions have hobbled uptake since the device came on the market. These notably include a somewhat different placement approach than operators need to learn. The device is not always offered as an option to patients by their clinicians “in part because of their lack of familiarity, and concern about inappropriate shocks,” she said in an interview. That’s despite the clear attractions of a leaderless device, which obviates issues of lead deterioration, lead placement complications like perforations and pneumothorax, and sizing issues that can come up for women with narrower veins, as well as cutting the risk both for infections overall and for infections that progress to bacteremia, noted Dr. Russo, who is president of the Heart Rhythm Society.
Device improvements boost performance
The low 1-year and 18-month rates of inappropriate shocks likely occurred because of new filtering and programming incorporated into the tested device. “By changing the filter, we could make it more like a transvenous device” that is not fooled by T wave over sensing. The programing also included a high beat threshold, with a conditional zone above 200 beats per minute and an “aggressive shock zone” of 250 bpm, Dr. Gold said. This helped make the tested S-ICD more immune to inappropriately shocking a supraventricular arrhythmia; the study recorded no inappropriate shocks of this type, he reported.
The UNTOUCHED study enrolled 1,116 patients at any of 110 sites in the United States and elsewhere who had a need for primary prevention of sudden cardiac death, a left ventricular ejection fraction of 35% or less, no need for pacing, and had successfully passed an S-ICD screening test. The investigators were able to include 1,111 of these patients in their endpoint analysis. Patients averaged 56 years of age, a quarter were women, and their average ejection fraction was 26%.
In addition to the primary endpoint and the 1-year inappropriate-shock rate, the results also showed an all-cause shock-free rate of 90.6% during 18-months’ follow-up, which significantly surpassed the prespecified performance goal for this metric of 85.8%. The tested device also appeared to successfully apply appropriate shocks when needed, delivering a total of 64 of these with just 1 shock failure, a case where the patient spontaneously reverted to normal rhythm. During the study period, 53 patients died (5%), including 3 arrhythmia-related deaths: 1 caused by asystole and 2 from pulseless electrical activity.
“The data show that in a standard ICD population, the device worked well, and was safe and effective,” Dr. Russo said. “These data say, at least consider this device along with a transvenous device” for appropriate patients. “It’s a great option for some patients. I’ve seen so may lead problems, and this avoids them.”
UNTOUCHED was sponsored by Boston Scientific, the company that markets the tested S-ICD. Dr. Gold has been a consultant to Boston Scientific and Medtronic and has been an investigator for trials sponsored by each of these companies. Dr. Russo served on the steering committee for UNTOUCHED but received no compensation and has no financial disclosures.
Patients with an indication for an implantable cardiac defibrillator for primary prevention of sudden cardiac death and a sharply reduced left ventricular ejection fraction of 35% or less safely received treatment from a refined, subcutaneous device that produced one of the lowest rates of inappropriate cardiac shocks ever seen in a reported ICD study, in a single-arm trial with 1,111 patients followed for 18 months.
The results showed “high efficacy and safety with contemporary devices and programming” despite being “the ‘sickest’ cohort studied to date” for use of a subcutaneous ICD (S-ICD), Michael R. Gold, MD, said at the annual scientific sessions of the Heart Rhythm Society, held online because of COVID-19. The 3.1% 1-year rate of patients who received at least one inappropriate shock was “the lowest reported for the S-ICD, and lower than in many transvenous ICD device studies,” and was also “the lowest 1-year rate reported to date for a multicenter ICD trial,” said Dr. Gold, a cardiac electrophysiologist and professor of medicine at the Medical University of South Carolina, Charleston. The upshot is that these data may help convince clinicians to be more liberal about offering a S-ICD device to patients with left ventricular function in this low range who need an ICD and do not need pacing.
The study’s primary endpoint was the rate of freedom from inappropriate shocks during 18 months of follow-up, which happened in 95.9% of patients and was highly statistically significant for meeting the prespecified performance goal of 91.6% that had been set using “standard Food and Drug Administration benchmarks,” with particular reliance on the performance shown in the MADIT-RIT trial (N Engl J Med. 2012 Dec 13;367[24]:2275-83).
S-ICDs maintain ‘niche’ status despite advantages
The S-ICD first received Food and Drug Administration clearance for U.S. use in 2012, but despite not requiring placement of a transvenous lead and thus eliminating the possibility for lead complications and deterioration, it so far has had very modest penetration into American practice. Recently, roughly 4% of U.S. patients who’ve received an ICD have had a subcutaneous model placed, relegating the S-ICD to “niche device” status, noted Andrea M. Russo, MD, director of electrophysiology and arrhythmia services at Cooper University Health Care in Camden, N.J. A major limitation of S-ICD devices is that they cannot provide chronic pacing and so aren’t an option for the many patients who also need this function in addition to protection from life-threatening ventricular arrhythmias.
“We have had a bias for whom we place an S-ICD,” explained Dr. Gold. “They have mostly been used in younger patients with less heart disease,” but when used in the current study cohort with markedly depressed heart function, the results showed that “we didn’t appear to harm patients in any way,” including no episodes of syncope because of an arrhythmia. Compared with other S-ICD studies, the patients in the new study, UNTOUCHED, had “lower ejection fractions, more heart failure diagnoses, and a higher rate of ischemic etiology.”
The tested S-ICD device appears to have safety and efficacy that is “just as good, and perhaps better” than many ICDs that use transvenous leads, “which was very surprising to us,” said Dr. Gold during a press briefing. “I think it will change practice” for ICD placement in patients who do not need pacing. “We found the device works even in the sickest patients.”
“This was a classic ICD population, with a low ejection fraction, and the results showed that the device performed well,” commented Dr. Russo, who served on the steering committee for the study. “I agree that the results will help” increase use of this device, but she added that other factors in addition to concerns about the inappropriate shock rate and the lack of most pacing functions have hobbled uptake since the device came on the market. These notably include a somewhat different placement approach than operators need to learn. The device is not always offered as an option to patients by their clinicians “in part because of their lack of familiarity, and concern about inappropriate shocks,” she said in an interview. That’s despite the clear attractions of a leaderless device, which obviates issues of lead deterioration, lead placement complications like perforations and pneumothorax, and sizing issues that can come up for women with narrower veins, as well as cutting the risk both for infections overall and for infections that progress to bacteremia, noted Dr. Russo, who is president of the Heart Rhythm Society.
Device improvements boost performance
The low 1-year and 18-month rates of inappropriate shocks likely occurred because of new filtering and programming incorporated into the tested device. “By changing the filter, we could make it more like a transvenous device” that is not fooled by T wave over sensing. The programing also included a high beat threshold, with a conditional zone above 200 beats per minute and an “aggressive shock zone” of 250 bpm, Dr. Gold said. This helped make the tested S-ICD more immune to inappropriately shocking a supraventricular arrhythmia; the study recorded no inappropriate shocks of this type, he reported.
The UNTOUCHED study enrolled 1,116 patients at any of 110 sites in the United States and elsewhere who had a need for primary prevention of sudden cardiac death, a left ventricular ejection fraction of 35% or less, no need for pacing, and had successfully passed an S-ICD screening test. The investigators were able to include 1,111 of these patients in their endpoint analysis. Patients averaged 56 years of age, a quarter were women, and their average ejection fraction was 26%.
In addition to the primary endpoint and the 1-year inappropriate-shock rate, the results also showed an all-cause shock-free rate of 90.6% during 18-months’ follow-up, which significantly surpassed the prespecified performance goal for this metric of 85.8%. The tested device also appeared to successfully apply appropriate shocks when needed, delivering a total of 64 of these with just 1 shock failure, a case where the patient spontaneously reverted to normal rhythm. During the study period, 53 patients died (5%), including 3 arrhythmia-related deaths: 1 caused by asystole and 2 from pulseless electrical activity.
“The data show that in a standard ICD population, the device worked well, and was safe and effective,” Dr. Russo said. “These data say, at least consider this device along with a transvenous device” for appropriate patients. “It’s a great option for some patients. I’ve seen so may lead problems, and this avoids them.”
UNTOUCHED was sponsored by Boston Scientific, the company that markets the tested S-ICD. Dr. Gold has been a consultant to Boston Scientific and Medtronic and has been an investigator for trials sponsored by each of these companies. Dr. Russo served on the steering committee for UNTOUCHED but received no compensation and has no financial disclosures.
Patients with an indication for an implantable cardiac defibrillator for primary prevention of sudden cardiac death and a sharply reduced left ventricular ejection fraction of 35% or less safely received treatment from a refined, subcutaneous device that produced one of the lowest rates of inappropriate cardiac shocks ever seen in a reported ICD study, in a single-arm trial with 1,111 patients followed for 18 months.
The results showed “high efficacy and safety with contemporary devices and programming” despite being “the ‘sickest’ cohort studied to date” for use of a subcutaneous ICD (S-ICD), Michael R. Gold, MD, said at the annual scientific sessions of the Heart Rhythm Society, held online because of COVID-19. The 3.1% 1-year rate of patients who received at least one inappropriate shock was “the lowest reported for the S-ICD, and lower than in many transvenous ICD device studies,” and was also “the lowest 1-year rate reported to date for a multicenter ICD trial,” said Dr. Gold, a cardiac electrophysiologist and professor of medicine at the Medical University of South Carolina, Charleston. The upshot is that these data may help convince clinicians to be more liberal about offering a S-ICD device to patients with left ventricular function in this low range who need an ICD and do not need pacing.
The study’s primary endpoint was the rate of freedom from inappropriate shocks during 18 months of follow-up, which happened in 95.9% of patients and was highly statistically significant for meeting the prespecified performance goal of 91.6% that had been set using “standard Food and Drug Administration benchmarks,” with particular reliance on the performance shown in the MADIT-RIT trial (N Engl J Med. 2012 Dec 13;367[24]:2275-83).
S-ICDs maintain ‘niche’ status despite advantages
The S-ICD first received Food and Drug Administration clearance for U.S. use in 2012, but despite not requiring placement of a transvenous lead and thus eliminating the possibility for lead complications and deterioration, it so far has had very modest penetration into American practice. Recently, roughly 4% of U.S. patients who’ve received an ICD have had a subcutaneous model placed, relegating the S-ICD to “niche device” status, noted Andrea M. Russo, MD, director of electrophysiology and arrhythmia services at Cooper University Health Care in Camden, N.J. A major limitation of S-ICD devices is that they cannot provide chronic pacing and so aren’t an option for the many patients who also need this function in addition to protection from life-threatening ventricular arrhythmias.
“We have had a bias for whom we place an S-ICD,” explained Dr. Gold. “They have mostly been used in younger patients with less heart disease,” but when used in the current study cohort with markedly depressed heart function, the results showed that “we didn’t appear to harm patients in any way,” including no episodes of syncope because of an arrhythmia. Compared with other S-ICD studies, the patients in the new study, UNTOUCHED, had “lower ejection fractions, more heart failure diagnoses, and a higher rate of ischemic etiology.”
The tested S-ICD device appears to have safety and efficacy that is “just as good, and perhaps better” than many ICDs that use transvenous leads, “which was very surprising to us,” said Dr. Gold during a press briefing. “I think it will change practice” for ICD placement in patients who do not need pacing. “We found the device works even in the sickest patients.”
“This was a classic ICD population, with a low ejection fraction, and the results showed that the device performed well,” commented Dr. Russo, who served on the steering committee for the study. “I agree that the results will help” increase use of this device, but she added that other factors in addition to concerns about the inappropriate shock rate and the lack of most pacing functions have hobbled uptake since the device came on the market. These notably include a somewhat different placement approach than operators need to learn. The device is not always offered as an option to patients by their clinicians “in part because of their lack of familiarity, and concern about inappropriate shocks,” she said in an interview. That’s despite the clear attractions of a leaderless device, which obviates issues of lead deterioration, lead placement complications like perforations and pneumothorax, and sizing issues that can come up for women with narrower veins, as well as cutting the risk both for infections overall and for infections that progress to bacteremia, noted Dr. Russo, who is president of the Heart Rhythm Society.
Device improvements boost performance
The low 1-year and 18-month rates of inappropriate shocks likely occurred because of new filtering and programming incorporated into the tested device. “By changing the filter, we could make it more like a transvenous device” that is not fooled by T wave over sensing. The programing also included a high beat threshold, with a conditional zone above 200 beats per minute and an “aggressive shock zone” of 250 bpm, Dr. Gold said. This helped make the tested S-ICD more immune to inappropriately shocking a supraventricular arrhythmia; the study recorded no inappropriate shocks of this type, he reported.
The UNTOUCHED study enrolled 1,116 patients at any of 110 sites in the United States and elsewhere who had a need for primary prevention of sudden cardiac death, a left ventricular ejection fraction of 35% or less, no need for pacing, and had successfully passed an S-ICD screening test. The investigators were able to include 1,111 of these patients in their endpoint analysis. Patients averaged 56 years of age, a quarter were women, and their average ejection fraction was 26%.
In addition to the primary endpoint and the 1-year inappropriate-shock rate, the results also showed an all-cause shock-free rate of 90.6% during 18-months’ follow-up, which significantly surpassed the prespecified performance goal for this metric of 85.8%. The tested device also appeared to successfully apply appropriate shocks when needed, delivering a total of 64 of these with just 1 shock failure, a case where the patient spontaneously reverted to normal rhythm. During the study period, 53 patients died (5%), including 3 arrhythmia-related deaths: 1 caused by asystole and 2 from pulseless electrical activity.
“The data show that in a standard ICD population, the device worked well, and was safe and effective,” Dr. Russo said. “These data say, at least consider this device along with a transvenous device” for appropriate patients. “It’s a great option for some patients. I’ve seen so may lead problems, and this avoids them.”
UNTOUCHED was sponsored by Boston Scientific, the company that markets the tested S-ICD. Dr. Gold has been a consultant to Boston Scientific and Medtronic and has been an investigator for trials sponsored by each of these companies. Dr. Russo served on the steering committee for UNTOUCHED but received no compensation and has no financial disclosures.
FROM HEART RHYTHM 2020
Coffee drinking linked with fewer arrhythmias
Moderate, daily coffee consumption had no apparent adverse effect for triggering incident heart arrhythmias, and even linked with a small but statistically significant drop in arrhythmias in an analysis of prospectively collected data from nearly 300,000 U.K. residents.
“In this large, population-based, prospective study, moderate habitual coffee drinking was associated with a lower risk of arrhythmia,” EunJeong Kim, MD, said at the annual scientific sessions of the Heart Rhythm Society, held online because of COVID-19.
Her analysis found that on average each additional daily cup of coffee that people said they drank reduced the incidence of arrhythmic episodes by a statistically significant 3%, compared with those who drank fewer daily cups. The relationship held for people who reported drinking as many as five or six cups of coffee daily.
“The main message of our study is that it does not appear to be deleterious to continue with moderate amounts of habitual coffee intake regarding a risk of overall arrhythmia,” said Dr. Kim, a cardiac electrophysiologist at the University of California, San Francisco.
Evidence builds for coffee’s safety
The finding adds to a substantial existing evidence base documenting the safety of moderate, habitual coffee drinking when it comes to heart rhythms. For example, a recent report from the Physicians Health Study of nearly 19,000 American men showed a statistically significant decrease in the incidence of atrial fibrillation during an average follow-up of 9 years among men who reported drinking one to three cups of coffee daily (J Am Heart Assoc. 2019 Aug 6;8[15]:e011346). In addition, a recent review of several reports found that “mild-to-moderate habitual consumption of caffeinated beverages, particularly a daily intake of 2-3 cups of coffee or tea, appears to be safe across a broad range of cardiovascular conditions, and may even be beneficial with respect to diabetes mellitus, atherosclerosis, heart failure, arrhythmia and total mortality,” but also concluded that “acute consumption of high doses of caffeine, particularly in the form of energy drinks, is best avoided”(Trends Cardiovasc Med. 2019 Aug;29[6]:345-50). Specifically about cardiac arrhythmias, the review said “while caffeine is commonly considered a trigger for arrhythmias by physicians and patients alike there is minimal evidence to support this misconception. Rather caffeine is associated with a mild reduction in the incidence of atrial fibrillation in observational studies.”
“There has been a lot of public interest about a possible association of caffeine and arrhythmias,” but an adverse effect from daily consumption of a moderate amount of coffee “is more legend and anecdote than fact based,” commented Andrew D. Krahn, MD, an electrophysiologist, professor of medicine, and head of cardiology at the University of British Columbia and St. Paul’s Hospital in Vancouver. “Increasingly we’re finding that there really is nothing here” when the proarrhythmic effects of moderate coffee undergo detailed assessment, he said in an interview.
What the study did
The study run by Dr. Kim and her associates used prospectively collected data from 296,227 participants in the UK Biobank during 2006-2016 who had complete data on their coffee intake and for the other covariables used in the analysis. During an average 5.25 years of follow-up, these people had more than 13,000 incident arrhythmic events, including 4,748 episodes of atrial fibrillation or flutter and 798 supraventricular tachycardia events, as well as fewer numbers of ventricular arrhythmias and many episodes of less clinically relevant events like skipped beats.
The multivariate analysis the researchers ran controlled for more than 20 demographic, lifestyle, and clinical variables, including adjustment for tea intake but not for consumption of other caffeine-containing drinks.
The adjusted analysis showed an average, statistically significant 3% incremental drop in both all incident arrhythmias and in incident atrial fibrillation episodes for each additional cup of coffee drunk a day, for up to 6 daily cups.
A strength of this study is that it included a large number of people, Dr. Krahn noted, and “the UK Biobank includes a very diverse, community-based sample” of people, said Dr. Kim. The analysis excluded people with prevalent arrhythmia at baseline, so the study couldn’t address the impact of coffee consumption in this setting. A limitation of the study is that participants in the UK Biobank are all volunteers, which could result in a selection bias, Dr. Krahn said.
What it tells us
While the main message from the results is that moderate daily coffee drinking is not arrhythmogenic, “it is also possible that coffee is beneficial” based on the small but statistically significant decline in new-onset events, Dr. Kim added. “Multiple studies revealed that caffeine and potentially other constituents in coffee have antioxidant and anti-inflammatory properties. Multiple studies have reported the potential benefit of coffee in multiple chronic medical conditions such as cardiovascular disease, diabetes, and certain types of cancers, as well as for all-cause mortality.”
“It’s plausible that a moderate amount of coffee intake a day will not cause big physiologic changes, and moderate coffee intake may link with other characteristics” of moderate behavior that result in average or better than average outcomes, Dr. Krahn commented. “These results add to the existing data in a different and large population,” which strengthens the case that moderate coffee intake isn’t harmful, he said.
The study received no commercial funding. Dr. Kim and Dr. Krahn had no disclosures. The senior author on Dr. Kim’s study, Gregory M. Marcus, MD, has been a consultant to Johnson & Johnson and Incardia, has an equity interest in Incardia, and has received research funding from Baylis, Eight Sleep, and Medtronic.
SOURCE: Kim EJ et al. Heart Rhythm 2020, abstract D-PO01-032.
Moderate, daily coffee consumption had no apparent adverse effect for triggering incident heart arrhythmias, and even linked with a small but statistically significant drop in arrhythmias in an analysis of prospectively collected data from nearly 300,000 U.K. residents.
“In this large, population-based, prospective study, moderate habitual coffee drinking was associated with a lower risk of arrhythmia,” EunJeong Kim, MD, said at the annual scientific sessions of the Heart Rhythm Society, held online because of COVID-19.
Her analysis found that on average each additional daily cup of coffee that people said they drank reduced the incidence of arrhythmic episodes by a statistically significant 3%, compared with those who drank fewer daily cups. The relationship held for people who reported drinking as many as five or six cups of coffee daily.
“The main message of our study is that it does not appear to be deleterious to continue with moderate amounts of habitual coffee intake regarding a risk of overall arrhythmia,” said Dr. Kim, a cardiac electrophysiologist at the University of California, San Francisco.
Evidence builds for coffee’s safety
The finding adds to a substantial existing evidence base documenting the safety of moderate, habitual coffee drinking when it comes to heart rhythms. For example, a recent report from the Physicians Health Study of nearly 19,000 American men showed a statistically significant decrease in the incidence of atrial fibrillation during an average follow-up of 9 years among men who reported drinking one to three cups of coffee daily (J Am Heart Assoc. 2019 Aug 6;8[15]:e011346). In addition, a recent review of several reports found that “mild-to-moderate habitual consumption of caffeinated beverages, particularly a daily intake of 2-3 cups of coffee or tea, appears to be safe across a broad range of cardiovascular conditions, and may even be beneficial with respect to diabetes mellitus, atherosclerosis, heart failure, arrhythmia and total mortality,” but also concluded that “acute consumption of high doses of caffeine, particularly in the form of energy drinks, is best avoided”(Trends Cardiovasc Med. 2019 Aug;29[6]:345-50). Specifically about cardiac arrhythmias, the review said “while caffeine is commonly considered a trigger for arrhythmias by physicians and patients alike there is minimal evidence to support this misconception. Rather caffeine is associated with a mild reduction in the incidence of atrial fibrillation in observational studies.”
“There has been a lot of public interest about a possible association of caffeine and arrhythmias,” but an adverse effect from daily consumption of a moderate amount of coffee “is more legend and anecdote than fact based,” commented Andrew D. Krahn, MD, an electrophysiologist, professor of medicine, and head of cardiology at the University of British Columbia and St. Paul’s Hospital in Vancouver. “Increasingly we’re finding that there really is nothing here” when the proarrhythmic effects of moderate coffee undergo detailed assessment, he said in an interview.
What the study did
The study run by Dr. Kim and her associates used prospectively collected data from 296,227 participants in the UK Biobank during 2006-2016 who had complete data on their coffee intake and for the other covariables used in the analysis. During an average 5.25 years of follow-up, these people had more than 13,000 incident arrhythmic events, including 4,748 episodes of atrial fibrillation or flutter and 798 supraventricular tachycardia events, as well as fewer numbers of ventricular arrhythmias and many episodes of less clinically relevant events like skipped beats.
The multivariate analysis the researchers ran controlled for more than 20 demographic, lifestyle, and clinical variables, including adjustment for tea intake but not for consumption of other caffeine-containing drinks.
The adjusted analysis showed an average, statistically significant 3% incremental drop in both all incident arrhythmias and in incident atrial fibrillation episodes for each additional cup of coffee drunk a day, for up to 6 daily cups.
A strength of this study is that it included a large number of people, Dr. Krahn noted, and “the UK Biobank includes a very diverse, community-based sample” of people, said Dr. Kim. The analysis excluded people with prevalent arrhythmia at baseline, so the study couldn’t address the impact of coffee consumption in this setting. A limitation of the study is that participants in the UK Biobank are all volunteers, which could result in a selection bias, Dr. Krahn said.
What it tells us
While the main message from the results is that moderate daily coffee drinking is not arrhythmogenic, “it is also possible that coffee is beneficial” based on the small but statistically significant decline in new-onset events, Dr. Kim added. “Multiple studies revealed that caffeine and potentially other constituents in coffee have antioxidant and anti-inflammatory properties. Multiple studies have reported the potential benefit of coffee in multiple chronic medical conditions such as cardiovascular disease, diabetes, and certain types of cancers, as well as for all-cause mortality.”
“It’s plausible that a moderate amount of coffee intake a day will not cause big physiologic changes, and moderate coffee intake may link with other characteristics” of moderate behavior that result in average or better than average outcomes, Dr. Krahn commented. “These results add to the existing data in a different and large population,” which strengthens the case that moderate coffee intake isn’t harmful, he said.
The study received no commercial funding. Dr. Kim and Dr. Krahn had no disclosures. The senior author on Dr. Kim’s study, Gregory M. Marcus, MD, has been a consultant to Johnson & Johnson and Incardia, has an equity interest in Incardia, and has received research funding from Baylis, Eight Sleep, and Medtronic.
SOURCE: Kim EJ et al. Heart Rhythm 2020, abstract D-PO01-032.
Moderate, daily coffee consumption had no apparent adverse effect for triggering incident heart arrhythmias, and even linked with a small but statistically significant drop in arrhythmias in an analysis of prospectively collected data from nearly 300,000 U.K. residents.
“In this large, population-based, prospective study, moderate habitual coffee drinking was associated with a lower risk of arrhythmia,” EunJeong Kim, MD, said at the annual scientific sessions of the Heart Rhythm Society, held online because of COVID-19.
Her analysis found that on average each additional daily cup of coffee that people said they drank reduced the incidence of arrhythmic episodes by a statistically significant 3%, compared with those who drank fewer daily cups. The relationship held for people who reported drinking as many as five or six cups of coffee daily.
“The main message of our study is that it does not appear to be deleterious to continue with moderate amounts of habitual coffee intake regarding a risk of overall arrhythmia,” said Dr. Kim, a cardiac electrophysiologist at the University of California, San Francisco.
Evidence builds for coffee’s safety
The finding adds to a substantial existing evidence base documenting the safety of moderate, habitual coffee drinking when it comes to heart rhythms. For example, a recent report from the Physicians Health Study of nearly 19,000 American men showed a statistically significant decrease in the incidence of atrial fibrillation during an average follow-up of 9 years among men who reported drinking one to three cups of coffee daily (J Am Heart Assoc. 2019 Aug 6;8[15]:e011346). In addition, a recent review of several reports found that “mild-to-moderate habitual consumption of caffeinated beverages, particularly a daily intake of 2-3 cups of coffee or tea, appears to be safe across a broad range of cardiovascular conditions, and may even be beneficial with respect to diabetes mellitus, atherosclerosis, heart failure, arrhythmia and total mortality,” but also concluded that “acute consumption of high doses of caffeine, particularly in the form of energy drinks, is best avoided”(Trends Cardiovasc Med. 2019 Aug;29[6]:345-50). Specifically about cardiac arrhythmias, the review said “while caffeine is commonly considered a trigger for arrhythmias by physicians and patients alike there is minimal evidence to support this misconception. Rather caffeine is associated with a mild reduction in the incidence of atrial fibrillation in observational studies.”
“There has been a lot of public interest about a possible association of caffeine and arrhythmias,” but an adverse effect from daily consumption of a moderate amount of coffee “is more legend and anecdote than fact based,” commented Andrew D. Krahn, MD, an electrophysiologist, professor of medicine, and head of cardiology at the University of British Columbia and St. Paul’s Hospital in Vancouver. “Increasingly we’re finding that there really is nothing here” when the proarrhythmic effects of moderate coffee undergo detailed assessment, he said in an interview.
What the study did
The study run by Dr. Kim and her associates used prospectively collected data from 296,227 participants in the UK Biobank during 2006-2016 who had complete data on their coffee intake and for the other covariables used in the analysis. During an average 5.25 years of follow-up, these people had more than 13,000 incident arrhythmic events, including 4,748 episodes of atrial fibrillation or flutter and 798 supraventricular tachycardia events, as well as fewer numbers of ventricular arrhythmias and many episodes of less clinically relevant events like skipped beats.
The multivariate analysis the researchers ran controlled for more than 20 demographic, lifestyle, and clinical variables, including adjustment for tea intake but not for consumption of other caffeine-containing drinks.
The adjusted analysis showed an average, statistically significant 3% incremental drop in both all incident arrhythmias and in incident atrial fibrillation episodes for each additional cup of coffee drunk a day, for up to 6 daily cups.
A strength of this study is that it included a large number of people, Dr. Krahn noted, and “the UK Biobank includes a very diverse, community-based sample” of people, said Dr. Kim. The analysis excluded people with prevalent arrhythmia at baseline, so the study couldn’t address the impact of coffee consumption in this setting. A limitation of the study is that participants in the UK Biobank are all volunteers, which could result in a selection bias, Dr. Krahn said.
What it tells us
While the main message from the results is that moderate daily coffee drinking is not arrhythmogenic, “it is also possible that coffee is beneficial” based on the small but statistically significant decline in new-onset events, Dr. Kim added. “Multiple studies revealed that caffeine and potentially other constituents in coffee have antioxidant and anti-inflammatory properties. Multiple studies have reported the potential benefit of coffee in multiple chronic medical conditions such as cardiovascular disease, diabetes, and certain types of cancers, as well as for all-cause mortality.”
“It’s plausible that a moderate amount of coffee intake a day will not cause big physiologic changes, and moderate coffee intake may link with other characteristics” of moderate behavior that result in average or better than average outcomes, Dr. Krahn commented. “These results add to the existing data in a different and large population,” which strengthens the case that moderate coffee intake isn’t harmful, he said.
The study received no commercial funding. Dr. Kim and Dr. Krahn had no disclosures. The senior author on Dr. Kim’s study, Gregory M. Marcus, MD, has been a consultant to Johnson & Johnson and Incardia, has an equity interest in Incardia, and has received research funding from Baylis, Eight Sleep, and Medtronic.
SOURCE: Kim EJ et al. Heart Rhythm 2020, abstract D-PO01-032.
FROM HEART RHYTHM 2020
Multisociety roadmap eyes restarting elective cardiac cases
As COVID-19 case levels plateau in some regions, 16 North American cardiovascular societies have released a framework for reintroducing cardiovascular services disrupted by the pandemic.
The consensus document outlines a phased approach to restarting invasive cardiovascular (CV) procedures and diagnostic tests that aims to reduce patient and health care provider exposure to the coronavirus and still provide essential care. It also emphasizes some of the ethical considerations in patient selection and the need for a collaborative approach.
“The key message in our document is we need a new unprecedented collaboration with public health officials so that we can carefully monitor the situation and we’re aware of what’s happening with the penetrance of the pandemic in the community, but they’re aware of the morbidity and mortality that’s occurring on our ever-growing waiting list,” lead author David A. Wood, MD, told theheart.org | Medscape Cardiology.
The recommendations were jointly published May 4 in the Canadian Journal of Cardiology , the Journal of the American College of Cardiology, and The Annals of Thoracic Surgery, and are endorsed by, among others, the American Heart Association, American College of Cardiology (ACC), and Canadian Cardiovascular Society.
The guidance comes as hospitals are facing revenue shortfalls because of canceled elective procedures and resource-intensive COVID-19 cases, prompting some healthcare systems to furlough, lay off, or even fire staff.
“It’s obvious that volumes are down between 40% and 60%,” said Wood, director of the cardiac catheterization laboratory at Vancouver General Hospital and professor of medicine at the University of British Columbia, Canada. “Part of that is that some areas have restricted case volumes totally appropriately and it’s partly because patients are very afraid of coming to the hospital and, unfortunately, are having bad events at home. And some are dying.”
The new report features a detailed table outlining three different response levels: reintroduction of some services (level 2); reintroduction of most services (level 1); and regular services (level 0). It covers a range of services from transthoracic echocardiography and exercise testing with imaging to care for acute coronary syndrome and ST-segment elevation myocardial infarction.
“We’ve learned that we can very quickly turn off the tap and go to doing only 10% of our normal volumes, whether that’s surgery, cath lab, EP, diagnostic tests,” Wood said. “It’s much more difficult to thoughtfully turn the tap part way back on or restart the engine … you don’t just go from 0 to 100 [mph]. You go from 0 to 30 to 60 then maybe to 80 [mph].”
The document also includes eight guiding principles such as:
- The expectation that response levels will be different between regions, and even within a given region.
- A “transparent collaborative plan” for COVID-19 testing and personal protective equipment (PPE) must be in place before restarting cases.
- A less invasive test or alternate imaging modality should be considered, if both tests have similar efficacy.
- In general, a minimally invasive procedure with a shorter length of stay is preferable, if both strategies have similar efficacy and safety.
Although previous reports on cath lab considerations during the pandemic or restarting elective surgeries peg various actions to specific thresholds or time intervals, the language here is noticeably and intentionally broad.
Instead of stating when cardiovascular services should resume, for example, the experts say it’s appropriate to put the guidance document into place if there’s a “sustained reduction” in the rate of new COVID-19 admissions and deaths in the relevant geographic region for a “prespecified time interval.”
As for when or how frequently patients and healthcare providers should be tested for COVID-19, the document encourages “routine screening of all patients prior to any cardiovascular procedure or test.”
Overly prescriptive language in previous documents wasn’t felt to be that helpful, whereas language like “selective” cases and “some” or “most” cardiovascular procedures gives clinicians, health systems, and policy makers flexibility when moving between response levels, Wood explained.
“Different regions might be at different levels based on principles of public health as far as the penetrance of the pandemic in that community, as well as how can you actually do the physical distancing in your hospital or ambulatory clinic. Because, I tell you, that is the Achilles heel,” he said. “Our run rates are going to be determined by testing, the availability of PPE, but also how we’re going to use our existing infrastructure and maintain physical distancing.”
That may mean using telehealth for initial visits, having clinics open earlier in the morning or on weekends, or doing partial volumes for surgery or in the cath lab so patients can be staggered and recover at different times and in different areas of the hospital. “These are very granular, specific infrastructure things that we’ve never really had to consider before,” Wood observed.
The document also had to be flexible and nimble enough to respond to a potential rebound of COVID-19 cases, which in newly released models are projected to rise sharply to 200,000 cases a day and be accompanied by some 3,000 deaths each day by June 1.
“This is my own personal opinion but I think it’s foolish to think that we are going to be able to come back to 100% of the cases we were doing before, even with testing, PPE, and all of that until we have a vaccine,” he said.
Similar to decisions made in preparation for the initial COVID-19 surge, the consensus document outlines the need for ethical considerations when turning the tap back on. This means prioritizing procedures and tests that are likely to benefit more people and to a greater degree, and ensuring that patients are treated fairly and consistently, regardless of their ethnicity, perceived social worth, or ability to pay, said coauthor and ACC President Athena Poppas, MD, Brown University School of Medicine, Providence, Rhode Island.
“It’s an ethical tenet that exists in a lot of places but it’s usually not overtly called out,” Poppas told theheart.org | Medscape Cardiology. “It’s not rationing care; I think people jump to that but it’s actually the opposite of rationing care. It’s about being thoughtful about prioritizing patients.”
“There’s a variety of data that should help in the prioritization, not only how much hospital resources are utilized, that’s on one side, but there’s also the patient risk of delaying or doing a procedure, and then the societal risk,” she said.
Susheel Kodali, MD, of New York–Presbyterian Hospital/Columbia University Irving Medical Center, who recently published recommendations on restructuring structural heart disease practice during the pandemic, said the document is timely as centers, including his own, are trying to restart some outpatient visits, as early as next week.
“They made a point about talking about cohesive partnerships with regional public health officials and I think that’s great. The question is how does that happen,” he told theheart.org | Medscape Cardiology. “In New York, we’re not allowed to do elective cases but what’s considered elective is not so clearly defined. An AS [aortic stenosis] patient that had a syncopal episode 2 weeks ago, is that considered elective or is that semi-urgent? I think that’s one of the challenges and that’s where these partnerships would be useful.”
Other challenges include the need for regional partnerships to better align hospitals, which in the New York area means half a dozen large healthcare systems, and to coordinate care between hospital departments – all of which will be scheduling imaging and OR time for their own backlog of hernia, knee, or hip surgeries.
Finally, there’s the need for a lot of conversation with the patient and their family about returning to a hospital amid a deadly pandemic.
“I had a patient today and the daughter was very concerned about bringing her in,” Kodali said. “She’s in class IV heart failure but her [daughter’s] big concern was: who is she going to be exposed to when she gets the echo? What kind of protection is there for her? Is the tech wearing a mask?
“It’s not just the health care providers that have to have the comfort, but it’s the patients and their families who have to feel comfortable bringing their loved ones here for treatment,” he said. “Because everyone is concerned about the environment.”
Wood reports receiving unrestricted grant support from Edwards Lifesciences and Abbott Vascular and serving as a consultant for Edwards Lifesciences, Medtronic, Abbott Vascular, and Boston Scientific. Poppas reports no relevant conflicts of interest. Kodali reports consultant (honoraria) from Admedus, Meril Life Sciences, JenaValve, and Abbott Vascular; SAB (equity) from Dura Biotech, MicroInterventional Devices, Thubrikar Aortic Valve, Supira, and Admedus; and institutional funding from Edwards Lifesciences, Medtronic, Abbott Vascular, Boston Scientific, and JenaValve.
This article first appeared on Medscape.com.
As COVID-19 case levels plateau in some regions, 16 North American cardiovascular societies have released a framework for reintroducing cardiovascular services disrupted by the pandemic.
The consensus document outlines a phased approach to restarting invasive cardiovascular (CV) procedures and diagnostic tests that aims to reduce patient and health care provider exposure to the coronavirus and still provide essential care. It also emphasizes some of the ethical considerations in patient selection and the need for a collaborative approach.
“The key message in our document is we need a new unprecedented collaboration with public health officials so that we can carefully monitor the situation and we’re aware of what’s happening with the penetrance of the pandemic in the community, but they’re aware of the morbidity and mortality that’s occurring on our ever-growing waiting list,” lead author David A. Wood, MD, told theheart.org | Medscape Cardiology.
The recommendations were jointly published May 4 in the Canadian Journal of Cardiology , the Journal of the American College of Cardiology, and The Annals of Thoracic Surgery, and are endorsed by, among others, the American Heart Association, American College of Cardiology (ACC), and Canadian Cardiovascular Society.
The guidance comes as hospitals are facing revenue shortfalls because of canceled elective procedures and resource-intensive COVID-19 cases, prompting some healthcare systems to furlough, lay off, or even fire staff.
“It’s obvious that volumes are down between 40% and 60%,” said Wood, director of the cardiac catheterization laboratory at Vancouver General Hospital and professor of medicine at the University of British Columbia, Canada. “Part of that is that some areas have restricted case volumes totally appropriately and it’s partly because patients are very afraid of coming to the hospital and, unfortunately, are having bad events at home. And some are dying.”
The new report features a detailed table outlining three different response levels: reintroduction of some services (level 2); reintroduction of most services (level 1); and regular services (level 0). It covers a range of services from transthoracic echocardiography and exercise testing with imaging to care for acute coronary syndrome and ST-segment elevation myocardial infarction.
“We’ve learned that we can very quickly turn off the tap and go to doing only 10% of our normal volumes, whether that’s surgery, cath lab, EP, diagnostic tests,” Wood said. “It’s much more difficult to thoughtfully turn the tap part way back on or restart the engine … you don’t just go from 0 to 100 [mph]. You go from 0 to 30 to 60 then maybe to 80 [mph].”
The document also includes eight guiding principles such as:
- The expectation that response levels will be different between regions, and even within a given region.
- A “transparent collaborative plan” for COVID-19 testing and personal protective equipment (PPE) must be in place before restarting cases.
- A less invasive test or alternate imaging modality should be considered, if both tests have similar efficacy.
- In general, a minimally invasive procedure with a shorter length of stay is preferable, if both strategies have similar efficacy and safety.
Although previous reports on cath lab considerations during the pandemic or restarting elective surgeries peg various actions to specific thresholds or time intervals, the language here is noticeably and intentionally broad.
Instead of stating when cardiovascular services should resume, for example, the experts say it’s appropriate to put the guidance document into place if there’s a “sustained reduction” in the rate of new COVID-19 admissions and deaths in the relevant geographic region for a “prespecified time interval.”
As for when or how frequently patients and healthcare providers should be tested for COVID-19, the document encourages “routine screening of all patients prior to any cardiovascular procedure or test.”
Overly prescriptive language in previous documents wasn’t felt to be that helpful, whereas language like “selective” cases and “some” or “most” cardiovascular procedures gives clinicians, health systems, and policy makers flexibility when moving between response levels, Wood explained.
“Different regions might be at different levels based on principles of public health as far as the penetrance of the pandemic in that community, as well as how can you actually do the physical distancing in your hospital or ambulatory clinic. Because, I tell you, that is the Achilles heel,” he said. “Our run rates are going to be determined by testing, the availability of PPE, but also how we’re going to use our existing infrastructure and maintain physical distancing.”
That may mean using telehealth for initial visits, having clinics open earlier in the morning or on weekends, or doing partial volumes for surgery or in the cath lab so patients can be staggered and recover at different times and in different areas of the hospital. “These are very granular, specific infrastructure things that we’ve never really had to consider before,” Wood observed.
The document also had to be flexible and nimble enough to respond to a potential rebound of COVID-19 cases, which in newly released models are projected to rise sharply to 200,000 cases a day and be accompanied by some 3,000 deaths each day by June 1.
“This is my own personal opinion but I think it’s foolish to think that we are going to be able to come back to 100% of the cases we were doing before, even with testing, PPE, and all of that until we have a vaccine,” he said.
Similar to decisions made in preparation for the initial COVID-19 surge, the consensus document outlines the need for ethical considerations when turning the tap back on. This means prioritizing procedures and tests that are likely to benefit more people and to a greater degree, and ensuring that patients are treated fairly and consistently, regardless of their ethnicity, perceived social worth, or ability to pay, said coauthor and ACC President Athena Poppas, MD, Brown University School of Medicine, Providence, Rhode Island.
“It’s an ethical tenet that exists in a lot of places but it’s usually not overtly called out,” Poppas told theheart.org | Medscape Cardiology. “It’s not rationing care; I think people jump to that but it’s actually the opposite of rationing care. It’s about being thoughtful about prioritizing patients.”
“There’s a variety of data that should help in the prioritization, not only how much hospital resources are utilized, that’s on one side, but there’s also the patient risk of delaying or doing a procedure, and then the societal risk,” she said.
Susheel Kodali, MD, of New York–Presbyterian Hospital/Columbia University Irving Medical Center, who recently published recommendations on restructuring structural heart disease practice during the pandemic, said the document is timely as centers, including his own, are trying to restart some outpatient visits, as early as next week.
“They made a point about talking about cohesive partnerships with regional public health officials and I think that’s great. The question is how does that happen,” he told theheart.org | Medscape Cardiology. “In New York, we’re not allowed to do elective cases but what’s considered elective is not so clearly defined. An AS [aortic stenosis] patient that had a syncopal episode 2 weeks ago, is that considered elective or is that semi-urgent? I think that’s one of the challenges and that’s where these partnerships would be useful.”
Other challenges include the need for regional partnerships to better align hospitals, which in the New York area means half a dozen large healthcare systems, and to coordinate care between hospital departments – all of which will be scheduling imaging and OR time for their own backlog of hernia, knee, or hip surgeries.
Finally, there’s the need for a lot of conversation with the patient and their family about returning to a hospital amid a deadly pandemic.
“I had a patient today and the daughter was very concerned about bringing her in,” Kodali said. “She’s in class IV heart failure but her [daughter’s] big concern was: who is she going to be exposed to when she gets the echo? What kind of protection is there for her? Is the tech wearing a mask?
“It’s not just the health care providers that have to have the comfort, but it’s the patients and their families who have to feel comfortable bringing their loved ones here for treatment,” he said. “Because everyone is concerned about the environment.”
Wood reports receiving unrestricted grant support from Edwards Lifesciences and Abbott Vascular and serving as a consultant for Edwards Lifesciences, Medtronic, Abbott Vascular, and Boston Scientific. Poppas reports no relevant conflicts of interest. Kodali reports consultant (honoraria) from Admedus, Meril Life Sciences, JenaValve, and Abbott Vascular; SAB (equity) from Dura Biotech, MicroInterventional Devices, Thubrikar Aortic Valve, Supira, and Admedus; and institutional funding from Edwards Lifesciences, Medtronic, Abbott Vascular, Boston Scientific, and JenaValve.
This article first appeared on Medscape.com.
As COVID-19 case levels plateau in some regions, 16 North American cardiovascular societies have released a framework for reintroducing cardiovascular services disrupted by the pandemic.
The consensus document outlines a phased approach to restarting invasive cardiovascular (CV) procedures and diagnostic tests that aims to reduce patient and health care provider exposure to the coronavirus and still provide essential care. It also emphasizes some of the ethical considerations in patient selection and the need for a collaborative approach.
“The key message in our document is we need a new unprecedented collaboration with public health officials so that we can carefully monitor the situation and we’re aware of what’s happening with the penetrance of the pandemic in the community, but they’re aware of the morbidity and mortality that’s occurring on our ever-growing waiting list,” lead author David A. Wood, MD, told theheart.org | Medscape Cardiology.
The recommendations were jointly published May 4 in the Canadian Journal of Cardiology , the Journal of the American College of Cardiology, and The Annals of Thoracic Surgery, and are endorsed by, among others, the American Heart Association, American College of Cardiology (ACC), and Canadian Cardiovascular Society.
The guidance comes as hospitals are facing revenue shortfalls because of canceled elective procedures and resource-intensive COVID-19 cases, prompting some healthcare systems to furlough, lay off, or even fire staff.
“It’s obvious that volumes are down between 40% and 60%,” said Wood, director of the cardiac catheterization laboratory at Vancouver General Hospital and professor of medicine at the University of British Columbia, Canada. “Part of that is that some areas have restricted case volumes totally appropriately and it’s partly because patients are very afraid of coming to the hospital and, unfortunately, are having bad events at home. And some are dying.”
The new report features a detailed table outlining three different response levels: reintroduction of some services (level 2); reintroduction of most services (level 1); and regular services (level 0). It covers a range of services from transthoracic echocardiography and exercise testing with imaging to care for acute coronary syndrome and ST-segment elevation myocardial infarction.
“We’ve learned that we can very quickly turn off the tap and go to doing only 10% of our normal volumes, whether that’s surgery, cath lab, EP, diagnostic tests,” Wood said. “It’s much more difficult to thoughtfully turn the tap part way back on or restart the engine … you don’t just go from 0 to 100 [mph]. You go from 0 to 30 to 60 then maybe to 80 [mph].”
The document also includes eight guiding principles such as:
- The expectation that response levels will be different between regions, and even within a given region.
- A “transparent collaborative plan” for COVID-19 testing and personal protective equipment (PPE) must be in place before restarting cases.
- A less invasive test or alternate imaging modality should be considered, if both tests have similar efficacy.
- In general, a minimally invasive procedure with a shorter length of stay is preferable, if both strategies have similar efficacy and safety.
Although previous reports on cath lab considerations during the pandemic or restarting elective surgeries peg various actions to specific thresholds or time intervals, the language here is noticeably and intentionally broad.
Instead of stating when cardiovascular services should resume, for example, the experts say it’s appropriate to put the guidance document into place if there’s a “sustained reduction” in the rate of new COVID-19 admissions and deaths in the relevant geographic region for a “prespecified time interval.”
As for when or how frequently patients and healthcare providers should be tested for COVID-19, the document encourages “routine screening of all patients prior to any cardiovascular procedure or test.”
Overly prescriptive language in previous documents wasn’t felt to be that helpful, whereas language like “selective” cases and “some” or “most” cardiovascular procedures gives clinicians, health systems, and policy makers flexibility when moving between response levels, Wood explained.
“Different regions might be at different levels based on principles of public health as far as the penetrance of the pandemic in that community, as well as how can you actually do the physical distancing in your hospital or ambulatory clinic. Because, I tell you, that is the Achilles heel,” he said. “Our run rates are going to be determined by testing, the availability of PPE, but also how we’re going to use our existing infrastructure and maintain physical distancing.”
That may mean using telehealth for initial visits, having clinics open earlier in the morning or on weekends, or doing partial volumes for surgery or in the cath lab so patients can be staggered and recover at different times and in different areas of the hospital. “These are very granular, specific infrastructure things that we’ve never really had to consider before,” Wood observed.
The document also had to be flexible and nimble enough to respond to a potential rebound of COVID-19 cases, which in newly released models are projected to rise sharply to 200,000 cases a day and be accompanied by some 3,000 deaths each day by June 1.
“This is my own personal opinion but I think it’s foolish to think that we are going to be able to come back to 100% of the cases we were doing before, even with testing, PPE, and all of that until we have a vaccine,” he said.
Similar to decisions made in preparation for the initial COVID-19 surge, the consensus document outlines the need for ethical considerations when turning the tap back on. This means prioritizing procedures and tests that are likely to benefit more people and to a greater degree, and ensuring that patients are treated fairly and consistently, regardless of their ethnicity, perceived social worth, or ability to pay, said coauthor and ACC President Athena Poppas, MD, Brown University School of Medicine, Providence, Rhode Island.
“It’s an ethical tenet that exists in a lot of places but it’s usually not overtly called out,” Poppas told theheart.org | Medscape Cardiology. “It’s not rationing care; I think people jump to that but it’s actually the opposite of rationing care. It’s about being thoughtful about prioritizing patients.”
“There’s a variety of data that should help in the prioritization, not only how much hospital resources are utilized, that’s on one side, but there’s also the patient risk of delaying or doing a procedure, and then the societal risk,” she said.
Susheel Kodali, MD, of New York–Presbyterian Hospital/Columbia University Irving Medical Center, who recently published recommendations on restructuring structural heart disease practice during the pandemic, said the document is timely as centers, including his own, are trying to restart some outpatient visits, as early as next week.
“They made a point about talking about cohesive partnerships with regional public health officials and I think that’s great. The question is how does that happen,” he told theheart.org | Medscape Cardiology. “In New York, we’re not allowed to do elective cases but what’s considered elective is not so clearly defined. An AS [aortic stenosis] patient that had a syncopal episode 2 weeks ago, is that considered elective or is that semi-urgent? I think that’s one of the challenges and that’s where these partnerships would be useful.”
Other challenges include the need for regional partnerships to better align hospitals, which in the New York area means half a dozen large healthcare systems, and to coordinate care between hospital departments – all of which will be scheduling imaging and OR time for their own backlog of hernia, knee, or hip surgeries.
Finally, there’s the need for a lot of conversation with the patient and their family about returning to a hospital amid a deadly pandemic.
“I had a patient today and the daughter was very concerned about bringing her in,” Kodali said. “She’s in class IV heart failure but her [daughter’s] big concern was: who is she going to be exposed to when she gets the echo? What kind of protection is there for her? Is the tech wearing a mask?
“It’s not just the health care providers that have to have the comfort, but it’s the patients and their families who have to feel comfortable bringing their loved ones here for treatment,” he said. “Because everyone is concerned about the environment.”
Wood reports receiving unrestricted grant support from Edwards Lifesciences and Abbott Vascular and serving as a consultant for Edwards Lifesciences, Medtronic, Abbott Vascular, and Boston Scientific. Poppas reports no relevant conflicts of interest. Kodali reports consultant (honoraria) from Admedus, Meril Life Sciences, JenaValve, and Abbott Vascular; SAB (equity) from Dura Biotech, MicroInterventional Devices, Thubrikar Aortic Valve, Supira, and Admedus; and institutional funding from Edwards Lifesciences, Medtronic, Abbott Vascular, Boston Scientific, and JenaValve.
This article first appeared on Medscape.com.
Hydroxychloroquine-triggered QTc-interval prolongations mount in COVID-19 patients
The potential for serious arrhythmias from hydroxychloroquine treatment of COVID-19 patients received further documentation from a pair of studies released on May 1, casting further doubt on whether the uncertain benefit from this or related drugs to infected patients is worth the clear risks the agents pose.
A report from 90 confirmed COVID-19 patients treated with hydroxychloroquine at one Boston hospital during March-April 2020 identified a significantly prolonged, corrected QT (QTc) interval of at least 500 msec in 18 patients (20%), which included 10 patients whose QTc rose by at least 60 msec above baseline, and a total of 21 patients (23%) having a notable prolongation (JAMA Cardiol. 2020 May 4. doi: 10.1001/jamacardio.2020.1834). This series included one patient who developed torsades de pointes following treatment with hydroxychloroquine and azithromycin, “which to our knowledge has yet to be reported elsewhere in the literature,” the report said.
The second report, from a single center in Lyon, France, included 40 confirmed COVID-19 patients treated with hydroxychloroquine during 2 weeks in late March, and found that 37 (93%) had some increase in the QTc interval, including 14 patients (36%) with an increase of at least 60 msec, and 7 patients (18%) whose QTc rose to at least 500 msec (JAMA Cardiol. 2020 May. doi: 10.1001/jamacardio.2020.1787). However, none of the 40 patients in this series developed an identified ventricular arrhythmia. All patients in both studies received hydroxychloroquine for at least 1 day, and roughly half the patients in each series also received concurrent azithromycin, another drug that can prolong the QTc interval and that has been frequently used in combination with hydroxychloroquine as an unproven COVID-19 treatment cocktail.
These two reports, as well as prior report from Brazil on COVID-19 patients treated with chloroquine diphosphate (JAMA Netw Open. 2020;3[4]:e208857), “underscore the potential risk associated with widespread use of hydroxychloroquine and the combination of hydroxychloroquine and azithromycin in ambulatory patients with known or suspected COVID-19. Understanding whether this risk is worth taking in the absence of evidence of therapeutic efficacy creates a knowledge gap that needs to be addressed,” wrote Robert O. Bonow, MD, a professor of medicine at Northwestern University in Chicago, and coauthors in an editorial that accompanied the two reports (JAMA Cardiol. 2020 May 4;doi: 10.1001/jamacardio.2020.1782). The editorial cited two recently-begun prospective trials, ORCHID and RECOVERY, that are more systematically assessing the safety and efficacy of hydroxychloroquine treatment in COVID-19 patients.
The findings lend further support to a Safety Communication from the U.S. Food and Drug Administration on April 24 that reminded clinicians that the Emergency Use Authorization for hydroxychloroquine and chloroquine in COVID-19 patients that the FDA issued on March 28 applied to only certain hospitalized patients or those enrolled in clinical trials. The Safety Communication also said that agency was aware of reports of adverse arrhythmia events when COVID-19 patients received these drugs outside a hospital setting as well as uninfected people who had received one of these drugs for preventing infection.
In addition, leaders of the American College of Cardiology, the American Heart Association, and the Heart Rhythm Society on April 10 issued a summary of considerations when using hydroxychloroquine and azithromycin to treat COVID-19 patients, and noted that a way to minimized the risk from these drugs is to withhold them from patients with a QTc interval of 500 msec or greater at baseline (J Am Coll Cardiol. 2020 Apr 10. doi: 10.1016/j.jacc.2020.04.016). The summary also highlighted the need for regular ECG monitoring of COVID-19 patients who receive drugs that can prolong the QTc interval, and recommended withdrawing treatment from patients when their QTc exceeds the 500 msec threshold.
None of the authors of the two reports and editorial had relevant commercial disclosures.
The potential for serious arrhythmias from hydroxychloroquine treatment of COVID-19 patients received further documentation from a pair of studies released on May 1, casting further doubt on whether the uncertain benefit from this or related drugs to infected patients is worth the clear risks the agents pose.
A report from 90 confirmed COVID-19 patients treated with hydroxychloroquine at one Boston hospital during March-April 2020 identified a significantly prolonged, corrected QT (QTc) interval of at least 500 msec in 18 patients (20%), which included 10 patients whose QTc rose by at least 60 msec above baseline, and a total of 21 patients (23%) having a notable prolongation (JAMA Cardiol. 2020 May 4. doi: 10.1001/jamacardio.2020.1834). This series included one patient who developed torsades de pointes following treatment with hydroxychloroquine and azithromycin, “which to our knowledge has yet to be reported elsewhere in the literature,” the report said.
The second report, from a single center in Lyon, France, included 40 confirmed COVID-19 patients treated with hydroxychloroquine during 2 weeks in late March, and found that 37 (93%) had some increase in the QTc interval, including 14 patients (36%) with an increase of at least 60 msec, and 7 patients (18%) whose QTc rose to at least 500 msec (JAMA Cardiol. 2020 May. doi: 10.1001/jamacardio.2020.1787). However, none of the 40 patients in this series developed an identified ventricular arrhythmia. All patients in both studies received hydroxychloroquine for at least 1 day, and roughly half the patients in each series also received concurrent azithromycin, another drug that can prolong the QTc interval and that has been frequently used in combination with hydroxychloroquine as an unproven COVID-19 treatment cocktail.
These two reports, as well as prior report from Brazil on COVID-19 patients treated with chloroquine diphosphate (JAMA Netw Open. 2020;3[4]:e208857), “underscore the potential risk associated with widespread use of hydroxychloroquine and the combination of hydroxychloroquine and azithromycin in ambulatory patients with known or suspected COVID-19. Understanding whether this risk is worth taking in the absence of evidence of therapeutic efficacy creates a knowledge gap that needs to be addressed,” wrote Robert O. Bonow, MD, a professor of medicine at Northwestern University in Chicago, and coauthors in an editorial that accompanied the two reports (JAMA Cardiol. 2020 May 4;doi: 10.1001/jamacardio.2020.1782). The editorial cited two recently-begun prospective trials, ORCHID and RECOVERY, that are more systematically assessing the safety and efficacy of hydroxychloroquine treatment in COVID-19 patients.
The findings lend further support to a Safety Communication from the U.S. Food and Drug Administration on April 24 that reminded clinicians that the Emergency Use Authorization for hydroxychloroquine and chloroquine in COVID-19 patients that the FDA issued on March 28 applied to only certain hospitalized patients or those enrolled in clinical trials. The Safety Communication also said that agency was aware of reports of adverse arrhythmia events when COVID-19 patients received these drugs outside a hospital setting as well as uninfected people who had received one of these drugs for preventing infection.
In addition, leaders of the American College of Cardiology, the American Heart Association, and the Heart Rhythm Society on April 10 issued a summary of considerations when using hydroxychloroquine and azithromycin to treat COVID-19 patients, and noted that a way to minimized the risk from these drugs is to withhold them from patients with a QTc interval of 500 msec or greater at baseline (J Am Coll Cardiol. 2020 Apr 10. doi: 10.1016/j.jacc.2020.04.016). The summary also highlighted the need for regular ECG monitoring of COVID-19 patients who receive drugs that can prolong the QTc interval, and recommended withdrawing treatment from patients when their QTc exceeds the 500 msec threshold.
None of the authors of the two reports and editorial had relevant commercial disclosures.
The potential for serious arrhythmias from hydroxychloroquine treatment of COVID-19 patients received further documentation from a pair of studies released on May 1, casting further doubt on whether the uncertain benefit from this or related drugs to infected patients is worth the clear risks the agents pose.
A report from 90 confirmed COVID-19 patients treated with hydroxychloroquine at one Boston hospital during March-April 2020 identified a significantly prolonged, corrected QT (QTc) interval of at least 500 msec in 18 patients (20%), which included 10 patients whose QTc rose by at least 60 msec above baseline, and a total of 21 patients (23%) having a notable prolongation (JAMA Cardiol. 2020 May 4. doi: 10.1001/jamacardio.2020.1834). This series included one patient who developed torsades de pointes following treatment with hydroxychloroquine and azithromycin, “which to our knowledge has yet to be reported elsewhere in the literature,” the report said.
The second report, from a single center in Lyon, France, included 40 confirmed COVID-19 patients treated with hydroxychloroquine during 2 weeks in late March, and found that 37 (93%) had some increase in the QTc interval, including 14 patients (36%) with an increase of at least 60 msec, and 7 patients (18%) whose QTc rose to at least 500 msec (JAMA Cardiol. 2020 May. doi: 10.1001/jamacardio.2020.1787). However, none of the 40 patients in this series developed an identified ventricular arrhythmia. All patients in both studies received hydroxychloroquine for at least 1 day, and roughly half the patients in each series also received concurrent azithromycin, another drug that can prolong the QTc interval and that has been frequently used in combination with hydroxychloroquine as an unproven COVID-19 treatment cocktail.
These two reports, as well as prior report from Brazil on COVID-19 patients treated with chloroquine diphosphate (JAMA Netw Open. 2020;3[4]:e208857), “underscore the potential risk associated with widespread use of hydroxychloroquine and the combination of hydroxychloroquine and azithromycin in ambulatory patients with known or suspected COVID-19. Understanding whether this risk is worth taking in the absence of evidence of therapeutic efficacy creates a knowledge gap that needs to be addressed,” wrote Robert O. Bonow, MD, a professor of medicine at Northwestern University in Chicago, and coauthors in an editorial that accompanied the two reports (JAMA Cardiol. 2020 May 4;doi: 10.1001/jamacardio.2020.1782). The editorial cited two recently-begun prospective trials, ORCHID and RECOVERY, that are more systematically assessing the safety and efficacy of hydroxychloroquine treatment in COVID-19 patients.
The findings lend further support to a Safety Communication from the U.S. Food and Drug Administration on April 24 that reminded clinicians that the Emergency Use Authorization for hydroxychloroquine and chloroquine in COVID-19 patients that the FDA issued on March 28 applied to only certain hospitalized patients or those enrolled in clinical trials. The Safety Communication also said that agency was aware of reports of adverse arrhythmia events when COVID-19 patients received these drugs outside a hospital setting as well as uninfected people who had received one of these drugs for preventing infection.
In addition, leaders of the American College of Cardiology, the American Heart Association, and the Heart Rhythm Society on April 10 issued a summary of considerations when using hydroxychloroquine and azithromycin to treat COVID-19 patients, and noted that a way to minimized the risk from these drugs is to withhold them from patients with a QTc interval of 500 msec or greater at baseline (J Am Coll Cardiol. 2020 Apr 10. doi: 10.1016/j.jacc.2020.04.016). The summary also highlighted the need for regular ECG monitoring of COVID-19 patients who receive drugs that can prolong the QTc interval, and recommended withdrawing treatment from patients when their QTc exceeds the 500 msec threshold.
None of the authors of the two reports and editorial had relevant commercial disclosures.
FROM JAMA CARDIOLOGY
Out-of-hospital cardiac arrests soar during COVID-19 in Italy
Out-of-hospital cardiac arrests increased 58% during the peak of the COVID-19 outbreak in the hard-hit region of Lombardy, Italy, compared with the same period last year, a new analysis shows.
During the first 40 days of the outbreak beginning Feb. 21, four provinces in northern Italy reported 362 cases of out-of-hospital cardiac arrest compared with 229 during the same period in 2019.
The increases in these provinces varied in magnitude from 18% in Mantua, where there were 1,688 confirmed COVID-19 cases, to 187% in Lodi, which had 2,116 COVID-19 cases. The Cremona province, which had the highest number of COVID-19 cases at 3,869, saw a 143% increase in out-of-hospital cardiac arrests.
The mortality rate in the field was 14.9 percentage points higher in 2020 than in 2019 among patients in whom resuscitation was attempted by emergency medical services (EMS), Enrico Baldi, MD, University of Pavia, Italy, and colleagues reported in a letter April 29 in the New England Journal of Medicine.
“The sex and age of the patients were similar in the 2020 and 2019 periods, but in 2020, the incidence of out-of-hospital cardiac arrest due to a medical cause was 6.5 percentage points higher, the incidence of out-of-hospital cardiac arrest at home was 7.3 percentage points higher, and the incidence of unwitnessed cardiac arrest was 11.3 percentage points higher,” the authors wrote.
Patients were also less likely to receive cardiopulmonary resuscitation from bystanders in 2020 vs 2019 (–15.6 percentage points) and were more likely to die before reaching the hospital when resuscitation was attempted by EMS (+14.9 percentage points).
Among all patients, the death rate in the field increased 11.4 percentage points during the outbreak, from 77.3% in 2019 to 88.7% in 2020.
The cumulative incidence of out-of-hospital cardiac arrest in 2020 was “strongly associated” with the cumulative incidence of COVID-19 (Spearman rank correlation coefficient, 0.87; 95% confidence interval, 0.83-0.91) and the spike in cases “followed the time course of the COVID-19 outbreak,” the researchers noted.
A total of 103 patients, who arrested out of hospital and were diagnosed with or suspected of having COVID-19, “account for 77.4% of the increase in cases of out-of-hospital cardiac arrest observed in these provinces in 2020,” the investigators noted.
As the pandemic has taken hold, hospitals and physicians across the United States are also voicing concerns about the drop in the number of patients presenting with myocardial infarction (MI) or stroke.
Nearly one-third of Americans (29%) report having delayed or avoided medical care because of concerns of catching COVID-19, according to a new poll released April 28 from the American College of Emergency Physicians (ACEP) and Morning Consult, a global data research firm.
Despite many emergency departments reporting a decline in patient volume, 74% of respondents said they were worried about hospital wait times and overcrowding. Another 59% expressed concerns about being turned away from the hospital or doctor’s office.
At the same time, the survey found strong support for emergency physicians and 73% of respondents said they were concerned about overstressing the health care system.
The drop-off in Americans seeking care for MI and strokes nationally prompted eight professional societies – including ACEP, the American Heart Association, and the Association of Black Cardiologists – to issue a joint statement urging those experiencing symptoms to call 911 and seek care for these life-threatening events.
The authors have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Out-of-hospital cardiac arrests increased 58% during the peak of the COVID-19 outbreak in the hard-hit region of Lombardy, Italy, compared with the same period last year, a new analysis shows.
During the first 40 days of the outbreak beginning Feb. 21, four provinces in northern Italy reported 362 cases of out-of-hospital cardiac arrest compared with 229 during the same period in 2019.
The increases in these provinces varied in magnitude from 18% in Mantua, where there were 1,688 confirmed COVID-19 cases, to 187% in Lodi, which had 2,116 COVID-19 cases. The Cremona province, which had the highest number of COVID-19 cases at 3,869, saw a 143% increase in out-of-hospital cardiac arrests.
The mortality rate in the field was 14.9 percentage points higher in 2020 than in 2019 among patients in whom resuscitation was attempted by emergency medical services (EMS), Enrico Baldi, MD, University of Pavia, Italy, and colleagues reported in a letter April 29 in the New England Journal of Medicine.
“The sex and age of the patients were similar in the 2020 and 2019 periods, but in 2020, the incidence of out-of-hospital cardiac arrest due to a medical cause was 6.5 percentage points higher, the incidence of out-of-hospital cardiac arrest at home was 7.3 percentage points higher, and the incidence of unwitnessed cardiac arrest was 11.3 percentage points higher,” the authors wrote.
Patients were also less likely to receive cardiopulmonary resuscitation from bystanders in 2020 vs 2019 (–15.6 percentage points) and were more likely to die before reaching the hospital when resuscitation was attempted by EMS (+14.9 percentage points).
Among all patients, the death rate in the field increased 11.4 percentage points during the outbreak, from 77.3% in 2019 to 88.7% in 2020.
The cumulative incidence of out-of-hospital cardiac arrest in 2020 was “strongly associated” with the cumulative incidence of COVID-19 (Spearman rank correlation coefficient, 0.87; 95% confidence interval, 0.83-0.91) and the spike in cases “followed the time course of the COVID-19 outbreak,” the researchers noted.
A total of 103 patients, who arrested out of hospital and were diagnosed with or suspected of having COVID-19, “account for 77.4% of the increase in cases of out-of-hospital cardiac arrest observed in these provinces in 2020,” the investigators noted.
As the pandemic has taken hold, hospitals and physicians across the United States are also voicing concerns about the drop in the number of patients presenting with myocardial infarction (MI) or stroke.
Nearly one-third of Americans (29%) report having delayed or avoided medical care because of concerns of catching COVID-19, according to a new poll released April 28 from the American College of Emergency Physicians (ACEP) and Morning Consult, a global data research firm.
Despite many emergency departments reporting a decline in patient volume, 74% of respondents said they were worried about hospital wait times and overcrowding. Another 59% expressed concerns about being turned away from the hospital or doctor’s office.
At the same time, the survey found strong support for emergency physicians and 73% of respondents said they were concerned about overstressing the health care system.
The drop-off in Americans seeking care for MI and strokes nationally prompted eight professional societies – including ACEP, the American Heart Association, and the Association of Black Cardiologists – to issue a joint statement urging those experiencing symptoms to call 911 and seek care for these life-threatening events.
The authors have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Out-of-hospital cardiac arrests increased 58% during the peak of the COVID-19 outbreak in the hard-hit region of Lombardy, Italy, compared with the same period last year, a new analysis shows.
During the first 40 days of the outbreak beginning Feb. 21, four provinces in northern Italy reported 362 cases of out-of-hospital cardiac arrest compared with 229 during the same period in 2019.
The increases in these provinces varied in magnitude from 18% in Mantua, where there were 1,688 confirmed COVID-19 cases, to 187% in Lodi, which had 2,116 COVID-19 cases. The Cremona province, which had the highest number of COVID-19 cases at 3,869, saw a 143% increase in out-of-hospital cardiac arrests.
The mortality rate in the field was 14.9 percentage points higher in 2020 than in 2019 among patients in whom resuscitation was attempted by emergency medical services (EMS), Enrico Baldi, MD, University of Pavia, Italy, and colleagues reported in a letter April 29 in the New England Journal of Medicine.
“The sex and age of the patients were similar in the 2020 and 2019 periods, but in 2020, the incidence of out-of-hospital cardiac arrest due to a medical cause was 6.5 percentage points higher, the incidence of out-of-hospital cardiac arrest at home was 7.3 percentage points higher, and the incidence of unwitnessed cardiac arrest was 11.3 percentage points higher,” the authors wrote.
Patients were also less likely to receive cardiopulmonary resuscitation from bystanders in 2020 vs 2019 (–15.6 percentage points) and were more likely to die before reaching the hospital when resuscitation was attempted by EMS (+14.9 percentage points).
Among all patients, the death rate in the field increased 11.4 percentage points during the outbreak, from 77.3% in 2019 to 88.7% in 2020.
The cumulative incidence of out-of-hospital cardiac arrest in 2020 was “strongly associated” with the cumulative incidence of COVID-19 (Spearman rank correlation coefficient, 0.87; 95% confidence interval, 0.83-0.91) and the spike in cases “followed the time course of the COVID-19 outbreak,” the researchers noted.
A total of 103 patients, who arrested out of hospital and were diagnosed with or suspected of having COVID-19, “account for 77.4% of the increase in cases of out-of-hospital cardiac arrest observed in these provinces in 2020,” the investigators noted.
As the pandemic has taken hold, hospitals and physicians across the United States are also voicing concerns about the drop in the number of patients presenting with myocardial infarction (MI) or stroke.
Nearly one-third of Americans (29%) report having delayed or avoided medical care because of concerns of catching COVID-19, according to a new poll released April 28 from the American College of Emergency Physicians (ACEP) and Morning Consult, a global data research firm.
Despite many emergency departments reporting a decline in patient volume, 74% of respondents said they were worried about hospital wait times and overcrowding. Another 59% expressed concerns about being turned away from the hospital or doctor’s office.
At the same time, the survey found strong support for emergency physicians and 73% of respondents said they were concerned about overstressing the health care system.
The drop-off in Americans seeking care for MI and strokes nationally prompted eight professional societies – including ACEP, the American Heart Association, and the Association of Black Cardiologists – to issue a joint statement urging those experiencing symptoms to call 911 and seek care for these life-threatening events.
The authors have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Yale’s COVID-19 inpatient protocol: Hydroxychloroquine plus/minus tocilizumab
Hydroxychloroquine is currently first-line, and tocilizumab second-line, for people hospitalized with polymerase chain reaction–confirmed COVID-19 in the Yale New Haven (Conn.) Health System, which operates hospitals across Connecticut, many of them hard hit by the pandemic.
Patients enter the treatment algorithm if they have an oxygen saturation at or below 93% on room air or chronic supplementation, or by being acutely ill with fever, respiratory signs, or opacities on chest x-ray, plus risk factors for severe illness such as age over 60 years, chronic heart or lung disease, immunosuppression, diabetes, hypertension, or obesity, which makes it harder to ventilate.
Physicians at Yale have seen both presentations – oxygen desaturation and frank illness – and “wanted to make sure we weren’t missing anyone,” said Nihar Desai, MD, a Yale cardiologist who is helping to coordinate the health system’s response to COVID-19.
In either case, the initial treatment is the same at Yale hospitals: hydroxychloroquine for 5 days, with tocilizumab (Actemra) considered when not contraindicated and oxygen requirements reach or pass 3 L, or 2 L with C-reactive protein levels above 70 mg/L.
Patients are put on prophylactic enoxaparin to thin the blood unless contraindicated; inflammatory, cardiac, kidney, and other markers are checked every 12 or 24 hours; and ECGs are taken daily if telemetry isn’t used. Chest x-rays are repeated if clinical signs worsen, and transthoracic echocardiograms are ordered for suspected heart problems.
ICUs are notified early if the clinical situation worsens because patients “can deteriorate very quickly; at the first sign of trouble, people are really aggressive,” said Dr. Desai, also the associate chief of clinical operations in the Section of Cardiovascular Medicine at the Yale University, New Haven.
The haze of battle
Yale has updated its algorithm several times since the virus first hit Connecticut weeks ago. A team including pulmonologists, critical care physicians, pharmacologists, infectious disease experts, and cardiologists, including Dr. Desai, are constantly monitoring the situation and making changes as new information comes in.
Much of what’s being done at Yale and elsewhere is empiric because there are simply not much data to go on. “We are trying to do the best we can” in “the haze of battle. People really came together quickly to develop this. One hopes we never have to go through anything like this again,” he said.
Hydroxychloroquine is first-line at Yale because in-vitro data show potent inhibition of the virus and possible clinical benefit, which is about as good as evidence gets at the moment. Also, “it’s cheap, it’s been used for decades, and people are relatively comfortable with it,” Dr. Desai said.
Tocilizumab, an interleukin-6 (IL-6) receptor antagonist, is second-line because it might counter the cytokine storm thought to be at least partly responsible for severe complications, and retrospective data suggest possible benefit. The antiviral remdesivir and IL-6 blocker sarulimab (Kevzara) are also potential candidates, available through clinical trials.
Dr. Desai wanted to share the algorithm with other providers because, he noted, “there are a lot of places that may not have all the resources we have.”
His home institution, Yale New Haven Hospital, is almost half full with COVID-19 patients, at more than 400.
A moving target
Yale’s approach is similar in confirmed COVID-19 cases already in respiratory failure, including those on mechanical ventilation and extracorporeal membrane oxygenation: hydroxychloroquine and possibly tocilizumab, but also methylprednisolone if clinical status worsens or inflammatory markers go up. The steroid is for additional help battling the cytokine storm, Dr. Desai said.
The degree of anticoagulation in the ICU is based on d-dimer levels or suspicion or confirmation of venous thromboembolism. Telemetry is monitored closely for QTc prolongation, and point of care ultrasound is considered to check left ventricular function in the setting of markedly increased cardiac troponin levels, ECG abnormalities, or hemodynamic instability.
Previous versions of Yale’s algorithm included HIV protease inhibitors, but they were pulled after a recent trial found no benefit. Frequency of monitoring was also reduced from every 8 hours because it didn’t improve decision making and put staff collecting specimens at risk (N Engl J Med. 2020 Mar 18. doi: 10.1056/NEJMoa2001282).
Anticoagulation was added to newer versions after it became clear that COVID-19 is prothrombotic. “We are still seeing thrombotic events that might warrant further intensification,” Dr. Desai said.
Newer algorithms also have Yale watching QTc intervals more closely. It’s unclear if the prolongation risk is caused by the infection or hydroxychloroquine.
On April 24, the Food and Drug Administration reiterated it’s concern about the arrhythmia risk with hydroxychloroquine and emphasized that it should only be used for COVID-19 patients when they are hospitalized and it is not feasible for them to participate in a clinical trial.
To help keep patients safe, ECGs from confirmed or suspected COVID-19 cases are now first in line to be reviewed by cardiologists across Yale hospitals to pick up prolongations and notify providers as soon as possible. Hydroxychloroquine is held if there are no other explanations.
Cardiologists are on the fontline at Yale and elsewhere, Dr. Desai said, because heart complications like myocarditis and arrhythmias emerged early as common problems in hospitalized patients.
[email protected]
This article was updated with the latest treatment algorithm on 5/6/2020.
Hydroxychloroquine is currently first-line, and tocilizumab second-line, for people hospitalized with polymerase chain reaction–confirmed COVID-19 in the Yale New Haven (Conn.) Health System, which operates hospitals across Connecticut, many of them hard hit by the pandemic.
Patients enter the treatment algorithm if they have an oxygen saturation at or below 93% on room air or chronic supplementation, or by being acutely ill with fever, respiratory signs, or opacities on chest x-ray, plus risk factors for severe illness such as age over 60 years, chronic heart or lung disease, immunosuppression, diabetes, hypertension, or obesity, which makes it harder to ventilate.
Physicians at Yale have seen both presentations – oxygen desaturation and frank illness – and “wanted to make sure we weren’t missing anyone,” said Nihar Desai, MD, a Yale cardiologist who is helping to coordinate the health system’s response to COVID-19.
In either case, the initial treatment is the same at Yale hospitals: hydroxychloroquine for 5 days, with tocilizumab (Actemra) considered when not contraindicated and oxygen requirements reach or pass 3 L, or 2 L with C-reactive protein levels above 70 mg/L.
Patients are put on prophylactic enoxaparin to thin the blood unless contraindicated; inflammatory, cardiac, kidney, and other markers are checked every 12 or 24 hours; and ECGs are taken daily if telemetry isn’t used. Chest x-rays are repeated if clinical signs worsen, and transthoracic echocardiograms are ordered for suspected heart problems.
ICUs are notified early if the clinical situation worsens because patients “can deteriorate very quickly; at the first sign of trouble, people are really aggressive,” said Dr. Desai, also the associate chief of clinical operations in the Section of Cardiovascular Medicine at the Yale University, New Haven.
The haze of battle
Yale has updated its algorithm several times since the virus first hit Connecticut weeks ago. A team including pulmonologists, critical care physicians, pharmacologists, infectious disease experts, and cardiologists, including Dr. Desai, are constantly monitoring the situation and making changes as new information comes in.
Much of what’s being done at Yale and elsewhere is empiric because there are simply not much data to go on. “We are trying to do the best we can” in “the haze of battle. People really came together quickly to develop this. One hopes we never have to go through anything like this again,” he said.
Hydroxychloroquine is first-line at Yale because in-vitro data show potent inhibition of the virus and possible clinical benefit, which is about as good as evidence gets at the moment. Also, “it’s cheap, it’s been used for decades, and people are relatively comfortable with it,” Dr. Desai said.
Tocilizumab, an interleukin-6 (IL-6) receptor antagonist, is second-line because it might counter the cytokine storm thought to be at least partly responsible for severe complications, and retrospective data suggest possible benefit. The antiviral remdesivir and IL-6 blocker sarulimab (Kevzara) are also potential candidates, available through clinical trials.
Dr. Desai wanted to share the algorithm with other providers because, he noted, “there are a lot of places that may not have all the resources we have.”
His home institution, Yale New Haven Hospital, is almost half full with COVID-19 patients, at more than 400.
A moving target
Yale’s approach is similar in confirmed COVID-19 cases already in respiratory failure, including those on mechanical ventilation and extracorporeal membrane oxygenation: hydroxychloroquine and possibly tocilizumab, but also methylprednisolone if clinical status worsens or inflammatory markers go up. The steroid is for additional help battling the cytokine storm, Dr. Desai said.
The degree of anticoagulation in the ICU is based on d-dimer levels or suspicion or confirmation of venous thromboembolism. Telemetry is monitored closely for QTc prolongation, and point of care ultrasound is considered to check left ventricular function in the setting of markedly increased cardiac troponin levels, ECG abnormalities, or hemodynamic instability.
Previous versions of Yale’s algorithm included HIV protease inhibitors, but they were pulled after a recent trial found no benefit. Frequency of monitoring was also reduced from every 8 hours because it didn’t improve decision making and put staff collecting specimens at risk (N Engl J Med. 2020 Mar 18. doi: 10.1056/NEJMoa2001282).
Anticoagulation was added to newer versions after it became clear that COVID-19 is prothrombotic. “We are still seeing thrombotic events that might warrant further intensification,” Dr. Desai said.
Newer algorithms also have Yale watching QTc intervals more closely. It’s unclear if the prolongation risk is caused by the infection or hydroxychloroquine.
On April 24, the Food and Drug Administration reiterated it’s concern about the arrhythmia risk with hydroxychloroquine and emphasized that it should only be used for COVID-19 patients when they are hospitalized and it is not feasible for them to participate in a clinical trial.
To help keep patients safe, ECGs from confirmed or suspected COVID-19 cases are now first in line to be reviewed by cardiologists across Yale hospitals to pick up prolongations and notify providers as soon as possible. Hydroxychloroquine is held if there are no other explanations.
Cardiologists are on the fontline at Yale and elsewhere, Dr. Desai said, because heart complications like myocarditis and arrhythmias emerged early as common problems in hospitalized patients.
[email protected]
This article was updated with the latest treatment algorithm on 5/6/2020.
Hydroxychloroquine is currently first-line, and tocilizumab second-line, for people hospitalized with polymerase chain reaction–confirmed COVID-19 in the Yale New Haven (Conn.) Health System, which operates hospitals across Connecticut, many of them hard hit by the pandemic.
Patients enter the treatment algorithm if they have an oxygen saturation at or below 93% on room air or chronic supplementation, or by being acutely ill with fever, respiratory signs, or opacities on chest x-ray, plus risk factors for severe illness such as age over 60 years, chronic heart or lung disease, immunosuppression, diabetes, hypertension, or obesity, which makes it harder to ventilate.
Physicians at Yale have seen both presentations – oxygen desaturation and frank illness – and “wanted to make sure we weren’t missing anyone,” said Nihar Desai, MD, a Yale cardiologist who is helping to coordinate the health system’s response to COVID-19.
In either case, the initial treatment is the same at Yale hospitals: hydroxychloroquine for 5 days, with tocilizumab (Actemra) considered when not contraindicated and oxygen requirements reach or pass 3 L, or 2 L with C-reactive protein levels above 70 mg/L.
Patients are put on prophylactic enoxaparin to thin the blood unless contraindicated; inflammatory, cardiac, kidney, and other markers are checked every 12 or 24 hours; and ECGs are taken daily if telemetry isn’t used. Chest x-rays are repeated if clinical signs worsen, and transthoracic echocardiograms are ordered for suspected heart problems.
ICUs are notified early if the clinical situation worsens because patients “can deteriorate very quickly; at the first sign of trouble, people are really aggressive,” said Dr. Desai, also the associate chief of clinical operations in the Section of Cardiovascular Medicine at the Yale University, New Haven.
The haze of battle
Yale has updated its algorithm several times since the virus first hit Connecticut weeks ago. A team including pulmonologists, critical care physicians, pharmacologists, infectious disease experts, and cardiologists, including Dr. Desai, are constantly monitoring the situation and making changes as new information comes in.
Much of what’s being done at Yale and elsewhere is empiric because there are simply not much data to go on. “We are trying to do the best we can” in “the haze of battle. People really came together quickly to develop this. One hopes we never have to go through anything like this again,” he said.
Hydroxychloroquine is first-line at Yale because in-vitro data show potent inhibition of the virus and possible clinical benefit, which is about as good as evidence gets at the moment. Also, “it’s cheap, it’s been used for decades, and people are relatively comfortable with it,” Dr. Desai said.
Tocilizumab, an interleukin-6 (IL-6) receptor antagonist, is second-line because it might counter the cytokine storm thought to be at least partly responsible for severe complications, and retrospective data suggest possible benefit. The antiviral remdesivir and IL-6 blocker sarulimab (Kevzara) are also potential candidates, available through clinical trials.
Dr. Desai wanted to share the algorithm with other providers because, he noted, “there are a lot of places that may not have all the resources we have.”
His home institution, Yale New Haven Hospital, is almost half full with COVID-19 patients, at more than 400.
A moving target
Yale’s approach is similar in confirmed COVID-19 cases already in respiratory failure, including those on mechanical ventilation and extracorporeal membrane oxygenation: hydroxychloroquine and possibly tocilizumab, but also methylprednisolone if clinical status worsens or inflammatory markers go up. The steroid is for additional help battling the cytokine storm, Dr. Desai said.
The degree of anticoagulation in the ICU is based on d-dimer levels or suspicion or confirmation of venous thromboembolism. Telemetry is monitored closely for QTc prolongation, and point of care ultrasound is considered to check left ventricular function in the setting of markedly increased cardiac troponin levels, ECG abnormalities, or hemodynamic instability.
Previous versions of Yale’s algorithm included HIV protease inhibitors, but they were pulled after a recent trial found no benefit. Frequency of monitoring was also reduced from every 8 hours because it didn’t improve decision making and put staff collecting specimens at risk (N Engl J Med. 2020 Mar 18. doi: 10.1056/NEJMoa2001282).
Anticoagulation was added to newer versions after it became clear that COVID-19 is prothrombotic. “We are still seeing thrombotic events that might warrant further intensification,” Dr. Desai said.
Newer algorithms also have Yale watching QTc intervals more closely. It’s unclear if the prolongation risk is caused by the infection or hydroxychloroquine.
On April 24, the Food and Drug Administration reiterated it’s concern about the arrhythmia risk with hydroxychloroquine and emphasized that it should only be used for COVID-19 patients when they are hospitalized and it is not feasible for them to participate in a clinical trial.
To help keep patients safe, ECGs from confirmed or suspected COVID-19 cases are now first in line to be reviewed by cardiologists across Yale hospitals to pick up prolongations and notify providers as soon as possible. Hydroxychloroquine is held if there are no other explanations.
Cardiologists are on the fontline at Yale and elsewhere, Dr. Desai said, because heart complications like myocarditis and arrhythmias emerged early as common problems in hospitalized patients.
[email protected]
This article was updated with the latest treatment algorithm on 5/6/2020.
Survey: Hydroxychloroquine use fairly common in COVID-19
One of five physicians in front-line treatment roles has prescribed hydroxychloroquine for COVID-19, according to a new survey from health care market research company InCrowd.
The most common treatments were acetaminophen, prescribed to 82% of patients, antibiotics (41%), and bronchodilators (40%), InCrowd said after surveying 203 primary care physicians, pediatricians, and emergency medicine or critical care physicians who are treating at least 20 patients with flulike symptoms.
On April 24, the Food and Drug Administration warned against the use of hydroxychloroquine or chloroquine outside of hospitals and clinical trials.
The InCrowd survey, which took place April 14-15 and is the fourth in a series investigating COVID-19’s impact on physicians, showed that access to testing was up to 82% in mid-April, compared with 67% in March and 20% in late February. The April respondents also were twice as likely (59% vs. 24% in March) to say that their facilities were prepared to treat patients, InCrowd reported.
“U.S. physicians report sluggish optimism around preparedness, safety, and institutional efforts, while many worry about the future, including a second outbreak and job security,” the company said in a separate written statement.
The average estimate for a return to normal was just over 6 months among respondents, and only 28% believed that their facility was prepared for a second outbreak later in the year, InCrowd noted.
On a personal level, 45% of the respondents were concerned about the safety of their job. An emergency/critical care physician from Tennessee said, “We’ve been cutting back on staff due to overall revenue reductions, but have increased acuity and complexity which requires more staffing. This puts even more of a burden on those of us still here.”
Support for institutional responses to slow the pandemic was strongest for state governments, which gained approval from 54% of front-line physicians, up from 33% in March. Actions taken by the federal government were supported by 21% of respondents, compared with 38% for the World Health Organization and 46% for governments outside the United States, InCrowd reported.
Suggestions for further actions by state and local authorities included this comment from an emergency/critical care physician in Florida: “Continued, broad and properly enforced stay at home and social distancing measures MUST remain in place to keep citizens and healthcare workers safe, and the latter alive and in adequate supply.”
One of five physicians in front-line treatment roles has prescribed hydroxychloroquine for COVID-19, according to a new survey from health care market research company InCrowd.
The most common treatments were acetaminophen, prescribed to 82% of patients, antibiotics (41%), and bronchodilators (40%), InCrowd said after surveying 203 primary care physicians, pediatricians, and emergency medicine or critical care physicians who are treating at least 20 patients with flulike symptoms.
On April 24, the Food and Drug Administration warned against the use of hydroxychloroquine or chloroquine outside of hospitals and clinical trials.
The InCrowd survey, which took place April 14-15 and is the fourth in a series investigating COVID-19’s impact on physicians, showed that access to testing was up to 82% in mid-April, compared with 67% in March and 20% in late February. The April respondents also were twice as likely (59% vs. 24% in March) to say that their facilities were prepared to treat patients, InCrowd reported.
“U.S. physicians report sluggish optimism around preparedness, safety, and institutional efforts, while many worry about the future, including a second outbreak and job security,” the company said in a separate written statement.
The average estimate for a return to normal was just over 6 months among respondents, and only 28% believed that their facility was prepared for a second outbreak later in the year, InCrowd noted.
On a personal level, 45% of the respondents were concerned about the safety of their job. An emergency/critical care physician from Tennessee said, “We’ve been cutting back on staff due to overall revenue reductions, but have increased acuity and complexity which requires more staffing. This puts even more of a burden on those of us still here.”
Support for institutional responses to slow the pandemic was strongest for state governments, which gained approval from 54% of front-line physicians, up from 33% in March. Actions taken by the federal government were supported by 21% of respondents, compared with 38% for the World Health Organization and 46% for governments outside the United States, InCrowd reported.
Suggestions for further actions by state and local authorities included this comment from an emergency/critical care physician in Florida: “Continued, broad and properly enforced stay at home and social distancing measures MUST remain in place to keep citizens and healthcare workers safe, and the latter alive and in adequate supply.”
One of five physicians in front-line treatment roles has prescribed hydroxychloroquine for COVID-19, according to a new survey from health care market research company InCrowd.
The most common treatments were acetaminophen, prescribed to 82% of patients, antibiotics (41%), and bronchodilators (40%), InCrowd said after surveying 203 primary care physicians, pediatricians, and emergency medicine or critical care physicians who are treating at least 20 patients with flulike symptoms.
On April 24, the Food and Drug Administration warned against the use of hydroxychloroquine or chloroquine outside of hospitals and clinical trials.
The InCrowd survey, which took place April 14-15 and is the fourth in a series investigating COVID-19’s impact on physicians, showed that access to testing was up to 82% in mid-April, compared with 67% in March and 20% in late February. The April respondents also were twice as likely (59% vs. 24% in March) to say that their facilities were prepared to treat patients, InCrowd reported.
“U.S. physicians report sluggish optimism around preparedness, safety, and institutional efforts, while many worry about the future, including a second outbreak and job security,” the company said in a separate written statement.
The average estimate for a return to normal was just over 6 months among respondents, and only 28% believed that their facility was prepared for a second outbreak later in the year, InCrowd noted.
On a personal level, 45% of the respondents were concerned about the safety of their job. An emergency/critical care physician from Tennessee said, “We’ve been cutting back on staff due to overall revenue reductions, but have increased acuity and complexity which requires more staffing. This puts even more of a burden on those of us still here.”
Support for institutional responses to slow the pandemic was strongest for state governments, which gained approval from 54% of front-line physicians, up from 33% in March. Actions taken by the federal government were supported by 21% of respondents, compared with 38% for the World Health Organization and 46% for governments outside the United States, InCrowd reported.
Suggestions for further actions by state and local authorities included this comment from an emergency/critical care physician in Florida: “Continued, broad and properly enforced stay at home and social distancing measures MUST remain in place to keep citizens and healthcare workers safe, and the latter alive and in adequate supply.”