In the Journals

Cardiovascular considerations of COVID-19: Current evidence and remaining knowledge gaps

Sahil A. Parikh

Two recently published reviews assessed the current literature relating to CV considerations of COVID-19 and identified knowledge gaps that remain

One review, authored by Kevin J. Clerkin, MD, MSc, assistant professor of medicine at Columbia University Vagelos College of Physicians and Surgeons, and colleagues, was published in Circulation. The other, authored by Elissa Driggin, MD, resident in internal medicine at NewYork-Presbyterian Hospital and Columbia University Irving Medical Center, and colleagues, was published in the Journal of the American College of Cardiology.

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Two reviews, one published in Circulation, the other in the Journal of the American College of Cardiology assessed the current literature relating to CV considerations of COVID-19 and identified knowledge gaps that remain.

The following are key points from both reviews:

  • CV comorbidities are common in patients with COVID-19. Early studies indicate the prevalence of hypertension in this population is 15% to 31%, 7% to 10% have diabetes and 2.5% to 15% have CHD or CVD. All of these comorbidity rates “are notably higher than the overall case-fatality rate (2.3%),” Driggin and colleagues wrote.
    “What we’ve learned is that patients with preexisting cardiovascular disease are at high risk as far as developing complications from COVID-19,” Sahil A. Parikh, MD, director of endovascular services at Columbia University Medical Center and assistant professor of medicine at the Columbia University College of Physicians and Surgeons, and an author of the review by Driggin and colleagues, told Healio. “We are learning minute-to-minute with this disease, both with our own experience and what is being reported around the world.”
  • CVD mechanisms overlap with the pathways regulating function of the immune system, so “prevalent CVD may be a marker of accelerated immunologic aging/dysregulation and relate indirectly to COVID-19 prognosis,” Driggin and colleagues wrote. “An increased frequency of adverse CVD events post COVID-19 infection might also play a role in prognosis, similar to other viral infections such as influenza with mechanistic underpinnings, which are complex, multifactorial and bidirectional.”
  • Although the precise mechanism of cardiac involvement with COVID-19 is not yet known, “one potential mechanism is direct myocardial involvement mediated via ACE2,” Clerkin and colleagues wrote. “Other suggested mechanisms of COVID-19-related cardiac involvement include a cytokine storm, mediated by an imbalanced response among subtypes of T helper cells, and hypoxia-induced excessive intracellular calcium leading to cardiac myocyte apoptosis.”
    Parikh said the virus appears to be affecting cells that express the ACE2 protein, including the myocardial and vascular cells. “We have seen episodes of myocardial injury that are detected by elevated biomarkers such as troponin,” he said. “Particularly difficult to manage is the acute myocarditis. A cadre of patients, especially the really sick ones, have myocarditis, often associated with congestive heart failure, if not cardiogenic shock. In those patients, the risk of a life-threatening outcome is even higher. Treatments are not well-established, and the treatments we offer from the respiratory and circulatory standpoints are mostly supportive. Some are managed with medications but some have required mechanical circulatory support, and by the time it gets to that, the outcomes are relatively grave and survival is very low.”
  • Because of the possible ACE2 pathway connection, there has been concern over whether renin-angiotensin-aldosterone system antagonists such as ACE inhibitors and angiotensin receptor blockers may confer COVID-19 risk, but there is no clear evidence. In March, the American Heart Association/Heart Failure Society of America/American College of Cardiology and the European Society of Cardiology issued statements to dispel misinformation circulating about this association between RAAS antagonists and COVID-19 risk, and recommended patients not stop taking those drugs for treatment of conditions such as hypertension, unless advised by a physician.
  • Past viral outbreaks have placed patients with heart transplants at elevated risk, and infection control measures must be stringently enforced when managing these patients. The cardiology societies recommend avoiding using hearts from donors with known or suspected COVID-19.
  • Myocardial injury, myocarditis and ACS appear to be risks in patients with COVID-19, but the true prevalence of these is not yet known. “It is not known if the presence of cardiovascular comorbid conditions poses independent risk or whether this is mediated by other factors (eg, age),” Clerkin and colleagues wrote. “Myocardial injury is present in more than a quarter of critical cases and presents in two patterns: acute myocardial injury and dysfunction on presentation and myocardial injury that develops as illness severity intensifies.”
  • Early studies have noted prevalence rates in patients with COVID-19 were 16.7% for arrhythmias and 23% for HF, but more must be learned about connections between the conditions.
    “There have been cases of cardiac arrest reported, but many appear to be because of hypoxemia or changes in the intracardiac pressures due to the lung disease,” Parikh told Healio. “Also, there is a coagulation disorder that goes along with severe COVID-19 illness. Paradoxically, these patients are at risk for developing clots and/or bleeding because of a condition called disseminating intravascular coagulation. There is dysregulation of the clotting cascade for reasons that are not entirely clear. Those are parameters that have to be watched very carefully.”
  • Certain treatments being tested for patients with COVID-19 may produce adverse CV events. For example, lopinavir/ritonavir may result in QT and PR prolongation, may interfere with P2Y12 inhibitors and may cause myopathy when used with statins; lopinavir/ritonavir and ribavirin may impact anticoagulant dosing; chloroquine may cause dilated or restrictive cardiomyopathy or conduction abnormalities and may interfere with certain beta-blockers; chloroquine and hydroxychloroquine may raise risk for torsades de pointes in patients with electrolyte abnormalities or those using other QT-prolonging drugs; and methylprednisolone can cause fluid retention, electrolyte derangement and hypertension and may interfere with warfarin, Driggin and colleagues wrote.

“Efficient use of resources, including leveraging of the telehealth capabilities, and optimal adherence to preventive population-wide and provider-level measures will enable the transition from this critical period until the disease outbreak is contained,” Driggin and colleagues wrote.

Also a problem, Parikh said, is that care for patients presenting with typical CVD and MI may be delayed because of resources being devoted to patients with COVID-19. “Even in the absence of being overwhelmed, we have been increasingly circumspect about our practices because we have to protect our staff,” he said. “For patients with STEMI, normally we would bypass the emergency department to speed up the reperfusion, but now we are having every patient come to the ER for screening for COVID-positive symptoms and a related condition like myocarditis, which could look like a STEMI.”

Healio and Cardiology Today are following this news and will report on new developments.

For the latest news on COVID-19 including case counts, information about the global public health response and emerging research, please visit the COVID-19 Resource Center on Healio. – by Erik Swain

For more information:

Sahil A. Parikh, MD, can be reached at CUMC/Herbert Irving Pavilion, 161 Fort Washington Ave.,  New York, NY 10032; email: sap2196@cumc.columbia.edu.

Disclosures: Clerkin and colleagues report no relevant financial disclosures. Driggin reports no relevant financial disclosures. Parikh reports he received institutional grants/research support from Abbott Vascular, the NIH, Shockwave Medical, Silk Road Medical, Surmodics and TriReme Medical; consultant fees from Abiomed and Terumo; and fees for advisory board participation from Abbott, Boston Scientific, Cardiovascular Systems Inc., Medtronic and Philips. Please see the Driggin study for all other authors’ relevant financial disclosures.

Sahil A. Parikh

Two recently published reviews assessed the current literature relating to CV considerations of COVID-19 and identified knowledge gaps that remain

One review, authored by Kevin J. Clerkin, MD, MSc, assistant professor of medicine at Columbia University Vagelos College of Physicians and Surgeons, and colleagues, was published in Circulation. The other, authored by Elissa Driggin, MD, resident in internal medicine at NewYork-Presbyterian Hospital and Columbia University Irving Medical Center, and colleagues, was published in the Journal of the American College of Cardiology.

#
Two reviews, one published in Circulation, the other in the Journal of the American College of Cardiology assessed the current literature relating to CV considerations of COVID-19 and identified knowledge gaps that remain.

The following are key points from both reviews:

  • CV comorbidities are common in patients with COVID-19. Early studies indicate the prevalence of hypertension in this population is 15% to 31%, 7% to 10% have diabetes and 2.5% to 15% have CHD or CVD. All of these comorbidity rates “are notably higher than the overall case-fatality rate (2.3%),” Driggin and colleagues wrote.
    “What we’ve learned is that patients with preexisting cardiovascular disease are at high risk as far as developing complications from COVID-19,” Sahil A. Parikh, MD, director of endovascular services at Columbia University Medical Center and assistant professor of medicine at the Columbia University College of Physicians and Surgeons, and an author of the review by Driggin and colleagues, told Healio. “We are learning minute-to-minute with this disease, both with our own experience and what is being reported around the world.”
  • CVD mechanisms overlap with the pathways regulating function of the immune system, so “prevalent CVD may be a marker of accelerated immunologic aging/dysregulation and relate indirectly to COVID-19 prognosis,” Driggin and colleagues wrote. “An increased frequency of adverse CVD events post COVID-19 infection might also play a role in prognosis, similar to other viral infections such as influenza with mechanistic underpinnings, which are complex, multifactorial and bidirectional.”
  • Although the precise mechanism of cardiac involvement with COVID-19 is not yet known, “one potential mechanism is direct myocardial involvement mediated via ACE2,” Clerkin and colleagues wrote. “Other suggested mechanisms of COVID-19-related cardiac involvement include a cytokine storm, mediated by an imbalanced response among subtypes of T helper cells, and hypoxia-induced excessive intracellular calcium leading to cardiac myocyte apoptosis.”
    Parikh said the virus appears to be affecting cells that express the ACE2 protein, including the myocardial and vascular cells. “We have seen episodes of myocardial injury that are detected by elevated biomarkers such as troponin,” he said. “Particularly difficult to manage is the acute myocarditis. A cadre of patients, especially the really sick ones, have myocarditis, often associated with congestive heart failure, if not cardiogenic shock. In those patients, the risk of a life-threatening outcome is even higher. Treatments are not well-established, and the treatments we offer from the respiratory and circulatory standpoints are mostly supportive. Some are managed with medications but some have required mechanical circulatory support, and by the time it gets to that, the outcomes are relatively grave and survival is very low.”
  • Because of the possible ACE2 pathway connection, there has been concern over whether renin-angiotensin-aldosterone system antagonists such as ACE inhibitors and angiotensin receptor blockers may confer COVID-19 risk, but there is no clear evidence. In March, the American Heart Association/Heart Failure Society of America/American College of Cardiology and the European Society of Cardiology issued statements to dispel misinformation circulating about this association between RAAS antagonists and COVID-19 risk, and recommended patients not stop taking those drugs for treatment of conditions such as hypertension, unless advised by a physician.
  • Past viral outbreaks have placed patients with heart transplants at elevated risk, and infection control measures must be stringently enforced when managing these patients. The cardiology societies recommend avoiding using hearts from donors with known or suspected COVID-19.
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  • Myocardial injury, myocarditis and ACS appear to be risks in patients with COVID-19, but the true prevalence of these is not yet known. “It is not known if the presence of cardiovascular comorbid conditions poses independent risk or whether this is mediated by other factors (eg, age),” Clerkin and colleagues wrote. “Myocardial injury is present in more than a quarter of critical cases and presents in two patterns: acute myocardial injury and dysfunction on presentation and myocardial injury that develops as illness severity intensifies.”
  • Early studies have noted prevalence rates in patients with COVID-19 were 16.7% for arrhythmias and 23% for HF, but more must be learned about connections between the conditions.
    “There have been cases of cardiac arrest reported, but many appear to be because of hypoxemia or changes in the intracardiac pressures due to the lung disease,” Parikh told Healio. “Also, there is a coagulation disorder that goes along with severe COVID-19 illness. Paradoxically, these patients are at risk for developing clots and/or bleeding because of a condition called disseminating intravascular coagulation. There is dysregulation of the clotting cascade for reasons that are not entirely clear. Those are parameters that have to be watched very carefully.”
  • Certain treatments being tested for patients with COVID-19 may produce adverse CV events. For example, lopinavir/ritonavir may result in QT and PR prolongation, may interfere with P2Y12 inhibitors and may cause myopathy when used with statins; lopinavir/ritonavir and ribavirin may impact anticoagulant dosing; chloroquine may cause dilated or restrictive cardiomyopathy or conduction abnormalities and may interfere with certain beta-blockers; chloroquine and hydroxychloroquine may raise risk for torsades de pointes in patients with electrolyte abnormalities or those using other QT-prolonging drugs; and methylprednisolone can cause fluid retention, electrolyte derangement and hypertension and may interfere with warfarin, Driggin and colleagues wrote.

“Efficient use of resources, including leveraging of the telehealth capabilities, and optimal adherence to preventive population-wide and provider-level measures will enable the transition from this critical period until the disease outbreak is contained,” Driggin and colleagues wrote.

Also a problem, Parikh said, is that care for patients presenting with typical CVD and MI may be delayed because of resources being devoted to patients with COVID-19. “Even in the absence of being overwhelmed, we have been increasingly circumspect about our practices because we have to protect our staff,” he said. “For patients with STEMI, normally we would bypass the emergency department to speed up the reperfusion, but now we are having every patient come to the ER for screening for COVID-positive symptoms and a related condition like myocarditis, which could look like a STEMI.”

Healio and Cardiology Today are following this news and will report on new developments.

For the latest news on COVID-19 including case counts, information about the global public health response and emerging research, please visit the COVID-19 Resource Center on Healio. – by Erik Swain

For more information:

Sahil A. Parikh, MD, can be reached at CUMC/Herbert Irving Pavilion, 161 Fort Washington Ave.,  New York, NY 10032; email: sap2196@cumc.columbia.edu.

Disclosures: Clerkin and colleagues report no relevant financial disclosures. Driggin reports no relevant financial disclosures. Parikh reports he received institutional grants/research support from Abbott Vascular, the NIH, Shockwave Medical, Silk Road Medical, Surmodics and TriReme Medical; consultant fees from Abiomed and Terumo; and fees for advisory board participation from Abbott, Boston Scientific, Cardiovascular Systems Inc., Medtronic and Philips. Please see the Driggin study for all other authors’ relevant financial disclosures.

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