April 01, 2020
By Douglas L. Jennings, PharmD, FACC, FAHA, FCCP, FHFSA, BCPS
The COVID-19 continues to ravage countries around the world, inflicting mass casualties, overwhelming healthcare systems, and paralyzing daily life for hundreds of millions of people. The vast majority of the narrative surrounding this virus has focused on the respiratory complications. However, COVID-19 interacts with cardiovascular system on multiple levels, increasing morbidity in patients with underlying cardiovascular conditions, and provoking myocardial injury.
The SARS-CoV-2 virus has a predilection for patients with cardiovascular diseases. The increased presence of cardiovascular comorbidities with COVID-19 was most notable among those with more severe disease. In one cohort of 191 patients from Wuhan, China, any comorbidity was present in 48% (67% of non-survivors), hypertension was present in 30% (48% of non-survivors), diabetes in 19% (31% of non-survivors), and cardiovascular disease in 8% (13% of non-survivors). Likewise, data from the National Health Commission (NHC) of China demonstrated that 35% of patients diagnosed with COVID-19 had hypertension and 17% had coronary heart disease.
In addition to disproportionately affecting patients with cardiovascular comorbidities, the SARS-CoV-2 virus can directly inflict injury to the myocardium. In one early study of 138 hospitalized patients with COVID-19 in Wuhan China, cardiac injury (elevated high sensitivity Troponin I or new ECG or echocardiographic abnormalities) was present in 7.2% of patients overall, and in 22% that required ICU care. Clinically this injury can manifest as mild heart failure symptoms in minor cases, but in more severe circumstances patients can deteriorate in cardiogenic shock and cardiovascular collapse.
The exact mechanism of cardiac involvement in COVID-19 remains under investigation. One potential mechanism is direct myocardial involvement mediated via ACE2. SARS-CoV-2 infection is caused by binding of the viral surface spike protein to the human angiotensin-converting enzyme 2 (ACE2) receptor following activation of the spike protein by transmembrane protease serine 2. ACE2 is expressed in the lung and appears to be the predominant portal of entry. ACE2 is also highly expressed in the heart, counteracting the effects of angiotensin II in states with excessive activation of the renin-angiotensin system such as hypertension.
ACE2 converts angiotensin II to angiotensin 1-7, thereby diminishing vasoconstriction mediated by the renin angiotensin system. The use of ACE inhibitors and angiotensin receptor blockers are common in cardiovascular disorders. There are conflicting data from studies demonstrating whether these drugs increase or have minimal effect on ACE2 levels, which is relevant as the ACE2 is required for viral entry into cells. On this basis losartan is being studied for potential mitigation of lung injury among both inpatients and outpatients with COVID-19. However at this time nearly all major cardiovascular societies have recommended against adding or stopping RAAS antagonists in this setting, unless done on clinical grounds independently of COVID-19. These recommendations are based on the lack of evidence currently available on their potential benefit or harm in patients with COVID-19.
In conclusion, cardiovascular complications are rapidly emerging as a key secondary threat in COVID-19 behind respiratory disease. Our understanding of the pathophysiology of myocardial injury is evolving, and clinicians caring for patients with COVID-19 must diligently monitor for myocardial dysfunction. At this time data are insufficient to guide pharmacists, and hence no recommendations should be made for either initiation or discontinuation of ACE inhibitors or angiotensin receptor blockers solely for the purpose of altering the risk of SARS-CoV-2 infection.
Dr Jennings is currently an Associate Professor of Pharmacy at Long Island University and the clinical pharmacist for the Heart Transplant and LVAD teams at NewYork- Presbyterian Hospital Columbia University Irving Medical Center. He is an active researcher in his field, and he has published over 120 peer-reviewed abstracts and manuscripts, primarily focusing on the pharmacotherapy of patients under mechanical circulatory support. As a recognized expert in this area, he has been invited to speak at numerous national and international venues, including meetings in France, Saudia Arabia, India. Finally, Dr. Jennings has been active in professional organizations throughout his career. He is a fellow of the American College of Clinical Pharmacy, the American College of Cardiology, the Heart Failure Society of America, and the American Heart Association.
Clerkin KJ, Fried JA, Raikhelkar J, et al. Coronavirus Disease 2019 (COVID-19) and Cardiovascular Disease [published online ahead of print, 2020 Mar 21]. Circulation. 2020;10.1161/CIRCULATIONAHA.120.046941. doi:10.1161/CIRCULATIONAHA.120.046941