Description and Proposed Management of the Acute COVID-19 Cardiovascular Syndrome

Abstract

Coronavirus disease 2019 (COVID-19) is a rapidly expanding global pandemic caused by severe acute respiratory syndrome coronavirus 2, resulting in significant morbidity and mortality. A substantial minority of patients hospitalized develop an acute COVID-19 cardiovascular syndrome, which can manifest with a variety of clinical presentations but often presents as an acute cardiac injury with cardiomyopathy, ventricular arrhythmias, and hemodynamic instability in the absence of obstructive coronary artery disease. The cause of this injury is uncertain but is suspected to be related to myocarditis, microvascular injury, systemic cytokine-mediated injury, or stress-related cardiomyopathy. Although histologically unproven, severe acute respiratory syndrome coronavirus 2 has the potential to directly replicate within cardiomyocytes and pericytes, leading to viral myocarditis. Systemically elevated cytokines are also known to be cardiotoxic and have the potential to result in profound myocardial injury. Prior experience with severe acute respiratory syndrome coronavirus 1 has helped expedite the evaluation of several promising therapies, including antiviral agents, interleukin-6 inhibitors, and convalescent serum. Management of acute COVID-19 cardiovascular syndrome should involve a multidisciplinary team including intensive care specialists, infectious disease specialists, and cardiologists. Priorities for managing acute COVID-19 cardiovascular syndrome include balancing the goals of minimizing healthcare staff exposure for testing that will not change clinical management with early recognition of the syndrome at a time point at which intervention may be most effective. This article aims to review the best available data on acute COVID-19 cardiovascular syndrome epidemiology, pathogenesis, diagnosis, and treatment. From these data, we propose a surveillance, diagnostic, and management strategy that balances potential patient risks and healthcare staff exposure with improvement in meaningful clinical outcomes.

Keywords: COVID-19; SARS-CoV-2; cardiomyopathies; heart failure; myocarditis.

Figure 1.

Spectrum of the acute coronavirus disease 2019 (COVID-19) cardiovascular syndrome (ACovCS). The spectrum of ACovCS encompasses a variety of cardiovascular syndromes described for patients presenting with COVID-19. Reports of pericardial effusions and cardiac tamponade in patients with COVID-19 have been published. Although the prevalence of pericardial effusion in ACovCS remains uncertain, significant effusions do not appear to be common. Clinical images are representative of the proposed ACovCS disease spectrum, and several, but not all, images are from patients with ACovCS. ^aReported with obstructive, nonobstructive, or no coronary artery disease (CAD). ^bIt is uncertain whether an abnormal troponin is required before the onset of ACovCS, and patients are reported to have either nonobstructive or no epicardial CAD. ^cSignificant uncertainty remains about the cause and prevalence of the acute myocardial injury for patients without obstructive CAD and COVID-19. Although myocarditis, cytokine storm, and stress cardiomyopathy are leading considerations, additional potential causes include hypoxemia and microvascular dysfunction from small vessel thrombosis. NSTEMI indicates non–ST-elevation myocardial infarction; and STEMI, ST-elevation myocardial infarction.

Figure 2.

Potential mechanisms of myocardial injury in acute coronavirus disease 2019 (COVID-19) cardiovascular syndrome. Multiple mechanisms have the potential to result in nonischemic myocardial injury in COVID-19. ^aMyocardial injury defined as cardiac troponin value >99th percentile of the upper reference limit.

Figure 3.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) host cell entry. A, Simplified mechanism of SARS-CoV-2 viral entry to host cells. The SARS-CoV-2 virus expresses spike proteins with an S1 subunit that binds to angiotensin-converting enzyme 2 (ACE2) expressed on host cells. B, After binding to host ACE2, the host transmembrane serine protease 2 (TMPRSS2) performs critical protein priming that leads to conformational changes, viral cell entry, and cell infection. C, Antibodies to the S1 subunit of the spike protein, ACE2, and TMPRSS2 are potential therapeutic targets that reduce viral infectivity.

Figure 4.

Proposed assessment and management of acute coronavirus disease 2019 (COVID-19) cardiovascular syndrome (ACovCS) with acute myocardial injury. Proposed assessment and management of ACovCS with acute myocardial injury. ^aIf the treating clinician has the ability to provide a point-of-care cardiac ultrasonography without increasing COVID-19 exposure or personal protective gear use, limited left ventricular ejection fraction (LVEF) assessment can be considered because a depressed systolic function would identify higher-risk patients. ^bRepeat troponin testing is indicated with a deterioration of clinical status. ^cThis pathway attempts to balance the imperfect tradeoffs of increased diagnostic uncertainty without compromising patient outcomes while minimizing unnecessary staff exposures and testing that will not immediately change clinical care. ^dThe 2015 Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities Task Force recommends abstinence from competitive sports or aerobic activity for a period of 3 to 6 months until resolution of myocardial inflammation. ^eAssessment of the LVEF should be considered at early follow-up for patients with an abnormal troponin during hospitalization either to identify patients with reduced systolic function or to complete a full cardiac assessment. Complete assessment should occur once a patient is no longer considered infectious in accordance with Centers for Disease Control and Prevention recommendations for the discontinuation of transmission-based precautions for patients with COVID-19. ^fThere are currently no evidence-based therapies for COVID-19 with robust clinical evidence of efficacy. Enrollment in a clinical trial should be strongly considered if available at the treating center. Additional treatment with antiviral, anticytokine, and other investigational drugs should be completed on a case-by-case basis after consultation with a multidisciplinary team. ^gPulmonary arterial catheters, inotropic, or mechanical support (ie, intra-aortic balloon pump, temporary left ventricular support device, veno-arterial extracorporeal membrane oxygenation) should be considered on a case-by-case basis, taking into account patient characteristics, availability of appropriately trained staff, and the ability of the healthcare institution to safely manage a support device. ^hEvidence of acute myocarditis by imaging or biopsy within myocardial tissue may modify the choice and dosing regimen of therapies. cMR indicates cardiac magnetic resonance; CT, computed tomography; MRI, magnetic resonance imaging; PA, pulmonary artery; and VT/VF, ventricular tachycardia/ventricular fibrillation.