The coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has significant implications for cardiovascular (CV) care. This review summarizes peer-reviewed and preprint reports pertaining to COVID-19-related CV considerations. The following are key points to remember:

Pathophysiology, Epidemiology, and Clinical Features of COVID-19:

• SARS-CoV-2 as well as other coronaviruses can use the angiotensin-converting enzyme 2 (ACE2) protein, highly expressed in lung alveolar cells, for cell entry. ACE2 serves a role in lung protection; viral binding to the receptor deregulates a protective pathway, contributing to viral pathogenicity.
• The infectivity of SARS-CoV-2 is greater than that of influenza.
• Based on available data through March 16, 2020, the crude case fatality rate is 3.8%. However, there is substantial variability in reported fatality rates due to asymptomatic or mildly symptomatic people, inadequate testing capabilities, and the delay between contagion and death.
• The clinical presentation of COVID-19 is variable, ranging from mild disease in approximately 81% to severe disease in approximately 14% and critical disease in approximately 5%. Mild disease may include fever, cough, dyspnea, myalgias, fatigue, and diarrhea. Severe disease may include pneumonia and acute respiratory distress syndrome (ARDS) with or without both distributive and cardiogenic shock.
• To date, there are no approved preventative vaccines or therapies available for COVID-19.

Prevalence of CV Disease (CVD) in Patients With COVID-19:

• Estimates of CVD prevalence among patients with COVID-19 likely is biased by more testing for COVID-19 among sicker patients who also may have more comorbidities compared to infected but not hospitalized patients.
• Increased age, diabetes, and dyslipidemia increase the risk of CVD, and also affect immune function; prevalent CVD may be a marker of immunologic aging and dysregulation, and relate indirectly to COVID-19 prognosis.
• Patients awaiting or having undergone heart transplantation represent an especially vulnerable group.

CV Sequelae Associated With COVID-19:

• Myocardial injury, myocarditis, and acute coronary syndrome (ACS): Elevated serum troponin levels are common among patients with COVID-19, and associated with worse prognosis. In addition, electrocardiographic (ECG) and echocardiographic abnormalities are common, and associated with more severe disease and worse prognosis. Respiratory disease and hypoxia can contribute to myocardial ischemia, and inflammation associated with infection can trigger plaque rupture. COVID-19 also may mimic acute coronary syndrome; a case report from Italy describes a patient with chest pain and ECG changes but no obstructive coronary lesions.
• Cardiac arrhythmia and cardiac arrest: Cardiac arrhythmias are common in COVID-19, potentially in part attributable to metabolic disarray, hypoxia, and neurohormonal or inflammatory stress.
• Cardiomyopathy and heart failure: Heart failure is commonly observed, but whether this is due to exacerbation of pre-existing left ventricular dysfunction or new cardiomyopathy is unknown.
• Cardiogenic and mixed shock: Cardiogenic shock can contribute to pulmonary pathology in COVID-19. Serum brain natriuretic peptide and echocardiography can help clarify whether there is a cardiac contribution; if inconclusive, then in select cases, right heart catheterization can help distinguish cardiogenic from noncardiogenic shock.
• Venous thromboembolic disease: Patients with COVID-19 are at increased risk of thromboembolic disease, potentially related to abnormal coagulation, immobilization, disseminated intravascular coagulation, and vascular inflammation.

Drug Therapy for COVID-19 and CV Implications:

• Antivirals are at the forefront of medications being studied for the treatment COVID-19, including ribavirin and remdesivir (that bind to the active site on the RNA-dependent RNA polymerase on SARS-CoV-2) and lopinavir/ritonavir (that inhibits replication of the RNA virus). Lopinavir/ritonavir can result in decreased serum concentrations of the active metabolites of clopidogrel and prasugrel, and increased serum concentrations of ticagrelor. Statins have the potential to interact with lopinavir/ritonavir. Remdesivir is an investigational drug previously evaluated in the Ebola epidemic; hypotension has been reported, but extensive CV toxicities and medication interactions have not yet been studied.
• Chloroquine and hydroxychloroquine have the potential for intermediate to delayed myocardial toxicity. Chloroquine cardiac toxicity presents as restrictive or dilated cardiomyopathy or conduction abnormalities. Chloroquine affects beta-blocker metabolism, and both chloroquine and hydroxychloroquine are associated with a risk of torsades de pointes in the setting of electrolyte abnormalities or concomitant use of agents that prolong the QT interval.
• Anecdotal evidence raised concern that ibuprofen can potentially contribute to severe disease in patients with COVID-19.
• Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) may up-regulate ACE2, possibly increasing susceptibility to the virus; however, other studies suggest that ACE inhibitors and ARBs may potentiate the lung protective function of ACE2. There are insufficient data to suggest any mechanistic connections involving ACE inhibitor/ARB therapy with contracting COVID-19 or with illness severity.

Considerations for Health Care Workers:

• Health care workers are at elevated risk for contracting the SARS-CoV-2 virus. Recommendations by the World Health Organization and Centers for Disease Control and Prevention are for standard contact precautions with face mask, eye protection, gown, and gloves. The performance of aerosol-generating procedures (transesophageal echocardiography, endotracheal intubation, cardiopulmonary resuscitation, and bag mask ventilation) require additional personal protective equipment (PPE). In teaching hospitals, exposure among trainees and nonessential staff should be minimized both for their own safety and for conservation of PPE.
• Telemedicine and minimizing nonessential/nonurgent interactions both are useful to minimize the risk of COVID-19 transmission to patients and to health care workers.

Considerations for Health Systems and Management of Noninfected Patients:

• Hospital systems should anticipate a significant increase in patients with COVID-19 while maintaining general health services for acute and severe chronic illnesses.
• Information on the most up-to-date evidence surrounding management and treatment of patients with COVID-19 should be widely disseminated and freely available.
• The COVID-19 pandemic has brought ethical dilemmas, including policy issues (focusing on containment and mitigation versus herd immunity) and clinical issues (triaging medical care when demand exceeds supply). Close interaction is necessary between patient advocates, government officials, physician groups, hospital administrators, and societal leaders.

Clinical Topics: Acute Coronary Syndromes, Anticoagulation Management, Arrhythmias and Clinical EP, Cardiac Surgery, COVID-19 Hub, Diabetes and Cardiometabolic Disease, Dyslipidemia, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Prevention, Vascular Medicine, ACS and Cardiac Biomarkers, Anticoagulation Management and ACS, Implantable Devices, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Cardiac Surgery and Arrhythmias, Cardiac Surgery and Heart Failure, Novel Agents, Statins, Acute Heart Failure, Heart Failure and Cardiac Biomarkers, Heart Transplant, Interventions and ACS, Interventions and Imaging, Interventions and Vascular Medicine, Echocardiography/Ultrasound

Keywords: Acute Coronary Syndrome, Anticoagulants, Angiotensin-Converting Enzyme Inhibitors, Angiotensin Receptor Antagonists, Antiviral Agents, Arrhythmias, Cardiac, Chloroquine, Coronavirus, COVID-19, Diabetes Mellitus, Dyslipidemias, Echocardiography, Electrocardiography, Heart Failure, Heart Transplantation, Hydroxychloroquine, Myocarditis, Natriuretic Peptide, Brain, Peptidyl-Dipeptidase A, Personal Protective Equipment, Primary Prevention, Respiratory Distress Syndrome, RNA-Dependent RNA Polymerase, SARS Virus, Shock, Cardiogenic, Takotsubo Cardiomyopathy, Troponin, Venous Thrombosis

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