THE CARDIOVASCULAR SYSTEM AND COVID-19
who had not yet received a positive test result for COVID-19 at the time of coronary angiography. These observations suggest that patients with COVID-19 can present without the hallmark symptoms of this infection. Importantly, a global decline in patients with myocardial infarction seeking medical care has been noted, perhaps owing to the fear of seeking medical care and risking exposure to the virus causing COVID-19. A global survey by the European Society of Cardiology reported a greater than 50% decline in the incidence of myocardial infarction during the peak of COVID-19 29 . Concomitantly, patients with cardiovascular illness and COVID-19 experienced higher mortality, perhaps related to late presentations in the course of their acute coronary syndromes 30 . Recommendations about the management of acute myocardial infarction during the COVID-19 pandemic are unchanged from those prior to the pandemic, with primary PCI still the standard of care for patients presenting with STEMI within 90 minutes of first medical contact 31 . Patients with NSTEMI and COVID-19 should be treated with optimal medical therapy, and urgent coronary angiography with possible percutaneous coronary intervention (PCI) offered to patients who have high risk presentation based on the presence of elevated cardiac biomarkers, sustained ventricular tachycardia, hemodynamic instability, recurrent ischemic chest pain despite ongoing medical management, new pulmonary edema or mitral regurgitation murmur, recent PCI (less than 6 months) or previous coronary artery bypass grafting (CABG) or new onset systolic heart failure (EF<40%) 31 . HEART FAILURE AND CARDIOGENIC SHOCK
Cardiovascular manifestations of COVID-19 include acute myocardial injury, acute coronary syndromes, myocarditis, congestive heart failure, cardiogenic shock, cardiac arrhythmias, as well as arterial and venous thromboembolism (VTE). MYOCARDIAL INJURY Acute myocardial injury is defined as a rise and/or fall of high sensitivity cardiac troponin (hs-cTn) values above the 99 th percentile of upper reference limit 18 . It is more prevalent in COVID-19 patients with more severe illness and underlying cardiovascular disease (CVD). Numerous studies have highlighted the correlation between elevated hs-cTn levels and disease severity 19,20,21,22 . A single center, retrospective case series of 187 patients with COVID-19 reported that patients with CVD were more susceptible to myocardial injury compared to patients without CVD (54.5% vs 13.2%) 19 . Similarly, in-hospital mortality for COVID-19 patients without CVD and normal cTn was 7.2% but 37.5% in patients who had CVD but normal cTn. In comparison, COVID-19 patients who had CVD and elevated cTn the mortality was 69.4%. Progressive increases in cTn portend worse outcomes. cTn levels were unchanged in survivors whereas they continued to rise in non-survivors till the time of death. The median time of death from symptom onset in this study was 18.5 days 23 . It is of paramount importance to accurately identify and differentiate myocardial injury from various types non-ST elevation myocardial infarction (NSTEMI) as their management differs significantly. Acute myocardial injury is managed by treating the underlying disease process. ACUTE CORONARY SYNDROME (ACS) The risk of atherosclerotic plaque disruption and acute coronary syndrome is increased in severe systemic inflammation 24 . ACS has been reported in patients with influenza and SARS infections 24,25,26 . The incidence of ACS in COVID-19 is unknown. In a case series involving 18 patients with COVID-19 and ST segment elevation, 9 patients underwent coronary angiography, 6 had obstructive coronary artery disease and 5 underwent percutaneous coronary intervention. Patients with non- obstructive disease had worse prognosis with a 72% in-hospital mortality 27 . Another case series from Italy involving 28 patients with COVID-19 and ST segment elevation myocardial infarction, assessment by coronary angiography showed that 17 patients had evidence of a culprit lesion that required revascularization 28 . Of note, ST segment elevation myocardial infarction was the first clinical manifestation of COVID-19 in 24 of these 28 patients
Nearly a quarter of people hospitalized for COVID-19 have acute heart failure with a mortality rate as high as 49%. 32,33 Elevated B-type natriuretic peptide (BNP) and pro-BNP levels are also commonly seen (50% of the hospitalized patients) and portend a worse prognosis 34 . A prospective study involving 100 hospitalized COVID-19 patients reported 39 patients with right ventricular (RV) dysfunction, 16 patients with left ventricular (LV) diastolic dysfunction and 10 patients with LV systolic dysfunction (2 patients had prior diagnosis of LV systolic dysfunction) 35 . In hospitalized patients, RV dysfunction/failure is precipitated by increased pulmonary vascular resistance or pulmonary pressure. This increase can result from pneumonia, pulmonary embolism, hypoxic pulmonary vasoconstriction, hypercarbia, decrease in lung volume, or use of positive end expiratory pressure and pressors in intubated patients 33 . Right ventricular longitudinal strain (RVLS) using echocardiography is a powerful predictor of morbidity and mortality has been found to be more accurate than RV fractional area change and tricuspid annular plane systolic excursion in predicting worse outcomes 36 . Acute decompensation in preexisting 25
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