COVID-19: Cardiac Manifestations in Adults By Dr. Anupam Jena, Consultant Cardiologist and Electro-physiologist, KIMS
Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; previously referred to as 2019-nCoV). Patients with COVID-19 typically present with symptoms and signs of respiratory tract infection, but cardiac manifestations, including signs of injury to heart muscles, are common.
Putative causes of myocardial injury in patients with COVID-19 include myocarditis; hypoxic injury; stress (takotsubo) cardiomyopathy; ischemic injury caused by cardiac microvascular dysfunction, small vessel cardiac vasculitis, endotheliitis, or epicardial coronary artery disease (with plaque rupture or demand ischemia); right heart strain (acute cor pulmonale, with causes including pulmonary embolism, adult respiratory distress syndrome, and pneumonia); and systemic inflammatory response syndrome (cytokine storm). However, the contribution of each of these putative causes to myocardial injury and adverse cardiovascular outcomes in this setting has not been determined. It is also unknown whether angiotensin-converting enzyme 2 receptor-related signaling pathways have a role in COVID-19-related cardiac injury.
Impact of preexisting cardiovascular disease:
Symptoms and signs of heart disease in a patient with COVID-19 may result from an acute disease process, from hemodynamic demands in the setting of chronic (preexisting) heart disease or may be caused by an acute exacerbation of chronic disease. Proposed mechanisms include impaired physiologic reserve (cardiovascular and pulmonary), impaired immune response, augmented inflammatory response, vulnerability to SARS-CoV-2-induced endothelial dysfunction, and effects mediated by the angiotensin-converting enzyme 2 receptor.
Spectrum of Clinical Presentations:
Patients with COVID-19 present with a broad spectrum of clinical cardiac presentations: some patients manifest no clinical evidence of heart disease, some have no symptoms of heart disease but have cardiac test abnormalities (such as serum cardiac troponin elevation, asymptomatic cardiac arrhythmias, or abnormalities on cardiac imaging), and some have symptomatic heart disease. Cardiac complications include myocardial injury, heart failure (HF), cardiogenic shock, and cardiac arrhythmias including sudden cardiac arrest.
Most patients with COVID-19 with abnormalities on cardiac testing have typical symptoms of COVID-19, including cough, fever, myalgia, headache, and dyspnea etc. A minority of patients with COVID-19 symptoms may suggest heart disease (such as palpitations or chest pain). These symptoms may or may not be accompanied by prior or concurrent symptoms typical of COVID-19 infection. Symptoms such as dyspnea and chest pain may be caused by noncardiac and/or cardiac causes.
1. Asymptomatic heart disease — Most patients with COVID-19 with cardiac test abnormalities (such as cardiac troponin elevation, electrocardiographic [ECG] abnormalities, or echocardiographic findings) lack symptoms of heart disease.
2.Myocardial injury — Myocardial injury as detected by troponin elevation is commonly identified in patients hospitalized with COVID-19, but the causes of myocardial injury have not been fully elucidated. Clinical conditions associated with myocardial injury include myocarditis, stress cardiomyopathy, and myocardial infarction (MI). The term “myocardial injury” encompasses all conditions causing cardiomyocyte death. Cardiac troponin elevation is the generally accepted marker for identifying myocardial injury. High-sensitivity cardiac troponin levels are sensitive markers of myocardial injury.
3.Stress cardiomyopathy — Stress (takotsubo) cardiomyopathy has been reported in patients with COVID-19. In addition, some case reports of clinically suspected myocarditis complicating COVID-19 have described marked recovery of left ventricular (LV) systolic function within days, suggestive of stress cardiomyopathy or fulminant myocarditis.
4. Myocardial infarction — Patients with COVID-19 are more prone to develop myocardial infarction (Heart attack).
5. Heart failure
General prevalence — HF in patients with COVID-19 may be precipitated by acute illness in patients with preexisting known or undiagnosed heart disease (e.g., coronary artery disease or hypertensive heart disease), acute hemodynamic stress (eg, acute cor pulmonale), or acute myocardial injury (e.g., acute MI, stress cardiomyopathy, cytokine storm. Cardiovascular risk factors and cardiovascular disease are highly prevalent in hospitalized patients with COVID-19. Patients with a known history of HF may suffer an acute worsening due to the development of COVID-19 disease.
Although acute HF incidence was not documented in some series of hospitalized patients with COVID-19, elevated natriuretic peptides (such as B-type natriuretic peptide [BNP] and N-terminal pro-BNP [NT-proBNP]) are common, particularly in patients with evidence of cardiac injury.
Right heart failure — Acute cor-pulmonale (right HF due to acute pulmonary hypertension) precipitated by acute pulmonary embolism or adult respiratory distress syndrome (ARDS) has been described in patients with COVID-19. Patients with COVID-19 are at risk for development of ARDS. Venous thromboembolism (including extensive blood clot formation in the deep veins of limbs and subsequent migration to lungs) is common in seriously ill patients with COVID-19.
Cardiogenic shock — Case reports have described patients with COVID-19 and acute onset of cardiogenic shock treated with inotrope (Medicines to increase blood pressure) and mechanical circulatory support and, in some cases, venoarterial extracorporeal membrane oxygenation (VA-ECMO)
Multisystem inflammatory syndrome in adults (MIS-A) — Multisystem inflammatory syndrome (MIS) was initially described in children (MIS-C) with recent COVID-19 infection as a Kawasaki-like illness associated with fever, gastrointestinal symptoms, shock, LV systolic dysfunction, and elevated inflammatory markers. Similar cases of MIS have been described in young to middle-aged adults (MIS-A) also presenting with fever, gastrointestinal symptoms, and shock with vasoplegia, LV systolic dysfunction, and elevated inflammatory markers. This syndrome appears to be highly responsive to parenteral steroids.
Cardiac arrhythmias — A variety of abnormal beating of the heart has been described in COVID-19 patients including- high heart rate, low heart date and sudden cardiac arrest.
Cardiac troponin and natriuretic peptide (B-type natriuretic peptide [BNP] and N-terminal pro-BNP [NT-proBNP]) biomarkers are commonly elevated among hospitalized patients with COVID-19 and are associated with increased risk of mortality.
1. Troponin — Cardiac troponin elevation is a marker of myocardial injury and is commonly identified in patients hospitalized with COVID-19, but the causes of troponin elevation have not been fully elucidated . The frequency of myocardial injury (as reflected by elevation in cardiac troponin levels) is variable among hospitalized patients with COVID-19, with reported frequencies of 7 to 36 percent with SARS-CoV-2 infection.
Studies have identified greater frequency and magnitude of troponin elevations in hospitalized patients with more severe disease and worse outcomes. Other clinical features associated with high risk of death are history of cardiovascular disease, acute kidney injury, increased procalcitonin, increased D-dimer, and thrombocytopenia.
Types of troponin elevation are:
●Mild – Patients hospitalized with COVID-19 commonly have mild troponin elevation.
●Moderate time-limited – Some patients have an early moderately elevated troponin level (which may approach or exceed the 99th percentile URL), which may fall on subsequent days.
●Progressive – Some patients with moderate troponin elevation at hospital admission suffer clinical deterioration with respiratory failure accompanied by progressive troponin elevation, along with elevations in other biomarkers (eg, D-dimer, interleukin 6, ferritin, and lactate dehydrogenase) with accelerated rise after the second week of hospitalization. This progression to cytokine storm has been described in nonsurvivors, with death occurring at a median of 18.5 days after symptom onset.
Other cardiac test abnormalities (such as ECG alterations and cardiac imaging findings) have been observed in patients with and without elevated troponin levels. The finding of a cardiac test abnormality without concurrent troponin elevation suggests a condition not associated with myocardial injury (including preexisting cardiac disease or a process not causing cardiomyocyte death) or a missed troponin level elevation due to limited troponin sampling or troponin elevation below 99th percentile URL thresholds.
2. Natriuretic peptides — Natriuretic peptides (BNP and NT-proBNP) are commonly elevated in hospitalized patients with COVID-19, and natriuretic peptide elevation is associated with mortality risk. Natriuretic peptide elevation is commonly associated with cardiac troponin elevation.
The various ECG findings observed in patients with COVID-19 likely reflect the combined effects of acute illness and chronic heart disease (since cardiovascular risk factors are highly prevalent in this population).
●Atrial fibrillation or flutter was observed in 5-7% percent. Atrial premature beats (APBs) were observed in 7-10% percent and premature ventricular contractions in 5% percent.
●Right bundle branch block (RBBB), left bundle branch block, and nonspecific intraventricular conduction delay (IVCD).
●Re-polarization abnormalities included localized ST elevation, localized T-wave inversion, and nonspecific repolarization abnormalities.
A variety of echocardiographic findings have been identified in patients with COVID-19.
●Transthoracic echocardiography (TTE) findings included right ventricular (RV) dilation and dysfunction, LV diastolic dysfunction, and LV systolic dysfunction. Patients with an elevated troponin level or worse clinical condition had worse RV function.
●Among the 20 percent of the patients with subsequent clinical deterioration, the most common echocardiographic findings were worsened RV function and worsened LV systolic and diastolic function. Femoral deep vein thrombosis was identified in 40-50% patients with RV failure.
Cardiovascular Magnetic Resonance
Cardiovascular magnetic resonance (CMR) abnormalities have been identified in patients with COVID-19 as well as in patients who have recently recovered from COVID-19, though most reported abnormalities have been nonspecific.
Myocardial histology and viral genome analysis
Myocarditis is commonly suspected in patients with COVID-19 and elevated cardiac troponin levels.
Further investigation, including histological examination of cardiac tissue in COVID-19 patients, is required to characterize the relationship between COVID-19 and myocardial injury. Since biopsy-proven myocarditis may occur in the absence of troponin release, autopsy studies of COVID-19 victims, regardless of troponin levels, are helpful in clarifying whether SARS-CoV-2 is a new cause of viral myocarditis.
Conclusion: COVID-19 affects the cardiovascular system globally. It increases the risk of heart attack (MI), heart failure, cardiac arrhythmia and sudden cardiac death. Early diagnosis and treatment can prevent and ameliorate many of these complications.