COVID-19 and Cardiovascular Disease
Patients with cardiovascular risk factors and established cardiovascular disease, including heart failure (HF), are particularly vulnerable when suffering from COVID‐19[4][5] and patients with cardiac injury in the context of COVID‐19 have an increased risk of morbidity and mortality.[6]
Guzik et al.[7] report a mortality rate ∼0.9% for patients with no comorbidities and much higher for patients with comorbidities (10.5% for patients with CV disease, 7.3% for those with diabetes, 6% for those with hypertension and 6.3% for those with chronic respiratory disease.[8]
SARS-CoV-2 anchors on transmembrane ACE2 to enter the host cells including type 2 pneumocytes, macrophages, endothelial cells, pericytes, and cardiac myocytes,[9] leading to inflammation, severe microvascular[10] and macrovascular dysfunction and multiorgan failure.
Furthermore, COVID-19 infection leads to systemic inflammation and immune cell overactivation, and a ‘cytokine storm’, with resultant release of in an elevated level of cytokines such as IL-6, IL-7, IL-22, and CXCL10. Subsequently, activated T cells and macrophages may infiltrate infected myocardium, resulting in the development of fulminant myocarditis and severe cardiac damage and impairment of left ventricular function.[11]
Thus, the mechanisms by which COVID-19 affects the cardiovascular system possibly include direct myocardial injury, indirect injury through sepsis, hypoxia, cytokine release, a prothrombotic state causing microvascular thrombosis, and exacerbation of underlying cardiovascular disease, for example, plaque rupture in susceptible patients.[12][13][14] Supply/demand mismatch (Type 2 myocardial infarction (MI)) or microvascular thrombosis can lead to left ventricular dysfunction and ventricular arrhythmias. Fulminant myocarditis can lead to rapidly progressive cardiogenic shock from decompensation in patients with known or subclinical cardiomyopathy. Among hospitalized patients, the presence of cardiac injury has been independently associated with a 4-fold increased risk of mortality in patients infected with COVID-19.[15]
In patients with COVID-19 infection, hypoxemic respiratory failure and ARDS can exacerbate pulmonary vasoconstriction and interstitial oedema, worsening pulmonary hypertension even in patients without pre-existing lung disease.[16] In patients with pre-existing biventricular failure, further elevation in pulmonary pressures secondary to ARDS can worsen right ventricular function.
In a large cohort study of 138 patients, 8.7% of patients presented with shock, 7.2% with acute cardiac injury and 16.7% with arrhythmias.[17] Various other reports show new-onset heart failure/cardiomyopathy in up to one-third of critically ill patients admitted with COVID-19 infection.[18][19]
A special population at risk for COVID‐19 includes patients supported with left ventricular assist devices (LVADs). These patients are chronically affected by long‐standing cardiovascular diseases and are subjected to variations of the normal cardiovascular physiology due to a non‐pulsatile blood flow, exposure of the blood to artificial surfaces, and risk of haemorrhagic and thrombotic events. Patients with advanced HF, including those with durable LVAD support, have severely reduced functional capacity[20][21], as measured by peak VO2, and impaired ability to augment cardiac output in response to physiological stressors. These factors collectively decrease their cardiopulmonary reserve.
Patients with COVID-19 infection are at higher risk for thrombosis in the arterial and venous circulations due to endothelial dysfunction, inflammation, oxidative stress, and platelet activation[22]; both may trigger decompensation of pre-existing HF or development of de novo acute HF. Right ventricular failure can also develop secondary to elevated pulmonary pressures in the setting of ARDS and/or pulmonary embolism.[23]
HF incidence, prevalence, and undertreatment will likely grow as a result of new COVID-19-related heart disease, delays in the recognition and treatment of ischemic heart disease, rising unemployment, and loss of income and health benefits for large segments of the population. Special considerations are needed for patients with advanced HF, including those supported by durable LVADs and heart transplantation (HT) recipients.