Cardiovascular disease in SARS-CoV-2 infection

Abstract

Pre-existing cardiovascular disease (CVD) increases the morbidity and mortality of COVID-19 and is strongly associated with poor disease outcomes. However, SARS-CoV-2 infection can also trigger de novo acute and chronic cardiovascular disease. Acute cardiac complications include arrhythmia, myocarditis and heart failure, which are significantly associated with higher in-hospital mortality. The possible mechanisms by which SARS-CoV-2 causes this acute cardiac disease include direct damage caused by viral invasion of cardiomyocytes as well as indirect damage through systemic inflammation. The long-term cardiac complications associated with COVID-19 are incompletely characterised and thought to include hypertension, arrhythmia, coronary atherosclerosis and heart failure. Although some cardiac-related symptoms can last over 6 months, the effect of these complications on long-term patient health remains unclear. The risk factors associated with long-term cardiovascular disease remain poorly defined. Determining which patients are most at-risk of long-term cardiovascular disease is vital so that targeted follow-up and patient care can be provided. The aim of this review was to summarise the current evidence of the acute and long-term cardiovascular consequences of SARS-CoV-2 infection and the mechanisms by which SARS-CoV-2 may cause cardiovascular disease.

Keywords: COVID‐19; SARS‐CoV‐2; cardiovascular disease.

Figure 1

Schematic representation of the putative mechanisms by which SARS‐CoV‐2 causes cardiovascular disease. SARS‐CoV‐2 binds to ACE‐2 in myocardium (1) to enter the target cell. This causes downregulation of ACE‐2, which converts vasoconstricting/inflammatory angiotensin II into vasodilating/anti‐inflammatory protein angiotensin 1–7. The concentration of angiotensin 1–7 decreases and that of angiotensin II increases, contributing to reduced coronary artery flow, myocardial ischaemia (2) and inflammation. Increased angiotensin II also cause vasoconstriction at the alveolar‐capillary bed, leading specific increased strain on a right heart that is already struggling because of the hypoxic pulmonary vasoconstriction and micro vascular thromboses. Cell injury such as myocardial fibrosis (3) and apoptosis (4) is caused by both direct viral involvement and systemic inflammation from an imbalance of T helper 1 and 2 responses, denoted by elevated serum cytokines (5), facilitating long‐term disease including arrhythmias (6) and hypercoagulability. Increased cardiometabolic demand leads to a reduced cardiac reserve, denoted by compensative left ventricular hypertrophy (7), further contributing to angiotensin‐aldosterone system dysregulation. Therapies used during the acute phase of infection, such as high‐dose steroid treatment, may increase plaque formation (8) and hypertension and decrease cardiac function. High‐dose steroid also could work as a stress hormone, inducing excess catecholamine, leading to excess oxygen consumption of myocardium and decrease cardiac function. Cardiac injury results in elevated cardiac troponin (CTN) and NT‐pro BNP levels (5). All mechanisms promote plaque destabilisation and increase wall shear stress (10). The image was created with Biorender.com.

Figure 2

Schematic representation of the long‐term cardiovascular complications of COVID‐19. Amongst studies of patients initially hospitalised with severe COVID‐19, signs of persistent cardiovascular disease appear to be relatively common, with patients continuing to suffer from chest pain, late gadolinium enhancement (LGE), LV dysfunction, myocardial infarction and palpitations 6 months post‐infection. Cardiovascular complication incidence amongst convalescent COVID‐19 patients who experienced mild illness is less well defined, with patients suffering from cardiac involvement, myocarditis and LGE earlier post‐infection but seeming to recover by 6 months post‐infection. Considering that some cases with mild illness still have cardiovascular complications at 6 months post‐infection, it cannot be concluded that mild cases of COVID‐19 never cause chronic cardiac complications. The image was created with Biorender.com.