COVID-19 and heart failure: from infection to inflammation and angiotensin II stimulation. Searching for evidence from a new disease

Abstract

Patients with cardiovascular disease and, namely, heart failure are more susceptible to coronavirus disease 2019 (COVID-19) and have a more severe clinical course once infected. Heart failure and myocardial damage, shown by increased troponin plasma levels, occur in at least 10% of patients hospitalized for COVID-19 with higher percentages, 25% to 35% or more, when patients critically ill or with concomitant cardiac disease are considered. Myocardial injury may be elicited by multiple mechanisms, including those occurring with all severe infections, such as fever, tachycardia, adrenergic stimulation, as well as those caused by an exaggerated inflammatory response, endotheliitis and, in some cases, myocarditis that have been shown in patients with COVID-19. A key role may be that of the renin-angiotensin-aldosterone system. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects human cells binding to angiotensin-converting enzyme 2 (ACE2), an enzyme responsible for the cleavage of angiotensin II into angiotensin 1-7, which has vasodilating and anti-inflammatory effects. Virus-mediated down-regulation of ACE2 may increase angiotensin II stimulation and contribute to the deleterious hyper-inflammatory reaction of COVID-19. On the other hand, ACE2 may be up-regulated in patients with cardiac disease and treated with ACE inhibitors or angiotensin receptor blockers. ACE2 up-regulation may increase the susceptibility to COVID-19 but may be also protective vs. angiotensin II-mediated vasoconstriction and inflammatory activation. Recent data show the lack of untoward effects of ACE inhibitors or angiotensin receptor blockers for COVID-19 infection and severity. Prospective trials are needed to ascertain whether these drugs may have protective effects.

Keywords: Angiotensin II; COVID-19; Heart failure.

Figure 1

Underlying mechanisms leading to acute myocardial injury in COVID‐19. Different mechanisms lead to cardiac damage in patients with COVID‐19, including general mechanisms related to the infection, immune response, and angiotensin converting enzyme 2 (ACE2) down‐regulation. Previous cardiac disease provides an unfavourable substrate. Ang II, angiotensin II; ARDS, acute respiratory distress syndrome; SARS‐CoV‐2, severe acute respiratory syndrome coronavirus 2.

Figure 2

Angiotensin‐converting enzyme 2 (ACE2) and severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). ACE2 is involved in the renin–angiotensin–aldosterone system pathway but it is also a functional receptor for SARS‐CoV‐2. Ang I, angiotensin I; Ang II, angiotensin II; AT1R, angiotensin II type 1 receptor; AT2R, angiotensin II type 2 receptor; ECE, endothelin‐converting enzyme; NEP, neutral endopeptidase; PCRP, prolycarboxypeptidase; PREP, prolylendopeptidase; RBD, receptor binding domain; PD, peptidase domain.

Figure 3

Deleterious and beneficial effects of angiotensin‐converting enzyme inhibitors (ACE‐i) and angiotensin receptor blockers (ARBs) in COVID‐19 patients. ACE2, angiotensin‐converting enzyme 2.