Covid-19 and development of heart failure: mystery and truth

Abstract

Coronavirus disease 2019 (Covid-19) is a novel worldwide pandemic caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). During Covid-19 pandemic, socioeconomic deprivation, social isolation, and reduced physical activities may induce heart failure (HF), destabilization, and cause more complications. HF appears as a potential hazard due to SARS-CoV-2 infection, chiefly in elderly patients with underlying comorbidities. In reality, the expression of cardiac ACE2 is implicated as a target point for SARS-CoV-2-induced acute cardiac injury. In SARS-CoV-2 infection, like other febrile illnesses, high blood viscosity, exaggerated pro-inflammatory response, multisystem inflammatory syndrome, and endothelial dysfunction-induced coagulation disorders may increase risk of HF development. Hypoxic respiratory failure, as in pulmonary edema, severe acute lung injury (ALI), and acute respiratory distress syndrome (ARDS) may affect heart hemodynamic stability due to the development of pulmonary hypertension. Indeed, Covid-19-induced HF could be through the development of cytokine storm, characterized by high proliferation pro-inflammatory cytokines. In cytokine storm-mediated cardiac dysfunction, there is a positive correlation between levels of pro-inflammatory cytokine and myocarditis-induced acute cardiac injury biomarkers. Therefore, Covid-19-induced HF is more complex and related from a molecular background in releasing pro-inflammatory cytokines to the neuro-metabolic derangements that together affect cardiomyocyte functions and development of HF. Anti-heart failure medications, mainly digoxin and carvedilol, have potent anti-SARS-CoV-2 and anti-inflammatory properties that may mitigate Covid-19 severity and development of HF. In conclusion, SARS-CoV-2 infection may lead to the development of HF due to direct acute cardiac injury or through the development of cytokine storms, which depress cardiomyocyte function and cardiac contractility. Anti-heart failure drugs, mainly digoxin and carvedilol, may attenuate severity of HF by reducing the infectivity of SARS-CoV-2 and prevent the development of cytokine storms in severely affected Covid-19 patients.

Keywords: Covid-19; Development; Heart failure; SARS-CoV-2.

Fig. 1

Role viral infections in the development of heart failure (HF): viral infections induce hypoxemia, sympathetic activation, release of pro-inflammatory cytokines, and cardiomyocyte injury. Sympathetic activation activates renin-angiotensin system (RAS) with induction of cardio-renal syndrome and volume overload. In addition, pro-inflammatory cytokines and RAS interacted together in the development of cardio-renal syndrome and reduction of cardiac contractility. These pathophysiological changes promote development of HF

Fig. 2

The association between Covid-19 and development of heart failure (HF): in Covid-19 hypoxia and hemodynamic instability lead to hypotension, oxidative stress and high blood viscosity may cardiomyocyte injury through induction of coronary dysfunction. As well, SARS-CoV-2 may cause direct acute myocardial injury (ACI) and development of HF. In addition, hyperferritinemia and activation of NLRP3/NF-κB signaling pathway contribute into ACI through induction of cytokine storm. Besides, downregulation of ACE2 by SARS-CoV-2 upregulates circulating AngII, which involved in cardiomyocyte injury and development of HF

Fig. 3

Role of digoxin in the attenuation Covid-19 induced-heart failure. Digoxin inhibits replication of SARS-CoV-2 and NF-κB, thereby inhibiting cytokine storm-induced heart failure