Cardiomyopathy and Death Following Chikungunya Infection: An Increasingly Common Outcome

Abstract

Chikungunya virus (CHIKV) is vectored by Aedes aegypti and Aedes albopictus mosquitoes and is found throughout tropical and sub-tropical regions. While most infections cause mild symptoms such as fever and arthralgia, there have been cases in which cardiac involvement has been reported. In adults, case reports include symptoms ranging from tachycardia and arrythmia, to myocarditis and cardiac arrest. In children, case reports describe symptoms such as arrythmia, myocarditis, and heart failure. Case reports of perinatal and neonatal CHIKV infections have also described cardiovascular compromise, including myocardial hypertrophy, ventricular dysfunction, myocarditis, and death. Myocarditis refers to inflammation of the heart tissue, which can be caused by viral infection, thus becoming viral myocarditis. Since viral myocarditis is linked as a causative factor of other cardiomyopathies, including dilated cardiomyopathy, in which the heart muscle weakens and fails to pump blood properly, the connection between CHIKV and the heart is concerning. We searched Pubmed, Embase, LILACS, and Google Scholar to identify case reports of CHIKV infections where cardiac symptoms were reported. We utilized NCBI Virus and NCBI Nucleotide to explore the lineage/evolution of strains associated with these outbreaks. Statistical analysis was performed to identify which clinical features were associated with death. Phylogenetic analysis determined that CHIKV infections with cardiac symptoms are associated with the Asian, the East Central South African, and the Indian Ocean lineages. Of patients admitted to hospital, death rates ranged from 26–48%. Myocarditis, hypertension, pre-existing conditions, and the development of heart failure were significantly correlated with death. As such, clinicians should be aware in their treatment and follow-up of patients.

Viral Myocarditis—From Pathophysiology to Treatment

“…Recently, the flaviviruses Zika virus (ZIKV), dengue virus (DENV) and West Nile virus (WNV), as well as the togavirus Chikungunya virus (CHIKV) and the lyssavirus rabies virus, all of which are endemic to tropical and subtropical regions, such as Latin America, and are neglected tropical diseases (NTD), have been found to be associated with cardiac diseases, such as myocarditis, in addition to neurological disorders. However, only a few case reports exist showing the association of these NTD virus infections with myocarditis [21][22][23][24][25]34,35,[40][41][42]158,159]. Similar observations with a suspicious association to myocarditis have been made for rubella, mumps and measles virus [56].…”

MAVS signaling is required for clearance of chikungunya heart infection and prevention of chronic inflammation in vascular tissue

“…It is established that cardiac complications account for more than 20% of CHIKV-associated deaths (de Lima et al, 2021; Sharp et al, 2021; Traverse et al, 2021). Here, we demonstrate that cardiac tissue, in particular cardiac fibroblasts, is a direct target of CHIKV infection.…”

“…Arthropod-borne viruses (arboviruses) such as Zika virus, dengue virus, and chikungunya virus (CHIKV) are associated with the development of cardiomyopathies in patients (Alvarez et al, 2017; Araiza-Garaygordobil et al, 2021; Minhas et al, 2017; Scatularo et al, 2022; Traverse et al, 2021). CHIKV-associated cardiac manifestations have been reported in more than 15 countries worldwide (Cotella et al, 2021; Traverse et al, 2021).…”

“…Arthropod-borne viruses (arboviruses) such as Zika virus, dengue virus, and chikungunya virus (CHIKV) are associated with the development of cardiomyopathies in patients (Alvarez et al, 2017; Araiza-Garaygordobil et al, 2021; Minhas et al, 2017; Scatularo et al, 2022; Traverse et al, 2021). CHIKV-associated cardiac manifestations have been reported in more than 15 countries worldwide (Cotella et al, 2021; Traverse et al, 2021). These complications occur mainly within the first week after symptoms onset (Traverse et al, 2021), and include symptoms ranging from arrhythmias, atrial fibrillation, abnormal echocardiograms and electrocardiograms (Villamil-Gomez et al, 2016), reduction of the ejection fraction (Farias et al, 2019), myocarditis (Crosby et al, 2016; de Lima et al, 2021; Villamil-Gomez et al, 2016), to heart failure, and death (de Lima et al, 2021; Farias et al, 2019; Samra et al, 2017; Sharp et al, 2021).…”

“…CHIKV-associated cardiac manifestations have been reported in more than 15 countries worldwide (Cotella et al, 2021; Traverse et al, 2021). These complications occur mainly within the first week after symptoms onset (Traverse et al, 2021), and include symptoms ranging from arrhythmias, atrial fibrillation, abnormal echocardiograms and electrocardiograms (Villamil-Gomez et al, 2016), reduction of the ejection fraction (Farias et al, 2019), myocarditis (Crosby et al, 2016; de Lima et al, 2021; Villamil-Gomez et al, 2016), to heart failure, and death (de Lima et al, 2021; Farias et al, 2019; Samra et al, 2017; Sharp et al, 2021). Indeed, more than 20% of the CHIKV-related mortality cases have been associated with cardiac complications (de Lima et al, 2021; Economopoulou et al, 2009; Sharp et al, 2021).…”