Chikungunya and the Heart

Abstract

<b><i>Introduction:</i></b> Neglected tropical diseases are a group of communicable diseases that occur in tropical and subtropical conditions and are closely related to poverty and inadequate sanitation conditions. Among these entities, chikungunya remains one of the most widely spread diseases. Although the main symptoms are related to a febrile syndrome, cardiovascular (CV) involvement has been reported, with short- and long-term implications. As part of the “Neglected Tropical Diseases and other Infectious Diseases involving the Heart” (NET-Heart) Project, the aim of this review is to compile all the information available regarding CV involvement of this disease, to help healthcare providers gain knowledge in this field, and contribute to improving early diagnosis, treatment, and prevention strategies. <b><i>Methods:</i></b> We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement in conducting and reporting this systematic review. The search was conducted using MEDLINE/PubMed, SciELO, and LILACS databases to identify any relevant studies or reviews detailing an association between chikungunya and cardiac involvement published from January 1972 to May 31, 2020. <b><i>Results:</i></b> Despite its mechanism not being fully understood, CV involvement has been described as the most frequent atypical presentation of chikungunya (54.2%). Myocarditis is the most prevalent CV complication. Different rhythm disturbances have been reported in 52% of cases, whereas heart failure was reported in 15% of cases, pericarditis in 5%, and acute myocardial infarction in 2%. Overall estimated CV mortality is 10%, although in patients with other comorbidities, it may increase up to 20%. In the proper clinical setting, the presence of fever, polyarthralgia, and new-onset arrhythmia suggests chikungunya virus-related myocarditis. <b><i>Conclusion:</i></b> Although most cases are rarely fatal, CV involvement in chikungunya infection remains the most frequent atypical presentation of this disease and may have severe manifestations. Timely diagnosis and appropriate management are necessary to improve patient outcomes.

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

“…CHIKV antigen in cardiac fibroblasts was previously identified in human necropsies of individuals who died from CHIKV (Sharp et al, 2021) and thus supports a similar tropism observed in humans. Indeed, both human and murine cardiac fibroblasts show high levels of expression of the CHIKV receptor Mxra8 (Cotella et al, 2021). The significant reduction in CHIKV genomes isolated from Mxra8 D8/D8 infected hearts, in addition to the significant levels of Mxra8 expression in cardiac fibroblasts, suggests that CHIKV heart infection is mediated in part by the expression of the CHIKV receptor Mxra8 (Zhang et al, 2018).…”

“…Elevated cardiac troponins have been observed in individuals with CHIKV-associated cardiac manifestations (Cotella et al, 2021;Farias et al, 2019;Gasque et al, 2016;Hsu et al, 2019). Therefore, to define whether CHIKV can lead to cardiac tissue damage in mice, we evaluated the serum levels of cardiac troponin-T (cTnT) at 2 and 5 dpi by ELISA.…”

“…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). CHIKVassociated 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).…”

Neglected Tropical Diseases and Sudden Cardiac Death: The NET-Heart Project

“…The selection of relevant NTDs to discuss was based on previous systematic reviews carried out as part of the Interamerican Society of Cardiology (SIAC) NET-Heart Project. The conditions identified as having a potential increased risk of SCD were included in this review [9][10][11][12][13][14][15][16].…”