ABC | Volume 110, Nº3, March 2018

Editorial Yellow Fever and Cardiovascular Disease: An Intersection of Epidemics Gláucia Maria Moraes de Oliveira 1 and Roberto Muniz Ferreira 1,2 Programa de Pós-Graduação em Medicina (Cardiologia) do Departamento de Clínica Médica da Faculdade de Medicina e do Instituto do Coração Édson Saad da Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ – Brazil 1 Hospital Samaritano, Rio de Janeiro, RJ – Brazil 2 Mailing Address: Gláucia Maria Moraes de Oliveira • Universidade Federal do Rio de Janeiro – R. Prof. Rodolpho P. Rocco, 255 – Pr dio do HU 8º andar – sala 6, UFRJ. Postal Code 21941-913, Cidade Universitária, RJ – Brazil E-mail: glauciam@cardiol.br , glauciamoraesoliveira@gmail.com Keywords Yellow Fever; Tropical Ecosystem, Arbovirus Infections; Aedes, Liver Failure; Kidney Failure, Chronic; Hemorrhage; Bradycardia; Drug-Eluting Stents / adverse effects. DOI: 10.5935/abc.20180041 Arboviral diseases are an important public health problem, especially in tropical and subtropical countries, such as Brazil, where viruses of the family Flaviviridae, responsible for dengue fever, zika and yellow fever (YF), and of the family Togaviridae , which cause chikungunya, predominate. In recent years, the number of cases has increased because of several factors, of which environmental changes, such as deforestation and climate changes, disorderly occupation of cities with low hygiene-sanitary conditions, in addition to the increased mobility of international travelers, stand out. Such factors have allowed the colonization of new areas by vectors, mainly Aedes aegypti , which can be found in 80% of the Brazilian territory. 1,2 Dengue virus, which has four different serotypes, has accounted for isolated epidemics or for co-infections in 1984–1985, 1997–1999 and 2004–2007. Chikungunya, whose virus originated in Africa, succeeded the dengue fever in Brazil in 2014, with similar clinical and laboratory presentation, hindering the differential diagnosis. In 2015, the first cases of zika were reported in Brazil. Table 1 summarizes the clinical manifestations of those arboviral diseases. 2-4 According to the World Health Organization, YF is endemic in Brazil since the year 1900, with sylvan and urban cycles, aggravated by the presence of Aedes aegypti in the cities. In the past decades, there has been a significant reduction in the number of cases because of the increase in vaccine coverage. However, the disease spread from endemic areas to the vicinities with similar ecological characteristics has enabled the emergence of the recent epidemic in the Brazilian states of Minas Gerais, Rio de Janeiro and São Paulo. 5 Table 2 shows the signs and symptoms of YF, highlighting hepatic and renal failures, in addition to bleedings that occur in the more severe forms. Most monkeys in Africa are resistant to the YF virus, differently from the neotropical species of primates of the Americas, which are more susceptible to fatal infections, mainly the Alouatta ssp, which serves as a sentinel species for the YF virus. In those animal models, YF is characterized by a hemorrhagic viral disease with multiple organ failure and cardiovascular shock, similarly to that affecting human beings. In Rhesus monkeys, marked lymphopenia has been reported preceding the spleen, liver, kidney and lymphoid tissue damages. Those findings are probably due to viral replication, release of cytokines, IL-4, IL-5, IL-6, IL-8, IL-12/23p40, IL-15, IL-17, G-CSF, GM-CSF, sCD40, RANTES, MCP-1 and INF Ɣ , and gene expression associated with immune response, ionic metabolism and apoptosis. 6,7 Cardiovascular involvement in arboviral diseases was described in 1822 in YF, with myocardial impairment characterized by bradycardia. Later, Lloyd 8 has reported prolongation of the atrioventricular conduction and ventricular repolarization changes. In 1965, bradycardia and hypotension were reported in chikungunya, and, in 1973, myocarditis, pericarditis and atrial fibrillation were reported in dengue fever. 9,10 A recent systematic review has reported that cardiovascular manifestations are common in chikungunya, mainly hypotension, shock, arrhythmias, myocarditis, dilated cardiomyopathy and congestive heart failure with troponin level elevation. 11 The histopathological assessment of the cardiac tissue of a fatal case of myocarditis and cardiogenic shock due to dengue fever in Brazil has shown muscular necrosis and interstitial edema with viral particles in cardiomyocytes and interstitial space, suggesting direct action of the virus in the myocardium. 12 Cases of myocarditis, heart failure, arrhythmia, atrial fibrillation and ventricular and supraventricular tachycardia have been reported in zika. 13 The varied clinical presentation of YF, from asymptomatic to severe forms, affects directly the disease’s therapeutic strategy. The malignant manifestations are associated with a mortality rate of up to 50%, requiring, thus, attention and differentiated care. 14 Although the disease has no effective specific treatment, respiratory, hemodynamic, metabolic and hemostatic supports, in addition to appropriate control of comorbidities, are fundamental to establish the patient’s recovery. Moreover, theMinistry of Health criteria for outpatient clinic follow‑up or hospitalization should be met in patients with heart diseases (Table 2). 14 However, some particularities of clinical management do apply to those patients. There is no study in the literature about the safest way to treat patients with coronary artery disease (CAD) and manifestations of YF. The experience in treating epidemics of other arboviral diseases in Brazil, however, could be a reference. In 2013, the Brazilian National Institute of Cardiology (Instituto Nacional de Cardiologia) issued recommendations for the use of antiplatelet drugs in patients with CAD and dengue fever, which were incorporated into the Ministry of Health Manual of Diagnosis and Clinical Management of dengue fever. 15 In that document, the recommendations for suspension of antiplatelet drugs acknowledged the importance of different levels of platelet count essentially in patients with bare‑metal or first-generation drug-eluting stents, who required at least 6 months of dual antiplatelet therapy to minimize the risk of thrombosis. 15 Since then, the most frequent use of second‑generation 207