In our study, evidence of myocardial involvement was found in 22% of patients who were hospitalized, among whom clinical manifestations ranged in severity from mild elevation of cardiac biomarker levels to myocarditis. Fortunately, these cardiac abnormalities were transient and did not necessitate specific treatment. Impairment of systolic function, characterized by a left ventricular ejection fraction of less than 45%, was found in other studies of severe dengue [4, 9, 16]. In another case report of 102 paediatric patients with DHF, 10 patients had fulminant myocarditis that necessitated early inotropic drug support for acute heart failure [13]. Prospective studies have reported various incidences of abnormal cardiac involvement in dengue: myocarditis in 15–27% of cases [6, 8, 12, 15, 20, 33] and functional cardiac abnormalities in up to 40% [4, 31, 34].
In contrast to these findings, myocarditis was suspected in two of our patients on the basis of clinical information, elevation of cardiac enzyme levels, and minimal depression of left ventricular ejection fraction. The difference in the incidence of myocarditis in other reports may be related to dengue severity, which can vary year by year; this study was conducted during a year when severe dengue was not prevalent. Our results are compatible with those of a report of dengue cases in Southeast Asia [7, 27] and a report from Sri Lanka [8]. Wichmann et al. [12] showed that 25% of patients with dengue had elevated levels of one or more cardiac biomarkers, such as myoglobin, CK-MB, troponin-T, N-terminal pro B-type natriuretic peptide, and heart-type fatty acid-binding protein. Myocardial involvement may result from a direct effect of the dengue virus or from cytokine-induced immune damage, in which high circulatory levels of pro-inflammatory cytokines cause depression of myocardial function [1, 2]. Another potential mechanism is regional vulnerability to coronary hypoperfusion [29]. Patients with elevated levels of cardiac biomarkers showed more inflammatory activity, such as higher white blood cell counts, but these findings were not statistically significant compared with previous studies [23].
Cardiac involvement in dengue, although often mild, can be severe, progressing to heart failure, according to several reports [ 4, 17, 32]. Cardiac and hemodynamic parameters are affected by cardiac function, volume status and autonomic responses [29]. Functional cardiac involvement in dengue was found to involve both diastolic and systolic function and was related to severity of plasma leakage [29]. Echocardiographic findings of myocardial injury in DVI have been demonstrated [9, 20, 23, 24, 30]. We found that abnormalities in cardiac parameters were related to the severity of DVI. Decreases in left ventricular ejection fraction, cardiac index and left ventricular diastolic inflow, and elevations in systemic vascular resistance in DHF are likely to be affected by reduced intravascular volume [29]. We found decreases in mitral valve early wave peak velocities, early diastolic mitral annular velocity (e´), left ventricular outflow tract mean and cardiac index in DHF. Lower e´ in this study may reflect diastolic dysfunction, as in previous studies [28, 29]. Cardiac functional assessment with the use of tissue Doppler imaging parameters revealed that e´ was significantly decreased in patients with severe dengue, which may reflect impaired left ventricular relaxation and diastolic defects [18, 29].
Fatal dengue-related myocarditis has also been reported. In a study of adult and paediatric cases in Brazil, the incidence of myocarditis amongst patients with clinical manifestations or elevated biomarker levels was approximately 15% [19]. In a subset of these cases, echocardiographic or magnetic resonance imaging (MRI) findings were abnormal [12, 15]. When dengue-related myocarditis occurs, good supportive care with optimal intravascular volume and maintenance fluid is crucial. According to many studies, myocarditis is transient and self-limiting. In particular, dengue with suspected cardiac involvement should not be treated with iatrogenic fluid overload [16, 19]. The decrease in heart rate on the day of defervescence that has been observed in DVI is attributed to increased parasympathetic activity [26]. In this study, we found that patients with severe DVI are likely to be at risk of cardiac involvement; however, the numbers of patients categorized by severity were small. Further studies are needed to evaluate the risk factors. We found that DHF was one of the associated risk factors for the development of cardiac involvement in DVI. This finding will increase physicians’ awareness of the possibility of cardiac involvement in patients with DHF.
This study had some limitations. First, we studied a population at only a single center in Thailand; our data may not be representative of all patients with dengue. Second, we studied hospitalized adults with DVI during a period when few cases of myocarditis related to dengue were reported; hence, the results may not be all patients with DVI. Third, we used cardiac biomarker elevation and serial echocardiography to screen for myocarditis in patients with DVI, but these are not ideal screening tools. Cardiac MRI is more sensitive than echocardiography for subclinical myocarditis, but is very expensive.