European Journal of Cardiovascular Medicine

Dengue fever, a mosquito-borne viral infection caused by the dengue virus, represents a significant public health concern, especially in tropical and subtropical regions. With an estimated 390 million infections occurring annually worldwide, dengue poses a substantial burden on healthcare systems and economies, particularly in endemic countries. The clinical manifestations of dengue range from mild febrile illness to severe and potentially life-threatening conditions such as dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Despite extensive research into its epidemiology and pathophysiology, the full spectrum of complications associated with dengue infection continues to be elucidated.^1-3

Among the myriad of complications, cardiac involvement in dengue fever has garnered increasing attention in recent years. Cardiac complications, though less commonly reported compared to hemorrhagic manifestations, can significantly impact patient outcomes and pose diagnostic and therapeutic challenges. The spectrum of cardiac complications includes myocarditis, pericarditis, arrhythmias, and heart failure, which can occur during the acute phase of the illness or as delayed sequelae. The pathophysiology underlying cardiac involvement in dengue is multifactorial, involving direct viral invasion, immune-mediated injury, and the systemic effects of cytokine storm and vascular leakage.^4-6

Despite the recognized significance of cardiac complications in dengue fever, there is a paucity of comprehensive studies that systematically evaluate their incidence, clinical profile, and outcomes. Most existing data are derived from case reports and small case series, limiting the generalizability of findings and the development of evidence-based management strategies. Understanding the cardiac manifestations of dengue is crucial for early diagnosis, appropriate management, and the prevention of severe morbidity and mortality.^7-10

This research aims to bridge this knowledge gap by systematically investigating the clinical profile, incidence, and outcomes of cardiac complications in patients with dengue fever admitted to our tertiary care hospital. Through detailed clinical assessments, electrocardiographic (ECG) monitoring, and echocardiographic evaluations, we seek to delineate the spectrum of cardiac involvement, identify potential risk factors, and provide insights into the pathophysiological mechanisms at play. By enhancing our understanding of these complications, we hope to contribute to improved clinical management and prognostication of dengue fever, ultimately reducing the burden of this pervasive infection on affected populations.

Study Design and Setting

This study was a prospective observational study conducted at Patna Medical College and Hospital, Patna. The study aimed to investigate the incidence, clinical profile, and outcomes of cardiac complications in patients diagnosed with dengue fever. The study was conducted over a period over January to November 2023.

Study Population

The study included patients of all age groups who were admitted to the hospital with a confirmed diagnosis of dengue fever, based on clinical criteria and laboratory confirmation (positive dengue NS1 antigen and/or dengue IgM antibodies). Patients with pre-existing cardiac conditions, known congenital heart diseases, or those on chronic cardiac medications were excluded to eliminate confounding factors. A total of 78 patients were included in the study based on the sample size calculation to ensure sufficient statistical power.

Data Collection

Clinical data were collected from patient medical records, including demographic information, clinical presentation, laboratory results, and treatment details. A standardized data collection form was used to ensure consistency and completeness of the recorded information.

Clinical Assessment and Monitoring

All patients underwent a thorough clinical assessment upon admission, including a detailed medical history and physical examination. Vital signs were monitored regularly, and specific attention was given to signs and symptoms indicative of cardiac involvement.

Electrocardiographic (ECG) Monitoring

Each patient had a 12-lead ECG performed upon admission and subsequently as clinically indicated. The ECGs were analyzed for abnormalities such as arrhythmias, conduction defects, ischemic changes, and other relevant findings. Serial ECGs were performed in patients showing initial abnormalities to monitor progression or resolution.

Echocardiographic Evaluations

Echocardiography was performed on all patients suspected of having cardiac complications based on clinical or ECG findings. The echocardiographic assessments included measurements of left ventricular function, wall motion abnormalities, pericardial effusion, and valvular integrity. Echocardiograms were interpreted by experienced cardiologists to ensure accuracy.

Laboratory Investigations

Routine laboratory investigations included complete blood counts, liver function tests, renal function tests, serum electrolytes, and markers of cardiac injury such as troponin I and creatine kinase-MB (CK-MB). These investigations were performed at baseline and as needed based on the clinical condition of the patients.

Outcome Measures

The primary outcome measure was the incidence of cardiac complications in patients with dengue fever. Secondary outcomes included the types and severity of cardiac complications, associated risk factors, duration of hospital stay, need for intensive care, and in-hospital mortality.

Statistical Analysis

Data were analyzed using SPSS software version 25. Descriptive statistics were used to summarize the demographic and clinical characteristics of the study population. Continuous variables were presented as means and standard deviations, while categorical variables were presented as frequencies and percentages. The incidence of cardiac complications was calculated, and potential risk factors were identified using univariate and multivariate logistic regression analyses. A p-value of less than 0.05 was considered statistically significant.

Ethical Considerations

The study was approved by the Institutional Ethics Committee of Patna Medical College and Hospital, Patna. Written informed consent was obtained from all participants or their legal guardians before inclusion in the study. The study was conducted in accordance with the Declaration of Helsinki and adhered to good clinical practice guidelines.

The study encompassed 78 patients diagnosed with dengue fever, with an average age of 35.4 ± 15.2 years. A gender distribution revealed a predominance of males (66.7%) over females (33.3%). Clinically, all patients presented with fever, while other symptoms included headache (57.7%), myalgia (50%), and rash (41%). Notably, 25.6% of patients exhibited hemorrhagic manifestations, and 12.8% experienced shock, underscoring the severity and varied clinical presentation of dengue fever in this cohort.

Table 1: Demographic and Clinical Characteristics of the Study Population

Cardiac complications were identified in a subset of patients, illustrating the diverse cardiac impact of dengue fever. Myocarditis was the most common complication, affecting 7.7% of the patients, followed by arrhythmias (5.1%), pericarditis (3.8%), and heart failure (2.6%). These findings highlight the significant, albeit less commonly reported, cardiac involvement in dengue fever and emphasize the need for vigilance in cardiac monitoring.

Table 2: Cardiac Complications in Dengue Fever Patients

A detailed analysis comparing patients with and without cardiac complications revealed notable differences. Patients with cardiac complications had a slightly higher average age (38.6 ± 16.4 years) compared to those without (34.6 ± 14.8 years), although this difference was not statistically significant (p=0.217). Gender distribution was identical in both groups, with males comprising 66.7% and females 33.3%. However, hemorrhagic manifestations (53.3% vs. 19%, p=0.018) and shock (33.3% vs. 7.9%, p=0.011) were significantly more prevalent in patients with cardiac complications, indicating these factors as potential risk indicators.

Table 3: Clinical Profile of Patients with Cardiac Complications

Electrocardiographic (ECG) abnormalities were prominent among patients with cardiac complications. Arrhythmias were observed in 4 patients, conduction defects in 5, and ischemic changes in 6. These ECG findings underscore the varied electrophysiological disturbances that dengue fever can precipitate, necessitating routine ECG monitoring in affected patients.

Table 4: ECG Findings in Patients with Cardiac Complications

Echocardiography provided further insights into the cardiac abnormalities in dengue patients. Reduced left ventricular ejection fraction was detected in 6 patients, pericardial effusion in 3, and wall motion abnormalities in 4. These echocardiographic findings highlight the structural and functional cardiac impacts of dengue fever, reinforcing the importance of echocardiographic evaluations in patients with suspected cardiac involvement.

Table 5: Echocardiographic Findings in Patients with Cardiac Complications

Laboratory assessments revealed elevated cardiac biomarkers in patients with cardiac complications, with elevated troponin I levels in 10 patients and elevated CK-MB levels in 8. These biomarkers are indicative of myocardial injury, corroborating the clinical and imaging findings of cardiac involvement in dengue fever.

Table 6: Laboratory Findings in Patients with Cardiac Complications

Statistical analysis identified significant risk factors for developing cardiac complications. Patients with hemorrhagic manifestations had an odds ratio (OR) of 3.75 (95% CI: 1.25-11.25, p=0.018), while those in shock had an OR of 4.89 (95% CI: 1.45-16.46, p=0.011). These findings suggest that severe clinical presentations, particularly hemorrhagic manifestations and shock, are strong predictors of cardiac complications in dengue fever.

Table 7: Risk Factors for Cardiac Complications

The clinical outcomes for patients with cardiac complications were notably worse than for those without. Patients with cardiac complications had a significantly longer duration of hospital stay (12.5 ± 4.2 days vs. 8.3 ± 2.1 days, p<0.001), a higher need for intensive care (66.7% vs. 12.7%, p<0.001), and increased in-hospital mortality (13.3% vs. 1.6%, p=0.032). These outcomes underscore the critical impact of cardiac complications on the prognosis of dengue fever patients and the need for timely and effective management strategies.

Table 8: Clinical Outcomes

This study provides a comprehensive examination of cardiac complications in patients with dengue fever, offering significant insights into the incidence, clinical profile, risk factors, and outcomes associated with these complications. The findings highlight the substantial cardiac involvement in dengue fever, which, although less commonly reported than hemorrhagic manifestations, has a critical impact on patient outcomes.

The study identified a notable incidence of cardiac complications, affecting 19.2% of patients with dengue fever. The spectrum of cardiac involvement included myocarditis (7.7%), arrhythmias (5.1%), pericarditis (3.8%), and heart failure (2.6%). These findings align with previous studies that have reported varying rates of cardiac complications in dengue, underscoring the importance of recognizing and addressing this aspect of the disease. Myocarditis, characterized by inflammation of the heart muscle, was the most prevalent cardiac complication, emphasizing the need for heightened clinical vigilance and early diagnostic efforts to identify this potentially life-threatening condition. Other studies have reported a lower incidence of myocarditis but a higher prevalence of arrhythmias, suggesting variability in cardiac manifestations across different populations and settings.^11-13

The clinical profile of patients with cardiac complications revealed that these patients tended to be older and had a higher prevalence of severe clinical manifestations, such as hemorrhagic manifestations and shock. The significant association of hemorrhagic manifestations (53.3% vs. 19%) and shock (33.3% vs. 7.9%) with cardiac complications underscores the interplay between severe dengue presentations and cardiac involvement. The odds ratios for hemorrhagic manifestations (OR: 3.75, p=0.018) and shock (OR: 4.89, p=0.011) as risk factors highlight the increased vulnerability of these patients to cardiac complications. This correlation suggests that the systemic inflammatory response and vascular leakage characteristic of severe dengue may predispose patients to cardiac injury. Similar findings were reported in other studies, which also identified hemorrhagic manifestations and shock as significant risk factors for cardiac complications.^12-14

The study's findings reinforce the critical role of diagnostic and monitoring strategies in managing cardiac complications in dengue fever. ECG abnormalities were prevalent among patients with cardiac complications, with arrhythmias, conduction defects, and ischemic changes being the most common findings. Routine ECG monitoring is thus essential for early detection of electrophysiological disturbances. Furthermore, echocardiographic evaluations revealed significant structural and functional cardiac abnormalities, including reduced left ventricular ejection fraction, pericardial effusion, and wall motion abnormalities. These imaging findings underscore the importance of echocardiography in the comprehensive cardiac assessment of dengue patients, particularly those presenting with severe symptoms or ECG abnormalities. Other studies have also emphasized the utility of ECG and echocardiography in detecting cardiac involvement in dengue patients, supporting our findings.^13-15

Laboratory assessments revealed elevated cardiac biomarkers in patients with cardiac complications, with elevated troponin I levels in 10 patients and elevated CK-MB levels in 8. These biomarkers are indicative of myocardial injury, corroborating the clinical and imaging findings of cardiac involvement in dengue fever. The use of these biomarkers in routine laboratory investigations can aid in the early identification of cardiac involvement, enabling timely intervention. The elevated troponin I levels in 66.7% of patients with cardiac complications suggest a direct cardiac injury, likely due to the combined effects of viral myocarditis, immune-mediated damage, and the systemic impact of the dengue infection. These findings are consistent with those reported in other studies, which highlighted the role of cardiac biomarkers in diagnosing myocardial injury in dengue patients.^12-14

The study highlights the adverse clinical outcomes associated with cardiac complications in dengue fever. Patients with cardiac complications experienced significantly longer hospital stays, a higher need for intensive care, and increased in-hospital mortality compared to those without cardiac complications. These findings underscore the critical impact of cardiac involvement on the prognosis of dengue patients and the necessity for prompt and effective management strategies. The increased duration of hospital stay (12.5 ± 4.2 days vs. 8.3 ± 2.1 days, p<0.001) and the substantial need for intensive care (66.7% vs. 12.7%, p<0.001) reflect the severe morbidity associated with cardiac complications. Similar adverse outcomes were reported in other studies, which also noted higher mortality rates among dengue patients with cardiac complications.^11,13,15

The pathophysiology of cardiac involvement in dengue fever is multifactorial, involving direct viral invasion of the myocardium, immune-mediated injury, and the systemic effects of cytokine storm and vascular leakage. The findings of this study, including the significant association of severe clinical manifestations with cardiac complications, support the hypothesis that the inflammatory and vascular response to dengue infection plays a crucial role in cardiac injury. Further research into the molecular and cellular mechanisms underlying these processes is essential to develop targeted therapeutic interventions.

Based on the study findings, several recommendations can be made for clinical practice. Routine ECG and echocardiographic monitoring for all patients with severe dengue, especially those with hemorrhagic manifestations or shock, should be implemented to enable early detection of cardiac complications. Incorporating cardiac biomarkers such as troponin I and CK-MB into the routine laboratory evaluation of dengue patients can aid in identifying myocardial injury early. Developing comprehensive management protocols that include close monitoring, timely diagnosis, and appropriate treatment of cardiac complications is crucial to improve patient outcomes. Additionally, further studies are needed to explore the pathophysiological mechanisms of cardiac involvement in dengue fever and to identify potential therapeutic targets for reducing cardiac morbidity and mortality.

In conclusion, this study underscores the significant burden of cardiac complications in dengue fever, identifies key risk factors, and highlights the critical need for comprehensive cardiac monitoring and management. Early identification and appropriate intervention for cardiac complications are essential to improve clinical outcomes and reduce the morbidity and mortality associated with dengue fever. By enhancing our understanding of the cardiac manifestations of dengue, we can develop better strategies for managing this pervasive infection and ultimately mitigate its impact on affected populations

1. Murray NE, Quam MB, Wilder-Smith A. Epidemiology of dengue: past, present and future prospects. Clin Epidemiol. 2013 Aug 20;5:299-309.
2. Ilic I, Ilic M. Global Patterns of Trends in Incidence and Mortality of Dengue, 1990-2019: An Analysis Based on the Global Burden of Disease Study. Medicina (Kaunas). 2024 Mar 1;60(3):425. 
3. Zerfu, B., Kassa, T. & Legesse, M. Epidemiology, biology, pathogenesis, clinical manifestations, and diagnosis of dengue virus infection, and its trend in Ethiopia: a comprehensive literature review. Trop Med Health.2023; 51:11.
4. Jadav N, Vaghela N, Verma N, Davis D, Sonani AA, Patoliya P. Unmasking the Hidden Threat of Cardiac Involvement in Dengue Fever: A Critical Longitudinal Study. Cureus. 2023 Sep 25;15(9):e45961.
5. Parchani A, Krishnan Vs G, Kumar VKS. Electrocardiographic Changes in Dengue Fever: A Review of Literature. Int J Gen Med. 2021 Sep 14;14:5607-5614.