|Year : 2019 | Volume
| Issue : 1 | Page : 30-34
Cardiac manifestations in dengue
Parag Viren Papalkar, Rajesh R Sarode, Sourya Acharya, Sunil Kumar
Department of Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences (Deemed to be University), Wardha, Maharashtra, India
|Date of Submission||03-Dec-2018|
|Date of Decision||28-Jan-2019|
|Date of Acceptance||05-Feb-2019|
|Date of Web Publication||18-Feb-2019|
Prof. Sunil Kumar
Department of Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences (Deemed to be University), Wardha, Maharashtra
Source of Support: None, Conflict of Interest: None
Aim: To study the prevalence of cardiac manifestations in patients of dengue fever. Settings and Design: This cross-sectional study was done in a tertiary care hospital conducted for a period of 2 years from September 2016 to October 2018. Methods: Patients with complaints of fever and suspected to have dengue were subjected to dengue serology. Confirmed cases of dengue were then classified according to the World Health Organization criteria into dengue fever, dengue hemorrhagic fever (DHF), and dengue shock syndrome. The assessment of cardiac manifestations was done based on electrocardiogram (ECG), echocardiogram, and cardiac marker. The data was analyzed using statistical significance tests. Results: Out of 60 patients, 36 (60%) were male and 24 (40%) were female, and the male-to-female ratio was 1.5:1. The mean age of the patients was 38 ± 16.69 years. Patients of dengue fever, DHF, and dengue shock syndrome were 51, 7, and 2 respectively. The most common ECG abnormality was sinus bradycardia seen in 9 (15%) patients, followed by sinus tachycardia in 6 (10%) and ST-T changes in 5 (8.33%). Echocardiography was normal in 54 (90%) patients, systolic dysfunction was found in 4 (6.67%) patients, and pericardial effusion was found in 2 (3.33%) patients. Eight (13.33%) patients had abnormal creatine kinase-muscle/brain values. Conclusion: Cardiac manifestations are common in dengue fever, seen in one-third of the patients. Platelet counts < 100,000/mm3 and a higher hematocrit are more likely to be associated with cardiac manifestations.
Keywords: Cardiac, dengue, echocardiography, electrocardiography
|How to cite this article:|
Papalkar PV, Sarode RR, Acharya S, Kumar S. Cardiac manifestations in dengue. Indian J Med Spec 2019;10:30-4
| Introduction|| |
Dengue fever is a life-threatening vector-borne tropical disease, causative agent being dengue virus (DENV). DENV-1, DENV-2, DENV-3, and DENV-4 are the four virus serotypes which are transmitted to humans mostly by the Aedes aegypti mosquito.
Clinical features suggesting cardiac involvement in dengue are diverse, and patients are often asymptomatic though chest pain, palpitations, irregularities of pulse, hypotension, pulmonary edema, and shock are some of the features that may be found.,
Cardiac manifestations in dengue may be seen in the form of asymptomatic bradycardia to life-threatening myocarditis.,, Sinus bradycardia, transient ventricular arrhythmias, prolongation of PR interval, nonspecific ST-segment and T-wave changes, and transient atrioventricular blocks are some of the findings that can be seen in cases of dengue.,,,,,,,,,
Various studies have stated involvement of myocardium in the form of myocarditis and acute injury leading to left ventricular systolic dysfunction, pericardial effusion, and regional wall motion abnormalities.,,,,,,,,,,,,
To date, no study has addressed the correlation of hematological indices such as platelets and hematocrit with cardiac manifestations in dengue. This study was performed with the aim to find the prevalence of cardiac manifestations in dengue patients presenting to a tertiary care hospital and to correlate cardiac involvement with platelets and hematocrit.
| Methods|| |
This cross-sectional study was carried out on 60 patients admitted to a tertiary care hospital from September 2016 to October 2018. Patients with age more than 16 years with positive dengue serology (NS-1/IgM/both) were included in the study.
Patients on medications affecting the heart rate/rhythm such as calcium channel blockers/beta-blockers or patients with a history of preexisting heart disease with previous electrocardiogram (ECG) abnormality were excluded from the study.
Ethical clearance was obtained from the Institutional Ethics Committee before the study, and written informed consent was obtained from the participating patients.
Admitted patients were included in the study and were classified into dengue fever, dengue hemorrhagic fever (DHF), and dengue shock syndrome based on the World Health Organization (WHO) criteria. Case definitions of dengue fever, DHF, and dengue shock syndrome were as follows:
Acute febrile illness with two or more of the following: headache, retro-orbital pain, myalgia, arthralgia/bone pain, rash, hemorrhagic manifestations, leukopenia (white blood cells ≤5000 cells/mm3), thrombocytopenia (platelet count <150,000 cells/mm3), and rising hematocrit (5%–10%).
And at least one of the following: supportive serology test, occurrence at the same location, and time as confirmed cases of dengue fever.
Dengue hemorrhagic fever
Four cardinal features of DHF as defined by the WHO are as follows:
- Fever or history of fever lasting 2-7 days occasionally biphasic
- Thrombocytopenia (<100 × 103/mm3)
- Hemorrhagic manifestations shown by anyone of the following – A positive tourniquet test, petechiae, ecchymosis, or purpura, bleeding from the mucosa or injection site, hematemesis, melena, and hematuria
- Evidence of plasma leakage owing to increased vascular permeability shown by any one of the following: rising hematocrit/hemoconcentration ≥20% from baseline, signs of plasma leakage such as pleural effusion, ascites, or hypoproteinemia.
Dengue shock syndrome
DHF plus circulatory failure with signs of shock such as rapid and weak pulse, narrow pulse pressure (<20 mmHg) or hypotension (<90 mmHg), cold clammy skin, and mental status alteration.
The WHO suggested a two-group classification in 2008, which categorized dengue into two groups: dengue fever with or without warning signs and severe dengue. Since this classification is currently being tested and is not finalized yet, the classification of dengue fever/DHF/dengue shock syndrome was used in this study.
On the day of admission, patients underwent general physical examination, systemic examination, and tests that included complete blood count with platelet count and hematocrit, electrocardiography, two-dimensional echocardiography, and cardiac enzyme – creatine kinase-muscle/brain (CK-MB) (normal range: 0–20 IU).
Electrocardiography was done on the day of admission when the patient was afebrile. The following parameters in the ECG were observed: heart rate, PR interval, ST-T changes, broad QRS complexes, and QT interval.
Echocardiography changes were interpreted as systolic dysfunction which refers to impaired ventricular contraction and pericardial effusion which refers to abnormal accumulation of fluid in the pericardial cavity.
Statistical analysis was done using descriptive and inferential statistics using Chi-square test, Student's unpaired t-test, and one-way ANOVA. Software used in the analysis SPSS 20.0 version developed by (IBM, USA and GraphPad Prism 6.0 version developed by GraphPad Software, Inc., California USA). P < 0.05 was considered as the level of significance.
| Results|| |
In this study of 60 patients, 35 (58.33%) patients were in the age group of 16–40 years, 17 (28.33%) patients were in the age group of 41–60 years, and 8 (13.34%) patients were above the age group of 60 years. There were total 51 (85%) patients of dengue fever, 7 (11.67%) of DHF, and 2 (3.33%) of dengue shock syndrome.
In 51 cases of dengue fever, 38 (74.51%) patients had normal ECG findings and 2 (3.92%) patients had sinus tachycardia while sinus bradycardia was present in 9 (17.65%) patients and ST-T changes in 2 (3.92%) patients. Sinus tachycardia was present in 3 (42.87%) out of 7 patients of DHF, while 2 (28.57%) patients had ST-T changes, 1 (14.28%) patient had prolonged PR interval, and 1 (14.28%) patient had normal ECG. In 2 patients of dengue shock syndrome, 1 (50%) had sinus tachycardia and 1 (50%) had ST-T changes. Abnormal ECG findings were compared using Chi-square test and were found to be statistically significant (P < 0.05) in dengue fever and DHF [Table 1].
|Table 1: Correlation of electrocardiogram findings to severity of dengue infection|
Click here to view
Echocardiography was normal in 54 (90%) patients. The most common 2D echocardiographic abnormality was systolic dysfunction seen in 4 (6.67%) patients, followed by pericardial effusion seen in 2 (3.33%) patients. Abnormal 2D echocardiographic findings were compared using Chi-square test and were found to be statistically significant (χ2 = 2.62, P < 0.05) in dengue fever and DHF [Table 2].
|Table 2: Correlation of two-dimensional echocardiographic findings to severity of dengue infection|
Click here to view
CK-MB was elevated in 8 (13.33%) of the 60 patients while it was normal in 52 (86.67%) patients, which was found to be statistically significant (χ2 = 3.03, P < 0.05) in dengue fever and DHF [Table 3].
|Table 3: Correlation of creatine kinase-muscle/brain to severity of dengue infection|
Click here to view
In our study, there were 13, 6, and 2 patients of dengue fever, DHF, and dengue shock syndrome, respectively, in which cardiac manifestations were present in the form of either ECG changes or 2D echocardiography findings or raised CK-MB. Hence, the overall incidence of cardiac manifestations was 21 patients (35%) out of the 60, which was statistically significant (χ2 = 13.65, P < 0.05).
Thrombocytopenia with platelet count less than equal to one lakh was found in 38 (63.33%) patients while 20 (36.67%) patients had platelet count more than one lakh. In the patients with platelet count less than or equal to one lakh, cardiac manifestations were present in 17 (44.74%) patients, while when platelet count was more than one lakh, cardiac manifestations were present in 4 (18.18%) patients (χ2 = 4.31, P < 0.05).
The mean value of hematocrit was 46.86 ± 9.10 in patients which showed cardiac manifestations and it was 40.41 ± 5.46 in patients in which cardiac manifestations were absent, which was statistically significant (Student's t-test value: 3.43, P < 0.05).
| Discussion|| |
Dengue is one of the most important emerging viral diseases globally. The incidence of dengue viral infection has seen an increasing trend in recent years in India. The majority of symptomatic infections result in a relatively benign disease course. Some patients develop severe clinical manifestations, including bleeding, organ impairment, and endothelial dysfunction with increased capillary permeability causing hypovolemic shock that can lead to cardiovascular collapse.
Dengue fever has been seen over all age groups in our study population of 60 patients. Mean age of the population was 38 ± 16.69 years with a male-to-female ratio of 1.5:1 indicating male preponderance.
Electrocardiography was normal in majority of the population (65%). The most common ECG abnormality noted was sinus bradycardia found in 15% patients, followed by sinus tachycardia found in 10% of the patients. Similarly, in a study conducted by Arora and Patil, sinus bradycardia was the most common ECG abnormality found in 8.77% of the patients, followed by sinus tachycardia in 3.51% of the patients.
In our study, we found that echocardiographic findings are often subclinical since most of the patients showed normal findings. The most common echocardiographic abnormality was systolic dysfunction found in 6.67%, followed by pericardial effusion found in 3.33%. Satarsinghe et al. in 2007 found that 24% out of 217 patients had echocardiographic abnormality while none had clinical features of overt myocarditis. All patients showed improvement at 3 months. A study by Miranda et al. found that two patients had reduced left ventricular function, two had left ventricular segmental hypokinesia, and one had pericardial effusion.
The increased production of cytokines including tumor necrosis factor-alpha and interferon-alpha and release of other chemical mediators is responsible for rise in vascular permeability and abnormal leakage of plasma leading to pericardial effusion. In our study, we found that pericardial effusion is often minimal and asymptomatic which resolves by the time a patient gets discharge from the hospital. The need for pericardiocentesis does not arise most of the times since capillary leakage causing pericardial effusion is transient and self limiting phenomenon. Similar findings were noted in a study by Yusoff et al. As a result, fluid resuscitation in dengue should be guided by hematocrit, blood pressure, and urine output as overzealous fluid therapy can cause pericardial effusion.
The postulated underlying mechanisms for reduced left ventricular ejection fraction are immune in origin although myocarditis may be a contributory factor. It is also postulated that the mechanism of cardiac dysfunction is direct infection of cardiac muscle cells by DENV.
ECG and echocardiographic abnormalities are common during dengue infection. These are asymptomatic and most are transient among patients with dengue fever and DHF. These conduction abnormalities are most likely manifestations of involvement of the cardiac conduction system in dengue infection. The pathophysiology of shock state in dengue shock syndrome may be attributed to direct involvement of myocardium by DENV, which was hitherto considered to be capillary permeability and plasma leakage.,,
In our study group of 60 patients, it was found that 52 patients (86.67%) had normal CK-MB levels and 8 patients had abnormal values (13.33%). In another study conducted by Yadav et al., abnormal CK-MB values were found in 39 (37.5%) patients among a study group of 104 patients.
In our study, we found that the incidence of cardiac manifestations was more common in DHF and dengue shock syndrome which was 85% and 100%, respectively. The overall incidence of cardiac manifestations was 35%. Similarly, in a study conducted by Arora and Patil, they found that the incidence of cardiac manifestations was 30%, 35.29%, and 53.33% in patients of dengue fever, DHF, and dengue shock syndrome, respectively. Since the number of patients in dengue fever and dengue shock syndrome categories was small, statistical differences though analyzed may not be robust.
Similarly, there was a statistically significant correlation between thrombocytopenia and occurrence of cardiac manifestations (P < 0.05). Comparison of hematocrit with cardiac manifestations revealed that mean value of hematocrit was significantly higher (46.86 ± 9.10) in patients who showed cardiac manifestations as compared to those without cardiac manifestations (40.41 ± 5.46). Thus, it can be concluded that cardiac involvement has a significant correlation with thrombocytopenia and hemoconcentration.
Other cardiac markers such as troponins and quantitative assay of biomarkers could not be assessed in our study due to financial constraints.
Cardiac manifestations are often transient and require repeated electrocardiographic and echocardiographic evaluation which was not done in this study because of poor compliance of the patients towards follow-up and repeated investigations.
| Conclusion|| |
Cardiac involvement in dengue fever is often underdiagnosed due to the low index of clinical suspicion and its overlapping clinical manifestations such as hypotension, tachycardia, pulmonary edema, and capillary leak associated with DENV infection. Depression of myocardial function is frequent in DHF and dengue shock syndrome. Follow-up studies are needed to evaluate the hemodynamic impact of myocardial involvement in patients with dengue. Most forms of treatment currently are purely supportive, but with better understanding of the pathophysiology of dengue, targeted treatment may become possible.
Financial support and sponsorship
This study was financially supported by the Department of Medicine, Jawaharlal Nehru Medical College, Sawangi (Meghe), Wardha, Maharashtra, India.
Conflicts of interest
There are no conflicts of interest.
| References|| |
Ross TM. Dengue virus. Clin Lab Med 2010;30:149-60.
Lee IK, Lee WH, Liu JW, Yang KD. Acute myocarditis in dengue hemorrhagic fever: A case report and review of cardiac complications in dengue-affected patients. Int J Infect Dis 2010;14:e919-22.
Promphan W, Sopontammarak S, Pruekprasert P, Kajornwattanakul W, Kongpattanayothin A. Dengue myocarditis. Southeast Asian J Trop Med Public Health 2004;35:611-3.
Wiwanitkit V. Dengue myocarditis, rare but not fatal manifestation. Int J Cardiol 2006;112:122.
Arora M, Patil RS. Cardiac manifestation in dengue fever. J Assoc Physicians India 2016;64:40-4.
Sheetal S, Jacob E. A study on the cardiac manifestations of dengue. J Assoc Physicians India 2016;64:30-4.
Yadav RK, Kumar S. To study cardiac manifestations in patients presenting with dengue infection and to find out the correlation of cardiac manifestations to warning signs of dengue. Int J Adv Med 2017;4:323-8.
Tarique S, Murtaza G, Asif S, Qureshi IH. Ecg manifestations in dengue infection. Ann King Edward Med Univ (Print) 2013;19:282-5.
Krishnan D. A cross sectional study of clinical profile and cardiac manifstations in patients with primary and secondary dengue fever in a tertiary care hospital. J Med Sci Clin Res 2016;4:11515-21.
Mahmod M, Darul ND, Mokhtar I, Nor NM, Anshar FM, Maskon O, et al.
Atrial fibrillation as a complication of dengue hemorrhagic fever: Non-self-limiting manifestation. Int J Infect Dis 2009;13:e316-8.
Horta Veloso H, Ferreira Júnior JA, Braga de Paiva JM, Faria Honório J, Junqueira Bellei NC, Vicenzo de Paola AA, et al.
Acute atrial fibrillation during dengue hemorrhagic fever. Braz J Infect Dis 2003;7:418-22.
Donegani E, Briceño J. Disorders of atrio-ventricular conduction in patients with hemorrhagic dengue. Minerva Cardioangiol 1986;34:477-80.
Kaushik JS, Gupta P, Rajpal S, Bhatt S. Spontaneous resolution of sinoatrial exit block and atrioventricular dissociation in a child with dengue fever. Singapore Med J 2010;51:e146-8.
Lateef A, Fisher DA, Tambyah PA. Dengue and relative bradycardia. Emerg Infect Dis 2007;13:650-1.
Weerakoon KG, Kularatne SA, Edussuriya DH, Kodikara SK, Gunatilake LP, Pinto VG, et al.
Histopathological diagnosis of myocarditis in a dengue outbreak in Sri Lanka, 2009. BMC Res Notes 2011;4:268.
Sam SS, Omar SF, Teoh BT, Abd-Jamil J, AbuBakar S. Review of dengue hemorrhagic fever fatal cases seen among adults: A retrospective study. PLoS Negl Trop Dis 2013;7:e2194.
Kirawittaya T, Yoon IK, Wichit S, Green S, Ennis FA, Gibbons RV, et al.
Evaluation of cardiac involvement in children with dengue by serial echocardiographic studies. PLoS Negl Trop Dis 2015;9:e0003943.
Sengupta SP, Nugurwar A, Jaju R, Khandheria BK. Left ventricular myocardial performance in patients with dengue hemorrhagic fever and thrombocytopenia as assessed by two-dimensional speckle tracking echocardiography. Indian Heart J 2013;65:276-82.
Yusoff K, Roslawati J, Sinniah M, Khalid B. Electrocardiographic and echocardiographic changes during the acute phase of dengue infection in adults. J Hong Kong Coll Cardiol 1993;1:93-6.
Virk HU, Inayat F, Rahman ZU. Complete heart block in association with dengue hemorrhagic fever. Korean Circ J 2016;46:866-9.
Miranda CH, Borges Mde C, Schmidt A, Pazin-Filho A, Rossi MA, Ramos SG, et al.
A case presentation of a fatal dengue myocarditis showing evidence for dengue virus-induced lesion. Eur Heart J Acute Cardiovasc Care 2013;2:127-30.
Marques N, Gan VC, Leo YS. Dengue myocarditis in Singapore: Two case reports. Infection 2013;41:709-14.
Salgado DM, Eltit JM, Mansfield K, Panqueba C, Castro D, Vega MR, et al.
Heart and skeletal muscle are targets of dengue virus infection. Pediatr Infect Dis J 2010;29:238-42.
World Health Organization and the Special Programme for Research and Training in Tropical Diseases (TDR). Dengue Guidelines for Diagnosis, Treatment, Prevention and Control: New Edition. Available from: https://www.who.int/rpc/guidelines/9789241547871/en/
. [Last accessed on 2019 Jan 31].
Satarsinghe R, Arultnithy K, Amerasena N, Bulugahapitiya U, Sahayam D. Asymptomatic myocardial involvement in acute dengue virus infection in a cohort of adult Sri Lankans admitted to a tertiary referral centre. Br J Cardiol 2007;14:171-3.
Miranda CH, Borges Mde C, Matsuno AK, Vilar FC, Gali LG, Volpe GJ, et al.
Evaluation of cardiac involvement during dengue viral infection. Clin Infect Dis 2013;57:812-9.
Singhi S, Kissoon N, Bansal A. Dengue and dengue hemorrhagic fever: Management issues in an intensive care unit. J Pediatr (Rio J) 2007;83:S22-35.
Kohli U, Saharan S, Lodha R, Kabra SK. Persistent thrombocytopenia following dengue shock syndrome. Indian J Pediatr 2008;75:82-3.
Fernandes AI, Mendes CL, Simões RH, Silva AE, Madruga CB, Brito CA, et al.
Cardiac tamponade in a patient with severe dengue fever. Rev Soc Bras Med Trop 2017;50:701-5.
Gupta VK, Gadpayle AK. Subclinical cardiac involvement in dengue haemorrhagic fever. J Indian Acad Clin Med 2010;11:107-11.
Yadav BL, Harshvardhan L, Yadav KS. Magnitude of cardiac involvement in dengue fever. J Evol Med Dent Sci 2017;6:570-4.
[Table 1], [Table 2], [Table 3]