Dengue beyond fever-fatal dengue myocarditis and complete heart block: A case report and brief overview of cardiac manifestations of dengue fever

Abstract

Dengue is an endemic viral fever transmitted by mosquitoes that may be asymptomatic or cause a nonspecific flu-like illness. The disease’s most severe manifestations are dengue hemorrhagic fever and dengue shock syndrome. Various atypical manifestations have been observed that constitute the expanded dengue syndrome. Although uncommon, it is now known to cause cardiac complications that can be life-threatening and difficult to diagnose. We illustrate a case of a 16-year-old boy infected with dengue who experienced syncope, dizziness, and lethargy. His electrocardiogram showed third degree atrioventricular block which did not resolve with atropine and fluid resuscitation. After excluding all possible causes of complete heart block, transvenous pacing was done. A detailed workup was carried out that favored a diagnosis of subclinical myocarditis leading to complete heart block. The patient did not regain a normal rhythm and was considered for permanent pacemaker implantation. Myocarditis, pericarditis, rhythm disturbances, first- and second-degree atrioventricular blocks, and rarely third-degree heart blocks have been seen in dengue patients. However, a case of dengue illness associated complete heart blocks that is irreversible and necessitates a permanent pacemaker has never been described in the literature, and this is the first such case being reported. This article intends to increase clinicians’ awareness, particularly those in dengue-endemic regions, about better recognition and comprehension of cardiac problems associated with dengue fever.

Introduction

Dengue fever is a swiftly spreading arboviral disease transmitted by the Aedes aegypti mosquito. It is caused by the dengue virus, a ssRNA virus of the Flaviviridae family. Four serotypes of the virus have been identified: DENV-1, DENV-2, DENV-3, and DENV-4. The disease is endemic in Central and South America, Africa, the Middle East, and south and southeast Asia. ¹ The severity of outbreaks has escalated, putting 2.5 billion people at risk worldwide with a yearly death rate of 20,000. Around 390 million individuals are infected each year, with 96 million developing a clinical disease. ²

Most people with dengue have no symptoms or a mild fever, but some may develop life threatening dengue hemorrhagic fever or dengue shock syndrome. A small proportion of patients may experience severe organ dysfunction affecting the liver, heart, and nervous systems. ¹ Dengue-associated cardiac involvement has varied incidence and presentation. Myocarditis, pericarditis, functional abnormalities, arrhythmias, atrioventricular conduction disorders, and non-specific electrocardiographic (ECG) abnormalities are some of the cardiac problems observed in dengue patients. ³ Although few cases of myocarditis have been reported, AV blocks, particularly complete heart blocks (CHBs), have infrequently been described.^4,5 This article describes a rare occurrence of third-degree heart block and subclinical myocarditis in the context of dengue fever.

Case presentation

A 16-year-old boy presented to the emergency department with complaints of dizziness, syncope, weakness, and fatigue. He was drowsy and had a blood pressure of 100/60 mmHg, pulse rate of 20 bpm, and oxygen saturation of 95%. He was febrile with a temperature of 37.7°C. Systemic examination was unremarkable, and his Glasgow Coma Scale score was 15/15. An urgent electrocardiogram (EKG) showed complete AV dissociation and ST segment depressions in leads I, II, and avL (Figure 1(a)). Atropine 1 mg IV was given, and an infusion of normal saline was started for hemodynamic support. A repeat ECG did not show any improvement. No history of using rate-limiting drugs was found. Subsequently, the patient was transferred to the cardiac cath lab, and a temporary pacemaker (transvenous) was placed. A paced rhythm was achieved, and the rate was set to 75 bpm (Figure 1(b)). The patient improved after that. Further history revealed that 6 days ago, the patient was taken to another hospital due to continuous high-grade fever, severe body aches, and an episode of epistaxis. He had stable vital signs. Apart from routine investigations, dengue serology was ordered which came out positive. There he was treated with IV paracetamol, antibiotics, and fluids. The patient refused hospital admission and was sent home on symptomatic treatment and necessary advice. We performed serial investigations that are shown in Table 1.

Figure 1.

(a) is the ECG on arrival that illustrates a third degree atrioventricular (AV) block. The red and black arrows show the p waves and QRS complexes respectively. Blue arrows indicate ST depressions. The P–P interval is constant. (b) is the ECG after temporary pacemaker placement at 75 beats per minute. Black arrows show pacing spikes, whereas red arrows indicate the Left bundle brach block morphology of QRS consistent with the pacing of right ventricle. (c) is the ECG when temporary pacemaker was switched off. This demonstrates complete AV dissociation with black arrows depicting atrial rate of 75/min independent of ventricular rate of 38/min as shown by red arrows.

Table 1.

Laboratory investigations.

Laboratory parameter	Normal value	Patient’s values
		Before admission	Day 1	Day 3	Day 5
Complete blood count
Hemoglobin	11.5–17.5 g/dL	14.8	12.9	11.9	11.9
Hematocrit	36–54%		35.5	36	35.3
Total leukocyte count	4–11 × 103/uL	12.4	16.34	23.3	18.29
Platelets	150–450 × 103/Ul	187	46	180	637
Urea	18–45 mg/dL		93	124	79
Renal functions
Creatinine	0.6–1.2 mg/dL		1.5	2.1	1.6
Serum electrolytes
Na+	135–155 mmol/L		128	128	138
K+	3.5–5.5 mmol/L		4	4.21	4.54
Liver function tests
Total bilirubin	0.1–1.0 mg/dL		0.68	0.8
Alanine transaminase	10–55 U/L		48	53
Aspartate transaminase	8–35 U/L		33	31
Alkaline phosphatase	<390 U/L		142	160
Thyroid profile
Thyroid stimulating hormone	0.3–4.2 IU/mL		2.37
Total T3	0.8–2.0 ng/mL		1.4
Total T4	5.1–14.1 g/dL		7.53
Inflammatory markers
Erthrocyte sedimentation rate	0–20 mm/h		38	46	44
C-Reactive protein	<0.5 mg/dL		5.1	5.5	5
Cardiac enzymes
Troponin I	<0.6 ng/mL		21	24	25
CK-MB	<25 U/L		73	87	81
Others
Lactate dehydrogenase	100–300 IU/L		580	674	655

The values in bold highlight the abnormal results.

His dengue IgM was again positive, and confirmatory dengue polymerase chain reaction showed DENV-2 serotype. The patient was commenced on IV antipyretics, IV cefoperazone–sulbactam 2 g twice daily, and fluids. Platelets were transfused due to low platelets count and an episode of epistaxis and hematemesis on one occasion. Serial troponin-I, CK-MB, ESR, CRP, and LDH levels remained persistently elevated. The patient’s blood culture, malarial antigen, typhoid serology, influenza virus, COVID-19, and diphtheria testing were negative. During hospitalization, he experienced only mild shortness of breath but no chest pain. His ejection fraction, systolic function, and valve anatomy were normal with no evidence of congenital heart disease on the echocardiogram (Figure 2). Based on the ECG findings and unusual cardiac enzymes changes, a clinical diagnosis of dengue myocarditis with CHB was made. A cardiac MRI was in the plan but contraindicated due to the temporary pacemaker (TPM) in place, so it could not be done. The family refused an endomyocardial biopsy. The patient remained TPM dependent for 1 week (Figure 1(c)) with no return of normal spontaneous rhythm. Ultimately, it was decided to place a permanent pacemaker. Unfortunately, the night before the surgery, the patient collapsed suddenly and died despite resuscitative efforts.

Figure 2.

Echocardiogram in apical four chamber view showing good left ventricular contractility (a) and the electrode of temporary pacemaker (yellow arrow) in the right ventricle (b).

Discussion

Dengue fever is a viral disease with an endemic presence in more than 100 countries and a remarkable rise in its occurrence worldwide. Clinical signs and symptoms can range from asymptomatic to mild to severe. The disease progresses in three phases: a febrile phase with common symptoms of fever, headache, retro-orbital pain, myalgias, arthralgias, and rashes; a critical phase marked by increased capillary permeability that may cause shock and hemorrhages; and a convalescence phase. ⁶ The WHO reclassified the disease in 2009 as “dengue with or without warning signs” and “severe dengue.” ⁶ A new category, the expanded dengue syndrome, has been introduced to include unusual manifestations like hepatitis, neurologic dysfunction, coagulopathy, and cardiac complications that may affect a small number of patients. ⁷

Cardiac involvement is usually associated with DENV-2 and DENV-3 serotypes. It may result from the direct viral invasion of cardiac myocytes, immunological damage caused by cytokines, or both.^8,9 In the literature, there is a wide range of incidence data for cardiac complications in dengue patients. Cardiac involvement has been reported to occur in 12.5% of patients (n = 120) from India, 62.5% of patients (n = 120) from Sri Lanka, and 35% of patients in a Vietnamese study.^10–12

Dengue sickness can result in a wide array of heart complications. Myocarditis, pericarditis, myocardial depression with heart failure, and shock are among these conditions. ³ Rhythm disturbances such as atrial fibrillation, ventricular tachyarrhythmias, ventricular ectopic beats, bundle branch blocks, sinus node dysfunction, first- and second-degree AV blocks, and rarely complete AV blocks have been described. ¹³ Nonspecific ECG changes, such as ST-T changes and abnormal Q waves, can occur in myocarditis. ¹⁴

Heart blocks can develop from a direct and primary electrical insult or secondary to myocarditis. CHB happens less often than first-degree and second-degree AV blocks.^4,5 There has never been any case of patients needing a permanent pacemaker due to an irreversible CHB.

Different myocarditis prevalence rates have been reported in studies, including 11.3% in China, 24% in Sri Lanka, 37.5% in India, and 2.47% by Miranda et al.^15–18 Dengue myocarditis can cause symptoms of heart failure or it can be asymptomatic, as it was in our patient, causing diagnostic challenges and delays. ¹⁹

CMR and endomyocardial biopsy are valuable diagnostic tools but are not always available or indicated. In suspected cases of myocarditis, EKG changes, echocardiography abnormalities, and elevated biomarkers of myonecrosis (Troponin, CK-MB, LDH, etc.) are especially helpful.^16,20 The changes in EKG and cardiac biomarkers seen in our patient were in favor of acute myocarditis as per the European Society of Cardiology criteria. ²¹ The possibility of acute coronary syndrome was ruled out by the inconclusive EKG changes, lack of symptoms, and risk factors. All other causes of heart block, that is, drugs, electrolyte abnormalities, and hypothyroidism, were excluded.

The management of dengue myocarditis depends on its presentation. The cornerstones of therapy continue to be early detection of cardiac involvement and restoration of hemodynamic stability while avoiding fluid overload in systolic dysfunction. Myocardial damage is usually transitory and can resolve spontaneously; however, symptomatic patients with advanced AV blocks may require a pacemaker.

This case study has a few limitations. The exact cause of the patient’s death could not be determined. However, the possibility of a bradyarrhythmia or tachyarrhythmia resulting from misplacement of the TPM lead could not be ruled out. Moreover, due to distinct presentations and rare existence, workup for uncommon tropical diseases was not done. Our patient presented in peak dengue season and had symptoms and laboratory findings of dengue illness.

Conclusion

While the incidence of dengue fever continues to rise, the range of presentation is broadening with the emergence of uncommon and atypical manifestations that are poorly recognized. Although identifying cardiac involvement might be challenging, suspected individuals should have serial EKGs, echocardiography, and cardiac enzyme testing. In dengue patients with elevated cardiac markers and abnormal EKG and/or echocardiographic findings, myocarditis should be considered a potential differential diagnosis. In rare instances, a CHB can occur and may not be reversible.