Dengue hemorrhagic fever and cardiac involvement

Table 1 Clinical presentation of the patients with acute myocarditis

	Clinical presentation of acute myocarditis
1	No clinical manifestations
2	Abnormal ECG or X-ray
3	Unexplained sinus tachycardia
4	Atrial or ventricular premature beats
5	Atrial or ventricular tachycardia
6	Partial or complete heart block
7	Ventricular fibrillation/cardiac arrest
8	Acute cardiac failure
9	Circulatory collapse (shock)

ECG: Electrocardiogram.

Table 2 Incidence and clinical manifestations of dengue viral infections with cardiac involvement

Ref.	Diagnosis	Study population	Incidence, %	Cardiac assessment methods	Main findings and clinical outcomes
Wali et al[24], 1998	DHF/DSS	17 (14-58 yr)	70.59	ECG. ECHO. Radionuclide ventriculography. Tc-99m pyrophosphate imaging	ECG showed ST and T wave changes (29.4%). Mean LVEF = 41.7%. Mean LVEF in DSS patients = 39.63%
Kabra et al[25], 1998	DF/DHF/DSS	54 (< 12 yr)	16.70	ECHO	LVEF < 50% in 16.7% of patients. LVEF < 35% in 3.7% of patients. Repeat ECHO after 2 mo showed improved LVEF
Khongphatthanayothin et al[26], 2003	DHF	24 (10.8 ± 2.8 yr)	-	ECHO (VCFC/ESS)	Lower LVEF, VCFC/ESS, CI, EDV and higher SVR during critical phase vs recovery phase
Kularatne et al[27], 2007	DF	120 (13-76 yr)	62.50	ECG. Cardiac markers	ECG abnormalities: (1) Sinus bradycardia; (2) ST-segment changes; (3) T wave changes; and (4) Right bundle branch block in 62.5% of patients; increased troponin levels in 29.4% of 17 patients
Khongphatthanayothin et al[28], 2007	DF/DHF/DSS	91 (5-15 yr)	17.58	ECHO. Cardiac markers	Reduced LVEF (< 50%) was found in 6.7%, 13.8%, and 36% of patients with DF, DHF, and DSS during the critical phase, respectively. No abnormal cardiac markers
Salgado et al[29], 2009	DF/DHF	102 (13 mo-10 yr)	10.70	ECG. ECHO	ECG: (1) Sinus bradycardia in 81.8% of 11 patients; and (2) Tachycardia in 18.2% of 11 patients, and T wave inversion in seven of 11 patients. ECHO: Pericardial effusions in 71.4% of 7 patients
La-Orkhun et al[30], 2011	DF/DHF/DSS	35 (5-15 yr)	29.00	ECG, 24-h Holter monitoring	During recovery phase: (1) Sinus arrhythmias; (2) First-degree AV block; (3) Mobitz type I second-degree AV block; (4) Atrial ectopic beats; and (5) Ventricular ectopic beats
Yacoub et al[18], 2012	DF/DHF/DSS	79 (8-46 yr)	35.00	ECG. ECHO. Cardiac markers	Abnormal ECG: (1) Sinus arrhythmias; (2) First-degree AV block; (3) T-wave changes; and (4) ST segment abnormalities. Systolic impairment in 45% of patients, diastolic impairment in 42%. Septal and right ventricular walls predominantly affected, worse in severe cases. 1 patient had elevated troponin I
Miranda et al[31], 2013	DF/DHF/DSS	81 (4 mo-81 yr)	14.81	Cardiac markers (troponin I and NTproBNP). ECHO. ECG. CMR	Elevated troponin I and/or NTproBNP in 14.81% of patients. 4/10 of patients had abnormal ECHO: (1) Functional abnormalities; and (2) Regional wall abnormalities. 4 patients had myocardial enhancement by CMR
Sengupta et al[32], 2013	DHF/Control	20 (DHF) (23 ± 8 yr); 20 (control) (23 ± 5 yr)	-	ECG. ECHO	LVEF reduced in DHF compared with controls (51.25 ± 0.96% vs 59.32 ± 1.26%; P = 0.032). DHF patients had: (1) Peak longitudinal strain in subendocardial region; (2) Circumferential strain in the subepicardial region; and (3) Radial strain
Yadav et al[33], 2013	DHF/DSS	67 (3 mo-14 yr)	48 (ECHO); 70 (Tei index)	ECG. ECHO. Cardiac markers	LVEF showed 48% cardiac involvement. Tei index showed 70% cardiac involvement. Tei index improved on discharge but did not normalize
Kirawittaya et al[34], 2015	DF/DHF/DSS	181 DF/DHF 35 Non-DF (< 15 yr)	14.50	ECG. ECHO. Cardiac markers	DHF patients with plasma leakage had: (1) Cardiac index (2695 vs 3188 L/min/m2); (2) LV myocardial performance index (0.413 vs 0.328); (3) Systemic vascular resistance (2478 vs 1820 dynes.s/cm-5) compared to those without plasma leakage; and (4) Cardiac dysfunction was most pronounced around the time of plasma leakage
Li et al[35], 2016	DHF/DSS	1782 (adult)	11.28	ECG. ECHO. Cardiac markers	NSD(WS+)/SD had 46.66% myocarditis. NSD(WS-) had 9.72% myocarditis. DHF with myocarditis had longer hospitalization. Prognosis of DHF patients with and without myocarditis had no significant difference
Bhatt et al[16], 2020	DHF/DSS	182 (30.2 ± 12.6 yr)	7.10	ECG. ECHO. Cardiac markers	ECG abnormality in 44/182 (24%). Cardiac markers’ elevation in 27/182 (14.83%). ECHO abnormality in 11/182 (6.04%)
Bhattacharjee et al[36], 2020	DF	84 (18-65 yr) (41 cases/43 controls)	-	ECG. ECHO. Cardiac markers	CK, CK-MB, troponin T and NT-proBNP levels in cases were higher than in controls. Troponin T was positively correlated with NTproBNP
Cabrera-Rego et al[37], 2021	DF/DHF/DSS	427 (> 18 yr)	19.70	ECG. ECHO	Rhythm disorders in 16.9%. Repolarization disorders in 3.0%. Pericarditis in 1.6%. Pericardial effusion in 0.9%. Myocarditis in 0.2%
Shah et al[38], 2021	DF	320 (> 18 yr)	35	ECG. ECHO. Cardiac markers	Sinus bradycardia in 19.7%. LVEF < 40% in 13.1%. Elevated troponin T in 15%. Elevated CK-MB in 10.6%. Elevated NTproBNP in 5.9%. Mortality rate was 4.38% with cardiac involvement

AV: Arterioventricular; CI: Cardiac index CK: Creatine kinase; CMR: Cardiac magnetic resonance; DF: Dengue fever; DHF: Dengue hemorrhagic fever; DSS: Dengue shock syndrome; ECHO: Echocardiography; EDV: End-diastolic volume; ECG: Electrocardiogram; LVEF: Left ventricular ejection fraction; NSD(WS)/SD: Non-severe dengue (warning sign)/severe dengue; SVR: Sustained virological response; VCFC/ESS: Velocity of circumferential fiber shortening adjusted for end-systolic meridional wall stress.

Table 3 Primary histopathological features of cardiac involvement in autopsy of dengue hemorrhagic fever patients

Ref.	Autopsy cases, n	Gross findings	Histopathological findings
Bhamarapravati et al[15], 1967	100	Focal areas of hemorrhage in the epicardium, sub endocardium, interstitial tissues, or combined	Separation of myocardial fibers with the interstitial tissue edema. Extensive hemorrhage in myocardium with condensation and acidophilic pattern of myocardial fibrils
Burke[39], 1968	12	Petechial hemorrhage in epicardium, sub endocardium, and myocardium	No evidence of myocarditis. Normal blood vessels
Weerakoon et al[20], 2011	5	Evidence of florid myocarditis	Interstitial edema with inflammatory cell infiltration and necrosis of myocardial fibers. Evidence of pericarditis
Kularatne et al[40], 2018	3	Petechial hemorrhage	Interstitial edema with infiltration of neutrophils and lymphocytes. Lymphocytic infiltration in endomyseum
Marques et al[41], 2013	1	NR	Acute myocarditis with multiple areas of myocardial necrosis sur-rounded by inflammatory cellular infiltrate
Rathi et al[42], 2013	6	Hemorrhagic spots over pericardium, epicardium. Mild ventricular hypertrophy	Lymphocytic myocarditis

NR: Not reported.