Evaluation of Cardiac Involvement in Children with Dengue by Serial Echocardiographic Studies

Background: Infection with dengue virus results in a wide range of clinical manifestations from dengue fever (DF), a self-limited febrile illness, to dengue hemorrhagic fever (DHF) which is characterized by plasma leakage and bleeding tendency. Although cardiac involvement has been reported in dengue, the incidence and the extent of cardiac involvement are not well defined. Methods and Principal Findings: We characterized the incidence and changes in cardiac function in a prospective in-patient cohort of suspected dengue cases by serial echocardiography. Plasma leakage was detected by serial chest and abdominal ultrasonography. Daily cardiac troponin-T levels were measured. One hundred and eighty one dengue cases were enrolled. On the day of enrollment, dengue cases that already developed plasma leakage had lower cardiac index (2695 (127) vs 3188 (75) (L/min/m2), p = .003) and higher left ventricular myocardial performance index (.413 (.021) vs .328 (.026), p = .021) and systemic vascular resistance (2478 (184) vs 1820 (133) (dynes·s/cm5), p = .005) compared to those without plasma leakage. Early diastolic wall motion of the left ventricle was decreased in dengue cases with plasma leakage compared to those without. Decreased left ventricular wall motility was more common in dengue patients compared to non-dengue cases particularly in cases with plasma leakage. Differences in cardiac function between DF and DHF were most pronounced around the time of plasma leakage. Cardiac dysfunction was transient and did not require treatment. Transient elevated troponin-T levels were more common in DHF cases compared to DF (14.5% vs 5%, p = 0.028). Conclusions: Transient left ventricular systolic and diastolic dysfunction was common in children hospitalized with dengue and related to severity of plasma leakage. The functional abnormality spontaneously resolved without specific treatment. Cardiac structural changes including myocarditis were uncommon. Author Summary: Dengue is a viral infection with a wide range of symptoms from a self-limiting fever called dengue fever (DF) to dengue hemorrhagic fever (DHF) which is characterized by leaky blood vessels and bleeding that can lead to shock in severe cases. Abnormal heart function has been reported but the frequencies and the progression of heart involvement are not well defined. In this study children with dengue had serial evaluation of their heart function during the course of the illness. Patients with DHF had comparatively low blood volume at the time of fever resolution and had decreased blood flow into the left lower heart chamber compared to DF cases. Relaxation and contraction of the left side of the heart were also relatively decreased in DHF. These abnormalities may contribute to the clinical response and complications of fluid replacement in dengue

Frequencies of abnormal TDI during the course of the illness.

<p>Percentages of DF (dotted lines) and DHF cases (solid lines) with low septal and lateral S wave (A, B) and septal and lateral Ea wave (C, D) and high E/Ea ratios (E) determined based on published age-specific normal values (21). * different from DF (<i>P</i> < .05).</p

Tissue Doppler imaging studies of LV function on the first study day in subjects with dengue.

<p>Values represent mean (SE), or number of cases.</p><p>^a two DHF cases did not have ultrasonography performed on the day of enrollment and were not included in this analysis. Differences between groups were analyzed by ANOVA with post hoc test or by Man Whitney’s test.</p><p>^<i>b</i>, ^<i>c</i> different from DHF without leakage at <i>P</i> < .05, and .005 respectively).</p><p>Tissue Doppler imaging studies of LV function on the first study day in subjects with dengue.</p

Plasma troponin-T levels in individual DF (white circles) or DHF cases (black circles) during the course of the illness.

<p>The horizontal line indicates a cut-off for an abnormal value at 30 pg/ml.</p

Left ventricular functions in dengue by fever day.

<p>Ejection fraction (A), early diastolic LV inflow flow (B), and late diastolic LV inflow (C) of dengue fever (dotted line) and dengue hemorrhagic fever cases (solid line) over the course of the illness. Fever day 0 denotes day of defervescence. * different from dengue fever (<i>P</i> < .05). The numbers of cases were: fever-day -3 (DF 4, DHF 5), fever-day-2 (DF 13, DHF 9), fever-day-1(DF 43, DHF 26), fever-day-0(DF 104, DHF 56), fever-day+1(DF 119, DHF 62), fever-day+2(DF 70, DHF 60), fever-day+3(DF 13, DHF 38).</p

Laboratory findings and cardiac function measurements on the first study day in subjects with dengue.

<p>Values represent mean (SE), or number of cases.</p><p>^a two DHF cases did not have ultrasonography performed on the day of enrollment and were not included in this analysis. Differences between groups were analyzed by ANOVA with post hoc test or by Man Whitney’s test.</p><p>^<i>b</i>, ^<i>c</i> different from DHF without leakage at <i>P</i> < .005, and .05 respectively).</p><p>Laboratory findings and cardiac function measurements on the first study day in subjects with dengue.</p

Tissue Doppler image of LV functions by fever day.

<p>Left ventricular lateral (A) and septal S wave (B), LV mean performance index (MPI) (C), lateral (D) and septal (E) annulus movement during early diastole, lateral (F) and septal (G) annulus movement during late diastole, and lateral (H) and medial (I) E/Ea ratios of dengue fever (dotted line) and dengue hemorrhagic fever (solid line) cases over the course of the illness. Fever day 0 denotes day of defervescence. * different from DF (<i>P</i> < .05). The numbers of cases were: fever-day -3 (DF 4, DHF 5), fever-day-2 (DF 13, DHF 9), fever-day-1(DF 43, DHF 26), fever-day-0(DF 104, DHF 56), fever-day+1(DF 119, DHF 62), fever-day+2(DF 70, DHF 60), fever-day+3(DF 13, DHF 38).</p

Comparison between cardiac function at fever day +1 and early convalescence.

<p>^a<i>P</i> value comparing values at fever day +1 and early convalescence (Student’s paired t-test).</p><p>Comparison between cardiac function at fever day +1 and early convalescence.</p

Clinical characteristics of study participants.

<p>Fever day and laboratory findings were from the day of study entry. Values represent mean (SE), or number of cases.</p><p>^<i>a</i> Different from non-dengue cases (<i>P</i> < .05)</p><p>^<i>b</i> different from DF (<i>P</i> < .05).</p><p>Clinical characteristics of study participants.</p

Hemodynamic status and plasma leakage in dengue by fever day.

<p>Heart rate (A), systolic blood pressure (B), diastolic blood pressure (C), inferior vena cava diameter (D), mean cardiac index (E), systemic vascular resistance (F), frequencies of cases with a pleural effusion or ascites (G), and daily fluid intake (H) of dengue fever (dotted line) and dengue hemorrhagic fever cases (solid line) over the course of the illness. Fever day 0 denotes day of defervescence. * different from dengue fever cases (<i>P</i> < .05). The numbers of cases were: fever-day -3 (DF 4, DHF 5), fever-day-2 (DF 13, DHF 9), fever-day-1(DF 43, DHF 26), fever-day-0(DF 104, DHF 56), fever-day+1(DF 119, DHF 62), fever-day+2(DF 70, DHF 60), fever-day+3(DF 13, DHF 38).</p