Outcomes Associated With Giant Coronary Artery Aneurysms After Kawasaki Disease: A Single-Center United States Experience.

OBJECTIVE: To determine the long-term outcomes among a cohort of patients with Kawasaki disease (KD) and a history of giant coronary artery aneurysms (CAA) at a single US center. RESULTS: There were 60 patients with KD and giant CAAs identified between 1989 and 2023. The majority of patients were male (71.7%) with median age at diagnosis of 0.9 years (0.2-13.3). Patients were followed for a median of 11 years, up to 34.5 years. MACE occurred in 13 (21.7%) patients at a median of 1.4 years (0.04-22.6) after KD diagnosis. The 10-, 20-, and 30-year MACE-free rates were 75%, 75%, and 60%. Patients with maximal CA z-scores ≥20 or bilateral CAA were more likely to have MACE. During follow-up, 26.7% of CAA regressed to normal luminal diameter at a median of 3.6 years (0.6-12.0). The 10-, 20- and 30-year likelihood of CA regression to normal luminal diameter was 36%, 46%, and 46%. CONCLUSIONS: Over 30 years, MACE occurred in nearly 22% of patients, more often in those with bilateral CAA or CA z-scores ≥20. Despite regression to normal luminal diameter in over 25% of CAA, patients with a history of KD-associated giant CAA require ongoing surveillance for cardiac complications, even years after the initial disease.

Left atrial stiffness and strain are novel indices of left ventricular diastolic function in children: validation followed by application in multisystem inflammatory syndrome in children due to COVID-19.

AIMS: We hypothesized left atrial (LA) stiffness may serve as a surrogate marker in children to differentiate elevated pulmonary capillary wedge pressure (PCWP) from normal and help detect diastolic dysfunction in myocardial injury due to multisystem inflammatory syndrome in children (MIS-C). METHODS AND RESULTS: We validated LA stiffness in 76 patients (median age 10.5 years), 33 had normal PCWP (<12 mmHg) and 43 had elevated PCWP (≥12 mmHg). LA stiffness was applied to 42 MIS-C patients [28 with myocardial injury (+) and 14 without myocardial injury (-)], defined by serum biomarkers. The validation group consisted of a group with and without cardiomyopathies, whose PCWP values ranged from normal to severely elevated. Peak LA strain was measured by speckle-tracking and E/e' from apical four chamber views. Noninvasive LA stiffness was calculated as: LAStiffness=E/e'LAPeakStrain (%-1). Patients with elevated PCWP showed significantly elevated LA stiffness [median 0.71%-1 vs. 0.17%-1, P < 0.001]. Elevated PCWP group showed significantly decreased LA strain (median: 15.0% vs. 38.2%, P < 0.001). Receiver operator characteristic (ROC) curve for LA stiffness yielded an area under the curve (AUC) of 0.88 and cutoff value of 0.27%-1. In MIS-C group, ROC curve yielded an AUC of 0.79 and cutoff value of 0.29%-1 for identifying myocardial injury. CONCLUSION: In children with elevated PCWP, LA stiffness was significantly increased. When applied to children with MIS-C, LA stiffness classified myocardial injury accurately. LA stiffness and strain may serve as noninvasive markers of diastolic function in the pediatric population.

Echocardiographic Findings in Pediatric Multisystem Inflammatory Syndrome Associated With COVID-19 in the United States.

BACKGROUND: Centers from Europe and United States have reported an exceedingly high number of children with a severe inflammatory syndrome in the setting of coronavirus disease 2019, which has been termed multisystem inflammatory syndrome in children (MIS-C). OBJECTIVES: This study aimed to analyze echocardiographic manifestations in MIS-C. METHODS: A total of 28 MIS-C, 20 healthy control subjects and 20 classic Kawasaki disease (KD) patients were retrospectively reviewed. The study reviewed echocardiographic parameters in the acute phase of the MIS-C and KD groups, and during the subacute period in the MIS-C group (interval 5.2 ± 3 days). RESULTS: Only 1 case in the MIS-C group (4%) manifested coronary artery dilatation (z score = 3.15) in the acute phase, showing resolution during early follow-up. Left ventricular (LV) systolic and diastolic function measured by deformation parameters were worse in patients with MIS-C compared with KD. Moreover, MIS-C patients with myocardial injury were more affected than those without myocardial injury with respect to all functional parameters. The strongest parameters to predict myocardial injury in MIS-C were global longitudinal strain, global circumferential strain, peak left atrial strain, and peak longitudinal strain of right ventricular free wall (odds ratios: 1.45 [95% confidence interval (CI): 1.08 to 1.95], 1.39 [95% CI: 1.04 to 1.88], 0.84 [95% CI: 0.73 to 0.96], and 1.59 [95% CI: 1.09 to 2.34], respectively). The preserved LV ejection fraction (EF) group in MIS-C showed diastolic dysfunction. During the subacute period, LVEF returned to normal (median from 54% to 64%; p < 0.001) but diastolic dysfunction persisted. CONCLUSIONS: Unlike classic KD, coronary arteries may be spared in early MIS-C; however, myocardial injury is common. Even preserved EF patients showed subtle changes in myocardial deformation, suggesting subclinical myocardial injury. During an abbreviated follow-up, there was good recovery of systolic function but persistence of diastolic dysfunction and no coronary aneurysms.

Enalapril to prevent cardiac function decline in long-term survivors of pediatric cancer exposed to anthracyclines.

PURPOSE: To determine whether an angiotensin-converting enzyme (ACE) inhibitor, enalapril, prevents cardiac function deterioration (defined using maximal cardiac index [MCI] on exercise testing or increase in left ventricular end-systolic wall stress [LVESWS]) in long-term survivors of pediatric cancer. PATIENTS AND METHODS: This was a randomized, double-blind, controlled clinical trial comparing enalapril to placebo in 135 long-term survivors of pediatric cancer who had at least one cardiac abnormality identified at any time after anthracycline exposure. RESULTS: There was no difference in the rate of change in MCI per year between enalapril and placebo groups (0.30 v 0.18 L/min/m(2); P =.55). However, during the first year of treatment, the rate of change in LVESWS was greater in the enalapril group than in the placebo group (-8.59 v 1.85 g/cm(2); P =.033) and this difference was maintained over the study period, resulting in a 9% reduction in estimated LVESWS by year 5 in the enalapril group. Six of seven patients removed from random assignment to treatment because of cardiac deterioration were initially treated with placebo (P =.11), and one has died as a result of heart failure. Side effects from enalapril included dizziness or hypotension (22% v 3% in the placebo group; P =.0003) and fatigue (10% v 0%; P =.013). CONCLUSION: Enalapril treatment did not influence exercise performance, but did reduce LVESWS in the first year; this reduction was maintained over the study period. Any theoretical benefits of LVESWS reduction in this anthracycline-exposed population must be weighed against potential side effects from ACE inhibitors when making treatment decisions.

Using health-related quality of life measures to predict cardiac function in survivors exposed to anthracyclines.

PURPOSE: As the number of pediatric cancer survivors increases, so does the number of survivors previously exposed to anthracyclines as part of their cancer therapy. Because screening is costly, some have suggested that health-related quality of life (HRQL) measures might be useful in focusing screening tests on those patients with cases most likely to display positive findings. This study reports on the predictive ability of HRQL measures to detect patients with abnormalities on serial cardiac testing. METHODS: Using 127 patients from the ACE-Inhibitor after Anthracycline (AAA) Trial, this study compared serial measures of the Short Form-36 (SF-36; for ages > 13 years) and Child Health Questionnaire-Child Form 87 (CHQ-CF87; for ages < or = 13 years) to serial cardiac performance tests including echocardiographic shortening fraction, left ventricular end systolic wall stress (LVESWS), LVESWS-index, and maximal cardiac index (MCI; a measure of cardiac output at peak exercise). RESULTS: Generally, there was no clinically or statistically significant correlation between any HRQL measure and any cardiac function measure except between MCI and vitality and physical functioning. For each of these measures, the correlation between MCI was statistically significant (P < .006), but each HRQL subscale could explain no more than 7% of the variation in MCI. HRQL measures were not predictive of any other cardiac function measure. CONCLUSION: HRQL measures should not be used in isolation as a screen for cardiac function abnormalities in patients exposed to anthracylines who already have a mild degree of ventricular dysfunction. Patient history appears to be no substitute for cardiac testing in this cohort.