Ming Hui Chen

In adults with hypertrophic cardiomyopathy (HCM), left ventricular outflow tract (LVOT) obstruction on exercise stress echocardiography (ESE) and reduced left atrial (LA) strain increase heart failure and cardiac outcome risk. However, limited pediatric data exist. We evaluated the association of exercise-induced LVOT obstruction and LA strain with cardiac events in young HCM patients. Patients who underwent ESE (n = 114, 32%F, median = 17 yrs) from 2014–2022 at a single center were stratified by LVOT gradients: Group 1 (n = 44, rest/exercise gradients < 30mmHg); Group 2 (n = 41, rest < 30mmHg; exercise ≥ 30mmHg); Group 3 (n = 29, rest/exercise ≥ 30mmHg). LA reservoir (LASr), conduit (LAScd), and contractile strain were analyzed with TOMTEC AutoStrain LA. Composite cardiac event included: heart failure, non-sustained/sustained ventricular tachycardia, cardiac syncope, heart transplantation, and HCM-related death. At follow-up (median = 2.0 years), there was a greater hazard of the composite event in Group 3 vs. 2 (hazard-ratio [HR] = 4.97, p = 0.013). Severe events were rare and largely observed in Group 3. Increased HR was seen in Group 2 vs. 1 but the difference was not significant. Adjusting for LVOT gradient (Group 3), lower LASr or LAScd or increased LA stiffness (E/e’ to LASr ratio) were associated with composite event (HR LASr = 1.57; LAScd = 1.70; LA stiffness = 1.31; all p < 0.01). Concordance indices were similar for these three strain/stiffness models (0.81–0.82) and higher than in models including LVOT group with traditional diastolic indices (LA volume index or E/e’; c-index = 0.76). In one of the largest pediatric HCM cohorts undergoing ESE, reduced LA strain demonstrated greater incremental value to LVOT gradient than traditional diastolic indices when evaluating association with cardiac events.

Reduced exercise capacity is common in young bilateral lung transplantation (Bi-LTx) recipients, but longer-term data on cardiac comorbidities are limited. We evaluate potential cardiac contributions to long-term exercise intolerance in this population. All Bi-LTx recipients at a single pediatric center, who completed routine clinical post-transplant cardiac assessment, including echocardiogram, cardiac exam, and cardiopulmonary exercise testing (CPET), were included. Cardiac risk factors (CRFs) were assessed by history and laboratory tests. CPET-derived peak and percent-predicted peak myocardial oxygen consumption (VO₂ peak, ppVO₂ peak) were used to quantitate exercise capacity. Percent-predicted peak oxygen pulse (pp peak O₂ pulse) assessed stroke volume. 15 patients (67% M; median age 21.6 years, median follow-up from Bi-LTx 7.0 years) were included. Almost all patients (14, 93%) had multiple CRFs; hypertension and hyperlipidemia/dyslipidemia were the most common. On CPET, 93% (n = 14) had abnormal (≤ 85%) ppVO₂ peak (median 59%). 73% (n = 11) had abnormal pp peak O₂ pulse (median 74%). Ten had blunted heart rate response to exercise. Nine had left ventricular diastolic dysfunction (LV-DD) on echocardiogram. Median percent-predicted forced expiratory volume in one second was 70%. One had severe chronic lung allograft dysfunction. Cardiac risk factors and exercise intolerance are common among young Bi-LTx recipients years post-transplant, even among those without significant pulmonary dysfunction. High prevalence of multiple CRFs, LV-DD, chronotropic dysfunction, and abnormal stroke volume suggest cardiac comorbidities may contribute to intolerance. Medical management of CRFs and tailored exercise may decrease cardiac risk and improve functional capacity for Bi-LTx survivors.

Background: Lifelong continuity of care is essential for patients with congenital heart disease (CHD) to maximize health outcomes; unfortunately, gaps in care (GIC) are common. Trends in GIC and of social determinants of health factors contributing to GIC are poorly understood. Methods and Results: This retrospective cohort study included patients with CHD, aged 0 to 34 years, who underwent surgery between January 2003 and May 2020, followed up at a pediatric subspeciality hospital. Patients were categorized as having simple, moderate, and complex CHD based on 2018 American Heart Association and American College of Cardiology guidelines. Social determinants of health, such as race, ethnicity, language, insurance status, and Child Opportunity Index, based on home address zip code, were analyzed. Of 2012 patients with CHD, a GIC of ≥3 years was identified in 56% (n=1119). The proportion of patients with GIC per year increased by 0.51% ( P <0.001). Multivariable longitudinal models showed that the odds of GIC were higher for patients who were ≥10.5 years old, had simple CHD, lived out of state, lived farther from care site, received public insurance, had less protection with additional insurance plans, and with low Child Opportunity Index. A separate model for patients with only moderate/complex CHD showed similar findings. Race and ethnicity were not associated with the odds of experiencing GIC over time. Conclusions: GIC have increased over time for patients with CHD. Social determinants of health, like insurance, access, and neighborhood opportunity, are key risk factors for increasing GIC. Efforts to reduce GIC in patients with CHD should focus on addressing the impact of specific social determinants of health.

Background: Thoracic aortic aneurysm (TAA) is associated with significant morbidity and mortality. Although individuals with family histories of TAA often undergo clinical molecular genetic testing, adults with nonsyndromic TAA are not typically evaluated for genetic causes. We sought to understand the genetic contribution of both germline and somatic mosaic variants in a cohort of adult individuals with nonsyndromic TAA at a single center. Methods and Results: One hundred eighty‐one consecutive patients 500×) targeted sequencing across 114 candidate genes associated with TAA and its related functional pathways. Samples from 354 age‐ and sex‐matched individuals without TAA were also sequenced, with a 2:1 matching. We found significant enrichments for germline (odds ratio [OR], 2.44, P =4.6×10 ⁻⁶ [95% CI, 1.67–3.58]) and also somatic mosaic variants (OR, 4.71, P =0.026 [95% CI, 1.20–18.43]) between individuals with and without TAA. Likely genetic causes were present in 24% with nonsyndromic TAA, of which 21% arose from germline variants and 3% from somatic mosaic alleles. The 3 most frequently mutated genes in our cohort were FLNA (encoding Filamin A), NOTCH3 (encoding Notch receptor 3), and FBN1 (encoding Fibrillin‐1). There was increased frequency of both missense and loss of function variants in TAA individuals. Conclusions: Likely contributory dominant acting genetic variants were found in almost one quarter of nonsyndromic adults with TAA. Our findings suggest a more extensive genetic architecture to TAA than expected and that genetic testing may improve the care and clinical management of adults with nonsyndromic TAA.