In-hospital Morbidity and Mortality After Modified Blalock-Taussig-Thomas Shunts.

BACKGROUND: The modified Blalock-Taussig-Thomas shunt is a critically important palliation for patients with insufficient pulmonary blood flow associated with congenital heart disease. After creating a modified Blalock-Taussig-Thomas shunt patients experience high rates of early postoperative morbidity and mortality. METHODS: This is a single-institution retrospective cohort study. A query of The Society of Thoracic Surgeons database identified relevant patients whose health records were manually queried for echocardiography and operative reports. Patients with ductal-dependent systemic circulation were excluded. Primary outcomes were early serious adverse events and in-hospital mortality. Secondary outcomes were time to primary outcomes and postoperative lengths of stay. We investigated the correlation of demographics, presence of competitive pulmonary blood flow, and surgical and anatomic factors on outcomes. RESULTS: After exclusions our cohort comprised 155 patients. Thirty-three patients (21.3%) experienced an early serious adverse event, 10 (6.5%) early shunt malfunction, and 11 (7.1%) in-hospital mortality. Smaller shunt size, smaller shunted pulmonary artery size, surgical approach, and site of proximal shunt anastomosis were independently associated with morbidity and mortality. CONCLUSIONS: Anatomic elements imparting increased resistance along the modified Blalock-Taussig-Thomas shunt predispose to increased morbidity and mortality, particularly in the early postoperative period. Despite the significant heterogeneity of patients receiving such shunts, similar risk profiles are observed regardless of lesion or presence of competitive flow. A surgical approach using thoracotomy with shunt anastomosis to the subclavian artery, where feasible, results in the subclavian artery as the point of natural resistance, allowing for placement of larger shunts and yielding lower morbidity and mortality.

Incidentally identified genetic variants in arrhythmogenic right ventricular cardiomyopathy-associated genes among children undergoing exome sequencing reflect healthy population variation.

BACKGROUND: With expanding use of clinical whole exome sequencing (WES), genetic variants of uncertain significance are increasingly identified. As pathologic mutations in genes associated with arrhythmogenic right ventricular cardiomyopathy (ARVC) carry a risk of sudden death, determining the diagnostic relevance of incidentally identified variants associated with these genes is critical. METHODS: WES variants from a large, predominantly pediatric cohort (N = 7,066 probands) were obtained for nine ARVC-associated genes (Baylor Miraca). For comparison, a control cohort was derived from the gnomAD database and an ARVC case cohort (N = 1,379 probands) was established from ARVC cases in the literature. Topologic mapping was performed and signal-to-noise analysis was conducted normalizing WES, or case variants, against control variant frequencies. Retrospective chart review was performed of WES cases evaluated clinically (Texas Children's Hospital). RESULTS: Incidentally identified variants occurred in 14% of WES referrals and localized to genes which were rare among ARVC cases yet similar to controls. Amino acid-level signal-to-noise analysis of cases demonstrated "pathologic hotspots" localizing to critical domains of PKP2 and DSG2 while WES variants did not. PKP2 ARM7 and ARM8 domains and DSG2 N-terminal cadherin-repeat domains demonstrated high pathogenicity while normalized WES variant frequency was low. Review of clinical data available on WES referrals demonstrated none with evidence of ARVC among variant-positive individuals. CONCLUSIONS: Incidentally identified variants are common among pediatric WES testing with gene frequencies similar to "background" variants. Incidentally identified variants are unlikely to be pathologic.