Transthoracic Echocardiography in the Preoperative Assessment of Newborn Coarctation: Limiting Risks Associated with Advanced Imaging Techniques.

A newborn male child with prenatally identified aortic arch hypoplasia presented to our facility for cardiac management. He had been started on prostaglandins at the delivery facility and was subsequently placed on a high-flow nasal cannula due to associated apnea. On the day of life three, the patient underwent cardiac computed tomography scan for delineation of his anatomy. The patient remained intubated after his imaging study in anticipation of surgical intervention, which took place at the age of 5 days. The patient required a peritoneal dialysis catheter placement 2 days after his procedure due to oliguria. He progressed into renal failure requiring continuous renal replacement therapy. This patient was subsequently discussed at our departmental morbidity and mortality conference. The short time frame between contrast administration for the computed tomography and surgical intervention was thought to have contributed to his renal failure. We discussed the adequacy of transverse aortic arch imaging by echocardiogram and the utility of advanced imaging in the fragile neonatal period. This discussion resulted in our department asking, "Is transthoracic echocardiography accurate when diagnosing and characterizing aortic coarctation at our institution? Are advanced imaging studies necessary in instances of simple coarctation?"

Multiple Giant Coronary Artery Aneurysms in a Pediatric Patient with Granulomatosis with Polyangiitis.

Granulomatosis with polyangiitis (GPA) is characterized by necrotizing vasculitis of small and medium sized vessels and is rarely present in the pediatric population. Cardiac manifestations in pediatric patients with GPA are extremely uncommon, with only two known reported cases associated with coronary artery aneurysms (Rehani and Nelson in Pediatrics 147:e20200932, 2021, https://doi.org/10.1542/peds.2020-0932 ;Aghaei Moghadam et al. in Case Rep Cardiol 2020:3417910, 2020, https://doi.org/10.1155/2020/3417910 ). We report a case of a 14-year-old male who presented with a 1 month history of fatigue and shortness of breath. He ultimately was found to have multiple giant coronary aneurysms in both the left and right coronaries including a giant aneurysm in the posterior descending; this has not been previously reported. The case highlights the need for complete multi-modality imaging of the coronary arteries in patients with GPA.

Gene-specific modifying effects of pro-LVH polymorphisms involving the renin-angiotensin-aldosterone system among 389 unrelated patients with hypertrophic cardiomyopathy.

AIMS: The purpose of this study was to determine whether the deletion/insertion (D/I) polymorphism in the ACE-encoded angiotensin-converting enzyme or the pooled gene effect of five renin-angiotensin-aldosterone system (RAAS) polymorphisms were disease modifiers in a large cohort of unrelated patients with genotyped hypertrophic cardiomyopathy (HCM). METHODS AND RESULTS: Five different RAAS polymorphism genotypes were established by PCR amplification of the surrounding polymorphic regions of genomic DNA in a cohort of 389 unrelated patients comprehensively genotyped for HCM-causing mutations in eight sarcomeric/myofilament genes. Patient clinical data were archived in a database blinded both to the primary myofilament defect and the polymorphism genotype. Each patient was assessed with respect to ACE genotype as well as composite pro-left ventricular hypertrophy (LVH) RAAS polymorphism score (0-5). Overall, no clinical parameter correlated independently with ACE genotype. Subset analysis of the two most common genetic subtypes of HCM, MYBPC3 (myosin binding protein C) and MYH7 (beta myosin heavy chain), demonstrated a significant pro-LVH effect of DD-ACE only in patients with MYBPC3-HCM. In MYBPC3-HCM, left ventricular wall thickness was greater in patients with DD genotype (25.8+/-5 mm) compared with DI (21.8+/-4) or II genotype (20.8+/-5, P=0.01). Moreover, extreme hypertrophy (>30 mm) was only seen in MYBPC3-HCM patients who also hosted DD-ACE. An effect of RAAS pro-LVH score was evident only in the subgroup of patients with no previously identified myofilament mutation. CONCLUSION: This study demonstrates that RAAS genotypes may modify the clinical phenotype of HCM in a disease gene-specific fashion rather than indiscriminately.

Prevalence and spectrum of thin filament mutations in an outpatient referral population with hypertrophic cardiomyopathy.

BACKGROUND: Thin filament mutations are reported to cause approximately 20% of cases of hypertrophic cardiomyopathy (HCM), and they have been associated with specific phenotypes. However, the frequency of these mutations and their associated phenotype(s) from a large tertiary referral center population are unknown. METHODS AND RESULTS: DNA was obtained from 389 unrelated patients with HCM. A mutational analysis of all protein coding exons of cardiac troponin T, cardiac troponin I, alpha-tropomyosin, and cardiac actin was performed using polymerase chain reaction, denaturing high-performance liquid chromatography, and DNA sequencing. The clinical data were extracted from patient records and maintained independent of the patient genotype. Overall, only 18 patients (4.6%) harbored isolated thin filament mutations: 8 had troponin T mutations, 6 had troponin I mutations, 3 had alpha-tropomyosin mutations, and 1 had an actin mutation. Of the 12 unique missense mutations identified, 9 (75%) were novel mutations. As a group, patients with thin filament mutations were not significantly different from the rest of the cohort in age at diagnosis, left ventricular wall thickness, left ventricular outflow tract obstruction, or family history of HCM or sudden cardiac death. CONCLUSIONS: Mutations in genes encoding thin filament proteins are less prevalent in HCM than previously estimated. Patients with mutations in troponin T, troponin I, alpha-tropomyosin, and actin do not invariably present with any distinct clinical feature, thus limiting the utility of gene status for risk stratification or of clinical phenotype in guiding individual genetic screening at this time.