Clinical Interpretation of Genetic Variants in the Evaluation and Management of Thoracic Aortic Aneurysm and Dissection.

BACKGROUND: We aimed to elucidate clinical implications of genetic variant interpretation in assessing disease severity and progression in thoracic aortic aneurysm and dissection (TAAD) patients. METHODS: Consecutive TAAD patients with aortic root and/or ascending aortic aneurysms seen between 2011 and 2020 were included. Serial echocardiography, family history of TAAD, and management information were retrospectively collected and analyzed. Patients were classified into gene-positive (Gen-P), variants of uncertain significance, and gene-negative (Gen-N) groups. RESULTS: A total of 407 patients were included: mean age 53.7 ± 15.4 years, 64.4% men, and 38% with reported family history of TAAD. Thirty-seven (9.1%) were Gen-P; 147 (36.1%) had a variant of uncertain significance. The maximal aneurysm diameter was 4.78 mm larger in Gen-P than the other groups (P < .001). In 162 unoperated TAAD patients with serial echocardiographic measurements, aneurysms enlarged at a significantly higher rate in the Gen-P (1.36 mm/year, 95% CI: 0.77-1.95) than variants of uncertain significance and Gen-N groups (0.83 mm/year vs 0.89 mm/year, respectively; P < .001). Aneurysms were 20% more likely to require surgical intervention for every millimeter increase in diameter. When considered on an individual basis, the highest growth rates were found in the variants of uncertain significance group. CONCLUSIONS: While aneurysms linked to variants of uncertain significance demonstrate average growth rates comparable to those in Gen-N, close follow-up and genetic counseling in the variants of uncertain significance group are recommended for assessment of pathogenicity on a case-by-case basis. Early familial gene testing in TAAD is important to develop individualized preventive and therapeutic criteria.

Hypertrophic cardiomyopathy in identical twins: a case series.

Background: Hypertrophic cardiomyopathy in identical twins is rare. Cases of hypertrophic cardiomyopathy with homogenous and heterogeneous phenotypes have been described in the literature. Case summary: We report a pair of monozygotic twins (Twin A and Twin B) with identical morphological expression of hypertrophic cardiomyopathy. On initial evaluation, both twins had resting left ventricular outflow tract obstruction, Grade II diastolic dysfunction, and New York Heart Association (NYHA) Class II symptoms, but they had a different clinical course afterward. Twin A progressed from NYHA Class II to Class III with a high left ventricular outflow tract pressure gradient that was unresponsive to medical treatment and required alcohol septal ablation. Twin B responded very well to medical treatment. Both patients had no risk factors for sudden cardiac death, and neither required an implantable cardioverter defibrillator. Discussion: The morphology of hypertrophic cardiomyopathy has a strong genetic basis, but epigenetic factors may affect disease expression.

Implantable cardioverter defibrillators in diabetics: efficacy and safety in patients at risk of sudden cardiac death.

Diabetes mellitus is a major risk factor for arrhythmogenesis and is associated with a two-fold increase in all-cause mortality and a four-fold increase in cardiovascular mortality including sudden cardiac death when compared with nondiabetics. Implantable cardioverter defibrillators (ICD) have been shown to effectively reduce arrhythmic death and all-cause mortality in patients with severe myocardial dysfunction. With a high competing risk of nonarrhythmic cardiac and noncardiac death, survival benefit of ICD in patients with diabetes mellitus could be reduced, but the subanalysis of diabetic patients in randomized clinical trials provides reassurance regarding a similar beneficial survival effect of ICD and cardiac resynchronization therapy in diabetics, as observed in the overall population with advanced heart disease. In this article, the authors highlight some of the clinical issues related to diabetes, summarize the data on the efficacy of ICD in diabetics when compared with nondiabetics and discuss concerns related to ICD implantation in patients with diabetes.

Cardiac resynchronization therapy in patients with challenging anatomy due to venous anomalies or adult congenital heart disease.

BACKGROUND: Cardiac resynchronization therapy (CRT) has proven salutary effects in patients with congestive heart failure, systolic dysfunction, and electromechanical dyssynchrony in the setting of ischemic, nonischemic, and congenital cardiomyopathy. While CRT device implants have become routine in the adult ischemic or nonischemic cardiomyopathy populations, patients with congenital heart disease offer special challenges due to unusual anatomic variations. METHODS: A comprehensive assessment of anatomic abnormalities is essential prior to implant. In addition, implant techniques and equipment must be tailored to the expected anatomy. A flexible approach is necessary-implant may require equipment and techniques adapted from vascular intervention. CONCLUSION: This article describes our approach to CRT implant in patients with congenital heart disease, and is illustrated by reports of several cases.

Isolated partial anomalous pulmonary venous connection: Diagnostic value of suprasternal color flow imaging and contrast echocardiography.

Isolated partial anomalous pulmonary venous connection is frequently missed even when patients present with mild right ventricular enlargement. We describe the value of imaging from suprasternal window with color flow and ultrasound contrast echocardiography in aiding the diagnosis.