Familial Recurrence Patterns in Congenitally Corrected Transposition of the Great Arteries: An International Study.

BACKGROUND: Congenitally corrected transposition of the great arteries (ccTGA) is a rare disease of unknown cause. We aimed to better understand familial recurrence patterns. METHODS: An international, multicentre, retrospective cohort study was conducted in 29 tertiary hospitals in 6 countries between 1990 and 2018, entailing investigation of 1043 unrelated ccTGA probands. RESULTS: Laterality defects and atrioventricular block at diagnosis were observed in 29.9% and 9.3%, respectively. ccTGA was associated with primary ciliary dyskinesia in 11 patients. Parental consanguinity was noted in 3.4% cases. A congenital heart defect was diagnosed in 81 relatives from 69 families, 58% of them being first-degree relatives, including 28 siblings. The most prevalent defects in relatives were dextro-transposition of the great arteries (28.4%), laterality defects (13.6%), and ccTGA (11.1%); 36 new familial clusters were described, including 8 pedigrees with concordant familial aggregation of ccTGA, 19 pedigrees with familial co-segregation of ccTGA and dextro-transposition of the great arteries, and 9 familial co-segregation of ccTGA and laterality defects. In one family co-segregation of ccTGA, dextro-transposition of the great arteries and heterotaxy syndrome in 3 distinct relatives was found. In another family, twins both displayed ccTGA and primary ciliary dyskinesia. CONCLUSIONS: ccTGA is not always a sporadic congenital heart defect. Familial clusters as well as evidence of an association between ccTGA, dextro-transposition of the great arteries, laterality defects and in some cases primary ciliary dyskinesia, strongly suggest a common pathogenetic pathway involving laterality genes in the pathophysiology of ccTGA.

Effectiveness of Extracorporeal Life Support for Patients With Cardiogenic Shock Due To Intractable Arrhythmic Storm.

OBJECTIVES: Extracorporeal life support is used for patients with severe heart failure as a bridge to heart transplantation or recovery. We aimed at analyzing the efficacy and safety of extracorporeal life support to treat refractory arrhythmic storm responsible for cardiogenic shock in patients resistant to antiarrhythmic drugs. DESIGN: Retrospective study. SETTING: University Hospital of Rennes, France. PATIENTS: Patients with refractory arrhythmic storm admitted between January 2005 and March 2015. INTERVENTIONS: Patients with intractable refractory arrhythmic storm and cardiogenic shock despite optimal medical therapy were implanted with an extracorporeal life support. Patients' characteristics and outcomes after extracorporeal life support implantation were analyzed. MEASUREMENTS AND MAIN RESULTS: Twenty-six patients (23 men, 52.4 ± 9.2 yr old) were included, most of them having ischemic cardiomyopathy (65.4%). Stable sinus rhythm restoration was immediate in 61.5% of patients and occurred after a median time of 3 hours after extracorporeal life support implantation for the remaining ones. Thirteen patients (50%) eventually died, none of them due to extracorporeal life support-related complications, but mostly due to the occurrence of multiple organ failure, and occurred after a median time of 4 days. The remaining 13 patients (50%) had extracorporeal life support withdrawn after 6.7 ± 3.6 days and were discharged after 34.7 ± 14.7 days after admission. Patients with repetitive ventricular tachycardia/ventricular fibrillation episodes alternating with periods of sinus rhythm at the time of implantation had a better survival than those in refractory ventricular fibrillation (p = 0.017). CONCLUSIONS: This is the largest database of patients temporary implanted with extracorporeal life support for refractory arrhythmic storm responsible for cardiogenic shock resistant to antiarrhythmic drugs. It provides efficient hemodynamic support and survival rate after the implantation is 50%.