NEXN Gene in Cardiomyopathies and Sudden Cardiac Deaths: Prevalence, Phenotypic Expression, and Prognosis.

BACKGROUND: Few clinical data are available on NEXN mutation carriers, and the gene's involvement in cardiomyopathies or sudden death has not been fully established. Our objectives were to assess the prevalence of putative pathogenic variants in NEXN and to describe the phenotype and prognosis of patients carrying the variants. METHODS: DNA samples from consecutive patients with cardiomyopathy or sudden cardiac death/sudden infant death syndrome/idiopathic ventricular fibrillation were sequenced with a custom panel of genes. Index cases carrying at least one putative pathogenic variant in the NEXN gene were selected. RESULTS: Of the 9516 index patients sequenced, 31 were carriers of a putative pathogenic variant in NEXN only, including 2 with double variants and 29 with a single variant. Of the 29 unrelated probands with a single variant (16 males; median age at diagnosis, 32.0 [26.0-49.0] years), 21 presented with dilated cardiomyopathy (prevalence, 0.33%), and 3 presented with hypertrophic cardiomyopathy (prevalence, 0.14%). Three patients had idiopathic ventricular fibrillation, and there were 2 cases of sudden infant death syndrome (prevalence, 0.46%). For patients with dilated cardiomyopathy, the median left ventricle ejection fraction was 37.5% (26.25-50.0) at diagnosis and improved with treatment in 13 (61.9%). Over a median follow-up period of 6.0 years, we recorded 3 severe arrhythmic events and 2 severe hemodynamic events. CONCLUSIONS: Putative pathogenic NEXN variants were mainly associated with dilated cardiomyopathy; in these individuals, the prognosis appeared to be relatively good. However, severe and early onset phenotypes were also observed-especially in patients with double NEXN variants. We also detected NEXN variants in patients with hypertrophic cardiomyopathy and sudden infant death syndrome/idiopathic ventricular fibrillation, although a causal link could not be established.

Accuracy of a new method for semi-quantitative assessment of right ventricular ejection fraction by cardiovascular magnetic resonance: right ventricular fractional diameter changes.

OBJECTIVE: Longitudinal shortening is traditionally considered the predominant part of global right ventricular (RV) systolic function. Less attention has been paid to transverse contraction. The aim of this study was to evaluate RV transverse motion by cardiovascular magnetic resonance (CMR) in a large cohort of patients and to assess its relationship with RV ejection fraction (RVEF). STUDY DESIGN: We retrospectively analyzed the CMR scans of 300 patients referred to our center in 2010. RVEF was determined from short axis sequences using the volumetric method. Transverse parameters called RV fractional diameter changes were calculated after measuring RV diastolic and systolic diameters at basal and mid-level in short axis view (respectively FBDC and FMDC). We also measured the tricuspid annular plane systolic excursion (TAPSE) as a longitudinal reference. RESULTS: Our population was divided into 2 groups according to RVEF. 250 patients had a preserved RVEF (>40%) and 50 had a RV dysfunction (RVEF ≤ 40%). Transverse and longitudinal motions were significantly reduced in the group with RV dysfunction (p<.0001). After ROC analysis, areas under the curve for FBDC, FMDC and TAPSE, were respectively 0.79, 0.82 and 0.72, with the highest specificity and sensitivity respectively of 88% and 68% for FMDC (threshold at 20%) for predicting RV dysfunction. FMDC had an excellent negative predictive value of 93%. CONCLUSION: RV fractional diameter changes, especially at the mid-level, appear to be accurate for semi-quantitative assessment of RV function by CMR. A cut-off of 20% for FMDC differentiates patients with a low (EF≤40%) or a preserved RVEF.