Novel Genetic Triggers and Genotype-Phenotype Correlations in Patients With Left Ventricular Noncompaction.

BACKGROUND: Left ventricular noncompaction (LVNC) is a genetically and phenotypically heterogeneous disease and, although increasingly recognized in clinical practice, there is a lack of widely accepted diagnostic criteria. We sought to identify novel genetic causes of LVNC and describe genotype-phenotype correlations. METHODS AND RESULTS: A total of 190 patients from 174 families with left ventricular hypertrabeculation (LVHT) or LVNC were referred for cardiac magnetic resonance and whole-exome sequencing. A total of 425 control individuals were included to identify variants of interest (VOIs). We found an excess of 138 VOIs in 102 (59%) unrelated patients in 54 previously identified LVNC or other known cardiomyopathy genes. VOIs were found in 68 of 90 probands with LVNC and 34 of 84 probands with LVHT (76% and 40%, respectively; P<0.001). We identified 0, 1, and ≥2 VOIs in 72, 74, and 28 probands, respectively. We found increasing number of VOIs in a patient strongly correlated with several markers of disease severity, including ratio of noncompacted to compacted myocardium (P<0.001) and left ventricular ejection fraction (P=0.01). The presence of sarcomeric gene mutations was associated with increased occurrence of late gadolinium enhancement (P=0.004). CONCLUSIONS: LVHT and LVNC likely represent a continuum of genotypic disease with differences in severity and variable phenotype explained, in part, by the number of VOIs and whether mutations are present in sarcomeric or nonsarcomeric genes. Presence of VOIs is common in patients with LVHT. Our findings expand the current clinical and genetic diagnostic approaches for patients with LVHT and LVNC.

Evaluation of factors affecting persistence of atrial fibrillation in patients with concomitant atrial flutter treated with percutaneous radiofrequency current ablation of the right atrial cavotricuspid isthmus.

BACKGROUND: Atrial fibrillation (AF) and atrial flutter (AFL) often coexist. In some patients, AF remission is seen after successful percutaneous radiofrequency current ablation of the cavotricuspid isthmus (CTI). AIM: To evaluate factors affecting AF remission in patients with typical AFL and concomitant AF who underwent CTI ablation. METHODS: The study included consecutive 69 patients with typical AFL and concomitant clinically documented AF who underwent successful CTI ablation in 2003-2010. Based on the follow-up data from medical records and telephone interviews, the patients were divided into two groups: with persistent AF (group A) and with remission of AF (group B). This distinction was based on arrhythmia symptoms reported by the patient, such as palpitation or irregular heartbeat, and confirmed electrocardiographically (12-lead ECG or Holter monitoring). RESULTS: Group A included 47 patients, and group B included 22 patients. The two groups did not differ significantly in regard to the New York Heart Association (NYHA) functional class and concomitant diseases including diabetes, ischaemic heart disease, previous myocardial infarction and arterial hypertension. The two groups also did not differ by echocardiographically determined mean left ventricular ejection fraction (LVEF) and left atrial dimension (43.5 ± 9.27 vs. 39.27 ± 5.76, p = 0.075). Multivariate logistic regression did not identify any independent risk factors of AF persistence after CTI ablation. Univariate logistic regression also did not show arterial hypertension, type 2 diabetes, previous myocardial infarction, LVEF, left ventricular dimension or age to affect AF persistence after successful ablation. CONCLUSIONS: Based on the results of our study, we were unable to identify factors determining remission of AF coexisting with AFL in patients after percutaneous CTI ablation. These findings may indicate the need for complex ablation procedure (involving both CTI and pulmonary venous ostia ablation) in patients in whom these two arrhythmias coexist.