The prevalence of acute PV conduction recovery was about 30% after PV isolation, which mostly occurred within 30 min after initial isolation. Re-isolation of recovered PV conduction contributed to the improvement in the success rate of ablation for paroxysmal AF.

In our series of paroxysmal AF patients, empirically adding SVCI to CPVI did not significantly reduce the AF recurrence after ablation. Superior vena cava isolation may be useful, however, in selected patients in whom the SVC is identified as a trigger for AF. However, because of the preliminary property of the study and its relatively small sample size, the impact of SVCI on clinical results should be evaluated in a large series of patients.

The current study reveals CASZ1 as a new gene responsible for human DCM, which provides novel mechanistic insight and potential therapeutic target for CASZ1-associated DCM, implying potential implications in improved prophylactic and therapeutic strategies for DCM, the most common type of primary myocardial disease.

Congenital heart disease (CHD) is the most common developmental abnormality, and is the leading noninfectious cause of mortality in neonates. Increasing evidence demonstrates that genetic defects play an important role in the pathogenesis of CHD. However, CHD exhibits substantial heterogeneity, and the genetic determinants for CHD remain unknown in the overwhelming majority of cases. In the current study, the coding exons and flanking introns of the HAND2 gene, which encodes a basic helix-loop-helix transcription factor essential for normal cardiovascular development, were sequenced in 192 unrelated patients with CHD, and a novel heterozygous mutation, p.S65I, was identified in a patient with congenital ventricular septal defect (VSD). Genetic analysis of the index patient’s pedigree revealed that the mutation was present in all seven affected family members available, but absent in the 13 unaffected family members examined. Besides, in addition to VSD, five of the proband’s close relatives also had pulmonary stenosis (PS), and the proband’s son also had double outlet right ventricle (DORV). The missense mutation, which altered an evolutionarily conserved amino acid, was absent in 300 unrelated, ethnically matched healthy individuals. Biological analyses using a dual-luciferase reporter assay system showed that the mutant HAND2 was associated with significantly diminished transcriptional activity. Furthermore, the mutation abolished the synergistic activation between HAND2 and GATA4, as well as NKX2.5—two other cardiac core transcriptional factors that have been causally linked to CHD. These findings indicate that HAND2 loss-of-function mutation contributes to human CHD, perhaps via its interaction with GATA4 and NKX2.5.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia associated with substantially increased morbidity and mortality. Growing evidence strongly implicates hereditary determinants in the pathogenesis of AF. However, AF is genetically heterogeneous and the genetic defects responsible for AF in the majority of cases remain to be identified. In this study, all the coding exons and splice junctions of GATA4, a gene encoding a zinc-finger transcription factor critical for normal cardiac morphogenesis, were sequenced in a cohort of 150 unrelated patients with idiopathic AF. The available relatives of the mutation carriers and a total of 200 unrelated ethnically matched healthy individuals used as controls were genotyped for the presence of mutations identified in index patients. The functional effect of the mutant GATA4 was characterized using a luciferase reporter assay system. As a result, two novel heterozygous GATA4 mutations (p.Y38D and p.P103A) were identified in 2 unrelated families with AF, respectively. In each family the mutation co-segregated with AF and was absent in the 400 control chromosomes. Functional analysis showed that the mutations of GATA4 were associated with a significantly decreased transcriptional activity. The findings expand the mutation spectrum of GATA4 linked to AF, and further support the notion that compromised GATA4 confers genetic susceptibility to AF.