Atsushi Takahashi

BACKGROUND: The end point for catheter ablation of pulmonary vein (PV) foci initiating atrial fibrillation (AF) has not been determined. METHODS AND RESULTS: Ninety patients underwent mapping during spontaneous or induced ectopy and/or AF initiation. Ostial PV ablation was performed by use of angiograms to precisely define targeted sites. Success defined by elimination of AF without drugs was correlated with the procedural end point of the abolition of distal PV potentials. A total of 197 arrhythmogenic PV foci (97%)-single in 31% and multiple in 69%-and 6 atrial foci were identified. A discrete radiofrequency (RF) application eliminated the PV potentials in 9 PV foci, whereas 2 foci from the same PV required RF applications at separate sites in 19 cases. In others, a wider region was targeted with progressive elimination of ectopy. In 49 patients, multiple sessions were necessary owing to recurrent or new ectopy. The clinical success rates were 93%, 73%, and 55% in patients with 1, 2, and > or =3 arrhythmogenic PV foci. Recovery of local PV potential and the inability to abolish it were significantly associated with AF recurrences (90% success rate with versus 55% without PV potential abolition). PV stenosis was noted acutely in 5 of 6 cases, remained unchanged at restudy, and was associated with RF power >45 W. CONCLUSIONS: Multiple PV foci are involved in initiation of AF, and elimination of PV muscle conduction is associated with clinical success.

Clinical measurements can be viewed as useful intermediate phenotypes to promote understanding of complex human diseases. To acquire comprehensive insights into the underlying genetics, here we conducted a genome-wide association study (GWAS) of 58 quantitative traits in 162,255 Japanese individuals. Overall, we identified 1,407 trait-associated loci (P < 5.0 × 10−8), 679 of which were novel. By incorporating 32 additional GWAS results for complex diseases and traits in Japanese individuals, we further highlighted pleiotropy, genetic correlations, and cell-type specificity across quantitative traits and diseases, which substantially expands the current understanding of the associated genetics and biology. This study identified both shared polygenic effects and cell-type specificity, represented by the genetic links among clinical measurements, complex diseases, and relevant cell types. Our findings demonstrate that even without prior biological knowledge of cross-phenotype relationships, genetics corresponding to clinical measurements successfully recapture those measurements’ relevance to diseases, and thus can contribute to the elucidation of unknown etiology and pathogenesis. A genome-wide association study (GWAS) of 58 traits using data from the Biobank Japan Project identifies 1,407 loci, 679 of which are novel. Comparison with disease GWASs and analysis of genetic correlations and cell-type enrichment show that these clinical measurements are relevant to human disease.