Carlos Oberti

Genome-Wide Linkage Scan Identifies a Novel Genetic Locus on Chromosome 5p13 for Neonatal Atrial Fibrillation Associated With Sudden Death and Variable Cardiomyopathy

Background—Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, and patients with AF have a significantly increased risk for ischemic stroke. Approximately 15% of all strokes are caused by AF. The molecular basis and underlying mechanisms and pathophysiology of AF remain largely unknown. Methods and Results—We have identified a large AF family with an autosomal recessive inheritance pattern. The AF in the family manifests with early onset at the fetal stage and is associated with neonatal sudden death and, in some cases, ventricular tachyarrhythmias and waxing and waning cardiomyopathy. Genome-wide linkage analysis was performed for 36 family members and generated a 2-point logarithm of the odds (LOD) score of 3.05 for marker D5S455. The maximum multipoint LOD score of 4.10 was obtained for 4 markers: D5S426, D5S493, D5S455, and D5S1998. Heterozygous carriers have significant prolongation of P-wave duration on ECGs compared with noncarriers (107 versus 85 ms on average; P=0.000012), but no differences between these 2 groups were detected for the PR interval, QRS complex, ST-segment duration, T-wave duration, QTc, and R-R interval (P>0.05). Conclusions—Our findings demonstrate that AF can be inherited as an autosomal recessive trait and define a novel genetic locus for AF on chromosome 5p13 (arAF1). A genetic link between AF and prolonged P-wave duration was identified. This study provides a framework for the ultimate cloning of the arAF1 gene, which will increase the understanding of the fundamental molecular mechanisms of atrial fibrillation.

Downstream coronary effects of drug-eluting stents

BACKGROUND Antiproliferative agents used in drug-eluting stents (DES) attenuate atherosclerosis, yet DES implantation has been linked to endothelial dysfunction. The downstream effects of DES on new lesion formation have not been previously directly examined. We sought to compare the development of de novo stenoses and need for treatment in the downstream coronary vessel of patients treated with DES or a bare-metal stent. METHODS Angiographic images and procedural information were prospectively collected on 463 adults who underwent implantation of a single stent in a proximal coronary artery, had an appropriate control vessel for comparison, and subsequently returned for intervention. Propensity matching identified 89 pairs of patients. End points were defined as angiographic identification of a de novo stenosis or need for secondary intervention in the downstream vessel within 12 months of initial intervention. RESULTS In the overall (P < .01) and propensity-matched cohort (P = .01), there was reduced risk of new lesions downstream to DES. No difference was seen in respective control vessels (P = .14 and P = .99). A reduced need for downstream intervention with DES was seen in both the overall (P = .01) and propensity-matched cohorts (P = .04). No difference was seen in the control vessels (P = .98 and P = .36). Multivariate proportional hazards modeling of known atherosclerosis risk factors identified stent type as the sole predictor for downstream lesions (P < .01) and downstream events (P = .02). CONCLUSIONS Patients receiving DES appear less likely to develop downstream stenoses and events compared with patients receiving bare-metal stents, suggesting beneficial downstream drug delivery.

Radiofrequency Ablation with an Enhanced-Irrigation Flexible-Tip Catheter versus a Standard-Irrigation Rigid-Tip Catheter

The flexible‐tip irrigated ablation catheter Cool Flex™ (St. Jude Medical, St. Paul, MN, USA) was introduced to enhance cooling of the catheter‐tissue interface and to conform to endocardial surface with better contact. Little is known about the performance of such catheter design compared to the widely used rigid‐tip catheters.