Background— Atrial dilatation and atrial standstill are etiologically heterogeneous phenotypes with poorly defined nosology. In 1983, we described 8-years follow-up of atrial dilatation with standstill evolution in 8 patients from 3 families. We later identified 5 additional patients with identical phenotypes: 1 member of the largest original family and 4 unrelated to the 3 original families. All families are from the same geographic area in Northeast Italy. Methods and Results— We followed up the 13 patients for up to 37 years, extended the clinical investigation and monitoring to living relatives, and investigated the genetic basis of the disease. The disease was characterized by: (1) clinical onset in adulthood; (2) biatrial dilatation up to giant size; (3) early supraventricular arrhythmias with progressive loss of atrial electric activity to atrial standstill; (4) thromboembolic complications; and (5) stable, normal left ventricular function and New York Heart Association functional class during the long-term course of the disease. By linkage analysis, we mapped a locus at 1p36.22 containing the Natriuretic Peptide Precursor A gene. By sequencing Natriuretic Peptide Precursor A , we identified a homozygous missense mutation (p.Arg150Gln) in all living affected individuals of the 6 families. All patients showed low serum levels of atrial natriuretic peptide. Heterozygous mutation carriers were healthy and demonstrated normal levels of atrial natriuretic peptide. Conclusions— Autosomal recessive atrial dilated cardiomyopathy is a rare disease associated with homozygous mutation of the Natriuretic Peptide Precursor A gene and characterized by extreme atrial dilatation with standstill evolution, thromboembolic risk, preserved left ventricular function, and severely decreased levels of atrial natriuretic peptide.

BackgroundFew data on the thromboembolic (TE) risk of paroxysmal and persistent atrial fibrillation (AF) are available. This study aimed to assess the incidence of TE events in paroxysmal and persistent AF.MethodsWe performed a subset post hoc analysis of 771 patients with paroxysmal and 463 with persistent AF enrolled in the multicenter, prospective, randomized, double-blind, placebo-controlled GISSI-AF trial - comparing the efficacy of valsartan versus placebo in preventing AF recurrences – where the choice of antithrombotic treatment was left to the judgment of the referring physician. TE and major outcome events were centrally validated. AF recurrences were detected by frequent clinic visits and a transtelephonic monitoring device with weekly and symptomatic transmissions.ResultsEighty-five percent of patients had a history of hypertension, and the 7.7% had heart failure, left ventricular dysfunction, or both. The mean CHADS2 score was 1.41±0.84. TE and major bleeding events were observed at a low incidence among the overall population at 1-year follow-up (0.97% and 0.81%, respectively). The univariate and multivariable analyses revealed no statistically significant differences in the incidence of TE, major bleeding events or mortality in paroxysmal and persistent AF patients. TE events were more common among women than men (p=0.02). The follow-up examination showed under- or overtreatment with warfarin in many patients, according to guideline suggestions. Warfarin was more frequently prescribed to patients with persistent AF (p<0.0001) and patients with AF recurrences (p<0.0001). AF recurrences were noninvasively detected in 632 (51.2%) patients. In patients without AF recurrences, the TE event rate was 0.5% versus 1.74%, 1.28%, and 1.18% for those with only symptomatic, only asymptomatic or both symptomatic and asymptomatic AF recurrences, respectively, but the difference was not statistically significant, even after adjusting for warfarin treatment and the CHADS2 score (HR 2.93; CI 95%; 0.8-10.9; p=0.11).ConclusionsTE and major bleeding events showed a very low incidence in the GISSI-AF trial population, despite under- or overtreatment with warfarin in many patients. TE events had a similar rate in paroxysmal and persistent AF.Trial registrationTrial registration number: NCT00376272

Background Epicardial placement of the left ventricular (LV) lead via a video‐assisted thoracoscopic (VAT) approach is an alternative to the standard transvenous technique. Hypothesis Long‐term safety and efficacy of VAT and transvenous LV lead implantation are comparable. To test it, we reviewed our experience and we compared the outcomes of patients who underwent implantation with the two techniques. Methods The VAT procedure is performed under general anesthesia, with oro‐tracheal intubation and right‐sided ventilation, and requires two 5 mm and one 15 mm thoracoscopic ports. After pericardiotomy at the spot of the epicardial target area, pacing measurements are taken and a spiral screw electrode is anchored at the final pacing site. The electrode is then tunneled to the pectoral pocket and connected to the device. Results 105 patients were referred to our center for epicardial LV lead implantation. After pre‐operative assessment, 5 patients were excluded because of concomitant conditions precluding surgery. The remaining 100 underwent the procedure. LV lead implantation was successful in all patients (median pacing threshold 0.8 ± 0.5 V, no phrenic nerve stimulation) and cardiac resynchronization therapy was established in all but one patient. The median procedure time was 75 min. During a median follow‐up of 24 months, there were no differences in terms of death, cardiovascular hospitalizations or device‐related complications vs the group of 100 patients who had undergone transvenous implantation. Patients of both groups displayed similar improvements in terms of ventricular reverse remodeling and functional status. Conclusions Our VAT approach proved safe and effective, and is a viable alternative in the case of failed transvenous LV implantation.