Animal models that mimic human electrical and mechanical dyssynchrony often associated with chronic heart failure would provide an essential tool to investigate factors influencing response to cardiac resynchronization therapy. A standardized closed-chest porcine model of left bundle branch block (LBBB) was developed using 16 pigs. Radiofrequency applications were performed to induce LBBB, which was confirmed by QRS widening, a surface electrocardiogram pattern concordant with LBBB, and a prolonged activation time from endocardial. Echocardiography confirmed abnormal motion of the septum, which was not present at the baseline echocardiogram. High susceptibility of pigs to ventricular fibrillation during the endocardial ablation was overcome by applying high-rate pacing during radiofrequency applications. This is the first study to devise a closed-chest porcine model of LBBB that closely reproduces abnormalities found in patients with electrical and mechanical cardiac dyssynchrony, and provides a useful tool to investigate the basic mechanisms underlying cardiac resynchronization therapy benefits in heart failure.

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In cardiac resynchronization therapy (CRT), specific changes in motion/deformation happen with left-bundle-branch-block (LBBB) and following treatment. However, they remain sub-optimally studied. We propose a two-fold improvement of their characterization. This includes controlling them through an experimental model and using more suitable quantification techniques. We used a swine model of acute LBBB and CRT with/without chronic infarct (pure-LBBB: N = 11; LBBB + left-anterior-descending infarct: N = 11). Myocardial displacement, velocity and strain were extracted from short-axis echocardiographic sequences using 2D speckle-tracking. The data was transformed to a single spatiotemporal system of coordinates to perform subject comparisons and quantify pattern changes at similar locations and instants. Pure-LBBB animals showed a specific intra-ventricular dyssynchrony pattern with LBBB (11/11 animals), and the recovery towards a normal pattern with CRT (10/11 animals). Pattern variability was low within the pure-LBBB population, as quantified by our method. This was not correctly assessed by more conventional measurements. Infarct presence affected the pattern distribution and CRT efficiency (improvements in 6/11 animals). Pattern changes correlated with global cardiac function (global circumferential strain) changes in all the animals (corrected: (pLBBBvsBaseline) < 0.001, (pCRTvsBaseline) = NS; non-corrected: (pLBBBvsBaseline) = NS, (pCRTvsBaseline) = 0.028). Our LBBB/CRT experimental model allowed controlling specific factors responsible for changes in mechanical dyssynchrony and therapy. We illustrated the importance of our quantification method to study these changes and their variability. Our findings confirm the importance of myocardial viability and of specific LBBB-related mechanical dyssynchrony patterns.

BACKGROUND Patients with atrial fibrillation (AF) often have sleep apnea (SA), but diagnosis of SA with polysomnography is costly. SA monitoring is a pacemaker feature that measures respiratory disturbance index, the sum of abnormal respiratory events divided by sleep duration. OBJECTIVE The purpose of this study was to evaluate the incidence and severity of SA and its association with AF in an unselected population fitted with pacemakers. METHODS RESPIRE (REgistry of Sleep APnea monItoring and Atrial Fibrillation in pacemakeR patients) was a multicenter, international, observational, open-label study following adult subjects for 18 months after implantation with an SA monitoring-enabled dual-chamber pacemaker. Severe SA was defined as average respiratory disturbance index 20 from implantation to follow-up visit. The first co-primary end point was the difference in significant AF (cumulative AF episodes lasting 24 hours over 2 consecutive days) between subjects with severe and those nonsevere SA at 12 months in the full analysis set (N 5 553). The second co-primary end point was the rate of major serious adverse events at 18 months in the modified intention-to-treat set (N 5 1024). RESULTS Severe SA was detected in 31.1% (172 of 553). A higher incidence of significant AF was reported in patients with severe SA than in patients with nonsevere SA (25.0% vs 13.9%; difference 11.1%; 95% confidence interval 3.7%-18.4%; P 5 .002). Significant AF increased with time in both groups, but at a faster rate in the severe SA group. No intergroup difference in the overall rate of major serious adverse events was observed (P 5 .065). CONCLUSION SA screening over 12 months identified severe SA in almost one-third of unselected patients fitted with pacemakers. Severe SA was associated with a higher incidence of significant AF.

BACKGROUND Inappropriate shocks (IS) continue to have a major negative impact on patients implanted with defibrillators.OBJECTIVE The purpose of this study was to assess IS reduction with the PARAD1 discrimination algorithm in a general population implanted for primary or secondary prevention. METHODS ISIS-ICD (Inappropriate Shock Reduction wIth PARAD1Rhythm DiScrimination-Implantable Cardioverter Defibrillator) was a 2-year international, interventional study in patients implanted with a dual implantable cardioverter-defibrillator (ICD) or triple-chamber defibrillator (cardiac resynchronization therapy-defibrillator [CRT-D]) featuring PARAD1. IS (shocks not delivered for ventricular tachycardia or fibrillation) were independently adjudicated. The primary endpoint was percentage of IS-free patients at 24 months. Primary and worst-case analyses of annual incidence rates of patients with 1 IS, overall and per defibrillator type, were conducted. RESULTSIn total, 1013 patients (80.7% male; age 67.1 6 11.4 years; 68%/30%/2% primary/secondary/other indication) were enrolled and followed for a median of 552 days (interquartile range 354; 725). Of 993 analyzed patients programmed with PARAD1, 14 had 1 IS, corresponding to a percentage free from IS of 98.1% (95% confidence interval [CI] 96.8%-98.9%). Annual incidence rates (per 100 personyears) of patients with IS were 1.0 (95% CI 0.59-1.69) and 2.1 (95% CI 1.46-3.02) in the primary and worst-case analyses, respectively. In ICD patients, rates were 1.2 (95% CI 0.68-2.23) and 2.3 (95% CI 1.47-3.53), and in CRT-D patients 0.59 (95% CI 0.19-1.83) and 1.8 (95% CI 0.93-3.44) per 100 person-years.CONCLUSION The annual rate of defibrillator patients with IS using the enhanced PARAD1 discrimination algorithm alone ranged from 1.0 to 2.1 per 100 person-years in a general population implanted for primary or secondary prevention.