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Background: Studies have reported that female sex predicts superior cardiac resynchronization therapy (CRT) response. One theory is that this association is related to smaller female heart size, thus increased relative dyssynchrony at a given QRS duration (QRSd). Our objective was to investigate the mechanisms of sex-specific CRT response relating to heart size, relative dyssynchrony, cardiomyopathy type, QRS morphology, and other patient characteristics., Methods and Results: This is a post hoc analysis of the MORE-CRT MPP (More Response on Cardiac Resynchronization Therapy with Multipoint Pacing)  trial (n=3739, 28% women), with a subgroup analysis of patients with nonischemic cardiomyopathy and left bundle-branch block (n=1308, 41% women) to control for confounding characteristics. A multivariable analysis examined predictors of response to 6 months of conventional CRT, including sex and relative dyssynchrony, measured by QRSd/left ventricular end-diastolic volume (LVEDV). Women had a higher CRT response rate than men (70.1% versus 56.8%, P <0.0001). In subgroup analysis, regression analysis of the nonischemic cardiomyopathy left bundle-branch block subgroup identified QRSd/LVEDV, but not sex, as a modifier of CRT response ( P <0.0039). QRSd/LVEDV was significantly higher in women (0.919) versus men (0.708, P <0.001). CRT response was 78% for female patients with QRSd/LVEDV greater than the median value, compared with 68% with QRSd/LVEDV less than the median value ( P =0.012). The association between CRT response and QRSd/LVEDV was strongest at QRSd <150 ms., Conclusions: In the nonischemic cardiomyopathy left bundle-branch block population, increased relative dyssynchrony in women, who have smaller heart sizes than their male counterparts, is a driver of sex-specific CRT response, particularly at QRSd <150 ms. Women may benefit from CRT at a QRSd <130 ms, opening the debate on whether sex-specific QRSd cutoffs or QRS/LVEDV measurement should be incorporated into clinical guidelines.

Aims: In bradycardia patients treated with dual-chamber pacing, we aimed to evaluate whether pacing with atrioventricular (AV) delay management [AV hysteresis (AVH)], compared with standard pacing with fixed AV delays, reduces unnecessary ventricular pacing percentage (VPP) and is associated with better clinical outcomes. Main study endpoints were the incidence of heart failure hospitalizations (HFH), persistent atrial fibrillation (AF), and cardiac death., Methods and Results: Data from two identical prospective observational studies, BRADYCARE I in the USA and BRADYCARE II in Europe, Africa, and Asia, were pooled. Overall, 2592 patients (75 ± 10 years, 45.1% female, 50% with AVH) had complete clinical and device data at 1-year follow-up and were analysed. Primary pacing indication was sinus node disease (SND) in 1177 (45.4%), AV block (AVB) in 974 (37.6%), and other indications in 441 (17.0%) patients. Pacing with AVH, compared with standard pacing, was associated with a lower 1-year incidence of HFH [1.3% vs. 3.1%, relative risk reduction (RRR) 57.5%, P = 0.002] and of persistent AF (5.3% vs. 7.7%, RRR = 31.1%, P = 0.028). Cardiac mortality was not different between groups (1.0% vs. 1.4%, RRR = 27.8%, P = 0.366). Pacing with AVH, compared with standard pacing, was associated with a lower (P < 0.001) median VPP in all patients (7% vs. 75%), in SND (3% vs. 44%), in AVB (25% vs. 98%), and in patients with other pacing indications (3% vs. 47%)., Conclusion: Cardiac pacing with AV delay management via AVH is associated with reduced 1-year incidence of HFH and persistent AF, most likely due to a reduction in VPP compared to standard pacing., Competing Interests: Conflict of interest: M.A. participated in clinical trials sponsored by Abbott and Biotronik; he received speaker honoraria from Biotronik. A.A. participated in clinical trials sponsored by Boston Scientific, Medtronic, EPD Philips, and XSpline; he received consultant or speaker fees from Abbott, Boston Scientific, Cairdac, Corvia, EP Solution, Microport CRM, Philips, Radcliffe Publishers, and XSpline, and he has intellectual properties with Boston Scientific, Biosense Webster, and Microport CRM. A.A. is the review editor of EP Europace and was not involved in the peer review process or publication decision. G.B. received speaker fees from Boston Scientific, Abbott, Daiichi, and Boehringer Ingelheim. A.P., W.L., and A.G. are Abbott employees. All remaining authors have declared no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Cardiac resynchronization therapy (CRT) is indicated in patients with systolic heart failure (HF), severe left ventricle (LV) dysfunction and interventricular dyssynchrony.In prospective observational research, we aimed to evaluate whether CRT-induced LV reverse remodelling and occurrence of ventricular arrhythmias (VT/VF) independently contribute to prognosis in patients with CRT defibrillators (CRT-D)., Methods: In 95 Italian cardiological centres, after a screening period of 6 months, patients were categorized according to VT/VF occurrence and CRT response, defined as LV end-systolic volume relative reduction >15% or LV ejection fraction absolute increase >5%. The main endpoint was death or HF hospitalizations., Results: Among 1308 CRT-D patients (80% male, mean age 66 years), at 6 months, follow-up 71% were identified as CRT responders and 12% experienced appropriate VT/VF detections. The main endpoint was significantly and independently associated with previous myocardial infarction, New York Heart Association Class, VT/VF occurrence and with CRT response. CRT nonresponder patients who suffered VT/VF in the screening period had a risk of death or HF hospitalizations [HR = 7.82, 95% confidence interval (CI) = 3.95-15.48] significantly (P < 0.001) higher than CRT responders without VT/VF occurrence. This risk is mitigated without VT/VF occurrence (HR = 3.47, 95% CI = 2.03-5.91, P < 0.001) or in case of CRT response (HR = 3.11, 95% CI = 1.44-6.72, P = 0.004)., Conclusion: Our data show that both CRT response and occurrence of VT/VF independently contribute to the risk of death or HF-related hospitalizations in CRT-D patients. Early VT/VF occurrence may be identified as a marker of disease severity than can be mitigated by CRT response both in terms of all-cause mortality and long-term VT/VF onset., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00147290 and NCT00617175., (Copyright © 2021 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Objective: Inappropriate implantable cardioverter defibrillators (ICD) therapies have been associated with multiple adverse effects, including worse quality of life and prognosis. We evaluated the possibility of predicting atrial fibrillation (AF)-related inappropriate ICD shocks through continuous monitoring of device diagnostics., Methods: 1404 ICD patients were prospectively followed in an observational research by 74 Italian cardiology centres. Device diagnostics stored daily information on AF duration and ventricular rate (VR) during AF. Uncontrolled VR was defined as mean VR>80 beats per minute (bpm) and maximum VR>110 bpm. Expert electrophysiologists reviewed the ventricular tachycardia/ventricular fibrillation (VT/VF) episodes electrograms, stored in the device memory, and classified appropriate detections, inappropriate detection mechanisms and ICD therapy outcomes., Results: Over a median follow-up of 31 months, 511 (36%) patients suffered spontaneous VT/VF, which were treated by ICD shocks in a subgroup of 189 (13%) patients. Inappropriate detections occurred in 232 (16%) patients, and inappropriate ICD shocks in 101 (7%) patients. AF was the cause of inappropriate shocks in 60 patients. AF caused 144 inappropriate shocks: 53% of all inappropriate shocks. The likelihood of experiencing AF-related inappropriate shocks was 2.4% at 1 year and 6% at 5 years. Uncontrolled VR during AF proved to be an independent predictor of AF-related inappropriate shocks (OR=3.02, p=0.006); an alarm set at a VR>90 bpm or 100 bpm was associated with prediction of AF-related inappropriate shocks with a sensitivity of 73% or 62%, respectively., Conclusions: AF is the most common cause of inappropriate shocks in ICD patients. Continuous remote monitoring of VR during AF would promptly and efficiently predict AF-related inappropriate shocks., Clinical Trial Registration: http://clinicaltrials.gov/ct2/show/NCT01007474.

Aims: Uncontrolled ventricular rate (VR) during atrial fibrillation (AF) may cause clinical deterioration in heart failure (HF) patients who need continuous biventricular pacing to achieve cardiac resynchronization therapy (CRT). We aimed at evaluating the association between AF, uncontrolled VR, and sub-optimal CRT, defined as low biventricular pacing percentage (BIVP%)., Methods and Results: All 1404 patients had HF, New York Heart Association (NYHA) ≥II, left ventricular ejection fraction (LVEF) ≤35%, and QRS ≥120 ms, and received an implantable CRT defibrillator (CRT-D). Occurrence of AF, VR during AF and lifetime BIVP% were estimated from device data. Ventricular rate during AF was defined as uncontrolled in patients with mean VR>80 bpm and maximum VR>110 bpm. Over a median follow-up of 18 months, AF was detected in 443 of 1404 patients (32%). In this sub-group of AF patients, VR during AF was uncontrolled in 150 of 443 patients (34%). Multivariate Cox regression analysis showed that age [hazard ratio (HR) = 1.03, 95% confidence interval (CI) = 1.00-1.06, P= 0.028], and uncontrolled VR [HR = 1.69 (CI = 1.01-2.83), P= 0.046] were the only independent predictors of clinical outcome, assessed by HF hospitalizations and death. The median lifetime BIVP% was 95% (25-75 percentile range 91-99%). Biventricular pacing percentage was significantly and inversely correlated to VR, decreasing by 7% for each 10 bpm increase in VR. Sub-optimal CRT, defined as BIVP% <95%, was predicted by the occurrence of persistent or permanent AF [odds ratio (OR) = 3.77, CI = 2.44-5.82, P< 0.001], and uncontrolled VR [OR = 2.25, CI = 1.35-3.73, P= 0.002]., Conclusion: Uncontrolled VR occurs in one-third of CRT-D patients, who experience AF, and is associated with HF hospitalizations and death and with sub-optimal CRT (lifetime BIVP%<95%).

Objectives: The purpose of this analysis was to evaluate the correlation between atrial tachycardia (AT) or atrial fibrillation (AF) and clinical outcomes in heart failure (HF) patients implanted with a cardiac resynchronization therapy defibrillator (CRT-D)., Background: In HF patients, AT and AF have high prevalence and are associated with compromised hemodynamic function., Methods: Forty-four Italian cardiological centers followed up 1,193 patients who received a CRT-D according to current guidelines for advanced HF, New York Heart Association functional class ≥ II, left ventricular ejection fraction ≤ 35%, and QRS complex ≥ 120 ms. All patients were in sinus rhythm at implant., Results: During a median follow-up period of 13 months, AT/AF >10 min occurred in 361 of 1,193 (30%) patients. The composite end point (deaths or HF hospitalizations) occurred in 174 of 1,193 (14.6%). Multivariate time-dependent Cox regression analyses showed that composite end point risk was higher among patients with device-detected AT/AF (hazard ratio [HR]: 2.16, p = 0.032), New York Heart Association functional class III or IV compared with II (HR: 2.09, p = 0.002), and absence of beta-blockers (HR: 1.36, p = 0.036). Furthermore, the composite end point risk was inversely associated with left ventricular ejection fraction (HR: 1.04, p = 0.045), increasing by a factor of 4% for each 1% decrease in left ventricular ejection fraction., Conclusions: In HF patients with CRT-D, device-detected AT/AF is associated with a worse prognosis. Continuous device diagnostics monitoring and Web-based alerts may inform the physician of AT/AF occurrences and identify patients at risk of cardiac deterioration or patients with suboptimal rate or rhythm control. (Italian ClinicalService Project; NCT01007474)., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The aim of the present study was to evaluate the incidence, predictors, and related outcomes of patients with heart failure (HF) treated with cardiac resynchronization therapy with an implantable cardioverter defibrillator (CRT-D) who experienced electrical storm (ES). Electrical storm was defined as the occurrence of >or=3 episodes in 24 hours of sustained ventricular tachyarrhythmias., Methods: A total of 631 patients with HF (90% male, mean 66+/-9 years) consecutively received a CRT-D device. At baseline, the mean left ventricular ejection fraction was 26%+/-7%, the QRS duration was 164+/-33 milliseconds, and the mean New York Heart Association class was 3.3+/-0.3., Results: During a mean follow-up of 19+/-11 months, 2,419 ventricular tachyarrhythmia episodes were appropriately detected in 141 (22%) patients. Electrical storm occurred in 45 (7%) of 631 patients. Kaplan-Meier analysis and multivariable Cox regression showed that ES is more frequent in secondary prevention (hazard ratio 2.3, 95% CI 1.2-4.3, P=.015) and in nonischemic patients (hazard ratio 2.0, 95% CI 1.1-3.8, P=.028). In patients who presented ES, CRT was associated with only marginal nonsignificant improvements of New York Heart Association class and left ventricular ejection fraction. Hospitalizations and death due to HF were more frequent in patients with ES compared with those without ES, amounting to 16.8 (4.3) versus 8.6 (0.9) per 100 patient-years (P = .018) and 7.7 versus 2.7 per 100 patient-years (P=.014), respectively., Conclusions: Electrical storm affect only 7% of CRT-D recipients and occurred more frequently in nonischemic patients with HF with biventricular implantable cardioverter defibrillators implanted for secondary prevention. Electrical storm was associated with worse HF morbidity and mortality.

Background: Atrial fibrillation (AF) induces loss of atrial contribution, heart rate irregularity, and fast ventricular rate., Objectives: The objectives of the study were to accurately measure AF incidence and to investigate the mutual temporal patterns of AF and heart failure (HF) in patients indicated to cardiac resynchronization therapy., Methods: Four hundred ten consecutive patients (70% male, age 69 +/- 11) with advanced HF (NYHA = 3.0 +/- 0.6), low ejection fraction (EF = 27 +/- 9%), and ventricular conduction delay (QRS = 165 +/- 29 ms) received a biventricular pacemaker. Enrolled patients were divided into two groups: G1 = 249 patients with no AF history, G2 = 161 patients with history of paroxysmal/persistent AF., Results: In a median follow-up of 13 months, AF episodes longer than 5 minutes occurred in 105 of 249 (42.2%) G1 patients and 76 of 161 (47.2%) G2 patients, while AF episodes longer than one day occurred in 14 of 249 (5.6%) G1 patients and in 36 of 161 (22.4%) G2 patients. Device diagnostics monitored daily values of patient activity, night heart rate (NHR), and heart rate variability (HRV). Comparing 30-day periods before AF onset and during persistent AF, significant (P < 0.0001) changes were observed in patient activity, which decreased from 221 +/- 13 to 162 +/- 12 minutes, and in NHR, which increased from 68 +/- 3 to 94 +/- 7 bpm. HRV significantly decreased (from 75 +/- 5 ms before AF onset to 60 +/- 6 ms after AF termination). NHR during AF was significantly (P < 0.01) and inversely correlated (R(2)= 0.73) with activity, with a significant lower activity associated with NHR >or= 88 bpm., Conclusion: AF is frequent in HF patients. Persistent AF is associated with statistically significant decrease in patient activity and HRV and NHR increase.

Background: Temporal patterns of ventricular tachyarrhythmia (VT/VF) have been studied only in patients who have received implantable cardioverter defibrillators (ICD) for secondary prevention of sudden death, and mainly in ischemic patients. The aim of this study was to evaluate VT/VF recurrence patterns in heart failure (HF) patients with biventricular ICD and to stratify results according to HF etiology and ICD indication., Methods and Results: We studied 421 patients (91% male, 66 +/- 9 years). HF etiology was ischemic in 292 patients and nonischemic in 129. ICD indication was for primary prevention in 227 patients and secondary prevention in 194. Baseline left ventricular ejection fraction (LVEF) was 26 +/- 7%, QRS duration 168 +/- 32 msec, and NYHA class 2.9 +/- 0.6. In a follow-up of 19 +/- 11 months, 1,838 VT/VF in 110 patients were appropriately detected. In 59 patients who had > or = 4 episodes, we tried to determine whether VT/VF occurred randomly or rather tended to cluster by fitting the frequency distribution of tachycardia interdetection intervals with exponential functions: VT/VF clusters were observed in 46 patients (78% of the subgroup of patients with > or = 4 episodes and 11% of the overall population). On multivariate logistic analysis, VT/VF clusters were significantly (P < 0.01) associated with ICD indication for secondary prevention (odds ratio [OR] = 3.12; confidence interval [CI] = 1.56-6.92), nonischemic HF etiology (OR = 4.34; CI = 2.02-9.32), monomorphic VT (OR = 4.96; CI = 2.28-10.8), and LVEF < 25% (OR = 3.34; CI = 1.54-7.23). Cardiovascular hospitalizations and deaths occurred more frequently in cluster (21/46 [46%]) than in noncluster patients (63/375 (17%), P < 0.0001)., Conclusions: In HF patients with biventricular ICDs, VT/VF clusters may be regarded as the epiphenomenon of HF deterioration or as a marker of suboptimal response to cardiac resynchronization therapy.

Aims In bradycardia patients treated with dual-chamber pacing, we aimed to evaluate whether pacing with atrioventricular (AV) delay management [AV hysteresis (AVH)], compared with standard pacing with fixed AV delays, reduces unnecessary ventricular pacing percentage (VPP) and is associated with better clinical outcomes. Main study endpoints were the incidence of heart failure hospitalizations (HFH), persistent atrial fibrillation (AF), and cardiac death. Methods and results Data from two identical prospective observational studies, BRADYCARE I in the USA and BRADYCARE II in Europe, Africa, and Asia, were pooled. Overall, 2592 patients (75 ± 10 years, 45.1% female, 50% with AVH) had complete clinical and device data at 1-year follow-up and were analysed. Primary pacing indication was sinus node disease (SND) in 1177 (45.4%), AV block (AVB) in 974 (37.6%), and other indications in 441 (17.0%) patients. Pacing with AVH, compared with standard pacing, was associated with a lower 1-year incidence of HFH [1.3% vs. 3.1%, relative risk reduction (RRR) 57.5%, P = 0.002] and of persistent AF (5.3% vs. 7.7%, RRR = 31.1%, P = 0.028). Cardiac mortality was not different between groups (1.0% vs. 1.4%, RRR = 27.8%, P = 0.366). Pacing with AVH, compared with standard pacing, was associated with a lower (P < 0.001) median VPP in all patients (7% vs. 75%), in SND (3% vs. 44%), in AVB (25% vs. 98%), and in patients with other pacing indications (3% vs. 47%). Conclusion Cardiac pacing with AV delay management via AVH is associated with reduced 1-year incidence of HFH and persistent AF, most likely due to a reduction in VPP compared to standard pacing. [ABSTRACT FROM AUTHOR]

Background. Cardiac resynchronization therapy (CRT) is a treatment for heart failure (HF) patients with prolonged QRS and impaired left ventricular (LV) systolic function. We aim to evaluate how the baseline PR interval is associated with outcomes (all-cause death or HF hospitalizations) and LV reverse remodeling (>15% relative reduction in LV end-systolic volume). Methods. Among 2224 patients with CRT defibrillators, 1718 (77.2%) had a device programmed at out-of-the-box settings (sensed AV delay: 100 ms and paced AV delay: 130 ms). Results. In this cohort of 1718 patients (78.7% men, mean age 66 years, 71.6% in NYHA class III/IV, LVEF = 27 ± 6%), echocardiographic assessment at 6-month follow-up showed that LV reverse remodeling was not constant as a function of the PR interval; in detail, it occurred in 56.4% of all patients but was more frequent (76.6%) in patients with a PR interval of 160 ms. In a median follow-up of 20 months, the endpoint of death or HF hospitalizations occurred in 304/1718 (17.7%) patients; in the multivariable regression analysis it was significantly less frequent when the PR interval was between 150 and 170 ms (hazard ratio = 0.79, 95% confidence interval (CI): 0.63–0.99, p = 0.046). The same PR range was associated with higher probability of CRT response (odds ratio = 2.51, 95% CI: 1.41–4.47, p = 0.002). Conclusions. In a large population of CRT patients, with fixed AV pacing delays, specific PR intervals are associated with significant benefits in terms of LV reverse remodeling and lower morbidity. These observational data suggest the importance of optimizing pacing programming as a function of the PR interval to maximize CRT response and patient outcome. [ABSTRACT FROM AUTHOR]

Aims: We sought to determine whether atrioventricular junction ablation (AVJA) in patients with cardiac resynchronization therapy (CRT) implantable cardioverter-defibrillator (ICD) and with permanent atrial fibrillation (AF) has a positive impact on ICD shocks and hospitalizations compared with rate-slowing drugs.Methods and Results: This is a pooled analysis of data from 179 international centres participating in two randomized trials and one prospective observational research. The co-primary endpoints were all-cause ICD shocks and all-cause hospitalizations. Out of 3358 CRT-ICD patients (2720 male, 66.6 years), 2694 (80%) were in sinus rhythm (SR) and 664 (20%) had permanent AF-262 (8%) treated with AVJA (AF + AVJA) and 402 (12%) treated with rate-slowing drugs (AF + Drugs). Median follow-up was 18 months. The mean (95% confidence intervals) annual rate of all-cause ICD shocks per 100 patient years was 8.0 (5.3-11.9) in AF + AVJA, 43.6 (37.7-50.4) in AF + Drugs, and 34.4 (32.5-36.5) in SR patients, resulting in incidence rate ratio (IRR) reductions of 0.18 (0.10-0.32) for AF + AVJA vs. AF + Drugs (P < 0.001) and 0.48 (0.35-0.66) for AF + AVJA vs. SR (P < 0.001). These reductions were driven by significant reductions in both appropriate ICD shocks [IRR 0.23 (0.13-0.40), P < 0.001, vs. AF + Drugs] and inappropriate ICD shocks [IRR 0.09 (0.04-0.21), P < 0.001, vs. AF + Drugs]. Annual rate of all-cause hospitalizations was significantly lower in AF + AVJA vs. AF + Drugs [IRR 0.57 (0.41-0.79), P < 0.001] and SR [IRR 0.85 (073-0.98), P = 0.027].Conclusion: In AF patients treated with CRT, AVJA results in a lower incidence and burden of all-cause, appropriate and inappropriate ICD shocks, as well as to fewer all-cause and heart failure hospitalizations.Clinical Trial Registration: NCT00147290, NCT00617175, NCT01007474. [ABSTRACT FROM AUTHOR]