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Continuous automatic optimisation of cardiac resynchronisation therapy (CRT), stimulating only the left ventricle to fuse with intrinsic right bundle conduction (synchronised left ventricular stimulation), might offer better outcomes than conventional CRT in patients with heart failure, left bundle branch block, and normal atrioventricular conduction. This study aimed to compare clinical outcomes of adaptive CRT versus conventional CRT in patients with heart failure with intact atrioventricular conduction and left bundle branch block. This global, prospective, randomised controlled trial was done in 227 hospitals in 27 countries across Asia, Australia, Europe, and North America. Eligible patients were aged 18 years or older with class 2–4 heart failure, an ejection fraction of 35% or less, left bundle branch block with QRS duration of 140 ms or more (male patients) or 130 ms or more (female patients), and a baseline PR interval 200 ms or less. Patients were randomly assigned (1:1) via block permutation to adaptive CRT (an algorithm providing synchronised left ventricular stimulation) or conventional biventricular CRT using a device programmer. All patients received device programming but were masked until procedures were completed. Site staff were not masked to group assignment. The primary outcome was a composite of all-cause death or intervention for heart failure decompensation and was assessed in the intention-to-treat population. Safety events were collected and reported in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT02205359, and is closed to accrual. Between Aug 5, 2014, and Jan 31, 2019, of 3797 patients enrolled, 3617 (95·3%) were randomly assigned (1810 to adaptive CRT and 1807 to conventional CRT). The futility boundary was crossed at the third interim analysis on June 23, 2022, when the decision was made to stop the trial early. 1568 (43·4%) of 3617 patients were female and 2049 (56·6%) were male. Median follow-up was 59·0 months (IQR 45–72). A primary outcome event occurred in 430 of 1810 patients (Kaplan-Meier occurrence rate 23·5% [95% CI 21·3–25·5] at 60 months) in the adaptive CRT group and in 470 of 1807 patients (25·7% [23·5–27·8] at 60 months) in the conventional CRT group (hazard ratio 0·89, 95% CI 0·78–1·01; p=0·077). System-related adverse events were reported in 452 (25·0%) of 1810 patients in the adaptive CRT group and 440 (24·3%) of 1807 patients in the conventional CRT group. Compared with conventional CRT, adaptive CRT did not significantly reduce the incidence of all-cause death or intervention for heart failure decompensation in the included population of patients with heart failure, left bundle branch block, and intact AV conduction. Death and heart failure decompensation rates were low with both CRT therapies, suggesting a greater response to CRT occurred in this population than in patients in previous trials. Medtronic.

In patients with reduced ejection fraction, mild heart failure, and prolonged QRS duration, CRT with a defibrillator improved survival, as compared with defibrillator therapy alone. The survival benefit was limited to patients with left bundle-branch block. The Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT) showed the safety and effectiveness of cardiac-resynchronization therapy (CRT) with a defibrillator (CRT-D) in patients with asymptomatic or mildly symptomatic heart failure, a reduced ejection fraction, and a prolonged QRS duration. 1 The study showed that treatment with CRT-D was associated with a 34% relative reduction in the risk of nonfatal heart-failure events or death from any cause, as compared with implantable cardioverter–defibrillator (ICD) therapy alone over a median follow-up period of 2.4 years. The benefit of CRT-D in the trial was primarily driven by a significant relative reduction of . . .

•Conduction system pacing, also termed physiologic pacing, is a novel alternative to biventricular resynchronization that may improve left ventricular remodeling while minimizing costs.•PhysioSync-HF is an investigator-led, randomized, multicenter clinical trial comparing conduction system pacing and biventricular resynchronization on heart failure-related outcomes in 179 patients with heart failure with reduced ejection fraction and left bundle branch block.•Half of trial participants are women, and most are non-White, ensuring patient representativeness and generalizability. Cardiac resynchronization therapy reduces heart failure hospitalizations and mortality in patients with heart failure with reduced ejection fraction (HFrEF) and left bundle branch block (LBBB). Conduction system pacing, which directly activates the His-Purkinje system, has emerged as a safe alternative to traditional biventricular resynchronization that may offer clinical benefits at lower costs. The PhysioSync-HF trial is an investigator-led, randomized, multicenter clinical trial designed to assess whether conduction system pacing is noninferior to biventricular resynchronization on heart failure-related outcomes in patients with HFrEF and LBBB. The study population consists of 179 adults with symptomatic heart failure (New York Heart Association [NYHA] class II-III), left ventricular ejection fraction (LVEF) ≤35%, and LBBB (QRS ≥130 ms). Patients were randomized 1:1 to receive conduction system pacing or biventricular resynchronization and followed for 12 months postprocedure. The primary endpoint is a hierarchy of all-cause death, any hospitalization for heart failure, any urgent visit for heart failure, and change in LVEF from baseline. The key secondary endpoint is the mean total direct medical cost per patient. Additional endpoints include assessments of health-related quality of life, functional capacity, and safety. Enrollment began in November 2022 and concluded in December 2023. PhysioSync-HF will determine whether conduction system pacing is noninferior to biventricular resynchronization on heart failure-related outcomes in patients with HFrEF with LBBB. NCT05572736. *In selected sites. 6MWT indicates 6-minute walk test; CPET, cardiopulmonary exercise test; ECG, electrocardiogram; EQ-5D, EuroQol Group 5-Dimensions questionnaire; HF, heart failure; KCCQ, Kansas City Cardiomyopathy Questionnaire; LVEF, left ventricular ejection fraction. [Display omitted]

ObjectiveMany patients undergoing transcatheter aortic valve implantation (TAVI) have a pre-existing, permanent pacemaker (PPM) or receive one as a consequence of the procedure. We hypothesised that chronic pacing may have adverse effects on TAVI outcomes.Methods and resultsFour groups of patients undergoing TAVI in the Placement of Aortic Transcatheter Valves (PARTNER) trial and registries were compared: prior PPM (n=586), new PPM (n=173), no PPM (n=1612), and left bundle branch block (LBBB)/no PPM (n=160). At 1 year, prior PPM, new PPM and LBBB/no PPM had higher all-cause mortality than no PPM (27.4%, 26.3%, 27.7% and 20.0%, p<0.05), and prior PPM or new PPM had higher rehospitalisation or mortality/rehospitalisation (p<0.04). By Cox regression analysis, new PPM (HR 1.38, 1.00 to 1.89, p=0.05) and prior PPM (HR 1.31, 1.08 to 1.60, p=0.006) were independently associated with 1-year mortality. Surviving prior PPM, new PPM and LBBB/no PPM patients had lower LVEF at 1 year relative to no PPM (50.5%, 55.4%, 48.9% and 57.6%, p<0.01). Prior PPM had worsened recovery of LVEF after TAVI (Δ=10.0 prior vs 19.7% no PPM for baseline LVEF <35%, p<0.0001; Δ=4.1 prior vs 7.4% no PPM for baseline LVEF 35–50%, p=0.006). Paced ECGs displayed a high prevalence of RV pacing (>88%).ConclusionsIn the PARTNER trial, prior PPM, along with new PPM and chronic LBBB patients, had worsened clinical and echocardiographic outcomes relative to no PPM patients, and the presence of a PPM was independently associated with 1-year mortality. Ventricular dyssynchrony due to chronic RV pacing may be mechanistically responsible for these findings.Trial registration number(ClinicalTrials.gov NCT00530894).

Background Left bundle branch area pacing (LBBaP) is a new physiological pacing strategy that produces comparable clinical effects to His bundle pacing (HBP). Objective The purpose of this study was to investigate the immediate clinical outcomes of LBBaP vs RVP. Methods and Results From April 2018 to September 2018, we included 44 patients under continuous pacemaker implantation. Patients were randomly divided into the LBBaP group and conventional RVP group. Compared to the RVP group, the LBBaP group displayed significantly increased operative (90.10 ± 19.68 minutes vs 61.57 ± 6.62 minutes, P < .001) and X‐ray exposure times (15.55 ± 5.62 minutes vs 4.67 ± 2.06 minutes, P < .001). The lead threshold of the LBBaP group was increased (0.68 ± 0.20 mV vs 0.51 ± 0.0 mV, P = .001), while the R‐wave amplitude and ventricular impedance did not significantly differ between the two groups. The conventional RVP procedure significantly widened the QRS complex (93.62 ± 8.28 ms vs 135.19 ± 12.21 ms, P = .001), whereas the LBBaP had no effect on QRS complex (130.13 ± 43.30 ms vs 112.63 ± 12.14 ms, P = .904). Furthermore, the LBBaP procedure significantly narrowed the QRS complex in patients with left bundle branch block (LBBB) (168.43 ± 38.870 ms vs 119.86 ± 6.69 ms, P = .019). Conclusion LBBaP is a new physiological, safe and effective pacing procedure with a high overall success rate. Compared to conventional RVP, LBBaP can correct LBBB, thereby improving cardiac electrical dyssynchrony.

Objective In MADIT-CRT, patients with non-LBBB (right bundle branch block or nonspecific ventricular conduction delay) and a prolonged PR-interval derived significant clinical benefit from cardiac resynchronization therapy with defibrillator (CRT-D) compared to an implantable cardioverter defibrillator (ICD)-only. We aimed to study the long-term outcome of non-LBBB patients by baseline PR-interval with CRT-D versus ICD-only. Methods Non-LBBB patients ( n  = 534) were dichotomized based on baseline PR-interval: normal PR (PR < 230 ms), and markedly prolonged PR (PR ≥ 230 ms). The primary end point was heart failure (HF) or death. Secondary end points were HF only and all-cause death. Results In patients with a prolonged PR-interval, CRT-D treatment related to a 67 % significant reduction in the risk of HF/death (HR = 0.33, 95 % CI 0.16–0.69, p  = 0.003), 69 % decrease in HF (HR = 0.31, 95 % CI 0.14–0.68, p  = 0.003), and 76 % reduction in the risk of death (HR = 0.24, 95 % CI 0.07–0.80, p  = 0.020) compared to ICD-only (median follow-up 5.8 years). In normal PR-interval patients, CRT-D therapy was associated with a trend towards increased risk of HF/death (HR = 1.49, 95 % CI 0.98–2.25, p  = 0.061), and significantly increased mortality (HR = 2.27, 95 % CI 1.16–4.44, p  = 0.014). Significant statistical interaction with the PR-interval was demonstrated for all end points. Results were consistent for QRS 130–150 ms and QRS > 150 ms. Conclusion In MADIT-CRT, non-LBBB patients with a prolonged PR-interval derive sustained long-term clinical benefit with reductions in heart failure or death from CRT-D implantation, compared to an ICD-only. Our findings support implantation of CRT-D in non-LBBB patients with prolonged PR-interval irrespective of baseline QRS duration.

Cardiac resynchronization therapy (CRT) has proven prognostic benefits in patients with heart failure (HF) with left bundle branch block (LBBB) QRS morphology. Electrocardiographic left atrial (LA) abnormality has been proposed as a noninvasive marker of atrial remodeling. We aimed to assess the impact of electrocardiographic LA abnormality for prognosis in patients with HF treated with CRT. Baseline resting 12-lead electrocardiograms recorded from 941 patients enrolled in the CRT arm of the Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy was processed automatically using Glasgow algorithm, which included automated assessment of P-wave terminal force in lead V1 (PTF-V1) as a marker of LA abnormality. A PTF-V1 of ≥0.04 mm⋅s was considered abnormal. The primary end point was HF event and/or death. Total mortality and appropriate defibrillator therapies were the secondary end points. At baseline 550, patients treated with CRT with a defibrillator had LBBB QRS morphology and normal PTF-V1. Normal PTF-V1 was associated with significant risk reduction for all assessed end points and for the primary end point comprised a hazard ratio of 0.55 (95% confidence interval 0.36 to 0.84) compared with patients with LBBB with abnormal PTF-V1 (n = 120), and a hazard ratio of 0.42 (95% confidence interval 0.32 to 0.55) compared with patients with implanted defibrillator (n = 729). In CRT-treated patients with HF, electrocardiographic LA abnormality appears to be an electrocardiographic indicator of poor long-term outcome in patients with LBBB. In conclusion, our data suggest that PTF-V1 bears additive prognostic information in the context of CRT, thus further strengthening the role of electrocardiographic diagnostics in risk stratification of patients with HF.

The current guidelines most strongly support cardiac resynchronization therapy (CRT) for patients with heart failure with a QRS width of ≥150 ms and left bundle branch block (LBBB). Our objective was to assess the potential benefit of echocardiographically guided left ventricular (LV) lead positioning for patients with a QRS width <150 ms or non-LBBB as a substudy of the Speckle Tracking Assisted Resynchronization Therapy for Electrode Region (STARTER) prospective, randomized controlled trial. The STARTER trial randomized 187 patients with heart failure, a QRS of ≥120 ms, and ejection fraction of ≤35% to LV lead guided to the site of latest mechanical activation by speckle tracking radial strain versus routine implantation. The predefined primary end point was heart failure hospitalization or death within 2 years. This substudy included 151 CRT patients with matching echocardiographic and LV lead position data and complete follow-up data. Patients with a QRS width of 120 to 149 ms or non-LBBB and LV lead concordant or adjacent to the site of latest mechanical activation had favorable outcomes after CRT similar to those with LBBB or a QRS width of ≥150 ms. In contrast, patients with a QRS of 120 to 149 ms or non-LBBB and remote LV leads had unfavorable outcomes (hazard ratio 5.45, 95% confidence interval 2.36 to 12.6, p <0.001, and hazard ratio 4.92, 95% confidence interval 2.12 to 11.39, p <0.001, respectively, with significant interaction after adjusting for baseline variables, p = 0.038 and p = 0.008). In conclusion, LV lead positioning with respect to the echocardiographic site of latest activation was significantly associated with more favorable clinical outcomes in patients with a QRS duration <150 ms and/or non-LBBB. Additional prospective study is warranted.

The recent results of the REVIVED-BCIS2 randomized clinical trial added further controversy on the utility of myocardial revascularization in patients with chronic coronary syndrome with reduced ejection fraction. However, coronary artery disease still represents the leading cause of heart failure with reduced ejection fraction, with the potential for functional recovery following complete revascularization due to the restoration of the so-called hibernating myocardium. We report an emblematic case of a patient with recovery of contractile function and normalization of the left bundle branch block after percutaneous coronary intervention of the right coronary artery chronic total occlusion.

Introduction Cardiac resynchronization therapy (CRT) may be pro‐arrhythmic in patients with non‐left bundle branch block (non‐LBBB). We hypothesized that combined assessment of risk factors (RF) for ventricular tachyarrhythmias (VTAs) can be used to stratify non‐LBBB patients for CRT implantation. Methods The study comprised 412 non‐LBBB patients from MADIT‐CRT randomized to CRT‐D (n = 215) versus ICD only (n = 197). Best‐subset regression analysis was performed to identify RF associated with increased VTA risk in CRT‐D patients without LBBB. The primary end point was first occurrence of sustained VTA during follow‐up. Secondary end points included VTA/death and appropriate shock. Results Four RFs were associated with increased VTA risk: blood urea nitrogen >25mg/dl, ejection fraction <20%, prior nonsustained VT, and female gender. Among CRT‐D patients, 114 (53%) had no RF, while 101 (47%) had ≥1 RF. The 4‐year cumulative probability of VTA was higher among those with ≥1 RF compared with those without RF (40% vs. 14%, p < .001). Multivariate analysis showed that in patients without RF, treatment with CRT‐D was associated with a 61% reduction in VTA compared with ICD‐only therapy (p = .002), whereas among patients with ≥1 RF, treatment with CRT‐D was associated with a corresponding 73% (p = .025) risk increase. Consistent results were observed when the secondary end points of VTA/death and appropriate ICD shocks were assessed. Conclusion Combined assessment of factors associated with increased risk for VTA can be used for improved selection of non‐LBBB patients for CRT‐D.