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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).

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.

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.

We have previously shown a reduction in HF events with cardiac resynchronization therapy with defibrillator (CRT-D) in patients with mild heart failure (HF) and diabetes mellitus (DM). It remains unknown whether HF remission in DM patients with CRT-D translates into reduced mortality. The effects of CRT-D versus an implantable cardioverter-defibrillator (ICD) alone to reduce long-term mortality were assessed in patients with left bundle branch block with DM (n = 386) and without DM (n = 982), enrolled in the Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT). We further subdivided DM patients by insulin and noninsulin therapy. Kaplan-Meier survival analyses and multivariate cox proportional hazards regression models were utilized. At the 7-year follow-up, CRT-D was associated with a lower mortality in DM patients compared with ICD alone (21% vs 42%, p = 0.02), similar to non-DM patients (16 vs 24%, p = 0.014). CRT-D was associated with a 41% reduction in the risk of long-term all-cause mortality in DM patients (hazard ratio [HR] 0.59, 95% confidence interval 0.36 to 0.96, p = 0.033) and a similar reduction in non-DM patients (HR 0.69, 95% confidence interval 0.48 to 0.99, p = 0.045, treatment-diabetes interaction p = 0.611). Among DM patients, mortality benefit was evident in insulin-treated patients only (HR 0.40, p = 0.030). Reductions in HF events were present in all groups. In the MADIT-CRT, patients with mild HF with DM derive significant long-term survival benefit from CRT-D, similar to those without DM. The mortality benefit from CRT-D within the DM subgroup seems to be confined to patients with insulin treated diabetes.

Purpose To assess the acute effect of triggered left ventricular pacing (tLVp) on left ventricular performance and contraction pattern in patients with heart failure, left bundle branch block (LBBB), and cardiac resynchronization therapy (CRT). Methods Twenty-three patients with pre-implant QRS complex >150 ms, QRS complex narrowing under CRT, and sinus rhythm were included ≥3 months after CRT implantation. Echocardiographic assessment of left ventricular ejection fraction (LVEF), global peak systolic longitudinal strain (GLS), and contraction pattern by 2D strain was performed during intrinsic conduction, tLVp, and BiV pacing and compared as paired data. Echocardiographic analysis was done blinded with respect to pacing mode. Results LVEF was significantly higher during BiV pacing (47 ± 11 %) compared with intrinsic conduction (43 ± 13 %, P  = 0.001) and tLVp (44 ± 13 %, P  = 0.001), while there was no difference between intrinsic conduction and tLVp ( P  = 0.28). GLS was higher during BiV (14 ± 3) than during intrinsic conduction (13 ± 3, P  = 0.01) and tLVp (13 ± 3, P  = 0.03). Difference in time-to-peak contraction between the basal septal and lateral walls was shorter during BiV pacing (−3 ± 44 ms) than during intrinsic conduction (129 ± 66, P  < 0.001) and tLVp (118 ± 118 ms, P  < 0.001), with no difference between tLVp and intrinsic conduction ( P  = 0.56). The electrocardiogram showed change in frontal axis from intrinsic conduction in only 2 (9 %) patients during tLVp and in 20 (87 %) patients during BiV pacing. Conclusions The acute effect of tLVp on LV systolic function and contraction pattern is significantly lower than the effect of BiV pacing and not different from intrinsic conduction in patients with LBBB and CRT.

Purpose Prolonged QRS duration is the main selection criterion for cardiac resynchronization therapy (CRT) which ameliorates left ventricular mechanical dyssynchrony (MD). However, consequences of post-CRT QRS prolongation and residual MD have been poorly evaluated. We aimed to define the predictors of persistent MD and hypothesized that CRT-induced QRS change (ΔQRS) might have an impact on residual MD after CRT. Methods A total of 80 patients receiving CRT were included in the study. ΔQRS was calculated as the difference between the baseline and paced QRS intervals. Residual MD was assessed early after device implantation with a longitudinal dyssynchrony index (Yu index). Significant MD was defined as a Yu index ≥ 33 msec. Two groups were created based on residual MD and compared according to clinical, electrocardiographic and echocardiographic features. Results Patients with persistent MD had longer paced QRS durations (182.5 ± 16.2 vs. 165.4 ± 22.5 msec, p  = 0.03) and were less likely to have left ventricular (LV) leads located in the posterolateral vein (53 % vs. 85 %, p  = 0.002). The linear correlation between the ΔQRS and the Yu index values was modest (Spearman’s rho = −0.341, p  = 0.002); additionally, a prolonged QRS was strongly associated with MD after CRT ( p  = 0.00008). Both LV lead localization and CRT-induced QRS prolongation emerged as the significant predictors of persistent MD. A biventricularly paced QRS more than 10 msec longer than the pre-paced QRS width was predictive of persistent MD after CRT (sensitivity = 80 %, specificity = 62 %). Conclusions ΔQRS was found to be associated with residual MD after CRT. Ten milliseconds of QRS prolongation predicted persistent MD after CRT.

Left bundle branch block (LBBB) is an important electrocardiographic (ECG) finding strongly associated with left ventricular systolic dysfunction (LVSD), a condition linked to poor clinical outcomes. Although early LVSD detection is crucial, standard diagnosis via echocardiography may not always be immediately accessible. In this study, we propose a fine-tuned ECG foundation model (FM) to enhance LVSD detection specifically in patients with LBBB. We conducted a retrospective multicenter analysis of 2,031 paired ECG-echocardiographic datasets from 892 LBBB patients. The ECG-FM was fine-tuned for optimal LVSD prediction and compared against baseline models, which were conventional deep learning methods, including Fully Convolutional Network (FCN), LSTM-FCN, ResNet, and InceptionTime. The proposed ECG-FM with single-step full fine-tuning outperformed baseline models, achieving accuracy, sensitivity, and AUROC of 0.758, 0.771, and 0.807, respectively. Additionally, sequential partial fine-tuning exhibited the highest sensitivity (0.787), enhancing screening capability. DeepLIFT analysis identified QRS complex and T wave features in leads V1–V4 as critical predictive factors. Our results demonstrated that the recommended fine-tuned ECG-FM significantly improves LBBB patient LVSD detection, potentially enabling earlier clinical diagnosis in such cases when echocardiography is not readily available, thereby potentially improving patient outcomes and clinical management.

Chronic kidney disease (CKD) is associated with cardiac conduction defects and is a strong risk factor for heart failure. Complete left bundle branch block (cLBBB), a cardiac conduction abnormality, may have an unfavorable effect on ventricular mechanical synchrony and lead to the progression of heart failure. Once heart failure develops, it seems to act together with underlying CKD in a vicious circle. Therefore, this study aimed to explore the influence of CKD in patients with cLBBB by assessing the estimated glomerular filtration rate (eGFR). We examined a hospital-based sample of 416 adult patients with cLBBB from 2010 to 2013. The eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Cox proportional hazard models were used to estimate the hazard ratio for all-cause mortality and cardiovascular mortality. A total of 416 adult patients with a mean age of 71 ± 13 years were enrolled. The median follow-up period was 3.6 years. After adjusting for clinical, electrocardiographic parameters, and medication use, cox regression analysis showed that total mortality was significantly associated with older age (Hazard Ratio (HR) = 1.03, 95% CI = 1.01–1.05, p  = 0.002), presence of congestive heart failure (HR = 2.39, 95% CI = 1.63–3.49, p  < 0.001), advanced CKD (HR = 2.48, 95% CI = 1.71–3.59, p  < 0.001), higher HR (HR = 1.02, 95% CI = 1.01–1.03, p  < 0.001) and without use of ACEI/ARB (HR = 0.59, 95% CI = 0.41–0.85, p  = 0.005) were independent predictors of the total mortality. Multivariate Cox hazard regression analysis demonstrated that, in comparison to patients lacking cLBBB, the coexistence of CKD (eGFR < 60 mL/min/1.73 m 2 ) among those with LBBB significantly heightened the risks of both total mortality (HR ratio of 5.01 vs. 2.40) and CV death (HR ratio of 61.78 vs. 14.41) even following adjustment for clinical covariates and ECG parameters. In summary, within patients exhibiting cLBBB, the presence of CKD serves as a significant risk factor for all-cause mortality.