Cardiac Resynchronization Therapy In Patients Research Articles

Improved all-cause mortality with left bundle branch area pacing compared to biventricular pacing in cardiac resynchronization therapy: a meta-analysis.

Left bundle branch area pacing (LBBAP) has emerged as a physiological alternative pacing strategy to biventricular pacing (BIVP) in cardiac resynchronization therapy (CRT). We aimed to assess the impact of LBBAP vs. BIVP on all-cause mortality and heart failure (HF)-related hospitalization in patients undergoing CRT. Studies comparing LBBAP and BIVP for CRT in patients with HF with reduced left ventricular ejection fraction (LVEF) were included. The coprimary outcomes were all-cause mortality and HF-related hospitalization. Secondary outcomes included procedural and fluoroscopy time, change in QRS duration, and change in LVEF. Thirteen studies (12 observational and 1 RCT, n = 3239; LBBAP = 1338 and BIVP = 1901) with a mean follow-up duration of 25.8months were included. Compared to BIVP, LBBAP was associated with a significant absolute risk reduction of 3.2% in all-cause mortality (9.3% vs 12.5%, RR 0.7, 95% CI 0.57-0.86, p < 0.001) and an 8.2% reduction in HF-related hospitalization (11.3% vs 19.5%, RR 0.6, 95% CI 0.5-0.71, p < 0.00001). LBBAP also resulted in reductions in procedural time (mean weighted difference- 23.2min, 95% CI - 42.9 to - 3.6, p = 0.02) and fluoroscopy time (- 8.6min, 95% CI - 12.5 to - 4.7, p < 0.001) as well as a significant reduction in QRS duration (mean weighted difference:- 25.3ms, 95% CI - 30.9 to - 19.8, p < 0.00001) and a greater improvement in LVEF of 5.1% (95% CI 4.4-5.8, p < 0.001) compared to BIVP in the studies that reported these outcomes. In this meta-analysis, LBBAP was associated with a significant reduction in all-cause mortality as well as HF-related hospitalization when compared to BIVP. Additional data from large RCTs is warranted to corroborate these promising findings.

Association between QRS shortening and mortality after cardiac resynchronization therapy: Results from the DANISH study

BackgroundChanges in QRS duration (∆QRS) are often used in the clinical setting to evaluate the effect of cardiac resynchronization therapy (CRT), although an association between ∆QRS and outcomes is not firmly established. We aimed to assess the association between mortality and ∆QRS after CRT in patients from the DANISH (Danish Study to Assess the Efficacy of ICDs in Patients with Non-Ischemic Systolic Heart Failure on Mortality) study. MethodsWe included all patients from DANISH who received a CRT device and had available QRS duration data before and after implantation. Cox proportional hazards models were used to assess associations between ∆QRS (post-CRT QRS minus pre-CRT QRS) and mortality. ResultsComplete data were available in 572 patients. Median baseline QRS duration was 160 ms (IQR [146;180]). Post-CRT QRS was recorded a median of 48 days (IQR [33;86]) after implantation, and the median ∆QRS was −14 ms (IQR [−38;-3]). During a median follow-up of 4.1 years (IQR [2.5;5.8]), 106 patients died. In crude Cox regression, all-cause mortality was reduced by 6% per 10 ms shortening of QRS (HR 0.94; CI: 0.88–1.00, p = 0.04). The effect did not remain significant after multivariable adjustment (HR 1.01, CI: 0.93–1.10, p = 0.77). Further, no association was found between ∆QRS and improvement of New York Heart Association functional class at 6 months (OR 1.03, CI: 0.96–1.10, p = 0.42). ConclusionIn a large cohort of patients with non-ischemic cardiomyopathy, reduction of QRS duration after CRT was not associated with changes in mortality during long-term follow-up.

Understanding the Application of Mechanical Dyssynchrony in Patients with Heart Failure Considered for CRT.

Over the past two decades of CRT use, the failure rate has remained around 30-35%, despite several updates in the guidelines based on the understanding from multiple trials. This review article summarizes the role of mechanical dyssynchrony in the selection of heart failure patients for cardiac resynchronization therapy. Understanding the application of mechanical dyssynchrony has also evolved during these past two decades. There is no role of lone mechanical dyssynchrony in the patient selection for CRT. However, mechanical dyssynchrony can complement the electrocardiogram and clinical criteria and improve patient selection by reducing the failure rate. An oversimplified approach to mechanical dyssynchrony assessment, such as just estimating time-to-peak delays between segments, should not be used. Instead, methods that can identify the underlying pathophysiology of HF and are representative of a substrate to CRT should be applied.

Long-Term Outcomes of Cardiac Resynchronization Therapy in Patients With Repaired Tetralogy of Fallot: A Multicenter Study.

A growing number of patients with tetralogy of Fallot develop left ventricular systolic dysfunction and heart failure, in addition to right ventricular dysfunction. Although cardiac resynchronization therapy (CRT) is an established treatment option, the effect of CRT in this population is still not well defined. This study aimed to investigate the early and late efficacy, survival, and safety of CRT in patients with tetralogy of Fallot. Data were analyzed from an observational, retrospective, multicenter cohort, initiated jointly by the Pediatric and Congenital Electrophysiology Society and the International Society of Adult Congenital Heart Disease. Twelve centers contributed baseline and longitudinal data, including vital status, left ventricular ejection fraction (LVEF), QRS duration, and NYHA functional class. Outcomes were analyzed at early (3 months), intermediate (1 year), and late follow-up (≥2 years) after CRT implantation. A total of 44 patients (40.3±19.2 years) with tetralogy of Fallot and CRT were enrolled. Twenty-nine (65.9%) patients had right ventricular pacing before CRT upgrade. The left ventricular ejection fraction improved from 32% [24%-44%] at baseline to 42% [32%-50%] at early follow-up (P<0.001) and remained improved from baseline thereafter (P≤0.002). The QRS duration decreased from 180 [160-205] ms at baseline to 152 [133-182] ms at early follow-up (P<0.001) and remained decreased at intermediate and late follow-up (P≤0.001). Patients with upgraded CRT had consistent improvement in left ventricular ejection fraction and QRS duration at each time point (P≤0.004). Patients had a significantly improved New York Heart Association functional class after CRT implantation at each time point compared with baseline (P≤0.002). The transplant-free survival rates at 3, 5, and 8 years after CRT implantation were 85%, 79%, and 73%. In patients with tetralogy of Fallot treated with CRT consistent improvement in QRS duration, left ventricular ejection fraction, New York Heart Association functional class, and reasonable long-term survival were observed. The findings from this multicenter study support the consideration of CRT in this unique population.

Relationship between sex, body size, and cardiac resynchronization therapy benefit: A patient-level meta-analysis of randomized controlled trials

BackgroundWomen might benefit more than men from cardiac resynchronization therapy (CRT) and do so at shorter QRS durations. ObjectiveThis meta-analysis was performed to determine whether sex-based differences in CRT effects are better accounted for by height, body surface area (BSA), or left ventricular end-diastolic dimension (LVEDD). MethodsWe analyzed patient-level data from CRT trials (MIRACLE, MIRACLE ICD, MIRACLE ICD II, REVERSE, RAFT, COMPANION, and MADIT-CRT) using bayesian hierarchical Weibull regression models. Relationships between QRS duration and CRT effects were examined overall and in sex-stratified cohorts; additional analyses indexed QRS duration by height, BSA, or LVEDD. End points were heart failure hospitalization (HFH) or death and all-cause mortality. ResultsCompared with men (n = 5628), women (n = 1439) were shorter (1.62 [interquartile range, 1.57–1.65] m vs 1.75 [1.70–1.80] m; P < .001), with smaller BSAs (1.76 [1.62–1.90] m2 vs 2.02 [1.89–2.16] m2; P < .001). In adjusted sex-stratified analyses, the reduction in HFH or death was greater for women (hazard ratio, 0.54; credible interval, 0.42–0.70) than for men (hazard ratio, 0.77; credible interval, 0.66–0.89; Pinteraction = .009); results were similar for all-cause mortality even after adjustment for height, BSA, and LVEDD. Sex-specific differences were observed only in nonischemic cardiomyopathy. The effect of CRT on HFH or death was observed at a shorter QRS duration for women (126 ms) than for men (145 ms). Indexing QRS duration by height, BSA, or LVEDD attenuated sex-specific QRS duration thresholds for the effects of CRT on HFH or death but not on mortality. ConclusionAlthough body size partially explains sex-specific QRS duration thresholds for CRT benefit, it is not associated with the magnitude of CRT benefit. Indexing QRS duration for body size might improve selection of patients for CRT, particularly with a “borderline” QRS duration. ClinicalTrials.gov registrationNCT00271154, NCT00251251, NCT00267098, NCT00180271

Multicenter Study of Survival Benefit of Cardiac Resynchronization Therapy in Pediatric and Congenital Heart Disease

BackgroundEvidence for the efficacy of cardiac resynchronization therapy (CRT) in pediatric and congenital heart disease (CHD) has been limited to surrogate outcomes. ObjectivesThis study aimed to assess the impact of CRT upon the risk of transplantation or death in a retrospective, high-risk, controlled cohort at 5 quaternary referral centers. MethodsBoth CRT patients and control patients were <21 years of age or had CHD; had systemic ventricular ejection fraction <45%; symptomatic heart failure; and significant electrical dyssynchrony (QRS duration z score >3 or single-site ventricular pacing >40%) at enrollment. Patients with CRT were matched with control patients via 1:1 propensity score matching. CRT patients were enrolled at CRT implantation; control patients were enrolled at the outpatient clinical encounter where inclusion criteria were first met. The primary endpoint was transplantation or death. ResultsIn total, 324 control patients and 167 CRT recipients were identified. Mean follow-up was 4.2 ± 3.7 years. Upon propensity score matching, 139 closely matched pairs were identified (20 baseline indices). Of the 139 matched pairs, 52 (37.0%) control patients and 31 (22.0%) CRT recipients reached the primary endpoint. On both unadjusted and multivariable Cox regression analysis, the risk reduction associated with CRT for the primary endpoint was significant (HR: 0.40; 95% CI: 0.25-0.64; P < 0.001; and HR: 0.44; 95% CI: 0.28-0.71; P = 0.001, respectively). On longitudinal assessment, the CRT group had significantly improved systemic ventricular ejection fraction (P < 0.001) and shorter QRS duration (P = 0.015), sustained to 5 years. ConclusionsIn pediatric and CHD patients with symptomatic systolic heart failure and electrical dyssynchrony, CRT was associated with improved heart transplantation-free survival.

Virtual pacing of a patient's digital twin to predict left ventricular reverse remodelling after cardiac resynchronization therapy.

Identifying heart failure (HF) patients who will benefit from cardiac resynchronization therapy (CRT) remains challenging. We evaluated whether virtual pacing in a digital twin (DT) of the patient's heart could be used to predict the degree of left ventricular (LV) reverse remodelling post-CRT. Forty-five HF patients with wide QRS complex (≥130 ms) and reduced LV ejection fraction (≤35%) receiving CRT were retrospectively enrolled. Echocardiography was performed before (baseline) and 6 months after CRT implantation to obtain LV volumes and 18-segment longitudinal strain. A previously developed algorithm was used to generate 45 DTs by personalizing the CircAdapt model to each patient's baseline measurements. From each DT, baseline septal-to-lateral myocardial work difference (MWLW-S,DT) and maximum rate of LV systolic pressure rise (dP/dtmax,DT) were derived. Biventricular pacing was then simulated using patient-specific atrioventricular delay and lead location. Virtual pacing-induced changes ΔMWLW-S,DT and ΔdP/dtmax,DT were correlated with real-world LV end-systolic volume change at 6-month follow-up (ΔLVESV). The DT's baseline MWLW-S,DT and virtual pacing-induced ΔMWLW-S,DT were both significantly associated with the real patient's reverse remodelling ΔLVESV (r = -0.60, P < 0.001 and r = 0.62, P < 0.001, respectively), while correlation between ΔdP/dtmax,DT and ΔLVESV was considerably weaker (r = -0.34, P = 0.02). Our results suggest that the reduction of septal-to-lateral work imbalance by virtual pacing in the DT can predict real-world post-CRT LV reverse remodelling. This DT approach could prove to be an additional tool in selecting HF patients for CRT and has the potential to provide valuable insights in optimization of CRT delivery.

The prevalence of frailty and its effect on the outcome in cardiac resynchronization therapy patients.

Frailty is a complex clinical syndrome associated with aging and comorbidities, which correlates with unfavorable outcomes. However, in heart failure patients, frailty is very common, data is scarce about those, who are eligible for Cardiac Resynchronization Therapy (CRT) implantation. We investigated the incidence of frailty and the association of Frailty Index (FI) with the outcome. Thirty baseline clinical parameters were used by the Rockwood cumulative deficit method to determine patients' FI in our single-center cohort. Based on previous studies, patients with FI ≤ 0.210 were considered as non-frail, those with FI 0.10-0.210 were classified in Frail-1, with FI > 0.10 in Frail-2 groups, respectively. Echocardiographic response after 12months and all-cause mortality were investigated by frailty groups. Among 1004 included patients, 75 (7%) were considered Non-frail, 271 (27%) grouped in Frail-1, and 658 (66%) in Frail-2 with a median FI of 0.36 (0.28-0.43). Patients in Frail-2 group were older, with more comorbidities compared with non-frail patients or those in Group Frail-1. During the median follow-up time of 4.8years, 29 (39%) patients died in the Non-frail, 140 (52%) in Frail-1, and 471 (72%) in the Frail-2 groups (log-rank p < 0.001). Group Frail-2 showed an unfavorable outcome compared to the non-frail (HR 2.49, 95%CI 1.92-3.22; p < 0.001) and the Frail-1 group (1.83, 95%CI 1.55-2.16; p < 0.001). In our HFrEF patients eligible for CRT implantation, patients were exceedingly vulnerable with a high prevalence of frailty. The calculated frailty index was associated with outcome and proved to be prevalent in individual risk stratification.

A new method using deep transfer learning on ECG to predict the response to cardiac resynchronization therapy

Background: Cardiac resynchronization therapy (CRT) has emerged as an effective treatment for heart failure patients with electrical dyssynchrony. However, accurately predicting which patients will respond to CRT remains a challenge. This study explores the application of deep transfer learning techniques to train a predictive model for CRT response. Methods: In this study, the short-time Fourier transform (STFT) technique was employed to transform ECG signals into two-dimensional images. A transfer learning approach was then applied to the MIT-BIT ECG database to pre-train a convolutional neural network (CNN) model. The model was fine-tuned to extract relevant features from the ECG images and then tested on our dataset of CRT patients to predict their response. Results: Seventy-one CRT patients were enrolled in this study. The transfer learning model achieved an accuracy of 72% in distinguishing responders from non-responders in the local dataset. Furthermore, the model showed good sensitivity (0.78) and specificity (0.79) in identifying CRT responders. The performance of our model outperformed clinic guidelines and traditional machine learning approaches. Conclusion: The utilization of ECG images as input and leveraging the power of transfer learning allows for improved accuracy in identifying CRT responders. This approach offers potential for enhancing patient selection and improving the outcomes of CRT.

Indications for Cardiac Resynchronization Therapy in Patients with Congenital Heart Disease.

Heart failure in patients with congenital heart disease (CHD) stems from unique causes compared with the elderly. Patients with CHD face structural abnormalities and malformations present from birth, leading to altered cardiac function and potential complications. In contrast, elderly individuals primarily experience heart failure due to age-related changes and underlying cardiovascular conditions. Cardiac resynchronization therapy (CRT) can benefit patients with CHD, although it presents numerous challenges. The complexities of CHD anatomy and limited access to appropriate venous sites for lead placement make CRT implantation demanding.

Techniques for Cardiac Resynchronization Therapy in Patients with Congenital Heart Disease.

Cardiac resynchronization therapy (CRT) for congenital heart disease has shown promising suucess as an adjunct to medical therapy for heart failure. While cardiac conduction defects and need for ventricular pacing are common in congential heart disease, CRT indications, techniques and long term outcomes have not been well establaished. This is a review of the techniques nad short term outcomes of CRT for the following complex congenital heart disease conditions: single ventricle physiology, systemic right ventricle, and the subpulmonic right ventricle.

Value of q waves in lateral and left precordial leads in patients with left bundle branch block to predict the response to cardiac resynchronizationtherapy.

The cardiac resynchronization therapy (CRT) non-response rate can reach 30% in heart failure (HF) patients with left bundle branch block (LBBB). This study aimed to evaluate the value of baseline q waves in leads I, V5, or V6 in predicting response to CRT in patients with HF and LBBB. Patients with HF (left ventricular ejection fraction ≤35%) and LBBB receiving CRT implantation were retrospectively enrolled. Baseline characteristics and electrocardiogram parameters, including lateral and left precordial q waves were evaluated. Non-response to CRT was defined as the improvement of left ventricular ejection fraction (LVEF)<5% at a 6-month follow-up. A total of 132 patients (mean age 63.0±10.4 years, 94 [71.2%] male) were included. Among them, 32 patients with q waves in leads I, V5, or V6 were classified into the qLBBB (+) group, and the rest without q waves in these leads were defined as the qLBBB (-) group. The CRT non-response rate in the qLBBB (+) group was markedly higher than that in the qLBBB (-) group (68.8%vs. 33.3%, p<.001). Multivariable logistic regression analysis revealed that the presence of baseline q waves in leads I, V5, or V6 remained significantly associated with a higher rate of CRT non-response in patients with HF and LBBB (odds ratio: 4.8, 95% confidence interval: 1.5-15.0, p=.007). Any q wave in leads I, V5, or V6 was an independent predictive factor for CRT non-response in patients with HF and LBBB.

Prognostic implications of invasive hemodynamics during cardiac resynchronization therapy: Stroke work outperforms dP/dtmax

Invasive measurements of left ventricular (LV) hemodynamic performance can evaluate acute response to cardiac resynchronization therapy (CRT). The study sought to determine which metric, maximum rate of LV pressure rise (LV dP/dtmax) or LV stroke work (LVSW), is more strongly associated with long-term prognosis. CRT patients were prospectively included from 3 academic centers. Invasive pressure-volume loop measurements during implantation were performed, and LV dP/dtmax and LVSW were determined at baseline and during biventricular pacing (BVP) as well as their relative increase (%Δ). Hazard ratios (HRs) for the primary outcome of 8-year all-cause mortality were derived using Cox proportional hazards. The secondary endpoint was echocardiographic response, defined as 6-month LV end-systolic volume reduction ≥15%. Paired data from 82 patients were analyzed (67% male; age 66 ± 9 years; QRS duration 158 ± 22 ms, median survival time 72 months). Survival was better when LVSW during BVP was ≥4400 mL∙mm Hg (HR 0.21, 95% CI 0.08-0.58, P < .003) or when ΔLVSW% was ≥10% (HR 0.22, 95% CI 0.08-0.65, P=.006). In multivariate analysis, following direct comparison of continuous measures of acute ΔLV dP/dtmax% and ΔLVSW%, only ΔLVSW% remained associated with the primary endpoint (HR 0.982 per percentage point, P = .028). In contrast to LV dP/dtmax (all P > .05), significant associations with echocardiographic response were found for stroke work during BVP (area under the receiver-operating characteristic curve 0.745, P = .001) and ΔLVSW% (area under the receiver-operating characteristic curve 0.803, P < .001). Stroke work, but not LV dP/dtmax, is consistently associated with long-term prognosis and response after CRT. Our results therefore favor the use of stroke work as the hemodynamic parameter to predict long-term outcome after CRT.

Clinical outcomes of left bundle branch area pacing compared with biventricular pacing in patients with heart failure requiring cardiac resynchronization therapy: systematic review and meta-analysis

Abstract Background Biventricular pacing (BVP) is recommended from the most recent ESC guidelines as the first line pacing strategy in patients with heart failure (HF) that require cardiac resynchronization therapy (CRT). (1) Many studies have shown its beneficial effects regarding morbidity and mortality in this population. (2, 3) However, 10% of patients cannot be treated by BVP due to unsuitable coronary sinus vein, while 30-40% are non-responders to BVP and experience no benefit from this treatment.(4) Left bundle branch area pacing (LBBAP) is a new pacing modality (5) that can achieve narrow QRS and improve left ventricular function in patients with HF, by engaging the intrinsic conduction pathway of the heart. Also, it appears to have better results in electrical and mechanical synchrony compared with BVP. Purpose We conducted a systematic review and meta-analysis to compare the two pacing modalities in terms of hard clinical outcomes, in patients with heart failure that require CRT. Methods Medline, Embase, Cochrane Central Register of Controlled Trials and Web of Science databases were systematically searched for studies comparing LBBAP with BVP for CRT in patients with HF. Outcomes of interest were all-cause mortality, Heart Failure Hospitalizations (HFH) and New York Heart Association (NYHA) class improvement. Two independent investigators identified studies, extracted data, and assessed the risk of bias using the Cochrane Risk of Bias 2 tool for randomized clinical trials and the Newcastle-Ottawa-Scale for observational studies. Pairwise meta-analysis was conducted using random and fixed effects models. Risk Ratios (RRs) and weighted mean difference (WMD) with 95% confidence intervals (CIs) were used to report dichotomous and continuous variables respectively. Heterogeneity was assessed with the I² statistic. Results In total, 764 studies were retrieved and finally 9 trials with 992 individuals (365 in LBBAP and 627 in BVP group) were included in the analysis. The mean follow-up duration was 13 ± 5.82 months and the average procedural success rate in the LBBAP group was 89.8%. The baseline characteristics were similar between the two groups. Pooled analysis showed that the two methods had no difference in terms of all-cause mortality (RR:0.87 CI 95%:0.38 to 2.02; I²=0%; p=0.750, Figure 1) with 8 (2.4%) vs 17 (2.9%) events occurring in LBBAP and BVP group respectively. However, LBBAP was found to have significantly lower risk for HFH (RR:0.58 CI 95%:0.38 to 0.91; I²=0%; p=0.020, Figure 2A) and to achieve more improvement in NYHA class compared with BVP (WMD: -0.40, CI 95%: -0.68 to -0.12; I²=72%; p=0.005; Figure 2B). Conclusions To the best of our knowledge this is the first meta-analysis that assesses exclusively the clinical outcomes of LBBAP compared to BVP in such an important number of patients. LBBAP presents better outcomes in HFH and NYHA class improvement, but it has no difference in all-cause mortality in comparison with BVP.Figure 1.All-cause mortalityFigure 2.A.HFH B.NYHA class improvement

Does scar burden predict sudden cardiac death in patients with cardiac resynchronization therapy? - A Systematic Review and Meta-Analysis

Abstract Background Based on latest guidelines, scar burden assessment may have a crucial role in appropriate device choice in cardiac resynchronization therapy (CRT), but no randomized controlled trials have been made yet.1 Scar burden is associated with a higher prevalence of ventricular arrhythmias (VA) and sudden cardiac death (SCD).2 Late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) can accurately evaluate the extent of myocardial scar.3. Purpose Our aim is to investigate the association between scar burden and SCD risk in cardiac resynchronization therapy patients. Methods We performed a systematic literature search on MEDLINE using the PubMed, Embase, Scopus, and CENTRAL databases. Heart failure patients with reduced ejection fraction and CRT therapy were collected. The primary endpoint was sudden cardiac death events. Meta-analyses were performed using the META and DMETAR packages in R, using a random-effects model. The risk of bias was assessed using Quips tool and the quality of evidence was evaluated using the GRADE assessment. Results 18 eligible articles have been included in our study, with a total of 2917 patients, of whom 830, 1324, and 391 have been implanted with an ICD, CRT-D, CRT-P respectively. Altogether 59,05 % of the total population were LGE-CMR positive. The average proportion of appropriate ICD shock was 15,65 % per the total population during the median follow-up time of 39,45 months. Based on the univariant analysis of 14 articles, the cumulative hazard ratio of developing sudden cardiac death events, in the scar burden positive population compared to scar burden negative was 1,95 with CI: 1,29- 2,96 p&amp;lt;0,001. The multivariant analysis shows the HR of 1,88 with CI: 1,20- 2,93 p&amp;lt;0,001. There were 4 articles using the competing risk model which is considered to be the highest evidence level. Based on that analysis we found only a trend with a HR of 1,55 CI: 0,75-2,92. Calculating from the event numbers based on 8 eligible articles, the high scar burden group had 5.55 higher odds of getting SCD events. (OR: 5.55. CI 2,52-12,22 p&amp;lt;0,001). Conclusion In our meta-analysis, LGE-CMR was associated with a trend toward appropriate device therapy and can identify a subgroup of patients with an increased risk of life-threatening VA. Based on our results performing an MRI before device implantation might be important to select high-risk patients for SCD.Forest plot O.R.Forest plot uni. H.R.

Functional mitral regurgitation and ventricular arrhythmias in patients with cardiac resynchronization therapy

Abstract Introduction In patients with heart failure (HF), the occurrence of ventricular arrhythmias (VAs) is associated with prognosis, and advanced HF can cause VAs. In HF patients developed moderate to severe functional mitral regurgitation (FMR), a transcatheter mitral valve repair therapy has significantly reduced the hospitalization and mortality rates compared to guideline-directed medical therapy. Although the mechanisms of arrhythmias are multiple, it is unclear whether FMR is involved in the development of VAs advanced HF patients. Methods and results We retrospectively examined 176 cardiac resynchronization therapy (CRT) patients (78% men, median age 67 years) without FMR before CRT implanted between 2010 and 2018. Worsening FMR was defined as developing moderate to severe FMR after CRT. During median follow-up of 40 (quartile range, 23-60) months, worsening FMR was detected in 26 (15%) patients at a median of 30 (quartile range, 12–75) months after CRT implantation. There was no difference in age, New York Heart Association functional class, QRS width before CRT and the rate of responders between patients with and without worsening FMR. Patients with worsening FMR had a tendency of larger left ventricular end-systolic dimension (58 [53-68] vs. 53 [47-60] mm, p&amp;lt;0.10), a significantly higher rate of female (38% vs. 19%, p&amp;lt;0.05) and a significantly larger left atrial volume index (LAVI) (63 [43-81] vs. 48 [35-62] ml/m2, p&amp;lt;0.05). By multivariate logistic regression analysis, female gender (odds ratio 4.3) and baseline LAVI (odds ratio 1.04 per a ml/m2 increase) were independent factors associated with worsening FMR. There was a significantly higher incidence of HF hospitalization (50% vs 15%, log-rank P&amp;lt;0.05) (Figure 1) and a higher incidence of VAs, defined as sustained ventricular tachyarrhythmias requiring implantable-cardioverter defibrillator therapy or external defibrillation, in patients with worsening FMR than patients without worsening FMR (65% vs 38%, log-rank P&amp;lt;0.05) (Figure 2). Multivariate analysis showed that worsening FMR was independently associated with the development of VAs (hazard ratio 2.77, 95% confidence interval 1.13-6.83). Conclusions In patients with HF and CRT, female gender and baseline LAVI were associated with worsening FMR after CRT. We need to pay attention to changes in the FMR that can be associated with developing VAs after CRT implantation.

Associations of 2013 and 2021 ESC definitions of left bundle-branch block with mechanical dyssynchrony and CRT-induced reverse remodeling

Abstract Background In 2021, a new and stricter ECG-based definition of LBBB was proposed and implemented in the European Society of Cardiology (ESC) guidelines on cardiac pacing and cardiac resynchronization therapy (CRT). Aim To investigate the association between the 2021 and the 2013 LBBB definitions with CRT-induced left ventricular (LV) reverse remodeling, as well as mechanical dyssynchrony. Methods CRT patients (n=191) were retrospectively investigated. Pre-CRT digitally stored ECGs were analyzed and categorized according to the LBBB definition of 2013 (LBBB-2013) and the 2021 (LBBB-2021). Mechanical dyssynchrony (Dyss) was assessed pre-CRT using 2D-echocardiography and was defined as the presence of apical rocking and/or septal flash. CRT-induced LV reverse remodeling was measured as the relative change of left ventricular end systolic volume (LVESV) at 12 ± 6 months after CRT compared to baseline. Results Patients’ characteristics were as follows; age 70 ± 10 years, 69% males and NYHA class 2.7 ± 0.5. QRS width was 156 ± 18 ms and LVEF 33 ± 11%, and 52% had ischemic etiology. Dyss was present in 59% of the population. The percentage of the cohort that was considered to have LBBB was considerably lower according to the LBBB-2021 than according to the LBBB-2013 (18 vs. 57% respectively). Similarly, percentages of patients with LBBB+Dyss were 16 and 46% according to LBBB-2021 and LBBB-2013 respectively, with a respective Kappa coefficient of 0.16 and 0.47 (Figure A). At CRT follow up, LBBB-2013 patients showed significantly more LV reverse remodeling compared to non-LBBB patients (P &amp;lt; 0.001), while there was no significant difference between patients with LBBB-2021 and non-LBBB (P = 0.09, Figure B). Conclusion The LBBB definition proposed in the 2021 ESC guidelines excludes many patients from a class I indication for CRT. It is less associated with mechanical dyssynchrony and with CRT-induced LV reverse remodeling than the 2013 LBBB definition. Therefore, the new LBBB definition appears to be counterproductive with regards to selection of CRT patients.

Abstract 15668: The Incidence and Predictors of Delayed and Late Response to Cardiac Re-Synchronization Therapy

Background: The incidence and predictors of delayed response to cardiac resynchronization therapy (CRT) have not been well established. Our study aimed to investigate the incidence and predictors of delayed and late response in CRT patients. Research Question: What patient-specific characteristics are associated with delayed or late response to CRT? Goal/Aim: To investigate the incidence and predictors of delayed and late response in CRT patients. Methods: We conducted a retrospective analysis of 201 patients who underwent CRT implantation with placement of a CS lead. Patients meeting the enrollment criteria were categorized into three groups: Group A comprised conventional responders with a response observed at the 6-month follow-up, Group B consisted of delayed responders with a response seen between 6 months and 1-year follow-up, and Group C included late responders with a response observed after 1 year of follow-up. CRT response was defined as an absolute increase of ≥ 5% in left ventricular ejection fraction. All echocardiograms were performed at the same institution. Only patients who were defined as responders to CRT were included in the analysis. Results: Among the patients analyzed, 59 patients (67.2 ± 12.3 years, 39 male) achieved a conventional response to CRT, while 40 patients (69.6 ± 9.5 years, 30 male) experienced a delayed response, and 29 patients exhibited a late response (66.1 ± 11.4 years, 18 male). The mean follow-up time was 267 days (± 341 days). The incidence of delayed and late responses was 19.9% and 14.43%, respectively. In univariable logistic regression analysis, a history of coronary artery disease (p = 0.047) was associated with delayed and late CRT responses. Conclusions: Our findings demonstrate a significant proportion of patients experiencing delayed and late responses to CRT. This study suggests the need for reconsidering the waiting time for CRT response, particularly in patients with a history of coronary artery disease. Keywords: cardiac resynchronization therapy, delayed response, heart failure

Abstract 14660: The Effect of Sacubitril/Valsartan Therapy on Hospitalization and Mortality in Patients Non-Respondent to Cardiac Resynchronization Therapy

Background: Non-responders to Cardiac Resynchronization Therapy (CRT-NR) have poor prognosis. Sacubitril/valsartan (SV) treatment improved the outcomes of heart failure patients with reduced left ventricular (LV) ejection fraction (HFrEF) in randomized trials; however, limited data are available on the specific cohort of CRT-NRs. Aim of the study: We have compared heart failure hospitalization (HFH) and mortality rates in three patient cohorts: CRT-NR patients on S/V versus on ACEi/ARB and general HFrEF patients on S/V. Methods: 275 HF patients, including 70 CRT-NRs receiving S/V at least for 6 months (Group I); 70 CRT-NRs on ACEi/ARB treatment (Group II); and 135 HFrEF patients without CRT indication on S/V therapy at least for 6 months (Group III) were included. CRT-NR was defined as a less than 10% improvement in left ventricular ejection fraction (LVEF) 6 months after device implantation. Rates of HFH and the composite of all-cause mortality/heart transplantation/LVAD therapy were compared with a mean follow-up of 21.5 months. A subgroup analysis was also performed in patients on S/V (Groups I and III) who demonstrated a more versus less than 10% increase in LVEF after 6 months of S/V treatment (S/V super-responders versus S/V moderate responders, respectively). Results: HFH rates were similar in Groups I and III (28.5% vs. 28.1%, respectively; p&gt;0.05), while significantly higher (54.2%) in Group II (p=0.02). No significant difference in the composite mortality endpoint was demonstrated between the three groups (22.8% vs. 24.2% vs. 22.2%, p=0.08). On S/V treatment, 13 out of the 70 (18.5%) CRT-NR patients (Group I) and 24 out of the 135 (17.8%) HFrEF patients (Group III) were found to be SV super-responders. Comparing these 37 patients with the 168 S/V moderate responders, neither the HFH (24.3% vs 30.9%, p=0.07), nor the composite mortality rates (24.3% vs 23.2%, p=0.53) demonstrated significant differences. Conclusion: S/V treatment in CRT-NRs improved hospitalization rates similarly to what was observed in a general HFrEF population. No benefit in mortality rates was demonstrated in this cohort. The extent of change in LVEF on S/V was not predictive of a better response on HFH or mortality.

Abstract 18037: Left Bundle Branch Area versus Biventricular Pacing in Cardiac Resynchronization Therapy: A Systematic Review and Meta-Analysis

Introduction: Cardiac resynchronization therapy (CRT) through biventricular pacing (BVP) is the standard treatment for heart failure with reduced ejection fraction (HFrEF) and left bundle-branch block (LBBB). Left bundle-branch area pacing (LBBAP) has emerged as a potentially more effective approach. However, its superiority over BVP remains unclear. Hypothesis: Is LBBAP more effective and safer than BVP for CRT in patients with HFrEF? Methods: We systematically searched PubMed, Embase, and Cochrane for randomized controlled trials (RCTs) or observational studies that reported adjusted effect estimates (i.e propensity score-matched populations or multivariate analysis), comparing the efficacy and safety of LBBAP versus BVP. We applied the random-effects model to calculate adjusted hazard ratio (aHR) and mean difference (aMD), with the corresponding 95% confidence interval. Heterogeneity was assessed using I 2 statistics. Statistical analysis was performed using R version 4.2.1. Results: Our analysis included 7 studies, yielding 2,743 patients, of whom 1,164 (42.4%) were assigned to LBBAP group. Compared with BVP, LBBAP was associated with a significant reduction of the composite of overall mortality and heart failure hospitalizations (aHR 0.67; 95% CI 0.56-0.80; I 2 =0%; p&lt;0.001; Figure 1A). Additionally, LBBAP demonstrated a significant increase in LVEF (aMD 5.77%; 95% CI 2.94-8.60; I 2 =68%; p&lt;0.001; Figure 1B) and shortening of QRS duration (aMD -25.71 ms; 95% CI -35.87 to -15.55; I 2 =0%; p&lt;0.001; Figure 2A) compared with BVP. Sub-analysis of patients with LBBB also demonstrated a significant reduction of the composite of overall mortality and heart failure hospitalizations (aHR 0.64; 95% CI 0.49 to 0.85; I 2 =0%; p&lt;0.001; Figure 2B) in LBBAP. Conclusions: This meta-analysis of RCTs and multivariable adjusted studies suggests that LBBAP is superior to BVP in patients with HFrEF undergoing CRT for both electrophysiological and clinical outcomes.