Cardiac Resynchronization Therapy In Patients Research Articles

Association between frailty and adverse outcomes after cardiac resynchronization therapy: a systematic review and meta-analysis.

To synthesize evidence, using data from published studies, on the association of frailty with the outcomes after cardiac resynchronization therapy (CRT). The systematic search of PubMed, Web of Science, Scopus, and Embase databases was done to identify observational studies (cohort/case-control/cross-sectional) that used an objective method for frailty assessment and had presented adjusted effect sizes. STATA version 15.0 was used to conduct analysis, which was based on random effects model. Fifteen studies were included. Frailty was found to be associated with an increased risk of in-hospital mortality (odds ratio (OR) 6.96, 95% confidence interval (CI) 5.48, 8.85). The effect of frailty on the response to CRT was not statistically significant (OR 0.55, 95% CI 0.19, 1.59). The pooled effect size indicated that frailty was associated with somewhat bigger but not statistically significant increase in the risk of complications (OR 1.70, 95% CI 0.93, 3.12). The risks of mortality and decompensated heart failure on long-term follow up were higher in frail patients (Hazard ratio (HR) 1.75, 95% CI 1.40, 2.17 and HR 3.03, 95% CI 1.33, 6.90, respectively) compared to patients without frailty. The risk of readmission was higher in frail patients, however, it did not achieve statistical significance (HR 2.63, 95% CI 0.89, 7.75). Frail CRT patients could be at higher risks of mortality, decompensated heart failure, and may have potentially higher rates of complications. Integrating frailty assessment into pre-CRT evaluation and customizing interventions for frail patients might be an essential steps towards enhancing outcomes in this population.

CineECG Repolarization Gradients Predict Acute Hemodynamic Response in CRT Patients.

A variable proportion of non-responders to cardiac resynchronization therapy (CRT) warrants the search for new approaches to optimize the position of the left ventricular (LV) lead and the CRT device programming. CineECG is a novel ECG modality proposed for the spatial visualization and quantification of myocardial depolarization and repolarization sequences. The present study aimed to evaluate CineECG-derived parameters in different pacing modes and to test their associations with acute hemodynamic responses in CRT patients. CineECG was used to construct the average electrical path within the cardiac anatomy from the 12-lead ECG. CineECG and LV dP/dt max were tested in 15 patients with nonischemic dilated cardiomyopathy and left bundle branch block (QRS: 170 ± 17 ms; LVEF: 26 ± 5.5%) under pacing protocols with different LV lead localizations. The CineECG-derived path directions were computed for the QRS and ST-T intervals for the anteroposterior (Xh), interventricular (Yh), and apicobasal (Zh) axes. In a multivariate linear regression analysis with adjustment for the pacing protocol type, the ST-T path direction Yh was independently associated with the increase in dP/dt max during CRT, [regression coefficient 639.4 (95% confidence interval: 187.9-1090.9), p = 0.006]. In ROC curve analysis, the ST-T path direction Yh was associated with the achievement of a 10% increase in dP/dt max (AUC: 0.779, p = 0.002) with the optimal cut-off > 0.084 (left-to-right direction) with sensitivity 0.67 and specificity 0.92. The acute hemodynamic response in CRT patients was associated with specific CineECG repolarization sequence parameters, warranting their further testing as potential predictors of clinical outcomes.

Echocardiographic Evaluation in Cardiac Resynchronization Therapy: A Single Center Experience.

Introduction Heart failure develops as a result of dysfunction in the cardiac muscle, which impairs the heart's ability to pump blood effectively. For this reason, many studies have shown that cardiac resynchronization therapy (CRT) has significantly reduced symptoms and improved cardiac function in patients with heart failure. Echocardiography is crucial in assessing CRT response, as it helps differentiate between patients who benefit from CRT and those who do not by evaluating key parameters like left ventricular ejection fraction (LVEF), a critical parameter in determining CRT eligibility. However, few studies focus specifically on the effectiveness of echocardiography for assessing CRT response, with existing research limited by a lack of standardized protocols and inadequate predictive tools. Accordingly, this study aims to assess the role of echocardiography in evaluating the efficacy of CRT in patients with heart failure at King Faisal Cardiac Center. Methodology This was a retrospective analytical cohort study that included all adult patients diagnosed with heart failure and underwent CRT between January 2017 and December 2021 at King Faisal Cardiac Center, King Abdulaziz Medical City, Jeddah, Saudi Arabia. Data were obtained from the Cardiac Non-invasive Lab, which was selected for its essential diagnostic tools for comprehensive echocardiographic evaluation of CRT efficacy. Study subjects were over 18 years old, diagnosed with heart failure with reduced ejection fraction (LVEF <35%), underwent CRT, and had echocardiograms at baseline and at least six months post-therapy. The collected data were retrieved from electronic medical records (BestCare; ezCaretech Co., Ltd,Seoul, South Korea), including relevant demographics and echocardiographic parameters such as end-systolic volume (ESV), end-diastolic volume (EDV), and ejection fraction (EF). Statistical analysis, paired t-tests,and Shapiro-Wilk test to assess data normality were conducted to evaluate pre- and post-CRT changes, with significance set at P<0.05. Results A total of 53 heart failure patients met the inclusion and exclusion criteria. The results of the study indicate statistically significant differences in the mean EF before and after CRT increased from 29.09±6.52% to 33.3±10.69% (p-value=0.0014). The mean ESV decreased from 114.46±60.63 mL to 97.13±65.89 mL, demonstrating a clinically significant improvement (p=0.056), and the mean EDVdecreased from 157.08±64.67 mL to 138.87±78.07 mL (p = 0.0158). Furthermore, the EF increased by 14.47%, and the ESV decreased by 15.14% after CRT.These findings indicate improvement in left ventricular function following CRT. Conclusion The study demonstrates significant improvements in echocardiographic parameters based on echocardiogram findings, particularly the outcomes of EF and ESV after CRT in patients with heart failure with reduced ejection fraction.These findings highlight the potential of CRT as an effective therapy and aid in detecting responders to treatment. Nevertheless, the study is limited by a relatively small sample size, exclusion of comorbidities, and short follow-up period. Therefore, further longitudinal studies with larger cohorts and consideration of comorbidities are recommended.

National health expenditure per capita is associated with CRT implantation practice: findings from the ESC CRT Survey II with 11 088 patients.

Cardiac resynchronization therapy (CRT) reduces morbidity and mortality in selected patients with heart failure (HF) and electrical dyssynchrony. This treatment receives class IA recommendations in European Society of Cardiology (ESC) guidelines. However, despite these strong recommendations, CRT implantation practice varies greatly in Europe. The purpose of the sub-analysis of CRT Survey II data was to describe how countries' health per capita expenditure affects CRT implantation practice. Between 2015 and 2016, two ESC associations, European Heart Rhythm Association and Heart Failure Association, conducted the CRT Survey II, a survey of CRT implantations in 11 088 patients in 42 ESC member states. We analysed CRT patient selection and guideline adherence in those countries according to high or low health expenditure per capita. There were 21 high health expenditure countries (n=6844 patients) and 21 (n=3852) with low health expenditure. The countries with the lowest health expenditure were more likely to implant CRT in patients who had strong guideline recommendations for implantation, younger patients and those recently hospitalized for HF or with symptomatic HF (67% vs. 58%, P<0.001). The ratio of CRT-Pacemaker (CRT-P) to CRT-Defibrillator (CRT-D) was similar in both spending groups, as was the percentage of CRT implantation in women. CRT Survey II has demonstrated a non-uniform delivery of healthcare. Countries with low health expenditure per capita appear to be reserving CRT therapy for younger patients, those with class IA indication and patients with more severe symptoms of heart failure.

Optimizing Patient Selection for Cardiac Resynchronization Therapy With or Without Defibrillator in a Multicenter Study of Japanese Patients - Assessment of the MADIT-ICD Benefit Score.

Although the MADIT-ICD benefit score (MBS) helps select suitable implantable cardioverter defibrillator (ICD) candidates, optimal indicators for cardiac resynchronization therapy (CRT) remain uncertain. Evaluating the applicability of the MBS in Japanese CRT patients is imperative. This multicenter study assessed the cumulative incidence of ventricular tachycardia/fibrillation (VT/VF) and non-arrhythmic mortality (AM) in CRT patients grouped according to potential benefit (lowest, highest, and intermediate). Among 400 primary prevention patients (mean age 65 years, 76% male), VT/VF occurred in 4 (7%), 68 (24%), and 14 (23%) patients in the lowest-, intermediate-, and highest-benefit groups, respectively (P=0.027), over a median follow-up of 34 months. Non-arrhythmic death was observed in 15 (25%), 91 (33%), and 9 (15%) patients in the lowest-, intermediate-, and highest-benefit groups, respectively (P=0.025). Multivariate analysis identified VT/VF score ≥7 (hazard ratio [HR] 2.14; 95% confidence interval [CI] 1.09-4.19; P=0.027) as a significant VT/VF predictor. The presence of left bundle branch block (HR 0.51; 95% CI 0.29-0.92; P=0.025) was associated with a reduced risk of VT/VF events. Non-AM score ≥3 (HR 1.70; 95% CI 1.01-2.88; P=0.047), systolic blood pressure <100 mmHg (HR 1.84; 95% CI 1.25-2.70; P=0.002), and estimated glomerular filtration rate <30 mL/min/1.73 m2(HR 1.98; 95% CI 1.23-3.20; P=0.005) were significant predictors of non-arrhythmic death. The MBS can identify suitable candidates for CRT-D among Japanese individuals.

The mechanistic interaction between mechanical dyssynchrony and filling pressure in cardiac resynchronization therapy candidates.

Both left ventricular (LV) mechanical dyssynchrony and filling pressure have been shown to be associated with outcome in heart failure patient treated with cardiac resynchronization therapy (CRT). To investigate the mechanistic link between mechanical dyssynchrony and filling pressure and to assess their combined prognostic value in CRT candidates. Left atrial pressure (LAP) estimation and quantification of mechanical dyssynchrony were retrospectively performed in 219 CRT patients using echocardiography. LAP was elevated (eLAP) in 49% of the population, normal (nLAP) in 40%, and indeterminate (iLAP) in 11%. CRT response was defined as %-decrease in LV end-systolic volume after 12±6 months CRT. Clinical endpoint was all-cause mortality during 4.8 years (interquartile range: 2.7-6.0 years). To investigate the mechanistic link between mechanical dyssynchrony and filling pressure, the CircAdapt computer model was used to simulate cardiac mechanics and hemodynamics in virtual hearts with LBBB and various causes of increased filling pressure. Patients with nLAP had more significant mechanical dyssynchrony than those with eLAP. The combined assessment of both parameters before CRT was significantly associated with reverse LV remodeling and post-CRT survival. Simulations revealed that mechanical dyssynchrony is attenuated by increased LV operational chamber stiffness, regardless of whether it is caused by passive or active factors, explaining the link between mechanical dyssynchrony and filling pressure. Our combined clinical-computational data demonstrate that in patients with LBBB, the presence of mechanical dyssynchrony indicates relatively normal LV compliance and low filling pressure, which may explain their strong association with positive outcomes after CRT.

CRT should be recommended for all heart failure patients with mechanical dyssynchrony and a ventricular conduction delay regardless of the QRS morphology

Abstract Introduction Two recent meta-analyses displayed the heterogeneous effect of cardiac resynchronization therapy (CRT) in patients with a non-left bundle branch block (non-LBBB) and found an increased burden of ventricular arrhythmias after CRT (1,2). Careful patient selection is therefore paramount. Evidence suggests the assessment of mechanical dyssynchrony may guide decision-making to CRT in this challenging population. Purpose To assess the effect of CRT in patients with and without mechanical dyssynchrony compared to medication only, and in particular in patients with a non-LBBB morphology. Methods We retrospectively screened for symptomatic heart failure patients who presented between 2012 and 2018 at our clinic with a QRS duration ≥130ms and a left ventricular ejection fraction (LVEF) ≤35%. We identified 361 patients who received CRT and 1107 patients who could have been considered for CRT. Patients were excluded if echocardiographic data was unavailable, they received CRT after 2018, were 80 years or older, or had other significant co-morbidities. We enrolled the remaining 220 CRT patients ("CRT") and 124 patients treated with medication only ("Control") for analysis. Patients were categorized for the presence of mechanical dyssynchrony on echocardiography, defined as the presence of either septal flash, apical rocking, or both. Multivariable-adjusted Cox regression analyses, including stratification by the presence of dyssynchrony, was performed to compare the effect of CRT to medication only. Hazard ratios (aHR) were obtained after adjustment for age, sex, atrial rhythm, QRS duration, QRS morphology, ischemic disease, kidney function, medication and presence of a defibrillator. Sensitivity analysis was performed in patients with a non-LBBB morphology. Results The CRT and Control group were comparable except for the QRS duration (163±22ms vs 152±16ms, p&amp;lt;0.001), the proportion of patients on optimal medical therapy (64% vs 47%, p=0.001), patients with a defibrillator (81% vs 19%, p&amp;lt;0.001), and patients with a LBBB morphology (75% vs 47%, p&amp;lt;0.001). During an average follow-up of 6.0(±3.2) years, 162 patients (47%) died. In the overall cohort, CRT did not significantly improve survival (aHR: 0.66, p=0.065). There was, however, a marked survival benefit for CRT over medication only in patients with mechanical dyssynchrony (aHR: 0.37, p=0.001). In patients without dyssynchrony there was a trend towards harm due to CRT (aHR: 2.05, p=0.062). These results were consistent in the sub-cohort of patients with a non-LBBB morphology. Conclusion CRT significantly improves the life expectancy of patients with mechanical dyssynchrony, including patients with a non-LBBB morphology. These results add to the evidence that all heart failure patients with LVEF≤35%, QRS≥130ms and mechanical dyssynchrony should be recommended (Class I) for CRT regardless of QRS morphology, while awaiting the results of ongoing randomized controlled trials.

Myocardial single photon emission computed tomography imaging to identify non-responders to cardiac resynchronization therapy in patients with non-left bundle branch block

Abstract Background Non-response to cardiac resynchronization therapy (CRT) is an important issue in the treatment of heart failure with reduced ejection fraction (HFrEF) and non-left bundle branch block (LBBB). Although the QRS duration and morphology are crucial parameters for selecting CRT candidates, electrocardiogram (ECG) markers may inadequately represent the mechanical activation patterns within the heart. Owing to limitations associated with the ECG criteria, there is increasing interest in advanced multimodality imaging to improve patient selection. Recently, myocardial single-photon emission computed tomography imaging (G-MPI) is used for assessing left ventricular (LV) dyssynchrony. This technique is mostly automatic and has high intra- and inter-observer reproducibility and repeatability. Objectives This study aimed to examine whether preoperative G-MPI evaluation could predict non-responsiveness to CRT in patients with HFrEF with non-LBBB. Methods Between January 2021 and December 2022, 128 patients underwent CRT, of whom 73 with pre-operative evaluation using G-MPI were selected. Forty-three patients with non-LBBB (21 and 22 CRT responders and non-responders, respectively) were assessed. These patients were divided into CRT responder and non-responder groups. We evaluated the cut-off and clinical impact of pre-operative G-MPI parameters in predicting non-responsiveness to CRT. In addition, 30 patients with LBBB were analyzed. Results Among patients with non-LBBB, CRT responders and non-responders showed no significant differences in baseline characteristics, except for the LV dimension. A receiver operating characteristic curve analysis identified 108° and 27.7° as the optimal cut-offs for the bandwidth and phase standard deviation (SD), respectively, to predict non-responsiveness to CRT (area under the curve [AUC]=0.762; 95% confidence interval [CI]: 0.601–0.923 and AUC=0.742; 95% CI: 0.576–0.909, respectively). A multivariate analysis revealed that a cut-off bandwidth of ≥108° and phase SD of ≥27.7° are independent predictors of non-responsiveness to CRT in patients with non-LBBB (hazard ratios 5.65; 95% CI: 1.53–20.9; P=0.009). In contrast, there were no relationships between G-MPI parameters and non-responsiveness to CRT in patients with LBBB. Conclusions Pre-operative G-MPI findings were associated with non-responsiveness to CRT in patients with non-LBBB. The identification of potentially nonresponsive patients could influence patient management and alter outcomes.

Impact of QRS complex fragmentation on all-cause mortality before and after cardiac resynchronization therapy

Abstract Introduction Cardiac resynchronization therapy (CRT) have demonstrated to reduce all-cause mortality in selected patients with HFrEF. However, there is still a high rate of non-responders, so risk stratification is crucial. Fragmentation of the QRS complex (QRSf) has been suggested as a valuable prognostic factor in different cardiac diseases, but the evidence in patients undergoing CRT is controversial and limited. Purpose To evaluate if changes in QRSf status before and after CRT implantation has a prognostic role in patients undergoing CRT in terms all-cause mortality. Methods Consecutive patients undergoing CRT were prospectively included from October 2009 to December 2022. Demographic clinical, electrocardiographic and echocardiographic variables were recorded. Prospective follow-up variables were collected from electronic clinical records and telephone interview. QRSf complex was defined by the presence of different RSR′ patterns including additional R-waves (R′) and notches of the R-wave and S-wave in two contiguous leads corresponding to a main coronary artery territory in a 12-lead electrocardiogram performed before and after CRT. Results A total of 244 patients (mean age 71.8 ± 9.8 years, 79.5% male) were included. The etiology of LV systolic disfunction was ischemic in 50.0%. Mean LVEF before implantation was 25 ± 9%. A CRT-D was implanted in 176 patients (72.2%). The mean width of the paced QRS was 141 ± 23 ms. At baseline, 150 patients had a QRSf. After CRT implantation, 69 (28.4%) patients experimented a change in QRSf status: 29 patients (11.9%) without prior QRSf developed QRSf, whereas 40 patients (16.5%) resolved QRSf after CRT. Median follow-up time was 36.0 months (interquartile range 18.2-75.7). During the follow-up period, 90 patients died. In the multivariate Cox regression survival analysis, the presence of QRSf before the implantation with or without paced QRSf after CRT were independently associated with all-cause mortality (HR 4.43; 95% CI 1.53-12.80 and HR 3.69; 95% CI 1.16-11.80 respectively). Those without QRSf prior implantation who developed QRSf after CRT did not present significantly higher risk of all-cause mortality. Univariate and multivariate Cox regression analyses for all-cause mortality are presented in Table 1. Figure 1 presents Kaplan-Meier curves for all-cause mortality according to QRSf status before and after CRT implantation. Conclusions According to our results, preimplantation QRSf is an independent predictor of all-cause mortality regardless the resolution or maintenance of QRSf after CRT in patients with HFrEF undergoing CRT. Therefore, patients with QRSf before CRT implantation regardless the paced QRSf status, should be followed more strictly because they are at higher mortality risk.Table 1.Cox Regression Analyses

Beating the clock: the impact of heart failure duration on CRT efficacy

Abstract Background Cardiac Resynchronization Therapy (CRT) stands as an established intervention for selected patients with heart failure (HF) presenting with a wide QRS complex. The optimal timing for CRT implantation remains uncertain. Current evidence suggests superior outcomes post-CRT in patients who have not been previously hospitalised for HF and those receiving the implant during their initial hospitalisation for HF.1 Purpose The primary objective of this study is to investigate the long-term clinical outcomes following CRT implantation relative to the duration of HF previous to the implant. It was analysed in a cohort of consecutive patients from a HF Unit who met the criteria for CRT as recommended by the ESC guidelines (QRS duration ≥150ms, left bundle branch block morphology, and left ventricular ejection fraction (LVEF) ≤35% despite optimal medical therapy). Methods We evaluated all patients who received CRT from January 2011 through September 2022. Follow-up ended in September 2023. Patients with CRT indicated for ventricular pacing due to high-degree atrioventricular block were excluded. Patients were categorized into two groups based on the duration of HF progression prior to CRT implantation: more than 3 years and 3 years or less. The primary outcome was all-cause mortality (ACM). Secondary outcomes included a composite of ACM and HF hospitalisation and the proportion of patients who demonstrated a significant improvement in LVEF (defined as an increase of ≥10% from baseline and a subsequent measurement of LVEF ≥40%). Results The cohort consisted of 127 patients, mean age 65.8±10.7 years, 23.6% were women, mean LVEF was 28.4±8.6% and 36.2% had ischaemic aetiology (Table 1). 62 patients either died or were hospitalized for HF. Mean follow-up was 4.9±2.7 years. After adjusting for age, sex and baseline LVEF, patients with HF for more than three years before CRT implantation had a worse prognosis: HRs of 2.31 for ACM (p=0.016) and 2.13 for the combined endpoint of ACM+HFH (p=0.010) (Figure 1). The proportion of patients with improved LVEF after CRT was significantly higher in the group with shorter HF duration (68.25%) compared to the group with longer HF duration (25%), p &amp;lt;0.001. Conclusions Our findings reveal that patients with a shorter history of HF (less than three years) prior to CRT implantation exhibit significantly better clinical outcomes. These results highlight the role of early intervention with CRT in patients with HF, suggesting that shorter HF duration prior to CRT may lead to more favourable long-term outcomes.

Interplay between strain pattern-based classification of dyssynchrony and myocardial scar in CRT patients

Abstract Introduction Echocardiography-derived septal strain patterns are valuable for predicting volumetric reverse remodelling and survival in patients undergoing cardiac resynchronization therapy (CRT). Nevertheless, presence of myocardial scarring in the left ventricle (LV) is known to attenuate CRT treatment response. Purpose This study aims to investigate the interplay between septal strain patterns and myocardial scarring in CRT candidates, and how they link to outcome after CRT. Methods In this prospective multicentre study, CRT candidates from five European institutions underwent pre-implantation assessments using speckle-tracking strain analysis on echocardiography and cardiac magnetic resonance imaging (CMR) with late gadolinium enhancement (LGE). Dyssynchrony was graded through analysis of septal strain curves, categorizing patients into five distinct patterns, denoted as strain Stage-0 through strain Stage-4 (Fig. A). LGE of the LV wall was quantitatively assessed using CMR (as a percentage). The study endpoints were volumetric reverse remodelling (volume responder = more than 15% decrease LV end-systolic volume) after one year, and all-time all-cause mortality. Results A total of 267 patients, with a mean age of 66±11 years (69% males, 90% left bundle branch block [LBBB]) presented with an average LV ejection fraction (EF) of 30±7%. With each stepwise increase in strain stage, global LV scarring decreased (p&amp;lt;0.01; Fig. B) and the proportion of volume responders increased (all p&amp;lt;0.0001; Fig. C). ROC curves demonstrated that the predictive power of strain stages for CRT volumetric response was not significantly improved when scarring percentage was added (AUC 0.78 [95% CI: 0.69-0.83] vs. 0.81 [95% CI: 0.71-0.90]; p&amp;gt;0.05; Fig. D). In a multivariate cox regression model – including clinical characteristics that were significantly related to survival in univariate analysis – a patients’ strain stage was the only significant predictor of survival, also outperforming scar burden as determinant of outcome (HR 0.68; p=0.041; Fig. E). Conclusions Septal strain patterns show a strong association with the extent of reverse remodelling and outcome in CRT-treated patients. An inverse relationship is observed between pre-implant strain stages and the extent of myocardial scarring. However, scar burden did not provide incremental predictive value over the strain stages. Strain-pattern-based dyssynchrony assessment is a meaningful predictive marker which integrates information on myocardial dysfunction due to dyssynchrony as well as scar burden.

Smaller intrinsic QRS area and smaller reduction of QRS area during cardiac resynchronisation therapy are associated with higher risk of ventricular arrhythmias and appropriate ICD therapy

Abstract Background Cardiac resynchronisation therapy (CRT) patients are at high risk for ventricular arrhythmias (VAs), and little is known about which characteristics are associated with an increased risk for arrhythmic events. Purpose To investigate the association between QRS area parameters and the risk for VAs in patients with heart failure undergoing primary preventive CRT with defibrillator (CRT-D) implantation. Methods All patients receiving CRT-D between 2015 and 2020 at a large-volume tertiary care center were retrospectively evaluated. Digital 12-lead electrocardiograms (ECGs) were collected before and after CRT implantation. Patients were included if they had native LBBB and were implanted with a primary preventive CRT-D. Kors’ regression transformation was used to derive vectorcardiographic QRS area from the 12-lead ECGs. QRS area parameters were analysed in relation to a primary endpoint of first appropriate ICD therapy, i.e., ATP or shock therapy. Results 177 patients with LBBB (68.9 years [60.7–73.8]; 21.5% female; 52.9% New York Heart Association (NYHA) class III-IV; LVEF 25.9±6.3%) were followed over a median follow-up time of 2.5 years [1.6–3.0] after CRT-D implantation. 27 patients reached the primary endpoint. The median pre-CRT QRS area was 134.5 μVs [102.3–163.8]. Multivariable Cox regression identified a small pre-CRT QRS area (HR, per 10 μVs decrease, 1.30; [1.12–1.51]; p=&amp;lt;.001) and a small post-CRT reduction in QRS area (HR, per 10 μVs decrease, 1.30; [1.13–1.49]; p=&amp;lt;.001) as independent predictors of an increased risk of appropriate ICD therapy. In analyses with a scoring variable combining pre-CRT QRS area and QRS area reduction both above or below median, the combination of a small pre-CRT QRS area and a small QRS area reduction was strongly associated with an increased risk of reaching the endpoint (HR, per point increase, 2.47; [1.2–4.9]; p=0.01). Conclusion A small intrinsic QRS area, by itself or in combination with a small reduction of post-CRT QRS area, was strongly associated with a higher risk of ventricular arrhythmias in this cohort of CRT-D treated patients. In conjunction with other parameters, further risk stratification for arrhythmic events could be achieved by assessing QRS area data pre- and post-CRT.Figure 1.K-M pre-CRT QRS area quartilesFigure 2.K-M QRS area score

Optimizing patient selection for cardiac resynchronization therapy in a multicenter study of Japanese patients: assessment of the MADIT-ICD benefit group

Abstract Background The MADIT-ICD benefit group, derived from ventricular tachycardia (VT)/ventricular fibrillation (VF) scores and non-arrhythmic mortality scores (Table 1), facilitates the appropriate selection of candidates for implantable cardioverter-defibrillator (ICD) therapy. While the 2021 European Society of Cardiology Guidelines have discussed the advantages and considerations of adding a defibrillator in patients undergoing cardiac resynchronization therapy (CRT), the optimal selection of CRT with or without a defibrillator remains unclear, particularly in Asian populations. This is especially relevant for primary prevention using ICD, which is characterized by fewer cases of ischemic etiology compared to Western countries. Purpose This study aimed to evaluate the utility of the MADIT-ICD benefit group in Japanese CRT patients and identify key indicators for determining the necessity of CRT with or without a defibrillator. Methods We conducted a retrospective, multicenter evaluation of 505 consecutive Japanese CRT patients enrolled between 2012 and 2020. Among these patients, 76% were male, with a mean age of 65 years and a mean body mass index of 22.5 kg/m2. Ischemic etiology was present in 25% of patients, with 20% undergoing secondary prevention. The study assessed the cumulative incidences of VT/VF and non-arrhythmic mortality based on the MADIT-ICD benefit group (lowest, intermediate, and highest). Predictors for each outcome were explored, and the MADIT-ICD benefit group was validated in the Japanese cohort. Results Of the 400 included patients, 60 (15%) were categorized into the lowest MADIT-ICD benefit group, 279 (70%) into the intermediate group, and 61 (15%) into the highest group. Over a median follow-up period of 34 months, VT/VF occurred in 4 (13%), 68 (24%), and 14 (23%) patients in the lowest, intermediate, and highest benefit groups, respectively (Gray’s test, P = 0.027, Figure 1A). Non-arrhythmic death occurred in 15 (25%), 91 (33%), and 9 (15%) patients in the lowest, intermediate, and highest benefit groups, respectively (Log-rank test, P = 0.025, Figure 1B). Multivariable analysis identified MADIT-ICD VT/VF score (hazard ratio [HR] 1.23; 95% confidence interval [CI] 1.12-1.35; P &amp;lt; 0.001) and left bundle branch block (LBBB) (HR 0.48; 95% CI 0.27-0.86; P = 0.014) as significant predictors for VT/VF, while MADIT-ICD non-arrhythmic mortality score (HR 1.16; 95% CI 1.07-1.27; P &amp;lt; 0.001), serum creatinine (Cr) (HR 1.28; 95% CI 1.13-1.45; P &amp;lt; 0.001), and mineral corticoid receptor antagonist (MRA) use (HR 1.84; 95% CI 1.21-2.79; P = 0.004) were significant predictors for non-arrhythmic death (Table 2). Conclusion The MADIT-ICD benefit group, in conjunction with left bundle branch block and renal function, may serve as valuable predictors for determining the necessity of cardioverter-defibrillator therapy in Japanese CRT patients.Table 1 and Figure 1

Rhythm and rate control strategies in patients with long-standing persistent atrial fibrillation treated with cardiac resynchronization: the results of the randomized Pilot-CRAfT study.

Atrial fibrillation (AF) is common in cardiac resynchronization therapy (CRT) recipients. It is a marker of impaired CRT response mainly mediated by the reduction of effectively captured biventricular paced beats (BiVp). There are no randomized trials comparing strategies to maintain high BiVp percentage. To compare the efficacy of rhythm vs rate control strategies in CRT recipients with long-standing persistent AF. We performed a randomized trial including CRT recipients with persistent AF resulting in low BiVp%. All patients received amiodarone, the rhythm control group received external electrical cardioversion (EC), and the rate control group received atrioventricular node ablation, if needed. The primary end-point was 12-month BiVp% (NCT). 43 patients were included in the analysis. The mean age was 68.4 (SD: ± 8.3) years and the mean BiVp% 82.4% ± 9.7%. AF lasted 25 ± 19 months. The mean baseline left ventricular ejection fraction (LVEF), left atrium area, and the maximal oxygen uptake (VO2max) were: 30 ± 8%, 33 ± 7 cm2, and 14 ± 5 mL/(kg*min), respectively. The EC success rate was 58%. 38% patients remained in sinus rhythm (SR) after 12 months. BiVp% increased similarly in both arms reaching 99% [95% CI 97.3-99.8] and 98% [94.0-99.0], P = 0.14 in rhythm and rate control groups, respectively. LVEF raised significantly only in the rhythm control group (ΔLVEF 4.1 (± 7.3), P = 0,018) which was driven by the patients who maintained SR. No differences in VO2max, QoL, clinical and safety end-points were observed. Despite comparable BiVp% in both groups, only restoration of SR led to improved left ventricular ejection fraction in CRT patients with long-standing AF. NCT01850277 registered on 22/04/2013.

Elevated B-Type Natriuretic Peptide Level as a Residual Risk Factor for Ventricular Arrhythmias Among Patients Undergoing Cardiac Resynchronization Therapy With Improved Left Ventricular Ejection Fraction.

Patients who achieve improved left ventricular ejection fraction (LVEF >35%) with cardiac resynchronization therapy (CRT) are at a lower risk of ventricular arrhythmia (VA). Little is known about the significance of the B-type natriuretic peptide (BNP) level for the risk of VA. This study investigated the risk factors for VA in CRT and the risk stratification of VA with BNP in CRT with improved LVEF. This study evaluated 352 CRT patients from 2012 to 2020. Patients were categorized into 2 groups: improved LVEF (impEF; LVEF >35%), and low LVEF (lowEF; LVEF ≤35%). The serum BNP levels 6 months after CRT device implantation were measured. The primary endpoint was defined as VA requiring treatment with anti-tachycardia pacing or shock or persisting for ≥30 s. Overall, 102 patients had improved LVEF. The impEF group had a significantly lower VA risk than the lowEF group. Patients with low BNP had a lower VA risk than those with high BNP; however, no significant difference was observed between patients with high BNP and those in the lowEF group. Univariate analysis revealed that high BNP was a predictor of VA in the impEF group. The VA risk is reduced with improved LVEF after CRT but not with high BNP levels. The post-BNP level after CRT implantation is a useful marker for predicting VA in patients with improved LVEF.

Conduction system pacing compared with biventricular pacing for cardiac resynchronization therapy in patients with heart failure and mildly reduced left ventricular ejection fraction: Results from International Collaborative LBBAP Study (I-CLAS) Group

BackgroundCardiac resynchronization therapy (CRT) is a guideline-recommended therapy in patients with heart failure with mildly reduced ejection fraction (HFmrEF, 36%–50%) and left bundle branch block or indication for ventricular pacing. Conduction system pacing (CSP) using left bundle branch area pacing or His bundle pacing has been shown to be a safe and physiologic alternative to biventricular pacing (BVP). ObjectiveThe aim of this study was to compare the clinical outcomes between BVP and CSP for patients with HFmrEF undergoing CRT. MethodsConsecutive patients who underwent BVP or CSP with HFmrEF between January 2018 and June 2023 at 16 international centers were included. The primary outcome was the composite end point of time to death or heart failure hospitalization (HFH). Secondary end points included change in left ventricular ejection fraction (LVEF) and individual end points of death and HFH. ResultsA total of 1004 patients met inclusion criteria: BVP, 178; CSP, 826 (His bundle pacing, 154; left bundle branch area pacing, 672). Mean age was 73 ± 13 years; female, 34%; and LVEF, 42% ± 5%. Paced QRS duration in CSP was significantly narrower compared with BVP (129 ± 21 ms vs 144 ± 19 ms; P < .001). LVEF improved during follow-up in both groups (49% ± 10% vs 48% ± 10%; P = .32). CSP was independently associated with significant reduction in the primary end point of time to death or HFH compared with BVP (22% vs 34%; hazard ratio, 0.64; 95% confidence interval, 0.43–0.94; P = .025). ConclusionCSP was associated with improved clinical outcomes compared with BVP in this large cohort of patients with HFmrEF undergoing CRT. Randomized controlled trials comparing CSP with BVP will be necessary to confirm these results.

Characterization of cardiac resynchronization therapy response through machine learning and personalized models

Introduction: The characterization and selection of heart failure (HF) patients for cardiac resynchronization therapy (CRT) remain challenging, with around 30% non-responder rate despite following current guidelines. This study aims to propose a novel hybrid approach, integrating machine-learning and personalized models, to identify explainable phenogroups of HF patients and predict their CRT response. Methods:The paper proposes the creation of a complete personalized model population based on preoperative CRT patient strain curves. Based on the parameters and features extracted from these personalized models, phenotypes of patients are identified thanks to a clustering algorithm and a random forest classification is provided. Results:A close match was observed between the 162 experimental and simulated myocardial strain curves, with a mean RMSE of 4.48% (±1.08) for the 162 patients. Five phenogroups of personalized models were identified from the clustering, with response rates ranging from 52% to 94%. The classification results show a mean area under the curves (AUC) of 0.86 ± 0.06 and provided a feature importance analysis with 22 features selected. Results show both regional myocardial contractility (from 22.5% to 33.0%), tissue viability and electrical activation delays importance on CRT response for each HF patient (from 55.8 ms to 88.4 ms). Discussion:The patient-specific model parameters’ analysis provides an explainable interpretation of HF patient phenogroups in relation to physiological mechanisms that seem predictive of the CRT response. These novel combined approaches appear as promising tools to improve understanding of LV mechanical dyssynchrony for HF patient characterization and CRT selection.

Investigating the clinical utility of global and regional myocardial work parameters in predicting response to cardiac resynchronization therapy in patients with heart failure and reduced ejection fraction.

Previous studies have indicated that despite adhering to current patient selection guidelines, there remains a 30% to 40% subset of patients who do not experience improvement in heart failure (HF) after receiving cardiac resynchronization therapy (CRT). We aim to utilize echocardiographic myocardial work parameters to serve as predictors of responsiveness to CRT in patients with heart failure and reduced ejection fraction (HFrEF). We prospectively recruited patients who underwent CRT at Sun Yat-sen Memorial Hospital from June 2019 to September 2022. Comprehensive preoperative information, clinical laboratory data, conventional echocardiographic parameters and myocardial work were collected for all participants, as well as follow-up data 6 months after CRT. Twenty-five patients (67.6%) showed response to CRT treatment, while twelve patients (32.4%) had no response. Compared with the non-response group, the response group had larger region constructive work [RCW: the sum of constructive work (CW) in the 9 segments of the basal, mid, and apical segments of the anterior, lateral, and posterior walls], region wasted work [RWW: the sum of wasted work (WW) in the 6 segments of the basal and mid segments of the anterior septum, posterior septum and anterior walls], and the combination of RCW and RWW (RCW + RWW) in baseline (RCW: 9,695.68±2,955.40 vs. 5,219.50±2,207.68 mmHg%, P<0.001; RWW: 3,612.08±1,723.80 vs. 1,674.33±995.23 mmHg%, P=0.001; RCW + RWW: 13,307.76±3,857.71 vs. 6,893.83±2,592.83 mmHg%, P<0.001). Furthermore, global constructive work (GCW), global wasted work (GWW), GCW + GWW, RCW, RWW, and RCW + RWW had areas under the receiver operating characteristic curve (AUCs) of 0.870, 0.770, 0.860, 0.890, 0.870, and 0.910, respectively, for predicting CRT responsiveness. The global and regional myocardial work parameters are associated with CRT response in CRT candidates. Particularly regional myocardial work parameters appear to be promising parameters to improve selection for CRT of patients with HFrEF.

Outcomes of Cardiac Resynchronization Therapy by New York Heart Association Class: A Patient-Level Meta-Analysis.

Data on the benefits of cardiac resynchronization therapy (CRT) in patients with severe heart failure symptoms are limited. We investigated the relative effects of CRT in patients with ambulatory New York Heart Association (NYHA) IV versus III functional class at the time of device implantation. In this meta-analysis, we pooled patient-level data from the MIRACLE (Multicenter InSync Randomized Clinical Evaluation), MIRACLE-ICD (Multicenter InSync Implantable Cardioversion Defibrillation Randomized Clinical Evaluation), and COMPANION (Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure) trials. Outcomes evaluated were time to the composite end point of the first heart failure hospitalization or all-cause mortality, and time to all-cause mortality alone. The association between CRT and outcomes was evaluated using a Bayesian hierarchical Weibull survival regression model. We assessed if this association differed between NYHA III and IV groups by adding an interaction term between CRT and NYHA class as a random effect. A sensitivity analysis was performed by including data from RAFT (Resynchronization-Defibrillation for Ambulatory Heart Failure). Our pooled analysis included 2309 patients. Overall, CRT was associated with a longer time to heart failure hospitalization or all-cause mortality (adjusted hazard ratio [aHR], 0.79 [95% credible interval [CI], 0.64-0.99]; posterior probability or P=0.044), with a similar association with time to all-cause mortality (aHR, 0.78 [95% CI, 0.59-1.03]; P=0.083). Associations of CRT with outcomes were not significantly different for those in NYHA III and IV classes (ratio of aHR, 0.72 [95% CI, 0.30-1.27]; P=0.23 for heart failure hospitalization/mortality; ratio of aHR, 0.70 [95% CI, 0.35-1.34]; P=0.27 for all-cause mortality alone). The sensitivity analysis, including RAFT data, did not show a significant relative CRT benefit between NYHA III and IV classes. Overall, there was no significant difference in the association of CRT with either outcome for patients in NYHA functional class III compared with functional class IV.

Is Conduction System Pacing Going to Be the New Gold Standard for Cardiac Resynchronization Therapy?

The current gold standard in device therapy for advanced heart failure (HF), which has been firmly established in HF management for more than 25 years, is classical biventricular pacing (BiV-CRT). In the last decade, a new pacing modality called conduction system pacing (CSP) has emerged as a variant for advanced cardiac device therapy. It provides pacing with preserved intrinsic cardiac activation by direct stimulation of the specific cardiac conduction system. The term CSP integrates the modalities of HIS bundle pacing (HBP) and left bundle branch area pacing (LBBAP), both of which have provided convincing data in smaller randomized and big non-randomized studies for the prevention of pacemaker-induced cardiomyopathy and for providing effective cardiac resynchronization therapy in patients with classical CRT-indication (primary approach or after failed CRT). Recent American guidelines proposed the term "cardiac physiological pacing" (CPP), which summarizes CSP including left ventricular septal pacing (LVSP), a technical variant of LBBAP together with classical BiV-CRT. The terms HOT-CRT (HIS-optimized CRT) and LOT-CRT (LBBP-optimized CRT) describe hybrid technologies that combine CSP with an additional coronary-sinus electrode, which is sometimes useful in patients with advanced HF and diffuse interventricular conduction delay. If CSP continues providing promising data that can be confirmed in big, randomized trials, it is likely to become the new gold standard for patients with an expected high percentage of pacing (>20%), possibly also for cardiac resynchronization therapy. CSP is a sophisticated new treatment option that has the potential to raise the term "cardiac resynchronization therapy" to a new level. The aim of this review is to provide basic technical, anatomical, and functional knowledge of these new pacemaker techniques in order to facilitate the understanding of the different modalities, as well as to provide an up-to-date overview of the existing randomized and non-randomized evidence, particularly in direct comparison to right ventricular and classical biventricular pacing.