Standard care vs. TRIVEntricular pacing in Heart Failure (STRIVE HF): a prospective multicentre randomized controlled trial of triventricular pacing vs. conventional biventricular pacing in patients with heart failure and intermediate QRS left bundle branch block.

AIMS: To determine whether triventricular (TriV) pacing is feasible and improves CRT response compared to conventional biventricular (BiV) pacing in patients with left bundle branch block (LBBB) and intermediate QRS prolongation (120-150 ms). METHODS AND RESULTS: Between October 2015 and November 2019, 99 patients were recruited from 11 UK centres. Ninety-five patients were randomized 1:1 to receive TriV or BiV pacing systems. The primary endpoint was feasibility of TriV pacing. Secondary endpoints assessed symptomatic and remodelling response to CRT. Baseline characteristics were balanced between groups. In the TriV group, 43/46 (93.5%) patients underwent successful implantation vs. 47/49 (95.9%) in the BiV group. Feasibility of maintaining CRT at 6 months was similar in the TriV vs. BiV group (90.0% vs. 97.7%, P = 0.191). All-cause mortality was similar between TriV vs. BiV groups (4.3% vs. 8.2%, P = 0.678). There were no significant differences in echocardiographic LV volumes or clinical composite scores from baseline to 6-month follow-up between groups. CONCLUSION: Implantation of two LV leads to deliver and maintain TriV pacing at 6 months is feasible without significant complications in the majority of patients. There was no evidence that TriV pacing improves CRT response or provides additional clinical benefit to patients with LBBB and intermediate QRS prolongation and cannot be recommended in this patient group. CLINICAL TRIAL REGISTRATION NUMBER: Clinicaltrials.gov: NCT02529410.

Native Electrocardiographic QRS Duration after Cardiac Resynchronization Therapy: The Impact on Clinical Outcomes and Prognosis.

BACKGROUND: We investigated whether reversed electrical remodeling (RER), defined as narrowing of the native electrocardiographic QRS duration after cardiac resynchronization therapy (CRT), might predict prognosis and improvement in echocardiographic outcomes. METHODS AND RESULTS: A total of 110 CRT recipients were retrospectively analyzed for the end points of death and hospitalization during 18 ± 3 months. Native QRS durations were recorded at baseline and 6 months after CRT (when pacing was switched off to obtain an electrocardiogram) to determine RER. CRT response and mitral regurgitation (MR) improvement were defined as ≥15% reduction in left ventricular end-systolic volume and absolute reduction in regurgitant volume (RegV) at 6 months, respectively. Overall, 48 patients (44%) had RER, which was associated with functional improvement (77% vs 34%; P < .001) and CRT response (81% vs 52%; P < .001) compared with those without RER. The change in the intrinsic QRS duration correlated with the reduction in RegV (r = 0.51; P < .001) and in tenting area (r = 0.34; P < .001). RER was a predictor of MR improvement (P = .023), survival (P = .043), and event-free survival (P = .028) according to multivariate analyses. CONCLUSIONS: Narrowing of the intrinsic QRS duration is associated with functional and echocardiographic CRT response, reduction in MR, and favorable prognosis after CRT.

Longer right to left ventricular activation delay at cardiac resynchronization therapy implantation is associated with improved clinical outcome in left bundle branch block patients.

AIMS: Data on longer right to left ventricular activation delay (RV-LV AD) predicting clinical outcome after cardiac resynchronization therapy (CRT) by left bundle branch block (LBBB) are limited. We aimed to evaluate the impact of RV-LV AD on N-terminal pro-B-type natriuretic peptide (NT-proBNP), ejection fraction (EF), and clinical outcome in patients implanted with CRT, stratified by LBBB at baseline. METHODS AND RESULTS: Heart failure (HF) patients undergoing CRT implantation with EF ≤ 35% and QRS ≥ 120 ms were evaluated based on their RV-LV AD at implantation. Baseline and 6-month clinical parameters, EF, and NT-proBNP values were assessed. The primary endpoint was HF or death, the secondary endpoint was all-cause mortality. A total of 125 patients with CRT were studied, 62% had LBBB. During the median follow-up of 2.2 years, 44 (35%) patients had HF/death, 36 (29%) patients died. Patients with RV-LV AD ≥ 86 ms (lower quartile) had significantly lower risk of HF/death [hazard ratio (HR): 0.44; 95% confidence interval (95% CI): 0.23-0.82; P = 0.001] and all-cause mortality (HR: 0.48; 95% CI: 0.23-1.00; P = 0.05), compared with those with RV-LV AD < 86 ms. Patients with RV-LV AD ≥ 86 ms and LBBB showed the greatest improvement in EF (28-36%; P<0.001), NT-proBNP (2771-1216 ng/mL; P < 0.001), and they had better HF-free survival (HR: 0.23, 95% CI: 0.11-0.49, P < 0.001) and overall survival (HR: 0.35, 95% CI: 0.16-0.75; P = 0.007). There was no difference in outcome by RV-LV AD in non-LBBB patients. CONCLUSION: Left bundle branch block patients with longer RV-LV activation delay at CRT implantation had greater improvement in NT-proBNP, EF, and significantly better clinical outcome.

The Effect of Cardiac Resynchronization Therapy on Right Ventricular Function: A Systematic Review and Meta-Analysis.

Background: Right ventricular (RV) failure is an important predicting factor regarding overall and event-free survival regardless of baseline left ventricular (LV) function in patients with severe heart failure (HF). Previous studies have indicated that cardiac resynchronization therapy (CRT) improves LV and RV reverse remodeling in patients with systolic dyssynchrony within the left ventricle. However, there is conflicting evidence regarding the role of CRT in RV function. The aim of this systematic review and meta-analysis was to examine the implications of CRT on RV function indices. Methods: A systematic literature search was conducted using the MedLine and EMBASE databases and the Cochrane Library from their inception until 18 March 2024. Eligible were studies providing information on RV function indices, both at baseline and after CRT. Evidence was summarized using random-effects meta-analytic models. Results: In total, 30 studies were deemed eligible. CRT resulted in a significant improvement in right ventricular fractional area change (mean difference (MD) 5.11%, 95% confidence interval (CI) 2.83 to 7.39), tricuspid annular plane systolic excursion (TAPSE, MD 1.63 mm, 95% CI 1.10 to 2.16), and myocardial systolic excursion velocity (MD 1.85 cm/s, 95% CI 1.24 to 2.47) as well as a significant decrease in pulmonary artery systolic pressure (MD -6.24 mmHg, 95% CI -8.32 to -4.16). A non-significant effect was observed on TAPSE to PASP ratio and right ventricular global longitudinal strain. Conclusions: Our meta-analysis demonstrates that CRT is associated with a significant improvement in echocardiographic parameters of RV function. Further investigation is necessary to elucidate how these changes, both independently and in conjunction with LV improvement, impact patients' long-term prognosis, and to identify the specific patient populations expected to derive the greatest benefit.

Impact of baseline right ventricular function on the response to cardiac resynchronization therapy - A meta-analysis.

Baseline right ventricular (RV) function potentially determines the response to Cardiac Resynchronization Therapy (CRT) but is not included in the current selection criteria. In this meta-analysis, we examined the value of echocardiographic indices of RV function as potential predictors of CRT outcomes in patients with standard indications for CRT. Baseline tricuspid annular plane systolic excursion was consistently higher in CRT responders, and this association appears independent of age, sex, ischemic etiology of heart failure, and baseline left ventricular ejection fraction. This proof-of-concept meta-analysis of observational data may justify a more detailed assessment of RV function as an additional component in the selection process of CRT candidates.

Multipoint left ventricular pacing with large anatomical separation improves reverse remodeling and response to cardiac resynchronization therapy in responders and non-responders to conventional biventricular pacing.

BACKGROUND: Multipoint pacing [Multipoint™ Pacing (MPP), Abbott] via a single left ventricular lead (Quartet™ LV lead, Abbott) improves acute left ventricular (LV) function and response to cardiac resynchronization therapy (CRT). Aim of this study was to examine additional benefits in terms of LV reverse remodeling and CRT response by activating MPP in responders and non-responders to conventional biventricular pacing (CONV). METHODS: 43 consecutive patients receiving CRT (Quadra Assura MP™, Abbott) received LV dP/dtmax optimized CONV programming for 6 months. MPP programming with large anatomical electrode separation (> 30 mm) and basal LV1 pacing location was activated afterwards. Echocardiographic and clinical parameters were obtained at baseline, 6- and 12-month follow-up (FU). The response was defined as an improvement of LVESV ≥ 15% and super-response as improvement ≥ 30% relative to baseline. RESULTS: 41 patients completed FU (one died of non-cardiac cause and one was lost to FU) and after 6 months CONV, 26 patients (63%) were classified as CRT responders. With MPP, the response rate increased to 90% (p < 0.001). Super-response also improved significantly with MPP compared to CONV (71% vs. 22%; p < 0.005). LV reverse remodeling in terms of LVESV improved significantly with MPP compared to CONV (79 ± 45 ml vs. 103 ± 64 ml; p < 0.001). NYHA-class only improved significantly with CONV relative to baseline (1,8 ± 0,7 vs. 2,7 ± 0,5; p < 0.001), but not further with MPP (1,7 ± 0,6 vs. 1,8 ± 0,7; p = 0.49). CONCLUSION: Multipoint pacing significantly improves response and super-response to CRT as well as LV reverse remodeling compared to conventional biventricular pacing.

Development of a biomarker panel to predict cardiac resynchronization therapy response: Results from the SMART-AV trial.

BACKGROUND: Predicting a favorable cardiac resynchronization therapy (CRT) response holds great clinical importance. OBJECTIVE: The purpose of this study was to examine proteins from broad biological pathways and develop a prediction tool for response to CRT. METHODS: Plasma was collected from patients before CRT (SMART-AV [SmartDelay Determined AV Optimization: A Comparison to Other AV Delay Methods Used in Cardiac Resynchronization Therapy] trial). A CRT response was prespecified as a ≥15-mL reduction in left ventricular end-systolic volume at 6 months, which resulted in a binary CRT response (responders 52%, nonresponders 48%; n = 758). RESULTS: Candidate proteins (n = 74) were evaluated from the inflammatory, signaling, and structural domains, which yielded 12 candidate biomarkers, but only a subset of these demonstrated predictive value for CRT response: soluble suppressor of tumorgenicity-2, soluble tumor necrosis factor receptor-II, matrix metalloproteinase-2, and C-reactive protein. These biomarkers were used in a composite categorical scoring algorithm (Biomarker CRT Score), which identified patients with a high/low probability of a response to CRT (P <.001) when adjusted for a number of clinical covariates. For example, a Biomarker CRT Score of 0 yielded 5 times higher odds of a response to CRT compared to a Biomarker CRT Score of 4 (P <.001). The Biomarker CRT Score demonstrated additive predictive value when considered against a composite of clinical variables. CONCLUSION: These unique findings demonstrate that developing a biomarker panel for predicting individual response to CRT is feasible and holds potential for point-of-care testing and integration into evaluation algorithms for patients presenting for CRT.

Improving cardiac resynchronization therapy response with multipoint left ventricular pacing: Twelve-month follow-up study.

BACKGROUND: Cardiac resynchronization therapy (CRT) with multipoint left ventricular (LV) pacing (MultiPoint™ Pacing [MPP], St. Jude Medical) improves acute LV function and LV reverse remodeling at 3 months. OBJECTIVE: The purpose of this study was to test the hypothesis that MPP can also improve LV function at 12 months. METHODS: Consecutive patients receiving a CRT implant (Unify Quadra MP™ or Quadra Assura MP™ CRT-D and Quartet™ LV lead, St. Jude Medical) were randomized to receive pressure-volume (PV) loop optimized biventricular pacing with either conventional cardiac resynchronization therapy (CONV) or MPP. CRT response was defined by a reduction in end-systolic volume (ESV) ≥15% relative to BASELINE as determined by a blinded observer and alive status. RESULTS: Forty-four patients (New York Heart Association class III, ejection fraction [EF] 29% ± 6%, QRS 152 ± 17 ms) were enrolled and randomized to either CONV (N = 22) or MPP (N = 22). During the observation period, 2 patients died of noncardiac causes and 2 patients were lost to follow-up. After 12 months, 12 of 21 patients (57%) in the CONV group and 16 of 21 patients (76%) in the MPP group were classified as CRT responders (P = .33). ESV reduction and EF increase relative to BASELINE were significantly greater with MPP than with CONV (ESV: median -25%, interquartile range [IQR] [-39% to -20%] vs median -18%, IQR [-25% to -2%], P = .03; EF: median +15%, IQR [8% to 20%] vs median +5%, IQR [-1% to 8%], P <.001). CONCLUSION: Sustaining the trend observed 3 months postimplant, PV loop-guided multipoint LV pacing resulted in greater LV reverse remodeling and increased LV function at 12 months compared to PV loop-guided conventional CRT.