Effects Of Cardiac Resynchronization Therapy Research Articles

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.

Association Between use of an Adaptive Cardiac Resynchronization Therapy Algorithm and Healthcare Utilization and Cost

To assess the association between use of adaptive pacing on clinical and economic outcomes of CRT recipients in a real-world analysis. The AdaptivCRTTM algorithm was shown in prior subgroup analyses of prospective trials to achieve clinical benefits, but a large prospective trial showed nonsignificant changes in the endpoint of mortality or heart failure hospitalizations. CRT-implanted patients from the Optum Clinformatics® database with ≥90 days of follow-up were included. Remote monitoring data was used to classify patients based on CRT setting - adaptive biventricular and left ventricular pacing (aCRT) vs. standard biventricular pacing (Standard CRT). Inverse probability of treatment weighting was used to adjust for baseline differences between groups. Mortality, 30-day readmissions, healthcare utilization, and payer and patient costs were evaluated post-implantation. This study included 2,412 aCRT and 1,638 Standard CRT patients (mean follow-up: 2.4 ± 1.4 years), with balanced baseline characteristics after adjustment. The aCRT group was associated with lower all-cause mortality (adjusted hazard ratio = 0.88 [95% confidence interval (CI):0.80, 0.96]), fewer all-cause 30-day readmissions (adjusted incidence rate ratio = 0.87 [CI:0.81, 0.94]), and fewer all-cause and HF-related inpatient, outpatient, and emergency department (ED) visits. The aCRT cohort was also associated with lower all-cause outpatient payer-paid amounts and lower all-cause and HF-related inpatient and ED patient-paid amounts. In this retrospective analysis of a large real-world cohort, use of an adaptive CRT algorithm was associated with lower mortality, reduced healthcare resource utilization, and lower payer and patient costs. While cardiac resynchronization therapy (CRT) improves quality of life and clinical outcomes for certain heart failure patients, some patients do not respond to this therapy. Adaptive CRT algorithms (aCRT), such as AdaptivCRTTM, have been developed with the goal of improving effectiveness of CRT, and consequently, clinical and economic outcomes. This research study used a large database of administrative claims data - which contains information on patient demographics, diagnoses, healthcare services received, mortality, and cost data - to compare clinical and economic outcomes between CRT patients with the aCRT algorithm turned on (aCRT group) and CRT patients with the aCRT algorithm turned off (standard CRT group). Statistical methods were used to adjust for baseline differences between the aCRT group and standard CRT groups. Ultimately, the aCRT group was found to have a lower risk of all-cause mortality, fewer all-cause 30-day readmissions, fewer hospital visits (including inpatient, outpatient, and emergency department visits), and lower costs to payers and patients for specific types of costs.

The effect of cardiac resynchronisation therapy upgrade from right ventricular pacing on symptoms and functional clinical outcomes, results from the BUDAPEST-CRT Upgrade trial

Abstract Background Based on the results of the BUDAPEST-CRT Upgrade trial, in patients with intermittent or permanent right ventricular (RV) pacing and reduced left ventricular ejection fraction (HFrEF) upgrade to cardiac resynchronization therapy (CRT) reduces morbidity and mortality. Purpose Whether the substantial treatment effect of the CRT upgrade could also be detected in a better functional and exercise capacity is scarcely investigated. We examined the changes of the prespecified tertiary endpoints such as symptoms, quality of life (QoL), exercise capacity and natriuretic peptide measurement from baseline to 12 months. Methods In the BUDAPEST CRT Upgrade trial 360 HFrEF patients with a priorly implanted PM or ICD and >20% of RV pacing burden were randomly assigned to CRT-D upgrade (n=215) or ICD (n=145) in a 3:2 ratio. The prespecified tertiary endpoints were changes in quality of life measured by EQ-5D-3L, New York Heart Association (NYHA) functional class, 6-minute walk test (6-MWT), and NT-proBNP. When data of trial patients were unavailable due to death at 12 months, imputed values were used as 0 (6MWT) and 0 score (EQ-5D-3L) or a 5th grade (NYHA class). Responders were defined as >15% change of left ventricular end-systolic volume at 12 months. Results From baseline to 12 months, NYHA functional class improved in the CRT-D upgrade arm compared with the ICD only group [adjusted odds ratio (OR) 0.50; 95% CI 0.32-0.80; P=0.003]. According to the adjusted model there was a statistically significant decrease in the NT-proBNP [adjusted difference -1257 pg/mL; 95% CI -2287 – (-228); P=0.017]. In responders, the changes in NT-proBNP levels were significantly greater than in non-responders [adjusted difference -1635 pg/mL; 95% CI -2811 - (-459); P=0.007]. The progression of worsening of QoL attributed to ageing was moderated only by CRT-D upgrade [EQ-5D-3L difference by age -0.01; 95% CI -0.02 - (-0.003); P=0.004; interaction P=0.003]. 6MWT did not improve significantly in either group. Conclusions Patients receiving CRT upgrade showed a substantial improvement in symptoms and a significant decrease in natriuretic peptide levels, as compared to ICD alone, which was more pronounced in responders. Moreover, CRT-D upgrade could moderate the progression of worsening of quality of life attributed to ageing in this vulnerable, older patient population.

Effect of adaptive cardiac resynchronization therapy in heart failure patients with pacemaker dependency

Effect of adaptive cardiac resynchronization therapy in heart failure patients with pacemaker dependency

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.

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.

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.

Assotiation of testosterone levels and oxidative stress activity with 10-year survival in men with cardiac resynchronization therapy

Aim. To investigate the association of testosterone levels (TES) and oxidative stress activity with 10-year survival in men with cardiac resynchronization therapy (CRT).Methods. 86 men with CRT (59.0±9.8 years; 66.3% ischemic cardiomyopathy) were divided into 4 groups: Gr.1 (n=19) TES&lt;median level (16.4nmol/l) + myeloperoxidase (MPO) &lt; median level (32.5 ng/mL); Gr.2 (n=18) TES&lt;median level + MPO&gt;median level; Gr.3 (n=23) TES&gt; medians + MPO &lt; median level; Gr.4 (n=26) TES &gt; median level + MPO &gt; median level. Echocardiography parameters, incidence of ventricular extrasystole, TES in plasma, estradiol, progesterone, dehydroepiandrosterone sulfate, norepinephrine, MPO, NT-proBNP, matrix metalloproteinase, tissue inhibitor of metalloproteinase were assessed. Prognostic level of NT-proBNP was assessed by ROC analysis; 10-year survival was measured by Kaplan-Meier method, factors associated with it were evaluated using Cox regression.Results. The majority of patients were NYHA II and NYHA III for Gr. 3 and Gr.4 respectively (р3-4=0,010). At baseline: there was no difference in echocardiography parameters, levels of NT-proBNP, MPO, steroids, matrix metalloproteinase between groups; tissue inhibitor of metalloproteinase was higher in Gr.2 and Gr.4; the highest norepinephrine levels was in Gr.4. Follow-up: reverse cardiac remodeling was associated with NT-proBNP decreasing and was registered in Gr.4 and Gr. 3. The level of MPO was decreased in Gr.3, Gr.4., and was the highest in Gr.4. The level of estradiol was increased in Gr.1; There were no difference in hormone levels in Gr.2. TES, dehydroepiandrosterone sulfate was increased, but progesterone was decreased in Gr.3 and in Gr.4. The norepinephrine`s levels were increased in all groups. The number of ventricular extrastimuli was increased in Gr.4. Predictive level of NT-proBNP was 756.0 pg/ml (AUC=0.685; p=0.003; sensitivity: 64%, specificity: 68%). The 10-year survival rate was 15.4%; 33.5%; 76.3%; 24.4% for Gr. 1-4 respectively (Log Rank test: Gr.1-2=0.378; Gr.1-3&lt;0.001; Gr.1-4=0.070; Gr.2-3=0.009; Gr.2-4=0.772; Gr.3-4=0.010). The survivance was higher in patients with the best CRT response time (p=0.004), the level of NT-proBNP&gt;756.0 pg/ml (p=0.001) in Gr.1, Gr.2; the best CRT response time (p=0.001), left ventricular ejection fraction (p=0.046), MPO&gt;median (p=0.041), amiodarone administration (0.008) in Gr. 3, Gr. 4.Conclusion. CRT modulates steroidogenesis. Increase of TES and dehydroepiandrosterone sulfate with lower oxidative stress activity is associated with greater reverse cardiac remodeling and better 10-year survival rate. The higher level of TES and simultaneously MPO more than 32.5 pg/ml were related to less reverse cardiac remodeling, higher rate of amiodarone administration by 5.2 times, increasment of ventricular arrhythmias rate and higher relative risk of death by 4.2 times. Relationship between 10-year survival rate and period of best CRT response indicates less physiological nature of forceful modulating effects of CRT.

Long-Term Outcomes of Resynchronization–Defibrillation for Heart Failure

BackgroundThe Resynchronization–Defibrillation for Ambulatory Heart Failure Trial (RAFT) showed a greater benefit with respect to mortality at 5 years among patients who received cardiac-resynchronization therapy (CRT) than among those who received implantable cardioverter–defibrillators (ICDs). However, the effect of CRT on long-term survival is not known.MethodsWe randomly assigned patients with New York Heart Association (NYHA) class II or III heart failure, a left ventricular ejection fraction of 30% or less, and an intrinsic QRS duration of 120 msec or more (or a paced QRS duration of 200 msec or more) to receive either an ICD alone or a CRT defibrillator (CRT-D). We assessed long-term outcomes among patients at the eight highest-enrolling participating sites. The primary outcome was death from any cause; the secondary outcome was a composite of death from any cause, heart transplantation, or implantation of a ventricular assist device.ResultsThe trial enrolled 1798 patients, of whom 1050 were included in the long-term survival trial; the median duration of follow-up for the 1050 patients was 7.7 years (interquartile range, 3.9 to 12.8), and the median duration of follow-up for those who survived was 13.9 years (interquartile range, 12.8 to 15.7). Death occurred in 405 of 530 patients (76.4%) assigned to the ICD group and in 370 of 520 patients (71.2%) assigned to the CRT-D group. The time until death appeared to be longer for those assigned to receive a CRT-D than for those assigned to receive an ICD (acceleration factor, 0.80; 95% confidence interval, 0.69 to 0.92; P=0.002). A secondary-outcome event occurred in 412 patients (77.7%) in the ICD group and in 392 (75.4%) in the CRT-D group.ConclusionsAmong patients with a reduced ejection fraction, a widened QRS complex, and NYHA class II or III heart failure, the survival benefit associated with receipt of a CRT-D as compared with ICD appeared to be sustained during a median of nearly 14 years of follow-up. (RAFT ClinicalTrials.gov number, NCT00251251.)

QRS Morphology and the Risk of Ventricular Tachyarrhythmia in Cardiac Resynchronization Therapy Recipients

BackgroundThere are conflicting data on the effect of cardiac resynchronization therapy with a defibrillator (CRT-D) on the risk of life-threatening ventricular tachyarrhythmia in heart failure patients. ObjectivesThe authors aimed to assess whether QRS morphology is associated with risk of ventricular arrhythmias in CRT recipients. MethodsThe study population comprised 2,862 patients implanted with implantable cardioverter defibrillator (ICD)/CRT-D for primary prevention who were enrolled in 5 landmark primary prevention ICD trials (MADIT-II [Multicenter Automated Defibrillator Implantation Trial], MADIT-CRT [Multicenter Automated Defibrillator Implantation Trial-Cardiac Resynchronization Therapy], MADIT-RIT [Multicenter Automated Defibrillator Implantation Trial-Reduction in Inappropriate Therapy], MADIT-RISK [Multicenter Automated Defibrillator Implantation Trial-RISK], and RAID [Ranolazine in High-Risk Patients With Implanted Cardioverter Defibrillators]). Patients with QRS duration ≥130 ms were divided into 2 groups: those implanted with an ICD only vs CRT-D. The primary endpoint was fast ventricular tachycardia (VT)/ventricular fibrillation (VF) (defined as VT ≥200 beats/min or VF), accounting for the competing risk of death. Secondary endpoints included appropriate shocks, any sustained VT or VF, and the burden of fast VT/VF, assessed in a recurrent event analysis. ResultsAmong patients with left bundle branch block (n = 1,792), those with CRT-D (n = 1,112) experienced a significant 44% (P < 0.001) reduction in the risk of fast VT/VF compared with ICD-only patients (n = 680), a significantly lower burden of fast VT/VF (HR: 0.55; P = 0.001), with a reduced burden of appropriate shocks (HR: 0.44; P < 0.001). In contrast, among patients with non-left bundle branch block (NLBBB) (N = 1,070), CRT-D was not associated with reduction in fast VT/VF (HR: 1.33; P = 0.195). Furthermore, NLBBB patients with CRT-D experienced a statistically significant increase in the burden of fast VT/VF events compared with ICD-only patients (HR: 1.90; P = 0.013). ConclusionsOur data suggest a potential proarrhythmic effect of CRT among patients with NLBBB. These data should be considered in patient selection for treatment with CRT.

Benefit of cardiac resynchronization therapy among older patients: A patient-level meta-analysis

Cardiac resynchronization therapy (CRT) reduces heart failure hospitalizations (HFH) and mortality for guideline-indicated patients with heart failure (HF). Most patients with HF are aged ≥70 years but such patients are often under-represented in randomized trials. Patient-level data were combined from 8 randomized trials published 2002-2013 comparing CRT to no CRT (n=6,369). The effect of CRT was estimated using an adjusted Bayesian survival model. Using age as a categorical (<70 vs ≥70 years) or continuous variable, the interaction between age and CRT on the composite end point of HFH or all-cause mortality or all-cause mortality alone was assessed. The median age was 67 years with 2436 (38%) being 70+; 1,554 (24%) were women; 2,586 (41%) had nonischemic cardiomyopathy and median QRS duration was 160 ms. Overall, CRT was associated with a delay in time to the composite end point (adjusted hazard ratio [aHR] 0.75, 95% credible interval [CI] 0.66-0.85, P=.002) and all-cause mortality alone (aHR of 0.80, 95% CI 0.69-0.96, P=.017). When age was treated as a categorical variable, there was no interaction between age and the effect of CRT for either end point (P > .1). When age was treated as a continuous variable, older patients appeared to obtain greater benefit with CRT for the composite end point (P for interaction=.027) with a similar but nonsignificant trend for mortality (P for interaction=.35). Reductions in HFH and mortality with CRT are as great or greater in appropriately indicated older patients. Age should not be a limiting factor for the provision of CRT.

Role of monocytes and dendritic cells in cardiac reverse remodelling after cardiac resynchronization therapy

Background and aimsMonocytes and dendritic cells (DC) are both key inflammatory cells, with recognized effects on cardiac repair. However, there are distinct subsets of monocytes with potential for beneficial or detrimental effects on heart failure (HF) pathogenesis. The connection between reverse cardiac remodelling, the potential anti-inflammatory effect of cardiac resynchronization therapy (CRT) and monocytes and DC homeostasis in HF is far from being understood. We hypothesized that monocytes and DC play an important role in cardiac reverse remodelling and CRT response. Therefore, we aimed to assess the potential role of baseline peripheral levels of blood monocytes and DC subsets and their phenotypic and functional activity for CRT response, in HF patients. As a secondary objective, we aimed to evaluate the impact of CRT on peripheral blood monocytes and DC subsets, by comparing baseline and post CRT circulating levels and phenotypic and functional activity.MethodsForty-one patients with advanced HF scheduled for CRT were included in this study. The quantification and phenotypic determination of classical (cMo), intermediate (iMo) and non-classical monocytes (ncMo), as well as of myeloid (mDC) and plasmacytoid DC (pDC) were performed by flow cytometry in a FACSCanto™II (BD) flow cytometer. The functional characterization of total monocytes and mDC was performed by flow cytometry in a FACSCalibur flow cytometer, after in vitro stimulation with lipopolysaccharide from Escherichia coli plus interferon (IFN)-γ, in the presence of Brefeldina A.Comparisons between the control and the patient group, and between responders and non-responders to CRT were performed.ResultsCompared to the control group, HF population presented a significantly lower frequency of pDC at baseline and a higher proportion of monocytes and mDC producing IL-6 and IL-1β, both before and 6-months after CRT (T6). There was a remarkable decrease of cMo and an increase of iMo after CRT, only in responders. The responder group also presented higher ncMo values at T6 compared to the non-responder group. Both responders and non-responders presented a decrease in the expression of CD86 in all monocyte and DC populations after CRT. Moreover, in non-responders, the increased frequency of IL-6-producing DC persisted after CRT.ConclusionOur study provides new knowledge about the possible contribution of pDC and monocytes subsets to cardiac reverse remodelling and response to CRT. Additionally, CRT is associated with a reduction on CD86 expression by monocytes and DC subsets and in their potential to produce pro-inflammatory cytokines, contributing, at least in part, for the well described anti-inflammatory effects of CRT in HF patients.

Evolution of Echocardiography-Derived Hemodynamic Force Parameters After Cardiac Resynchronization Therapy

Echocardiography-derived hemodynamic forces (HDF) allow calculation of intraventricular pressure gradients from routine transthoracic echocardiographic images. The evolution of HDF after cardiac resynchronization therapy (CRT) has not been investigated in large cohorts. The aim was to assess HDF in patients with heart failure implanted with CRT versus healthy controls. HDF were assessed before and 6months after CRT. The following HDF parameters were calculated: (1) apical-basal strength, (2) lateral-septal strength, (3) the ratio of lateral-septal to apical-basal strength ratio, and (4) the force vector angle (1 and 2 representing the magnitude of HDF, 3 and 4 representing the orientation of HDF). In the propulsive phase of systole, the apical-basal impulse and the systolic force vector angle were measured. A total of 197 patients were included (age 64 ± 11years, 62% male), with left ventricular ejection fraction ≤35%, QRS duration ≥130ms and left bundle branch block. The magnitude of HDF was significantly lower and the orientation was significantly worse in patients with heart failure versus healthy controls. Immediately after CRT implantation, the apical-basal impulse and systolic force vector angle were significantly increased. Six months after CRT, improvement of apical-basal strength, lateral-septal to apical-basal strength ratio and the force vector angle occurred. When CRT was deactivated at 6months, the increase in the magnitude of apical-basal HDF remained unchanged while the systolic force vector angle worsened significantly. In conclusion, HDF in CRT recipients reflect the acute effect of CRT and the effect of left ventricular reverse remodeling on intraventricular pressure gradients. Whether HDF analysis provides incremental value over established echocardiographic parameters, remains to be determined.

Time-trend treatment effect of cardiac resynchronization therapy with or without defibrillator on mortality: a systematic review and meta-analysis.

This study aimed to investigate the impact of cardiac resynchronization therapy with a defibrillator (CRT-D) on mortality, comparing it with CRT with a pacemaker (CRT-P). Additionally, the study sought to identify subgroups, evaluate the time trend in treatment effects, and analyze patient characteristics, considering the changing indications over the past decades. PubMed, CENTRAL, and Embase up to October 2021 were screened for studies comparing CRT-P and CRT-D, focusing on mortality. Altogether 26 observational studies were selected comprising 128 030 CRT patients, including 55 469 with CRT-P and 72 561 with CRT-D device. Cardiac resynchronization therapy with defibrillator was able to reduce all-cause mortality by almost 20% over CRT-P [adjusted hazard ratio (HR): 0.85; 95% confidence interval (CI): 0.76-0.94; P < 0.01] even in propensity-matched studies (HR: 0.83; 95% CI: 0.80-0.87; P < 0.001) but not in those with non-ischaemic aetiology (HR: 0.95; 95% CI: 0.79-1.15; P = 0.19) or over 75 years (HR: 1.08; 95% CI 0.96-1.21; P = 0.17). When treatment effect on mortality was investigated by the median year of inclusion, there was a difference between studies released before 2015 and those thereafter. Time-trend effects could be also observed in patients' characteristics: CRT-P candidates were getting older and the prevalence of ischaemic aetiology was increasing over time. The results of this systematic review of observational studies, mostly retrospective with meta-analysis, suggest that patients with CRT-D had a lower risk of mortality compared with CRT-P. However, subgroups could be identified, where CRT-D was not superior such as non-ischaemic and older patients. An improved treatment effect of CRT-D on mortality could be observed between the early and late studies partly related to the changed characteristics of CRT candidates.

Effectiveness of conduction system pacing for cardiac resynchronization therapy: A systematic review and network meta-analysis.

Cardiac resynchronization therapy (CRT) with biventricular pacing (BiV-CRT) is ineffective in approximately one-third of patients. CRT with Conduction system pacing (CSP-CRT) may achieve greater synchronization. We aimed to assess the effectiveness of CRT with His pacing (His-CRT) or left bundle branch pacing (LBB-CRT) in lieu of biventricular CRT. The PubMed, Embase, Web of Science, Scopus, and the Cochrane Library were systematically searched until August 19, 2023, for original studies including patients with reduced left ventricular ejection fraction (LVEF) who received His- or LBB-CRT, that reported either CSP-CRT success, LVEF, QRS duration (QRSd), or New York Heart Association (NYHA) classification. Effect measures were compared with frequentist network meta-analysis. Thirty-seven publications, including 20 comparative studies, were included. Success rates were 73.5% (95% CI: 61.2-83.0) for His-CRT and 91.5% (95% CI: 88.0-94.1) for LBB-CRT. Compared to BiV-CRT, greater improvements were observed for LVEF (mean difference [MD] for His-CRT +3.4%; 95% CI [1.0; 5.7], and LBB-CRT: +4.4%; [2.5; 6.2]), LV end-systolic volume (His-CRT:17.2mL [29.7; 4.8]; LBB-CRT:15.3mL [28.3; 2.2]), QRSd (His-CRT: -17.1ms [-25.0; -9.2]; LBB-CRT: -17.4ms [-23.2; -11.6]), and NYHA (Standardized MD [SMD]: His-CRT:0.4 [0.8; 0.1]; LBB-CRT:0.4 [-0.7; -0.2]). Pacing thresholds at baseline and follow-up were significantly lower with LBB-CRT versus both His-CRT and BiV-CRT. CSP-CRT was associated with reduced mortality (R = 0.75 [0.61-0.91]) and hospitalizations risk (RR = 0.63 [0.42-0.96]). This study found that CSP-CRT is associated with greater improvements in QRSd, echocardiographic, and clinical response. LBB-CRT was associated with lower pacing thresholds. Future randomized trials are needed to determine CSP-CRT efficacy.

Diagnostic criteria for proximal left bundle branch block and their significance in predicting the success of cardiac resynchronization therapy

Aim. To develop diagnostic criteria for proximal left bundle branch block (LBBB) based on non-invasive methods and to determine the significance of these criteria in predicting the effect of cardiac resynchronization therapy (CRT).Material and methods. To develop criteria, 58 patients (21 men, mean age, 76,1±7,1 years) with LBBB occurred immediately after transcatheter aortic valve implantation (TAVI) were included. To assess the significance of the developed criteria, the second group included 22 patients (11 men, mean age, 57,9±9,3 years) with dilated cardiomyopathy (DCM), who had indications for CRT. The effectiveness of CRT was assessed by echocardiography 6 months after implantation. All patients in the DCM group and 15 patients in the TAVI group underwent superficial epiand endocardial non-invasive mapping using Amycard 01C EP Lab (EP Solutions SA, Switzerland). Patients in the DCM group underwent contrast-enhanced cardiac magnetic resonance imaging (MRI) before device implantation.Results. The criteria for proximal LBBB included 3 electrocardiographic features: QRS complex &gt;130 ms in women and 140 ms in men, QSor rS-configuration in V1 lead, notch in two or more lateral leads (I, avL, V5, V6), and 2 mapping criteria: characteristic location of block line and delayed activation point. In the DCM group, the criteria were positive in 13 of 22 patients (59%). The developed criteria for proximal LBBB showed a relatively strong, significant relationship with the positive effect of CRT (сhi-square test =5,46, p=0,02, Cramer test =0,5, odds ratio (OR)=15,0, 95% confidence interval (CI), 1,32-169,9, p=0,002). An additional analysis showed that both the criteria for proximal block and CRT effect are associated with myocardial fibrosis according to MRI. In particular, intramural stria-shaped contrast accumulation in the interventricular septum leads to a change in characteristic of proximal block mapping phenomena — displacement of delayed activation point (chi-square test =13,9, p&lt;0,001, Cramer test =0,79) and displacement or absence of conduction block lines (chi-square test =6,92, p=0,009, Cramer test =0,56) and prevents the CRT effect (OR =8,67, 95% CI, 1,05-71,57 p=0,03).Conclusion. Proximal LBBB is only one of the factors determining the effectiveness of CRT. Proximal LBBB may mask significant myocardial structural changes that prevent the CRT success.

Mechanical Dyssynchrony Combined with Septal Scarring Reliably Identifies Responders to Cardiac Resynchronization Therapy.

Background and aim: The presence of mechanical dyssynchrony on echocardiography is associated with reverse remodelling and decreased mortality after cardiac resynchronization therapy (CRT). Contrarily, myocardial scar reduces the effect of CRT. This study investigated how well a combined assessment of different markers of mechanical dyssynchrony and scarring identifies CRT responders. Methods: In a prospective multicentre study of 170 CRT recipients, septal flash (SF), apical rocking (ApRock), systolic stretch index (SSI), and lateral-to-septal (LW-S) work differences were assessed using echocardiography. Myocardial scarring was quantified using cardiac magnetic resonance imaging (CMR) or excluded based on a coronary angiogram and clinical history. The primary endpoint was a CRT response, defined as a ≥15% reduction in LV end-systolic volume 12 months after implantation. The secondary endpoint was time-to-death. Results: The combined assessment of mechanical dyssynchrony and septal scarring showed AUCs ranging between 0.81 (95%CI: 0.74-0.88) and 0.86 (95%CI: 0.79-0.91) for predicting a CRT response, without significant differences between the markers, but significantly higher than mechanical dyssynchrony alone. QRS morphology, QRS duration, and LV ejection fraction were not superior in their prediction. Predictive power was similar in the subgroups of patients with ischemic cardiomyopathy. The combined assessments significantly predicted all-cause mortality at 44 ± 13 months after CRT with a hazard ratio ranging from 0.28 (95%CI: 0.12-0.67) to 0.20 (95%CI: 0.08-0.49). Conclusions: The combined assessment of mechanical dyssynchrony and septal scarring identified CRT responders with high predictive power. Both visual and quantitative markers were highly feasible and demonstrated similar results. This work demonstrates the value of imaging LV mechanics and scarring in CRT candidates, which can already be achieved in a clinical routine.

Comorbidities and clinical response to cardiac resynchronization therapy: Patient-level meta-analysis from eight clinical trials.

Patients with heart failure usually have several other medical conditions that might alter the effects of interventions. We investigated whether the burden of comorbidity modified the clinical response to cardiac resynchronization therapy (CRT). Original patient-level data from eight randomized trials exploring the effects of CRT versus no CRT were pooled (BLOCK-HF, MIRACLE, MIRACLE-ICD, MIRACLE-ICD II, RAFT, COMPANION, MADIT-CRT and REVERSE). A prior history of the following comorbidities was considered: episodic or persistent atrial fibrillation (n = 920), coronary artery disease (n = 3732), diabetes (n = 2171), and hypertension (n = 3353). Patients were classified into three groups based on the number of comorbidities: 0, 1-2, or ≥3. The outcomes of interest were time to all-cause mortality and time to the composite outcome of heart failure hospitalization (HFH) or all-cause mortality. Outcomes were evaluated within each comorbidity group using a Bayesian hierarchical Weibull survival regression model. Of 6324 patients, 970 (15%) had no comorbidities, 4052 (64%) had 1-2 and 1302 (21%) had ≥3 comorbidities. The adjusted hazard ratio (aHR) for CRT versus no CRT for all-cause mortality in the overall cohort was 0.79 (95% credible interval [CI] 0.68-0.93) (p = 0.010); for no comorbidities the aHR was 0.54 (95% CI 0.34-0.86), for 1-2 comorbidities was 0.81 (95% CI 0.67-0.97) and for ≥3 comorbidities was 0.83 (95% CI 0.64-1.07) (no significant interaction between CRT and comorbidity burden: p = 0.13). For the endpoint of HFH or all-cause mortality, the aHR for the overall cohort was 0.74 (95% CI 0.65-0.84) (p = 0.001), for no comorbidities was 0.69 (95% CI 0.50-0.94), for 1-2 comorbidities was 0.77 (95% CI 0.66-0.90) and for ≥3 comorbidities was 0.68 (95% CI 0.55-0.82) (no significant interaction between CRT and comorbidity burden: p = 0.081). In a meta-analysis of patient-level data from eight major trials, the totality of evidence suggests that CRT reduces HFH and/or all-cause mortality even when several comorbid diseases are present. NCT00271154, NCT00251251, NCT00267098, NCT00180271.

The evolving state of cardiac resynchronization therapy and conduction system pacing: 25 years of research at EP Europace journal.

Cardiac resynchronization therapy (CRT) was proposed in the 1990s as a new therapy for patients with heart failure and wide QRS with depressed left ventricular ejection fraction despite optimal medical treatment. This review is aimed first to describe the rationale and the physiologic effects of CRT. The journey of the landmark randomized trials leading to the adoption of CRT in the guidelines since 2005 is also reported showing the high level of evidence for CRT. Different alternative pacing modalities of CRT to conventional left ventricular pacing through the coronary sinus have been proposed to increase the response rate to CRT such as multisite pacing and endocardial pacing. A new emerging alternative technique to conventional biventricular pacing, conduction system pacing (CSP), is a promising therapy. The different modalities of CSP are described (Hirs pacing and left bundle branch area pacing). This new technique has to be evaluated in clinical randomized trials before implementation in the guidelines with a high level of evidence.

Right Ventricular Response to Cardiac Resynchronization Therapy: A Three-Dimensional and Speckle Tracking Echocardiographic Study

Cardiac resynchronization therapy (CRT) induces left ventricle reverse remodeling; however, its effects on right ventricular (RV) volumes and function were not well described. This study aimed to assess the effects of CRT on RV. Of 112 patients, 63 enrolled with a mean age of 62.77±7.23years, including 40 males (63.5%). All patients met criteria for CRT implantation and were followed at 3-month and 6-month intervals. Standard 2-dimensional/3-dimensional (3D) echocardiography and speckle-tracking analyses were conducted for assessment of LV and left atrium (LA). RV maximum diameters, tricuspid lateral annular systolic velocity, tricuspid annular plane systolic excursion, fractional area change, RV global (RV 4-chamber strain (RV4CSL), and RV free wall strain (RVFWSL), in addition to 3D echocardiographic assessment of RV, were done before CRT implantation and at follow-up visits. Mean follow-up period was 6.76±1.25months. A total of 48 patients (76.2%) were LV responders (LVR) whereas the rest were nonresponders (LVNR). Both groups had similar baseline characteristics, risk factors, device implantation, and programming values. Only LVR had significant reduction in RV basal diameter, together with significant improvement of RV systolic performance: systolic velocity, fractional area change, RV4CSL, RVFWSL, and 3D-derived RV volumes and ejection fraction, compared with baseline values. In addition, pulmonary arterial systolic pressure decreased in LVR with reduction of tricuspid regurgitation severity. LV response, percentage change of RV4CSL, LA end-systolic volume index, and LA emptying fraction at 3-month follow-up were the most independent predictors of RV response by multivariate analysis. Reduced left ventricular end-systolic volume >13.5% had 92.3% sensitivity and 81.8% specificity. In conclusion, CRT-induced RV reverse remodeling and improved RV-arterial coupling. These effects were associated with left side response to CRT.