Effects Of Cardiac Resynchronization Therapy Research Articles

Pressure-volume analysis by three-dimensional echocardiography: a novel and superior method to predict response following cardiac resynchronization therapy

Abstract Introduction Long-term response to cardiac resynchronization therapy (CRT) is primarily assessed by 2D echocardiography. The combination of 3D echocardiography and left ventricular (LV) pressure curve estimation allows for pressure-volume (PV) analysis and LV work efficiency (LVWE) estimation which may be superior to today’s methods. Aim To investigate if PV-analysis by 3D echocardiography is superior to 2D volumes at predicting long-term survival in CRT. Methods In a recent prospective multicenter study, non-invasive PV-analysis (n=106) and 2D volume analysis by biplane Simpson’s method (n=195) were performed, before and 6 months after CRT. The LV pressure curve was estimated by aligning a reference pressure curve with mitral and aortic valve events obtained from echocardiography. The amplitude of the curve was adjusted to brachial systolic cuff pressure and combined with 3D volumes for PV-analysis. As shown in figure 1, LVWE was calculated as the ratio of estimated stroke work (red area) to total mechanical energy (red + blue areas). The cutoff value for change in LV end-systolic volume (ESV) was set at 15% and at >35% for LVWE using Receiver Operator Curve analysis. Volumetric non-responders were subdivided into response based on LVWE. Results After 6±2 years follow-up, 47 (23%) patients had died. Relative change in 3D and 2D LV ESV showed similar ability to predict long-term all-cause mortality (log rank p<0.001 for both) (Figure 2). However, LVWE identified patients with a positive effect of CRT who were volumetric non-responders. These patients had similar outcomes as volumetric responders (HR 1.91, 95% CI: 0.54-6.81) (Figure 3). LVWE also identified non-responders with particularly adverse outcomes (HR 3.46, 95% CI: 1.32-9.10 vs volumetric non-response and LVWE >35%). Conclusions PV-analysis by 3D-echoardiography identifies a new group of patients who respond to CRT without a 15% reduction in ESV who have similar outcomes to volumetric responders. In our data, 3D echocardiography was superior to 2D volumes at predicting long-term all-cause mortality after CRT. LV work efficiency before and after CRT LV work efficiency and survival

Role of magnetic resonance imaging in predicting the efficiency of cardiac resynchronization therapy in patients with left ventricular non-compaction and heart failure

Aim. To evaluate the role of magnetic resonance imaging (MRI) in predicting the efficacy of cardiac resynchronization therapy (CRT) in patients with left ventricular non-compaction (LVNC) and heart failure (HF).Material and methods. This observational retrospective study included 26 patients with a morphological signs of LVNC cardiomyopathy according to echocardiography (Chin, Jenni, Stollberger criteria) and MRI (Petersen criterion). All patients underwent CRT implantation. The changes of the left ventricular size and function were assessed using echocardiography. Before the CRT procedure, all patients underwent contrast-enhanced cardiac MRI.Results. According to a response to CRT, patients were divided into 3 following groups: responders (a decrease in left ventricular (LV) end-diastolic volume (EDV) according to echocardiography from 15 to 30%, a decrease in HF functional class), super-responders (a decrease in LV EDV by more than 30%) and non-responders (failure to meet the response criteria). The study identified factors influencing the CRT results, the most significant of which were the familial LVNC cardiomyopathy, sex and age of patients, as well as following parameters of cardiac morphology: myocardial fibrosis according to MRI, myocardial non-compaction severity, LV volume index.Conclusion. MRI is a technique that can make a significant contribution to predicting the CRT effectiveness in patients with LVNC and HF. Therefore, it should be performed in all patients before CRT to optimize the selection procedure and exclude patients who are unlikely to benefit from CRT.

Why Is the Group of Non-responders to Cardiac Resynchronization Therapy so Large? Some Ethical and Medical Aspects of the Topic

The aim of this single centre study (“St. Ekaterina” Hospital) is to assess the effect of a second successful cardiac resynchronization therapy (CRT) in patients who had already had an unsuccessful implantation of a CRT system at other medical centres in Bulgaria and were defined as “non-responders”. This is a prospective observational study. The patients have previously had an unsuccessful implantation of a left ventricular (LV) lead or the latter has not been placed in the target vessel. After the successful implantation of a new LV lead in another target vessel, the post-procedure criteria for echocardiographic (EchoCG) and clinical response were monitored. Over the period 2017–2019, 18 CRT systems have been implanted in 18 patients with an average age 65±1 years with initial heart failure (HF) according to the Classification of the New York Heart Association (NYHA) class III. The average LV ejection fraction (LVEF) was 28±1%. After the successful implantation of a new LV lead, patients presented with HF class II–III and LVEF 36±1%. In the new “upgrading” procedure, 15 patients (83%) had a good clinical and EchoCG response, and two of those 15 patients were “super responders”. The remaining three patients (17%) were “poor responders”. After the good clinical and echocardiographic response to the therapy with a second successful implantation of a LV lead in another target vessel, an important question arises, whether all “non-responders” to the CRT are actually supposed to be defined as such.

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<0.001), the proportion of patients on optimal medical therapy (64% vs 47%, p=0.001), patients with a defibrillator (81% vs 19%, p<0.001), and patients with a LBBB morphology (75% vs 47%, p<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.

Heart Rate Recovery Index and Improved Diastolic Dyssynchrony in Fusion Pacing Cardiac Resynchronization Therapy.

Background: Restoring electrical synchrony with cardiac resynchronization therapy (CRT) reverses the heart failure phenotype developed by left-ventricular (LV) dyssynchrony. This study aimed to identify new predictors of response to LV-only fusion pacing CRT. Methods: A select group of patients with CRT-P indications received a right atrium (RA)/LV DDD pacing system. LV dyssynchrony was assessed via offline TDI timing focusing on the temporal difference between peak septal (E″T) and lateral wall (A"T) motion. CRT effectiveness was evaluated at each follow-up, involving the heart rate recovery index (HRRI) parameter (acceleration/deceleration time) derived from exercise testing along with the echocardiographic parameters. Patients were classified into super-responders (SR), responders (R), and non-responders (NR). Results: Baseline initial characteristics: 62 patients (35 male) aged 62 ± 11 y.o. with non-ischemic dilated cardiomyopathy (DCM). Ejection fraction (EF) 27 ± 5.2%; QRS 164 ± 18 ms; 29% had type III diastolic dysfunction (DD), 63% type II DD, and 8% type I DD. Average follow-up was 45 ± 19 months: 34% of patients were SR, 61% R, and 5% NR. The E″T decreased from 90 ± 20 ms to 25 ± 10 ms in SR, with a shorter deceleration time (DT) during exercise test compared to NR (109 ± 68 ms vs. 330 ± 30 ms; p < 0.0001). The responders present a higher HRRI (2.87 ± 1.47 vs. 0.98 ± 0.08; p = 0.03) compared to NR and a significantly decrease in E"T and A"T from 76 ± 13 ms to 51 ± 11 ms (p < 0.0001). Prolonged DT was associated with an accentuated LV dyssynchrony and nonoptimal response to CRT. Conclusions: The study identified new parameters for assessing responsiveness to LV-only fusion pacing CRT, which could improve candidate selection and CRT implementation.

Multicenter Hemodynamic Assessment of the LOT-CRT Strategy: When Does Combining Left Bundle Branch Pacing and Coronary Venous Pacing Enhance Resynchronization?: Primary Results of the CSPOT Study.

Left bundle branch area pacing (LBBAP) may be an alternative to biventricular pacing (BVP) for cardiac resynchronization therapy (CRT). We sought to compare the acute hemodynamic and ECG effects of LBBAP, BVP, and left bundle-optimized therapy CRT (LOT-CRT) in CRT candidates with advanced conduction disease. In this multicenter study, 48 patients with either nonspecific interventricular conduction delay (n=29) or left bundle branch block (n=19) underwent acute hemodynamic testing to determine the change in left ventricular pressure maximal first derivative (LV dP/dtmax) from baseline atrial pacing to BVP, LBBAP, or LOT-CRT. Atrioventricular-optimized increases in LV dP/dtmax for LOT-CRT (mean, 25.8% [95% CI, 20.9%-30.7%]) and BVP (26.4% [95% CI, 20.2%-32.6%]) were greater than unipolar LBBAP (19.3% [95% CI, 15.0%-23.7%]) or bipolar LBBAP (16.4% [95% CI, 12.7%-20.0%]; P≤0.005). QRS shortening was greater in LOT-CRT (29.5 [95% CI, 23.4-35.6] ms) than unipolar LBBAP (11.9 [95% CI, 6.1-17.7] ms), bipolar LBBAP (11.7 ms [95% CI, 6.4-17.0]), or BVP (18.5 [95% CI, 11.0-25.9] ms), all P≤0.005. Compared with patients with left bundle branch block, patients with interventricular conduction delay experienced less QRS reduction (P=0.026) but similar improvements in LV dP/dtmax (P=0.29). Bipolar LBBAP caused anodal capture in 54% of patients and resulted in less LV dP/dtmax improvement than unipolar LBBAP (18.6% versus 23.7%; P<0.001). Subclassification of LBBAP capture (European Heart Rhythm Association criteria) indicated LBBAP or LV septal pacing in 27 patients (56%) and deep septal pacing in 21 patients (44%). The hemodynamic benefit of adding left ventricular coronary vein pacing to LBBAP depended on baseline QRS duration (P=0.031) and success of LBBAP (P<0.004): LOT-CRT provided 14.5% (5.0%-24.1%) greater LV dP/dtmax improvement and 20.8 (12.8-28.8) ms greater QRS shortening than LBBAP in subjects with QRS ≥171 ms and deep septal pacing capture type. In a CRT cohort with advanced conduction disease, LOT-CRT and BVP provided greater acute hemodynamic benefit than LBBAP. Subjects with wider QRS or deep septal pacing are more likely to benefit from the addition of a left ventricular coronary vein lead to implement LOT-CRT. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04905290.

Outcomes of cardiac resynchronization therapy (CRT) in cardiac sarcoidosis patients with a range of ejection fractions.

In cardiac sarcoidosis (CS) patients, the benefit of cardiac resynchronization therapy (CRT) remains unclear. We sought to assess the short-term and long-term effects of CRT in CS patients with a range of left ventricular (LV) ejection fractions (LVEFs). Consecutive CS patients with heart failure with reduced ejection fraction (HFrEF; LVEF≤40%), mildly reduced ejection fraction (HFmrEF; LVEF 41%-49%) and preserved ejection fraction (HFpEF; LVEF≥50) treated with CRT under the care of a tertiary UK centre between 2008 and 2023 were reviewed. CRT response was defined by >5% improvement in serial LVEF. The primary endpoint was a composite of all-cause mortality, cardiac transplantation or unplanned hospitalization for decompensated heart failure. The secondary endpoint included ventricular arrhythmic events. Of the 100 patients enrolled (age 58±10years; 71% male), 63 had HFrEF, 17 had HFmrEF and 20 had HFpEF. After short-term follow-up (9.8±5.4months), HFrEF patients demonstrated significant LVEF response (P<0.01). On Kaplan-Meier analysis (follow-up 38±32months), HFrEF non-responders had significantly worse event-free survival compared with HFrEF responders for the primary (P<0.001) and secondary (P=0.001) endpoints. Despite short-term LV function improvement, CRT responders still had worse event-free survival compared with HFmrEF/HFpEF patients for the primary endpoint (P<0.001). On multivariable Cox analysis, age [hazard ratio (HR) 1.05, 95% confidence interval (CI) 1.01-1.10, P=0.008] and HFrEF CRT non-response (HR 12.33, 95% CI 2.45-61.87, P=0.002) were associated with the primary endpoint. In CS patients with HFrEF, CRT response is associated with a better long-term prognosis than non-response. However, HFrEF CRT responders still have worse long-term prognosis than HFmrEF/HFpEF patients.

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 the Use of an Adaptive Cardiac Resynchronization Therapy Algorithm and Health Care Use 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 &amp;gt;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 &amp;gt;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.

An adaptive cardiac resynchronization therapy (aCRT) algorithm allows continuous adjustments of pacing timings of atrioventricular delays by periodic automatic evaluation of electrical conduction. This applies to patients with an atrioventricular block and is effective in cardiac resynchronization therapy (CRT) devices; however, whether this algorithm benefits patients with pacemaker dependency is uncertain. This study examined the clinical impact of an aCRT algorithm in patients diagnosed with heart failure with reduced ejection fraction and pacemaker dependency. A total of 359 patients underwent CRT between January 2016 and December 2022. Patients undergoing pacemaker-dependent CRT with the aCRT algorithm function were selected. Sixty-four patients with pacemaker dependency (31 with aCRT algorithm and 33 without) were included. Pacemaker dependency was defined as the absence of spontaneous ventricular activity during the sensing test at VVI 30bpm or prolonged atrioventricular delay (> 300 ms). The primary endpoint was the composite clinical outcome of all-cause death or hospitalization for heart failure. No significant differences were observed in baseline characteristics between groups. During a median follow-up of 1,067 days (interquartile range 553-1,776 days), aCRT reduced the risk of composite clinical outcomes in patients with pacemaker dependency (log-rank P = 0.028). In addition, using the aCRT algorithm was an independent predictor of the composite clinical outcomes in the multivariate analysis (hazard ratio 0.34, 95% confidence interval: 0.12-0.94, P = 0.038). The aCRT algorithm significantly reduced the risk of adverse clinical outcomes in patients with pacemaker dependency. This algorithm may be an important tool for managing such patients.

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.