Cardiac Resynchronization Therapy Trial Research Articles

Cardiac Resynchronization Therapy in Ischemic Versus Nonischemic Cardiomyopathy: Patient-Level Meta-Analysis of 7 Randomized Clinical Trials

BackgroundData on whether cardiac resynchronization therapy (CRT) results in better clinical and echocardiographic outcomes in patients with nonischemic cardiomyopathy (NICM) vs ischemic cardiomyopathy (ICM) are conflicting. ObjectivesThe authors conducted this meta-analysis of 7 clinical trials of CRT to determine the association between etiology of cardiomyopathy and clinical and echocardiographic outcomes. MethodsThe authors analyzed patient-level data using Bayesian Hierarchical Weibull survival regression modeling to determine the association between etiology of cardiomyopathy and time to all-cause death or heart failure hospitalization (HFH). Linear regression was used to assess the association between etiology of cardiomyopathy and echocardiographic measurements. ResultsOf 6,252 patients included, 4,717 (75%) were men, median age was 66 years (IQR: 58-73 years), 3,704 (59%) had ICM, and 3,778 (60%) received CRT. CRT increased the time to HFH or all-cause death (HR: 0.67; 95% credible interval [CrI]: 0.56-0.82; P < 0.001) with no difference by etiology of cardiomyopathy (HR ratio: 1.06 [95% CrI: 0.87-1.29]; P = 0.57). Likewise, CRT increased the time to all-cause death (HR: 0.71 [95% CrI: 0.55-0.93]; P = 0.019) with no difference by etiology of cardiomyopathy (HR ratio: 1.06 [95% CrI: 0.80-1.43]; P = 0.70). Echocardiographic data that were available for 2,430 (39%) patients showed that CRT improvements in left ventricular ejection fraction, left ventricular end-diastolic diameter, and left ventricular end-systolic diameter were larger for patients with NICM. ConclusionsAlthough CRT led to greater increases in left ventricular ejection fraction and reductions in ventricular dimensions for patients with NICM compared with those with ICM, CRT significantly increased the time to HFH or all-cause death independently of the etiology of cardiomyopathy. Further studies on improving patient selection for CRT are needed.

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.

His-Purkinje Conduction System Pacing Optimized Trial of Cardiac Resynchronization Therapy vs Biventricular Pacing: HOT-CRT Clinical Trial

BackgroundHis-Purkinje conduction system pacing (HPCSP) using His bundle pacing (HBP) or left bundle branch pacing (LBBP) has emerged as an alternative to biventricular pacing (BVP) in patients requiring cardiac resynchronization therapy (CRT). ObjectivesThe aim of the study was to compare the feasibility and clinical efficacy of HOT-CRT (His-Purkinje conduction system pacing Optimized Trial of Cardiac Resynchronization Therapy) with BVP in patients with heart failure, reduced ejection fraction, and indication for CRT. MethodsThis was a prospective, randomized, controlled trial of HOT-CRT and BVP in patients with LVEF <50% and indications for CRT. If HPCSP resulted in incomplete electrical resynchronization, a coronary sinus (CS) lead was added. The primary outcome was the change in left ventricular ejection fraction (LVEF) at 6 months. The primary safety endpoint was freedom from major complications. ResultsA total of 100 patients (female 31%, aged 70 ± 12 years, LVEF 31.5% ± 9.0%) were randomized. HOT-CRT was successful in 48 of 50 (96%) and BVP-CRT in 41 of 50 (82%) patients (P = 0.03). QRS duration significantly decreased from 164 ± 26 ms to 137 ± 20 ms with HOT-CRT and 166 ± 28 ms to 141 ± 19 ms with BVP. Fluoroscopy results (18.8 ± 12.4 min vs 23.8 ± 12.4 min, P = 0.05) and procedure duration (119 ± 42 min vs 114 ± 36 min, P = 0.5) were similar. The primary outcome of change in LVEF at 6 months was greater in HOT-CRT than in BVP (12.4% ± 7.3% vs 8.0% ± 10.1%, P = 0.02). The primary safety endpoint was similar (98% vs 94%, P = 0.62). Echocardiographic response of improvement in LVEF >5% occurred in 80% vs 61% (P = 0.06). Complications occurred in 3 (6%) in HOT-CRT vs 10 (20%) in BVP (P = 0.03). ConclusionsHPCSP-guided CRT resulted in greater change in LVEF compared with BVP. Randomized clinical trials with long-term follow-up are necessary. (His-Purkinje Conduction System Pacing Optimized Trial of Cardiac Resynchronization Therapy [HOT-CRT]; NCT04561778)

Association of left ventricular remodeling with cardiac resynchronization therapy outcomes

Cardiac resynchronization therapy (CRT) response stratified by left ventricular (LV) remodeling revealed differing mortality profiles for distinct patient cohorts. Measuring functional end points, as well as mortality, may better assess CRT efficacy and inform patient management. However, the association between LV remodeling and functional outcomes after CRT is not well understood. The purpose of this study was to evaluate long-term CRT outcomes by extent of LV remodeling. REsynchronization reVErses Remodeling in Systolic Left vEntricular dysfunction (Clinical Trials.gov identifier NCT00271154) was a prospective, double-blind, randomized trial of CRT. Patients were classified on the basis of LV end-systolic volume (LVESV) change from baseline to 6 months post-CRT: worsened (increase), stabilized (0%-≤15% reduction), responder (>15%-<30% reduction), and super-responder (≥30% reduction). Subjects were evaluated annually for 5 years. The analyses included 353 patients randomized to CRT-ON arm. All-cause mortality was higher in the worsened group than in the other 3 response groups (29.8% vs 8.0%; P < .0001), with no difference in survival among those groups (P = .87). A significant interaction between the LVESV group and time was observed for health status and quality of life (P = .02 for both). The interaction was not significant for 6-minute hall walk (P=.79); however, super-responders had increased walk distance compared with the other 3 response groups (P = .03). Preventing further increase in LVESV with CRT was associated with reduced mortality, whereas functional measure improvement was associated with LV remodeling magnitude. These results support the consideration of functional and mortality end points to assess CRT efficacy and provide further evidence that the dichotomous "responder and nonresponder" classification should be modified.

Baseline clinical characteristics of heart failure patients with reduced ejection fraction enrolled in the BUDAPEST-CRT Upgrade trial.

The BUDAPEST-CRT Upgrade study is the first prospective, randomized, multicentre clinical trial investigating the outcomes after cardiac resynchronization therapy (CRT) upgrade in heart failure (HF) patients with intermittent or permanent right ventricular (RV) pacing with wide paced QRS. This report describes the baseline clinical characteristics of the enrolled patients and compares them to cohorts from previous milestone CRT studies. This international multicentre randomized controlled trial investigates 360 patients having a pacemaker (PM) or implantable cardioverter defibrillator (ICD) device for at least 6 months prior to enrolment, reduced left ventricular ejection fraction (LVEF ≤35%), HF symptoms (New York Heart Association [NYHA] functional class II-IVa), wide paced QRS (&gt;150 ms), and ≥20% of RV pacing burden without having a native left bundle branch block. At enrolment, the mean age of the patients was 73 ± 8 years; 89% were male, 97% were in NYHA class II/III functional class, and 56% had atrial fibrillation. Enrolled patients predominantly had conventional PM devices, with a mean RV pacing burden of 86%. Thus, this is a patient cohort with advanced HF, low baseline LVEF (25 ± 7%), high N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels (2231 pg/ml [25th-75th percentile 1254-4309 pg/ml]), and frequent HF hospitalizations during the preceding 12 months (50%). When compared with prior CRT trial cohorts, the BUDAPEST-CRT Upgrade study includes older patients with a strong male predominance and a high burden of atrial fibrillation and other comorbidities. Moreover, this cohort represents an advanced HF population with low LVEF, high NT-proBNP, and frequent previous HF events. ClinicalTrials.gov NCT02270840.

Cardiac resynchronization therapy in patients with a history of atrial fibrillation: insights from five major clinical trials

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): National Heart, Lung, and Blood Institute Background Many patients with heart failure who are considered for cardiac resynchronization therapy (CRT) have a history of (h/o) atrial fibrillation (AF) but there are doubts about the efficacy of CRT in patients with AF. Purpose To investigate the association of CRT on morbidity and mortality among patients with and without a h/o AF. Methods Original, patient-level data from five clinical trials of CRT that permitted enrolment of patients with a h/o AF were included: COMPANION, MADIT-CRT, BLOCK HF, REVERSE, and MIRACLE trial. Patients with permanent or persistent AF were excluded from these trials, and therefore from this analysis. The outcomes of interest were the composite endpoint of time to heart failure hospitalization (HFH) or all-cause mortality or all-cause mortality alone. The association of CRT (versus no CRT) with outcomes for patients with and without a h/o AF was assessed using a Bayesian-Weibull survival regression model with random terms for the trial-specific treatment effects and the trial-specific baseline hazard functions including an interaction between history of paroxysmal AF and CRT. All results are presented as hazard ratios (HRs) with 95% posterior credible intervals (CIs) and posterior probabilities of no association, adjusting for baseline characteristics. Results A total of 4062 patients were included, 661 (16.3%) of whom had a h/o AF. Patients with a h/o AF were older (mean [SD] age 68 [10] years versus 64 [11] years) and had a higher proportion of ischemic cardiomyopathy (67% versus 53%, p&amp;lt;0.001), a higher baseline serum creatinine (1.3 mg/dl versus 1.2 mg/dl, p&amp;lt;0.001), and a lower left ventricular ejection fraction (25% versus 26%, p&amp;lt;0.001). The HRs for all outcomes and the interaction term are shown in Table 1. For the overall population, CRT delayed the time to HFH or all-cause mortality (HR: 0.74, 95% CI: 0.62 – 0.87, p=0.005); for patients with a h/o AF, it did not (HR: 0.87, 95% CI: 0.64 to 1.19, p=0.37). In this patient-level meta-analysis, CRT was not associated with a reduction in mortality, overall or by h/o AF. Howevber, the interaction (estimate shown as a ratio of HRs) between those with or without a h/o AF and the effects of CRT was not significant for either outcome (Table 1). Conclusion In the largest post hoc analysis to date, we confirm the benefits of CRT in patients without a h/o AF in reducing HFH or mortality. There was no statistically significant interaction between CRT and h/o AF for any analysed outcome.

Evolving concept of dyssynchrony and its utility.

The role of electromechanical dyssynchrony in heart failure gained prominence in literature with the results of trials of cardiac resynchronization therapy (CRT). CRT has shown to significantly decrease heart failure hospitalization and mortality in heart failure patients with dyssynchrony. Current guidelines recommend the use of electrical dyssynchrony based on a QRS > 150 ms and a left bundle branch block pattern on surface electrocardiogram to identify dyssynchrony in patients who will benefit from CRT implantation. However, predicting response to CRT remains a challenge with nearly one-third of patients gaining no benefit from the device. Multiple echocardiographic measures of mechanical dyssynchrony have been studied over the past two decade. However, trials where mechanical dyssynchrony used as an additional or lone criteria for CRT failed to show any benefit in the response to CRT. This shows that a deeper understanding of cardiac mechanics should be applied in the assessment of dyssynchrony. This review discusses the evolving role of imaging techniques in assessing cardiac dyssynchrony and their application in patients considered for device therapy.

Atrial fibrillation in cardiac resynchronization therapy.

Patients with atrial fibrillation (AF) were largely excluded from the major clinical trials of cardiac resynchronization therapy (CRT), despite the presence of AF in up to 40% of patients receiving CRT in clinical practice. AF appears to attenuate the response to CRT, by the combination of a reduction in biventricular pacing and the loss of atrioventricular synchrony. In addition, remodeling secondary to CRT may influence the progression of AF. Management options for patients with AF and CRT include rate control, with drugs or atrioventricular node ablation, or rhythm control, with electrical cardioversion and antiarrhythmic therapy, or AF catheter ablation. The evidence for these therapies in patients with CRT is largely limited to observational studies or inferred from randomized studies in the general heart failure population. In this review, we explore the complex interaction between AF, heart failure, and CRT and discuss the evidence for the treatment options in this difficult patient cohort.

Comparative effectiveness of cardiac resynchronization therapy in older patients with heart failure: Systematic review and meta-analysis

BackgroundPivotal CRT trials enrolled patients with HFrEF significantly younger than the typical contemporary patient with HFrEF. Thus, the risks and benefits in this older population with HFrEF are largely unknown. We sought to perform meta-analyses comparing safety and effectiveness of cardiac resynchronization therapy (CRT) in older vs younger patients with heart failure with reduced ejection fraction (HFrEF). Methods and ResultsPubMed, The Cochrane Library, Scopus, and Web of Science were queried for comparative effectiveness studies of CRT in older patients with HFrEF. Title, abstract, and full-text screening was performed to identify studies comparing at least 1 prespecified end point between older and younger adult patients with at least 50 participants. Random effects meta-analysis in the left ventricular ejection fraction (LVEF) mean difference (older minus younger) and the relative risk (RR) of death, improvement in New York Heart Association (NYHA) functional class, and complications are reported along with estimates of heterogeneity. In 7 studies, there was similar LVEF improvement between groups (mean difference 1.14, 95% confidence interval [CI] –0.04 to 2.32, P = .06, I2 = 53%). Older patients were equally likely as younger patients to see an improvement in NYHA functional class of at least 1 in 6 studies (RR 0.99, 95% CI 0.93–1.06, P = .76, I2 = 25%). No significant differences in the incidence of hematoma, pneumothorax, lead dislodgment, cardiac perforation, or infection requiring explant was observed. The RR of mortality in 11 studies demonstrated higher risk of all-cause mortality in older patients (RR 1.05, 95% CI 1.03–1.08, P < .01, I2 = 0%). ConclusionsCompared with younger patients, older patients receiving CRT were equally likely to experience improvement in LVEF, left ventricular end-diastolic diameter, and NYHA functional class. There was no difference in procedural complications. The higher rate of all-cause mortality in older patients likely reflects a greater underlying risk of death from competing causes.

Radial strain imaging-guided lead placement for improving response to cardiac resynchronization therapy in patients with ischaemic cardiomyopathy: the Raise CRT trial.

To evaluate the benefit of speckle tracking radial strain imaging (STRSI)-guided left ventricular (LV) lead (LVL) positioning in cardiac resynchronization therapy (CRT) in patients (pts) with ischaemic cardiomyopathy with CRT indication. We conducted a prospective randomized controlled trial. Patients were enrolled in nine centres with 2:1 randomization into two groups (guided vs. control). Patients underwent STRSI to identify the optimal LV position from six LV segments at midventricular level. Implantation via STRSI was attempted for recommended segment in the guided group only. Follow-up included echocardiography (6 months) and clinical evaluation (6 and 12 months). The primary endpoint was comparison % reduction in LV end-systolic volume at 6 months with baseline. Secondary endpoints included hospitalizations for heart failure and death, and improvement in additional echocardiographic measurements and quality of life score. A total of 172 patients (115 guided vs. 57 control) were enrolled. In the guided group, 60% of the implanted LV leads were adjudicated to be successfully located at the recommended segment, whereas in the control group 44% reached the best STRSI determined segment. There was no difference between the groups in any of the primary or secondary endpoints at 6 and 12 months. Our findings suggest that echo-guided implantation of an LV lead using STRSI does not improve the clinical or echocardiographic response compared with conventional implantation.

Redefining the Classifications of Response to Cardiac Resynchronization Therapy: Results From the REVERSE Study.

This study sought to assess the impact of a more detailed classification of response on survival. Cardiac resynchronization therapy (CRT) improves functional status and outcomes in selected populations with heart failure (HF). However, approximately 30% of patients do not improve with CRT by various metrics, and they are traditionally classified as nonresponders. REVERSE (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction) was a randomized trial of CRT among patients with mild HF. Patients were classified as Improved, Stabilized, or Worsened using prespecified criteria based on the clinical composite score (CCS) and change in left ventricular end-systolic volume index (LVESVi). All-cause mortality across CRT ON subgroups at 5 years was compared. Of the 406 subjects surviving 1 year, 5-year survival differed between CCS subgroups (p=0.03), with increased mortality in the Worsened response group. Of the 353 subjects with adequate echocardiograms, survival differed significantly between response groups (p<0.001), also due to increased mortality in the Worsened group. When combining CCS and LVESVi results, the lowest survival was observed among subjects who worsened for both measures, whereas the highest survival occurred in subjects who did not worsen by either endpoint. Multivariate analysis showed that LVESVi worsening with CRT at 6months, baseline LVESVi, and gender were independent predictors of survival. For both CCS and reverse remodeling, patients who worsen with CRT have a high mortality, although remodeling was the more important endpoint. Patients who stabilize early with CRT have a much better prognosis than previously recognized, suggesting that the current convention of nonresponder classification should be modified. (REVERSE [Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction]; NCT00271154).

A multicenter prospective randomized controlled trial of cardiac resynchronization therapy guided by invasive dP/dt.

BackgroundNo periprocedural metric has demonstrated improved cardiac resynchronization therapy (CRT) outcomes in a multicenter setting.ObjectiveWe sought to determine if left ventricular (LV) lead placement targeted to the coronary sinus (CS) branch generating the best acute hemodynamic response (AHR) results in improved outcomes at 6 months.MethodsIn this multicenter randomized controlled trial, patients were randomized to guided CRT or conventional CRT. Patients in the guided arm had LV dP/dtmax measured during biventricular (BIV) pacing. Target CS branches were identified and the final LV lead position was the branch with the best AHR and acceptable threshold values. The primary endpoint was the proportion of patients with a reduction in LV end-systolic volume (LVESV) of ≥15% at 6 months.ResultsA total of 281 patients were recruited across 12 centers. Mean age was 70.8 ± 10.9 years and 54% had ischemic etiology. Seventy-three percent of patients in the guided arm demonstrated a reduction in LVESV of ≥15% at 6 months vs 60% in the conventional arm (P = .02). Patients with AHR ≥ 10% were more likely to demonstrate a reduction of ESV ≥ 15% (84% of patients with an AHR ≥10% vs 28% with an AHR <10%; P < 0.001). Procedure duration and fluoroscopy times were longer in the pressure wire–guided arm (104 ± 39 minutes vs 142 ± 39 minutes; P < .001 and 20 ±16 minutes vs 28 ± 15 minutes; P = .002).ConclusionsAHR determined by invasively measuring LV dP/dtmax during BIV pacing predicts reverse remodeling 6 months after CRT. Patients in whom LV dP/dtmax was used to guide LV lead placement demonstrated better rates of reverse remodeling.

Differences in clinical characteristics and reported quality of life of men and women undergoing cardiac resynchronization therapy.

AimsResponse to cardiac resynchronization therapy (CRT) is known to be associated with a number of clinical characteristics, including QRS duration and morphology, gender, height, and the aetiology of heart failure (HF). We assessed the relation of gender and baseline characteristics with QRS duration and Kansas City Cardiomyopathy Questionnaire.Methods and resultsAdaptResponse is a global randomized trial. The trial enrolled CRT‐indicated patients with New York Heart Association classes II–IV HF, left bundle branch block (QRS ≥ 140 ms in men, ≥130 ms in women), and baseline PR interval ≤200 ms. In total, 3620 patients were randomized, including 1569 women (43.3%) approaching the actual proportion of women in the HF population. Women were older and more often New York Heart Association class III or IV than men (55.6% vs. 48.7%), had less frequent ischaemic cardiomyopathy (21.2% vs. 39.5%), and had a 5.1 ms shorter QRS duration than men. Women were more often depressed (18.5% vs. 9.7%), had a significantly lower Kansas City Cardiomyopathy Questionnaire score, and had differences in medication prescriptions.ConclusionsAdaptResponse is the largest randomized CRT trial and enrolled more women than any other landmark CRT trial. Women differed from men with regard to baseline characteristics and quality of life. Whether these differences translate into clinical outcome differences will be examined further in the AdaptResponse trial.

P1166Women as candidates for CRT: Are they less but better?

Abstract Introduction Women have been under-represented in trials of cardiac resynchronization therapy (CRT). Most available data suggest that CRT has a greater clinical benefit in women than in men. However, further studies are needed to investigate the exact reasons for these results. Purpose To compare the prognostic impact and response rate of CRT in women and man. Methods Prospective study, single-center study that included pts undergoing CRT implant from 2015 to 2019. Clinical and echocardiographic evaluation were made before CRT implant and between 6-12 months post-implant. Pts with EF elevations≥10% or LV end-systolic volume (ESV) reductions≥15% were classified as responders. Patients with EF elevations ≥ 20% or ESV reductions≥30% were classified as super-responders. All the parameters were compared between women and man. Prognostic impact of CRT was evaluated as total mortality by the Cox regression and Kaplan-Meier methods. Results From 2015-2019, 561 patients were submitted to CRT implant with a follow-up duration of 18.9 ± 15.8 months. From these 148 (26.4%) were female (mean age 72.2 ± 10 years, 22.4% ischemic, LVEF &amp;lt; 30% in 70.2%). The cardiovascular risk factors and comorbidities were similar in both populations (women and men). In the female group, dilated cardiomyopathy was more frequent than in men (71% vs 50.8%, p &amp;lt; 0.01), with ischemic heart disease being the second most frequent etiology of heart failure. The frequency of LBBB was similar in both groups (63.9% in women and 57.0% in men, p = NS) however the QRS duration was higher in women (164 ± 17 vs 160 ± 24, p = 0.017). The baseline mean EF was similar (30.5 ± 10.3ms in women and 30.3 ± 11.4ms in men) but the ESV was lower (109.7 ± 59.9 vs 138.4 ± 64.6, p &amp;lt; 0.001). The prevalence of complications and need for surgical revision were similar in both groups. The rate of CRT responders was similar in both groups, although tendentially higher in women (64.3% in women vs 55.2% in men, p = NS). On the other hand, super-responder rate was statistically significant (38% in women vs 25.1% in men, p = 0.004). The long-term survival was similar in both groups. Conclusion The rate of super-responders was higher in women than in men. This may be explained by the higher prevalence of dilated cardiomyopathy in this subgroup of patients and by the fact that women have smaller hearts and a larger QRS duration at baseline, most likely to have a real LBBB. Long-term mortality of CRT was not gender related Abstract Figure. Long-term survival by gender

A randomized controlled trial of cardiac resynchronization therapy in patients with prolonged atrioventricular interval: the REAL-CRT pilot study.

A prolonged PR interval is known to be associated with increased mortality and a higher risk of developing atrial fibrillation (AF). We tested the hypothesis that cardiac resynchronization therapy (CRT) is superior to conventional dual-chamber pacing with algorithms for right ventricular pacing avoidance (DDD-VPA) in preserving systolic and diastolic function and in preventing new-onset AF in patients with normal systolic function, indication for pacing and prolonged atrioventricular conduction (PR interval ≥220 ms). We randomly assigned 82 patients with ejection fraction >35%, indication for pacing and PR interval ≥220 ms to CRT or to DDD-VPA. On 12-month follow-up examination, the study and control arms did not differ in terms of left ventricular end-systolic volume (44 ± 17 mL vs. 47 ± 16 mL, P = 0.511) or ejection fraction (55 ± 6% vs. 57 ± 8%, P = 0.291). The E to A mitral wave amplitude ratio was higher in the CRT arm (1.3 ± 1.3 vs. 0.8 ± 0.4, P = 0.046) and the E wave deceleration time was longer (262 ± 83 ms vs. 205 ± 51 ms, P = 0.027). Left atrial volume was smaller in the CRT arm (64 ± 17 mL vs. 84 ± 25 mL, P = 0.035). Moreover, the functional class was lower in CRT patients (1.4 ± 0.6 vs. 1.8 ± 0.5, P = 0.010). During follow-up, CRT was associated with a lower risk of new-onset AF [hazard ratio = 0.37 (0.13-0.98), P = 0.046]. Cardiac resynchronization therapy proved superior to DDD-VPA in terms of better diastolic function, less left atrial enlargement and lower risk of new-onset AF, at 12 months. These data need to be confirmed in a larger trial with longer follow-up. URL: http://clinicaltrials.gov/ Identifier: NCT02150538.

P5679Utility of late iodine enhancement computed tomography with image subtraction in the evaluation of cardiac resynchronization therapy response

Abstract Background Despite the impressive results of the large CRT trials, it has been observed that, on an individual basis, about 30% of patients fail to respond to cardiac resynchronization therapy (CRT). The evaluation of left ventricular (LV) dyssynchrony, myocardial scar, and coronary venous anatomy by image subtraction in Late Iodine Enhancement Computed Tomography (LIE-CT) has the potential to comprehensively characterize non-responders. Purpose To assess the feasibility and the utility of image subtraction in LIE-CT in CRT patients and compare findings between responders and non-responders. Methods Monocentric prospective study of CRT patients at least 6 months after implantation who underwent post-procedural CT between March and October 2018. CRT-responders were defined as patients with an absolute increase in LV ejection fraction &gt;5%. CT-derived residual global and segmental dyssynchrony metrics, extent and location of myocardial scar, coronary venous anatomy, and position of LV lead relative to scar and segment of latest mechanical contraction were analyzed. Results Among the 29 patients (mean age 71±12 years; 72% men), 18 were responders (62%). All CT metrics evaluating residual dyssynchrony such as wall motion indexand wall thickness indexwere worse in non-responders (p&lt;0.0001 for both). In LIE-CT, predictive factors of CRT-non-response were an LV lead localized in an region of myocardial scar (p=0.0007), in a region with akinesia or dyskinesia (p=0.007), and with myocardial thickness &lt;6mm (p=0.002). Percentage of fibrosis of the myocardial mass and the presence of fibrosis in postero-lateral region were not predictive of CRT-non-response (p=0.9 and p=0.3, respectively). Of the 11 non-responder patients, 8 (73%) had at least one other coronary venous branch visualized by CT; and among those, 3 (38%) were located in an non-akinetic area with late segmental contraction. Wall Motion and LIE-CT Conclusion Image subtraction in LIE-CT in patients who had CRT is feasible and allows better characterization of CRT-non-responders, who have a greater amount of residual dyssynchrony than responders. Distribution of fibrosis in relation to the LV lead and presence of alternative venous branches may help patient management.

&lt;p&gt;Heart failure hospitalization reduction and cost savings achieved by improved delivery of effective biventricular pacing: economic implications of the OLE study under the US setting&lt;/p&gt;

Background: The hOLter for Efficacy analysis (OLE) study demonstrated that current device pacing diagnostics overestimate the amount of cardiac resynchronization therapy (CRT) pacing that effectively stimulates the cardiac tissue. Sub-optimal pacing increases mortality, hospitalizations, and associated health-care costs. We sought to estimate the expected number of hospital admissions due to heart failure (HF) and its respective financial impact in patients with maximized effective pacing versus conventional pacing.Methods: A Markov model was developed to project HF hospitalizations and quantify the costs that could be avoided if pacing was maximally effective. OLE data were used to inform the prevalence of ineffective pacing among CRT patients and and average loss of pacing by causes. Adaptive CRT trial data quantified the reduction in underlying hospitalization risk by increasing effective pacing delivered. Survival was informed by a meta-analysis of 5 randomized clinical trials. Costs were analyzed from a US payer perspective.Results: Projected average hospitalizations totaled 4.58 over a lifetime horizon for CRT patients with conventional pacing. Maximizing effective pacing delivery was projected to avoid 1.83 HF admissions/patient over the lifetime. This equates to a savings of 40% (US$22,802) compared with conventional pacing from the Medicare perspective. In a sensitivity analysis, CRT with effective pacing was projected to provide cost savings in all scenarios.Conclusions: Maximized effective pacing leads to a lower number of HF hospitalizations, thus allowing significant cost offsets in the US setting.

Long-term outcomes of cardiac resynchronization therapy in adult congenital heart disease.

Background and AimsRandomized, controlled trials of cardiac resynchronization therapy (CRT) excluded patients with adult congenital heart disease (ACHD). We sought to explore long‐term clinical outcomes.Methods and ResultsIn this single‐center, observational study, events were collected from hospital records on patients with structural ACHD (sACHD) and adults with ischemic (ICM) or nonischemic (NICM) cardiomyopathy undergoing CRT. Patients with sACHD (n = 23, age: 41.6 ± 13.5 years [mean ± standard deviation]) and adults with ICM (n = 533) or NICM (n = 458) were followed‐up for 4.1 years (median; interquartile range: 2.2‐6.1). Total mortality was 5/23 (21.7%; 4.4 per 100 person‐years) in sACHD, 221/533 (41.5%; 11.8 per 100 person‐years) in ICM, and 154/458 (33.6%; 9.7 per 100 person‐years) in NICM. In univariate analyses, total mortality in sACHD was lower than in ICM (hazard ratio [HR]: 0.38; 95% confidence interval [CI] 0.15‐0.91), but similar to NICM (HR: 0.48, 95% CI 0.20‐1.16). Cardiac mortality in sACHD was similar to ICM (HR: 0.78, 95% CI 0.32‐1.92) and NICM (HR: 1.12, 95% CI 0.45‐2.78). Heart failure (HF) hospitalization rates were similar to ICM (HR: 0.44, 95% CI 0.11‐1.77) and NICM (HR: 0.75, 95% CI 0.18‐3.08). In multivariate analyses, no differences emerged in total mortality, cardiac mortality, or HF hospitalization between sACHD and NICM or ICM, after adjustment for age, sex, New York Heart Association class, diabetes, atrial rhythm, QRS duration, QRS morphology, systemic ventricular ejection fraction, and medical therapy.ConclusionTotal mortality, cardiac mortality, and HF hospitalization after CRT in patients with sACHD was similar to adults with ICM or NICM.

Renal function and the long-term clinical outcomes of cardiac resynchronization therapy with or without defibrillation.

Background and AimsPatients with moderate‐to‐severe chronic kidney disease (CKD) are underrepresented in clinical trials of cardiac resynchronization therapy (CRT)‐defibrillation (CRT‐D) or CRT‐pacing (CRT‐P). We sought to determine whether outcomes after CRT‐D are better than after CRT‐P over a wide spectrum of CKD.Methods and ResultsClinical events were quantified in relation to preimplant estimated glomerular filtration rate (eGFR) after CRT‐D (n = 410 [39.2%]) or CRT‐P (n = 636 [60.8%]) implantation. Over a follow‐up period of 3.7 years (median, interquartile range: 2.1–5.7), the eGFR < 60 group (n = 598) had a higher risk of total mortality (adjusted hazard ratio [aHR]: 1.28; P = 0.017), total mortality or heart failure (HF) hospitalization (aHR: 1.32; P = 0.004), total mortality or hospitalization for major adverse cardiac events (MACEs, aHR: 1.34; P = 0.002), and cardiac mortality (aHR: 1.33; P = 0.036), compared to the eGFR ≥ 60 group (n = 448), after covariate adjustment. In analyses of CRT‐D versus CRT‐P, CRT‐D was associated with a lower risk of total mortality (eGFR ≥ 60 HR: 0.65; P = 0.028; eGFR < 60 HR: 0.64, P = 0.002), total mortality or HF hospitalization (eGFR ≥ 60 aHR: 0.66; P = 0.021; eGFR < 60 aHR: 0.69, P = 0.007), total mortality or hospitalization for MACEs (eGFR ≥ 60 aHR: 0.70; P = 0.039; eGFR < 60 aHR: 0.69, P = 0.005), and cardiac mortality (eGFR ≥ 60 aHR: 0.60; P = 0.026; eGFR < 60 aHR: 0.55; P = 0.003).ConclusionIn CRT recipients, moderate CKD is associated with a higher mortality and morbidity compared to normal renal function or mild CKD. Despite less favorable absolute outcomes, patients with moderate CKD had better outcomes after CRT‐D than after CRT‐P.

Abstract 17058: Generalizability of Outcomes From Cardiac Resynchronization Therapy Trials to African-Americans

Generalizability of Outcomes from Cardiac Resynchronization Therapy Trials to African-Americans Introduction: Underrepresentation of African-Americans in clinical trials calls to question the generalizability of the observed results to this population. Methods: We studied 294 Caucasians and African-Americans and compared outcomes with those reported in major cardiac resynchronization therapy trials (CRT). Results from MIRACLE, COMPANION, CARE-HF, REVERSE, and MADIT-CRT were analyzed. Kaplan-Meier survival analysis and Cox proportional hazards regression were applied to our dataset. Results: We included 294 patients (45% African-Americans). In African-Americans the mean age was 65±12 compared with 70±13 for Caucasians, (p=0.0003). The median follow-up was 8.1± 6 years. Baseline characteristics were similar to landmark trials in age, ejection fraction, proportion with ischemic cardiomyopathy (ICM), diabetes mellitus and glomerular filtration rate (GFR). African-Americans had similar NYHA functional class as in MIRACLE, COMPANION, and CARE-HF. Survival in our patients was 7.6±0.3 years (95% CI 6.9-8.2). There was no difference in mortality between African-Americans (28%,) and Caucasians (37%, P=0.19) compared with that reported in MADIT-CRT (29 and 22%, respectively). Treatment with an aldosterone antagonist and a GFR greater than 60 were associated with lower mortality (P=0.04 and P=0.005, respectively). In African-Americans lack of treatment with an angiotensin converting-enzyme inhibitor (ACEI), GFR less than 60, and ischemic cardiomyopathy (ICM) were associated with increased mortality when compared with Caucasians (P=0.01, P=0.03, and P=0.04, respectively). In Caucasians, none of these variables were associated with increased mortality. Conclusions: Despite lack of specificity in details from the major trials, African-Americans had similar mortality outcomes as reported in the initial trials. These results support extrapolations of outcomes from landmark trials to African-Americans.