An individual patient meta-analysis of five randomized trials assessing the effects of cardiac resynchronization therapy on morbidity and mortality in patients with symptomatic heart failure

AimsCardiac resynchronization therapy (CRT) with or without a defibrillator reduces morbidity and mortality in selected patients with heart failure (HF) but response can be variable. We sought to identify pre-implantation variables that predict the response to CRT in a meta-analysis using individual patient-data.Methods and resultsAn individual patient meta-analysis of five randomized trials, funded by Medtronic, comparing CRT either with no active device or with a defibrillator was conducted, including the following baseline variables: age, sex, New York Heart Association class, aetiology, QRS morphology, QRS duration, left ventricular ejection fraction (LVEF), and systolic blood pressure. Outcomes were all-cause mortality and first hospitalization for HF or death. Of 3782 patients in sinus rhythm, median (inter-quartile range) age was 66 (58-73) years, QRS duration was 160 (146-176) ms, LVEF was 24 (20-28)%, and 78% had left bundle branch block. A multivariable model suggested that only QRS duration predicted the magnitude of the effect of CRT on outcomes. Further analysis produced estimated hazard ratios for the effect of CRT on all-cause mortality and on the composite of first hospitalization for HF or death that suggested increasing benefit with increasing QRS duration, the 95% confidence bounds excluding 1.0 at ~140 ms for each endpoint, suggesting a high probability of substantial benefit from CRT when QRS duration exceeds this value.ConclusionQRS duration is a powerful predictor of the effects of CRT on morbidity and mortality in patients with symptomatic HF and left ventricular systolic dysfunction who are in sinus rhythm. QRS morphology did not provide additional information about clinical response. ClinicalTrials. NCT00170300, NCT00271154, NCT00251251. © The Author 2013

The Association of Left Ventricular Remodeling with CRT Outcomes

International audienceBACKGROUND: Cardiac resynchronization therapy (CRT) response stratified by left ventricular (LV) remodeling revealed differing mortality profiles for distinct patient cohorts. Measuring functional endpoints, 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. OBJECTIVE: To evaluate long-term CRT outcomes by extent of LV remodeling. METHODS: REsynchronization reVErses Remodeling in Systolic Left vEntricular Dysfunction (NCT00271154) was a prospective, double-blind, randomized CRT trial. Patients were classified based on LV end-systolic volume (LVESV) change from baseline to 6-months post-CRT: Worsened (increase); Stabilized (0 to ≤15% reduction); Responder (>15 to < 30% reduction); and Super-responder (≥30% reduction). Subjects were evaluated annually for 5 years. RESULTS: The analyses included 353 patients randomized to CRT-ON arm. All-cause mortality was higher in the worsened group compared with the 3 other response groups (29.8% vs 8.0%, p<0.0001), with no difference in survival among those groups (p=0.87). A significant interaction between LVESV group and time was observed for health status and quality of life (both p=0.02). The interaction was not significant for 6-minute hall walk (p=0.79); however, super-responders had increased walk distance compared to the 3 other response groups (p=0.03). CONCLUSION: 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 consideration of functional and mortality endpoints to assess CRT efficacy and provide further evidence the dichotomous ’responder and non-responder’ classification should be modified

The interaction of sex, height, and QRS duration on the effects of cardiac resynchronization therapy on morbidity and mortality: an individual-patient data meta-analysis

AIMS: To explore possible associations that may explain the greater benefit from cardiac resynchronization therapy (CRT) reported amongst women. METHODS AND RESULTS: In an individual-patient data meta-analysis of five randomized controlled trials, all-cause mortality and the composite of all-cause mortality or first hospitalization for heart failure (HF) were compared among 794 women and 2702 men assigned to CRT or a control group. Multivariable analyses were performed to assess the impact of sex, QRS duration, HF aetiology, left ventricular end-diastolic diameter (LVEDD), and height on outcome. Women were shorter, had smaller LVEDD, more often left bundle branch block, and less often ischaemic heart disease, but QRS duration was similar between sexes. Women tended to obtain greater benefit from CRT but sex was not an independent predictor of either outcome. For all-cause mortality, QRS duration was the only independent predictor of CRT benefit. For the composite outcome, height and QRS duration, but not sex, were independent predictors of CRT benefit. Further analysis suggested increasing benefit with increasing QRS duration amongst shorter patients, of whom a great proportion were women. CONCLUSIONS: In this individual-patient data meta-analysis, CRT benefit was greater in shorter patients, which may explain reports of enhanced CRT benefit among women. Further analyses are required to determine whether recommendations on the QRS threshold for CRT should be adjusted for height. (ClinicalTrials.gov numbers: NCT00170300, NCT00271154, NCT00251251)

Left atrial function, a new predictor of response to cardiac resynchronization therapy?: Left atrium and resynchronization

International audienceBackground - Cardiac resynchronization therapy (CRT) improves left ventricular (LV) function and induces LV remodeling, and it is an established therapy for advanced heart failure with prolonged QRS duration. One third of patients will not benefit from this invasive therapy. Objective - The purpose of this study was to evaluate whether left atrial (LA) strain imaging (ε) parameters could help in predicting the response in terms of LV reverse remodeling after CRT. Methods - A total of 79 patients who underwent CRT were evaluated with echography before implantation. LA function and LV function were assessed with M-mode, 2-dimensional echocardiography, Doppler, tissue Doppler velocity, and ε. LV reverse remodeling was defined as a >15% reduction in LV end-systolic volume. Results - At 6 months, 54 patients (68%) were responders to CRT. In multivariable logistic regression, LA systolic peak of strain rate (SRA) (odds ratio [OR} 10.5, 95% confidence interval [CI] 1.76-62.1, P = .01), left bundle branch block (OR 6.8, 95% CI 1.06-43.9, P = .04), ischemic cardiomyopathy (OR 3.93, 95% CI 1.07-14.4, P = .04), and LV preejection index (OR 1.03, 95% CI 1.01-1.05, P = .01) were associated with CRT response. With an SRA cutoff of -0.75%, the negative predictive value for predicting CRT response was 0.62. Conclusion - This study demonstrated the possible relevance of assessing LA function before CRT. SRA appeared to be a good predictor of CRT response. Integrating this LA function analysis into the multivariable assessment of patient candidates for CRT should be considered

0548: Heart failure with preserved ejection fraction: an echocardiographic based approach to assess the prognosis. A report from the large prospective KaRen study

BackgroundKaRen is a prospective study designed to characterize and follow a cohort of heart failure with preserved ejection fraction (HFpEF) patients. HFpEF remains a challenging syndrome. Patients have clinical signs linked to congestion but left ventricular (LV) EF is > 45%. We sought to test the relevance of echocardiographic parameters as predictors of death or hospitalization for cardiovascular reasons.Methods and resultsFollowing an acute HF accompanied with NT-proBNP >300pg/ml (BNP >100pg/ml) and LVEF >45%, patients were included (n=349). The patients were reassessed by echo-Doppler after 4-8 weeks. Echocardiographies were standardized and the analysis centralized. LVEF was 62±13%, LV global longitudinal strain: – 15±3%, E/e’:12.9±6.2, Left atrial volume: 49±18ml/m², Tricuspid regurgitation: 2.9±0.9m/s. Two parameters are correlated with the survival without any death or hospitalisation for cardiovascular reason and could be combined in a score: 2 x (E / e’) + RA area. This score has a theoretical range between 0 and 14. Based on tertiles of the score, censoring (frequencies of death or hospitalization for heart failure) were 48 (37.80), 67 (57.76) and 85 (75.22) in the 1st tertile – poor prognosis (N = 127), the 2nd tertile – intermediate (N = 116) and the 3rd tertile – good prognosis (N = 113), respectively.ConclusionCombination of simple echocardiographic criteria (right atrial area and E/e’ ratio) was found relevant to predict the long term prognosis in a large cohort of patients diagnosed for heart failure with preserved ejection fraction

Implantable Defibrillators Improve Survival in Patients With Mildly Symptomatic Heart Failure Receiving Cardiac Resynchronization Therapy:Analysis of the Long-Term Follow-Up of Remodeling in Systolic Left Ventricular Dysfunction (REVERSE)

International audienceBackground- Cardiac resynchronization therapy (CRT) decreases mortality, improves functional status, and induces reverse left ventricular remodeling in selected populations with heart failure. These benefits have been noted with both CRT-pacemakers as well as those devices with defibrillator backup (CRT-D). However, there are little data comparing mortality between these 2 device types. Methods and Results- REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction (REVERSE) was a multicenter, randomized trial of CRT among patients with mild heart failure. Long-term annual follow-up for 5 years was preplanned. The present analysis was confined to the 419 patients who were randomized to active CRT group. CRT-pacemakers or CRT-D devices were implanted based on national guidelines at the time of enrollment, with 74 patients receiving CRT pacemaker devices and the remaining 345 patients receiving CRT-D devices. After 12 months of CRT, changes in the clinical composite score, left ventricular end systolic volume index, 6-minute walk time, and quality of life indices were similar between CRT pacemaker and CRT-D patients. However, long-term follow-up showed lower morality in the CRT-D group. Specifically, multivariable analysis showed that CRT-D (hazard ratio, 0.35; P=0.003) was a strong independent predictor of survival. Female sex, longer unpaced QRS duration, and smaller baseline left ventricular end systolic volume index also were also associated with better survival. Conclusions- REVERSE demonstrated that the addition of implantable cardioverter-defibrillator therapy to CRT is associated with improved long-term survival compared with CRT pacing alone in mild heart failure. Clinical Trial Registration- URL: http://clinicaltrials.gov. Unique Identifier: NCT00271154

Pilot study using 3D-longitudinal strain computation in a multi-parametric approach for best selecting responders to cardiac resynchronization therapy

International audienceBACKGROUND: Almost all attempts to improve patient selection for cardiac resynchronization therapy (CRT) using echo-derived indices have failed so far. We sought to assess: the performance of homemade software for the automatic quantification of integral 3D regional longitudinal strain curves exploring left ventricular (LV) mechanics and the potential value of this tool to predict CRT response. METHODS: Forty-eight heart failure patients in sinus rhythm, referred for CRT-implantation (mean age: 65 years; LV-ejection fraction: 26%; QRS-duration: 160 milliseconds) were prospectively explored. Thirty-four patients (71%) had positive responses, defined as an LV end-systolic volume decrease ≥15% at 6-months. 3D-longitudinal strain curves were exported for analysis using custom-made algorithms. The integrals of the longitudinal strain signals (I L,peak) were automatically measured and calculated for all 17 LV-segments. RESULTS: The standard deviation of longitudinal strain peak (SDI L,peak ) for all 17 LV-segments was greater in CRT responders than non-responders (1.18% s(-1) [0.96; 1.35] versus 0.83% s(-1) [0.55; 0.99], p = 0.007). The optimal cut-off value of SDI L,peak to predict response was 1.037%.s(-1). In the 18-patients without septal flash, SDI L,peak was significantly higher in the CRT-responders. CONCLUSIONS: This new automatic software for analyzing 3D longitudinal strain curves is avoiding previous limitations of imaging techniques for assessing dyssynchrony and then its value will have to be tested in a large group of patients