Cardiac Resynchronization Therapy With Defibrillator Therapy Research Articles

P2856Risk factors for the first and second inappropriate implantable cardioverter-defibrillator therapy: a subanalysis of the NIPPON storm study

Abstract Background Implantable cardioverter-defibrillator (ICD) including cardiac resynchronization therapy with defibrillator (CRT-D) has become an established therapeutic option to reduce the risk of sudden cardiac death. However, there are risks for the first and second inappropriate ICD shock events, which have not been well clarified. Objective To clarify the risk factors for the first and second inappropriate ICD therapy events. Methods We conducted a post-hoc, secondary analysis of the data from a multicenter, prospective, observational study (the Nippon Storm Study), designed to clarify the risk factors for electrical storm. The analysis included the data of 1549 of the 1570 patients with ICD or CRT-D enrolled into the study. An inappropriate event was defined as any inappropriate ICD or CRT-D therapy delivered, including antitachycardia pacing (ATP) or ICD shock for sinus tachycardia, atrial fibrillation (AF)/ atrial flutter (AFL), regular supraventricular tachycardia, or for non-arrhythmic events Results Over a median follow-up of 28 months, 293 inappropriate ICD therapy events occurred in 153 of the 1549 patients (10.0%) in the study sample, with 106 inappropriate ICD shock events identified in 72 (4.6%) patients. Inappropriate therapy events were unlikely during sleep. On multivariate Cox regression analysis, the risk factors for the first inappropriate ICD therapy included, younger age (hazard ratio (HR), 0.986; 95% confidence interval (CI), 0.973–0.998; p=0.028), AF/AFL (AF/AFL; HR, 2.324; 95% CI, 1.372–3.939; p=0.002), ICD implantation (HR, 2.377; 95% CI, 1.332–4.244; p=0.004), and multiple versus single stimulation zone (HR, 1.852; 95% CI, 1.163–2.951, p=0.010). After the first inappropriate ICD therapy event, any interventions were performed, including a change in the ICD programming (n=122), initiation or change in medication (n=33) and catheter ablation (n=7), or a combination of interventions. The rate of the second inappropriate ICD therapy event after treatment of the first was 37.6% at one year. The patients who underwent an intervention after the first inappropriate ICD event showed a lower risk of the second event, compared to those without any intervention (1.0% versus 6.0% at one week, 4.2% versus 22.3% at one month, 27.3% versus 57.4% at one year, log-rank p<0.001). On multivariate Cox regression analysis, the risk factors for the second inappropriate ICD therapy was no-intervention after the first inappropriate ICD therapy (HR, 3.521; 95% CI, 1.773–6.993; p=0.001). Conclusions The risk for the first inappropriate ICD therapy increased for younger patients, use of ICD versus CRT-D and a prior history of AF/AFL. Intervention after the first inappropriate ICD therapy could reduce the risk of the second inappropriate event.

Cardiac Resynchronization Defibrillator Therapy for Nonspecific Intraventricular Conduction Delay Versus Right Bundle Branch Block

BackgroundThe benefits of cardiac resynchronization therapy (CRT) in patients with non-left bundle branch block (LBBB) conduction abnormality have not been fully explored. ObjectivesThis study sought to evaluate clinical outcomes among Medicare-aged patients with nonspecific intraventricular conduction delay (NICD) versus right bundle branch block (RBBB) in patients eligible for implantation with a CRT with defibrillator (CRT-D). MethodsUsing the National Cardiovascular Data Registry implantable cardioverter-defibrillator (ICD) registry data between 2010 and 2013, the authors compared outcomes in CRT-eligible patients implanted with CRT-D versus ICD-only therapy among patients with NICD and RBBB. Also, among all CRT-D–implanted patients, the authors compared outcomes in those with NICD versus RBBB. Survival curves and multivariable adjusted hazard ratios (HRs) were used to assess outcomes including hospitalization and death. ResultsIn 11,505 non-LBBB CRT-eligible patients, after multivariable adjustment, among patients with RBBB, CRT-D was not associated with better outcomes, compared with ICD alone, regardless of QRS duration. Among patients with NICD and a QRS ≥150 ms, CRT-D was associated with decreased mortality at 3 years compared with ICD alone (HR: 0.602; 95% confidence interval [CI]: 0.416 to 0.871; p = 0.0071). Among 5,954 CRT-D–implanted patients, after multivariable adjustment NICD compared with RBBB was associated with lower mortality at 3 years in those with a QRS duration of ≥150 ms (HR: 0.757; 95% CI: 0.625 to 0.917; p = 0.0044). ConclusionsAmong non-LBBB CRT-D–eligible patients, CRT-D implantation was associated with better outcomes compared with ICD alone specifically in NICD patients with a QRS duration of ≥150 ms. Careful patient selection should be considered for CRT-D implantation in patients with non-LBBB conduction.

Association of body mass index with cardiac resynchronization therapy intention and left ventricular lead implantation failure: insights from the NCDR implantable cardioverter-defibrillator registry.

Cardiac resynchronization therapy with defibrillator (CRT-D) implantation involves left ventricular (LV) lead placement for biventricular pacing and is more complex than implantable cardioverter-defibrillator (ICD)-only implantation. Differences in the prescription of CRT-D versus ICD may result from clinician biases based on patient body habitus, and body habitus may be associated with LV lead implantation failure. We sought to evaluate whether patient body mass index (BMI) was associated with planned use and implantation failure of CRT-D therapy. We studied all patients enrolled in the National Cardiovascular Data Registry ICD Registry who met standard CRT-D criteria and received either an ICD or CRT-D between 2010 and 2012. BMI was categorized based on World Health Organization classification. Using hierarchical logistic regression, two multivariate models adjusted for patient demographic and clinical characteristics were fit based on the following outcome variables: (1) planned implantation with CRT-D versus ICD and (2) failed versus successful LV lead placement. Of 337,547 patients, 41,872 met inclusion criteria for the first analysis and 35,186 met criteria for the second analysis. After multivariable adjustment, patients with extreme (BMI > 40kg/m2) obesity were less likely to receive guideline-concordant CRT-D compared with patients with normal weight (adjusted odds ratio (AOR), 0.86; 95% confidence interval (CI), 0.75-0.99; p = 0.04). Extreme (BMI > 40kg/m2) obesity was associated with higher odds of failed LV lead placement (AOR, 1.35; 95% CI, 1.07-1.72, p = 0.01). Compared with normal weight patients, extremely obese (BMI > 40kg/m2) CRT-D eligible patients were less likely to be prescribed CRT-D and were at higher odds for failed LV lead placement.

Long-term outcomes of cardiac resynchronization therapy by left ventricular ejection fraction.

Despite our prior report suggesting heart failure (HF) risk reduction from cardiac resynchronization therapy with defibrillator (CRT-D) in mild HF patients with higher left ventricular ejection fraction (LVEF > 30%), data on mortality benefit in this cohort are lacking. We aimed to assess long-term mortality benefit from CRT-D in mild HF patients by LVEF > 30%. Among 1274 patients with mild HF and left bundle branch block enrolled in MADIT-CRT, we analysed long-term effects of CRT-D vs. implantable cardioverter defibrillator (ICD) therapy only, and reverse remodelling to CRT-D (left ventricular end-systolic volume percent change ≥ median at 1 year), on all-cause mortality and HF for the LVEF ≤ 30% and LVEF > 30 subgroups using Kaplan-Meier and Cox analyses. During long-term follow-up, CRT-D vs. ICD was associated with reduction in all-cause mortality in both patients with LVEF > 30% and LVEF ≤ 30% [hazard ratio (HR)0.47, 95% confidence interval (CI) 0.25-0.85, P = 0.036 vs. HR 0.69, 95% CI 0.49-0.98, P = 0.013, interaction P = 0.261]. The efficacy of CRT-D vs. ICD only to reduce HF was similar in those with LVEF above and below 30% (HR 0.36, 95% CI 0.35-0.61, P < 0.001 vs. HR 0.46, 95% CI 0.35-0.61, P < 0.001; interaction P = 0.342). Patients with CRT-D-induced reverse remodelling had significant mortality reduction when compared to ICD, with either LVEF > 30% or LVEF ≤ 30% (HR 0.17 and 0.39), but no mortality benefit was seen in patients with less reverse remodelling. HF events, however, were reduced in both CRT-D-induced high and low reverse remodelling vs. ICD only, in both LVEF subgroups. In MADIT-CRT, left bundle branch block patients with higher LVEF (> 30%) derive long-term mortality benefit from CRT-D when exhibiting significant reverse remodelling. ClinicalTrials.gov ID NCT00180271, NCT01294449, and NCT02060110.

Should Cardiac Resynchronization Therapy Be a Rescue Therapy for Inotrope-Dependent Patients With Advanced Heart Failure?

BackgroundAlthough the “off-label usage” of cardiac resynchronization therapy with defibrillator (CRT-D) has spread recently in advanced heart failure (HF) patients in the real-world practice, its clinical effect remained uncertain. Methods and ResultsA total of 84 in-hospital <65-year old patients with advanced HF undergoing CRT-D were enrolled. Seventeen patients (20%) had been dependent on inotropes at the time of CRT-D implantation, and 17 suffered cardiac death within a year. Both inotrope dependence and elevated plasma levels of B-type natriuretic peptide (BNP) (>690 pg/mL) at the time of CRT-D implantation were independent predictors of cardiac death within a year by Cox regression analyses (P < 0.05 for both). These 2 parameters could significantly stratify 1-year ventricular assist device (VAD)-free survival: inotrope-free low (1) or high BNP (2), or inotrope-dependent low (3) or high BNP groups (4) (98, 77, 57, and 17%, respectively, P < 0.001). In contrast, there were no significant differences in actual 1-year survival among the four groups. ConclusionPatients dependent on inotropes sometimes receive CRT-D therapy as the last treatment resort in clinical practice, but LVAD implantation should be considered instead of CRT-D in advanced HF patients because of their poor prognosis with CRT-D therapy.

PR interval identifies clinical response in patients with non-left bundle branch block: a Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy substudy.

In Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy (MADIT-CRT), patients with non-left bundle branch block (LBBB; including right bundle branch block, intraventricular conduction delay) did not have clinical benefit from cardiac resynchronization therapy with defibrillator (CRT-D). We hypothesized that baseline PR interval modulates clinical response to CRT-D therapy in patients with non-LBBB. Non-LBBB patients (n=537; 30%) were divided into 2 groups based on their baseline PR interval as normal (including minimally prolonged) PR (PR <230 ms) and prolonged PR (PR ≥230 ms). The primary end point was heart failure or death. Separate secondary end points included heart failure events and all-cause mortality. Cox proportional hazards regression models were used to compare risk of end point events by CRT-D to implantable cardioverter defibrillator therapy in the PR subgroups. There were 96 patients (22%) with a prolonged PR and 438 patients (78%) with a normal PR interval. In non-LBBB patients with a prolonged PR interval, CRT-D treatment was associated with a 73% reduction in the risk of heart failure/death (hazard ratio, 0.27; 95% confidence interval, 0.13-0.57; P<0.001) and 81% decrease in the risk of all-cause mortality (hazard ratio, 0.19; 95% confidence interval, 0.13-0.57; P<0.001) compared with implantable cardioverter defibrillator therapy. In non-LBBB patients with normal PR, CRT-D therapy was associated with a trend toward an increased risk of heart failure/death (hazard ratio, 1.45; 95% confidence interval, 0.96-2.19; P=0.078; interaction P<0.001) and a more than 2-fold higher mortality (hazard ratio, 2.14; 95% confidence interval, 1.12-4.09; P=0.022; interaction P<0.001) compared with implantable cardioverter defibrillator therapy. The data support the use of CRT-D in MADIT-CRT non-LBBB patients with a prolonged PR interval. In non-LBBB patients with a normal PR interval, implantation of a CRT-D may be deleterious. http://clinicaltrials.gov; Unique Identifier: NCT00180271.

The Influence of Left Ventricular Ejection Fraction on the Effectiveness of Cardiac Resynchronization Therapy

The aim of this study was to evaluate the relationship between left ventricular (LV) ejection fraction and clinical outcome to cardiac resynchronization therapy (CRT) in mild heart failure patients enrolled in MADIT-CRT [corrected]. Left ventricular ejection fraction (LVEF) is a surrogate marker of heart failure (HF) status and associated risk. Data on the effectiveness of cardiac resynchronization therapy with defibrillator (CRT-D) in patients with mild HF and better LVEF are limited. In the MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy) study, the echocardiography core laboratory assessed baseline LVEF independent of the enrolling centers and identified a range of LVEFs, including those >30% (i.e., beyond the eligibility criteria). Echocardiographic response with CRT, defined as percent change in left ventricular end-diastolic volume (LVEDV), was analyzed in 3 prespecified LVEF groups: >30%, 26% to 30%, and ≤25%. The primary endpoint was HF or death. Secondary endpoint included all-cause mortality. LVEF was evaluated in 1,809 study patients. There were 696 (38%) patients with LVEF >30% (in the range of 30.1% to 45.3%); 914 patients (50.5%) with LVEF 26% to 30%; and 199 patients with LVEF ≤25% (11%). The mean reduction in LVEDV with CRT-D therapy at the 1-year follow-up was directly related to increasing LVEF (LVEF >30%: 22.3%; LVEF 26% to 30%: 20.1%; and LVEF ≤25%: 18.7% reduction, respectively [p = 0.001]). CRT-D treatment similarly reduced the risk of HF/death in patients with LVEF >30% (hazard ratio [HR]: = 0.56 [95% confidence interval (CI): 0.39 to 0.82], p = 0.003), LVEF 26% to 30% (HR: 0.67: [95% CI: 0.50 to 0.90], p = 0.007), and LVEF ≤25% (HR: 0.57 [95% CI: 0.35 to 0.95], p = 0.03; all p values for LVEF-by-treatment interactions >0.1). In MADIT-CRT, the clinical benefit of CRT was evident regardless of baseline LVEF, including those with LVEF >30%, whereas the echocardiographic response was increased with increasing LVEF, indicating that CRT might benefit patients with better LVEF. (Multicenter Automatic Defibrillator Implantation With Cardiac Resynchronization Therapy [MADIT-CRT]; NCT00180271).

Effectiveness of Cardiac Resynchronization Therapy with Defibrillator in At‐Risk Black and White Cardiac Patients

There are limited data regarding racial differences in response to cardiac resynchronization therapy with defibrillator (CRT-D). We assessed the effectiveness of CRT-D, as compared to implantable cardioverter defibrillator (ICD) therapy alone, in reducing the risk of heart failure (HF) or death and changes in cardiac volumes among 1638 (90%) white patients and 143 (8%) black patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT). Enrolled black patients displayed a higher frequency of diabetes mellitus, treated hypertension, higher creatinine levels, and a lower distance walked in the baseline 6-minute walk test. Kaplan-Meier survival analysis showed that at 3 years of follow-up the cumulative probability of HF or death was higher among blacks (29%) as compared with whites (22%; P = 0.05). Both black and white patients experienced similar and pronounced reductions in cardiac volumes with CRT-D therapy (all P values for comparison between the two groups >0.10). Risk reduction conferred by CRT-D therapy as not significantly different between blacks and whites (hazard ratio = 0.78 and 0.60, respectively; P for the difference = 0.44). However, possibly due to sample size limitations the CRT-D versus ICD only adjusted risk for HF/death in blacks was not statistically significant. Black patients in MADIT-CRT experienced increased risk of HF or death as compared with whites, but displayed a similar magnitude echocardiographic response to CRT-D. These findings suggest that cardiac resynchronization therapy may be an effective therapeutic modality in black patients. However, further studies are needed to assess the clinical response to CRT-D in this high-risk population.

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Hsu et al (J Am Coll Cardiol 2012;59:2366–2373, PMID 22698490) investigated predictors of left ventricular ejection fraction (LVEF) super response to cardiac resynchronization therapy with defibrillator (CRT-D) and whether this response translated into improved event-free survival in patients with mildly symptomatic heart failure (HF). Patients were assigned to CRT-D with paired echocardiograms at baseline and at 12 months (n = 752). Super response was defined by the top quartile of LVEF change. All 191 super responders experienced an LVEF increase of ≥14.5% (mean LVEF increase 17.5% ± 2.7%). Six predictors were associated with LVEF super response to CRT-D therapy: female sex (odds ratio [OR] 1.96; P = .001), no prior myocardial infarction (OR 1.80; P = .005), QRS duration ≥150 ms (OR 1.79; P = .007), left bundle branch block (OR 2.05; P = .006), body mass index <30 kg/m2 (OR 1.51; P = .035), and smaller baseline left atrial volume index (OR 1.47; P <.001). The probability of HF or all-cause death at 2 years was 4% in super responders, 11% in responders, and 26% in hypo-responders (P <.001). The authors conclude that 6 baseline factors predicted LVEF super response in CRT-D-treated patients with mild HF. Super response was associated with a reduced risk of subsequent cardiac events.

Predictors of Super-Response to Cardiac Resynchronization Therapy and Associated Improvement in Clinical Outcome: The MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy) Study

The authors investigated predictors of left ventricular ejection fraction (LVEF) super-response to cardiac resynchronization therapy with defibrillator (CRT-D) and whether super-response translated into improved event-free survival in patients with mildly symptomatic heart failure (HF). Few data exist on predictors of super-response to CRT-D and associated morbidity and mortality in mildly symptomatic HF populations. Patients were assigned to CRT-D with paired echocardiograms at baseline and at 12 months (n = 752). Super-response was defined by the top quartile of LVEF change. Best-subset regression analysis identified predictors of LVEF super-response. Kaplan-Meier survival analysis and Cox proportional hazards regression were performed to investigate associations of response category with development of nonfatal HF event or all-cause death. All 191 super-responders experienced an LVEF increase of ≥14.5% (mean LVEF increase 17.5 ± 2.7%). Six predictors were associated with LVEF super-response to CRT-D therapy: female sex (odds ratio [OR]: 1.96; p = 0.001), no prior myocardial infarction (OR: 1.80; p = 0.005), QRS duration ≥150 ms (OR: 1.79; p = 0.007), left bundle branch block (OR: 2.05; p = 0.006), body mass index <30 kg/m(2) (OR: 1.51; p = 0.035), and smaller baseline left atrial volume index (OR: 1.47; p < 0.001). Cumulative probability of HF or all-cause death at 2 years was 4% in super-responders, 11% in responders, and 26% in hypo-responders (log-rank p < 0.001 overall). In multivariate analysis, hyporesponse was associated with increased risk of HF or all-cause death, compared with super-response (hazard ratio: 5.25; 95% confidence interval: 2.01 to 13.74; p = 0.001). Six baseline factors predicted LVEF super-response in CRT-D-treated patients with mild HF. Super-response was associated with reduced risk of subsequent cardiac events. (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy [MADIT-CRT]; NCT00180271).

Baseline functional capacity and the benefit of cardiac resynchronization therapy in patients with mildly symptomatic heart failure enrolled in MADIT-CRT

Mildly symptomatic heart failure (HF) patients were shown to derive substantial clinical benefit from cardiac resynchronization therapy with defibrillator (CRT-D) in Multicenter Automatic Defibrillator Implantation Trial in Cardiac Resynchronization Therapy. However, the relationship between functional capacity (FC) and CRT-D benefit in the trial was not assessed. To evaluate the association between FC and response to CRT-D in Multicenter Automatic Defibrillator Implantation Trial in Cardiac Resynchronization Therapy. We evaluated the association between preimplantation FC and the benefit of CRT-D in reducing the risk of HF or death in Multicenter Automatic Defibrillator Implantation Trial in Cardiac Resynchronization Therapy. Functional status was assessed by a 6-minute walk test (6MWT), dichotomized at the median value as poor (<350 m) or good (≥350 m). Implantable cardioverter-defibrillator-only patients with a poor FC had an adjusted 73% increased risk for HF or death (P <.001) and a 2.4-fold (P = .001) increased risk for all-cause mortality. CRT-D therapy was associated with 63% (P <.001) and 44% (P <.001) reductions in the risk of HF or death among left bundle branch block patients with a poor FC and a good FC, respectively (P for interaction = .10). Among left bundle branch block patients with a poor FC, CRT-D was also associated with a significant reduction in the risk of all-cause mortality (hazard ratio 0.52; P = .015) whereas the survival benefit of CRT-D was not observed among those who had a higher FC at enrollment (hazard ratio 1.01; P = .98; P for interaction = .10). Poor FC is a strong independent predictor for mortality and HF events in patients with mildly symptomatic HF. Left bundle branch block patients with poor baseline FC derive a pronounced benefit from CRT-D, manifest by a significant reduction in mortality.

Improved Outcome with Preventive Cardiac Resynchronization Therapy in the Elderly: A MADIT‐CRT Substudy

Elderly patients comprise a large portion of patients with heart failure (HF). Limited data exist on the effectiveness of cardiac resynchronization therapy with defibrillator (CRT-D) in patients with mild HF symptoms in this population. The benefit of CRT-D compared with ICD-only therapy in reducing HF or death was assessed by age categories (prespecified as <60 [n = 548], 60-74 [n = 941], and ≥75 [n = 331] years) among 1,820 patients in MADIT-CRT. In patients with ICD-only, there was a graded age-related increase in the Kaplan-Meier cumulative probability of HF or death at 3-year follow-up (19%, 33%, and 36%, in patients aged <60, 60-74, and ≥75 years, respectively, P = 0.003). Multivariate analysis demonstrated that CRT-D therapy was associated with a significant reduction in the risks of HF or death in patients aged 60-74, and ≥75 years (HR = 0.57, P = <0.001 and HR = 0.59, P = 0.017, respectively), and no significant benefit in patients aged <60 years (HR = 0.81, P = 0.3; P-value for all treatment-by-age interactions >0.10). There was no significant difference in the rate of device-related adverse events within 90 days following CRT-D implantation among age-subgroups (16.7%, 15.7%, and 11.7%, in patients <60, 60-74, and ≥75 years, respectively, P = 0.42). CRT-D was associated with a significant clinical benefit in older patients (≥60 years) during an average 2.4-year follow-up. These effects were preserved for the elderly patients ≥75 years of age but attenuated in patients <60 years. Elderly patients had no increase in device-related adverse events compared with younger patients.

Cardiac Resynchronization Therapy Is More Effective in Women Than in Men: The MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy) Trial

The purpose of this study was to investigate the factors related to sex-specific outcomes for death and heart failure events in the MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy) trial. In the MADIT-CRT trial, women seemed to achieve a better result from resynchronization therapy than men. All 1,820 patients (453 female and 1,367 male) enrolled in the MADIT-CRT trial were included in this sex-specific outcome analysis that compared the effect of cardiac resynchronization therapy with defibrillator (CRT-D) relative to implanted cardioverter-defibrillator (ICD) on death or heart failure (whichever came first), heart failure only, and death at any time. Female patients were more likely to have nonischemic cardiomyopathy and left bundle branch block and less likely to have renal dysfunction than male patients. Overall, female patients had a better result from CRT-D therapy than male patients, with a significant 69% reduction in death or heart failure (hazard ratio: 0.31, p < 0.001) and 70% reduction in heart failure alone (hazard ratio: 0.30, p < 0.001). Women had a significant 72% reduction in all-cause mortality in the total population (hazard ratio: 0.28, p = 0.02) and significant 82% and 78% reductions in mortality in those with QRS ≥150 ms and with left bundle branch block conduction disturbance, respectively, with sex-by-treatment interactions for mortality reduction significant at p < 0.05 in each of these 3 patient groups. These beneficial CRT-D effects among women were associated with consistently greater echocardiographic evidence of reverse cardiac remodeling in women than in men. Women in the MADIT-CRT trial obtained significantly greater reductions in death or heart failure (whichever came first), heart failure alone, and all-cause mortality with CRT-D therapy than men, with consistently greater echocardiographic evidence of reverse cardiac remodeling in women than in men. (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy [MADIT-CRT]; NCT00180271 ).

Time-dependent benefit of preventive cardiac resynchronization therapy after myocardial infarction

Cardiac remodelling is a progressive process after myocardial infarction (MI). However, currently there are no data regarding the effect of s:elapsed time from MI on the benefit of cardiac resynchronization therapy with defibrillator (CRT-D). The present study was designed to evaluate the relationship between elapsed time from MI and the benefit of preventive CRT-D therapy in patients with ischaemic cardiomyopathy (ICM). The risk of heart failure (HF) or death as a function of elapsed time from MI to enrolment, by treatment with CRT-D vs. implantable cardioverter defibrillator (ICD)-only therapy, was assessed among 704 ICM patients with a documented MI enrolled in MADIT-CRT, and separately in a subset of ICM patients without a documented prior MI (n = 237). In ICD patients, the adjusted risk of HF or death increased by 4% (P = 0.01) for each year elapsed from MI. Multivariate analysis demonstrated that patients with remote MI [categorized at the median value (≥8 years)] derived a significantly greater benefit from CRT-D [HR = 0.42 (P < 0.001)] than those with a more recent MI [HR = 1.26 (P = 0.35); P-value for interaction <0.001]. Consistently, the benefit of CRT-D was directly related to increasing quartiles of elapsed time from MI [Q(1) (<3 years): HR = 1.67; P = 0.20, Q(2) (3-8 years): HR = 1.12; P = 0.71, Q(3) (8-15 years): HR = 0.47; P = 0.02, and Q(4) (≥15 years): HR = 0.38; P = 0.001]. The ICM subgroup with no documented MI also derived enhanced benefit from CRT-D (HR = 0.43; P = 0.003). In patients with ischaemic cardiomyopathy, the risk of HF or death and the magnitude of CRT-D benefit are directly related to elapsed time from MI.