Cardiac Resynchronization Therapy With Defibrillator 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.

4178Insulin treatment is associated with increased risk of device-treated ventricular tachyarrhythmia in patients with diabetes and heart failure

Abstract Background It is debated whether insulin use is associated with a pro-arrhythmic effect. There is paucity of studies investigating this aspect in patients with heart failure (HF), where use of insulin is associated with an increased mortality risk. Purpose We aimed to investigate whether patients receiving insulin had higher risk of device-treated ventricular tachyarrhythmia (VTA) in a population of HF patients with medically treated diabetes and primary prevention implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy with defibrillator (CRT-D). Methods Information on ICD/CRT-D implantation and therapy, comorbidities, diabetes, diabetes-related complications and medication were obtained through Danish nationwide registers. From 2007 through 2016 we identified all primary prevention ICD/CRT-D implantations in HF patients with diabetes, defined as treatment with antidiabetic medication within one year prior to implantation. Patients were divided into two groups; Insulin treated vs. non-insulin treated patients. Endpoints of interest were VTA, defined as appropriate ICD therapy, and all-cause mortality. Cumulative incidence curves and adjusted Cox proportional Hazards regression analyses were used to assess risk of outcomes. Adjustment variables included age, gender, ischemic heart disease (IHD), left ventricular ejection fraction (LVEF), ICD vs. CRT-D, diuretic use (as a proxy for severity of HF), prior VTA and diabetes-related complications, identified from diagnosis codes for diabetic nephro-, retino-, and neuropathy, multiple diabetic complications and unspecified diabetic complications. Results We identified 1240 patients with HF and diabetes with a primary prevention ICD/CRT-D. The majority of patients had type 2 diabetes (94%). Of these 479 patients (39%) were treated with insulin and 761 (61%) were not. Patients were primarily male (85%) with mean age of 66.9±8.3 years, mean LVEF of 25.6±7.5%, 42% had CRT-D and 58% ICD, without differences between the groups. The insulin-treated group had a higher occurrence of diabetes-related complications (81% vs. 42%, p<0.01) and IHD (95% vs. 90%, p<0.01). During a mean follow-up of 3.1±2.1 years, 74 insulin treated patients (16%) and 86 non-insulin treated patients (11%) experienced VTA (p=0.034), with higher 5-year cumulative incidence of VTA in the insulin group. Insulin treatment was associated with significantly increased risk of VTA (HR = 1.45; 95% CI [1.04–2.03], p=0.031) and all-cause mortality (HR=1.27; 95% CI [1.03–1.58], p=0.027), as compared with non-insulin treated patients. Figure 1 Conclusion In HF patients with diabetes implanted with a primary prevention ICD/CRT-D, treatment with insulin was associated with a significant 45% increased risk of device-treated ventricular tachyarrhythmias and 27% increased risk of all-cause mortality. These findings support further clinical trials to evaluate the safety of insulin in patients with HF and type 2 diabetes.

Predictors of Recurring Hospitalizations for Heart Failure during Long-Term Follow-Up in MADIT-CRT

Background There are limited data regarding predictors of recurrent hospitalization for heart failure (HHF) in mild heart failure (HF) patients during long-term follow-up. Objective We aimed to evaluate baseline risk factors for first and subsequent HHF among mild HF patients in MADIT-CRT. Methods Data regarding recurring HHF were prospectively collected for MADIT-CRT participants during long-term (7-year) follow-up. Multivariate regression analysis was used to identify predictors of recurring HHF, adjusting for treatment with cardiac resynchronization therapy with defibrillator (CRT-D). Results During long-term follow-up, 1442 patients had 0 HHF, 209 had 1 HHF, 90 had 2 HHF, and 77 had ≥3 HHFs. Predictors of first HHF included: atrial arrhythmia prior to enrollment, diabetes, prior coronary revascularization, glomerular filtration rate Conclusions Our data from the long-term follow-up of MADIT-CRT show that there are multiple baseline risk factors for first HHF following device implantation in mild HF patients, many of which do not predict subsequent HHF. These findings suggest a need to identify novel time-dependent risk factors for recurrent HHF.

Cardiac Resynchronization in Women: A Substudy of the Resynchronization-Defibrillation for Ambulatory HeartFailure Trial.

This study sought to evaluate the effect of cardiac resynchronization therapy with defibrillator (CRT-D) as compared with implantable cardioverter-defibrillator (ICD) on mortality, heart failure (HF) hospitalization, and ventricular arrhythmia in women versus men. CRT-D has demonstrated reduced mortality and HF hospitalizations with greater benefit observed in women compared with men. However, whether CRT-D prevented ventricular arrhythmias in women compared with men was unclear. The RAFT (Resynchronization-Defibrillation for Ambulatory HeartFailure Trial) study randomized 1,798 patients to an ICD or CRT-D. In this post hoc analysis, women and men were compared by randomized group. By using a multivariable model, the outcomes of death and HF hospitalization and incidence of ventricular arrhythmia were compared between men and women. There were 1,490 (83%) men (732, ICD; 758, CRT-D) and 308 (17%) women (172, ICD; 136, CRT-D) included in the analysis. Women with CRT-D had a significantly reduced incidence of death and HF hospitalization compared with men with CRT-D (hazard ratio: 0.52; 95% confidence interval: 0.33 to 0.81; p<0.001) on multivariable analysis. Women with a primary prevention indication and CRT-D had the lowest rate of ventricular arrhythmia compared with men (hazard ratio: 0.59; 95% confidence interval: 0.39 to 0.91; p=0.016). Women have improved rates of death and HF hospitalization with CRT-D and were less likely to experience ventricular arrhythmia when compared with men, after adjusting for differences in baseline characteristicsover a prolonged follow-up. Whether these improved outcomes reflect inherent sex differences in theunderlying myocardial substrate resulting in an enhanced response to CRT-D requires further research.

Body mass index and outcomes of cardiac resynchronization with implantable cardioverter-defibrillator therapy in older patients with heart failure.

To assess the association of body mass index (BMI) with heart failure (HF) outcomes after cardiac resynchronization therapy with defibrillator (CRT-D) implantation. Medicare beneficiaries with HF aged ≥ 65 years (n=18 922) undergoing first-time CRT-D from the National Cardiovascular Data Registry (NCDR) Implantable Cardioverter-Defibrillator Registry between 2010 and 2013, were followed for 3 years post-implantation. Survival curves and covariate adjusted hazard ratio (aHR) or odds ratio were used to assess the risks for death, readmission, and device-related complications by BMI status. Of 18 922 HF patients receiving CRT-D, 5265 (27.8%) were normal weight, 6896 (37%) were overweight, 6318 (33.4%) were obese, and 353 (1.8%) were underweight. Compared to those of normal weight (BMI 18.5-24.9 kg/m2 ), underweight patients had a higher 3-year post-device implantation risk of death [aHR: 1.34 (95% confidence interval 1.09-1.65); P < 0.001] and of readmission [sub-aHR: 1.25 (1.09-1.42); P < 0.001]. The corresponding 3-year aHRs for death were 0.83 (0.77-0.89) for overweight, 0.74 (0.67-0.82) for obesity class I (BMI 30-34.9 kg/m2 ), 0.78 (0.68-0.90) for obesity class II (BMI 35-39.9 kg/m2 ), and 0.75 (0.60-0.93) for obesity class III (BMI ≥ 40 kg/m2 , P for all categories < 0.001). Individuals with class III obesity had a higher risk of readmission [sub-aHR: 1.17 (1.06-1.30)]. There were no differences in rates of device-related complications within 90 days across BMI categories. Most elderly patients with HF receiving CRT-D were overweight or obese. While being underweight was associated with greater risks of death and hospitalization, overweight and obese patients were at lower risk of death after CRT-D.

Effectiveness of CRT-D Versus ICD on Prevention of Electrical Storm: Big Data from the USA.

Patients with implantable cardioverter-defibrillator (ICD) are at the risk of electrical storm (ES) occurrence associated with mortality and poor quality of life. Cardiac resynchronization therapy with defibrillator (CRT-D) minimizes inappropriate ICD shocks. However, limited reports exist on the impact of CRT-D versus traditional ICD on ES occurrences in real-life cohorts. We evaluated the implanted-device characteristics associated with ES events in a large data based on daily stored device-summaries obtained from remote monitoring data in US.Between 2004 and 2016, 19,935 US patients were implanted. Survival analyses with Cox regression for device-shock therapy were performed between patients who experienced at least one ES and those without ES. CRT-D devices (bi-ventricular) were implanted in 5522 (28%) patients during this period, and their ES events over time were compared to ICD recipients implanted with RV lead. Primary endpoint was the first ES event.ES occurred with the rate of 7.26% for all patients during the period. Cox regression analyses revealed significantly an increase risk in ES occurrences (the p-value <; 0.05 and hazard ratio >> 1) with shock therapy. CRT-D implant led to lower ES risk comparing with patients received traditional ICD (RV only).

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.

Mid-term feasibility and safety of downgrade procedure from defibrillator to pacemaker with cardiac resynchronization therapy

BackgroundsSome patients who undergo implantation of cardiac resynchronization therapy with defibrillator (CRT-D) survive long enough, thus requiring CRT-D battery replacement. Defibrillator therapy might become unnecessary in patients who have had significant clinical improvement and recovery of left ventricular ejection fraction (LVEF) after CRT-D implantation. MethodsForty-nine patients who needed replacement of a CRT-D battery were considered for exchange of CRT-D for cardiac resynchronization therapy with pacemaker (CRT-P) if they met the following criteria: LVEF >45%; the indication for an implantable cardioverter defibrillator was primary prevention at initial implantation and no appropriate implantable cardioverter defibrillator therapy was documented after initial implantation of the CRT-D. ResultsSeven patients (14.2%) were undergone a downgrade from CRT-D to CRT-P without any complications. No ventricular tachyarrhythmic events were observed during a mean follow-up of 39.7 ± 21.1 months and there was no significant change in LVEF between before and 1 year after device replacement (53.5% ± 6.2% vs. 56.4% ± 7.3%, P = 0.197). ConclusionsThis study confirmed mid-term feasibility and safety of downgrade from CRT-D to CRT-P alternative to conventional replacement with CRT-D.

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.

Cardiac resynchronization therapy improves myocardial conduction.

Cardiac resynchronization therapy (CRT) reverses left ventricular remodeling and improves left ventricular systolic function. However, little is known about whether CRT improves ventricular conduction. To determine the relationship between CRT response and QRS narrowing. The study included consecutive patients who underwent CRT with defibrillator (CRT-D) implantation between January 2002 and December 2012 and had subsequent generator replacement (GR). At the time of GR, super-responder was defined as those who had left ventricular ejection fraction (LVEF) of 50% or more; patients who had an LVEF of 36-49% with an increase of more than 5% were considered responders, and the others were nonresponders. All patients were assessed 6 months after CRT-D implantation and at the time of GR. Of 114 study patients, 58 (50.9%) were nonresponders, 29 (25.4%) responders, and 27 (23.7%) super-responders. QRS narrowing at 6 months was significant in super-responders (175.4 ± 21.4 to 159.7 ± 20.7 ms, P=0.001) and responders (169.0 ± 21.3 to 157.7 ± 17.6 ms, P=0.008). At time of GR, only super-responders had further QRS narrowing (159.7 ± 20.7 to 146.3 ± 19.2 ms, P<0.001). QRS duration change after 6 months was independently associated with super-response (hazard ratio: 1.20 for every 5 ms QRS duration narrowing; 95% confidence interval, 1.06-1.38; P=0.005), and QRS narrowing of 10 ms or more was associated with lower risk of all-cause mortality after GR. Continuous QRS narrowing after CRT, as an electrical marker, is associated with a super-response to CRT. Further QRS narrowing 6 months after CRT implantation was associated with lower risk of mortality after GR.

Atrioventricular Block During Catheter Ablation for Ventricular Arrhythmias.

This study sought to evaluate the incidence and significance of atrioventricular (AV) block associated with ventricular arrhythmia (VA) ablation. Attempted ablation of VAs that arise from the septum carries a risk of AV block. Data from 1,418 patients who had catheter ablation for drug-refractory VAs were evaluated. Two analyses were conducted. The first analysis assessed the patient and procedure characteristics associated with ablation-induced AV block. The second analysis investigated outcome differences between patients with and without AV block. For the second analysis, patients with AV block (Group I) were compared with a 1:2 propensity score-matched control group (Group II) and with patients with pre-existing AV block before ablation (Group III). Twenty-one (1.6%) patients developed AV block. In multivariable analysis, nonischemic cardiomyopathy (odds ratio: 3.33; 95% confidence interval: 1.32 to 8.40; p = 0.011) and transcoronary ethanol ablation (odds ratio: 46.50; 95% confidence interval: 14.10 to 153.00; p< 0.001) were independently associated with AV block. Subsequent to the AV block, 9 patients were upgraded from an implantable cardioverter-defibrillator to cardiac resynchronization therapy with defibrillator (CRT-D), 2 had de novo CRT-D implantation, 5 had pre-existing CRT-D, and 5 had pacing without CRT. VAs recurred in 33% of patients in Group I, 17% in Group II (log-rank p= 0.842), and 35% in Group III (p= 0.636). The composite outcome of heart failure hospitalization, heart transplantation, or death occurred in 29% of patients in Group I, 17% in Group II (p= 0.723), and 45% in Group III (p= 0.303). Complete AV block occurs in fewer than 2% of patients undergoing VA ablation and does not appeartobe associated with the worse outcome of heart failure hospitalization, heart transplantation, or death.

Predictors of long-term mortality with cardiac resynchronization therapy in mild heart failure patients with left bundle branch block.

Cardiac resynchronization therapy (CRT) is highly beneficial in patients with heart failure (HF) and left bundle branch block (LBBB); however, up to 30% of patients in this selected group are nonresponders. We hypothesized that clinical and echocardiographic variables can be used to develop a simple mortality risk stratification score in CRT. Best-subsets proportional-hazards regression analysis was used to develop a simple clinical risk score for all-cause mortality in 756 patients with LBBB allocated to the CRT with defibrillator (CRT-D) group enrolled in the multicenter automatic defibrillator implantation trial with cardiac resynchronization therapy. The score was used to assess the mortality risk within the CRT-D group and the associations with mortality reduction with CRT-D vs implantable cardioverter defibrillator (ICD) in each risk category. Four clinical variables comprised the risk score: age ≥ 65, creatinine ≥ 1.4 mg/dL, history of coronary artery bypass graft, and left ventricular ejection fraction (LVEF) < 26%. Every 1 point increase in the score was associated with 2-fold increased mortality within the CRT-D arm (P < 0.001). CRT-D was associated with mortality reduction as compared with ICD only in patients with moderate risk: score 0 (HR = 0.80, P = 0.615), score 1 (HR = 0.54, P = 0.019), score 2 (HR = 0.54, P = 0.016), score 3-4 risk factors (HR = 1.08, P = 0.811); however, the device by score interaction was not significant (P = 0.306). The score was also significantly predictive of left ventricular reverse remodeling (P < 0.001). Four clinical variables can be used for improved mortality risk stratification in mild HF patients with LBBB implanted with CRT-D.

Left Ventricular Lead Location and Long-Term Outcomes in Cardiac Resynchronization Therapy Patients.

The authors aimed to evaluate the association of left ventricular (LV) lead location and long-term outcomesin MADIT-CRT (Multicenter Automatic Defibrillator Implantation With Cardiac Resynchronization Therapy). There is limited data on the association of lead location with long-term clinical outcomes in patients with cardiac resynchronization therapy with defibrillator (CRT-D). The LV lead location was classified in 797 patients with CRT-D, in 569 patients with left bundle branch block (LBBB), in 228 patients with non-LBBB, and in 505 patients with an implantable cardioverter-defibrillator (ICD) only. Leads were classified into apical (n= 83) and non-apical (n= 486); with the non-apical LV leads further categorized into anterior (n= 99) and posterior/lateral (n= 387) within LBBB. All-cause mortality and heart failure (HF) events were assessed using Kaplan-Meier and Cox analyses. In CRT-D patients with LBBB and posterior/lateral LV lead location, there was an association with a significant reduction in long-term all-cause mortality (hazard ratio [HR]: 0.54, 95% confidence interval [CI]: 0.37 to 0.79; p=0.001), and HF events (HR: 0.44, 95% CI: 0.33 to 0.60; p< 0.001) compared to an ICD only, accompanied withbetter LV reverse remodeling. CRT-D patients with LBBB and an anterior LV lead location were shown to be associated with a significant reduction in HF events compared to an ICD only (anterior HR: 0.50, 95% CI: 0.30 to 0.82; p= 0.006); however, no association with mortality reduction was observed from CRT-D versus an ICD only. CRT-D wasnot associated with improved outcomes in non-LBBB patients, regardless of LV lead location. In mild HF patients with LBBB and an implanted CRT-D, lateral/posterior, and anterior LV lead locations are similarly associated with reduction in the risk of HF or death events compared to ICD alone. Mortality benefit derived from CRT-D is associated only with patients with lateral/posterior LV lead location. An apical LV lead location should be avoided due to the early risk of death whenever possible. (Multicenter Automatic Defibrillator Implantation With Cardiac Resynchronization Therapy [MADIT-CRT], NCT00180271; Multicenter Automatic Defibrillator Implantation Trial WithCardiac Resynchronization Therapy Post Approval Registry [MADIT-CRT-PAR], NCT01294449; and MADIT-CRT Long-Term International Follow-Up Registry - Europe, NCT02060110).

Comparison of Long-Term Survival Benefits With Cardiac Resynchronization Therapy in Patients With Mild Heart Failure With Versus Without Diabetes Mellitus (from the Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy [MADIT-CRT

We have previously shown a reduction in HF events with cardiac resynchronization therapy with defibrillator (CRT-D) in patients with mild heart failure (HF) and diabetes mellitus (DM). It remains unknown whether HF remission in DM patients with CRT-D translates into reduced mortality. The effects of CRT-D versus an implantable cardioverter-defibrillator (ICD) alone to reduce long-term mortality were assessed in patients with left bundle branch block with DM (n = 386) and without DM (n = 982), enrolled in the Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT). We further subdivided DM patients by insulin and noninsulin therapy. Kaplan-Meier survival analyses and multivariate cox proportional hazards regression models were utilized. At the 7-year follow-up, CRT-D was associated with a lower mortality in DM patients compared with ICD alone (21% vs 42%, p = 0.02), similar to non-DM patients (16 vs 24%, p = 0.014). CRT-D was associated with a 41% reduction in the risk of long-term all-cause mortality in DM patients (hazard ratio [HR] 0.59, 95% confidence interval 0.36 to 0.96, p = 0.033) and a similar reduction in non-DM patients (HR 0.69, 95% confidence interval 0.48 to 0.99, p = 0.045, treatment-diabetes interaction p = 0.611). Among DM patients, mortality benefit was evident in insulin-treated patients only (HR 0.40, p = 0.030). Reductions in HF events were present in all groups. In the MADIT-CRT, patients with mild HF with DM derive significant long-term survival benefit from CRT-D, similar to those without DM. The mortality benefit from CRT-D within the DM subgroup seems to be confined to patients with insulin treated diabetes.

THE EFFECT OF CARDIAC RESYNCHRONIZATION THERAPY ON OUTCOMES IN WOMEN: A SUBSTUDY OF THE RESYNCHRONIZATION-DEFIBRILLATION FOR AMBULATORY HEART FAILURE TRIAL

Cardiac resynchronization therapy with defibrillator (CRT-D) has demonstrated reduced mortality and heart failure (HF) hospitalizations in patients with left ventricular dysfunction. Prior studies have suggested that women may benefit more than men from CRT-D. Using a post hoc analysis of the

Impact of quadripolar LV leads on heart failure hospitalization rates among patients implanted with CRT-D: data from the Israeli ICD Registry.

Cardiac resynchronization therapy (CRT) is an effective treatment for heart failure (HF); however, a third of patients are non-responders. The development of quadripolar left ventricular (LV) lead was shown, mainly in single manufactures' registry, to improve LV remodeling and overall mortality. However, limited reports exist on the impact of quadripolar LV leads on HF hospitalization rates in real-life cohorts. We evaluated the clinical outcomes associated with quadripolar LV leads in a large nation-wide registry including all patients implanted with a cardiac resynchronization therapy with defibrillator (CRT-D). Between July 2010 and October 2016, 2913 consecutive patients were implanted with a CRT-D and all were prospectively enrolled in the Israeli ICD Registry. Quadripolar LV leads were implanted in 973 (33.4%) patients during this period, and their clinical outcomes were compared to CRT-D recipients implanted with a bipolar LV lead. Primary endpoint was HF hospitalization rate. Quadripolar leads were implanted more in patients with non-ischemic cardiomyopathy and for primary prevention indication and less in post-infarction patients and for secondary prevention of sudden death. Longer QRS duration was observed with quadripolar leads (147 ± 23 vs 143 ± 25; p < 0.001). Outcome event rate for 100 patient years revealed no difference in HF hospitalization rates between bipolar and quadripolar LV leads. Quadripolar lead implant led to lower cardiac mortality, with no influence on overall mortality. Multivariate analysis revealed no significant differences in study endpoints between bipolar and quadripolar LV leads. In a large real-life registry, implantation of quadripolar LV leads in patients with CRT-D did not influence HF hospitalization rates.

Heart failure severity, inappropriate ICD therapy, and novel ICD programming: a MADIT-RIT substudy.

The effects of heart failure (HF) severity on risk of inappropriate implantable cardioverter-defibrillator (ICD) therapy have not been thoroughly investigated. We aimed to study the association between HF severity and inappropriate ICD therapy in MADIT-RIT. MADIT-RIT randomized 1,500 patients to three ICD programming arms: conventional (Arm A), high-rate cut-off (Arm B: ≥200beats/min), and delayed therapy (Arm C: 60-second delay for ≥170beats/min). We evaluated the association between New York Heart Association (NYHA) class III (n=256) versus class I-II (n=251) and inappropriate ICD therapy in Arm A patients with ICD-only and cardiac resynchronization therapy with defibrillator (CRT-D). We additionally assessed benefit of novel ICD programming in Arms B and C versus Arm A by NYHA classification. In Arm A, the risk of inappropriate therapy was significantly higher in those with NYHA III versus NYHA I-II for both ICD (hazard ratio [HR]=2.55, confidence interval [CI]: 1.51-4.30, P<0.001) and CRT-D patients (HR=3.73, CI: 1.14-12.23, P=0.030). This was consistent for inappropriate ATP and inappropriate ICD therapy<200beats/min, but not for inappropriate shocks. Novel ICD programming significantly reduced inappropriate therapy in patients with both NYHA III (Arm B vs Arm A: HR=0.08, P<0.001; Arm C vs Arm A: HR=0.17, P<0.001) and NYHA I-II (Arm B vs Arm A: HR=0.25, P<0.001; Arm C vs Arm A: HR=0.28, P<0.001). Patients with more severe HF are at increased risk for inappropriate ICD therapy, particularly ATP due to arrhythmias<200beats/min. Novel programming with high-rate cut-off or delayed detection reduces inappropriate ICD therapies in both mild and moderate HF.

Predictors and outcomes of cardiac resynchronization therapy extended to the second generator

A proportion of patients who receive cardiac resynchronization therapy with defibrillator (CRT-D) live to receive a second generator. Controversy exists on whether an implantable cardioverter-defibrillator (ICD) should be offered to patients who have normalized or near-normalized left ventricular ejection fraction (LVEF) at the time of generator replacement (GR). The purpose of this study was to evaluate incidence of appropriate ICD therapy after CRT-D GR. This series involved 1026 consecutive patients who underwent CRT-D implant between January 1, 2002 and December 31, 2012. Echocardiography was assessed before the initial device implant and before GR. ICDs were monitored at our device clinic in person or remotely, or both. Of the cohort, 227 patients (22.1%) underwent CRT-D GR at our institution. Approximately 48% of the patients who received new CRT-D generators were no longer meeting the guidelines indication for ICD use at the time of GR. These patients received subsequent appropriate ICD therapies at a significantly lower rate than those with LVEF <35% (12% vs 35%; P < .001). Of these patients, 47 (20.7%) had LVEF improvement to ≥50% at the time of GR. ICD therapy for ventricular arrhythmia in the ischemic group was 18.2%, while no patient in the nonischemic group received ICD therapy from the second generator after GR. Improvement in LVEF after CRT-D GR is associated with significantly reduced incidence of appropriate ICD therapy. Ventricular arrhythmia is less likely to develop with normalized LVEF in nonischemic cardiomyopathy.

Outcomes of Cardiac Resynchronization Therapy With or Without Defibrillation in Patients With Nonischemic Cardiomyopathy

BackgroundRecent studies have cast doubt on the benefit of cardiac resynchronization therapy (CRT) with defibrillation (CRT-D) versus pacing (CRT-P) for patients with nonischemic cardiomyopathy (NICM). Left ventricular myocardial scar portends poor clinical outcomes. ObjectivesThe aim of this study was to determine whether CRT-D is superior to CRT-P in patients with NICM either with (+) or without (−) left ventricular midwall fibrosis (MWF), detected by cardiac magnetic resonance. MethodsClinical events were quantified in patients with NICM who were +MWF (n = 68) or −MWF (n = 184) who underwent cardiac magnetic resonance prior to CRT device implantation. ResultsIn the total study population, +MWF emerged as an independent predictor of total mortality (adjusted hazard ratio [aHR]: 2.31; 95% confidence interval [CI]: 1.45 to 3.68), total mortality or heart failure hospitalization (aHR: 2.02; 95% CI: 1.32 to 3.09), total mortality or hospitalization for major adverse cardiac events (aHR: 2.02; 95% CI: 1.32 to 3.07), death from pump failure (aHR: 1.95; 95% CI: 1.11 to 3.41), and sudden cardiac death (aHR: 3.75; 95% CI: 1.26 to 11.2) over a maximum follow-up period of 14 years (median 3.8 years [interquartile range: 2.0 to 6.1 years] for +MWF and 4.6 years [interquartile range: 2.4 to 8.3 years] for −MWF). In separate analyses of +MWF and −MWF, total mortality (aHR: 0.23; 95% CI: 0.07 to 0.75), total mortality or heart failure hospitalization (aHR: 0.32; 95% CI: 0.12 to 0.82), and total mortality or hospitalization for major adverse cardiac events (aHR: 0.30; 95% CI: 0.12 to 0.78) were lower after CRT-D than after CRT-P in +MWF but not in −MWF. ConclusionsIn patients with NICM, CRT-D was superior to CRT-P in +MWF but not −MWF. These findings have implications for the choice of device therapy in patients with NICM.