Cardiac Resynchronization Therapy With A Defibrillator Research Articles

Incidence and Predictors of Appropriate Implantable Cardioverter Defibrillator Therapy in Japanese Ischemic Heart Disease Patients.

Although the efficacy of an implantable cardioverter defibrillator (ICD) in preventing sudden cardiac death is well established, the incidence and predictors of appropriate ICD therapy in Japanese ischemic heart disease (IHD) patients remain unclear. We retrospectively studied Japanese 141 IHD patients undergoing transvenous ICD or cardiac resynchronization therapy with a defibrillator (CRT-D) implantation for primary or secondary prevention at Hirosaki University Hospital. Over a mean (±SD) follow-up period of 5.5±2.8 years, the incidence of appropriate ICD therapy was similar in the primary and secondary prevention groups, although it was relatively more frequent in the first 2 years in the secondary prevention group. Four patients died due to sustained ventricular tachycardia (VT) or ventricular fibrillation (VF), mainly due to post-shock pulseless electrical activity. Once patients had received their first appropriate ICD therapy, 49.2% received second appropriate ICD therapy within 6 months. Cox proportional hazard analysis revealed that sustained VT as an index life-threatening ventricular tachyarrhythmia before ICD/CRT-D implantation was an independent predictor of appropriate ICD therapy, but VF was not. The incidence of appropriate ICD therapy was comparable in primary and secondary prevention among Japanese IHD patients. We need to recognize the high-risk period for second appropriate ICD therapy after the first therapy and sustained VT as index life-threatening ventricular tachyarrhythmia as a risk factor for appropriate ICD therapy.

QRS Morphology and the Risk of Ventricular Tachyarrhythmia in Cardiac Resynchronization Therapy Recipients

BackgroundThere are conflicting data on the effect of cardiac resynchronization therapy with a defibrillator (CRT-D) on the risk of life-threatening ventricular tachyarrhythmia in heart failure patients. ObjectivesThe authors aimed to assess whether QRS morphology is associated with risk of ventricular arrhythmias in CRT recipients. MethodsThe study population comprised 2,862 patients implanted with implantable cardioverter defibrillator (ICD)/CRT-D for primary prevention who were enrolled in 5 landmark primary prevention ICD trials (MADIT-II [Multicenter Automated Defibrillator Implantation Trial], MADIT-CRT [Multicenter Automated Defibrillator Implantation Trial-Cardiac Resynchronization Therapy], MADIT-RIT [Multicenter Automated Defibrillator Implantation Trial-Reduction in Inappropriate Therapy], MADIT-RISK [Multicenter Automated Defibrillator Implantation Trial-RISK], and RAID [Ranolazine in High-Risk Patients With Implanted Cardioverter Defibrillators]). Patients with QRS duration ≥130 ms were divided into 2 groups: those implanted with an ICD only vs CRT-D. The primary endpoint was fast ventricular tachycardia (VT)/ventricular fibrillation (VF) (defined as VT ≥200 beats/min or VF), accounting for the competing risk of death. Secondary endpoints included appropriate shocks, any sustained VT or VF, and the burden of fast VT/VF, assessed in a recurrent event analysis. ResultsAmong patients with left bundle branch block (n = 1,792), those with CRT-D (n = 1,112) experienced a significant 44% (P < 0.001) reduction in the risk of fast VT/VF compared with ICD-only patients (n = 680), a significantly lower burden of fast VT/VF (HR: 0.55; P = 0.001), with a reduced burden of appropriate shocks (HR: 0.44; P < 0.001). In contrast, among patients with non-left bundle branch block (NLBBB) (N = 1,070), CRT-D was not associated with reduction in fast VT/VF (HR: 1.33; P = 0.195). Furthermore, NLBBB patients with CRT-D experienced a statistically significant increase in the burden of fast VT/VF events compared with ICD-only patients (HR: 1.90; P = 0.013). ConclusionsOur data suggest a potential proarrhythmic effect of CRT among patients with NLBBB. These data should be considered in patient selection for treatment with CRT.

Improved outcomes of cardiac resynchronization therapy with a defibrillator in systolic heart failure: Analysis of the Japan cardiac device treatment registry database.

Temporal change in outcomes of heart failure patients receiving cardiac resynchronization therapy with a defibrillator (CRT-D) is unknown. We assess outcomes and underlying heart diseases of patients receiving CRT-D with analyzing database of the Japan cardiac device treatment registry (JCDTR) at the implantation year 2011-2015 and New JCDTR at the implantation year 2018-2021. Proportion of nonischemic heart diseases was about 70% in both the groups (JCDTR: 69%; New JCDTR: 72%). Cardiac sarcoidosis increased with the rate of 5% in the JCDTR to 9% in the New JCDTR group. During an average follow-up of 21 months, death from any cause occurred in 167 of 906 patients in the JCDTR group (18%) and 79 of 611 patients in the New JCDTR group (13%) (adjusted hazard ratio [aHR] in the New JCDTR group, 0.72; 95% confidence interval [CI]: 0.55-0.94; p = .017). The superiority was mainly driven by reduction in the risk of noncardiac death. With regard to appropriate and inappropriate implantable cardioverter-defibrillator (ICD) therapy, there was a significant reduction in the New JCDTR group versus the JCDTR group (aHR in the New JCDTR group, 0.76; 95% CI: 0.59-0.98; p = .032 for appropriate ICD therapy; aHR in the New JCDTR group, 0.24; 95% CI: 0.12-0.50; p < .0001 for inappropriate ICD therapy). All-cause mortality was reduced in CRT-D patients implanted during 2018-2021 compared to those during 2011-2015, with a significant reduction in noncardiac death.

Abstract 13917: Predictors of Ventricular Arrhythmias in Patients With Left Ventricular Ejection Fraction Improvement to &gt;35% Following Cardiac Resynchronization Therapy

Introduction: Patients undergoing cardiac resynchronization therapy with a defibrillator (CRT-D) show significant improvement in LVEF. We designed this study to identify predictors of ventricular arrhythmic (VA) events among patient with LVEF improvement &gt; 35% after one year of treatment with CRT-D. Hypothesis: We hypothesized that LVEF improvement &gt; 35% is associated with a decreased risk of VA events. Methods: Patients randomized to CRT-defibrillator from the Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT) trial with LVEF &gt; 35% at 12 months were included in this analysis (N=651). Predictors of an appropriate ICD therapy for VA subsequent to one year were evaluated by cox regression model. Cumulative probability of first event was analyzed by Kaplan Meier Method with time for follow-up beginning at 1 year after device implantation. Results: The average follow-up was 2.04 ± 0.83 years. We identified 3 independent predictors of VA among patients treated with CRT-D subsequent to LVEF improvement to &gt; 35%: (1) baseline non-LBBB morphology (HR=1.93; 95% CI,1.23-3.04; p= 0.004); (2) the occurrence of VA during first year post CRT-D implant (HR=4.91 [95% CI, 2.99-8.07]; p&lt;0.001); and (3) lower range improvement in LVEF (36-40% vs. &gt;40%; HR =1.97 [95% CI 1.21-3.20]; p= 0.006). When compared with patients with 0 risk factors, having one and 2 or more risk factors had significantly higher risk of VTA (2-year rate of VT/VF = 4%, 11% and 32% respectively; HRs = 2.9 [p=0.002]and 7.9 [p=&lt;0.001], respectively [Figure]). Conclusions: We identify a sub-group of patients who remain at high risk of VTA despite improvement in LVEF &gt; 35% with CRT-D. Having a baseline non-LBBB morphology, experiencing VA during the first year post CRT-D, and lower-range LVEF improvement are associated with high risk of future arrhythmias, with a cumulative effect.

Time-trend treatment effect of cardiac resynchronization therapy with or without defibrillator on mortality: a systematic review and meta-analysis.

This study aimed to investigate the impact of cardiac resynchronization therapy with a defibrillator (CRT-D) on mortality, comparing it with CRT with a pacemaker (CRT-P). Additionally, the study sought to identify subgroups, evaluate the time trend in treatment effects, and analyze patient characteristics, considering the changing indications over the past decades. PubMed, CENTRAL, and Embase up to October 2021 were screened for studies comparing CRT-P and CRT-D, focusing on mortality. Altogether 26 observational studies were selected comprising 128 030 CRT patients, including 55 469 with CRT-P and 72 561 with CRT-D device. Cardiac resynchronization therapy with defibrillator was able to reduce all-cause mortality by almost 20% over CRT-P [adjusted hazard ratio (HR): 0.85; 95% confidence interval (CI): 0.76-0.94; P < 0.01] even in propensity-matched studies (HR: 0.83; 95% CI: 0.80-0.87; P < 0.001) but not in those with non-ischaemic aetiology (HR: 0.95; 95% CI: 0.79-1.15; P = 0.19) or over 75 years (HR: 1.08; 95% CI 0.96-1.21; P = 0.17). When treatment effect on mortality was investigated by the median year of inclusion, there was a difference between studies released before 2015 and those thereafter. Time-trend effects could be also observed in patients' characteristics: CRT-P candidates were getting older and the prevalence of ischaemic aetiology was increasing over time. The results of this systematic review of observational studies, mostly retrospective with meta-analysis, suggest that patients with CRT-D had a lower risk of mortality compared with CRT-P. However, subgroups could be identified, where CRT-D was not superior such as non-ischaemic and older patients. An improved treatment effect of CRT-D on mortality could be observed between the early and late studies partly related to the changed characteristics of CRT candidates.

Topological data analysis to identify cardiac resynchronization therapy patients exhibiting benefit from an implantable cardioverter-defibrillator

BackgroundCurrent guidelines recommend considering multiple factors while deciding between cardiac resynchronization therapy with a defibrillator (CRT-D) or a pacemaker (CRT-P). Nevertheless, it is still challenging to pinpoint those candidates who will benefit from choosing a CRT-D device in terms of survival.ObjectiveWe aimed to use topological data analysis (TDA) to identify phenogroups of CRT patients in whom CRT-D is associated with better survival than CRT-P.MethodsWe included 2603 patients who underwent CRT-D (54%) or CRT-P (46%) implantation at Semmelweis University between 2000 and 2018. The primary endpoint was all-cause mortality. We applied TDA to create a patient similarity network using 25 clinical features. Then, we identified multiple phenogroups in the generated network and compared the groups’ clinical characteristics and survival.ResultsFive- and 10-year mortality were 43 (40–46)% and 71 (67–74)% in patients with CRT-D and 48 (45–50)% and 71 (68–74)% in those with CRT-P, respectively. TDA created a circular network in which we could delineate five phenogroups showing distinct patterns of clinical characteristics and outcomes. Three phenogroups (1, 2, and 3) included almost exclusively patients with non-ischemic etiology, whereas the other two phenogroups (4 and 5) predominantly comprised ischemic patients. Interestingly, only in phenogroups 2 and 5 were CRT-D associated with better survival than CRT-P (adjusted hazard ratio 0.61 [0.47–0.80], p < 0.001 and adjusted hazard ratio 0.84 [0.71–0.99], p = 0.033, respectively).ConclusionsBy simultaneously evaluating various clinical features, TDA may identify patients with either ischemic or non-ischemic etiology who will most likely benefit from the implantation of a CRT-D instead of a CRT-P.Graphical abstractTopological data analysis to identify phenogroups of CRT patients in whom CRT-D is associated with better survival than CRT-P. AF atrial fibrillation, CRT cardiac resynchronization therapy, CRT-D cardiac resynchronization therapy defibrillator, CRT-P cardiac resynchronization therapy pacemaker, DM diabetes mellitus, HTN hypertension, LBBB left bundle branch block, LVEF left ventricular ejection fraction, MDS multidimensional scaling, MRA mineralocorticoid receptor antagonist, NYHA New York Heart Association

Cardiac resynchronization therapy with a defibrillator in non-ischemic and ischemic patients for primary and secondary prevention of sudden cardiac death: Analysis of the Japan cardiac device treatment registry database.

Panoramic studies in patients with cardiac resynchronization therapy with a defibrillator (CRT-D) focusing on the etiology and indication are scarce. Besides, a controversy exists regarding requirement of a defibrillator in non-ischemic patients for primary prevention with CRT. Annual trends of de novo CRT-D implantations from 2011 to 2020 and outcomes of those between January 2011 and August 2015 were analyzed from the Japan cardiac device treatment registry (JCDTR) and New JCDTR database. From 2011 to 2020, 8062 CRT-D recipients were registered, whose dominant indication was primary prevention of sudden cardiac death with a steady rate of about 70%. There was no significant temporal change of the proportion of non-ischemic patients being about 70% and 65% for primary and secondary prevention, respectively. Non-ischemic patients for primary prevention were associated with increased odds of appropriate ICD therapy [adjusted hazard ratio (aHR): 1.66; 95% confidence interval (CI): 1.01-2.75; p = .047] and reduced odds of any death (aHR: 0.66; 95% CI: 0.44-0.99; p = .046) as compared to ischemic patients. Proportion of non-ischemic etiology was much higher than that of ischemic one in the CRT-D cohort. Based on the higher odds of appropriate ICD therapy, non-ischemic patients for primary prevention appear to be prudently selected in Japan.

Defibrillator capability and all-cause mortality in patients receiving cardiac resynchronization therapy for non-ischemic cardiomyopathy: a Korean nationwide cohort study

Abstract Funding Acknowledgements Type of funding sources: None. Background Concerns exist about the benefit of cardiac resynchronization therapy with a defibrillator (CRT-D) compared to those without a defibrillator (CRT-P), especially in patients with non-ischemic cardiomyopathy. We evaluated the association between defibrillator capability and all-cause mortality in patients receiving cardiac resynchronization therapy (CRT) for non-ischemic cardiomyopathy. Methods From patients with nationally registered cardiomyopathy in the Korea National Health Insurance Service (KNHIS) database, after the exclusion of those with ischemic heart disease, 1,478 patients with newly-implanted CRT-P (n=258) or CRT-D (n=1220) were identified from 2008 to 2020. The association between defibrillator capability and all-cause mortality was assessed with propensity score (PS) weighting to correct for differences between the groups. Results Compared with patients receiving CRT-D, those receiving CRT-P included more subjects older than 75. After PS weighting, over a mean follow-up period of 52.9 months (interquartile interval: 23.5-75.8), CRT-D was associated with a lower rate of mortality (6.5 vs 9.2 per 100 person-years) compared with CRT-P. The weighted risk of all-cause death in patients with CRT-D was lower than those with CRT-P within 1 year (hazard ratio [HR]: 0.70 [95% CI, 0.53–0.91]; p = 0.009) and 5 years (HR: 0.71 [95% CI, 0.61–0.83]; p &amp;lt; 0.001). Results were consistent regardless of subgroups, such as age, sex, year of registration, and comorbidities. Conclusions In Korean patients with non-ischemic cardiomyopathy, the defibrillator capability of CRT was associated with reduced 1-year and 5-year all-cause mortality. This association was consistent across all the investigated subgroups.

The Effect of Sacubitril-Valsartan on Ventricular Arrhythmia Burden in Patients With Heart Failure With Reduced Ejection Fraction.

Introduction Heart failure with reduced ejection fraction (HFrEF) patients are prone to developing ventricular arrhythmias. In the PARADIGM-HF trial, sacubitril-valsartan (SV) showed a reduction in the composite endpoint of death and HF hospitalization in HFrEF patients; subgroup analysis of this trial revealed a reduction in both sudden death and deaths from worsening HF. The mechanism by which SV may affect the incidence of ventricular arrhythmias is currently under debate, and the literature provides conflicting results. The aim of our study was to evaluate the potential antiarrhythmic effect of this drug in patients with HFrEF carrying an implantable cardiac defibrillator (ICD) or a cardiac resynchronization therapy with a defibrillator (CRT-D). Methods This was a single-center, observational and retrospective study. Inclusion criteria were implantation of an ICD or CRT-D device between 2009 and 2019, age ≥18 years, left ventricle ejection fraction (LVEF) ≤40%, New York Heart Association (NYHA) functional class ≥II, and treatment with an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker for at least 12 months, followed by replacement with SV. Exclusion criteria were NYHA class IV, frequent alterations in chronic medication for HFrEF, and implantation of an ICD or CRT-D after the introduction of SV. The primary outcome was the occurrence of ventricular arrhythmias in the form of appropriate device shocks, ventricular fibrillation, or ventricular tachycardia. The comparisons were performed between two periods of time (12 months before and 12 months after SV) in the same group of patients. Results Fifty-four patients met the inclusion criteria. The mean age was 69.5 ± 1.65 years, and 74.1% of patients were male. The number of patients experiencing appropriate shocks was significantly lower after SV initiation (2% vs. 18%; p=0.016). The percentage of VT (13 vs. 20%; p=0.549) and VF episodes (4% vs. 13% for VF; p=0.289) were also lower, but these differences were not statistically significant. There were no significant differences in the value of NT-proBNP (1128 vs. 775 pg/mL; p=0.858), LVEF (28.4 vs. 29.6%; p=0.315), and left ventricular end-diastolic diameter (65.0 vs. 66.0 mm; p=0.5492). Conclusion SV seems to reduce the risk of arrhythmic events requiring appropriate shock therapy.

Ventricular arrhythmia events in heart failure patients with cardiac resynchronization therapy with or without a defibrillator for primary prevention.

It is uncertain whether cardiac resynchronization therapy with a defibrillator (CRT-D) provides better survival benefits than a CRT-pacemaker (CRT-P) in heart failure patients with a reduced ejection fraction (≦35%, HFrEF) treated with contemporary HF therapy. We retrospectively analyzed the ventricular arrhythmia (VAs; sustained ventricular tachycardia/fibrillation) events in HFrEF patients who underwent CRT without a prior history of VAs or aborted sudden cardiac death before the CRT implantation. Between January/2010 and December/2020, a CRT device was implanted in 79 HFrEF patients (mean age: 69 ± 12 years, male: 57, ischemic cardiomyopathy: 16). CRT-D and CRT-P devices were implanted in 50 and 29 patients, respectively, at each physician's discretion. CRT-Ds were indicated in younger patients than were CRT-Ps (66 ± 12 vs. 73 ± 12 years, p=0.03), but the gender distribution did not differ (female, 24% [12 of 50] vs. 35% [10 of 29], p=0.44). The VA events during a median follow-up of 3.5-years (interquartile range [IQR]:1.6-5.5) and their predictors were analyzed. VA events occurred in 9 patients with CRT-Ds (18%) and one with a CRT-P (3%, p=0.08). The VA event rate was significantly lower in patients without a prior non-sustained ventricular tachycardia (NSVT: ≥3 beats; rate, ≥120 bpm; lasting <30 s, HR 0.05; 95% CI 0.01-0.30; p < 0.01) and females (HR 0.11; 95% CI 0.01-0.93; p=0.04). Of note, no female patients without a prior history of NSVT experienced VA events. HFrEF CRT candidates without a prior history of NSVT and females may obtain less benefit from a primary preventive defibrillator indication.

Add-on Therapy With Sacubitril/Valsartan and Clinical Outcomes in CRT-D Nonresponder Patients.

:No data on the add-on sacubitril/valsartan (S/V) therapy among cardiac resynchronization therapy with a defibrillator (CRT-D) nonresponder patients are currently available in literature. We conducted a prospective observational study including 190 CRT-D nonresponder patients with symptomatic heart failure with reduced ejection fraction despite the optimal medical therapy from at least 1 year. The primary endpoint was the rate of additional responders (left ventricular end-systolic volume reduction >15%) at 12 months from the introduction of S/V therapy. At the end of the 12 months follow-up, 37 patients (19.5%) were deemed as “additional responders” to the combination use of CRT + S/V therapy. The only clinical predictor of additional response was a lower left ventricular ejection fraction [OR 0.881 (0.815–0.953), P = 0.002] at baseline. At 12 months follow-up, there were significant improvements in heart failure (HF) symptoms and functional status [New York Heart Association 2 (2–3) vs. 1 (1–2), P < 0.001; physical activity duration/day: 10 (8–12) vs. 13 (10–18) hours, P < 0.001]. Compared with the 12 months preceding S/V introduction, there were significant reductions in the rate of HF rehospitalization (35.5% vs. 19.5%, P < 0.001), in atrial tachycardia/atrial fibrillation burden [6.0 (5.0–8.0) % vs. 0 (0–2.0) %, P < 0.001] and in the proportions of patients experiencing ventricular arrhythmias (21.6% vs. 6.3%; P < 0.001). Our results indicate that S/V add-on therapy in CRT-D nonresponder patients is associated with 19.5% of additional responders, a reduction in HF symptoms and rehospitalizations, AF burden, and ventricular arrhythmias.

Abstract 11912: Risk Stratification of Life Threatening Ventricular Tachyarrhythmias in Patients With Non-Ischemic Cardiomyopathy

Background: The implantable cardioverter defibrillator is effective in reducing mortality among patients with heart failure (HF) due to ischemic heart disease. More recent clinical trial data have called into question the benefit of an ICD in patients with HF due to non-ischemic cardiomyopathy (NICM). Objective: The purpose of this study was to identify a risk stratification score among patients with NICM receiving a primary prevention ICD. Methods: The study population comprised 1842 patients with NICM who were enrolled in the MADIT and RAID trials. We used Fine and Gray analysis to develop a model for the occurrence of ventricular tachycardia/fibrillation (VT/VF), while accounting for the competing risk of death. Patients were grouped into 3 strata based on their risk score. Results: Five factors associated with increased risk of VT/VF were identified: ICD vs cardiac resynchronization therapy with a defibrillator (CRT-D), prior history of non-sustained VT, male gender, ejection fraction ≤ 25%, and Black Race. A score was generated based on this model and the patients were stratified into three risk groups. The four-year cumulative incidences of VT/VF in the low-, intermediate-, and high-risk groups were 19%, 37%, 52%, respectively (p&lt;0.001 for the overall difference; Figure). Internal validation using a bootstrapping yielded a median c-statistic of 0.69 (95% CI 0.66-0.74). Conclusions: Our findings suggest that patients with NICM can be risk stratified for VT/VF using a combination of clinical and echocardiographic findings.

Prognosis of Japanese Patients With Coronary Artery Disease Who Underwent Implantable Cardioverter Defibrillator Implantation - The JID-CAD Study.

Background: There has been no large multicenter clinical trial on the prognosis of implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy with a defibrillator (CRT-D) in Japanese patients with coronary artery disease (CAD). The aim of the present study was to compare differences in the prognoses of Japanese patients with CAD between primary and secondary prevention, and to identify potential predictors of prognosis.Methods and Results: We investigated 392 CAD patients (median age 69 years, 90% male) treated with ICD/CRT-D enrolled in the Japan Implantable Devices in CAD (JID-CAD) Registry. The primary endpoint was all-cause death, and the secondary endpoint was appropriate ICD therapies. Endpoints were assessed by dividing patients into primary prevention (n=165) and secondary prevention (n=227) groups. The mean (±SD) follow-up period was 2.1±0.9 years. The primary endpoint was similar in the 2 groups (P=0.350).Conclusions: The mortality rate in Japanese patients with CAD who underwent ICD/CRT-D implantation as primary prevention was not lower than that of patients who underwent ICD/CRT-D implantation as secondary prevention, despite the lower cardiac function in the patients undergoing ICD/CRT-D implantation as primary prevention.

Current status and role of programmed ventricular stimulation in patients without sustained ventricular arrhythmias and reduced ejection fraction: Analysis of the Japan cardiac device treatment registry database.

BackgroundThe aim of this study was to clarify the current status and role of programmed ventricular stimulation in patients without sustained ventricular arrhythmias and reduced left ventricular ejection fraction (LVEF).MethodsThe follow‐up data of the Japan cardiac device treatment registry (JCDTR) was analyzed in 746 patients with LVEF ≦35% and no prior history of sustained ventricular arrhythmias who underwent de novo implantable cardioverter‐defibrillator (ICD) or cardiac resynchronization therapy with a defibrillator (CRT‐D) implantation between January 2011 and August 2015.ResultsElectrophysiological study (EPS) with programmed ventricular stimulation had been performed before the device implant in 118 patients (15.8%, EPS group). During the mean follow‐up of 21 ± 12 months, the rate of freedom from any death and appropriate defibrillator therapy was not significantly different between EPS group (n = 118) and No EPS group (n = 628). NYHA class II‐IV, and QRS duration were negatively associated with performing EPS. Among patients in the EPS group, the rate of ventricular tachycardia (VT)/ventricular fibrillation (VF) induction was 48%. The inducibility was not a predictor of appropriate defibrillator therapy, whereas BNP ≧535 pg/mL and no use of amiodarone were significantly associated with a risk of the appropriate therapy.ConclusionEPS for induction of VT/VF had been performed in about 16% of patients with reduced LVEF before primary prevention ICD/CRT‐D implantation. Elevated BNP levels and no use of amiodarone, but not inducibility of VT/VF, appeared to be associated with appropriate defibrillator therapy in these populations.

AnaLysIs of Both sex and device specific factoRs on outcomes in pAtients with non-ischemic cardiomyopathy (BIO-LIBRA): Design and clinical protocol.

BackgroundOutcomes of patients with nonischemic cardiomyopathy and low ejection fraction implanted with an implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy with a defibrillator (CRT-D), especially in contemporary, real-life cohorts, are not fully understood.ObjectiveWe aimed to better characterize outcomes of death and ventricular tachyarrhythmias in patients with nonischemic cardiomyopathy, implanted with an ICD or CRT-D, and specifically assess differences by sex.MethodsThe AnaLysIs of Both Sex and Device Specific FactoRs on Outcomes in PAtients with Non-Ischemic Cardiomyopathy (BIO-LIBRA) study was designed to prospectively assess outcomes of device-treated ventricular tachyarrhythmias and all-cause mortality events in nonischemic cardiomyopathy patients, indicated for an ICD or CRT-D implantation for the primary prevention of sudden cardiac death (SCD), with a specific focus on sex differences. We will enroll a total of 1000 subjects across 50 U.S. sites and follow patients for up to 3 years.ResultsThe primary objective of BIO-LIBRA is to evaluate the combined risk of all-cause mortality and treated ventricular tachycardia (VT) or ventricular fibrillation (VF) events by subject sex and by implanted device type. We will also assess all-cause mortality, VT or VF alone, cardiac death, and SCD in the total cohort, as well as by subject sex and by the implanted device type. In addition, the previously validated Seattle Proportional Risk Model (SPRM) will be used to compare the SPRM predicted incidence of SCD to the observed incidence.ConclusionsThe BIO-LIBRA study will provide novel and contemporary information regarding outcomes in patients with a NICM who receive a defibrillator.

Why is the clinical response to cardiac resynchronization better in LBBB patients?

AimsThe improved clinical response in patients with left bundle branch block (LBBB) over LBBB‐free patients treated with cardiac resynchronization therapy with a defibrillator (CRT‐D) is commonly attributed to an LBBB abnormality. We aimed to find an alternative explanation.Methods and resultsWe analysed an immediate effect of selecting the LBBB group of patients in a cohort of 63 non‐ischaemic cardiomyopathy (non‐ICM) and 83 ischaemic cardiomyopathy (ICM) patients treated with CRT‐D; 75% of non‐ICM and 51% of ICM patients had an LBBB abnormality on the electrocardiogram, with a significant difference (P = 0.0032 by χ 2). As a result of this difference, the proportion of non‐ICM patients increased from 43% in the primary cohort to 53% in LBBB selection and decreased to 28% in non‐LBBB group. By nonparametric survival analysis, the hazard ratio in non‐ICM patients in the LBBB selection decreased from 0.48 (P = 0.0488) to 0.36 (P = 0.0251) and increased in the non‐LBBB group to 0.75 (P = 0.6496). Any comparison of LBBB and non‐LBBB groups must compare sets with a significantly altered proportion of patients of different aetiologies. Most publications on LBBB patients are erroneous because they compare LBBB with non‐LBBB groups, not taking into account that the groups have been substantially changed by the selection process.ConclusionsThe declared outcome of the LBBB groups reflects inevitably the survival outcome of their non‐ICM patients and not the intended outcome of patients with LBBB. CRT‐D in patients with different aetiologies of cardiomyopathy calls for separate evaluation.

A novel index combining diastolic and systolic tissue Doppler parameters for predicting cardiac resynchronization therapy response.

Identification of patients who are nonresponders to cardiac resynchronization therapy (CRT) with the use of simple and objective parameters may be helpful in tailoring treatment. The aim of this study is to investigate whether E/(Ea×Sa) could be a predictor of CRT nonresponders (E=early diastolic transmitral velocity, Ea=early diastolic mitral annular velocity, Sa=systolic mitral annular velocity). In total, 53 heart failure patients were evaluated for this study, and 33 patients were included according to the study criteria. Before and 6months after CRT-D(CRT with a defibrillator) implantation, E, Ea, and Sa were determined at the medial and lateral mitral annular sites, and the average values were obtained. E/(Ea×Sa) was calculated (medial, lateral, average). The patients were followed for 6months to monitor their CRT response. A responder was defined as a patient with a reduction in end-systolic volume of ≥15% and an increase in 6-minute walking distance of 50m. At a 6-month follow-up, 24 (72.7%) of the 33 patients responded to CRT. At the 6-month follow-up, in the responder group, the E/Ea ratio, lateral mitral, and average E/(Ea×Sa) indices were significantly reduced (P<.01 for all). The baseline lateral mitral, medial mitral, and average E/(Ea×Sa) indices were significantly lower in the responder group than in the nonresponder group (P≤.01 for all). The receiver operating characteristic analysis showed that all the E/(Ea×Sa) indices predict the CRT nonresponder patients. The AUC values were 0.89 (lateral E/(Ea×Sa)), 0.85 (average E/(Ea×Sa)), and 0.77 (medial E/(Ea×Sa)) (P≤.01 for all). We found that the E/(Ea×Sa) index is a novel predictor of CRT nonresponder patients.

Trends in the use of implantable cardioverter-defibrillator and cardiac resynchronization therapy device in advancing age: Analysis of the Japan cardiac device treatment registry database.

BackgroundTrends of de novo implantation of cardiac implantable electronic devices (CIEDs) including implantable cardioverter‐defibrillator (ICD) and cardiac resynchronization therapy with a defibrillator (CRT‐D) or pacemaker (CRT‐P) in advancing age are unknown.MethodsAnalysis of data from the Japan cardiac device treatment registry (JCDTR) with an implantation date between January 2006 and December 2016 was performed focusing on advancing age of ≧75 years.ResultsThe cohort included 17 564 ICD, 9470 CRT‐D and 1087 CRT‐P recipients for de novo implantation. The rate of patients ≧75 years of age increased from 17.1% to 20.5% in ICD implantation (P = .052), from 19.7% to 30.0% in CRT‐D implantation (P < .0001), and from 40.0% to 64.0% in CRT‐P implantation (P = .17). There was an apparent increase in the percentage of nonischemic patients aged ≧75 years receiving ICD (10.9% in 2006 to 16.4% in 2016, P = .0008) and CRT‐D (17.1% in 2006 to 27.8% in 2016, P = .0001). The implantation for primary prevention ICD (P = .059) and CRT‐D (P = .012) was also associated with a temporal increase in the percentage of patients aged ≧75 years.ConclusionsProportion of patients ≧75 years of age for de novo CIED implantation gradually increased from 2006 to 2016, presumably because of the growing number of nonischemic cardiomyopathy and heart failure patients requiring primary prevention of sudden cardiac death.

Risk of Ventricular Tachyarrhythmic Events in Patients Who Improved BeyondGuidelines for a Defibrillator inMADIT-CRT.

This study assessed the arrhythmic risk of cardiac resynchronization therapy (CRT) patients who improved beyond Heart Rhythm Society/European Society of Cardiology guidelines for an implantable cardioverter-defibrillator (ICD) (ischemic cardiomyopathy: left ventricular ejection fraction [LVEF] >35% or New York Heart Association [NYHA] functional class I and if LVEF was 31% to 35%; nonischemic cardiomyopathy: LVEF >35% or NYHA functional class I and if LVEF was≤35%). It is currently unknown whether protection with a defibrillator is still warranted in patients who respond to CRT. This study compared the risk of ICD therapy for any ventricular tachyarrhythmia (VTA) and for fast VTA (≥200 beats/min) among patients implanted with a CRT with a defibrillator (CRT-D) in the MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy) (N=734) who improved at 1year beyond guideline recommendations for primary ICD therapy (group A) with those who remained within guideline recommendations for an ICD at 1 year (group B). Most patients implanted with a CRT-D device improved at 1 year beyond guideline indications for an ICD(90%). Multivariate analysis showed lower risks for any VTA and fast VTA among group A patients versus group Bpatients(57% risk reduction; p=0.0006 and 46% risk reduction; p=0.068, respectively). However, the 2-year rates of any VTA and fast VTA among CRT patients who improved beyond guidelines indications for an ICD was still substantial (VTA: 13% and 29%, and fast VTA: 7% and 16%, respectively). Most patients with mild heart failure implanted with a CRT device experience an improvement in left ventricular function and/or NYHA functional class beyond guideline recommendations for primary ICD therapy. However,despite this pronounced CRT response, there remains a substantial VTA risk, and protection with a defibrillator may stillbe warranted in this population.

Left Ventricular Reverse Remodeling in Cardiac Resynchronization Therapy and Long-TermOutcomes.

The aim of this study was to evaluate the association between improvement in left ventricular end-systolic volume (LVESV) with cardiac resynchronization therapy (CRT) and mortality and whether this relationship was modified by the presence of a left bundle branch block (LBBB) electrocardiographic pattern. Left ventricular reverse remodeling in patients receiving CRT has been shown to predict outcomes. However, the extent to which reverse remodeling contributes to long-term survival is not well understood. Changes in LVESV were assessed in MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy) patients receiving CRT with a defibrillator (CRT-D) and echocardiograms available at 1 year (n=752), stratified by LBBB, relative to long-term all-cause mortality, compared with those with implantable cardioverter-defibrillators (ICDs) only (n=684). In patients with LBBB, a reduction in LVESV of >35% (median) translated into significantly lower risk for long-term mortality (hazard ratio [HR]: 0.34; p<0.001), heart failure (HF) events (HR: 0.21; p<0.001), and HF or death (HR: 0.27; p<0.001) compared with patients with ICDs only. Patients with reductions in LVESV≤35% had a significantly lower risk for HF, and HF or death, and a nonsignificantly lower rate of death compared with those with ICDs only (HR:0.74; p=0.13). Risk reduction in HF events was uniform across all LVESV quartiles. In patients without LBBB, there was no survival benefit (HR: 0.68; p=0.271) despite an LVESV reduction greater than the median (>27.6%). CRT-D patients without LBBB with the least reverse remodeling (quartile 1) had a more than 3-fold increased risk for death compared with those with ICDs only (HR: 3.11; p<0.001). In patients with LBBB, CRT-D-induced reduction in LVESV at 1 year is associated with long-term survival benefit. Despite left ventricular reverse remodeling with CRT-D, there is no survival benefit and potential harm in patients without LBBB.