Implantable Cardioverter-defibrillator Trials Research Articles

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.

Sex-Related Differences in Ventricular Tachyarrhythmia Events in Patients With Implantable Cardioverter-Defibrillator and Prior Ventricular Tachyarrhythmias

BackgroundData on the risk of ventricular tachycardia (VT), ventricular fibrillation (VF), and death by sex in patients with prior VT/VF are limited. ObjectivesThis study aimed to assess sex-related differences in implantable cardioverter-defibrillator (ICD)-treated VT/VF events and death in patients implanted for secondary prevention or primary prevention ICD indications who experienced VT/VF before enrollment in the RAID (Ranolazine Implantable Cardioverter-Defibrillator) trial. MethodsSex-related differences in the first and recurrent VT/VF requiring antitachycardia pacing or ICD shock and death were evaluated in 714 patients. ResultsThere were 124 women (17%) and 590 men observed during a mean follow-up of 26.81 ± 14.52 months. Compared to men, women were at a significantly lower risk of VT/VF/death (HR: 0.67; P = 0.029), VT/VF (HR: 0.68; P = 0.049), VT/VF treated with antitachycardia pacing (HR: 0.59; P = 0.019), and VT/VF treated with ICD shock (HR: 0.54; P = 0.035). The risk of recurrent VT/VF was also significantly lower in women (HR: 0.35; P < 0.001). HR for death was similar to the other endpoints (HR: 0.61; P = 0.162). In comparison to men, women presented with faster VT rates (196 ± 32 beats/min vs 177 ± 30 beats/min, respectively; P = 0.002), and faster shock-requiring VT/VF rates (258 ± 56 beats/min vs 227 ± 57 beats/min, respectively; P = 0.30). There was a significant interaction for the risk of VT/VF by race (P = 0.013) with White women having significantly lower risk than White men (HR: 0.36; P < 0.001), whereas Black women had a similar risk to Black men (HR: 1.06; P = 0.851). ConclusionsWomen with a history of prior VT/VF experienced a lower risk recurrent VT/VF requiring ICD therapy when compared to men. Black Women had a risk similar to men, whereas the lower risk for VT/VF in women was observed primarily in White women. (Ranolazine Implantable Cardioverter-Defibrillator Trial; NCT01215253)

Outcomes Following Implantable Cardioverter-Defibrillator Insertion in Patients 80 Years of Age or Older: A Statewide Population Cohort Study

BackgroundPatients ≥ 80 years of age are underrepresented in major implantable cardioverter-defibrillator (ICD) trials, and real-world data are lacking. In this study, we sought to assess ICD utilisation, outcomes, and their predictors, in an unselected statewide population including patients ≥ 80 years old. MethodsWe extracted details of ICDs implanted from 2009 to 2018 in New South Wales (NSW), Australia from the Centre for Health Record Linkage administrative data sets. Analysis was stratified into age groups of < 60 years, 60-79 years, and ≥ 80 years. ResultsA total of 9304 patients (mean age 66.1 ± 13.1 years; 12.1% ≥ 80 years) had de novo ICD placement at an average rate of 1163 ± 122 patients per annum, with more implants in men in all age groups. After adjusting for NSW population size by sex, age group, and calendar year, mean implantation rates were 5.5 ± 0.6, 63.2 ± 8.6, and 52.7 ± 10.8 per 100,000 persons per annum in patients aged < 60 years, 60-79 years, and ≥ 80 years, respectively. In-hospital mortality was 0.4% and did not differ among age groups. However, 1-year mortality was 2.1%, 5.9%, and 10.7%, in those < 60 years, 60-79 years, and ≥ 80 years of age, respectively (P < 0.001), with hazard ratios for those aged ≥ 80 years of 4.3 (95% confidence interval [CI] 3.1-6.0) and those aged 60-79 years of 2.6 (95% CI 1.9-3.5) relative to those aged < 60 years (both P < 0.001) after adjusting for ICD indications, sex, implantation year, referral source, and comorbidities. In those aged ≥ 80 years, age > 83 years, congestive cardiac failure, chronic renal failure, neurodegenerative disease, and a higher Charlson comorbidity index score were each independent predictors of 1-year mortality. ConclusionsICD use in patients aged ≥ 80 years and 60-79 years was 10-fold that in patients aged < 60 years, and perioperative outcomes were good in all ages, but there was substantially increased 1-year mortality in those aged ≥ 80 years. Careful selection based on age and comorbidity may further reduce 1-year mortality in patients ≥ 80 years old receiving ICDs.

Impact of Cardiac Magnetic Resonance to Arrhythmic Risk Stratification in Nonischemic Cardiomyopathy.

Left ventricular ejection fraction-based arrhythmic risk stratification in nonischemic cardiomyopathy (NICM) is insufficient and has led to the failure of primary prevention implantable cardioverter defibrillator trials, mainly due to the inability of selecting patients at high risk for sudden cardiac death (SCD). Cardiac magnetic resonance offers unique opportunities for tissue characterization and has gained a central role in arrhythmic risk stratification in NICM. The presence of myocardial scar, denoted by late gadolinium enhancement, is a significant, independent, and strong predictor of ventricular arrhythmias and SCD with high negative predictive value. T1 maps and extracellular volume fraction, which are able to quantify diffuse fibrosis, hold promise as complementary tools but need confirmatory results from large studies.

Effect of Carvedilol vs Metoprolol on Atrial and Ventricular Arrhythmias Among Implantable Cardioverter-Defibrillator Recipients

BackgroundBoth selective and nonselective beta-blockers are used to treat patients with heart failure (HF). However, the data on the association of beta-blocker type with risk of atrial arrhythmia and ventricular arrhythmia (VA) in HF patients with a primary prevention implantable cardioverter-defibrillator (ICD) are limited. ObjectivesThis study sought to evaluate the effect of metoprolol vs carvedilol on the risk of atrial tachyarrhythmia (ATA) and VA in HF patients with an ICD. MethodsThis study pooled primary prevention ICD recipients from 5 landmark ICD trials (MADIT-II, MADIT-CRT, MADIT-RIT, MADIT-RISK, and RAID). Fine and Gray multivariate regression models, stratified by study, were used to evaluate the risk of ATA, inappropriate ICD shocks, and fast VA (defined as ventricular tachycardia ≥200 beats/min or ventricular fibrillation) by beta-blocker type. ResultsAmong 4,194 patients, 2,920 (70%) were prescribed carvedilol and 1,274 (30%) metoprolol. The cumulative incidence of ATA at 3.5 years was 11% in patients treated with carvedilol vs 15% in patients taking metoprolol (P = 0.003). Multivariate analysis showed that carvedilol treatment was associated with a 35% reduction in the risk of ATA (HR: 0.65; 95% CI: 0.53-0.81; P < 0.001) when compared to metoprolol, and with a corresponding 35% reduction in the risk of inappropriate ICD shocks (HR: 0.65; 95% CI: 0.47-0.89; P = 0.008). Carvedilol vs metoprolol was also associated with a 16% reduction in the risk of fast VA. However, these findings did not reach statistical significance (HR: 0.84; 95% CI: 0.70-1.02; P = 0.085). ConclusionsThese findings suggests that HF patients with ICDs on carvedilol treatment experience a significantly lower risk of ATA and inappropriate ICD shocks when compared to treatment with metoprolol.

Arrhythmia and Survival Outcomes Among Black Patients and White Patients With a Primary Prevention Defibrillator.

Black Americans have a higher risk of nonischemic cardiomyopathy (NICM) than White Americans. We aimed to evaluate differences in the risk of tachyarrhythmias among patients with an implantable cardioverter-defibrillator (ICD). The study population comprised 3895 ICD recipients in the United States enrolled in primary prevention ICD trials. Outcome measures included ventricular tachyarrhythmia (VTA), atrial tachyarrhythmia (ATA), ICD therapies, VTA burden (using Andersen-Gill recurrent event analysis), death, and the predicted benefit of the ICD. All events were adjudicated blindly. Outcomes were compared between self-reported Black patients versus White patients with cardiomyopathy (ischemic and NICM). Black patients were more likely to be female (35% versus 22%) and younger (57±12 versus 62±12 years) with a higher frequency of comorbidities. In NICM, Black patients had a higher rate of first VTA, fast VTA, ATA, and appropriate and inappropriate ICD therapy (VTA ≥170 bpm, 32% versus 20%; VTA ≥200 bpm, 22% versus 14%; ATA, 25% versus 12%; appropriate therapy, 30% versus 20%; and inappropriate therapy, 25% versus 11%; P<0.001 for all). Multivariable analysis showed that Black patients with NICM experienced a higher risk of all types of arrhythmia or ICD therapy (VTA ≥170 bpm, hazard ratio [HR] 1.71; VTA ≥200 bpm, HR 1.58; ATA, HR 1.87; appropriate therapy, HR 1.62; inappropriate therapy, HR 1.86; P≤0.01 for all), higher burden of tachyarrhythmias or therapies (VTA, HR 1.84; appropriate therapy, HR 1.84; P<0.001 for both), and a higher risk of death (HR 1.92; P=0.014). In contrast, in ischemic cardiomyopathy, the risk of all types of tachyarrhythmia, ICD therapy, or death was similar between Black patients and White patients. Both Black patients and White patients derived a significant and similar benefit from ICD implantation. Among patients with NICM with an ICD for primary prevention, Black patients compared with White patients had a high risk and burden of VTA, ATA, and ICD therapies with a lower survival rate. Nevertheless, the overall benefit of the ICD was maintained and was similar to that of White patients.

PO-05-079 SMOKING AND THE RISK OF VENTRICULAR TACHYARRHYTHMIAS AMONG IMPLANTABLE CARDIOVERTER DEFIBRILLATOR RECIPIENTS FOR PRIMARY PREVENTION OF SUDDEN CARDIAC DEATH

Smoking has been linked to increased morbidity and mortality in patients with cardiovascular disease. However, limited data exist regarding the arrhythmic effects of smoking in patients at risk for sudden cardiac death (SCD). We aimed to evaluate the relationship between smoking and the risk of ventricular tachyarrhythmias and SCD. The study population comprised 5,015 patients implanted with an implantable cardioverter defibrillator (ICD) from five landmark randomized ICD trials (MADIT-II, MADIT-CRT, MADIT-RIT, MADIT-RISK, and RAID trials). Patients were categorized into three groups based on smoking status at the time of ICD implantation: non-smokers, past smokers, and current smokers. The primary endpoint was the first occurrence of ventricular tachycardia ≥170 bpm or fibrillation (VT/VF). Secondary endpoints included the composite endpoint of VT/VF or SCD and inappropriate ICD shocks. A competing risk analysis was carried out using the Fine and Gray method to generate cumulative incidence function (CIF) curves and regression models for the defined endpoints. The 5-year cumulative incidence of a first episode of VT/VF was higher in current smokers (32%) than in past- (29%) and non-smokers (25%) (p=0.009, [Figure, left panel]). Consistent results were obtained for the endpoint of inappropriate ICD shocks (10%, 9%, 6%%, respectively; p=0.007, [Figure, right panel]). Multivariate current smoking vs. non-smoking was associated with a significant 25% increased risk of VT/VF (HR=1.25, p=0.034); with a corresponding 28% increased risk of the composite endpoint of VT/VF or SCD (HR=1.28, p=0.014); and with a 49% increased risk of inappropriate ICD shocks (HR=1.49, p=0.03). Conversely, the risk of the aforementioned endpoints was not significantly difference between past-smokers and never-smokers. Patients who smoke at the time of ICD implantation experience a significantly increased risk of VT/VF and inappropriate ICD shocks.

PO-04-226 RISK OF VENTRICULAR RECURRENT TACHYARRHYTHMIA IN PATIENTS RECEIVING PRIMARY PREVENTION IMPLANTABLE CARDIOVERTER-DEFIBRILLATORS

Implantable cardioverter-defibrillators (ICDs) have demonstrated efficacy in reducing mortality attributable to sustained ventricular tachyarrhythmia (VTA) and have been used for primary prevention of sudden death. However, patients with primary prevention ICDs remain at risk for first and recurrent VTA, which are associated with increased morbidity and mortality. Currently, there are limited data on factors associated with recurrent VTA after the occurrence of a first episode in this population. Improved risk stratification may help tailor advanced therapies, such as catheter ablation or antiarrhythmic medications, to patients at a high risk for recurrence. The objective of this study was to quantify the risk for recurrent VTA after the occurrence of a first VTA episode among patients with a primary prevention ICD. The population comprised patients enrolled in five landmark ICD trials (MADIT-II, MADIT-Risk, MADIT-CRT, MADIT-RIT, RAID) who experienced a first episode of VTA (defined as ventricular tachycardia [VT] ≥170 bpm or ventricular fibrillation [VF]) after ICD implantation (N=789). The primary endpoint was recurrent VTA after a first episode. All-cause mortality associated with recurrent VTA was a secondary endpoint. Among 789 study patients who experienced a first VTA after ICD implantation, mean age was 63 ± 11 years, 17% were women, 64% had ischemic cardiomyopathy, and mean left ventricular ejection fraction (EF) was 24 ± 7%. Kaplan Meier analysis showed the risk of recurrent VTA after a first episode was very high (60% at 3 years [Figure - A]). Findings were consistent regardless of baseline risk factors, including age, sex, NYHA Class, EF. Furthermore, the burden of multiple VTA episodes after a first episode was also high (average of 3.6 episodes per patient at 3 years [Figure B]). Recurrent VTA was associated with a significant two-fold increased risk of subsequent death (HR=2.15, 95% CI 1.40-3.32, p=0.001 [Figure - C]). Among primary prevention ICD recipients who experience a first VTA, the burden of recurrent VTA and subsequent mortality increase is very high regardless of baseline risk factors. Intensification of therapies, including early catheter ablation, should be considered in primary prevention ICD recipients who experience a first VTA.

Age and the Risk of Ventricular Tachyarrhythmia in Patients With an Implantable Cardioverter-Defibrillator

BackgroundThe benefit of implantable cardioverter-defibrillators (ICDs) in elderly patients is controversial. ObjectivesThe aims of this study were to evaluate the risk for ventricular tachyarrhythmia (VTA) and ICD shocks by age groups and to assess the competing risk for VTA and death without prior VTA. MethodsThe study included 5,170 primary prevention ICD recipients enrolled in 5 landmark ICD trials (MADIT [Multicenter Automatic Defibrillator Implantation Trial] II, MADIT-Risk, MADIT-CRT [MADIT Cardiac Resynchronization Therapy], MADIT-RIT [MADIT Reduce Inappropriate Therapy], and RAID [Ranolazine in High-Risk Patients With Implanted Cardioverter-Defibrillator]). Fine and Gray regression analysis was used to evaluate the risk for fast VTA (ventricular tachycardia ≥200 beats/min or ventricular fibrillation) vs death without prior fast VTA in 3 prespecified age groups: <65, 65 to <75, and ≥75 years. ResultsThe cumulative incidence of fast VTA at 3 years was similar for patients <65 years of age and those 65 to <75 years of age (17% vs 15%) and was lowest among patients ≥75 years of age (10%) (P < 0.001). Multivariate Fine and Gray analysis showed a 40% lower risk for fast VTA in patients ≥75 years of age (HR: 0.60; 95% CI: 0.46-0.78; P < 0.001) compared with patients <65 years of age. In patients ≥75 years of age, a risk reversal was observed whereby the risk for death without prior fast VTA exceeded the risk for developing fast VTA. A history of nonsustained ventricular tachycardia, male sex, and the presence of nonischemic cardiomyopathy were identified as predictors of fast VTA in patients ≥75 years of age. ConclusionsPatients ≥75 years of age have a significantly lower risk for VTA and ICD shocks compared with younger patients. Aging is associated with a higher risk for death compared with the risk for fast VTA, the reverse of what is seen in younger patients.

Outcome and safety of intraoperative defibrillation testing during device replacement: the Simpler trial.

Intraoperative defibrillation testing (DT) during implant or replacement of implantable cardioverter-defibrillators (ICDs) has been a matter of debate for many years. This debate was put to rest by the Simple and Nordic ICD trials, and the practice of testing during new implantations has essentially been almost abandoned. Old registries demonstrated an increased incidence of significant findings in DT during replacements. The aim of the present study was to evaluate frequency of significant findings and safety of DT in subjects undergoing device replacement. A prospective observational multi-centre study included consecutive patients undergoing ICD generator replacement. The primary outcome was a failure to terminate induced ventricular fibrillation (VF) with a single shock 10 J below the maximal capacity of the device. Secondary outcomes included complications of DT. Patients were followed-up at 1- and 6-months post-procedure. A total of 92 patients were eligible, and consented to the study, of which 84 underwent DT during battery replacement. The median age was 68 years and 79.8% were males. Induction of VF was successful in 84 patients as was a successful conversion on the first attempt in all. There were no procedure-related complications. During follow up one patient had two appropriate ICD shock events. In four patients, ICD programming was changed. None suffered inappropriate shock. There was no evidence of lead malfunction. Two deaths occurred, none of which was related to arrhythmia. The present study found DT was not associated with complications in patients undergoing ICD generator replacement but produced no clinically important information.

Intraoperative defibrillation testing during replacements of implantable cardioverter-defibrillators: The Simpler trial

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Maurice Kahn Foundation via the Mayo- Sheba Collaboration Fund. Background The need for intraoperative defibrillation testing (DFT) during implant and/or replacement of implantable cardioverter-defibrillators (ICDs) has been a matter of debate for many years. This debate was put to rest by the Simple and the Nordic ICD trials, and the practice of testing during new implantations has practically been nearly abandoned. Nevertheless, induction of VF for testing purposes (VFT) may still have an important role in selective populations at risk for defibrillation failure, who were not included in the SIMPLE and Nordic trials. One such population includes those who undergo device replacements. Old registries demonstrated an increased incidence of significant findings in VFT during replacements. In the present study, we sought to test this observation. Objectives Evaluate frequency of significant findings and the safety of VFT in subjects undergoing device replacement. Methods A prospective observational multi-center study of VFT included consecutive patients undergoing ICD generator replacement in 5 centers in Israel, Europe, and the US. All centers followed the same VFT protocol. The primary outcome was defined as failure to terminate induced VF with a single shock at 10 Joules below the maximal capacity of the device. Secondary outcomes included complications of VFT. Patients were followed-up at 1 month and 6 months post-procedure. Data collection included documentation of any peri-operative complications and clinical endpoints (occurrence of appropriate shock, inappropriate shocks, lead failure, need for re-intervention, and infection). Results A total of 92 patients were eligible, and consented for the study, of which 84 underwent DFT during battery replacement. The median age was 68 years and 79.8% were male subjects. Induction of VF was successful in all 84 patients as well as VFT with a successful conversion on first attempt. During follow up one patient had two appropriate ICD shock events. In four patients, the ICD programming was changed. None suffered an inappropriate shock. There was no evidence of lead malfunction. A total of two deaths occurred, none of which were related to the device. Conclusion The present study found VFT was not associated with complications in patients undergoing ICD/CRTD generator replacement but produced no clinically important information.

Underrepresentation of women in implantable cardioverter defibrillator trials

There are sex differences in the epidemiology and presentation of ventricular arrhythmias. Sudden cardiac death (SCD) is less common in women than in men. Women have been under-represented in implantable cardioverter defibrillator (ICD) trials evaluating the benefit of ICD therapy for primary and secondary prevention of SCD. Following ICD implantation, women are less likely to experience appropriate ICD therapy for ventricular arrhythmias, consistent with epidemiological findings of a lower rate of SCD in women. Sex differences in ICD implantation rates have also been noted for primary and secondary prevention of SCD in registries and large observational cohort studies. Reasons for these differences are unclear. Age and comorbidities at the time of presentation may be partially responsible, although sex bias, patient preference, or contribution of social determinants of health cannot be excluded. There are many unanswered questions regarding reasons for sex differences in ICD usage and under-representation of women in clinical device trials. Additional investigation is needed to better understand these differences to improve outcome of all patients who are at risk for sudden cardiac arrest.

Abstract 11967: Benefit of Implantable Cardioverter Defibrillator Therapy in Patients With Advanced Renal Impairment: A Competing Risk Analysis From the MADIT Trials

Introduction: The life-saving benefit of the implantable cardioverter defibrillator (ICD) in patients with advanced chronic kidney disease (A-CKD) is still controversial. This is possibly due to a higher risk of dying from non-arrhythmic causes in A-CKD patients, and thereby die prior to receiving therapy from the ICD. We aimed to evaluate the competing risk for ventricular tachycardia/fibrillation (VT/VF) vs. death without prior VT/VF in ICD recipients by renal function. Methods: The study population comprised 3953 patients with an ICD enrolled in the landmark MADIT trials, categorized by renal function into: A-CKD (estimated Glomerular Filtration Rate [eGFR] ≤40 ml/min/1.73 m 2 [N=403]; Moderate CKD (eGFR 41-60 ml/min/1.73 m 2 [N=995]); and No-CKD (eGFR &gt;60 ml/min/1.73 m 2 [N=2555)). Cumulative incidence function curves were used to display the rate of fast VT/VF (&gt;200 bpm) and the competing risk of death without experiencing prior fast VT/VF using the Fine and Gray method. Results: At 4-years of follow-up, patients in the A-CKD group had a significantly lower cumulative incidence of VT/VF compared to patients with Moderate-CKD and No-CKD (13%, 17%, and 20%, respectively; p=0.006 for the overall difference [Figure: left panel]). In contrast, the corresponding 4-year rates of death without experiencing prior fast VT/VF were significantly highest among patients with A-CKD and attenuated among those with Moderate- and No-CKD (28%, 17%, and 9%, respectively; p&lt;0.001 for the overall difference [Figure: right panel]). Conclusion: Our data from 4 landmark primary prevention ICD trials show significant differences in the risk of VT/VF vs the competing risk of death without experiencing prior VT/VF by renal function. This suggests an attenuated benefit of ICD therapy with declining renal function.

Abstract 11977: Cardiac Resynchronization Therapy and the Risk of Ventricular Tachyarrhythmia

Introduction: Cardiac Resynchronization Therapy (CRT) was shown to be associated with clinically significant benefit by lowering mortality, heart failure hospitalizations, and improving quality of life in patients with reduced left ventricular function and a wide QRS. However, there are conflicting data on the effect of CRT on the risk of ventricular tachycardia or ventricular fibrillation (VT/VF) in implantable cardioverter defibrillator (ICD) recipients. Methods: The study population comprised 4531 patients enrolled in the 5 landmark ICD trials (MADIT-II, MADIT-CRT, MADIT-RIT, MADIT-RISK, and RAID) implanted with an ICD. Three patient groups were generated: ICD with a narrow QRS complex (n=2208), ICD alone with a wide QRS (n=1105), and patients with both ICD and a CRT (CRT-D) (n=2198). We compared the cumulative incidence of VT/VF in each group while accounting for the competing risk of non-arrhythmic mortality using the Fine and Gray Method. Results: Recipients of a CRT-D were more likely to be female, to use a beta blocker, and have a higher New York Heart Association Functional Class. The cumulative incidence of VT/VF at 4 years of follow-up in patients with a CRT-D was significantly lower (24%) as compared with patients with an ICD with or without a wide QRS (31% for both; p&lt;0.001 for the overall difference). Findings were consistent for the endpoints of appropriate ICD shocks and fast VT/VF (&gt;200 bpm). Multivariate analysis showed that compared to ICD-only therapy (with wide QRS), treatment with CRT-D was associated with a significant 20% (p=0.006), in the endpoint of VT/VF and 36% reduction in the endpoint of appropriate shock for VT/VF (p&lt;0.001). Conclusion: Our data from 5 landmark clinical trials suggest that cardiac resynchronization therapy exerts important antiarrhythmic properties, leading to a significant reduction in the risk of ventricular tachyarrhythmia and appropriate ICD shocks in patients implanted with an ICD for primary prevention.

Untying the Gordian knot of sex and heart failure therapy

Untying the Gordian knot of sex and heart failure therapy

Sex-specific differences in outcome and risk stratification of ventricular arrhythmias in implantable cardioverter defibrillator patients.

AimsRisk stratification models of sudden cardiac death (SCD) are based on the assumption that risk factors of SCD affect risk to a similar extent in both sexes. The aim of the study is to evaluate differences in clinical outcomes between sexes and evaluate whether risk factors associated with appropriate device therapy (ADT) differ between men and women.Methods and resultsWe performed a cohort study of implantable cardioverter defibrillator (ICD) patients referred for primary or secondary prevention of SCD between 2009 and 2018. Multivariable Cox regression models for prediction of ADT were constructed for men and women separately. Of 2300 included patients, 571 (25%) were women. Median follow‐up was 4.6 (inter‐quartile range: 4.4–4.9) years. Time to ADT was shorter for men compared with women [hazard ratio (HR) 1.71, P < 0.001], as was time to mortality (HR 1.37, P = 0.003). In women, only secondary prevention ICD therapy (HR 1.82, P < 0.01) was associated with ADT, whereas higher age (HR 1.20, P < 0.001), absence of left bundle branch block (HR 0.72, P = 0.01), and secondary prevention therapy (HR 1.80, P < 0.001) were independently associated with ADT in men. None of the observed parameters showed a distinctive sex‐specific pattern in ADT.ConclusionsMale ICD patients were at higher risk of ADT and death compared with female ICD patients, irrespective of an ischaemic or non‐ischaemic underlying cardiomyopathy. Our study highlights the importance to stratify outcomes of ICD trials by sex, as study results differ between men and women. However, none of the available clinical parameters showed a clear sex‐specific relation to ventricular arrhythmias. As a consequence, sex‐specific risk stratification models of SCD using commonly available clinical parameters could not be derived.

Survival After Implantable Cardioverter-Defibrillator Shocks

BackgroundThere are conflicting data on the impact of implantable cardioverter-defibrillator (ICD) shocks on subsequent mortality. ObjectivesThe aim of this study was to determine whether the arrhythmic substrate leading to ICD therapy or the therapy itself increases mortality. MethodsThe study cohort included 5,516 ICD recipients who were enrolled in 5 landmark ICD trials (MADIT-II, MADIT-RISK, MADIT-CRT, MADIT-RIT, RAID). The authors evaluated the association of device therapy with subsequent mortality in 4 separate time-dependent models: model I, type of ICD therapy; model II, type of arrhythmia for which ICD therapy was delivered; model III, combined assessment of all arrhythmia and therapy types during follow-up; and model IV, incremental risk associated with repeated ICD shocks. ResultsWhen analyzed by the type of ICD therapy (model I), a first appropriate ICD shock was associated with increased risk of subsequent mortality with or without concomitant occurrence of inappropriate shock during follow-up (hazard ratio [HR]: 2.78 and 2.31; p < 0.001 and p = 0.12), whereas inappropriate shock alone was not associated with mortality risk (HR: 1.23; p = 0.42). Similarly, ICD therapy for ventricular tachycardia (VT) ≥200 beats/min or ventricular fibrillation (VF) (model II) was associated with increased risk of death with or without concomitant therapy for VT <200 beats/min (HRs: 2.25 and 2.62; both p < 0.001), whereas appropriate therapy for VT <200 beats/min or inappropriate therapy (regardless of etiology) did not reach statistical significance (all p > 0.10). Combined assessment of all therapy and arrhythmia types during follow-up (model III) showed that appropriate ICD shocks for VF, shocks for fast VT (≥200 beats/min) without prior antitachycardia pacing (ATP), as well as shocks for fast VT delivered after failed ATP, were associated with the highest risk of subsequent death (HR: all >2.8; p < 0.001). Finally, 2 or more ICD appropriate shocks were not associated with incremental risk to the first appropriate ICD shock (model IV). ConclusionThe combined data from 5 landmark ICD trials suggest that the underlying arrhythmic substrate rather than the ICD therapy is the more important determinant of mortality in ICD recipients.

Abstract 17496: The Effect of Statin on Ventricular Tachyarrhythmia Burden

Introduction: Statins may reduce risk for ventricular tachyarrhythmia (VTA) in patients with implantable cardioverter defibrillator (ICD). Ranolazine was shown to increase plasma concentrations of statin. Objective: To evaluate the effect of statin on recurrent VTA, and to explore the interaction with both Ranolizine and cardiomyopathy (CMP) origin. Methods: The Andersen-Gill extension of the Cox proportional hazards regression was used to assess the association between statin treatment and the risk for recurrent VTA among 1012 ICD patients enrolled in the Ranolazine Implantable Cardioverter-Defibrillator Trial (RAID). Interaction-term analysis with ranolazine and ischemic status were performed. Number of events was limited to a maximum of 10 VTA events per patient to avoid any patients having an undue influence on model estimates. Results: A total of 740 (73%) RAID patients were treated with statins. Multivariable analysis showed that statin use was associated with an overall 30% reduction in the risk for recurrent VTA (HR=0.70; p&lt;0.001)(Figure). Interaction analysis showed that the benefit of statin use was seen only among patients with non-ischemic CMP (HR=0.53 [95%CI 0.41-0.69]; p&lt;0.001), whereas there was no evidence of benefit among patients with ischemic CMP for recurrent VTA (HR=1.03 [95%CI 0.70-1.54] p=0.70), with an interaction p-value of &lt;0.01 for the differential effect of statin use on recurrent VTA by CMP origin. The effect of statin was relatively consistent and did not differ significantly between the ranolazine and placebo arms (Figure). Statin use was not associated with increased adverse events, and ranolazine discontinuation was higher among those who were not treated with statins vs. those who received statin therapy (53% vs 42%, respectively; p&lt;0.01). Conclusion: Our findings suggest that treatment with statin (regardless if with or without ranolazine) is highly effective in reducing VTA burden in non-ischemic ICD recipients.

Who is shocked and who survives? A multi-state analysis of the NORDIC ICD trial

Abstract Background/Purpose The interaction between the risk of arrhythmic death and a competing non-arrhythmic risk of death in patients suitable for implantable cardioverter defibrillator (ICD) implantation is not well understood. Commonly, identification of subpopulations with the largest benefit of ICD implantation has been performed by separate risk models for the outcomes death and appropriate shock therapy. The interrelation between the outcomes was not sufficiently studied. Methods Data were derived from the safety population of the multinational, prospectively randomized NORDIC ICD trial (N=1067) with real-word patients implanted with a single, dual or triple chamber ICD for primary or secondary prevention. Since all outcome adjudication was performed by an independent Clinical Event Committee supported by full telemonitoring data transmission, a high validity of ICD interventions could be achieved. To investigate the impact of baseline characteristics on time to first appropriate shock, death without prior appropriate shock therapy and death after appropriate shock therapy, a multi-state Cox model was computed. Missing data have been multiply imputed before analysis. Results At 36 months follow-up, 86.4% of the patients were alive (7.8% after appropriate shock). 11.0% and 2.6% patients died without or after a foregoing appropriate shock, respectively. The primary randomization allocation showed no significant effect on the 3 outcome types. Higher age (per 5 years) and NYHA functional class (≥III vs. ≤II) were associated with an increased risk of death without appropriate shock (HR 1.31, 95% CI 1.14–1.50, p&amp;lt;0.001, and HR 2.17, 95% CI 1.26–3.74, p=0.005, fig.1, accordingly). The presence of diabetes mellitus at baseline was associated with the reduced risk of the occurrence of an appropriate shock (HR 0.57, 95% CI 0.35–0.92, p=0.022). Patients with secondary prevention indication for an ICD had very high risk for an appropriate shock after ICD implantation (HR 3.21, 95% CI 2.02–5.11, p&amp;lt;0.001), but not for death without or with previous appropriate shock (HR 1.42, 95% CI 0.72–2.79, p=0.306, or HR 0.73, 95% CI 0.23–2.34, p=0.594 after ICD shock). Renal insufficiency and ischemic vs. nonischemic disease showed a significantly increased global effect on all three transitions (HR 1.63, 95% CI 1.18–2.24, p=0.003 and HR 1.53, 95% CI 1.06–2.20, p=0.025, respectively). Conclusion The new multi-state model shows the interrelation between appropriate shocks and death, as well a remarkable variation of risk factors for the transitions. Specifically, the presence of higher age and NYHA functional class ≥III at baseline were strong prognostic factors for all-cause mortality without a foregoing shock therapy, but were not predictive for an appropriate shock therapy. In this all-comer study, a significant discriminator predictive for appropriate shock therapy, but not for death was an indication for secondary prevention of sudden cardiac death. Multi-state graph for NYHA class Funding Acknowledgement Type of funding source: Private company. Main funding source(s): This work was supported by Biotronik SE &amp; Co. KG (Berlin, Germany)

P1464A question of gender equality. Sex-related differences in survival after primary prevention implantable cardioverter-defibrillator implantation for dilated cardiomyopathy An analysis from POLKARD

Abstract OnBehalf POLKARD Polish ICD Registry Background The protective effects of implantable cardioverter defibrillators (ICDs) in the primary prevention of sudden cardiac death of patients presenting with left ventricular (LV) systolic dysfunction are unequivocal. Nevertheless, female underrepresentation has been a consistent finding in all randomized controlled primary prevention ICD trials. Surprisingly, there is a vast body of literature on female primary prevention ICD patients exhibit a lower overall mortality. Purpose Therefore, we analyzed data from a large, nationwide POLKARD registry to evaluate the effect of sex on survival after primary prevention cardioverter-defibrillator implantation for dilated cardiomyopathy. Methods All patients enrolled in the Polish ICD Registry from 2008 to 2014 were identified. Patients were included in the study if they were designated as receiving an ICD for primary prevention of SCD after documented non-ischeamic cardiomyopathy. Kaplan-Meier survival analysis was used to assess all-cause mortality. Results Of the 964 ICD recipients, 241 (25%) were women (mean age of 64± 0,45 years). During a mean follow-up of 5,53 ± 2,48 years 32% of women and 42% of men died. Kaplan-Meier curve depicted a significantly lower mortality for women than for men (p = 0,05). The median survival time was 6,73 years (55 deaths per 1000 person-years) versus 6,37 years (78 deaths per 1000 person-years) for women and men, respectively. Conclusions In agreement with previous studies, our data indicate that primary prevention implantation rates for dilated cardiomyopathy are lower in women. However, the reasons are not entirely understood.