Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate Therapy Research Articles

Primary results from the Japanese Heart Failure and Sudden Cardiac Death Prevention Trial (HINODE).

AimsThe HINODE study aimed to analyse rates of mortality, appropriately treated ventricular arrhythmias (VA), and heart failure in Japanese patients and compared with those in Western patients.Methods and resultsAfter treatment decisions following contemporary practice in Japan, patients were prospectively enrolled into four cohorts: (i) internal cardioverter‐defibrillator (ICD), (ii) cardiac resynchronization therapy (CRT) defibrillator (CRT‐D), (iii) standard medical therapy (‘non‐device’: ND), or (iv) pacing (indicated for CRT; received pacemaker or CRT pacing). Cohorts 1–3 required a left ventricular ejection fraction ≤35%, a history of heart failure, and a need for primary prevention of sudden cardiac death based on two to five previously identified risk factors. Endpoint outcomes were adjudicated by the independent committees. ICD and CRT‐D cohorts, considered as high‐voltage (HV) cohorts, were pooled for Kaplan–Meier analysis and propensity‐matched to Multicenter Automatic Defibrillator Implantation Trial‐Reduce Inappropriate Therapy (MADIT‐RIT) arm B and C patients. The study enrolled 354 patients followed for 19.6 ± 6.5 months, with a minimum of 12 months. Propensity‐matched HV cohorts showed comparable VA (P = 0.61) and mortality rates (P = 0.29) for HINODE and MADIT‐RIT. The ND cohort presented a high crossover rate to ICD therapy (6.1%, n = 7/115), and the CRT‐D cohort showed elevated mortality rates. The pacing cohort revealed that patients implanted with pacemakers had higher mortality (26.0%) than those with CRT‐Pacing (8.4%, P = 0.05).ConclusionsThe mortality and VA event rates of landmark trials are applicable to patients with primary prevention in Japan. Patients who did not receive guideline‐indicated CRT devices had poor outcomes.

Reassessing the role of antitachycardia pacing in fast ventricular arrhythmias in primary prevention implantable cardioverter-defibrillator recipients: Results from MADIT-RIT

In Multicenter Automatic Defibrillator Implantation Trial - Reduce Inappropriate Therapy (MADIT-RIT), high-rate cutoff (arm B) and delayed therapy (arm C) reduced the risk of inappropriate implantable cardioverter-defibrillator (ICD) interventions when compared with conventional programming (arm A); however, appropriate but unnecessary therapies were not evaluated. The purpose of this study was to assess the value of antitachycardia pacing (ATP) for fast ventricular arrhythmias (VAs) ≥ 200 beats/min in patients with primary prevention ICD. We compared ATP only, ATP and shock, and shock only rates in patients in MADIT-RIT treated for VAs ≥ 200 beats/min. The only difference between these randomized groups was the time delay between ventricular tachycardia detection and therapy (3.4 seconds vs 4.9 seconds vs 14.4 seconds). In arm A, 11.5% patients had events, the initial therapy was ATP in 10.5% and shock in 1%, and the final therapy was ATP in 8% and shock in 3.5%. In arm B, 6.6% had events, 4.2% were initially treated with ATP and 2.4% with shock, and the final therapy was ATP in 2.8% and shock in 3.8%. In arm C, 4.7% had events, 2.5% were initially treated with ATP and 2.3% with shock, and the final therapy was ATP in 1.4% and shock in 3.3%. The final shock rate was similar in arm A vs arm B (3.5% vs 3.8%; P = .800) and in arm A vs arm C (3.5% vs 3.3%; P = .855) despite the marked discrepancy in initial ATP therapy utilization. In MADIT-RIT, there was a significant reduction in ATP interventions with therapy delays due to spontaneous termination, with no difference in shock therapies, suggesting that earlier interventions for VAs ≥ 200 beats/min are likely unnecessary, leading to an overestimation of the value of ATP in primary prevention ICD recipients.

Implantable cardioverter-defibrillator programming after first occurrence of ventricular tachycardia in the Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate Therapy (MADIT-RIT).

BackgroundImplantable cardioverter-defibrillator (ICD) programming to novel settings can reduce the risk of inappropriate therapies.ObjectiveThe purpose of this study was to evaluate the impact of novel ICD programming after the first occurrence of ventricular tachycardia (VT).MethodsIn MADIT-RIT (Multicenter Automatic Defibrillator Implantation Trial–Reduce Inappropriate Therapy) patients who experienced a first occurrence of VT, the risk of subsequent inappropriate and appropriate ICD therapies and adverse cardiovascular events by ICD programming to Arm A (conventional: VT ≥170 bpm), Arm B (high rate: VT ≥200 bpm), or Arm C (duration delay: ≥60-second delay before therapy ≥170 bpm) was determined.ResultsAmong 205 patients, ICD programming changes were made in 30 patients (15%) after they experienced a VT episode; 117 patients (57%) were programmed to Arm A settings and 88 patients (43%) to Arm B/C settings. At 15-month follow-up, the cumulative probability of inappropriate ICD therapy was significantly lower in Arm B/C compared to Arm A (9% vs 20%; log-rank P = .029 for overall difference). The rate of appropriate ICD therapy also was significantly lower in Arm B/C compared to Arm A (32% vs 64%; log-rank P = .001 for overall difference). Multivariate analysis showed that patients programmed to Arm B/C after the occurrence of VT had a 71% reduction (P = .02) in the risk of inappropriate ICD therapies and a 43% reduction (P = .02) in the risk of appropriate ICD therapies compared to Arm A.ConclusionThe benefit of high-rate cutoff or duration delay settings in patients with an ICD is maintained after the first occurrence of VT.

Predictors and outcomes of atrial tachyarrhythmia among patients with implantable defibrillators

Atrial tachyarrhythmias (ATAs) are common among heart failure (HF) patients. The purpose of this study was to assess predictors for the development of new ATA and its components (atrial fibrillation/flutter [AF], supraventricular tachycardia [SVT]), and their association with subsequent clinical outcomes. We assessed predictors for first and recurrent ATA, AF, and SVT among 1500 patients in MADIT-RIT (Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate Therapy). We also investigated the association of new ATA, AF, or SVT with subsequent ventricular arrhythmia (VA), adverse events (HF hospitalization, syncope, or death), or death by time-dependent analysis. During 17 months of follow-up, 286 patients (19%) developed new ATA, of whom 92 (6%) had AF and 194 (12%) had SVT. Younger age (≤65 years), diastolic blood pressure ≥72 mm Hg, heart rate ≥63 bpm, absence of diabetes, and prior atrial arrhythmia were independent predictors of ATA. Prior atrial arrhythmia was the only predictor of AF (hazard ratio 3.14; P <.001). New ATA was associated with significantly increased risk for subsequent VA (HR 2.12; P <.001), increased adverse events (HR 1.42; P <.001), and death (HR 1.85; P = .038). New AF and new SVT were both independently associated with >2-fold increased risk for the development of subsequent VA (HR 2.21; P= .012l and HR 2.15; P <.001, respectively) and adverse events. Among MADIT-RIT patients, younger age, absence of diabetes, higher blood pressure, higher heart rate, and prior atrial arrhythmia predicted device-detected ATA. Both AF and SVT were associated with increased risk for subsequent VA and adverse events. Aggressive management should be considered in HF patients who develop new-onset, device-detected ATA to improve clinical outcomes.

2179Clinical significance of device-derived activity in ICD and CRT-D patients - Data from MADIT-RIT

Abstract Background The Multicenter Automatic Defibrillator Implantation Trial – Reduce Inappropriate Therapy (MADIT-RIT) enrolled 1500 patients and showed that novel ICD programming reduced inappropriate therapy and improved survival. However, the role of device-derived patient activity to predict mortality is not known. Methods In 1500 patients enrolled in MADIT-RIT, device-derived patient activity was captured daily. Device-derived activity was averaged for the first 30 days following randomization, and utilized in this study to predict mortality post-30 days. Kaplan-Meier survival analysis and multivariate Cox proportional hazards regression models were used to evaluate all-cause mortality by 30-day device derived patient activity quintiles, and as a 3-level function of 30-day device derived patient activity (Q1, Q2–3, Q4–5). Results There were a total of 1463 patients with data available (98%), 66 of them died during the follow-up post-30 days. Patients in the lowest quintile (Q1: 4%∼1 hour daily activity) of device-derived activity were older, they were more often female, and they more often had diabetes and NYHA class III HF symptoms. Patients in the lowest quintile of 30-day device derived median activity (1 hour daily activity) had the highest risk of mortality, 15% in 2 years as compared to Q2–3 (1–2 hours daily activity, 8–7% 2-year mortality), and Q4–5 (&gt;2 hours daily activity, 2–3% 2-year mortality) (Figure, p&lt;0.001 for the overall duration). Each quintile decrease in device-derived 30-day median patient activity was associated with a significant, 41% increase in mortality (HR=1.41, 95% CI: 1.15–1.71, p=0.001). Patients with the lowest level of 30-day median patient activity (Q1) had 4.13-times higher risk of mortality as compared to the highest level of activity patients, Q4–5 (HR=4.13, 95% CI: 1.89–9.03, p&lt;0.001). Patients with intermediate levels of activity (Q2–3) still had a 2.8-fold increase in death as compared to the highest activity level cohort of patients (HR=2.79, 95% CI: 1.31–5.91, p=0.008). Figure 1 Conclusions Device-derived 30-day median patient activity predicted subsequent all-cause mortality in ICD and CRT-D patients enrolled in MADIT-RIT. Patients with low and moderate levels of 30-day device-derived median patient activity (less than 2 hours daily activity) were at a significantly higher risk of death, and these cohorts warrant further investigation and management to improve outcomes. Acknowledgement/Funding MADIT-RIT was funded by an unrestricted research grant from Boston Scientific to the University of Rochester.

P2277Utility of cardiovascular implantable electronic device (CIED)-derived patient activity, a novel digital biomarker, to predict inappropriate therapy

Abstract Background The role of cardiovascular implantable electronic device (CIED)-derived activity to predict inappropriate implantable cardioverter-defibrillator (ICD) therapy is not known. The Multicenter Automatic Defibrillator Implantation Trial – Reduce Inappropriate Therapy (MADIT-RIT) enrolled 1500 patients with contemporary indication for an ICD or a CRT-D. We aimed to identify whether activity, as a digital biomarker, predicted inappropriate therapy. Methods In 1500 patients enrolled in MADIT-RIT, CIED-derived patient activity was acquired daily. CIED-derived activity was averaged for the first 30 days following randomization and utilized in this study to predict inappropriate therapy post- 30-day. Kaplan-Meier survival analysis and multivariate Cox proportional hazards regression models were used to evaluate first inappropriate therapy by 30-day CIED-derived patient activity quintiles, and by 30-day device derived patient activity as a continuous measurement. Results There were a total of 1463 patients with activity data available (90%), 135 patients received at least one inappropriate therapy during the post-30 day follow-up period. Patients in the highest quintile (Q5) of CIED-derived activity (more active) were younger, more often males and more likely to have had a prior ablation of an atrial arrhythmia. Patients in the highest quintile of 30-day CIED-derived median activity had the highest risk of receiving inappropriate therapy, 21% at 2 years as compared 7–11% in the other four quintiles (Figure, p&lt;0.001 for the overall duration). Patients with the highest level of 30-day median patient activity (Q5) had 1.75 times higher risk of any inappropriate therapy as compared with lower levels of activity, Q1-Q4 (HR=1.75, 95% CI: 1.23–2.50, p&lt;0.002). Each 10% increase in CIED-derived 30-day median patient activity was associated with a significant, 73% increase in risk of receiving inappropriate therapy (HR=1.73, 95% CI: 1.17–2.54, p=0.005). Patients in the highest quintile for activity had a 68% increase in the risk of SVT excluding atrial fibrillation, atrial flutter or atrial tachycardia (HR=1.69, 95% CI: 1.26–2.25, p=0.004), despite 96% receiving beta-blocker medications. Inappropriate ICD Therapies by Activity Conclusions CIED-derived 30-day median patient activity predicted subsequent inappropriate therapy in ICD and CRT-D patients enrolled in MADIT-RIT. Patients with high levels of 30-day CIED-derived median patient activity were at a significantly higher risk of receiving inappropriate therapy. Activity, as a digital biomarker, may have utility in predicting and managing the risk of inappropriate therapy in this population. Acknowledgement/Funding Boston Scientific

Effects of implantable cardioverter/defibrillator shock and antitachycardia pacing on anxiety and quality of life: A MADIT-RIT substudy

We evaluated changes in QoL from baseline to 9-month follow-up using the EQ-5D questionnaire in patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate Therapy (MADIT-RIT) (n=1,268). We assessed anxiety levels using the Florida Shock Anxiety Scale (1-10 score) in patients with appropriate or inappropriate shocks or ATP compared to those with no ICD therapy during the first 9 months postimplant. The analysis was stratified by number of ATP or shocks (0-1 vs ≥2) and adjusted for covariates. In MADIT-RIT, 15 patients (1%) had ≥2 appropriate shocks, 38 (3%) had ≥2 appropriate ATPs. Two or more inappropriate shocks were delivered in 16 patients (1%); ≥2 inappropriate ATPs, in 70. In multivariable analysis, patients with ≥2 appropriate shocks had higher levels of shock-related anxiety than those with ≤1 appropriate shock (P<.01). Furthermore, ≥2 inappropriate shocks produced more anxiety than ≤1 inappropriate shock (P=.005). Consistently, ≥2 appropriate ATPs resulted in more anxiety than ≤1 (P=.028), whereas the number of inappropriate ATPs showed no association with anxiety levels (P=.997). However, there was no association between QoL and appropriate or inappropriate ATP/shock (all P values > .05). In MADIT-RIT, ≥2 appropriate or inappropriate ICD shocks and ≥2 appropriate ATPs are associated with more anxiety at 9-month follow-up despite no significant changes in the assessment of global QoL by the EQ-5D questionnaire. Innovative ICD programming reducing inappropriate therapies may help deal with patient concerns about the device.

Electrophysiology Updates in Adult Congenital Heart Disease.

Electrophysiology Updates in Adult Congenital Heart Disease.

Novel ICD Programming and Inappropriate ICD Therapy in CRT-D Versus ICD Patients

The Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate therapy (MADIT-RIT) trial showed a significant reduction in inappropriate implantable cardioverter defibrillator (ICD) therapy in patients programmed to high-rate cut-off (Arm B) or delayed ventricular tachycardia therapy (Arm C), compared with conventional programming (Arm A). There is limited data on the effect of cardiac resynchronization therapy with a cardioverter defibrillator (CRT-D) on the effect of ICD programming. We aimed to elucidate the effect of CRT-D on ICD programming to reduce inappropriate ICD therapy in patients implanted with CRT-D or an ICD, enrolled in MADIT-RIT. The primary end point of this study was the first inappropriate ICD therapy. Secondary end points were inappropriate anti-tachycardia pacing and inappropriate ICD shock. The study enrolled 742 (49%) patients with an ICD and 757 (51%) patients with a CRT-D. Patients implanted with a CRT-D had 62% lower risk of inappropriate ICD therapy than those with an ICD only (hazard ratio [HR] =0.38, 95% confidence interval: 0.25-0.57; P<0.001). High-rate cut-off or delayed ventricular tachycardia therapy programming significantly reduced the risk of inappropriate ICD therapy compared with conventional ICD programming in ICD (HR=0.14 [B versus A]; HR=0.21 [C versus A]) and CRT-D patients (HR=0.15 [B versus A]; HR=0.23 [C versus A]; P<0.001 for all). There was a significant reduction in inappropriate anti-tachycardia pacings in both group and a significant reduction in inappropriate ICD shock in CRT-D patients. Patients implanted with a CRT-D have lower risk of inappropriate ICD therapy than those with an ICD. Innovative ICD programming significantly reduces the risk of inappropriate ICD therapy in both ICD and CRT-D patients. http://clinicaltrials.gov; Unique identifier: NCT00947310.

Relationship between age and inappropriate implantable cardioverter-defibrillator therapy in MADIT-RIT (Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate Therapy)

There is limited data regarding the relationship between age and inappropriate therapy among patients with an implantable cardioverter-defibrillator (ICD) and resynchronization therapy. We aimed to investigate this relationship and the effect of ICD programming on inappropriate therapy by age. In the Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate Therapy (MADIT-RIT) 1500 patients were randomized to 3 ICD programming arms: (A) conventional with ventricular tachycardia (VT) therapy ≥170; (B) high-rate cutoff with VT therapy ≥200, and (C) prolonged 60-second delay for VT therapy ≥170. We investigated the relationship between age, the risk of inappropriate ICD therapy (including antitachycardia pacing [ATP] or shock), and ICD programming. Cumulative incidence function Kaplan-Meier graphs showed an inverse relationship between increasing quartiles of age (Q1: ≤55, Q2: 56-64, Q3: 65-71, and Q4: ≥72 years) and the risk for inappropriate therapy. Multivariate analyses showed that each increasing decade of life was associated with 34% (P < .001), 27% (P < .001), and 26% (P < .001) reduction in the risk of inappropriate shock, inappropriate ATP, and any inappropriate therapy, respectively. Treatment arms B and C as compared with arm A were associated with a significant reduction in the risk of inappropriate therapies across all age quartiles (P < .001 for all). Among patients with a primary prevention indication for an ICD, there is an inverse relationship between age and inappropriate ICD therapy. Innovative ICD programming of high-rate cutoff or prolonged delay for VT therapy is associated with significant reductions in inappropriate therapy among all age groups.

Abstract 12708: Similar Risk of Heart Failure Hospitalization in MADIT-RIT Programming Arms

Background: In MADIT-RIT (Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate Therapy), we reported a significant reduction in inappropriate ICD therapy and mortality with novel ICD programming, either a high-rate cut-off (VT zone ≥ 200 bpm, Arm B) or 60-sec delayed therapy in the VT zone 170-199 bpm (Arm C), as compared to conventional programming (VT zone&gt;170 bpm, Arm A). However, the effect of novel ICD programming on heart failure (HF) events has not been investigated. Methods: In MADIT-RIT patients (n=1500), we assessed risk of hospitalization with heart failure (HF) in the three programming arms. Brief summaries of each hospitalization were independently reviewed by three experienced cardiologists and HF events identified according to pre-specified criteria. Discrepancies were resolved by a fourth cardiologist. Kaplan-Meier cumulative probabilities and multivariable Cox hazards regression analyses were performed. Results: There was a similar probability of HF hospitalization (p=0.341) and HF hospitalization or death (p=0.207) in all three programming arms in MADIT-RIT (Figure). There were no differences in HF hospitalization in Arm B vs. A (HR=0.91, 95%CI: 0.63-1.33, p=0.629) or Arm C vs. A (HR=1.20, 95%CI: 0.84-1.72, p=0.310) after multivariable adjustments for age, NYHA class, diabetes, ICD vs. CRT-D, ejection fraction, and ischemic vs. non-ischemic cardiomyopathy. Similarly, there were no differences in HF or death in Arm B vs. A (HR=0.78, 95%CI: 0.56-1.10, p=0.154), or in Arm C vs. A (HR=1.06, 95%CI: 0.77-1.45, p=0.723) after multivariable adjustments. Risk of multiple hospitalizations was also the similar in the three programming arms. Conclusions: In MADIT-RIT, the mortality benefit seen with novel ICD programming was not accompanied by reduction in heart failure events. Conversely, greater mortality risk with conventional ICD programming was not associated with increased risk of heart failure hospitalization.

Mortality reduction in relation to implantable cardioverter defibrillator programming in the Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate Therapy (MADIT-RIT).

The benefit of novel implantable cardioverter defibrillator (ICD) programming in reducing inappropriate ICD therapy and mortality was demonstrated in Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate Therapy (MADIT-RIT). However, the cause of mortality reduction remains incompletely evaluated. We aimed to identify factors associated with mortality, with focus on ICD therapy and programming in the MADIT-RIT population. In MADIT-RIT, 1500 patients with a primary prophylactic indication for ICD or cardiac resynchronization therapy with defibrillator were randomized to 1 of 3 different ICD programming arms: conventional programming (ventricular tachycardia zone ≥170 beats per minute), high-rate programming (ventricular tachycardia zone ≥200 beats per minute), and delayed programming (60-second delay before therapy ≥170 beats per minute). Multivariate Cox models were used to assess the influence of time-dependent appropriate and inappropriate ICD therapy (shock and antitachycardia pacing) and randomized programming arm on all-cause mortality. During an average follow-up of 1.4±0.6 years, 71 of 1500 (5%) patients died: cardiac in 40 patients (56.3%), noncardiac in 23 patients (32.4%), and unknown in 8 patients (11.3%). Appropriate shocks (hazard ratio, 6.32; 95% confidence interval, 3.13-12.75; P<0.001) and inappropriate therapy (hazard ratio, 2.61; 95% confidence interval, 1.28-5.31; P=0.01) were significantly associated with an increased mortality risk. There was no evidence of increased mortality risk in patients who experienced appropriate antitachycardia pacing only (hazard ratio, 1.02; 95% confidence interval, 0.36-2.88; P=0.98). Randomization to conventional programming was identified as an independent predictor of death when compared with patients randomized to high-rate programming (hazard ratio, 2.0; 95% confidence interval, 1.06-3.71; P=0.03). In MADIT-RIT, appropriate shocks, inappropriate ICD therapy, and randomization to conventional ICD programming were independently associated with an increased mortality risk. Appropriate antitachycardia pacing was not related to an adverse outcome. clinicaltrials.gov Unique identifier: NCT00947310.

Select Articles Published on the Topic of Arrhythmia and Electrophysiogy in 2013

Select Articles Published on the Topic of Arrhythmia and Electrophysiogy in 2013

Response to Letter Regarding Article, “Survival After Implantable Cardioverter-Defibrillator Implantation in the Elderly”

We thank Barra and Agarwal for their interest in our examination of implantable cardioverter-defibrillator (ICD) outcomes and therapies in different age groups, focusing on the elderly.1 We agree that rates of device therapies with conventional programming may overestimate the potential benefit of ICD implantation. Barra and Agarwal suggest that device programming approaches that were used in the Primary Prevention Parameters Evaluation (PREPARE),2 Multicenter Automatic Defibrillator Implantation Trial - Reduce Inappropriate Therapy (MADIT-RIT),3 and Avoid Delivering Therapies for Non-sustained Arrhythmias in ICD Patients III (ADVANCE III)4 trials would lead to rates of appropriate shock and therapy that better reflect the occurrence of ventricular tachyarrhythmia episodes that would more likely have been associated with an arrhythmic death. Early after the initiation of the Ontario ICD Database, the PREPARE study was published, the potential benefits of delaying ICD-delivered therapies were recognized, and participating sites adapted …

Circulation : Clinical Summaries

<i>Circulation</i> : Clinical Summaries

Syncope in High-Risk Cardiomyopathy Patients With Implantable Defibrillators: Frequency, Risk Factors, Mechanisms, and Association With Mortality

Background— There is a relative paucity of studies investigating the mechanisms of syncope among heart failure patients with implantable cardioverter-defibrillators, and it is controversial whether nonarrhythmogenic syncope is associated with increased mortality. Methods and Results— The Multicenter Automatic Defibrillator Implantation Trial–Reduce Inappropriate Therapy (MADIT-RIT) randomized 1500 patients to 3 different implantable cardioverter-defibrillator programming arms: (1) Conventional programming with therapy for ventricular tachycardia ≥170 bpm; (2) high-rate cutoff with therapy for ventricular tachycardia ≥200 bpm and a monitoring zone at 170 to 199 bpm, and (3) prolonged 60-second delay with a monitoring zone before therapy. Syncope was a prespecified safety end point that was adjudicated independently. Multivariable Cox models were used to identify risk factors associated with syncope and to analyze subsequent risk of mortality. During follow-up, 64 of 1500 patients (4.3%) had syncope. The incidence of syncope was similar across the 3 treatment arms. Prognostic factors for all-cause syncope included the presence of ischemic cardiomyopathy (hazard ratio [HR], 2.48; 95% confidence interval [CI], 1.42–4.34; P =0.002), previous ventricular arrhythmias (HR, 2.99; 95% CI, 1.18–7.59; P =0.021), left ventricular ejection fraction ≤25% (HR, 1.65; 95% CI, 0.98–2.77; P =0.059), and younger age (by 10 years; HR, 1.25; 95% CI, 1.00–1.52; P =0.046). Syncope was associated with increased risk of death regardless of its cause (arrhythmogenic syncope: HR, 4.51; 95% CI, 1.39–14.64, P =0.012; nonarrhythmogenic syncope: HR, 2.97; 95% CI, 1.07–8.28, P =0.038). Conclusions— Innovative programming of implantable cardioverter-defibrillators with therapy for ventricular tachycardia ≥200 bpm or a long delay is not associated with increased risk of arrhythmogenic or all-cause syncope, and syncope caused by slow ventricular tachycardias (&lt;200 bpm) is a rare event. The clinical risk factors associated with syncope are related to increased cardiovascular risk profile, and syncope is associated with increased mortality irrespective of the cause. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00947310.

Circulation : Clinical Summaries

<i>Circulation</i> : Clinical Summaries

Influence of Diabetes Mellitus on Inappropriate and Appropriate Implantable Cardioverter-Defibrillator Therapy and Mortality in the Multicenter Automatic Defibrillator Implantation Trial–Reduce Inappropriate Therapy (MADIT-RIT) Trial

The relationship between diabetes mellitus and risk of inappropriate or appropriate therapy in patients receiving an implantable cardioverter-defibrillator (ICD) and resynchronization therapy has not been investigated thoroughly. The effect of innovative ICD programming on therapy delivery in these patients is unknown. The Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate Therapy (MADIT-RIT) randomized patients with a primary prophylactic ICD indication to 3 different types of ICD programming: conventional programming with a ventricular tachycardia zone of 170 to 199 bpm (arm A), high-rate cutoff with a ventricular tachycardia zone ≥200 bpm (arm B), or 60-second-delayed therapy (arm C). The end points of inappropriate therapy, appropriate therapy, and death were assessed among 485 patients with and 998 without diabetes mellitus. Innovative ICD programming reduced the risk of inappropriate therapy regardless of diabetes mellitus, although a trend toward a more pronounced effect of high-rate cutoff programming was seen in patients without diabetes mellitus (P for interaction=0.06). Diabetes mellitus was associated with a decreased risk of inappropriate therapy (hazard ratio, 0.54; 95% confidence interval, 0.36-0.80; P=0.002) and increased risk of appropriate therapy (hazard ratio, 1.58; 95% confidence interval, 1.17-2.14; P=0.003). In diabetic patients, there was significantly increased risk of death in those who had inappropriate therapy (hazard ratio, 4.17; 95% confidence interval, 1.52-11.40; P=0.005) and appropriate therapy (hazard ratio, 2.49; 95% confidence interval, 1.06-5.87; P=0.037) compared with those who did not. Innovative high-rate cutoff or delayed ICD programming was associated with a reduction in inappropriate therapy in patients with and without diabetes mellitus. Diabetes mellitus was associated with lower risk of inappropriate therapy but higher risk of appropriate therapy. Appropriate and inappropriate ICD therapy was associated with increased mortality in diabetic patients. URL: http://www.clinicaltrials.gov. UNIQUE IDENTIFIER: NCT00947310.

The benefit of implantable cardioverter defibrillator programming in MADIT-RIT: more for less?

Multicenter Automatic Defibrillator Implantation Trial—Reduce Inappropriate Therapy (MADIT-RIT) confirmed the benefit of optimizing the programming of implantable cardioverter defibrillator (ICD) therapy for the reduction of inappropriate therapy and all-cause mortality, with no impact on the incidence of syncope.1 The true effectiveness of this intervention can be better illustrated by estimating the number needed to treat (NNT)2 ( Table 1 ): to avoid one death, 29 patients had to be programmed using high-rate therapy and 43 with delayed therapy, as compared with conventional programming. This means that physicians may start saving lives (see numbers above for NNT) in primary prevention patients more effectively than avoiding inappropriate shocks (NNT of 59–82 patients, according to the treatment arm) by …