The implantable cardioverter defibrillator (ICD) is highly effective in reducing mortality due to cardiac arrhythmias in high-risk cardiac patients. However, inappropriate therapies caused predominantly by supraventricular tachyarrhythmias (SVTs) remain a significant side effect of ICD therapy despite medical treatment, affecting 8-40% of patients. The MADIT-RIT is a global, prospective, randomized, nonblinded, three-arm, multicenter clinical investigation to be performed in the Unites States, Europe, Canada, Israel and Japan, and will utilize approximately 90 centers with plan to enroll 1500 patients programmed to three treatment arms. The objective of the MADIT-RIT trial is to determine if dual-chamber ICD or CRT-D devices with high rate cutoff (MADIT-RIT-Arm B) and/or long delay in combination with detection enhancements (MADIT-RIT-Arm C) are associated with fewer patients experiencing inappropriate therapies than standard programming (MADIT-RIT-Arm A) during postimplant follow-up of patients with indication for primary prevention device therapy. This paper describes design and analytic plan for the MADIT-RIT trial.

A strategy of maintaining sinus rhythm long-term with an IAD is feasible in a proportion of patients. However, patient selection is critical, and technical improvements (i.e. higher shock energies, dual-chamber pacing and additional preventive and anti-tachycardia pacing algorithms) are required to increase the number of patients having long term benefit, and frequent arrhythmia recurrences and patient intolerance to repeated cardioversion shocks remain a major limitation.

Background: Various lead designs have been developed to accommodate different coronary sinus anatomies. Our objectives were to compare electrical parameters of straight and spiral left ventricular leads, to evaluate capture thresholds and impedances using different pacing vectors, and to study evolution of thresholds over time. Methods:The RALLY-X4 study enrolled patients implanted with a lead from the Acuity X4 family (straight, spiral short, or spiral long). Electrical parameters (including capture thresholds from all 17 vectors) were measured at baseline and follow-up. Results: Data from 795 patients who were successfully implanted were analyzed. Straight and spiral leads had similar proportions of patients with thresholds <2.5 V/0.4 ms using the distal electrode (61-65% of patients) or from at least one of the proximal (E2-E4) electrodes (81-83% of patients). Unipolar vectors had significantly lower thresholds and impedances than bipolar vectors, with similar measurements compared to extended bipolar configurations. Capture thresholds increased with more proximal electrodes for all leads. Over a mean follow-up of 1 year, a slight decrease in capture thresholds was observed. Conclusion: Straight and spiral quadripolar leads allow to obtain clinically acceptable capture thresholds from at least one of the proximal electrodes in >80% of patients. Pacing vectors significantly affect electrical parameters, with higher thresholds in more proximal electrodes and lower thresholds with unipolar and extended bipolar configurations. Capture thresholds slightly decreased over a mean follow-up of 1 year. K E Y W O R D S capture threshold, Cardiac resynchronization therapy, impedance, pacing leads 1018

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). Conclusions The 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.

Background Randomized trials in Western countries have provided evidence that prophylactic implantable cardioverter‐defibrillator (ICD) therapy reduces mortality in heart failure (HF) patients with reduced left ventricular ejection fraction. However, the risk of life‐threatening ventricular arrhythmias in Japanese HF patients sharing similar risk factors is still unknown. Methods The Heart Failure Indication and Sudden Cardiac Death Prevention Trial Japan trial (NCT03185832) is a prospective, multicenter registry designed to collect data on ventricular arrhythmia, HF events, and mortality in Japanese HF patients. Japanese patients with HF and 2‐5 predefined risk factors who were indicated for cardiac device implantation based on European Society of Cardiology guidelines were enrolled in four treatment arms: implantable cardioverter‐defibrillator (ICD), cardiac resynchronization therapy defibrillator (CRT‐D), HF pacing (PA; Pacemaker and cardiac resynchronization pacemaker), and nondevice (ND) cohorts and followed for a minimum of 12 months. Since it is anticipated that some baseline patient characteristics and risk factors will differ significantly from those reported in predominantly Western populations, event rates will be compared to a propensity‐matched population from the MADIT RIT trial. Primary endpoints are composite rates of first appropriately treated ventricular arrhythmias (VA) or/and life‐threatening VA symptoms for the ICD and CRT‐D cohorts. For nondevice and PA cohorts, the primary outcome is all‐cause mortality. Conclusions The Heart Failure Indication and Sudden Cardiac Death Prevention Trial Japan is a large prospective multicenter registry with defined device treatment cohorts and will provide data for risk stratification for cardiovascular events in Japanese HF patients.