Should We Implant ICD In Patients With NICMP (Cons) Alireza - PowerPoint PPT Presentation

Should We Implant ICD In Patients With NICMP (Cons) Alireza Ghorbani Sharif, MD Interventional Electrophysiologist Tehran Arrhythmia Clinic March 2018

Introduction • Implantation of an ICD for primary prevention of SCD in patients with NICMP and EF < 35% has a Class I, level of evidence B. (European Guidelines) • Implantation of an ICD for primary prevention of SCD in patients with ICMP and EF < 35% has a Class I, level of evidence A. (AHA and European Guidelines) NICMP (Non-Ischemic cardiomyopathy), ICMP (Ischemic cardiomyopathy) Europace (2017) 19, 660 – 664

Introduction • The use of ICDs has been a major advancement in patients with ICMP with reduced ejection fraction <35%. • The data supporting the use of ICDs are robust in patients with ICMP, limited randomized controlled clinical trial (RCT) data exist for similar benefit in patients with NICMP. Circulation. 2017;135:201-203

ICD Trials • A prior meta-analysis that included both primary and secondary prevention ICD trial in 2004 by Desai et al demonstrated a 31% reduction in all-cause mortality with ICD use in patients with NICMP. • The data became the back bone of the current ACC/AHA guidelines for ICD implantation in patients with NICMP. ACC/AHA (American College of Cardiology/American Heart Association ) Circulation. 2017;135:201-203

ICD Trials in NICMP • The history of the trials performed for ICDs, particularly in NICMP: 1. (Cardiomyopathy Trial) CAT 2. (Amiodarone Versus Implantable Cardioverter-Defibrillator Randomized Trial) AMIOVIRT 3. (Prophylactic defibrillator implantation in patients with NICMP) DEFINITE 4. (Sudden Cardiac Death in Heart Failure Trial) SCD-HeFT

DEFINITE Trial • This was only one moderate-size trial has shown a trend to mortality reduction in the NICMP population, but which did not reach statistical significance. Europace (2017) 19, 660 – 664

SCD-HeFT • In the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) which compared conventional therapy with placebo, amiodarone, or ICD in a population of ICMP and NICMP patients, the mortality reduction associated with ICD implantation was 23%. Europace (2017) 19, 660 – 664

Result of ICD Trial in NICM P • When it has been pretty well established in the community that ICDs reduce mortality? • It was obvious that it can help in treating sudden cardiac death in patients with NICMP. • Why did we need another trial for investigating of prophylactic ICD implantation in these patients?

We needed another trial because: • The indication for primary prophylactic ICD in patients with NICMP was based on small to medium-sized trials with neutral outcomes (DEFINITE Trial). • Positive effect of ICD confined to New York Heart Association (NYHA) class II, and no patients received concomitant CRT (SCD-HeFT).

We needed another trials because: • Large proportion of these patients have been received CRT, and the impact of ICD implantation in this setting is not well known (SCD-HeFT). • No trials have reported added benefit of ICDs in patients with CRT. • Medical therapy has improved since the ICD trials (SCD-HeFT). • ICD implantation confers a risk of device-related complications.

This was probably an ideal time: • Reassess the presence of ICDs on top of the medical management? • Did CRT confer an incremental benefit compared with ICD or not?

DANISH Trial • That was the background under which the DANISH trial was conducted, the trial started in 2007. • DANISH trial investigated the effect of ICD implantation in patients with HF not caused by CAD who receive contemporary HF therapy including CRT. The New England Journal of Medicine. 2016. epub 2016-08-28:1-10.

DANISH Trial • From February 7, 2008, to June 30, 2014, total of 1116 patients were enrolled at five centers; 556 patients were randomly assigned to the ICD group, and 560 patients were assigned to the control group. • The median follow-up period was 67.6 months (interquartile range, 49 to 85), and no patients were lost to follow-up for the primary outcome • Follow-up data for all outcomes were available through June 30, 2016. The New England Journal of Medicine. 2016. epub 2016-08-28:1-10.

DANISH Trial • The patients were divided into two groups: 1. First group receiving an ICD in addition to optimal medical management and CRT whenever indicated. 2. A second group did not receive an ICD but did get a CRT-P if indicated, in addition to optimal medical management. • In both groups, 58% of patients received CRT. The New England Journal of Medicine. 2016. epub 2016-08-28:1-10.

Characteristics of the Patients at Baseline * Mineralocorticoid-receptor antagonist The New England Journal of Medicine . 2016. epub 2016-08-28:1-10.

Inclusion criteria • Clinical HF. • Non-ischemic etiology. • Optimal medical treatment. • NYHA functional class II or III (patients in NYHA class IV could be included if planned for CRT). • LVEF ≤35 %. • NT-proBNP 200 pg/mL (23.6 pmol/L). The New England Journal of Medicine. 2016. epub 2016-08-28:1-10.

Inclusion criteria • Non-ischemic etiology was determined by coronary angiogram, although a normal computed tomography angiogram or nuclear myocardial perfusion imaging study was acceptable. • Patients could be included despite having 1 or 2 coronary artery stenoses, if the extent of coronary artery disease did not explain the reduced left ventricular systolic function. • Decision to implant a CRT device made before randomization. The New England Journal of Medicine. 2016. epub 2016-08-28:1-10.

Exclusion criteria • Permanent AF (resting heart rate >100 beats/min). • Uncorrected CHD or valve obstruction, obstructive CMP, active myocarditis, constrictive pericarditis, untreated hypothyroidism or hyperthyroidism, adrenal insufficiency, and active vasculitis due to collagen vascular disease. • On the urgent waiting list for a heart transplant. • Major organ transplant. The New England Journal of Medicine. 2016. epub 2016-08-28:1-10.

Exclusion criteria (Contd) • Receiving or having received cytotoxic or chemotherapy and/or radiation therapy for malignancy within 6 m before or clinical evidence of current malignancy, with the following exceptions: BCC of the skin, cervical intraepithelial neoplasia, prostate CA (if stable localized disease, with a life expectancy of 2.5 years in the opinion of the investigator). • Known to be HIV positive, with life expectancy of less than 5 years. The New England Journal of Medicine. 2016. epub 2016-08-28:1-10.

Exclusion criteria (Contd) • CKD treated with dialysis. • Recent (within 3 m) history of alcohol or illicit drug abuse disorder, based on self-report. • Any condition (eg, psychiatric illness) or situation that, in the investigator's opinion, could put the participant at significant risk. • Lack of informed consent. The New England Journal of Medicine. 2016. epub 2016-08-28:1-10.

Methods (Contd.) • Follow-up – • 2 months. • Every 6 months. • Patients who receive ICD undergo regular follow-up by implantation center. n engl j med 375;13 nejm.org September 29, 2016

DANISH Trial • The real difference in the DANISH trial was that roughly 58% of patients in both arms had CRT devices. • This was not a study of medical therapy vs. medical therapy and device as most of the previous studies have been. • This was about: • The best heart-failure therapy • The best drugs; add CRT to that • And then does a defibrillator help or not? The New England Journal of Medicine. 2016. epub 2016-08-28:1-10.

Primary Outcomes • Death from any cause. The New England Journal of Medicine. 2016. epub 2016-08-28:1-10.

Secondary Outcomes • Time to cardiovascular death. • Time to sudden cardiac death. • Time to resuscitated cardiac arrest or sustained ventricular tachycardia. • Change in quality of life from baseline (Quality of life is assessed by the Minnesota Living with Heart Failure Questionnaire). The New England Journal of Medicine. 2016. epub 2016-08-28:1-10.

Primary outcome – Death from any cause • When you look at the survival curve , at 2 years, you start to see a separation: ICD was beneficial ,after 5 years, the survival curves start to converge. • Older patents were starting to die from other causes. The New England Journal of Medicine. 2016. epub 2016-08-28:1-10.

Primary outcome – Death from any cause • Primary outcome, death from any cause, occurred in 120 patients (21.6%) in the ICD group (4.4 events per 100 person-years) and in 131 patients (23.4%) in the control group (5.0 events per 100 person- years) • The hazard ratio for death from any cause in the ICD group, as compared with the control group, was 0.87 (95% confidence interval [CI] 0.68 to 1.12; P = 0.28) The New England Journal of Medicine. 2016. epub 2016-08-28:1-10.

Secondary outcome – Sudden cardiac death • The chance of sudden cardiac death in ICD group was about 50% less than in patients who did not have an ICD. • Subgroup analysis, showed that patients younger than 68 years of age had mortality benefit from an ICD compared with older patients. The New England Journal of Medicine. 2016. epub 2016-08-28:1-10.