MADIT-CRT trial

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MADIT-CRT trial : 

MADIT-CRT trial The Multicenter Automatic Defibrillator Implantation Trial – Cardiac Resynchronization Therapy (MADIT-CRT) October 1, 2009 vol. 361 no. 14

Background : 

Background

Slide 3: 

Pat with cardiac dis & < LV fnx are at > risk for arrhythmia-related sudden death & CHF. ICD improves survival & < risk of sudden death in selected pats with cardiac dis. H/E, life-prolonging defib t/t is a/w > risk of 1st & recurrent HF events.

Slide 4: 

CRT with biventricular pacing - effective adjunctive t/t to pharmac. t/t in < rate of hospitalization in : symptomatic pats with advanced HF symp. (NYHA class III or IV), EF ≤ 35%, & I-V conduction delay of ≥ 120 msec

Slide 5: 

MADIT-CRT, was designed to determine whether prophylactic CRT in combi. with an ICD (CRT–ICD) would < risk of death/nonfatal HF events in pats with EF of ≤ 30%, QRS duration of ≥ 130 msec & NYHA class I or II symptoms, as compared with pats receiving only an ICD

Methods : 

Methods

Trial Design and Oversight : 

Trial Design and Oversight Dec 22, ’04 - April 23, ‘08, -1820 pats enrolled Primary hypothesis - CRT–ICD t/t would be a/w < risk of death or nonfatal HF events, as compared with ICD-only t/t Authors anticipated a < annual mortality, since enrolled pats would be in NYHA class I/ II,& pats in both study gps would receive an ICD.

Inclusion criteria : 

Inclusion criteria Either sex > 21 years ICMP (NYHA class I or II) or Non ICMP (NYHA class II only), EF of ≤ 30%, QRS duration of ≥ 130 msec

Exclusion criteria : 

Exclusion criteria Existing indication for CRT; ‘ving an implanted pacemaker, ICD/ resynchronization device; NYHA class III/ IV symptoms, Previous CABG, PCI, +ve MI within 3 mths before enrollment; AF within 1 mth before enrollment

Follow Up : 

Follow Up Pats followed-up at 1 mth after randomization & then at 3-mth intervals until termination of trial. Clinical evaluation & device testing were carried out at each follow-up visit. Treating physicians were aware of study-gp assignments.

Randomization : 

Randomization Baseline clinical history, 12-lead ECG, 2 D-ECHO & 6-min walk test. Pats -randomly assigned in a 3:2 ratio to receive either CRT with ICD (CRT–ICD gp) or only ICD (ICD-only gp)

ECHO : 

ECHO 2 D ECHO-at baseline & at 1-yr follow-up – LV volumes & EF in study gps. At 1 yr, evaluated 746 pats in CRT–ICD gp & 620 pats in ICD-only gp. Volumes -averaging those derived from 2 & 4 chamber views by Simpson’s method, & EF calculated in usual fashion

Therapy : 

Therapy Commercially available transvenous devices (Boston Scientific) were used in trial. Standard techniques were used to implant CRT–ICD & ICD-only devices.

Therapy : 

Therapy In CRT–ICD gp, programmed mode was DDD with a lower rate of 40 bpm & hysteresis off. In ICD-only gp, programmed pacing mode was VVI for single-chamber units & DDI for dual-chamber units, with lower rates of 40 bpm & hysteresis off in both single- & dual-chamber units.

Primary End Point : 

Primary End Point PEP- death from any cause/nonfatal HF events. Diagnosis of HF- required s/s consistent with CHF that was responsive to IV decongestive t/t on an outpatient basis or an augmented decongestive regimen with oral/ parenteral medications during an in-hospital stay.

Results : 

Results

Slide 19: 

Of 1089 pats in CRT–ICD gp, 11 (1.0%); Of 731 pats in ICD-only gp, 19 (2.6%) did n’t receive a device. Thus, implantation of device was achieved in 98.4% of pats , with 95.4% of pats receiving device to which they had been assigned

Slide 20: 

Devices removed during trial for variety of reasons in 14 pats in CRT–ICD gp (1.3%) & in 5 in ICD-only gp (0.7%). Total of 44 pats in CRT–ICD gp (4.0%) & 55 in ICD-only gp (7.5%) declined to continue participating in study, were withdrawn by a physician, or were lost to follow-up.

Primary End Point : 

Primary End Point

Slide 25: 

Exploratory analyses suggested –women not men had a benefit from CRT–ICD t/t independent of QRS duration. Among 182 pats with NYHA III/ IV symps > 3 mths before enrollment & 213 pats with h/o AF > 1 mth before enrollment, CRT–ICD had less effect on outcome than in pats without.

LV remodeling : 

LV remodeling

Discussion : 

Discussion

Slide 28: 

Study showed, use of CRT +ICD in asymptomatic or mildly symptomatic pats with hrt dis & <EF & > QRS was a/w 34% < in risk of death/HF, as compared to ICD alone. Benefit was driven by a 41% < in risk of HF, a finding that was evident primarily in a prespecified subgp of pats with a QRS duration of ≥150 msec.

Slide 29: 

Superiority of CRT was evident in pats with ICMP & non ICMP ECHO studies showed substantial < in LVEDV & LVESV & improvement in EF 1 yr after initiation of CRT–ICD t/t.

Slide 30: 

CRT has been shown to < symptoms & rates of hospitalization & death in pats with NYHA III & IV HF. The findings of this study shows effectiveness of CRT in reducing risk of HF events in asymptomatic/ mildly symptomatic pats.

Slide 31: 

Difference in freq of HF in 2 study gps is not likely to be due to > in rate of pacemaker induced HF in ICD-only gp, since demand pacing rate was programmed to 40 bpm, a backup bradycardia rate that has not been a/w an > HF rate. Reduction in HF with CRT was not a/w < in mortality in this prevention trial.

Biases : 

Biases Members of hrt-failure adjudication committee were unaware of study-gp assignments, but investigators who decided on t/t or hospital admission for pats with HF were aware of such assignments. It is possible that investigators’ knowledge of study-gp contributed in some way to < freq. of HF in CRT–ICD gp.

Biases : 

Biases Another bias- 201 pats in CRT–ICD gp underwent 1-yr ECHO evaluation with CRT device turned off, & these pats were not included in paired vol & EF studies. This resulted in 746 paired studies in CRT–ICD gp, a large # but not randomly selected.

Biases : 

Biases In view of size of effects observed, authors believe general conclusions from these ECHO results are reliable.

Slide 35: 

In 2008 guidelines for implantation of cardiac devices,CRT with/ without an ICD is a class I indication for pats with a LV EF ≤ 35%, QRS duration of ≥120 msec, & sinus rhythm who ‘ve NYHA III or ambulatory class IV HF symptoms while receiving optimal medical t/t.

Slide 36: 

This study was designed to address a preventive indication for CRT–ICD t/t in relatively asymptomatic patients receiving appropriate medical t/t who ‘ve ischemic hrt dis with class I or II symp or non-ischemic hrt dis with class II symp, a < EF, a > QRS, & sinus rhythm.

Slide 37: 

This study provides evidence that preventive CRT–ICD t/t < risk of HF events in vulnerable pats with ischemic or non-ischemic hrt dis who ‘ve minimal HF symp but a >QRS complex.

Take home message : 

Take home message

Slide 39: 

In asymptomatic or mild HF, patients with >QRS, LV dysfunction, and on stable optimal HF pharmacologic t/t, CRT-D, vs ICD, was significantly a/w: An acceptable safety profile Primary endpoint showed: 34% reduction (p < 0.001) in the risk of all-cause mortality/HF. --Secondary endpoint showed: 43% reduction (p = 0.001) in the risk of recurrent HF events

Slide 40: 

Thank You

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