MADIT Studies: CRT in the Non-LBBB Patient and Other Findings. Arthur J. Moss, MD

Transcription

1 MADIT Studies: CRT in the Non-LBBB Patient and Other Findings Arthur J. Moss, MD University of Rochester Medical Cntr. Rochester, NY 13 th Annual New Frontiers in Heart Failure Rx NYC, NY January 26, 2013

2 DISCLOSURE INFORMATION Arthur J. Moss, MD Company Boston Scientific Relationship Research Grant Hold no stock or stock options in any device company. Not a member of any corporate advisory group or speakers bureau.

3 THERAPUETIC ELECTRICAL DEVICES FOR CARDIAC DISORDERS Innovation and Patents (year) Pacemaker: Chardack & Greatbatch (1959) Implantable Defibrillator: Mirowski & Mower (1968) Cardiac Resynchronization: Mower & Mirowski (1990)

4 Mieczyslaw (Michel) Mirowski Mordechai Frydman Automatic Implantable Defibrillator (AID)

5 MADIT FAMILY OF Trials MADIT: 1996 NEJM (n=196; mortality) MADIT-II: 2002 NEJM (n=1232; mortality) MADIT-II LTFU: 2009 Circulation (benefit persists) MADIT-CRT: 2009 NEJM (n=1820; HF/death) MADIT-RIT: 2012 NEJM (n=1500; inappropriate therapy & death with improved ICD programming) MADIT trials have been sponsored by Boston Scientific, but were independently conducted by the MADIT Executive Committee and the Heart Research Follow-up Program of the University of Rochester Medical Center.

6 MADIT-I HR=0.46 P=0.009 Elig: Hx MI, EF<0.30, NSVT, +EP study N=196 Moss AJ, et al. NEJM 1996

7 MADIT-II HR=0.69 P=0.016 Risk Factors for Appropriate ICD Rx Hazard Ratio P-value HF event* MI/UA* Elig: Hx MI, EF<30% N=1232 Moss AJ, et al. NEJM 2002

8 MADIT-CRT Elig: IHD or NIHD, NYHA I/II, EF<0.30, QRS>130ms N = 1820 Hazard Ratio = 0.66 P= Moss AJ, et al. NEJM 2009

9 CRT-D:ICD Hazard Ratios for Prespecified Subgroups Variable Age <65 yr >65 yr Sex* Male Female NYHA Class Ischemic I Ischemia II Nonischemic II QRS ms* <150 >150 LVEF <0.25 >0.25 LVEDV <240ml >240ml LVESV <170 >170 All patients Hazard Ratio Significant Sex-Rx Interaction Significant QRS-Rx Interaction CRT-D Better ICD-only Better

10 Mean Changes in Echo LV Volumes and EF from Baseline to 1-year by Treatment Group N=620 N=746 ICD-only CRT-D ml P<0.001 P<0.001 P<0.001 = -37ml ml = -39ml EF = ml vs. 52 ml in LVEDV from baseline 18 ml vs. 57ml in LVESV from baseline 0.03 vs in LVEF from baseline LVEDV LVESV LVEF CRT-D associated with significant reduction in heart size and improvement in heart function.

11 MADIT-CRT: Changes in Dyssynchrony (Regional Strain) from Baseline to 12 Months with CRT-D Baseline 12-Months MADIT-CRT Echo Core Lab

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13 MADIT-CRT: Outcome by LBBB & Non-LBBB HR=0.45 P=0.001 HR=1.25 P=0.25

14 MADIT-CRT: Outcomes in LBBB & Non-LBBB 0.65 (0.41, 0.99) LBBB was a consistent discriminator across multiple outcomes Background Overview Effectiveness Safety Conclusions Add l Outcomes

15 MADIT-CRT: Lead Position and Outcome We analyzed the impact of left ventricular lead position on clinical outcome in patients randomized to CRT-D in the MADIT-CRT study

16 LV Lead Position & Clinical Outcome Death &/or Heart Failure Anterior, posterior and lateral position Apical versus Non-apical position No difference amonganterior, Posterior and Lateral lead positions Apical lead positions associated with a significantly worse clinical outcome Singh J, et al. Circulation 2011

17 2012 AHA/ACC/HRS Focused Update and Change in CRT Guidelines Class I recommendation: - NYHA Class II - IV - EF< LBBB - QRS>150ms Class Ila recommendation: - NYHA Class II - IV - EF< LBBB and QRS 120 to 149ms - Non-LBBB and QRS>150ms

18 MADIT-RIT Reduce Inappropriate Therapy Moss AJ, et al. NEJM 2012

19 MADIT-RIT: BACKGROUND ICD is highly effective in reducing mortality in high-risk cardiac pts. Despite sophisticated device-detection algorithms, 8-40% of ICD therapies are inappropriate with adverse side effects Question: can ICD devices be reprogrammed to safely reduce inappropriate therapies?

20 ICD therapy: DEFINITIONS - ATP = antitachycardia pacing to terminate VT - Shock = to terminate VT Inappropriate ICD therapy: device therapy (ATP or Shock) rendered for non-ventricular tachyarrhythmias:

21 MADIT-RIT: Hypothesis Dual-chamber ICD or CRT-D devices with: - high-rate cutoff (>200bpm) or - duration-delay (initial 60sec delayed plus Rhythm ID detection will be associated with fewer 1 st inappropriate therapies than standard/conventional programming (2.5sec >170bpm) without increase in mortality Randomized, 3-arm study in primary prevention patients using Boston Scientific devices

22 MADIT-RIT: Three Treatment Arms* Randomization Arm B Arms C Arm A (Conventional) (High-rate) Zone 1: Zone 1: Zone 1: (Duration-delay) >170 bpm, 2.5s delay 170 bpm >170 bpm, 60s delay Onset/Stability Detection Enhancements ON ATP + Shock Monitor only Rhythm ID Detection Enhancements ON ATP + Shock Zone 2: Zone 2: Zone 2: >200 bpm, 1s delay >200 bpm, 2.5s delay >200 bpm, 12s delay Quick Convert ATP Shock Quick Convert ATP Shock Rhythm ID Detection Enhancements ON ATP + Shock Zone 3 : >250 bpm, 2.5s delay Quick Convert ATP + Shock * All programming is within approved labeling

23 Cumulative Probability of First Inappropriate Therapy by Treatment Group Moss AJ, et al. NEJM 2012

24 Cumulative Probability of Death by Treatment Group Moss AJ, et al. NEJM 2012

25 INAPPROPRIATE THERAPY, DEATH, AND SYNCOPE BY RX GROUP Treatment Groups Treatment Group Comparisons Events # of patients B vs. A C vs. A A B C n=514 n=500 n=486 Hazard Ratio P-value Hazard Ratio P-value First Inappropriate Therapy < <0.001 Death st Syncope

26 MADIT CONCLUSIONS ICD reduces mortality by 50% in high-risk cardiac patients (2002) CRT-D reduces HF/death by 40% in NYHA I & II in those with EF<30% (2009) CRT primarily effective in LBBB (2009) ICD programming to >200bpm associated with 79% reduction in inappropriate therapy and a 55% additional reduction in death (2012)