MIRACLE_Trial_Presentation.pptx for cardiologist

Miracle trial for CRT

1. MIRACLE Trial — Cardiac Resynchronization Therapy (CRT) Multicenter InSync Randomized Clinical Evaluation Dr Saad

2. Description The goal of the MIRACLE trial was to compare the effect of cardiac resynchronization therapy (CRT) versus no CRT on the quality of life and functional capacity in patients with chronic heart failure (CHF) and ventricular dysynchrony , as well as to assess the safety of CRT using the Medtronic InSync ® System in patients with CHF.

3. Background & Rationale Problem: Advanced HFrEF with electrical dyssynchrony (wide QRS) → inefficient LV contraction & MR Hypothesis: Biventricular pacing resynchronizes LV activation → improves hemodynamics and symptoms Device: Medtronic InSync ® system providing simultaneous RV + LV pacing

4. Background & Rationale Pre-MIRACLE evidence: small, unblinded /short studies suggested symptom gains Need: A large, randomized, double‑blind, controlled trial to test efficacy & safety Clinical question: In NYHA III–IV HFrEF with QRS ≥130 ms , does CRT improve patient-centered outcomes?

5. Key Eligibility NYHA III–IV; LVEF ≤35 % (mean 22) ; QRS ≥130 ms (mean 165 ms ) LVEDD ≥55 mm (mean 69 mm); 6‑min walk ≤450 m On stable HF therapy (ACE‑I/ARB ± β‑blocker)

6. Study Design & Methodology Design: Prospective, randomized, double‑blind, controlled (device on vs. off) Participants: 453 enrolled; minimum follow‑up 6 months Randomization: After successful lead placement control group (no CRT, n=225 ) CRT group ( n=228) ; electrophysiologist unblinded ; patient & HF team blinded Control arm could cross over to CRT after blinded 6‑month phase

7. Study Design & Methodology — Endpoints Primary: (1) Minnesota Living with HF QOL, (2) NYHA class, (3) 6‑minute walk distance Secondary: Peak O₂ consumption , treadmill time, LVEF & LV dimensions, MR severity, QRS duration, clinical composite response Concomitant therapy: Background HF meds kept stable where possible

8. Study Design & Methodology— Procedures & Safety Implant success ≈92%; notable complications: refractory hypotension/ brady /asystole (rare), C arotid S inus perforation Analysis : Between‑group changes at 6 months + composite clinical status

9. Key Findings & Outcomes— Primary Endpoints CRT improved 6‑minute walk (+39 vs +10 m; p=0.005 ) -CRT group’s mean change: they walked 39 meters more, on average - control group’s mean change: they walked 10 meters more, on average More patients improved ≥1 NYHA class (68% vs 38%; p<0.001) Greater QOL improvement (−18.0 vs −9.0 points; p=0.001)

10. Key Findings & Outcomes— Secondary/Remodeling Peak VO₂: +1.1 vs +0.2 ml/kg/min (p=0.009) LVEF: +4.6% vs −0.2% (p<0.001); LV volumes improved; MR improved QRS duration shortened (−20 vs 0 ms; p<0.001)

11. Key Findings & Outcomes — Clinical Composite & Events Clinical composite: improved 67% vs 39% (p<0.001); worsened 16% vs 27% HF hospitalization/IV therapy lower with CRT (hospitalization 8% vs 15%; IV meds 7% vs 15%) Death or worsening HF hospitalization: 28% vs 44% (HR 0.60; 95% CI 0.37–0.96; p=0.03)

12. Clinical Significance— What it Changed Established CRT as an effective adjunct in symptomatic HFrEF with dyssynchrony Shifted focus to electrical criteria (QRS width/LBBB) alongside LVEF & symptoms Catalyzed subsequent trials (MIRACLE‑ICD, COMPANION, CARE‑HF, MADIT‑CRT) and guideline adoption

13. Clinical Significance— Who Responds Best Typical responders: Sinus rhythm, LBBB morphology, QRS ≥150 ms , non‑ischemic cardiomyopathy Less robust in non‑LBBB or narrower QRS; AF requires special programming/ablation considerations Real‑world: device/lead issues, optimization needed ( AV delay /VV timing ) .

14. Clinical Significance— Practical Takeaways Consider CRT in NYHA III–IV, LVEF ≤35%, QRS ≥130 ms (esp. LBBB ≥150 ms) despite GDMT Expect improvements in symptoms, exercise capacity, QOL, and reverse remodeling within 6 months MIRACLE was not powered for mortality, but later trials showed morbidity/mortality benefits

15. References Abraham WT et al. N Engl J Med 2002;346:1845–53 (MIRACLE) Young JB et al. JAMA 2003;289:2685–94 (MIRACLE‑ICD) ACC.org Clinical Trial Summaries (MIRACLE & MIRACLE‑ICD) CARE‑HF, COMPANION, MADIT‑CRT for outcomes beyond symptoms

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