MIRACLE ICD trial

The effects of CRT in mild heart failure have not been established. There have been two large-scale trials that included patients with NYHA functional class II heart failure—the CONTAK CD trial and the MIRACLE ICD trial [115, 116]. Although there was no consistent clinical benefit seen in either trial, both studies revealed evidence of reverse... 

Young JB, Abraham WT, Smith AL, et al. Combined cardiac resynchronization and implantable cardioversion defibrillation in advanced chronic heart failure the MIRACLE ICD Trial, [see comment]. JAMA 2003 289 2685-94. 

Although resynchronization is proven to prolong survival compared with standard medical therapy of heart failure, it should be noted that there is no direct evidence that resynchronization therapy improves survival when compared with ICD therapy alone (24). It is also curious to note that the addition of resynchronization did not reduce ICD therapies for ventricular tachy-cardia/ventricular fibrillation in either the CONTAK CD or MIRACLE ICD trials (10,11). It is possible that these observations may reflect the relatively large proportion of secondary prevention patients enrolled in these trials (28), as well as the relatively short duration of follow-up. Indeed, a recent retrospective analysis of the InSync III Marquis trial showed that responders to CRT demonstrated significantly fewer single premature ventricular contractions beats, or PVC runs, and fewer treated episodes of ventricular tachycardia or fibrillation (VT/VF) (P = 0.050) than nonresponders by 6 months of follow-up (29). 

MIRACLE trial MIRACLE-ICD trial Insync III trial Total... 

The Multicenter InSync ICD Randomized Clinical Evaluation (MIRACLE ICD) trial was a randomized, double-blind, parallel-controlled trial of a high-risk population that included patients with left ventricular ejection fraction < 0.35, QRS duration > 130ms and New York Heart Association Functional Class III or IV despite optimal medical beatment. Patients received devices with combined CRT and ICD capabilities and were randomized to the ICD therapy on or off. At 6 months, patients assigned to CRT had a greater improvement in median quality of life score and functional class as compared to controls. No significant differences were observed in changes in left ventricular size or function, overall heart failure status, survival, and rates of hospitalization. No proarrhythmia was observed and arrhythmia termination capabilities were not impaired (82). 

Pires, L.A., et al.. Clinical predictors and timing of New York Heart Association class improvement with cardiac resynchronization therapy in patients with advanced chronic heart failure results from the Multicenter InSync Randomized Clinical Evaluation (MIRACLE) and Multicenter InSync ICD Randomized Clinical Evaluation (MIRACLE-ICD) trials. Am Heart J, 2006. 151(4) p. 837-13. 

In such trials as MUSTIC (7), PATH-CHF (8), MIRACLE (9), CONTAK CD (10), MIRACLE ICD (11), and PATH-CHF II (12), resynchronization therapy consistently improved functional capacity and reduced symptoms. Specifically, resynchronization was associated with a 1% to 23% improvement in 6-minute hall walk distance, a 7% to 10% increase in V02max, and an 11% to 31% improvement in quality of life scores. 

MUSTIC, PATH-CHF, MIRACLE, CONTAK CD, MIRACLE ICD, and PATH-CHF II enrolled patients with (a) moderate to severely symptomatic (NYHA class III—IV) CHF despite optimal medical therapy (b) severe left ventricular systolic dysfunction (LVEF <35%) (c) a wide QRS complex (generally defined as a QRS >120-130 msec) and (d) sinus rhythm. As a result, these inclusion criteria have become the standard indications for CRT. The effects in these conventional indication trials are robust—indeed, far more robust than the effects observed with conventional pharmacologic therapy of heart failure (Figure 5.1). For instance, improvement in 6-minute hall walk distance was observed in only 2 of 6 trials of ACE-inhibitors, 3 of 17 trials of beta blockers, and 1 of 4 trials of digoxin (13). Trials of both beta-blockers and ACE inhibitors have likewise shown inconsistent results with respect to V02max (14,15) and quality of life (16,17). 

In addition to improving symptoms, CRT has been demonstrated to improve survival in conventionally indicated populations. Although the early randomized clinical trials of CRT were not large enough to include mortality as a primary endpoint, a meta-analysis of MUSTIC, MIRACLE, MIRACLE ICD, and CONTAK CD concluded that resynchronization therapy, with or without concomitant use of a defibrillator, reduced mortality due to progressive heart failure by 51% (24). comparison of... 

With the publications of the Miracle (1), Miracle ICD (2), COMPANION (3) and CARE-HF (4) trials, biventricular pacing is now an undisputed adjunctive therapy for heart failure, demonstrating an additive symptom and survival benefit over pharmacological therapies alone. Its wider application has been hampered, in part, by the technical challenges of left ventricular lead implantation encountered by the operating physician. (Table 5.1)... 

The Multicenter InSync ICD Randomized Clinical Evaluation II (MIRACLE ICD II) was a follow-up randomized, double-blind, parallel-conlrolled clinical trial of CRT in New York Heart Association Functional Class II heart failure patients on optimal medical therapy with a left ventricular ejection fraction < 0.35, a QRS > 130ms and a Class I indication for an ICD. Patients were randomized to control group (ICD activated, CRT off) and to CRT group (ICD activated, cardiac-resynchronization therapy on). No significant differences were noted in 6-min walk distance or quality of life scores or peak V02. There were significant improvements in left ventricular diastolic and systolic volumes and in left ventricular ejection fraction (198). 

Conceptually, the potential complications of CRT-pacemaker or CRT-defibrillator implantation include the known complications of transvenous pacemaker or ICD implant (bleeding, infection, pneumothorax, vascular injury, cardiac perforation/tamponade, and cardiac decompensation from defibrillation testing) as well as the potential complications of LV lead implant (coronary venous dissection/perforation, contrast nephropathy, and perhaps elevated risk of infection or heart failure exacerbation due to prolonged procedure times). In addition, the passive fixation nature of LV leads raises the rates of post-procedure lead dislodgement. However, the rates of serious adverse events from the implantation procedure reported in the large clinical trials have been low. In MIRACLE, 2 patients (of 571) died as a result of the procedure. Correspondingly, 6% had a dissection or perforation of a coronary vein, but only 3 of those 35 patients required intervention and... 

---