This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on ISI (317)  • Contact me when this article is cited  Related Content  • Related article  • Similar articles in JAMA  Topic Collections  • Pacemakers/ Defibrillators  • Randomized Controlled Trial  • Arrhythmias  • Congestive Heart Failure/ Cardiomyopathy  • Cardiovascular Intervention  • Alert me on articles by topic

The MIRACLE ICD Trial

James B. Young, MD; William T. Abraham, MD; Andrew L. Smith, MD; Angel R. Leon, MD; Randy Lieberman, MD; Bruce Wilkoff, MD; Robert C. Canby, MD; John S. Schroeder, MD; L. Bing Liem, DO; Shelley Hall, MD; Kevin Wheelan, MD; for The Multicenter InSync ICD Randomized Clinical Evaluation (MIRACLE ICD) Trial Investigators

JAMA. 2003;289:2685-2694.

Context  Cardiac resynchronization therapy (CRT) through biventricular pacing is an effective treatment for heart failure (HF) with a wide QRS; however, the outcomes of patients requiring CRT and implantable cardioverter defibrillator (ICD) therapy are unknown.

Objective  To examine the efficacy and safety of combined CRT and ICD therapy in patients with New York Heart Association (NYHA) class III or IV congestive HF despite appropriate medical management.

Design, Setting, and Participants  Randomized, double-blind, parallel-controlled trial conducted from October 1, 1999, to August 31, 2001, of 369 patients with left ventricular ejection fraction of 35% or less, QRS duration of 130 ms, at high risk of life-threatening ventricular arrhythmias, and in NYHA class III (n = 328) or IV (n = 41) despite optimized medical treatment.

Interventions  Of 369 randomized patients who received devices with combined CRT and ICD capabilities, 182 were controls (ICD activated, CRT off) and 187 were in the CRT group (ICD activated, CRT on).

Main Outcome Measures  The primary double-blind study end points were changes between baseline and 6 months in quality of life, functional class, and distance covered during a 6-minute walk. Additional outcome measures included changes in exercise capacity, plasma neurohormones, left ventricular function, and overall HF status. Survival, incidence of ventricular arrhythmias, and rates of hospitalization were also compared.

Results  At 6 months, patients assigned to CRT had a greater improvement in median (95% confidence interval) quality of life score (–17.5 [–21 to –14] vs –11.0 [–16 to –7], P = .02) and functional class (–1 [–1 to –1] vs 0 [–1 to 0], P = .007) than controls but were no different in the change in distance walked in 6 minutes (55 m [44-79] vs 53 m [43-75], P = .36). Peak oxygen consumption increased by 1.1 mL/kg per minute (0.7-1.6) in the CRT group vs 0.1 mL/kg per minute (–0.1 to 0.8) in controls (P = .04), although treadmill exercise duration increased by 56 seconds (30-79) in the CRT group and decreased by 11 seconds (–55 to 12) in controls (P<.001). No significant differences were observed in changes in left ventricular size or function, overall HF status, survival, and rates of hospitalization. No proarrhythmia was observed and arrhythmia termination capabilities were not impaired.

Conclusions  Cardiac resynchronization improved quality of life, functional status, and exercise capacity in patients with moderate to severe HF, a wide QRS interval, and life-threatening arrhythmias. These improvements occurred in the context of underlying appropriate medical management without proarrhythmia or compromised ICD function.

Author Affiliations: Cleveland Clinic Foundation, Cleveland, Ohio (Drs Young and Wilkoff); University of Kentucky, Lexington (Dr Abraham); Emory University School of Medicine, Atlanta, Ga (Drs Smith and Leon); Harper Hospital, Detroit, Mich (Dr Lieberman); Texas Cardiac Arrhythmia, Austin (Dr Canby); Stanford University Medical Center, Stanford, Calif (Drs Schroeder and Liem); and Baylor University Medical Center, Dallas, Tex (Drs Hall and Wheelan). Dr Abraham is now with Ohio State University, Columbus.

RELATED ARTICLE

Combining Resynchronization and Defibrillation Therapies for Heart Failure
David J. Bradley
JAMA. 2003;289(20):2719-2721.
EXTRACT | FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Cardiac Resynchronization in Patients With Atrial Fibrillation: A Meta-Analysis of Prospective Cohort Studies
Upadhyay et al.
J Am Coll Cardiol 2008;52:1239-1246.
ABSTRACT | FULL TEXT  

Biventricular pacing for end-stage heart failure: early experience in surgical vs. transvenous left ventricular lead placement
Atoui et al.
ICVTS 2008;7:839-844.
ABSTRACT | FULL TEXT  

Randomized Trial of Cardiac Resynchronization in Mildly Symptomatic Heart Failure Patients and in Asymptomatic Patients With Left Ventricular Dysfunction and Previous Heart Failure Symptoms
Linde et al.
J Am Coll Cardiol 2008;0:j.jacc.2008.08.027v1-14198.
ABSTRACT | FULL TEXT  

Longitudinal Strain Delay Index by Speckle Tracking Imaging: A New Marker of Response to Cardiac Resynchronization Therapy
Lim et al.
Circulation 2008;118:1130-1137.
ABSTRACT | FULL TEXT  

Assessment of a remote monitoring system for implantable cardioverter defibrillators
Masella et al.
J Telemed Telecare 2008;14:290-294.
ABSTRACT | FULL TEXT  

Use of Cardiac Resynchronization Therapy in Patients Hospitalized With Heart Failure
Piccini et al.
Circulation 2008;118:926-933.
ABSTRACT | FULL TEXT  

Strategic Programming of Detection and Therapy Parameters in Implantable Cardioverter-Defibrillators Reduces Shocks in Primary Prevention Patients: Results From the PREPARE (Primary Prevention Parameters Evaluation) Study
Wilkoff et al.
J Am Coll Cardiol 2008;52:541-550.
ABSTRACT | FULL TEXT  

Impact of interventricular lead distance and the decrease in septal-to-lateral delay on response to cardiac resynchronization therapy
Buck et al.
Europace 2008;0:eun208v1-7.
ABSTRACT | FULL TEXT  

Interventricular interaction as a possible mechanism for the presence of a biphasic systolic velocity profile in normal left ventricular free walls
Marciniak et al.
Heart 2008;94:1058-1064.
ABSTRACT | FULL TEXT  

Heart Failure Care in the Outpatient Cardiology Practice Setting: Findings From IMPROVE HF
Fonarow et al.
Circ Heart Fail 2008;1:98-106.
ABSTRACT | FULL TEXT  

Benefit of cardiac resynchronization therapy in atrial fibrillation patients vs. patients in sinus rhythm: the role of atrioventricular junction ablation
Ferreira et al.
Europace 2008;10:809-815.
ABSTRACT | FULL TEXT  

Results of the Predictors of Response to CRT (PROSPECT) Trial
Chung et al.
Circulation 2008;117:2608-2616.
ABSTRACT | FULL TEXT  

Acute hemodynamic and functional effects of surgical ventricular restoration and heart transplantation in patients with ischemic dilated cardiomyopathy.
Cotrufo et al.
J. Thorac. Cardiovasc. Surg. 2008;135:1054-1060.
ABSTRACT | FULL TEXT  

Symptomatic heart failure is the most important clinical correlate of impaired quality of life, anxiety, and depression in implantable cardioverter-defibrillator patients: a single-centre, cross-sectional study in 610 patients
Johansen et al.
Europace 2008;10:545-551.
ABSTRACT | FULL TEXT  

Randomized, double blind study of non-excitatory, cardiac contractility modulation electrical impulses for symptomatic heart failure
Borggrefe et al.
Eur Heart J 2008;29:1019-1028.
ABSTRACT | FULL TEXT  

Improvement in cardiac sympathetic nerve activity in responders to resynchronization therapy
Burri et al.
Europace 2008;10:374-378.
ABSTRACT | FULL TEXT  

Effect of cardiac resynchronisation therapy on occurrence of ventricular arrhythmia in patients with implantable cardioverter defibrillators undergoing upgrade to cardiac resynchronisation therapy devices
Lin et al.
Heart 2008;94:186-190.
ABSTRACT | FULL TEXT  

Instantaneous effects of resynchronisation therapy on exercise performance in heart failure patients: the mechanistic role and predictive power of total isovolumic time
Salukhe et al.
Heart 2008;94:59-64.
ABSTRACT | FULL TEXT  

Cardiac-Resynchronization Therapy in Heart Failure with Narrow QRS Complexes
Beshai et al.
NEJM 2007;357:2461-2471.
ABSTRACT | FULL TEXT  

Nuclear Imaging in Cardiac Resynchronization Therapy
Henneman et al.
JNM 2007;48:2001-2010.
ABSTRACT | FULL TEXT  

Cardiac resynchronization therapy: clinical results and evolution of candidate selection
Leclercq et al.
Eur Heart J Suppl 2007;9:I94-I106.
ABSTRACT | FULL TEXT  

Acute Effects of Initiation and Withdrawal of Cardiac Resynchronization Therapy on Papillary Muscle Dyssynchrony and Mitral Regurgitation
Ypenburg et al.
J Am Coll Cardiol 2007;50:2071-2077.
ABSTRACT | FULL TEXT  

Differential effects of left ventricular pacing sites in an acute canine model of contraction dyssynchrony
Johnson et al.
Am. J. Physiol. Heart Circ. Physiol. 2007;293:H3046-H3055.
ABSTRACT | FULL TEXT  

Diminished Left Ventricular Dyssynchrony and Impact of Resynchronization in Failing Hearts With Right Versus Left Bundle Branch Block
Byrne et al.
J Am Coll Cardiol 2007;50:1484-1490.
ABSTRACT | FULL TEXT  

The BRIGHT study: bifocal right ventricular resynchronization therapy: a randomized study
Res et al.
Europace 2007;9:857-861.
ABSTRACT | FULL TEXT  

Guidelines for cardiac pacing and cardiac resynchronization therapy: The Task Force for Cardiac Pacing and Cardiac Resynchronization Therapy of the European Society of Cardiology. Developed in Collaboration with the European Heart Rhythm Association
Authors/Task Force Members et al.
Europace 2007;9:959-998.
FULL TEXT  

Impact of left ventricular lead position on the efficacy of cardiac resynchronisation therapy: a two-dimensional strain echocardiography study
Becker et al.
Heart 2007;93:1197-1203.
ABSTRACT | FULL TEXT  

Guidelines for cardiac pacing and cardiac resynchronization therapy: The Task Force for Cardiac Pacing and Cardiac Resynchronization Therapy of the European Society of Cardiology. Developed in Collaboration with the European Heart Rhythm Association
Authors/Task Force Members et al.
Eur Heart J 2007;28:2256-2295.
FULL TEXT  

Importance of contractile reserve for CRT
Lim et al.
Europace 2007;9:739-743.
ABSTRACT | FULL TEXT  

CRT-D use in heart failure: too little or too much?
Hohnloser and Prystowsky
Eur Heart J Suppl 2007;9:G9-G16.
ABSTRACT | FULL TEXT  

Implantation of cardiac resynchronization therapy systems in the CARE-HF trial: procedural success rate and safety
Gras et al.
Europace 2007;9:516-522.
ABSTRACT | FULL TEXT  

Cardiac Resynchronization Therapy for Patients With Left Ventricular Systolic Dysfunction: A Systematic Review
McAlister et al.
JAMA 2007;297:2502-2514.
ABSTRACT | FULL TEXT  

Mode of Death in Patients With Systolic Heart Failure
Patel and Heywood
J CARDIOVASC PHARMACOL THER 2007;12:127-136.
ABSTRACT  

Impact of left ventricular lead position in cardiac resynchronization therapy on left ventricular remodelling. A circumferential strain analysis based on 2D echocardiography
Becker et al.
Eur Heart J 2007;28:1211-1220.
ABSTRACT | FULL TEXT  

Interventional Electrophysiology and Cardiac Resynchronization Therapy: Delivering Electrical Therapies for Heart Failure
Burkhardt and Wilkoff
Circulation 2007;115:2208-2220.
ABSTRACT | FULL TEXT  

Effect of left ventricular endocardial activation pattern on echocardiographic and clinical response to cardiac resynchronization therapy
Fung et al.
Heart 2007;93:432-437.
ABSTRACT | FULL TEXT  

Digoxin and Reduction in Mortality and Hospitalization in Geriatric Heart Failure: Importance of Low Doses and Low Serum Concentrations
Ahmed
J. Gerontol. A Biol. Sci. Med. Sci. 2007;62:323-329.
ABSTRACT | FULL TEXT  

Effect of Cardiac Resynchronization on Morbidity and Mortality of Diabetic Patients With Severe Heart Failure
Hoppe et al.
Diabetes Care 2007;30:722-724.
FULL TEXT  

Cardiac resynchronization therapy: predictive factors of unsuccessful left ventricular lead implant
Macias et al.
Eur Heart J 2007;28:450-456.
ABSTRACT | FULL TEXT  

Ventricular Epicardial Lead Placement for Resynchronization by Determination of Paced Depolarization Intervals: Technique and Rationale
Edgerton et al.
Ann. Thorac. Surg. 2007;83:89-92.
ABSTRACT | FULL TEXT  

The long-term cost-effectiveness of cardiac resynchronization therapy with or without an implantable cardioverter-defibrillator
Yao et al.
Eur Heart J 2007;28:42-51.
ABSTRACT | FULL TEXT  

Left ventricular electromechanical delay in patients with heart failure and normal QRS duration and in patients with right and left bundle branch block
Badano et al.
Europace 2007;9:41-47.
ABSTRACT | FULL TEXT  

The Cardiovascular Disease Continuum Validated: Clinical Evidence of Improved Patient Outcomes: Part II: Clinical Trial Evidence (Acute Coronary Syndromes Through Renal Disease) and Future Directions
Dzau et al.
Circulation 2006;114:2871-2891.
FULL TEXT  

Predictors of Sudden Cardiac Death and Appropriate Shock in the Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) Trial
Saxon et al.
Circulation 2006;114:2766-2772.
ABSTRACT | FULL TEXT  

Response to Abraham
Abraham
Circulation 2006;114:2692-2698.
FULL TEXT  

Effects of cardiac resynchronization therapy on overall mortality and mode of death: a meta-analysis of randomized controlled trials
Rivero-Ayerza et al.
Eur Heart J 2006;27:2682-2688.
ABSTRACT | FULL TEXT  

Abnormal Conduction Increases Risk of Adverse Outcomes From Right Ventricular Pacing
Hayes et al.
J Am Coll Cardiol 2006;48:1628-1633.
ABSTRACT | FULL TEXT  

Coronary artery bypass grafting and biventricular pacing efficacy: Do past trials dictate a change in future practice?
Hajiseyedjavadi et al.
J. Thorac. Cardiovasc. Surg. 2006;132:974-975.
FULL TEXT  

Extent of Viability to Predict Response to Cardiac Resynchronization Therapy in Ischemic Heart Failure Patients
Ypenburg et al.
JNM 2006;47:1565-1570.
ABSTRACT | FULL TEXT  

Tissue Doppler velocity is superior to displacement and strain mapping in predicting left ventricular reverse remodelling response after cardiac resynchronisation therapy
Yu et al.
Heart 2006;92:1452-1456.
ABSTRACT | FULL TEXT  

ACC/AHA/ESC 2006 Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death)
Developed in Collaboration With the European Heart et al.
J Am Coll Cardiol 2006;48:e247-e346.
FULL TEXT  

ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: A report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death) Developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society
Writing Committee Members et al.
Europace 2006;8:746-837.
FULL TEXT  

Longer-term effects of cardiac resynchronization therapy on mortality in heart failure [the CArdiac REsynchronization-Heart Failure (CARE-HF) trial extension phase]
Cleland et al.
Eur Heart J 2006;27:1928-1932.
ABSTRACT | FULL TEXT  

Benefit of Combined Resynchronization and Defibrillator Therapy in Heart Failure Patients With and Without Ventricular Arrhythmias
Ypenburg et al.
J Am Coll Cardiol 2006;48:464-470.
ABSTRACT | FULL TEXT  

Biventricular pacing.
Jarcho
NEJM 2006;355:288-294.
FULL TEXT  

Effect of Cardiac Resynchronization on the Incidence of Atrial Fibrillation in Patients With Severe Heart Failure
Hoppe et al.
Circulation 2006;114:18-25.
ABSTRACT | FULL TEXT  

Cardiac resynchronization pacing without defibrillator capability: is this a viable option?
Ermis and Benditt
Europace 2006;8:499-501.
ABSTRACT | FULL TEXT  

The Frequency and Incremental Cost of Major Complications Among Medicare Beneficiaries Receiving Implantable Cardioverter-Defibrillators
Reynolds et al.
J Am Coll Cardiol 2006;47:2493-2497.
ABSTRACT | FULL TEXT  

Causes and Consequences of Heart Failure After Prophylactic Implantation of a Defibrillator in the Multicenter Automatic Defibrillator Implantation Trial II
Goldenberg et al.
Circulation 2006;113:2810-2817.
ABSTRACT | FULL TEXT  

Selecting patients for cardiac resynchronization therapy: electrical or mechanical dyssynchrony?
Hawkins et al.
Eur Heart J 2006;27:1270-1281.
ABSTRACT | FULL TEXT  

Effects of cardiac resynchronization therapy on disease progression in chronic heart failure
Donal et al.
Eur Heart J 2006;27:1018-1025.
ABSTRACT | FULL TEXT  

Gender and heart failure: a population perspective
Mehta and Cowie
Heart 2006;92:iii14-iii18.
FULL TEXT  

The effect of ventricular sequential contraction on helical heart during pacing: high septal pacing versus biventricular pacing
Tomioka et al.
Eur. J. Cardiothorac. Surg. 2006;29:S198-S206.
ABSTRACT | FULL TEXT  

Additional Information
JAMA 2006;295:E1-E6.
FULL TEXT  

Implantable Cardioverter-Defibrillators: Expanding Indications and Technologies
Goldberger and Lampert
JAMA 2006;295:809-818.
ABSTRACT | FULL TEXT  

How many patients with heart failure are eligible for cardiac resynchronization? Insights from two prospective cohorts
McAlister et al.
Eur Heart J 2006;27:323-329.
ABSTRACT | FULL TEXT  

Sustained Reverse Left Ventricular Structural Remodeling With Cardiac Resynchronization at One Year Is a Function of Etiology: Quantitative Doppler Echocardiographic Evidence From the Multicenter InSync Randomized Clinical Evaluation (MIRACLE)
St John Sutton et al.
Circulation 2006;113:266-272.
ABSTRACT | FULL TEXT  

Digoxin and reduction in mortality and hospitalization in heart failure: a comprehensive post hoc analysis of the DIG trial
Ahmed et al.
Eur Heart J 2006;27:178-186.
ABSTRACT | FULL TEXT  

Role of resynchronisation therapy and implantable cardioverter defibrillators in heart failure
Ellery et al.
Postgrad. Med. J. 2006;82:16-23.
ABSTRACT | FULL TEXT  

Cardiac Resynchronization Therapy: Part 1--Issues Before Device Implantation
Bax et al.
J Am Coll Cardiol 2005;46:2153-2167.
ABSTRACT | FULL TEXT  

Significance of QRS Complex Duration in Patients With Heart Failure
Kashani and Barold
J Am Coll Cardiol 2005;46:2183-2192.
ABSTRACT | FULL TEXT  

Management of Heart Failure After Cardiac Resynchronization Therapy: Integrating Advanced Heart Failure Treatment With Optimal Device Function
Aranda et al.
J Am Coll Cardiol 2005;46:2193-2198.
ABSTRACT | FULL TEXT  

Why Should We Care About CARE-HF?
Ellenbogen et al.
J Am Coll Cardiol 2005;46:2199-2203.
ABSTRACT | FULL TEXT  

There Is Plenty of Room for Cardiac Resynchronization Therapy Devices Without Back-Up Defibrillators in the Electrical Treatment of Heart Failure
Daubert et al.
J Am Coll Cardiol 2005;46:2204-2207.
ABSTRACT | FULL TEXT  

Impact of Upgrade to Cardiac Resynchronization Therapy on Ventricular Arrhythmia Frequency in Patients With Implantable Cardioverter-Defibrillators
Ermis et al.
J Am Coll Cardiol 2005;46:2258-2263.
ABSTRACT | FULL TEXT  

Resynchronization Therapy in Pediatric and Congenital Heart Disease Patients: An International MultiCenter Study
Dubin et al.
J Am Coll Cardiol 2005;46:2277-2283.
ABSTRACT | FULL TEXT  

Resynchronization in Pediatrics: Who Needs It?
Dubin
J Am Coll Cardiol 2005;46:2290-2291.
FULL TEXT  

Cardiac Resynchronization With Sequential Biventricular Pacing for the Treatment of Moderate-to-Severe Heart Failure
Leon et al.
J Am Coll Cardiol 2005;46:2298-2304.
ABSTRACT | FULL TEXT  

Cost Effectiveness of Cardiac Resynchronization Therapy
Hlatky
J Am Coll Cardiol 2005;46:2322-2324.
FULL TEXT  

Fluoroscopically Guided Implantation of Modern Cardiac Resynchronization Devices: Radiation Burden to the Patient and Associated Risks
Perisinakis et al.
J Am Coll Cardiol 2005;46:2335-2339.
ABSTRACT | FULL TEXT