Rationale and design of a randomized clinical trial to assess the safety and efficacy of cardiac resynchronization therapy in patients with advanced heart failure: The multicenter InSync randomized clinical evaluation (MIRACLE)

On behalf of the multicenter insync randomized clinical evaluation (miracle) investigators and coordinators

Research output: Contribution to journalArticle

143 Citations (Scopus)

Abstract

Up to 50% of patients with chronic systolic heart failure have interventricular conduction delays, such as left bundle branch block, that result in abnormal electrical depolarization of the heart. Prolonged QRS duration results in abnormal interventricular septal wall motion, decreased contractility, reduced diastolic filling time, and prolonged duration of mitral regurgitation, which places the failing heart at a significant mechanical disadvantage. Prolonged QRS duration has been associated with poor outcome in heart failure patients. Atrial-synchronized, biventricular pacing or cardiac resynchronization therapy optimizes atrial-ventricular delay, narrows QRS duration, and seems promising in the management of advanced heart failure patients. Initial studies show improved quality of life and functional capacity compared with baseline or with no pacing. These studies, however, were either uncontrolled or poorly controlled, unblinded or only single-blinded, and enrolled small numbers of patients. The Multicenter InSync Randomized Clinical Evaluation (MIRACLE) is a large, prospective, randomized, double-blind, controlled trial designed to more definitively evaluate the clinical efficacy and safety of cardiac resynchronization for heart failure. The study is being completed in 3 phases (an initial pilot phase, a pivotal phase, and an expansion phase), enrolling 500 patients with New York Heart Association (NYHA) class III and IV systolic heart failure and QRS durations of 130 ms or more. Prospectively defined primary end points for the pivotal phase include evaluation of safety (implant success rate, freedom from stimulator- and ventricular-lead-related complications) and effects on functional status (quality of life, NYHA class, 6-minute hall walk distance) at 6 months. A variety of secondary end points will further define the efficacy and mechanism(s) of action of cardiac resynchronization in heart failure. The pivotal phase of MIRACLE will conclude in January 2001.

Original languageEnglish (US)
Pages (from-to)369-380
Number of pages12
JournalJournal of Cardiac Failure
Volume6
Issue number4
DOIs
StatePublished - Jan 1 2000

Fingerprint

Cardiac Resynchronization Therapy
Randomized Controlled Trials
Heart Failure
Safety
Systolic Heart Failure
Quality of Life
Bundle-Branch Block
Mitral Valve Insufficiency

Keywords

  • Biventricular pacing
  • Cardiac resynchronization
  • Conduction defects
  • Heart failure
  • Randomized controlled trial
  • Ventricular dysynchrony

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Rationale and design of a randomized clinical trial to assess the safety and efficacy of cardiac resynchronization therapy in patients with advanced heart failure : The multicenter InSync randomized clinical evaluation (MIRACLE). / On behalf of the multicenter insync randomized clinical evaluation (miracle) investigators and coordinators.

In: Journal of Cardiac Failure, Vol. 6, No. 4, 01.01.2000, p. 369-380.

Research output: Contribution to journalArticle

@article{a743e064c70b4dc59d94a7829a48aa43,
title = "Rationale and design of a randomized clinical trial to assess the safety and efficacy of cardiac resynchronization therapy in patients with advanced heart failure: The multicenter InSync randomized clinical evaluation (MIRACLE)",
abstract = "Up to 50{\%} of patients with chronic systolic heart failure have interventricular conduction delays, such as left bundle branch block, that result in abnormal electrical depolarization of the heart. Prolonged QRS duration results in abnormal interventricular septal wall motion, decreased contractility, reduced diastolic filling time, and prolonged duration of mitral regurgitation, which places the failing heart at a significant mechanical disadvantage. Prolonged QRS duration has been associated with poor outcome in heart failure patients. Atrial-synchronized, biventricular pacing or cardiac resynchronization therapy optimizes atrial-ventricular delay, narrows QRS duration, and seems promising in the management of advanced heart failure patients. Initial studies show improved quality of life and functional capacity compared with baseline or with no pacing. These studies, however, were either uncontrolled or poorly controlled, unblinded or only single-blinded, and enrolled small numbers of patients. The Multicenter InSync Randomized Clinical Evaluation (MIRACLE) is a large, prospective, randomized, double-blind, controlled trial designed to more definitively evaluate the clinical efficacy and safety of cardiac resynchronization for heart failure. The study is being completed in 3 phases (an initial pilot phase, a pivotal phase, and an expansion phase), enrolling 500 patients with New York Heart Association (NYHA) class III and IV systolic heart failure and QRS durations of 130 ms or more. Prospectively defined primary end points for the pivotal phase include evaluation of safety (implant success rate, freedom from stimulator- and ventricular-lead-related complications) and effects on functional status (quality of life, NYHA class, 6-minute hall walk distance) at 6 months. A variety of secondary end points will further define the efficacy and mechanism(s) of action of cardiac resynchronization in heart failure. The pivotal phase of MIRACLE will conclude in January 2001.",
keywords = "Biventricular pacing, Cardiac resynchronization, Conduction defects, Heart failure, Randomized controlled trial, Ventricular dysynchrony",
author = "{On behalf of the multicenter insync randomized clinical evaluation (miracle) investigators and coordinators} and Abraham, {William T.} and Durand, {Jean Bernard} and John Seger and John Seger and William Spencer and Donna Killip and Kattie Becker and Stevenson, {Lynne Warner} and Michael Sweeney and Laurie Roberts and Melanie Brophy and Joseph Caplan and George Wong and Evelyn Daniel and Julie Brockhaus and Carlos Rizo-Patron and John Zias and Karen Belco and Marc Silver and Muyhladeen Dia and Julie Tischer and Kelly Wesselhoff and James Young and Bruce Wilkoff and Juliet Pryce and Jeanne Shewchik and Evelyn Horn and Henry Spotnitz and Madeline Yushak and Norma Medina and {Ann Kral}, Mary and David Delurgio and Angel Leon and Judith Schmidt and Paige Smith and {O’ Conner}, Christopher and Robert Sorrentino and Sorrentino, {Robert A} and Andrew Smith and Jonathan Langberg and Peter McCullough and Claudio Schuger and Deb Frankovich and Judy Lehman and William Wickemeyer and Johnson, {W. Ben} and Becky Sollinger and Judi Greene and Raymond Yee and Jane Finan",
year = "2000",
month = "1",
day = "1",
doi = "10.1054/jcaf.2000.20841",
language = "English (US)",
volume = "6",
pages = "369--380",
journal = "Journal of Cardiac Failure",
issn = "1071-9164",
publisher = "Churchill Livingstone",
number = "4",

}

TY - JOUR

T1 - Rationale and design of a randomized clinical trial to assess the safety and efficacy of cardiac resynchronization therapy in patients with advanced heart failure

T2 - The multicenter InSync randomized clinical evaluation (MIRACLE)

AU - On behalf of the multicenter insync randomized clinical evaluation (miracle) investigators and coordinators

AU - Abraham, William T.

AU - Durand, Jean Bernard

AU - Seger, John

AU - Seger, John

AU - Spencer, William

AU - Killip, Donna

AU - Becker, Kattie

AU - Stevenson, Lynne Warner

AU - Sweeney, Michael

AU - Roberts, Laurie

AU - Brophy, Melanie

AU - Caplan, Joseph

AU - Wong, George

AU - Daniel, Evelyn

AU - Brockhaus, Julie

AU - Rizo-Patron, Carlos

AU - Zias, John

AU - Belco, Karen

AU - Silver, Marc

AU - Dia, Muyhladeen

AU - Tischer, Julie

AU - Wesselhoff, Kelly

AU - Young, James

AU - Wilkoff, Bruce

AU - Pryce, Juliet

AU - Shewchik, Jeanne

AU - Horn, Evelyn

AU - Spotnitz, Henry

AU - Yushak, Madeline

AU - Medina, Norma

AU - Ann Kral, Mary

AU - Delurgio, David

AU - Leon, Angel

AU - Schmidt, Judith

AU - Smith, Paige

AU - O’ Conner, Christopher

AU - Sorrentino, Robert

AU - Sorrentino, Robert A

AU - Smith, Andrew

AU - Langberg, Jonathan

AU - McCullough, Peter

AU - Schuger, Claudio

AU - Frankovich, Deb

AU - Lehman, Judy

AU - Wickemeyer, William

AU - Johnson, W. Ben

AU - Sollinger, Becky

AU - Greene, Judi

AU - Yee, Raymond

AU - Finan, Jane

PY - 2000/1/1

Y1 - 2000/1/1

N2 - Up to 50% of patients with chronic systolic heart failure have interventricular conduction delays, such as left bundle branch block, that result in abnormal electrical depolarization of the heart. Prolonged QRS duration results in abnormal interventricular septal wall motion, decreased contractility, reduced diastolic filling time, and prolonged duration of mitral regurgitation, which places the failing heart at a significant mechanical disadvantage. Prolonged QRS duration has been associated with poor outcome in heart failure patients. Atrial-synchronized, biventricular pacing or cardiac resynchronization therapy optimizes atrial-ventricular delay, narrows QRS duration, and seems promising in the management of advanced heart failure patients. Initial studies show improved quality of life and functional capacity compared with baseline or with no pacing. These studies, however, were either uncontrolled or poorly controlled, unblinded or only single-blinded, and enrolled small numbers of patients. The Multicenter InSync Randomized Clinical Evaluation (MIRACLE) is a large, prospective, randomized, double-blind, controlled trial designed to more definitively evaluate the clinical efficacy and safety of cardiac resynchronization for heart failure. The study is being completed in 3 phases (an initial pilot phase, a pivotal phase, and an expansion phase), enrolling 500 patients with New York Heart Association (NYHA) class III and IV systolic heart failure and QRS durations of 130 ms or more. Prospectively defined primary end points for the pivotal phase include evaluation of safety (implant success rate, freedom from stimulator- and ventricular-lead-related complications) and effects on functional status (quality of life, NYHA class, 6-minute hall walk distance) at 6 months. A variety of secondary end points will further define the efficacy and mechanism(s) of action of cardiac resynchronization in heart failure. The pivotal phase of MIRACLE will conclude in January 2001.

AB - Up to 50% of patients with chronic systolic heart failure have interventricular conduction delays, such as left bundle branch block, that result in abnormal electrical depolarization of the heart. Prolonged QRS duration results in abnormal interventricular septal wall motion, decreased contractility, reduced diastolic filling time, and prolonged duration of mitral regurgitation, which places the failing heart at a significant mechanical disadvantage. Prolonged QRS duration has been associated with poor outcome in heart failure patients. Atrial-synchronized, biventricular pacing or cardiac resynchronization therapy optimizes atrial-ventricular delay, narrows QRS duration, and seems promising in the management of advanced heart failure patients. Initial studies show improved quality of life and functional capacity compared with baseline or with no pacing. These studies, however, were either uncontrolled or poorly controlled, unblinded or only single-blinded, and enrolled small numbers of patients. The Multicenter InSync Randomized Clinical Evaluation (MIRACLE) is a large, prospective, randomized, double-blind, controlled trial designed to more definitively evaluate the clinical efficacy and safety of cardiac resynchronization for heart failure. The study is being completed in 3 phases (an initial pilot phase, a pivotal phase, and an expansion phase), enrolling 500 patients with New York Heart Association (NYHA) class III and IV systolic heart failure and QRS durations of 130 ms or more. Prospectively defined primary end points for the pivotal phase include evaluation of safety (implant success rate, freedom from stimulator- and ventricular-lead-related complications) and effects on functional status (quality of life, NYHA class, 6-minute hall walk distance) at 6 months. A variety of secondary end points will further define the efficacy and mechanism(s) of action of cardiac resynchronization in heart failure. The pivotal phase of MIRACLE will conclude in January 2001.

KW - Biventricular pacing

KW - Cardiac resynchronization

KW - Conduction defects

KW - Heart failure

KW - Randomized controlled trial

KW - Ventricular dysynchrony

UR - http://www.scopus.com/inward/record.url?scp=0034522062&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034522062&partnerID=8YFLogxK

U2 - 10.1054/jcaf.2000.20841

DO - 10.1054/jcaf.2000.20841

M3 - Article

C2 - 11145762

AN - SCOPUS:0034522062

VL - 6

SP - 369

EP - 380

JO - Journal of Cardiac Failure

JF - Journal of Cardiac Failure

SN - 1071-9164

IS - 4

ER -