ContextCardiac 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.ObjectiveTo 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 ParticipantsRandomized, 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.InterventionsOf 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 MeasuresThe 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.ResultsAt 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.ConclusionsCardiac 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.

https://jamanetwork.com/journals/jama/articlepdf/1108361/JOC30332.pdf

Combined cardiac resynchronization and implantable cardioversion defibrillation in advanced chronic heart failure: the MIRACLE ICD Trial.

ContextProgressive heart failure is the most common mechanism of death among
patients with advanced heart failure. Cardiac resynchronization, a pacemaker-based
therapy for heart failure, enhances cardiac performance and quality of life,
but its effect on mortality is uncertain.ObjectiveTo determine whether cardiac resynchronization reduces mortality from
progressive heart failure.Data SourcesMEDLINE (1966-2002), EMBASE (1980-2002), the Cochrane Controlled Trials
Register (Second Quarter, 2002), The National Institutes of Health ClinicalTrials.gov
database, the US Food and Drug Administration Web site, and reports presented
at scientific meetings (1994-2002). Search terms included pacemaker, pacing, heart
failure, dual-site, multisite, biventricular, resynchronization, and left ventricular preexcitation.Study SelectionEligible studies were randomized controlled trials of cardiac resynchronization
for the treatment of chronic symptomatic left ventricular dysfunction. Eligible
studies reported death, hospitalization for heart failure, or ventricular
arrhythmia as outcomes. Of the 6883 potentially relevant reports initially
identified, 11 reports of 4 randomized trials with 1634 total patients were
included in the meta-analysis.Data ExtractionTrial reports were reviewed independently by 2 investigators in an unblinded
standardized manner.Data SynthesisFollow-up in the included trials ranged from 3 to 6 months. Pooled data
from the 4 selected studies showed that cardiac resynchronization reduced
death from progressive heart failure by 51% relative to controls (odds ratio
[OR], 0.49; 95% confidence interval [CI], 0.25-0.93). Progressive heart failure
mortality was 1.7% for cardiac resynchronization patients and 3.5% for controls.
Cardiac resynchronization also reduced heart failure hospitalization by 29%
(OR, 0.71; 95% CI, 0.53-0.96) and showed a trend toward reducing all-cause
mortality (OR, 0.77; 95% CI, 0.51-1.18). Cardiac resynchronization was not
associated with a statistically significant effect on non–heart failure
mortality (OR, 1.15; 95% CI, 0.65-2.02). Among patients with implantable cardioverter
defibrillators, cardiac resynchronization had no clear impact on ventricular
tachycardia or ventricular fibrillation (OR, 0.92; 95% CI, 0.67-1.27).ConclusionsCardiac resynchronization reduces mortality from progressive heart failure
in patients with symptomatic left ventricular dysfunction. This finding suggests
that cardiac resynchronization may have a substantial impact on the most common
mechanism of death among patients with advanced heart failure. Cardiac resynchronization
also reduces heart failure hospitalization and shows a trend toward reducing
all-cause mortality.

Cardiac resynchronization and death from progressive heart failure: a meta-analysis of randomized controlled trials.

Background— The effects of cardiac resynchronization therapy (CRT) in patients with mildly symptomatic heart failure have not been fully elucidated. Methods and Results— The Multicenter InSync ICD Randomized Clinical Evaluation II (MIRACLE ICD II) was a randomized, double-blind, parallel-controlled clinical trial of CRT in NYHA class II heart failure patients on optimal medical therapy with a left ventricular (LV) ejection fraction ≤35%, a QRS ≥130 ms, and a class I indication for an ICD. One hundred eighty-six patients were randomized: 101 to the control group (ICD activated, CRT off) and 85 to the CRT group (ICD activated, CRT on). End points included peak Vo2, Ve/Vco2, NYHA class, quality of life, 6-minute walk distance, LV volumes and ejection fraction, and composite clinical response. Compared with the control group at 6 months, no significant improvement was noted in peak Vo2, yet there were significant improvements in ventricular remodeling indexes, specifically LV diastolic and systolic volume...

Effects of Cardiac Resynchronization on Disease Progression in Patients With Left Ventricular Systolic Dysfunction, an Indication for an Implantable Cardioverter-Defibrillator, and Mildly Symptomatic Chronic Heart Failure

Retiming the failing heart: principles and current clinical status of cardiac resynchronization.

Resynchronization therapy in pediatric and congenital heart disease patients: an international multicenter study.

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Jon Allen

Papers

Usefulness of suppression of ventricular arrhythmia by biventricular pacing in severe congestive cardiac failure.