Published Online
on December 11, 2006

A more recent version of this article appeared on December 19, 2006

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Submitted on August 26, 2005
Revised on October 5, 2006
Accepted on October 13, 2006

Predictors of Sudden Cardiac Death and Appropriate Shock in the Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) Trial

Leslie A. Saxon MD^*, Michael R. Bristow MD, John Boehmer MD, Steven Krueger MD, David A. Kass MD, Teresa De Marco MD, Peter Carson MD, Lorenzo DiCarlo MD, Arthur M. Feldman MD, PhD, Elizabeth Galle MS, and Fred Ecklund MS

From the Keck School of Medicine at the University of Southern California (L.A.S.), Los Angeles; University of Colorado Health Sciences Center (M.R.B.), Denver; Milton S. Hershey Medical Center (J.B.), Hershey, Pa; Bryan Memorial Hospital (S.K.), Lincoln, Neb; Johns Hopkins Hospital (D.A.K.), Baltimore, Md; University of California at San Francisco (T.D.M.), San Francisco; Veterans Affairs Medical Center (P.C.), Washington, DC; Pfizer Global Research and Development (L.D.), Ann Arbor, Mich; Jefferson Medical College (A.M.F.), Philadelphia, Pa; and Guidant Corporation (E.G., F.E.), St. Paul, Minn.

^* To whom correspondence should be addressed. E-mail: saxon{at}usc.edu.

Background--The factors that determine the risk for sudden death or implantable cardioverter defibrillator therapy in patients receiving cardiac resynchronization therapy (CRT) therapies are largely unknown.

Methods and Results--We hypothesized that clinical measures of heart failure severity and the presence of comorbid conditions would predict the risk of malignant arrhythmias in the 1520 patients enrolled in the Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) Trial. Outcomes in the CRT group after implantable cardioverter defibrillator therapy were also evaluated. The CRT-defibrillator device reduced the risk of sudden death by 56% compared with drug therapy (17 of 595 [2.9%] versus 18 of 308 [5.8%], P<0.02). CRT therapy was not associated with sudden death risk reduction (48 of 617 [7.8%]). Other factors associated with reduced sudden death risk were left ventricular ejection fraction >20% (HR, 0.55 [95% CI, 0.35 to 0.87]; P=0.01), QRS duration >160 ms (HR, 0.63 [95% CI, 0.40 to 0.997]; P=0.05), and female gender (HR, 0.56 [95% CI, 0.34 to 0.94]; P=0.003). The risk for sudden death was increased by advanced New York Heart Association class IV heart failure (HR, 2.62 [95% CI, 1.61 to 4.26]; P<0.011) and renal dysfunction (HR, 1.69 [95% CI, 1.06 to 2.69]; P=0.03). An appropriate shock was experienced in 88 (15%) of the 595 CTR-D patients. In the CRT-defibrillator patients, female gender (HR, 0.54 [95 % CI, 0.31 to 0.94]; P=0.03) and use of neurohormonal antagonists were associated with reduced risk. Class IV heart failure status increased risk. Appropriate implantable cardioverter defibrillator therapy was positively associated with risk of death or all-cause hospitalization (HR, 1.57; P<0.002), pump failure death or hospitalization (HR, 2.35; P<0.001), and sudden death (HR, 2.99; P=0.03), but not total mortality (HR, 1.3; P=0.28).

Conclusions--In CRT candidates, sudden cardiac death risk is associated with higher New York Heart Association class and renal dysfunction. In CRT-defibrillator recipients, reduction in the risk of an appropriate shock is associated with medical therapy with neurohormonal antagonists, female gender, and New York Heart Association functional class III versus IV clinical status. Shock therapy was associated with worse outcome.

Key words: arrhythmia • death, sudden • defibrillation • electrophysiology • heart failure • implantable cardioverter-defibrillators

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