Cardiac resynchronization in advanced heart failure

• intraventricular conduction delays are associated with dyssynchronous left ventricular contraction caused by regional delays in the electrical activation of the chamber
  • this phenomenon, which occurs in 15 to 30 percent of patients with heart failure due to dilated cardiomyopathy, reduces systolic function and increases systolic volume
  • in patients with primary or secondary dilated cardiomyopathies characterized by intraventricular conduction delays, biventricular stimulation synchronizes the activation of the intraventricular septum and left ventricular free wall and thus improves left ventricular systolic function
  • short-term studies, cardiac-resynchronization therapy in the form of biventricular stimulation improved symptoms, improved the quality of life, and increased exercise tolerance and partially reversed maladaptive remodeling
• in the Comparison of Medical Therapy, Pacing and Defibrillation in Heart Failure (COMPANION) trial
  • 1520 patients who had advanced heart failure (New York Heart Association class III or IV) due to ischemic or nonischemic cardiomyopathies and a QRS interval of at least 120 msec were randomly assigned in a 1:2:2 ratio to receive optimal pharmacologic therapy (diuretics, angiotensin-converting–enzyme inhibitors, beta-blockers, and spironolactone) alone or in combination with cardiac-resynchronization therapy with either a pacemaker or a pacemaker–defibrillator
  • primary composite end point was the time to death from or hospitalization for any cause
  • as compared with optimal pharmacologic therapy alone, cardiac-resynchronization therapy with a pacemaker decreased the risk of the primary end point (hazard ratio, 0.81; P=0.014), as did cardiac-resynchronization therapy with a pacemaker–defibrillator (hazard ratio, 0.80; P=0.01)
    • risk of the combined end point of death from or hospitalization for heart failure was reduced by 34 percent in the pacemaker group (P<0.002) and by 40 percent in the pacemaker-defibrillator group (P<0.001 for the comparison with the pharmacologic-therapy group). A pacemaker reduced the risk of the secondary end point of death from any cause by 24 percent (P=0.059), and a pacemaker–defibrillator reduced the risk by 36 percent (P=0.003)
    • results indicate that the use of biventricular stimulation to resynchronize left ventricular contraction can improve major clinical outcomes in patients with a prolonged QRS interval and advanced, symptomatic heart failure as a result of moderate-to-severe left ventricular systolic dysfunction
      • rate of death from any cause or hospitalization for any cause was reduced by approximately 20 percent in both groups that received cardiac-resynchronization therapy in addition to optimal pharmacologic therapy, as compared with the group that received optimal pharmacologic therapy alone
      • the larger reduction in the outcome of death from or hospitalization for heart failure suggests that much of the reduction was related to the favorable effects of the devices on the clinical syndrome of heart failure
      • the addition of a defibrillator to cardiac-resynchronization therapy incrementally increased the survival benefit, resulting in a substantial, 36 percent reduction in the risk of death (P=0.003), as compared with optimal pharmacologic therapy
      • the authors concluded
        • ....in selected patients, cardiac-resynchronization therapy with a pacemaker or a pacemaker-defibrillator can improve the clinical course of chronic heart failure due to a dilated cardiomyopathy. The pacemaker is associated with a reduction in hospitalizations and symptoms and improved exercise tolerance and quality of life, and the addition of a defibrillator to cardiac-resynchronization therapy further reduces mortality
        • a further analysis concluded (2) that the use of CRT with or without a defibrillator in advanced heart failure patients was associated with marked reductions in all-cause, cardiac, and heart failure hospitalization rates in an analysis that accounted for the competing risk of mortality and unequal follow-up time

Reference:

• 1. Bristow MR, Saxon LA, Boehmer J, Krueger S, Kass DA, DeMarco T, Carson P, DiCarlo L, DeMets D, White BG, DeVries DW, Feldman AM. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med. 2004; 350: 2140-2150
• 2. Anand IS et al. Cardiac resynchronization therapy reduces the risk of hospitalizations in patients with advanced heart failure: results from the Comparison of Medical Therapy, Pacing and Defibrillation in Heart Failure (COMPANION) trial.Circulation. 2009 Feb 24;119(7):969-77