Cardiac Resynchronization-Heart Failure

The CARE-HF (Cardiac Resynchronization-Heart Failure) study was designed specifically to evaluate the effects of CRT on morbidity and mortality (1). This trial was started in January 2001 and was published in April 2005. Eight hundred nineteen patients with EF <35% and evidence dyssyn-chrony were randomized to optimal medical therapy or CRT. Dyssynchrony was defined as either a QRS duration > 150 ms or a QRS duration of 120-149 ms with echocardiographic evidence of dyssynchrony. In the CRT group, there was a 37% risk reduction (p < 0.001) in the primary endpoint, which was a composite of death from any canse or unplanned hospitalization for a major cardiac event (Fig. 11.3). In terms of all-cause mortality (secondary endpoint), there was a 36% risk reduction (p < 0.002) in the CRT group compared to optimal medical therapy. This study went beyond COMPANION by showing that CRT alone, even without the defibrillator, could improve survival. 

A series of pilot studies began with multisite pacing for patients with heart failure and dilated cardiomyopathy in the early 1990s [52, 105-111]. An improvement in LV function and symptoms of heart failure were demonstrated. This provided the interest in biventricular pacing for heart failure. The term cardiac resynchronization therapy was coined to refer to pacing therapies that attempt to enhance cardiac performance by using pacing to correct electrical conduction abnormalities in the heart. The most common form of this therapy is atrial-synchronous... 

Auricchio A, Kloss M, Trautmann SI, Rodner S, Klein H. Exercise performance following cardiac resynchronization therapy in patients with heart failure and ventricular conduction delay. Am. J. Cardiol. 2002 89 198-203. 

Stellbrink C, Breithardt OA, Franke A, et al. Impact of cardiac resynchronization therapy using hemodynami-cally optimized pacing on left ventricular remodeling in patients with congestive heart failure and ventricular conduction disturbances, [see comment]. J. Am. Coll. Cardiol. 2001 38 1957-65. 

Young JB, Abraham WT, Smith AL, et al. Combined cardiac resynchronization and implantable cardioversion defibrillation in advanced chronic heart failure the MIRACLE ICD Trial, [see comment]. JAMA 2003 289 2685-94. 

Bristow MR, Saxon LA, Boehmer J, et al. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure, [see comment]. N. Engl. J. Med. 2004 350 2140-50. 

St John Sutton MG, Plappert T, Abraham WT, et al. Effect of cardiac resynchronization therapy on left ventricular size and function in chronic heart failure, [see comment]. Circulation 2003 107 1985-90. 

McAlister F, Ezekowitz J, Wiebe N, et al. Cardiac resynchronization therapy for congestive heart failure. Evid. Rep. Technol. Assess (Summ.) 2004 106 1-8. 

Molhoek SG, Van Erven L, Bootsma M, Steendijk P, Van Der Wall EE, Schalij MJ. QRS duration and shortening to predict clinical response to cardiac resynchronization therapy in patients with end-stage heart failure. Pacing Clin. Electrophysiol. 2004 27 308-13. 

Linde C, Abraham WT, Gold MR, St John Sutton M, Ghio S, Daubert C. Randomized trial of cardiac resynchronization in mildly symptomatic heart failure patients and in asymptomatic patients with left ventricular dysfunction and previous heart failure symptoms. J. Am. Coll. Cardiol. 2008 52 1834-A3. 

Patients with normal sinus rhythm and a wide QRS interval, eg, greater than 120 ms, have impaired synchronization of ventricular contraction. Poor synchronization of left ventricular contraction results in diminished cardiac output. Resynchronization, with left ventricular or biventricular pacing, has been shown to reduce mortality in patients with chronic heart failure who were already receiving optimal medical therapy. 

Cleland JCF et al The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med 2005 352 1539. [PMID 15753115]... 

Recent studies demonstrate that cardiac resynchronization therapy (CRT) offers a promising approach to selected patients with chronic heart failure. Delayed electrical activation of the left ventricle, characterized on the ECG by a QRS duration that exceeds 120 ms, occurs in approximately one-third of patients with moderate to severe systolic heart failure. Since the left and right ventricles normally activate simultaneously, this delay results in asynchronous contraction of the left and right ventricles, which contributes to the hemodynamic abnormalities of this disorder. Implantation of a speciahzed biventricular pacemaker to restore synchronous activation of the ventricles can improve ventricular contraction and hemodynamics. Recent trials show improvements in exercise capacity, NYHA classification, quality of life, hemodynamic function, and hospitalizations. A device that combined CRT with an implantable cardioverter-defibrillator (ICD) improved survival in addition to functional status. CRT is currently indicated only in NYHA class ni-IV patients receiving optimal medical therapy (ACE inhibitors, diuretics, -blockers, and digoxin) and... 

Abraham WT, Hayes DL. Cardiac resynchronization therapy for heart failure. Circulation 2003 108 2596-2603. 

FIGURE 1.5 Summary of evidence supporting defibrillator implantation as stratified by ejection fraction and heart failure class in patients with ischemic cardiomyopathy (A) and nonischemic cardiomyopathy (B). For details of COMPANION trial, see Chapter 5. (CRT, cardiac resynchronization therapy EPS, electrophysiology study NYHA,New York Heart Association.)... 

Cardiac resynchronization therapy (CRT) for systolic congestive heart failure (CHF) represents a new paradigm in cardiology the use of an electrical therapy (cardiac pacing) to treat a mechanical problem. Multiple randomized clinical trials have proven that resynchronization therapy improves symptoms and functional status, increases quality of life, reduces hospitalizations, and prolongs survival in appropriately selected patients. As a result, this therapy has been quickly established as a standard treatment for patients with severe left ventricular dysfunction, moderate-to-severely symptomatic CHF despite optimal medical therapy, and prolonged QRS duration (1,2). 

CRT reduces symptoms of CHF and improves cardiac performance in patients with moderate-to-severely symptomatic heart failure, severe left ventricular systolic dysfunction, normal sinus rhythm and a wide QRS complex. Resynchronization therapy significantly reduces hospitalizations in these patients and is highly cost-effective. Perhaps most important, resynchronization therapy for heart failure improves survival for these patients, particularly when employed in conjunction with an implantable defibrillator. However, randomized clinical trials show that a substantial minority of patients are clinical nonresponders. Therefore, critical questions remain with respect to identifying appropriate candidates for CRT, optimal device programming, and left ventricular lead placement. 

Abraham WT, Fisher WG, Smith AL, et al. Cardiac resynchronization in chronic heart failure. N Engl J Med 2002 346 1845-53. 

Higgins SL, Hummel JD, Niazi IK, et al. Cardiac resynchronization therapy for the treatment of heart failure in patients with intraventricular conduction delay and malignant ventricular tachyarrhythmias. J Am Coll Cardiol 2003 42 1454-9. 

Auricchio A, Stellbrink C, Butter C, et al. Clinical efficacy of cardiac resynchronization therapy using left ventricular pacing in heart failure patients stratified by severity of ventricular conduction delay. J Am Coll Cardiol 2003 42 2109-16. 

Adamson PB, Kleckner KJ, VanHout WL, Srinivasan S, Abraham WT. Cardiac resynchronization therapy improves heart rate variability in patients with symptomatic heart failure. Circulation 2003 108 266-9. 

Fruhwald FM, Fahrleitner-Pammer A, Berger R, et al. Early and sustained effects of cardiac resynchronization therapy on N-terminal pro-B-type natriuretic peptide in patients with moderate to severe heart failure and cardiac dyssynchrony. Eur Heart J 2007 28 1592-7. 

Bradley DJ, Bradley EA, Baughman KL, et al. Cardiac resynchronization and death from progressive heart failure a meta-analysis of randomized controlled trials. JAMA 2003 289 730-40. 

Cleland JG, Daubert JC, Erdmann E, et al. Longer-term effects of cardiac resynchronization therapy on mortality in heart failure). Eur Heart J 2006 27 1928-32. 

Hoppe UC, Casares JM, Eiskjaer H, et al. Effect of cardiac resynchronization on the incidence of atrial fibrillation in patients with severe heart failure. Circulation 2006 114 18-25. 

Auricchio A, Ding J, Spinelli JC, et al. Cardiac resynchronization therapy restores optimal atrioventricular mechanical timing in heart failure patients with ventricular conduction delay. 

Boriani G, Muller CP, Seidl KH, et al. Randomized comparison of simultaneous biventricular stimulation versus optimized interventricular delay in cardiac resynchronization therapy. The Resynchronization for the HemodYnamic Treatment for Heart Failure Management II implantable cardioverter defibrillator (RHYTHM IIICD) study. Am Heart J 2006 151 1050-8. 

Cardiac resynchronization therapy (CRT) to restore the normal activation sequence of contraction in the hearts of some patients with heart failure... 

---