Cardiac-Resynchronization Therapy in Heart Failure
http://www.100md.com
《新英格兰医药杂志》
To the Editor: A well-designed study aimed at showing the effect of cardiac resynchronization on mortality among patients with cardiac dyssynchrony, the Cardiac Resynchronization–Heart Failure (CARE-HF) Study (April 14 issue),1 demonstrated improvements in quality of life and survival well beyond those expected. The question remains as to whether these patients should receive a combination device with both cardioversion and defibrillation capabilities.2
Conclusions drawn from a randomized study are very sensitive to the characteristics of the studied population. In CARE-HF, 62 percent of the patients had nonischemic cardiomyopathy. This high percentage raises the question of the generalizability of the results. In a recent meta-analysis of patients with nonischemic cardiomyopathy, Desai et al.3 concluded that the use of implantable defibrillators reduced mortality. However, their conclusions were based in part on subgroup analyses, which are known to be less reliable than analyses of genuinely randomized study groups. None of the studies that have focused on patients with nonischemic cardiomyopathy have shown a significant reduction in mortality.3
Therefore, the impressive effect observed in the CARE-HF Study might not be improved by the addition of a defibrillator in patients with cardiomyopathy. Conversely, the effect of resynchronization on mortality in patients with ischemic cardiomyopathy remains questionable.
Gilbert A. Kirkorian, M.D.
H?pital Louis Pradel
69677 Bron, France
gilbert.kirkorian@chu-lyon.fr
References
Cleland JGF, Daubert J-C, Erdmann E, et al. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med 2005;352:1539-1549.
Jarcho JA. Resynchronizing ventricular contraction in heart failure. N Engl J Med 2005;352:1594-1597.
Desai AS, Fang JC, Maisel WH, Baughman KL. Implantable defibrillators for the prevention of mortality in patients with nonischemic cardiomyopathy: a meta-analysis of randomized controlled trials. JAMA 2004;292:2874-2879.
To the Editor: In the landmark CARE-HF Study, the investigators state that biventricular pacing improves outcomes in patients with cardiac dyssynchrony. This statement is misleading, since only patients with a QRS duration of 120 to 149 msec were required to have echocardiographic evidence of dyssynchrony, and this subgroup made up only 11 percent of the total study population.1 Thus, the presence of dyssynchrony was not a prerequisite in the majority of patients in this trial, nor was it a prerequisite in any other major study, such as the Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) trial2 or the Multicenter InSync Randomized Clinical Evaluation (MIRACLE).3 In the future, echocardiography may indeed play a role in identifying patients who will not have a response to biventricular pacing, but so far no marker has been universally established as being able to do so. In the meantime, it would be wrong to deny patients who fulfill standard criteria for biventricular pacing a potentially valuable therapy4 on the basis of the possibility that they may not have echocardiographic evidence of dyssynchrony.
Haran Burri, M.D.
University Hospitals of Geneva
1206 Geneva, Switzerland
haran.burri@hcuge.ch
References
Cleland JG, Daubert JC, Erdmann E, et al. Baseline characteristics of patients recruited into the CARE-HF study. Eur J Heart Fail 2005;7:205-214.
Bristow MR, Saxon LA, Boehmer J, et al. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med 2004;350:2140-2150.
Abraham WT, Fisher WG, Smith AL, et al. Cardiac resynchronization in chronic heart failure. N Engl J Med 2002;346:1845-1853.
Gregoratos G, Abrams J, Epstein AE, et al. ACC/AHA/NASPE 2002 guideline update for implantation of cardiac pacemakers and antiarrhythmia devices: summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/NASPE Committee to Update the 1998 Pacemaker Guidelines). Circulation 2002;106:2145-2161.
The authors reply: Dr. Burri suggests that current criteria for measuring cardiac dyssynchrony are essentially untested in clinical trials and therefore are inadequate for the selection of patients for cardiac-resynchronization therapy. This interpretation of the existing data is correct but narrow. As with all clinical trials, important questions remain, even when the results are clear.
Atriobiventricular pacing is clinically effective in patients with a high prevalence of dyssynchrony and appears somewhat more effective in those with echocardiographic evidence of interventricular mechanical delay,1 whereas conventional right ventricular pacing is associated with an adverse outcome in patients with heart failure.2 These considerations effectively rule out mechanisms other than resynchronization, by which pacing might induce benefit. Many, but not all, patients with a QRS duration of more than 149 msec benefited from cardiac-resynchronization therapy in the CARE-HF Study. Clearly, there is much more to learn about the measurement of cardiac dyssynchrony to ensure optimal use of cardiac-resynchronization therapy, but ultimately it is cardiac dyssynchrony rather than a broad QRS interval that is the treatment target. Dr. Burri's concerns about the adequacy of current measures of dyssynchrony are legitimate. Practical and reliable means of assessing dyssynchrony will be required to identify patients with less severe symptoms who may benefit from this technology.
Dr. Kirkorian suggests that patients with ischemic heart disease may not have benefited from cardiac-resynchronization therapy. In the CARE-HF Study, more than 40 percent of the patients randomly assigned to cardiac-resynchronization therapy had definite coronary disease, and in an additional 25 percent coronary disease was not ruled out.3 There was no evidence of heterogeneity in outcomes between patients with ischemic heart disease and those without it. It is likely that there is a subgroup of patients with extensive myocardial scarring in whom resynchronization is not satisfactory, but for many patients with ischemic heart disease and dyssynchrony cardiac-resynchronization therapy does appear to be effective. There is no evidence that the relative benefits of implantable defibrillators vary according to the presence or absence of ischemic heart disease.4,5 Clearly, investigation of the incremental benefit of defibrillators in addition to cardiac-resynchronization therapy in patients with dyssynchrony will be needed to ensure that the safest, most effective, and most cost-effective therapy is being delivered.
John G.F. Cleland, M.D.
Castle Hill Hospital
Kingston-upon-Hull HU16 5JQ, United Kingdom
Jean-Claude Daubert, M.D.
H?pital Pontchaillou
FR-35033 Rennes, France
Luigi Tavazzi, M.D.
Policlinico San Matteo
IT-27100 Pavia, Italy
for the CARE-HF Study Investigators
References
Adamson PB, St John Sutton MG, Plappert T, Abraham WT, Hilpisch KE, Hill MSR. Echo-defined ventricular dyssynchrony predicts magnitude of response to cardiac resynchronisation. J Card Fail 2002;8:S50-S50.
Wilkoff BL, Cook JR, Epstein AE, et al. Dual-chamber pacing or ventricular backup pacing in patients with an implantable defibrillator: the Dual Chamber and VVI Implantable Defibrillator (DAVID) Trial. JAMA 2002;288:3115-3123.
Cleland JGF, Daubert JC, Erdmann E, et al. Baseline characteristics of patients recruited into the CARE-HF study. Eur J Heart Fail 2005;7:205-214.
Bardy GH, Lee KL, Mark DB, et al. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med 2005;352:225-237.
Conclusions drawn from a randomized study are very sensitive to the characteristics of the studied population. In CARE-HF, 62 percent of the patients had nonischemic cardiomyopathy. This high percentage raises the question of the generalizability of the results. In a recent meta-analysis of patients with nonischemic cardiomyopathy, Desai et al.3 concluded that the use of implantable defibrillators reduced mortality. However, their conclusions were based in part on subgroup analyses, which are known to be less reliable than analyses of genuinely randomized study groups. None of the studies that have focused on patients with nonischemic cardiomyopathy have shown a significant reduction in mortality.3
Therefore, the impressive effect observed in the CARE-HF Study might not be improved by the addition of a defibrillator in patients with cardiomyopathy. Conversely, the effect of resynchronization on mortality in patients with ischemic cardiomyopathy remains questionable.
Gilbert A. Kirkorian, M.D.
H?pital Louis Pradel
69677 Bron, France
gilbert.kirkorian@chu-lyon.fr
References
Cleland JGF, Daubert J-C, Erdmann E, et al. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med 2005;352:1539-1549.
Jarcho JA. Resynchronizing ventricular contraction in heart failure. N Engl J Med 2005;352:1594-1597.
Desai AS, Fang JC, Maisel WH, Baughman KL. Implantable defibrillators for the prevention of mortality in patients with nonischemic cardiomyopathy: a meta-analysis of randomized controlled trials. JAMA 2004;292:2874-2879.
To the Editor: In the landmark CARE-HF Study, the investigators state that biventricular pacing improves outcomes in patients with cardiac dyssynchrony. This statement is misleading, since only patients with a QRS duration of 120 to 149 msec were required to have echocardiographic evidence of dyssynchrony, and this subgroup made up only 11 percent of the total study population.1 Thus, the presence of dyssynchrony was not a prerequisite in the majority of patients in this trial, nor was it a prerequisite in any other major study, such as the Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) trial2 or the Multicenter InSync Randomized Clinical Evaluation (MIRACLE).3 In the future, echocardiography may indeed play a role in identifying patients who will not have a response to biventricular pacing, but so far no marker has been universally established as being able to do so. In the meantime, it would be wrong to deny patients who fulfill standard criteria for biventricular pacing a potentially valuable therapy4 on the basis of the possibility that they may not have echocardiographic evidence of dyssynchrony.
Haran Burri, M.D.
University Hospitals of Geneva
1206 Geneva, Switzerland
haran.burri@hcuge.ch
References
Cleland JG, Daubert JC, Erdmann E, et al. Baseline characteristics of patients recruited into the CARE-HF study. Eur J Heart Fail 2005;7:205-214.
Bristow MR, Saxon LA, Boehmer J, et al. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med 2004;350:2140-2150.
Abraham WT, Fisher WG, Smith AL, et al. Cardiac resynchronization in chronic heart failure. N Engl J Med 2002;346:1845-1853.
Gregoratos G, Abrams J, Epstein AE, et al. ACC/AHA/NASPE 2002 guideline update for implantation of cardiac pacemakers and antiarrhythmia devices: summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/NASPE Committee to Update the 1998 Pacemaker Guidelines). Circulation 2002;106:2145-2161.
The authors reply: Dr. Burri suggests that current criteria for measuring cardiac dyssynchrony are essentially untested in clinical trials and therefore are inadequate for the selection of patients for cardiac-resynchronization therapy. This interpretation of the existing data is correct but narrow. As with all clinical trials, important questions remain, even when the results are clear.
Atriobiventricular pacing is clinically effective in patients with a high prevalence of dyssynchrony and appears somewhat more effective in those with echocardiographic evidence of interventricular mechanical delay,1 whereas conventional right ventricular pacing is associated with an adverse outcome in patients with heart failure.2 These considerations effectively rule out mechanisms other than resynchronization, by which pacing might induce benefit. Many, but not all, patients with a QRS duration of more than 149 msec benefited from cardiac-resynchronization therapy in the CARE-HF Study. Clearly, there is much more to learn about the measurement of cardiac dyssynchrony to ensure optimal use of cardiac-resynchronization therapy, but ultimately it is cardiac dyssynchrony rather than a broad QRS interval that is the treatment target. Dr. Burri's concerns about the adequacy of current measures of dyssynchrony are legitimate. Practical and reliable means of assessing dyssynchrony will be required to identify patients with less severe symptoms who may benefit from this technology.
Dr. Kirkorian suggests that patients with ischemic heart disease may not have benefited from cardiac-resynchronization therapy. In the CARE-HF Study, more than 40 percent of the patients randomly assigned to cardiac-resynchronization therapy had definite coronary disease, and in an additional 25 percent coronary disease was not ruled out.3 There was no evidence of heterogeneity in outcomes between patients with ischemic heart disease and those without it. It is likely that there is a subgroup of patients with extensive myocardial scarring in whom resynchronization is not satisfactory, but for many patients with ischemic heart disease and dyssynchrony cardiac-resynchronization therapy does appear to be effective. There is no evidence that the relative benefits of implantable defibrillators vary according to the presence or absence of ischemic heart disease.4,5 Clearly, investigation of the incremental benefit of defibrillators in addition to cardiac-resynchronization therapy in patients with dyssynchrony will be needed to ensure that the safest, most effective, and most cost-effective therapy is being delivered.
John G.F. Cleland, M.D.
Castle Hill Hospital
Kingston-upon-Hull HU16 5JQ, United Kingdom
Jean-Claude Daubert, M.D.
H?pital Pontchaillou
FR-35033 Rennes, France
Luigi Tavazzi, M.D.
Policlinico San Matteo
IT-27100 Pavia, Italy
for the CARE-HF Study Investigators
References
Adamson PB, St John Sutton MG, Plappert T, Abraham WT, Hilpisch KE, Hill MSR. Echo-defined ventricular dyssynchrony predicts magnitude of response to cardiac resynchronisation. J Card Fail 2002;8:S50-S50.
Wilkoff BL, Cook JR, Epstein AE, et al. Dual-chamber pacing or ventricular backup pacing in patients with an implantable defibrillator: the Dual Chamber and VVI Implantable Defibrillator (DAVID) Trial. JAMA 2002;288:3115-3123.
Cleland JGF, Daubert JC, Erdmann E, et al. Baseline characteristics of patients recruited into the CARE-HF study. Eur J Heart Fail 2005;7:205-214.
Bardy GH, Lee KL, Mark DB, et al. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med 2005;352:225-237.