Implantable Cardioverter–Defibrillator Therapy after Myocardial Infarction
http://www.100md.com
《新英格兰医药杂志》
To the Editor: Hohnloser et al. (Dec. 9 issue),1 who conducted the Defibrillator in Acute Myocardial Infarction Trial (DINAMIT), assume that implantable cardioverter–defibrillator (ICD) therapy early after myocardial infarction decreases the rate of death due to arrhythmia but that the patients die of other cardiac disease. We believe alternatives must be considered.
First, it should not be assumed that the mechanism of death has been changed by the ICD; rather, the presence of an ICD will affect classification (a doctor or committee member will be less likely to believe a death is due to arrhythmia if a patient has a device). It is more likely that ICD implantation has led to worsening cardiac function.
Second, the implantation and testing of a defibrillator may negatively interrupt the adaptive remodeling in the dynamic postinfarction myocardium. Shocks delivered during testing of the device result in myocyte necrosis.2 Furthermore, the effects of the implantation of the device on hemodynamic variables, including blood pressure and heart rate, predispose the myocardium to further ischemia and infarction. Neurohormonal activation and inflammation could also lead to maladaptive remodeling, hastening the downward spiral of chronic heart failure.3 All these factors might be particularly detrimental immediately after a myocardial infarction.
Keyur B. Shah, M.D.
Stephen S. Gottlieb, M.D.
University of Maryland Medical Center
Baltimore, MD 21201
References
Hohnloser SH, Kuck KH, Dorian P, et al. Prophylactic use of an implantable cardioverter-defibrillator after acute myocardial infarction. N Engl J Med 2004;351:2481-2488.
Joglar JA, Kessler DJ, Welch PJ, et al. Effect of repeated electrical defibrillation on cardiac troponin I levels. Am J Cardiol 1999;83:270-2, A6.
Bode F, Wiegand U, Raasch W, Richardt G, Potratz J. Differential effects of defibrillation on systemic and cardiac sympathetic activity. Heart 1998;79:560-567.
To the Editor: Ventricular tachyarrhythmias treated by ICD in DINAMIT were a harbinger of imminent death due to pump failure,1 and the ICD merely transformed sudden death to another form of death in a considerable number of patients.2 The authors should substantiate this message by providing more information about the type of ICD treatment (shock vs. pacing) and its success, additional ICD treatment, and other treatment later on, the interval between ICD implantation and death, and the cause of death. What was the study outcome for the 10 percent of patients needing mechanical ventilation and the 6 percent needing the balloon pump in the acute phase?3 Overall, the DINAMIT findings seem to suggest that a mean left ventricular ejection fraction of 28 percent in the acute phase of myocardial infarction signifies a heart that is too damaged to benefit from ICD implantation.
Gerhard Steinbeck, M.D.
Ludwig Maximilians University
81377 Munich, Germany
gerhard.steinbeck@med.uni-muenchen.de
Dietrich Andresen, M.D.
Krankenhaus Am Urban Vivantes
10967 Berlin, Germany
Jochen Senges, M.D.
Herzzentrum
67063 Ludwigshafen, Germany
Drs. Steinbeck, Andresen, and Senges report having received lecture fees from the following ICD manufacturers: Medtronic, Guidant, and Biotronic.
References
Dorian P, Connolly S, Hohnloser SH. Why don't ICDs decrease all-cause mortality after MI? Insights from the DINAMIT study. Circulation 2004;110:Suppl III:III-502. abstract.
Hohnloser SH, Kuck KH, Dorian P, et al. Prophylactic use of an implantable cardioverter-defibrillator after acute myocardial infarction. N Engl J Med 2004;351:2481-2488.
Connolly SJ, Hohnloser SH. DINAMIT: Defibrillator IN Acute Myocardial Infarction Trial. ACC 2004. Late Breaking Trials I. (Accessed February 17, 2005, at http://www.acc04online.acc.org/.)
To the Editor: Hohnloser and colleagues report that prophylactic ICD therapy in patients with a recent myocardial infarction and an impaired left ventricular ejection fraction did not affect overall mortality. Despite a significant reduction in the mortality due to arrhythmia in the ICD group, as compared with the control group, the mortality from nonarrhythmic causes in the ICD group was significantly higher. The authors do not report data regarding aldosterone-blockade therapy in their study population. It is important to know whether the rate of use of aldosterone-blockade therapy differed between the two groups. Eplerenone was shown to reduce mortality among patients with a recent myocardial infarction and a left ventricular ejection fraction of 0.4 or less.1 Early aldosterone-blockade therapy for patients with an impaired left ventricular ejection fraction (0.4 or less) and symptomatic heart failure after a myocardial infarction is recommended.2 In both groups, about 50 percent of patients had heart failure, and the mean (±SD) left ventricular ejection fraction was 0.28±0.05. Thus, a high proportion of patients met the criteria for receiving aldosterone-blockade therapy. The authors should provide data regarding aldosterone-blockade therapy in the two groups and rule out its potential effect on the study outcomes.
Fausta Micheletta, M.D.
Silvia Natoli, M.D.
Luigi Iuliano, M.D.
University La Sapienza
00100 Rome, Italy
fausta.micheletta@uniroma1.it
References
Pitt B, Remme W, Zannad F, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 2003;348:1309-1321. [Erratum, N Engl J Med 2003;348:2271.][Abstract/Full Text]
Antman EM, Anbe DT, Armstrong PW, et al. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction -- executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2004;110:588-636.
The authors reply: Drs. Shah and Gottlieb raise the possibility that in DINAMIT, the classification of death could have been influenced by the presence or absence of an ICD. However, as stated in our article, adjudication of deaths was carried out in a blinded manner without relying on information from the devices. Their second argument, that ICD testing and implantation may further damage the myocardium, leading to excess mortality, is not substantiated by our data. In fact, there was no implantation-related morbidity or death. Furthermore, patients who were randomly assigned to ICD therapy had changes in the left ventricular ejection fraction that were similar to those in the control group six weeks after the initial assessment. Thus, we do not believe that ICD implantation itself had any detrimental effects.
Dr. Steinbeck and colleagues request further information about several important trial-related issues. We have already published information on some of these issues,1 and additional analyses are currently being performed. Regarding patients in need of mechanical ventilation or balloon pumping during the acute phase of their infarction, we would like to reemphasize that only a small number of patients received one of these forms of therapy and that these patients were randomly assigned to both study groups. In this small subgroup of patients, there was no significant difference in outcome between those who received ICD therapy and those who did not. The statement that patients with an acute myocardial infarct and an average left ventricular ejection fraction of 0.28 are simply too sick to benefit from ICD therapy appears to be oversimplified. The mean left ventricular ejection fraction at six weeks was approximately 0.30, which was one of the inclusion criteria in the Multicenter Automatic Defibrillator Implantation Trial II.2
Dr. Micheletta and colleagues are correct in emphasizing the importance of early aldosterone blockade. In our trial, only a minority of patients were receiving this medication at baseline. It is important to note, however, that the decisive trial on the benefits of early aldosterone antagonism after myocardial infarction was published in 2003, approximately nine years after our trial was designed.3
Stefan H. Hohnloser, M.D.
J.W. Goethe University
60590 Frankfurt, Germany
hohnloser@em.uni-frankfurt.de
Stuart J. Connolly, M.D.
McMaster University
Hamilton, ON L8L 2X2, Canada
Michael Gent, D.Sc.
Henderson Research Center
Hamilton, ON L8V 1C3, Canada
First, it should not be assumed that the mechanism of death has been changed by the ICD; rather, the presence of an ICD will affect classification (a doctor or committee member will be less likely to believe a death is due to arrhythmia if a patient has a device). It is more likely that ICD implantation has led to worsening cardiac function.
Second, the implantation and testing of a defibrillator may negatively interrupt the adaptive remodeling in the dynamic postinfarction myocardium. Shocks delivered during testing of the device result in myocyte necrosis.2 Furthermore, the effects of the implantation of the device on hemodynamic variables, including blood pressure and heart rate, predispose the myocardium to further ischemia and infarction. Neurohormonal activation and inflammation could also lead to maladaptive remodeling, hastening the downward spiral of chronic heart failure.3 All these factors might be particularly detrimental immediately after a myocardial infarction.
Keyur B. Shah, M.D.
Stephen S. Gottlieb, M.D.
University of Maryland Medical Center
Baltimore, MD 21201
References
Hohnloser SH, Kuck KH, Dorian P, et al. Prophylactic use of an implantable cardioverter-defibrillator after acute myocardial infarction. N Engl J Med 2004;351:2481-2488.
Joglar JA, Kessler DJ, Welch PJ, et al. Effect of repeated electrical defibrillation on cardiac troponin I levels. Am J Cardiol 1999;83:270-2, A6.
Bode F, Wiegand U, Raasch W, Richardt G, Potratz J. Differential effects of defibrillation on systemic and cardiac sympathetic activity. Heart 1998;79:560-567.
To the Editor: Ventricular tachyarrhythmias treated by ICD in DINAMIT were a harbinger of imminent death due to pump failure,1 and the ICD merely transformed sudden death to another form of death in a considerable number of patients.2 The authors should substantiate this message by providing more information about the type of ICD treatment (shock vs. pacing) and its success, additional ICD treatment, and other treatment later on, the interval between ICD implantation and death, and the cause of death. What was the study outcome for the 10 percent of patients needing mechanical ventilation and the 6 percent needing the balloon pump in the acute phase?3 Overall, the DINAMIT findings seem to suggest that a mean left ventricular ejection fraction of 28 percent in the acute phase of myocardial infarction signifies a heart that is too damaged to benefit from ICD implantation.
Gerhard Steinbeck, M.D.
Ludwig Maximilians University
81377 Munich, Germany
gerhard.steinbeck@med.uni-muenchen.de
Dietrich Andresen, M.D.
Krankenhaus Am Urban Vivantes
10967 Berlin, Germany
Jochen Senges, M.D.
Herzzentrum
67063 Ludwigshafen, Germany
Drs. Steinbeck, Andresen, and Senges report having received lecture fees from the following ICD manufacturers: Medtronic, Guidant, and Biotronic.
References
Dorian P, Connolly S, Hohnloser SH. Why don't ICDs decrease all-cause mortality after MI? Insights from the DINAMIT study. Circulation 2004;110:Suppl III:III-502. abstract.
Hohnloser SH, Kuck KH, Dorian P, et al. Prophylactic use of an implantable cardioverter-defibrillator after acute myocardial infarction. N Engl J Med 2004;351:2481-2488.
Connolly SJ, Hohnloser SH. DINAMIT: Defibrillator IN Acute Myocardial Infarction Trial. ACC 2004. Late Breaking Trials I. (Accessed February 17, 2005, at http://www.acc04online.acc.org/.)
To the Editor: Hohnloser and colleagues report that prophylactic ICD therapy in patients with a recent myocardial infarction and an impaired left ventricular ejection fraction did not affect overall mortality. Despite a significant reduction in the mortality due to arrhythmia in the ICD group, as compared with the control group, the mortality from nonarrhythmic causes in the ICD group was significantly higher. The authors do not report data regarding aldosterone-blockade therapy in their study population. It is important to know whether the rate of use of aldosterone-blockade therapy differed between the two groups. Eplerenone was shown to reduce mortality among patients with a recent myocardial infarction and a left ventricular ejection fraction of 0.4 or less.1 Early aldosterone-blockade therapy for patients with an impaired left ventricular ejection fraction (0.4 or less) and symptomatic heart failure after a myocardial infarction is recommended.2 In both groups, about 50 percent of patients had heart failure, and the mean (±SD) left ventricular ejection fraction was 0.28±0.05. Thus, a high proportion of patients met the criteria for receiving aldosterone-blockade therapy. The authors should provide data regarding aldosterone-blockade therapy in the two groups and rule out its potential effect on the study outcomes.
Fausta Micheletta, M.D.
Silvia Natoli, M.D.
Luigi Iuliano, M.D.
University La Sapienza
00100 Rome, Italy
fausta.micheletta@uniroma1.it
References
Pitt B, Remme W, Zannad F, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 2003;348:1309-1321. [Erratum, N Engl J Med 2003;348:2271.][Abstract/Full Text]
Antman EM, Anbe DT, Armstrong PW, et al. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction -- executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2004;110:588-636.
The authors reply: Drs. Shah and Gottlieb raise the possibility that in DINAMIT, the classification of death could have been influenced by the presence or absence of an ICD. However, as stated in our article, adjudication of deaths was carried out in a blinded manner without relying on information from the devices. Their second argument, that ICD testing and implantation may further damage the myocardium, leading to excess mortality, is not substantiated by our data. In fact, there was no implantation-related morbidity or death. Furthermore, patients who were randomly assigned to ICD therapy had changes in the left ventricular ejection fraction that were similar to those in the control group six weeks after the initial assessment. Thus, we do not believe that ICD implantation itself had any detrimental effects.
Dr. Steinbeck and colleagues request further information about several important trial-related issues. We have already published information on some of these issues,1 and additional analyses are currently being performed. Regarding patients in need of mechanical ventilation or balloon pumping during the acute phase of their infarction, we would like to reemphasize that only a small number of patients received one of these forms of therapy and that these patients were randomly assigned to both study groups. In this small subgroup of patients, there was no significant difference in outcome between those who received ICD therapy and those who did not. The statement that patients with an acute myocardial infarct and an average left ventricular ejection fraction of 0.28 are simply too sick to benefit from ICD therapy appears to be oversimplified. The mean left ventricular ejection fraction at six weeks was approximately 0.30, which was one of the inclusion criteria in the Multicenter Automatic Defibrillator Implantation Trial II.2
Dr. Micheletta and colleagues are correct in emphasizing the importance of early aldosterone blockade. In our trial, only a minority of patients were receiving this medication at baseline. It is important to note, however, that the decisive trial on the benefits of early aldosterone antagonism after myocardial infarction was published in 2003, approximately nine years after our trial was designed.3
Stefan H. Hohnloser, M.D.
J.W. Goethe University
60590 Frankfurt, Germany
hohnloser@em.uni-frankfurt.de
Stuart J. Connolly, M.D.
McMaster University
Hamilton, ON L8L 2X2, Canada
Michael Gent, D.Sc.
Henderson Research Center
Hamilton, ON L8V 1C3, Canada