|Year : 2016 | Volume
| Issue : 1 | Page : 6-10
Implantable cardioverter defibrillator in postmyocardial infarction patients for prevention of sudden cardiac death: Where do we stand?
Arindam Pande, Rabin Chakraborty
Department of Cardiology, Apollo Gleneagles Hospital, Kolkata, West Bengal, India
|Date of Web Publication||13-Jan-2016|
Apartment U 302, Binayak Enclave, 59 K C Ghosh Road, Kolkata - 700 050, West Bengal
Source of Support: None, Conflict of Interest: None
The indications for implantable cardioverter-defibrillators (ICDs) for the prevention of sudden cardiac death have rapidly expanded over the past 15 years. Clinical trial data have quickly been implemented into guidelines. Ventricular arrhythmias still account for significant proportion of mortality observed in patients discharged after an acute myocardial infarction, in spite of massive developments in revascularization strategy and adjuvant medical management. At present, we have the results of clinical trials that show ICD use is associated with improved survival in this group of patients with left ventricular dysfunction and either demonstrated or anticipated risk for arrhythmic death. Despite the fact that there are few interventions that in multiple trials settings have consistently produced a 20–30% reduction in total mortality, ICD treatment is largely underutilized. Keeping in mind, in fact that devices fail, and in unpredictable subsets, especially in patients who get inappropriate shocks, quality of life is decreased, we need to use this powerful tool in the most appropriate manner based on the guidelines that resulted from the trials.
Keywords: Implantable cardioverter defibrillator, left ventricular ejection fraction, ST elevated myocardial infarction, sudden cardiac death
|How to cite this article:|
Pande A, Chakraborty R. Implantable cardioverter defibrillator in postmyocardial infarction patients for prevention of sudden cardiac death: Where do we stand?. Nig J Cardiol 2016;13:6-10
|How to cite this URL:|
Pande A, Chakraborty R. Implantable cardioverter defibrillator in postmyocardial infarction patients for prevention of sudden cardiac death: Where do we stand?. Nig J Cardiol [serial online] 2016 [cited 2019 Dec 13];13:6-10. Available from: http://www.nigjcardiol.org/text.asp?2016/13/1/6/165162
| Introduction|| |
Since, the first descriptions of external defibrillation, in 1960s; and the first human implantable cardioverter defibrillator (ICD), in 1980 by Mirowski et al., the paradigm for the prevention of sudden cardiac death (SCD) shifted away from both antiarrhythmic drug and ablative strategies. The indications of ICDs for the prevention of SCD have rapidly expanded over the past 15 years. Clinical trial data have quickly been implemented into guidelines. Postmyocardial infarction (MI) arrhythmias or left ventricular systolic dysfunction account for a major share of ICD implantation indications worldwide. In spite of significant reduction in total mortality observed in patients discharged after an acute MI, ventricular arrhythmias still account for 30–40% of deaths. This figure, which was initially provided by studies carried out in the prethrombolytic era had been subsequently confirmed when most of the patients had been revascularized by thrombolysis or percutaneous coronary intervention (PCI).
| Initial Enthusiasm to Pharmacotherapy Versus Implantable Cardioverter-Defibrillators|| |
Due to lack of efficacy of class I antiarrhythmic drugs, in general, when used for primary and secondary prevention of SCDs interest shifted to the use of amiodarone and implantable defibrillators. The two major trials of amiodarone in post-MI patients, European Myocardial Infarct Amiodarone Trial  and Canadian Amiodarone Myocardial Infarction Arrhythmia Trial, one of which required ejection fractions lower than 40%, demonstrated no total mortality benefit, even though both trials demonstrated antiarrhythmic benefit expressed as a reduction in arrhythmic deaths, or resuscitated ventricular fibrillation (VF). Subgroup analyzes have suggested that the concomitant use of beta blockers does confer a mortality benefit. Multicenter Automatic Defibrillator Implantation Trial (MADIT) was the first randomized controlled trial comparing antiarrhythmic therapy (primarily amiodarone) with ICD therapy. It assigned patients with prior MI who had ejection fractions lower than 35%, nonsustained ventricular tachycardia (VT) during ambulatory recording, and inducible VT that was not suppressible by procainamide. This very high-risk group demonstrates a 54% reduction in total mortality with ICD therapy versus drug therapy, primarily amiodarone.
| Identification of Patients at Risk|| |
Early revascularization and a more generalized use of beta blockers, angiotensin-converting enzyme inhibitors, statins, and antiplatelet agents have largely contributed to the improvement in the prognosis of patients presenting with an ST-elevated acute MI. Nevertheless, the identification of patients at risk remains an issue far from being adequately addressed. There is a general consensus that depressed ventricular function, as reflected by a left ventricular ejection fraction (LVEF) <40%, represents the strongest negative prognostic factor in these patients. Different cut-off values have proved effective in recent clinical trials, and an LVEF <30% has been used as a single inclusion criteria in studies aimed to evaluate, for example, the beneficial effect of ICD after MI. After the publication of MADIT II results  that have clearly indicated a significant reduction of total and arrhythmic mortality in post-MI patients with ICD when compared with controls, ICD implantation has been recommended for almost all post-MI patients with an LVEF <30%. The issue has become even more controversial after the publication of the results of the Defibrillator in Acute Myocardial Infarction Trial (DINAMIT) study. More than 600 patients with a recent acute, MI and reduced left ventricular function (LVEF <35%) were randomized to ICD and control. Revascularization rate (either thrombolysis or PCI) was −62%. The so-called “best” medical treatment was provided to most of the patients. The main result of the study was that prophylactic ICD therapy did not reduce overall mortality in this high-risk population. Moreover, by considering the type of death, it was evident that the reduction in the rate of death due to arrhythmia was offset by an increase in the rate of death from nonarrhythmic causes.
A careful comparison of MADIT II with DINAMIT study characteristics provides a partial explanation for such a difference. In addition to the inevitable differences in study population and patient management, it is evident that in MADIT II, the mean time for enrollment was 81 months, whereas in DINAMIT it was 6–40 days. Thus, timing of implantation in relation to the index event was a critical factor not fully considered in the original report. Indeed on a report by MADIT II study group, it is evident that no benefit from ICD could be observed in patients with a less remote MI (<18 months), whereas a tendency for a favorable effect or a significant benefit from ICD was detectable, respectively, at 18–59 months or longer (from 60 to >120 months) after the acute event. One could therefore extrapolate that according to DINAMIT and MADIT II, ICD benefit cannot be detected in the first 2 years after an acute MI, thus casting additional doubts to the recommendation of an early ICD implantation in all patients with a depressed LVEF. The lack of benefit from ICD implantation in the first 2 years after an acute MI could be interpreted as indirect evidence in which, in the reperfusion era, the risk of arrhythmic death becomes predominant only several months after the acute event.
| Limitations of Left Ventricular Ejection Fraction as Risk Predictor|| |
Yap et al. provide a precise description of the temporal trends on the risk of arrhythmic versus nonarrhythmic deaths after an acute MI. Data were retrieved from the placebo limbs of five major studies carried out in the thrombolytic era on high-risk patients according to the presence of either a depressed ventricular function (LVEF <40%), or ambient ventricular arrhythmias (more than 10 ventricular premature beats per hour or a run of nonsustained VT at Holter). The main conclusion of the study was that the overall risk of arrhythmic death from either the index event or day 45 after MI was persistently higher than that of nonarrhythmic death and that this trend did not change over time in a 2-year follow-up period. Moreover, the absolute risk of both arrhythmic and nonarrhythmic death was higher in the first 6 months after MI and decreased with time. These results confirm previous reports and provide a strong rationale for what should be carried out before discharge in patients with an ST-elevated acute MI: Early stratification and if suggested by guidelines, ICD implantation.
It is not clear, why ICD trials in post-MI patients fail to demonstrate a clear benefit when the risk of arrhythmic death is greater. The results of DINAMIT study  may provide some answers to this question. The authors reported that in ICD carriers, there was indeed a reduction of arrhythmic mortality in the time frame characterized by the greatest risk of arrhythmic death, but this benefit was offset by an increase in nonarrhythmic mortality. It has been suggested that patients saved from arrhythmic death died, at a greater extent than controls, from other cardiac causes. In addition, in DINAMIT, as well as in other previous studies, almost half of the patients did not present major ventricular arrhythmias during the 1st year after ICD implantation. Thus, identification of patients with the greatest arrhythmic risk remains a real clinical challenge that urges the reconsideration of the clinical value of available prognostic markers. For example, it is possible that depressed LVEF, which is the strongest predictor of total mortality, might be less effective for arrhythmic risk stratification, in patients with an LVEF <30% who are at higher risk for death from other cardiac causes. Indeed, data from the MUSST study  confirm that ejection fraction by itself does not discriminate between modes of deaths, whereas inducible tachyarrhythmias identify patients for whom death, if it occurs, is significantly more likely to be arrhythmic especially if the ejection fraction is ≥ 30%. Results of the Yap study  confirm that the risk of arrhythmic versus nonarrhythmic death was not different in patients with LVEF <30% or >30%.
| Other Risk Stratification Markers|| |
The evaluation of autonomic tone has been used to improve risk stratification in DINAMIT patients, but SDNN (standard deviation of normal RR intervals), that is, the most accepted prognostic parameter of heart rate variability, failed to identify patients with greater arrhythmic risk. A partial explanation for these negative findings is the fact that measures of autonomic tone like SDNN or baroreflex sensitivity are inversely correlated with LVEF and, therefore, are less effective in risk stratification of high-risk post-MI patients with depressed left ventricular function.,
In order to identify, post-MI patients with increased arrhythmic risk and possible benefit from ICD therapy, attention has been redirected to noninvasive parameters known to reflect alterations of ventricular electrical properties such as QRS duration, ventricular late potential, or microvolt T-wave alternans (MTWA). Hohnloser et al. identified 129 patients with LVEF <30% from two previously published clinical trials in which MTWA was prospectively assessed within 2 months after an acute MI. At follow-up, no SCD or cardiac arrest was observed in patients with a negative test, whereas an event rate of 15.6% was detected in patients with abnormal MTWA. Report by Bloomfield et al. provides additional support to the potential value of this methodology in the identification of patients at risk. These authors studied 177 MADIT II-like patients with a remote MI. Abnormal QRS duration (>120 ms) and MTWA were detected in, respectively, 32 and 68% of patients. Patients with an abnormal MTWA had a 2-year actuarial mortality rate of 17.8%, whereas patients with a normal test had a very low mortality rate (3.2%). QRS duration did not add any significant additional prognostic information. MTWA testing was therefore highly effective in identifying two subgroups of patients early, and late after MI with low LVEF: Those at high-risk for arrhythmic event and those who will not experience ventricular tachyarrhythmia and thus, likely, will not benefit from ICD implantation. These results, if confirmed in larger prospective studies, could indeed improve our capability of identifying patients at high and low arrhythmic risk not only in the remote, but also in the post-acute phase of MI.
In addition to that, myocardial scar characterization with cardiac magnetic resonance imaging (CMR) may predict the occurrence of ventricular tachyarrhythmia and appropriate ICD therapy in patients with an ischemic cardiomyopathy (ICMP). A higher ratio of periinfarction to total infarction mass and higher relative infarction mass may both indicate higher vulnerability for ventricular tachyarrhythmia. Thus, CMR scar characterization could be useful in risk stratification in patients with ICMP.
| Additional Risk Predictors|| |
Yap et al. provide additional relevant information on the timing of arrhythmic risk in relation to gender, age, hypertension, and smoking habit. While female patients had a similar risk of arrhythmic versus nonarrhythmic death in the initial months after MI, cardiac nonarrhythmic deaths became predominant later on. This finding, in addition to the small number of women enrolled in ICD trials, makes the interpretation of the effects of ICD implantation in the female gender even more difficult. In contrast, a history of hypertension was associated with a higher ratio of arrhythmic versus nonarrhythmic deaths. Interference of left ventricular hypertrophy with the remodeling process and persistent adrenergic activation related to hypertension and acute MI may indeed provide an explanation for such a finding and a target for therapeutical strategy. Quite surprisingly and at variance with common expectations, no interactions between mode of cardiac death and smoking status and the presence of diabetes were found. Whereas in long-term follow-up of MADIT II, a constant annualized risk of approximately, 8.5% was estimated in survivors with the most powerful risk predictors being age older than 65 years, class III or IV heart failure, diabetes, nonsinus rhythm, and elevated blood urea nitrogen levels.
| Is Implantable Cardioverter-Defibrillators Uderused?|| |
Treatment with ICD has increased continuously, but their use varies significantly by sex, ethnicity, hospitals, and between industrialized countries.,, Implant in the USA is more frequent than in Europe. There are several explanations why ICD treatment is underused despite similar guidelines. Such reasons could be financial restraints, lack of knowledge, insufficient routines, or referral patterns, individual physician's preference regarding ICD therapy and safety of the devices.
| Dark Side of Implantable Cardioverter-Defibrillators|| |
There is a dark side to ICD therapy also. Devices fail, and in unpredictable subsets, especially patients who get inappropriate shocks, quality of life is decreased. Unfortunately, life is not perfect. According to some, the clinical benefit of ICD therapy has been overestimated in clinical trials; the adverse effects on morbidity, quality of life, and the potential for proarrhythmia has been underestimated and unfavorable cost-effectiveness of ICD therapy is understated. Although, like all clinical trials, those evaluating ICD therapy have limitations from the perspective of evidence-based medicine, there are few interventions that in multiple trial settings have consistently over a ≥10-year period produced a 20–30% reduction in total mortality [Figure 1]. ICD therapy has done just that. We need to use this powerful tool in the most appropriate manner based on the guidelines that resulted from the trials.
|Figure 1: The major implantable cardioverter-defibrillators (ICD) trials – hazard ratios (vertical line) and 95% confidence intervals (horizontal lines) for death from any cause in the ICD group compared with the non-ICD group. *Includes only ICD and amiodarone patients from CASH. AVID – Antiarrhythmics Versus Implantable Defibrillators Trial; CABG – Coronary artery bypass graft surgery; CASH – Cardiac Arrest Study Hamburg; CIDS – Canadian Implantable Defibrillator Study; DEFINITE – Defibrillator in Nonischemic Cardiomyopathy Treatment Evaluation Trial; DINAMIT – Defibrillator in Acute Myocardial Infarction Trial; EP – Electrophysiological study; LVD – Left ventricular dysfunction; LVEF – Left ventricular ejection fraction; MADIT – Multicenter Automatic Defibrillator Implantation Trial; MI – Myocardial infarction; NICM – Nonischemic cardiomyopathy; NSVT – Nonsustained ventricular tachycardia; PVC – Premature ventricular complex; SAECG – Signal-averaged electrocardiogram; SCD-HeFT – Sudden Cardiac Death in Heart Failure Trial|
Click here to view
| Our Experience of Implantable Cardioverter-Defibrillators in Post-Myocardial Infarction Patients|| |
We implanted 142 ICDs in last 3 years at our Tertiary Care Center. Among them, 82 ICDs were implanted in post-MI patients. [Table 1] shows the clinical details of the post-MI ICD patients. Most of the ICDs were implanted in male patients (63 male out of total 82 patients). Mean LVEFs of our patients were 28%. We are keeping a registry to monitor the clinical progress of these patients. Though the time interval is short, it will be useful to state the outcome, mortality, etc., in these patients in our context.
|Table 1: Clinical details of the post-MI ICD patients over last 3 years in our center (n=82)|
Click here to view
| Conclusion|| |
All the guidelines recognize that ICD implantation will be more cost-effective when used for patients at high-risk of arrhythmic death and low-risk of other causes of death. Specific patient populations are now recognized for whom the benefit of ICD therapy outweighs any risks. However, until data are available that may reliably allow us to focus more precisely, the prescription of ICD therapy to patients who may benefit most and avoid adverse effects on quality of life, we are left with the results of clinical trials that in the aggregate show improved survival in a broad selection of patients with left ventricular dysfunction and either demonstrated or anticipated risk for arrhythmic death. Evidence-based medicine, the rigorous process of guideline writing, review, approval, and the ethical consideration of offering proven life-prolonging therapies to all patients provide a compelling rationale for the clinician to carefully consider the guidelines in their clinical decision making.
| ACCF/AHA/HRS Recommendations for Implantable Cardioverter Defibrillators in ST Elevated Myocardial Infarction Patients|| |
Class I recommendations
ICD therapy is indicated in patients (Assuming patients are on chronic, optimal medical therapy, and have a reasonable expectation of survival with good functional status for >1 year):
Level of evidence: A
With LVEF ≤ 35% due to prior MI, who are at least 40 days post-MI and are in New York Heart Association (NYHA) functional Class II or III.
With LV dysfunction due to prior MI, who are at least 40 days post-MI have an LVEF ≤30%, and are in NYHA functional Class I.
Level of evidence: B
With nonsustained VT due to prior MI, LVEF <40% and inducible VF or sustained VT at electrophysiological study.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Mirowski M, Reid PR, Mower MM, Watkins L, Gott VL, Schauble JF, et al.
Termination of malignant ventricular arrhythmias with an implanted automatic defibrillator in human beings. N Engl J Med 1980;303:322-4.
Lombardi F. Timing of arrhythmic death after myocardial infarction: Does it affect timing of ICD implantation? Eur Heart J 2005;26:1350-2.
Julian DG, Camm AJ, Frangin G, Janse MJ, Munoz A, Schwartz PJ, et al.
Randomised trial of effect of amiodarone on mortality in patients with left-ventricular dysfunction after recent myocardial infarction: EMIAT. European Myocardial Infarct Amiodarone Trial Investigators. Lancet 1997;349:667-74.
Cairns JA, Connolly SJ, Roberts R, Gent M. Randomised trial of outcome after myocardial infarction in patients with frequent or repetitive ventricular premature depolarisations: CAMIAT. Canadian Amiodarone Myocardial Infarction Arrhythmia Trial Investigators. Lancet 1997;349:675-82.
Cohen TJ. The Multicenter Automatic Defibrillator Implantation Trial (MADIT) Revisited: The first in a series of prophylactic defibrillator trials. J Invasive Cardiol 1997;9:200-202.
Moss AJ, Zareba W, Hall WJ, Klein H, Wilber DJ, Cannom DS, et al.
Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med 2002;346:877-83.
Hohnloser SH, Kuck KH, Dorian P, Roberts RS, Hampton JR, Hatala R, et al
. Prophylactic use of an implantable cardioverter-defibrillator after acute myocardial infarction. N Engl J Med 2004;351:2481-8.
Yap YG, Duong T, Bland M, Malik M, Torp-Pedersen C, Køber L, et al.
Temporal trends on the risk of arrhythmic vs. non-arrhythmic deaths in high-risk patients after myocardial infarction: A combined analysis from multicentre trials. Eur Heart J 2005;26:1385-93.
Tapanainen JM, Still AM, Airaksinen KE, Huikuri HV. Prognostic significance of risk stratifiers of mortality, including T wave alternans, after acute myocardial infarction: Results of a prospective follow-up study. J Cardiovasc Electrophysiol 2001;12:645-52.
Buxton AE, Lee KL, Hafley GE, Wyse DG, Fisher JD, Lehmann MH, et al.
Relation of ejection fraction and inducible ventricular tachycardia to mode of death in patients with coronary artery disease: An analysis of patients enrolled in the multicenter unsustained tachycardia trial. Circulation 2002;106:2466-72.
Lombardi F. Clinical implications of present physiological understanding of HRV components. Card Electrophysiol Rev 2002;6:245-9.
Hohnloser SH, Ikeda T, Bloomfield DM, Dabbous OH, Cohen RJ. T-wave alternans negative coronary patients with low ejection and benefit from defibrillator implantation. Lancet 2003;362:125-6.
Bloomfield DM, Steinman RC, Namerow PB, Parides M, Davidenko J, Kaufman ES, et al.
Microvolt T-wave alternans distinguishes between patients likely and patients not likely to benefit from implanted cardiac defibrillator therapy: A solution to the Multicenter Automatic Defibrillator Implantation Trial (MADIT) II conundrum. Circulation 2004;110:1885-9.
Demirel F, Adiyaman A, Timmer JR, Dambrink JHE, Boeve WJ, Elvan A. Association between appropriate ICD therapy and myocardial infarction scar characteristics assessed by cardiac magnetic resonance imaging. Eur Heart J 2013;34 suppl: 341-2.
Matlock DD, Peterson PN, Heidenreich PA, Lucas FL, Malenka DJ, Wang Y, et al.
Regional variation in the use of implantable cardioverter-defibrillators for primary prevention: Results from the national cardiovascular data registry. Circ Cardiovasc Qual Outcomes 2011;4:114-21.
Giammaria M, Bruna C, Gnavi R, Sezione Piemontese of the Associazione Italiana di Aritmologia e Cardiostimolazione. Trend in implantable cardioverter defibrillators and relation to need. J Cardiovasc Med (Hagerstown) 2010;11:265-70.
McComb JM, Plummer CJ, Cunningham MW, Cunningham D. Inequity of access to implantable cardioverter defibrillator therapy in England: Possible causes of geographical variation in implantation rates. Europace 2009;11:1308-12.
John Camm A, Nisam S. European utilization of the implantable defibrillator: Has 10 years changed the 'enigma'? Europace 2010;12:1063-9.
Tung R, Zimetbaum P, Josephson ME. A critical appraisal of implantable cardioverter-defibrillator therapy for the prevention of sudden cardiac death. J Am Coll Cardiol 2008;52:1111-21.
Epstein AE. Benefits of the implantable cardioverter-defibrillator. J Am Coll Cardiol 2008;52:1122-7.
Tracy CM, Epstein AE, Darbar D, Dimarco JP, Dunbar SB, Estes NA 3rd
, et al
. 2012 ACCF/AHA/HRS focused update of the 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2012;60:1297-313.