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Background The MADIT II investigators had concluded that prophylactic use of an ICD improved survival in patients with prior myocardial infarction reduced left ventricular ejection fraction. Whether MADIT II criteria for ICD implantation are appropriate for Indian patients also is unclear and not studied. Methods A total of 144 patients, Mean age 56.23 ± 10.9 years who met MADIT II criteria were prospectively followed for 20.78 + 5.9 months. Results During the follow-up period, 26 (18.1%) patients died. 18 were sudden cardiac deaths and 8 were non SCD deaths. Total mortality did not correlate with Age, NYHA class, NSVT on Holter, PVC >10/hours, QRS width, or use of statins. Multivariate logistic regression model identified the following variables associated with increase all-cause mortality: No use of beta blocker (odd ratio:13.068, p = 0.021), No past revascularization (odd ratio:11.613,p = 0.007) and Increase serum creatinine level (odd ratio: 4.066, p = 0.035). The mortality rate in the present series was comparable with that in the MADIT II conventional therapy group though patient in present study are younger, less diabetic, hypertensive, smokers and better treated with beta-blockers, ACE/ARB and statin. Conclusion Indian patients with prior MI (more than one month back) and left ventricular ejection fraction of 30% or less had a cardiac mortality similar to western population who are not treated with prophylactic ICD. Patients of Indian origin should derive a similar benefit with prophylactic implantation of ICD as per MADIT II criteria as would a western population.

Aims: The primary aim of this retrospective study was to determine the proportion of patients with myocardial infarction (MI) who fulfil the criteria of the Multicenter Automatic Defibrillator Implantation Trial (MADIT) II and the implications of MADIT II criteria in practice. Methods: We performed a retrospective analysis of three hundred and ninety four admissions to the Coronary Care Unit (CCU) of the Royal Infirmary of Edinburgh. We selected those with myocardial infarction (MI) and attempted to retrieve electronic copies of their echocardiogram reports. When available, these were used to assess requirement for primary-prevention Implantable Cardioverter Defibrillator (ICD) therapy based on reported left ventricular function. Results: One hundred and ninety patients were admitted to the CCU with a diagnosis of MI. Of these, 100 patients (51.5%) had an echocardiogram. Requirement for ICD therapy was unlikely in 87 (87%), probable in 6 (6%) and necessary in 7 (7%). Since a significant number of patients in the probable category were also likely to meet MADIT II criteria, we concluded that the proportion of patients requiring primary-prevention ICD therapy would be no less than 7% and more likely to be 13%. Conclusion: In the context of a busy teaching hospital, a figure of 13% for the requirement of ICD therapy in MI patients represents annual implantation activity of at least 100 per million. This is likely to have very significant resource implications.

INTRODUCTION Approximately 10-20% of ICD recipients receive inappropriate device therapies. The purpose of this study was to compare the frequency of inappropriate therapies (IT) between men and women enrolled in MADIT II and MADIT-CRT, and assess for potential adverse outcomes. METHODS The electrograms for each ICD or CRT-D therapy, defined as either ATP or shock, were reviewed by adjudication committees for both studies. ICD therapy was considered inappropriate if it was delivered for reasons other than VT/VF. The rhythm triggering IT was categorized as atrial fibrillation/flutter, SVT, or inappropriate sensing when possible. RESULTS One thousand nine hundred and fifty-four men and 556 women received ICD or CRT-D devices. The risk of IT was significantly lower in women than men (9.2% vs. 13.5%, P = 0.006). The most common cause of IT in men was atrial fibrillation (38%) and SVT in women (43%). Inappropriate shock was not associated with increased mortality in either women (HR 0.82 [95% CI 0.11-6.08]; P = NS) or men (HR 1.37 [95% CI 0.75-2.48]; P = NS) by multivariate analysis. Conversely, appropriate shock therapy strongly correlated with increased risk of death during subsequent post-shock follow-up in women (HR 5.99 [95% CI 2.75-13.02]; P < 0.0001) and men (HR 2.61 [95% CI 1.82-3.74]; P < 0.0001). CONCLUSIONS Women experience significantly less IT than men, partially explained by the increased frequency of atrial fibrillation in men. IT was not associated with increased mortality in either sex. Appropriate shock therapy was a strong predictor of death in both, with women showing a 2-fold higher risk than men during post-shock long-term follow-up.

Background Identifying which patients might benefit the most from ICD therapy remains challenging. We hypothesize that increased T-wave alternans (TWA) and QT variability (QTV) provide complementary information for predicting appropriate ICD therapy in patients with previous myocardial infarction and reduced ejection fraction. Methods We analyzed 10-min resting ECGs from MADIT-II patients with baseline heart rate > 80 beats/min. TWA indices IAA and IAA 90 were computed with the multilead Laplacian Likelihood ratio method. QTV indices QTVN and QTVI were measured using a standard approach. Cox proportional hazard models were adjusted considering appropriate ICD therapy and sudden cardiac death (SCD) as endpoints. Results TWA and QTV were measured in 175 patients. Neither QTV nor TWA predicted SCD. Appropriate ICD therapy was predicted by combining IAA 90 and QTVN after adjusting for relevant correlates. Conclusion Increased TWA and QTV are independent predictors of appropriate ICD therapy in MADIT-II patients with elevated heart rate at baseline.

Coronary Revascularization and Long-Term Mortality in MADIT-II. Introduction: Coronary revascularization (CR) may reduce arrhythmia risk and improve long-term outcome in patients with left ventricular dysfunction. This study was designed to evaluate the effect of elapsed time from CR on long-term mortality and arrhythmic risk among patients who receive an implantable cardioverter defibrillator (ICD). Methods and Results: We evaluated the risk of 8-year mortality by elapsed time from CR to ICD implantation (categorized as: no CR; recent CR [

BACKGROUND: Changes in P-wave morphology have recently been shown to be associated with interatrial conduction route used, without noticeable changes of P-wave duration. This study aimed at exploring the association between P-wave morphology and future atrial fibrillation (AF) development in the Multicenter Automatic Defibrillator Trial II (MADIT II) population. METHODS: Patients included in MADIT-II without a history of AF with sinus rhythm at baseline who developed AF during the study ("Pre-AF") were compared to matched controls without AF development ("No-AF"). Patients were followed for a mean of 20 months. A 10-minute high-resolution bipolar ECG recording was obtained at baseline. Signal-averaged P waves were analyzed to determine orthogonal P-wave morphology, P-wave duration, and RMS20. The P-wave morphology was subsequently classified into one of three predefined types using an automated algorithm. RESULTS: Thirty patients (age 68 +/- 7 years) who developed AF during MADIT-II were compared with 60 patients (age 68 +/- 8 years) who did not. P-wave duration and RMS20 in the Pre-AF group was not significantly different from the No-AF group (143 +/- 21 vs 139 +/- 30 ms, P=0.26, and 2.0 +/- 1.3 vs 2.1 +/- 1.0 muV, P=0.90). The distribution of P-wave morphologies was shifted away from Type 1 in the Pre-AF group when compared to the No-AF group (Type 1/2/3/atypical; 25/60/0/15% vs 10/63/10/17%, P=0.04). CONCLUSIONS: This study is the first to describe changes in P-wave morphology in patients prior to AF development. The results indicate that abnormal interatrial conduction may play a role in AF development in patients with prior myocardial infarction and congestive heart failure.

Currently, there is no method to predict if a patient dies, the likelihood that the death will be a sudden death (potentially preventable with an ICD) vs. a non sudden death. We tested the concept that a patient a higher estimated proportion of sudden death, with a similar annual mortality, will

The guidelines for the implantation of cardioverter defibrillators recommend the primary prevention of sudden cardiac death based on the results of MADIT II, Companion and SCD-HeFT. The main risk factors for ventricular arrhythmias are previous myocardial infarction, depressed left ventricular function, and chronic heart failure. The presented case reports demonstrate the indication for a defibrillator or biventricular defibrillator as a basis of clinical pathways.

The aim of this study was to examine the effectiveness of implantable cardioverter-defibrillator (ICD) therapy in whites and blacks who were enrolled in the Multicenter Automatic Defibrillator Implantation Trial-II (MADIT-II). The study population involved 1,232 subjects, with 1,073 white patients (87%) and 102 black patients (8%). Univariate analyses revealed a significant reduction in mortality in white patients treated with ICD therapy (p0.02), but not in black patients (p = 0.96). White patients had a significant reduction of sudden cardiac death (p0.01), but no benefit was evident in black patients (p = 0.62). Adjusting for relevant covariates, the ICD therapy/conventional therapy hazard ratios for total mortality were favorable in whites (0.75, 95% confidence interval [CI] 0.55 to 1.02), but not in blacks (1.25, 95% CI 0.42 to 3.60); the hazard ratios for sudden cardiac death were significantly (p = 0.04) lower in whites (0.29, 95% CI 0.17 to 0.49) than in blacks (1.71, 95% CI 0.33 to 8.84). Interaction analyses revealed a pattern of progressive improvement in ICD efficacy in whites as the end point became more specific for arrhythmic death, with exactly the reverse for blacks. In conclusion, ICD therapy in MADIT-II was associated with a reduction in total mortality, cardiac death, and sudden cardiac death in whites but not in blacks.

Objectives This study was designed to compare the cost-effectiveness of implantable cardioverter-defibrillator (ICD) placement with and without risk stratification with microvolt T-wave alternans (MTWA) testing in the MADIT-II (Second Multicenter Automatic Defibrillator Implantation Trial) eligible population. Background Implantable cardioverter-defibrillators have been shown to prevent mortality in the MADIT-II population. Microvolt T-wave alternans testing has been shown to be effective in risk stratifying MADIT-II–eligible patients. Methods On the basis of published data, cost-effectiveness of three therapeutic strategies in MADIT-II–eligible patients was assessed using a Markov model: 1) ICD placement in all; 2) ICD placement in patients testing MTWA non-negative;, and 3) medical management. Outcomes of expected cost, quality-adjusted life-years (QALYs), and incremental cost-effectiveness were determined for patient lifetime. Results Under base-case assumptions, providing ICDs only to those who test MTWA non-negative produced a gain of 1.14 QALYs at an incremental cost of $55,700 when compared to medical therapy, resulting in an incremental cost-effectiveness ratio (ICER) of $48,700/QALY. When compared with a MTWA risk-stratification strategy, placing ICDs in all patients resulted in an ICER of $88,700/QALY. Most (83%) of the potential benefit was achieved by implanting ICDs in the 67% of patients who tested MTWA non-negative. Results were most sensitive to the effectiveness of MTWA as a risk-stratification tool, MTWA negative screen rate, cost and efficacy of ICD therapy, and patient risk for arrhythmic death. Conclusions Risk stratification with MTWA testing in MADIT-II–eligible patients improves the cost-effectiveness of ICDs. Implanting defibrillators in all MADIT-II–eligible patients, however, is not cost-effective, with one-third of patients deriving little additional benefit at great expense.

The MADIT-II study (Moss et al., N Engl J Med 2002;346:877-883) demonstrated that implantation of a cardioverter/defibrillator (ICD) reduced mortality from 19.8% to 14.2% during 20 months of follow-up in patients with prior myocardial infarction and left ventricular ejection fractionor=0.30. Concerns have been raised both about the cost and potential morbidity of implanting ICDs in a large group of patients when only a small fraction of the patients would be expected to benefit from the treatment. This concern has given rise to the hope that an effective means of risk stratifying the MADIT-II population might be developed so that ICD therapy can be directed to only those patients who are at significant risk and thus likely to benefit from treatment for purposes of primary prevention of arrhythmic death. Electrophysiology study (EPS) is probably not suitable for this purpose because of its established relatively high false negative rate and because it is itself an invasive procedure. QRS width has been proposed for this purpose but prospective data demonstrating its effectiveness in stratifying the MADIT-II population for risk of arrhythmic death are absent. Initial data suggest that microvolt T-wave alternans (MTWA) testing does appear to be a suitable candidate for risk stratifying the MADIT-II population. These data indicate that approximately 30% of the MADIT-II population test negative for MTWA and that these patients are at extremely low risk for sudden cardiac death and cardiac arrest. Furthermore, MTWA is an inexpensive non-invasive test which can be repeated over time to monitor whether a patient who initially tests negative develops arrhythmic risk with the progression of the underlying disease. As studies of MTWA testing in the MADIT-II population come to publication, a database will likely be formed which will establish MTWA as an effective means of stratifying the MADIT-II population. ICD therapy may not be indicated in patients who test MTWA negative, and conversely the remaining patients may enjoy a greater mortality benefit than that observed in the MADIT-II trial. Furthermore, widespread MTWA testing might have the further benefit in those patients who do not test negative of serving as a call to action to referring physicians to direct those patients to ICD therapy, thereby greatly increasing the number of appropriate patients who actually receive potentially life saving therapy.

Background: The long-awaited dramatically positive outcome of the Multicenter Automatic Defi-brillator Implantation Trial (MADIT II), just published by Moss et al.,14 has generated cardiologists’interest on the implementation into clinical practice of that trial. Important lessons may be learned by examining the clinical implementation of two preceding randomized, prospective, prophylactic ICD trials: the original MADIT trial, published late 1996, and the Multicenter Unsustained Tachycardia Trial (MUSTT), published late 1999. Both demonstrated that implantable cardioverter defi-brillators reduce all-cause mortality by over 50% in high risk patients without previous sustained arrhythmias. Methods: In early 2000, we surveyed 133 active electrophysiology centers (47 American, 81 European, 5 Canadian) to determine the extent to which these practices have been implemented in clinical practice during 1999, and the responses were compared to a similar survey for the year 1998. Results: ICDs implanted for MADIT or MUSTT criteria accounted for 18% of new ICD implants in 1999, 65% greater than in 1998, increasing from 6% to 11% in Europe, and from 15% to 24% in America. During 1999, 53% of patients receiving ICDs for these indications were inpatients identified during hospitalization, 27% were outpatients referred specifically for MADIT/MUSTT indications, and 20% were identified by routine screening. Per the survey, in 1999 68% of responders were “somewhat 10–20%)” and 14% were “considerably (>20%)” more likely to implant ICDs for all indications. Conclusions: Extrapolating the results of this survey to all initial ICD implants for 1999, we estimate that 8500 implants for MADIT/MUSTT criteria took place in 1999, with the overall number of such implants substantially increased over the previous year, irrespective of geographic location, and influenced significantly by the publication of MUSTT. However, screening and implant practices between centers continue to vary over a broad spectrum. It will be interesting to observe whether similar patterns will follow with MADIT II. A.N.E. 2002;7(4):399–405

This article continues a series of reports summarising recent research developments of particular interest to those involved in the management of patients with heart failure. A number of relevant presentations were made at the American Heart Association Scientific Sessions in Anaheim, California, between 11–14 November 2001. Summaries of the following Clinical Trials are included: The Heart Protection Study, IONA, CARISA, ENRICHD, ACUTE, ALIVE, MADIT II and REMATCH.

In this issue of the Journal , Daubert et al. ([1][1]) report on the details of inappropriate implantable cardioverter-defibrillator (ICD) shocks in the MADIT II (Multicenter Automatic Defibrillator Trial II). The MADIT II study ([2][2]) was a primary prevention ICD trial in which patients with

Risk stratification after myocardial infarction (MI) is important to select greater-risk patients who warrant more aggressive strategies for prevention of future serious events such as reinfarction or sudden death. The results of the MADIT II (Multicenter Automatic Defibrillator Implantation) trial

Background Implantable cardioverter defibrillator (ICD)-delivered shocks can cause substantial distress, warranting consideration of ICD deactivation at end of life. This study was designed to describe the patterns of end-of-life management in patients with ICDs. Methods There was a retrospective chart review of 98 patients who died in the ICD arm of multicenter automated defibrillator implantation trial II (MADIT II). The pattern of ICD management and the frequency of ICD shocks delivered before death were reviewed. Results We identified three groups: Group 1 consisting of individuals who underwent ICD, deactivation, 15 (15%); Group 2 patients without ICD deactivation who were in hospice or with “do not resuscitate” (DNR) orders, 36 (37%); and Group 3 patients without ICD deactivation who were not in hospice care and did not have DNR orders, 47 (48%). Out of 15 deactivations, 11 (73%) occurred in the week before death. None of the patients in Group 1 received an ICD shock in the 24-hour period before death. However, one (3%) patient from Group 2 and nine (19%) patients from Group 3 had shocks during the 24 hours before death (P = 0.03). In the last week before death, three (20%), two (6%), and six (13%) patients received ICD shocks in the three groups, respectively (P = 0.28). Conclusions In patients with terminal conditions who are at risk for imminent death, active management of the patient's ICD, including timely discussions regarding ICD deactivation, may reduce the risk of ICD shocks during the end of life.

Implantable cardioverter defibrillators (ICDs) improve survival and extend lives of patients with severe heart disease.We sought to evaluate the impact of ICDs on health-related quality of life (HRQOL) during the first 3 years after implantation.A total of 1089 patients from the Multicenter Automatic Defibrillator Implantation Trial II (MADIT II) were randomized to an ICD or medical treatment only.Health Utility Index (HUI3) at baseline, 3, 12, 24, and 36 months following randomization; survival data.We constructed mean profiles of HRQOL for living patients, estimated overall quality-adjusted life years (QALYs), separately by treatment arm, and calculated cumulative QALY gains/losses as the difference between the areas under the treatment specific HRQOL profiles. Multivariate fixed effect regression models were developed to impute the missing HRQOL data using baseline patient characteristics (age, gender, treatment, HUI3 score, diabetes, diuretics use, and NYHA class). Bootstrapped standard errors were calculated for the estimated differences in HRQOL gains/losses between treatment arms. Similarly, we performed subgroup analyses (by gender, age, and baseline NYHA class, blood urine nitrogen, ejection fraction, and QRS).There were no differences in QALYs loss for living patients by treatment group (-0.037, P = 0.64) or in overall QALYs loss by treatment group (0.043, P = 0.37) over 3 years. In subgroup analysis, female subjects demonstrated a trend towards greater survival benefit (0.298, P = 0.07) and overall QALYs (0.261, P = 0.14).Adverse effects of the ICD on HRQOL together with lower HRQOL among survivors may offset the 3-year survival benefits of ICDs.

The MADIT II study and the SCD-HeFT studies suggest that the ICD reduces total mortality in patients with patients with LV dysfunction. However, the cost-effectiveness of this treatment makes it far from affordable. Better selection of patients that could benefit from an ICD might increase the cost-effectiveness and decrease the percentage of patients in whom an ICD will only produce inappropriate discharges and other undesirable effects. Subgroup analysis has demonstrated a progressive increase in effectiveness of the ICD as QRS duration increases. Little benefit was derived in patients with a QRS of less than 0.12 s, whereas if a QRS duration of 0.15 s was used as a cut-off, a marked reduction in SCD was observed, comparable to that in MUSTT and MADIT I. Similarly, in the SCD-HeFT trial the relative benefits of ICD therapy appeared greater in patients with NYHA class II heart failure, the group in which sudden death is expected to predominate. There seemed to be no benefit in patients with NYHA class III heart failure.

Le mieux est l’ennemi du bien —by Voltaire The first transvenous high-voltage implantable cardioverterdefibrillator (ICD) lead failure occurred in 1988 when a patient with an investigative lead received multiple inappropriate shocks due to noise generated by a conductor fracture. This failure was the harbinger of multiple ICD lead debacles that would affect 4500,000 patients with failed or recalled leads during the next 20 years. Indeed, no other implantable medical device has been plagued by so many problems. In retrospect, physicians, the Food and Drug Administration (FDA), and industry could have done many things differently to avert this costly cascade of lead failures and recalls. Physicians could have resisted the enticement of smaller diameter leads, which have not been shown to be more effective in preventing sudden cardiac death than the original 12-F Endotak; the FDA could have insisted on long-term clinical trials before new leads were approved for widespread use; and industry could have exercised better judgment in bringing new designs and materials to market without human safety data. What physicians should do now is use the good leads with a track record of long-term reliability and demand that industry leave them alone. The development of an effective transvenous ICD lead was a critical milestone that allowed the conduct of primary prevention trials such as MADIT II and SCD-HeFT as well as the safe application of defibrillation therapy in millions of patients worldwide. Most patients today have an ICD lead with 1 or 2 shocking coils that reliably defibrillate the heart by using the pulse generator can as a separate electrode. The implant procedure is safe in experienced hands, with hospital mortality o1% and major 30-day complications o5%. However, it is the ICD lead’s long-term durability—or lack thereof—that has driven adverse outcomes. Fragile conductors and flawed insulating materials have caused serious complications, including failure to deliver therapy, inappropriate shocks, and death. Tens of thousands of patients have had surgical revisions to replace failed or suspect leads, and many thousands will likely need revisions in the future. Indeed, ICD lead

The results of the MADIT II study have generated a great deal of controversy in the world of electrophysiology. Much of the controversy appears related to the sheer numbers of potential Implantable Cardioverter Defibrillator (ICD) implants and their potential cost to the healthcare system. Two federal regulatory agencies, the Food and Drug Administration (FDA) and the Centers for Medicare and Medicaid Services (CMS) have been highly visible in discussions. The FDA approved the MADIT II indications for Guidant ICDs, while CMS covered a limited subset of the patients studied. This review explores some the issues surrounding the trial and the key participants in this discussion with emphasis on the role of the Food and Drug Administration (FDA) and how regulatory decisions may impact on clinical practice.

In MADIT-II, prophylactic ICD therapy was effective in improving survival in patients with prior myocardial infarction and an ejection fractionor=0.30, and a host of prespecified secondary analyses indicate that life-saving effect of ICD therapy is consistent across all studied subgroups. We have not been able to identify any traditional risk factors that will permit selection of patients who will receive a significantly better effect from the ICD within any subgroup. The ICD provides appropriate therapy for life-threatening ventricular arrhythmias on at least one occasion in over a third of the patients during the first 4 years after device implantation. Computations from the MADIT-II database indicate that 9 patients need to be treated with an ICD to save one life during a 4-year period. The findings from MADIT-II have implications for patients, physicians, and society.

One of the most relevant problems in current cardiological practice is the possibility of implementing, in patients who have a specific indication, a series of treatments of proven efficacy but of high cost. This problem involves percutaneous transluminal coronary angioplasty (PTCA) and cardioverter-defibrillators (CDs) [1]. Table 1 shows the number of procedures performed in the year 2000 in the European Union (15 countries) and in the whole of Europe (33 countries). As the table shows, the increase in population obtained by adding 18 countries to those within the European Union is not followed by a parallel increase in the number of high-cost procedures, suggesting marked difficulties due to economic reasons in using these treatments in routine daily practice.

The landmark Multicenter Automatic Defibrillator Implantation Trial II (MADIT II) demonstrated that the implantable defibrillator (ICD) improved survival in post-infarction patients with left ventricular ejection fractions of 30 or lower [1]. Despite rigorous scrutiny, the study has resulted in acceptance of this recommendation by numerous regulatory agencies, both in the United States and Europe. MADIT II has been heralded as one of the most important research studies in cardiology in the past 20 years.

The possibility of using implantable cardioverter-defibrillators (ICDs) for primary prevention of sudden death in selected high-risk patients has prompted a series of prospective controlled studies. Recently, the MADIT II study highlighted the possibility of effective primary prevention of sudden death in patients with coronary artery disease selected by straightforward clinical data and without expensive screening (electrophysiological study). For patients with previous myocardial infarction and low left ventricular ejection fraction (/=30%), ICD implantation may reduce mortality risk by approximately 31% in the following 2 years. Implementation of this therapeutic strategy threatens to impact on public health-care spending. Possible cost-limiting mechanisms include price cuts because of increasing usage (market forces); identification of subgroups at higher risk of sudden death and use of cheaper devices with limited diagnostic and therapeutic options. Further long-term evaluation of the cost-effectiveness and cost-utility of ICDs should identify subgroups of patients for whom implantation is affordable despite current economic constraints. For heart failure patients, randomized controlled trials are currently evaluating the effects on overall survival of both conventional ICDs and devices with biventricular pacing capabilities. In this perspective, data from the COMPANION trial are expected to stimulate the use of devices with defibrillation back-up in candidates for biventricular pacing.

This chapter briefly reviews the aims and outcome of antiarrhythmic drug therapy in ICD recipients. It should be stated at the outset that very few controlled trials of antiarrhytlunic drug therapy in ICD recipients have been reported. Early ICD trials were designed to allow comparisons between patients randomized to ICD therapy or “conventional therapy”. The conventional therapy groups received heterogeneous treatments with various antiarrhytlunic drugs such as amiodarone (1, 2, 3, 4, 5, 6, 7), dl-sotalol (3, 4 7), class I antiarrhytlunics (1, 2, 3, 4 7), calcium blockers (2 3 5), and beta blockers (Table 1) (2 5 6). In most of these early trials, antiarrhythmic drug therapy in the ICD treatment groups was left to the discretion of the investigators (1-7). With the exception of the CIDS trial (4), few ICD patients received adjunctive amiodarone, dl-sotalol, or class I agents, whereas up to 70% received unspecified beta blockers in unknown dosages (Table 1). Therefore, previous ICD trials provided little specific information on adjunctive drug therapy in ICD groups. Two recent ICD trials still partly in progress, SCD-HeFT and MADIT II (8), are also not designed to assess effects of adjunctive drug therapy.

The follow-up of 1440 consecutive post-MI patients (68.9±10.9 years) with an LVEF≤40% was analyzed in 19 Italian hospitals to evaluate how many patients with clinical nonsustained VT and inducible sustained VT or VF underwent post-discharge risk assessment (RA). During 38 (range, 4–76) months follow-up, 611 patients (42.4%) qualified for and 294 (20.4%) effectively underwent RA combining LVEF assessment and Holter monitoring, 29 (2.0%) subsequently underwent programmed electrical stimulation and 19 (1.3%) received an ICD.

Although the results from the trials pooled by Cowie et al. 1 show no statistical heterogeneity, there is a marked clinical heterogeneity between those trials. Three out of the six studies enrolled patients with non-ischaemic heart disease only. A difference in baseline mortality ranging between 4.5% (CAT) and 17.1% (MADIT I) suggests substantial clinical differences between patients. The presence of clinical heart failure, a major determinant of sudden death, was no prerequisite for inclusion in some studies. In MADIT II, 39% of controls were in NYHA class I, whereas in CAT and SCD-HeFT, such patients were excluded. There was also a wide variation in the use of beta-blockers across the trials.2 Assuming a constant risk of cardiac death over time in the model is unrealistic. For example, …

We read with interest the editorial commenting on our modelling of the cost-effectiveness of primary prophylactic implantable cardioverter defibrillator (ICD) implantation according to the current European guidelines in a European population,1 claiming that our analysis overstated the likely cost-effectiveness of such therapy due to inappropriate assumptions around key determinants of cost and efficacy. Meine et al. mistakenly suggest that the results of our analysis2 were materially different from those from the MADIT II3 and SCD-HeFT4 trials. Our analysis had a life-time model time horizon (as recommended in most recent national and international guidelines for health economic analyses5–7), whereas the two US cost-effectiveness analyses took a (rather arbitrary) 12-year time horizon. If we had taken this time horizon, the incremental cost-effectiveness ratio (ICER) at that point in our analysis would have been €43 752 ($61 253 per QALY at exchange rate of €1: $1.40), similar to the MADIT II ($78 600–$114 000 per life year) and SCD-HeFT analyses ($58 510 per QALY). The more appropriate life-time horizon in our analysis gave an ICER of €31 717 per QALY gained ($44 404). The editorial also suggests that there is a lack of a treatment effect for ICDs in …

In a recent issue of the Journal , Daubert et al. ([1][1]) reported the impact of inappropriate implantable cardioverter-defibrillator (ICD) shocks on health outcomes in the MADIT II (Multicenter Automatic Defibrillator Trial II). The incidence of 1 or more inappropriate shocks was 11.5%

b l The combination of clinical trial data and expanded eimbursement coverage has led to exponential growth in he use of implantable cardioverter-defibrillators (ICDs) for rimary prevention. However, a dark side of the therapy is hat more than one third of shocks delivered to patients reated with ICDs for primary prevention are inappropriate, ost commonly due to atrial arrhythmias but also to overensing of normal cardiac signals, such as T waves or ultiple-component long-duration R waves, and sensing of xternal electrical noise and of noise artifacts from faulty eads. Furthermore, with the shift to primary prevention, he proportion of inappropriate shocks has actually inreased. In the secondary prevention Antiarrhythmics Versus Imlantable Defibrillators (AVID) trial, an ICD shock was elivered to 45% of the patients at 1 year and to 62% of the atients at 2 years. However, 11% had at least one episode lassified as inappropriate therapy due to atrial fibrillation nd 9% due to supraventricular tachycardia (SVT). The first arrhythmia” detected was due to ICD malfunction or inppropriate sensing 3% of the time. For patients receiving ICDs for primary prevention, alhough appropriate ICD therapy occurs less frequently than n patients receiving ICDs for secondary prevention, inapropriate shocks are especially problematic. In the Multienter Automatic Defibrillator Implantation Trial (MADIT) I study, 24% of the patients with an ICD received approriate therapy during the 17.2-month average follow-up. owever, 12.2% of patients received inappropriate shocks. rom another perspective, of the 806 therapies delivered by n ICD in MADIT II, 36.4% were inappropriate. Of those, 8% were due to atrial fibrillation, 34% to another SVT, and 7% to abnormal sensing. Multiple attempts to decrease the occurrence of inapproriate shocks have been made. The earliest generation ICDs ncorporated a probability density function (PDF) to differ