Multicenter Automatic Defibrillator Implantation Trial Research Articles

Impact of the Multicenter Automatic Defibrillator Implantation Trial on Clinical Practice

The first multicenter automatic defibrillator implantation trial (MADIT-I) was a landmark study that identified a significant reduction in mortality among high-risk patients with ischemic cardiomyopathy treated prophylactically with an implantable cardioverter defibrillator (ICD), yet the direct and indirect impact of this trial on clinical practice is unknown. We performed a retrospective analysis of the 679 patients who underwent primary ICD implantation between 1994 and 2000 at a single academic center. The baseline characteristics of each patient were determined at the time of ICD implantation, and the vital status of all patients was determined as of January 1, 2004. The number of patients who received an ICD based on the MADIT-I criteria increased from 1.4% in 1994 to 6.1% in 2000. An additional 60 patients were identified that met many but not all of the trial criteria and consisted of patients with a history of a recent revascularization or myocardial infarction, syncope, or an ejection fraction >or=35%. The number of patients who received ICDs in this expanded MADIT-I subset also grew from 5.6% in 1994 to 14.6% in 2000. Mortality during a mean follow-up of 4.7 years was significantly higher in the MADIT-I group than in the expanded MADIT-I, or the remaining primary prevention and secondary prevention subsets. The MADIT-I has not only led to an increase in the number of patients undergoing prophylactic ICD implantation, but in clinical practice it has also been extrapolated to a broader population that has a different degree of risk than originally studied.

Implantable Cardioverter–Defibrillators: A New Preventive Medical Option

Implantable cardioverter-defibrillator (ICD or defibrillator) therapy has revolutionized the fields of cardiology and electrophysiology. Hundreds of thousands of patients at risk for sudden cardiac death receive them each year. The devices are not much larger than a pacemaker, and they have full pacemaker capabilities in addition to being able to shock patients out of life-threatening ventricular arrhythmias. The Multicenter Automatic Defibrillator Implantation Trial (MADIT) in 1996 was a landmark trial that showed for the first time a mortality benefit of ICD therapy over medications in patients at high risk for sudden death. Multicenter Automatic Defibrillator Implantation Trial II, published in 2002, extended these results to all patients with ischemic heart failure with depressed heart function. Candidates for ICD implantation include most patients with an ejection fraction of <30%, especially those with coronary artery disease. More work needs to be done to define those patients with nonischemic cardiomyopathies who will benefit from ICDs and biventricular pacing for heart failure.

Predictive Value of Ventricular Arrhythmia Inducibility for Subsequent Ventricular Tachycardia or Ventricular Fibrillation in Multicenter Automatic Defibrillator Implantation Trial (MADIT) II Patients

In the Multicenter Automatic Defibrillator Implantation Trial (MADIT) II, implantable cardioverter-defibrillator (ICD)-randomized patients underwent electrophysiologic testing. Both inducible and noninducible patients received an ICD. We correlated inducibility with the occurrence of subsequent ventricular tachycardia (VT) or ventricular fibrillation (VF). Intracardiac ICD electrograms for subsequent events were analyzed to categorize the spontaneous arrhythmia as VT or VF. The two-year Kaplan-Meier event rate for VT in inducible patients was 29.0% versus 19.3% in noninducible patients. However, ICD therapy for spontaneous VF was less common at two years in inducible patients (3.2%) than in noninducible patients (8.6%). In the MADIT II study, inducibility predicted an increased likelihood of VT but decreased VF. We correlated electrophysiologic inducibility with spontaneous ventricular tachycardia (VT) or ventricular fibrillation (VF) in the Multicenter Automatic Defibrillator Implantation Trial (MADIT) II. In the MADIT II study, 593 (82%) of 720 implantable cardioverter-defibrillator (ICD) randomized patients underwent electrophysiologic testing. Patients received an ICD whether they were inducible or not. A "standard" inducibility definition included sustained monomorphic or polymorphic VT induced with three or fewer extrastimuli or VF induced with two or fewer extrastimuli. We compared a narrow inducibility definition (only monomorphic VT) and a broad definition (standard definition plus VF with three extrastimuli). We used ICD-stored electrograms to categorize spontaneous VT or VF. Inducible patients (standard definition) had a greater likelihood of experiencing ICD therapy for VT than noninducible patients (p = 0.023). Unexpectedly, ICD therapy for spontaneous VF was less common (p = 0.021) in inducible patients than in noninducible patients. The two-year Kaplan-Meier event rate for VT or VF was 29.4% for inducible patients and 25.5% for noninducible patients. Standard inducibility did not predict the combined end point of VT or VF (p = 0.280, by log-rank analysis). The narrow inducibility definition outperformed the standard definition, whereas the broad definition appeared inferior to the standard definition. In the MADIT II study patients, inducibility was associated with an increased likelihood of VT. Noninducible MADIT II study subjects using this electrophysiologic protocol had a considerable VT event rate and a higher VF event rate than inducible patients. Induction of polymorphic VT or VF, even with double extrastimuli, appears less relevant than induction of monomorphic VT.

Clinical Course and Implantable Cardioverter Defibrillator Therapy in Postinfarction Women with Severe Left Ventricular Dysfunction

There are limited data regarding implantable cardioverter defibrillator (ICD) therapy in postinfarction women with severe left ventricular dysfunction. The aim of this study was to evaluate the risk of cardiac events and effects of ICD therapy in women as compared to men enrolled in the Multicenter Automatic Defibrillator Implantation Trial II (MADIT II). Among 1,232 patients enrolled in MADIT II, there were 192 (16%) women and 1,040 (84%) men. When compared to men, women had an increased frequency of NYHA class > or =II (70 vs 63%; P = 0.067), hypertension (60% vs 52%; P = 0.047), diabetes (42% vs 34%; P = 0.027), and LBBB (25% vs 17%; P = 0.011), and less frequent CABG surgery (42% vs 60%; P < 0.001). The 2-year cumulative mortality in patients randomized to conventional therapy was not significantly different in women and men (30% and 20%, respectively; P = 0.19). Adjusting for relevant clinical covariates, the hazard ratios for ICD effectiveness were similar in women (0.57; 95% CI = 0.28-1.18; P = 0.132) and men (0.66; 95% CI = 0.48-0.91; P = 0.011). The risk of appropriate ICD therapy for VT/VF was lower in women than in men (hazard ratio = 0.60 for female vs male gender; 95% CI = 0.37-0.98; P = 0.039). MADIT II women had similar mortality and similar ICD effectiveness when compared to men. MADIT II women with ICDs had a lower risk of arrhythmic events with fewer episodes of ventricular tachycardia than men.

Factors Influencing Appropriate Firing of the Implanted Defibrillator for Ventricular Tachycardia/Fibrillation: Findings From the Multicenter Automatic Defibrillator Implantation Trial II (MADIT-II)

The purpose of this study was to prospectively examine the role of clinical, laboratory, echocardiographic, and electrophysiological variables as predictors of appropriate initial implantable cardioverter-defibrillator (ICD) therapy for ventricular tachycardia (VT) or ventricular fibrillation (VF) or death in the Multicenter Automatic Defibrillator Implantation Trial II (MADIT-II) population. There is limited information regarding the determinants of appropriate ICD therapy in patients with reduced ventricular function after a myocardial infarction. We used secondary analysis in one arm of a multicenter randomized clinical trial in patients with a previous myocardial infarction and reduced left ventricular function. We analyzed baseline and follow-up data on 719 patients enrolled in the ICD arm of the MADIT-II study. Appropriate ICD therapy was observed in 169 subjects. Clinical, laboratory, echocardiographic, and electrophysiological variables, along with measures of clinical instability such as interim hospitalization for congestive heart failure (IH-CHF) and interim hospitalization for coronary events (IH-CE), were examined with proportional hazards models and Kaplan-Meier time-to-event curves before and after first interim hospitalization. Interim hospitalization-CHF, IH-CE, no beta-blockers, digitalis use, blood urea nitrogen (BUN) >25, body mass index (BMI) > or =30 kg/m2, and New York Heart Association functional class >II were associated with increased risk for appropriate ICD therapy for VT, VF, or death. In a multivariate (stepwise selection) analysis, IH-CHF was associated with an increased risk for the end point of either VT or VF (hazard ratio [HR] 2.52, 95% confidence interval [CI] 1.69 to 3.74, p < 0.001) and for the combined end point of VT, VF, or death (HR 2.97, 95% CI 2.15 to 4.09, p < 0.001). Interim hospitalization-CE was associated with an increased risk for VT, VF, or death (HR 1.66, 95% CI 1.09 to 2.52, p = 0.02). These results provide important mechanistic information, suggesting that worsening clinical condition and cardiac instability, as reflected by an IH-CHF or IH-CE, are subsequently associated with a significant increase in the risk for appropriate ICD therapy (for VT/VF) and death.

Cost-Effectiveness of Implantable Cardioverter–Defibrillators

Eight randomized trials have evaluated whether the prophylactic use of an implantable cardioverter-defibrillator (ICD) improves survival among patients who are at risk for sudden death due to left ventricular systolic dysfunction but who have not had a life-threatening ventricular arrhythmia. We assessed the cost-effectiveness of the ICD in the populations represented in these primary-prevention trials. We developed a Markov model of the cost, quality of life, survival, and incremental cost-effectiveness of the prophylactic implantation of an ICD, as compared with control therapy, among patients with survival and mortality rates similar to those in each of the clinical trials. We modeled the efficacy of the ICD as a reduction in the relative risk of death on the basis of the hazard ratios reported in the individual clinical trials. Use of the ICD increased lifetime costs in every trial. Two trials--the Coronary Artery Bypass Graft (CABG) Patch Trial and the Defibrillator in Acute Myocardial Infarction Trial (DINAMIT)--found that the prophylactic implantation of an ICD did not reduce the risk of death and thus was both more expensive and less effective than control therapy. For the other six trials--the Multicenter Automatic Defibrillator Implantation Trial (MADIT) I, MADIT II, the Multicenter Unsustained Tachycardia Trial (MUSTT), the Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) trial, the Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) trial, and the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT)--the use of an ICD was projected to add between 1.01 and 2.99 quality-adjusted life-years (QALY) and between 68,300 dollars and 101,500 dollars in cost. Using base-case assumptions, we found that the cost-effectiveness of the ICD as compared with control therapy in these six populations ranged from 34,000 dollars to 70,200 dollars per QALY gained. Sensitivity analyses showed that this cost-effectiveness ratio would remain below 100,000 dollars per QALY as long as the ICD reduced mortality for seven or more years. Prophylactic implantation of an ICD has a cost-effectiveness ratio below 100,000 dollars per QALY gained in populations in which a significant device-related reduction in mortality has been demonstrated.

Differences in Outcomes Between Patients Treated with Single‐ versus Dual‐Chamber Implantable Cardioverter Defibrillators: A Substudy of the Multicenter Automatic Defibrillator Implantation Trial II

We sought to evaluate the influence of single- versus dual-chamber implantable cardioverter defibrillators (ICDs) on the occurrence of heart failure and mortality as well as appropriate and inappropriate ICD therapy in the Multicenter Automatic Defibrillator Implantation Trial II (MADIT-II). In MADIT-II, ICD therapy in patients with a prior myocardial infarction and ejection fraction < or =0.30 was associated with a 31% reduction in risk of mortality when compared to conventionally treated patients. An unexpected finding was an increased occurrence of hospitalization for heart failure in the ICD group. Data from 717 patients randomized to ICD therapy with single- or dual-chamber pacing devices in MADIT-II were retrospectively analyzed. Endpoints selected for analysis included death from any cause, new or worsening heart failure requiring hospitalization, death or heart failure, appropriate therapy for ventricular tachycardia (VT) or ventricular fibrillation (VF), and inappropriate ICD therapy for atrial fibrillation or supraventricular tachycardia. A total of 404 single-chamber ICDs (S-ICDs) and 313 dual-chamber ICDs (D-ICDs) were implanted. Patients receiving D-ICDs were at a higher risk at baseline than those receiving S-ICDs, with older age, higher NYHA class, more frequent prior CABG, wider QRS complex, more LBBB, higher BUN level, a history of more atrial arrhythmias requiring treatment, and a longer time interval from their index myocardial infarction to enrollment. While there was a trend toward an increase in adverse outcomes in the D-ICD group, no statistically significant differences in heart failure or mortality were observed between S-ICD versus D-ICD groups. Patients with D-ICDs had a nonsignificant trend toward higher mortality and heart failure rates than patients with S-ICDs.

Ventricular Arrhythmias after LV Remodelling: Surgical Ventricular Restoration or ICD?

Ventricular arrhythmias cause ~50% of deaths in remodeled ventricles after myocardial infarction, and the Multicenter Automatic Defibrillator Implantation Trial (MADIT II) showed that the Implantable Cardioverter Defibrillator (ICD) saved lives in high risk coronary patients with advanced left ventricular dysfunction. We studied 382 patients with remodeled hearts by preoperative Ventricular stimulation (PVS) to evaluate surgical ventricular restoration (SVR) that excludes scar and lower ventricular volume alters the early and late arrhythmia process without ICD utilization. Clinical and hemodynamic results before and after SVR in post-infarction patients, are compared to contrast spontaneous and/or inducible ventricular tachycardia to patients without arrhythmias. Study arrhythmia groups included: Spontaneous in 87 patients with clinical documented ventricular arrhythmias and inducible or not inducible ventricular tachycardia: Inducible in 105 patients without clinical ventricular arrhythmias but PVS inducible ventricular tachycardia; and No arrhythmias in 190 patients without spontaneous or PVS inducible ventricular tachycardia. Preoperative LV end systolic volume index helped define preoperative arrythmia potential: Spontaneous > 120/m(2), inducible > 100 ml/m(2), and none < 100ml/m(2). Overall operative mortality rate was 7.6% (29/382). Sudden cardiac death rate was 2.5% causing 18.7% of all deaths. Surgical management reduced inducible ventricular tachycardia, from 41% preoperatively (144/352) to 8% (26/307) at early study, and 8% (14/177) one year later. Cardiac mortality was low at 5-years and not different between groups, despite use of only one late ICD device. Favorable electrical success rate and low mortality always included volume reduction to interrupt functional re-entry circuits, but also added endocardiectomy, cryoablation, CABG and mitral repair when needed. Overall SVR findings show volume and shape alteration limits ventricular arrhythmias that impair prognosis, and suggests ICD devices are not needed.

Can microvolt T-wave alternans testing reduce unnecessary defibrillator implantation?

The Multicenter Automatic Defibrillator Implantation Trial II (MADIT II) and the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) have established that patients with a reduced ejection fraction gain an overall mortality benefit from prophylactic implantable cardioverter-defibrillator therapy. Only a small proportion of the patients in these studies, however, have received life-saving therapy from the defibrillator. Because defibrillator therapy is invasive and expensive, patients with a low ejection fraction would benefit from effective risk stratification so that defibrillator therapy was used only in those at significant risk. In this review, we analyze prospective clinical trials that have evaluated microvolt T-wave alternans (MTWA) testing as a predictor of ventricular tachyarrhythmic events in populations of patients similar to those studied in MADIT II or SCD-HeFT; that is, patients with a reduced ejection fraction who were not selected on the basis of a history of ventricular tachyarrhythmias. In these studies, the average annual rate of fatal and nonfatal ventricular tachyarrhythmic events among the patients who tested negative for MTWA was around 1%. This rate is so low that it is unlikely that such patients would benefit from implantable cardioverter-defibrillator therapy. The mortality, moreover, was lower among MTWA-negative patients who did not receive implantable defibrillators than that observed in the MADIT II and SCD-HeFT patients who received implantable cardioverter-defibrillators. In response, patients with a low ejection fraction who are being considered for implantable cardioverter-defibrillator therapy should undergo MTWA testing as part of their evaluation.

Amino-Terminal Pro-Brain Natriuretic Peptide Predicts Ventricular Arrhythmogenesis in Patients With Ischemic Cardiomyopathy and Implantable Cardioverter-Defibrillators

Even in high-risk population groups, not all patients have the same risk of sudden cardiac death (SCD). Given the emerging data about the amino-terminal fragment of the brain natriuretic peptide prohormone (NT-proBNP) value in heart failure, we planned to evaluate the importance of NT-proBNP levels in predicting the occurrence of malignant arrhythmias in patients with ischemic cardiomyopathy and implantable cardioverter-defibrillators (ICDs). Prospective study. Tertiary referral center. Thirty five ambulatory patients with previous myocardial infarction, left ventricular ejection fraction < 35%, and ICDs for primary prevention of SCD according to Multicenter Automatic Defibrillator Implantation Trial I criteria. Venous blood samples for plasma NT-proBNP measurement were obtained after 30 min of supine rest from all patients at the beginning of the study. Patients were evaluated every 2 months, or sooner in cases of device discharges, during a 1-year follow-up period. Data concerning arrhythmias and device therapy were stored at the time of device interrogation on each follow-up visit. During 1-year follow-up, 11 of 35 patients (31.4%) received 18 antiarrhythmic device therapies for ventricular tachyarrhythmia (VT). Patients who experienced such arrhythmias had NT-proBNP levels of 997.27 +/- 335.14 pmol/L (mean +/- SD), whereas those without VT had NT-proBNP levels of 654.87 +/- 237.87 pmol/L (p = 0.001). An NT-proBNP cutoff value of 880 pmol/L had a sensitivity of 73%, a specificity of 88%, a positive predictive value of 80%, and a negative predictive value of 88% for the prediction of occurrence-sustained VT events. To achieve the maximum benefit by ICD therapy, more precise risk stratification is required, even in high-risk, post-myocardial infarction patients. Plasma NT-proBNP levels comprise a promising method that could help in the better identification of a patient group with an even higher risk of sudden death.

Comparison of Efficacy of Implanted Cardioverter-Defibrillator in Patients With Versus Without Diabetes Mellitus

In the second Multicenter Automatic Defibrillator Implantation Trial, patients with a previous myocardial infarction and left ventricular ejection fraction < or =0.30 benefited significantly from prophylactic implantable cardioverter-defibrillator (ICD) placement. Diabetic patients who had a myocardial infarction had a worse prognosis compared with nondiabetics. The present study used data from the second Multicenter Automatic Defibrillator Implantation Trial to assess the efficacy of ICD placement on survival in diabetic patients. Of the 1,232 patients in the second Multicenter Automatic Defibrillator Implantation Trial, 489 were characterized as diabetic. They were more likely to be New York Heart Association class II to IV, be hypertensive, have renal dysfunction, have an increased body mass index, and to take diuretic drugs. Diabetic patients had a 24% greater adjusted risk of death than nondiabetic patients. The hazard ratio (HR) for the risk of death in patients treated with the ICD compared with conventional therapy was similar in diabetics (HR 0.61; 95% confidence interval [CI] 0.38 to 0.98) and nondiabetics (HR 0.71; 95% CI 0.49 to 1.05), with no evidence of interaction. Thus, diabetic patients derive a similar benefit from ICD therapy despite being sicker and having a higher mortality rate overall.

Implantable Cardioverter-Defibrillator Efficacy in Patients With Heart Failure and Left Ventricular Dysfunction (from the MADIT II Population)

The Multicenter Automatic Defibrillator Implantation Trial II demonstrated a significant 31% reduction in the risk of mortality in postinfarction patients with low ejection fraction (EF < or =30%). Recently, results from the Sudden Death in Heart Failure Trial indicated that a subgroup of patients with New York Heart Association (NYHA) class III heart failure had less benefit from an implantable cardioverter-defibrillator (ICD) than patients with less advanced heart failure. This study evaluates the association between NYHA class, EF, and blood urea nitrogen (BUN) levels as measures of heart failure and left ventricular dysfunction, and ICD benefit in reducing mortality as well as the association of these parameters with ICD therapy for ventricular tachyarrhythmias. NYHA class I was identified in 442 patients (36%), class II in 425 (35%), and class III in 350 patients (29%). EF < or =20% was present in 472 patients (38%), EF of 21% to 25% in 359 patients (29%), and EF of 26% to 30% in 401 patients (33%). BUN < or =25 mg/dl was present in 850 patients (70%) and >25 mg/dl in 368 patients (30%). Patients with higher NYHA class and BUN had higher mortality (34%) and a higher risk of arrhythmic events (33% to 35%) than patients in lower functional groups (16% to 20%). EF did not differentiate the risk. There was no evidence for significant interactions between mortality, ICD therapy, and tested parameters. In conclusion, patients with more advanced heart failure have a higher risk of mortality and arrhythmic events than patients with less severe disease. However, there is no significant difference in the benefit from ICD therapy among the above subgroups of patients in the Multicenter Automatic Defibrillator Implantation Trial.

Ejection Fraction and QRS Width as Predictors of Event Rates in Patients with Implantable Cardioverter Defibrillators

The Multicenter Automatic Defibrillator Implantation Trial II in 2002 recommended implantable cardioverter defibrillators (ICDs) prophylactically for all patients with a prior myocardial infarction and ejection fraction (EF) of 30% or less. In June of 2003, the Centers for Medicare and Medicaid Services approved reimbursement for ICD placement in patients with an EF of 30% or less who have a QRS interval greater than 120 ms. The purpose of this study was therefore to determine the value of QRS duration in predicting the occurrence of ventricular arrhythmias within the first year after ICD implantation. These ICDs were placed over the past 5 years for various indications. EF cut points of 30% or less and 31% or greater and QRS duration of 120 ms or less and 121 ms or greater were used to assess the risk of events. There was a significant increase in events in subjects with EF of 30% or less, compared with patients with EF of 31% or greater (P < 0.05), and there was a trend toward increased likelihood of arrhythmias in patients with widened QRS width. This study confirms the conclusion of the Multicenter Automatic Defibrillator Implantation Trial II and implies that the Centers for Medicare and Medicaid Services criteria for reimbursement may not be scientifically valid.

Time dependence of defibrillator benefit after coronary revascularization in the multicenter automatic defibrillator implantation trial

Time dependence of defibrillator benefit after coronary revascularization in the multicenter automatic defibrillator implantation trial

New Graduated Pressure Regimen for External Counterpulsation Reduces Mortality and Improves Outcomes in Congestive Heart Failure: A Report From the Cardiomedics External Counterpulsation Patient Registry

External counterpulsation (ECP) has been shown to increase exercise tolerance and reduce angina episodes, Canadian Cardiovascular Society Functional (CCSF) class, anginal medication usage, and hospitalizations in refractive CCSF class III and IV stable angina. However, the high pressures and resulting 1.5:1-2:1 peak diastolic to peak systolic pressure (D/S) ratios shown to be optimal in the treatment of angina can cause excessive preload and adverse effects in congestive heart failure (CHF) patients, particularly those with left ventricular ejection fractions <40%. Data were retrospectively analyzed from the Cardiomedics ECP Registry on 127 New York Heart Association (NYHA) class II-IV CHF patients (79.6% men; average age +/- SD, 68.2+/-15.6 years), with a comorbidity of CCSF class III-IV refractive angina, who were serially treated with 35 hours of ECP (1 h/d, 5 d/wk for 7 weeks) at unconventionally low pressures and D/S ratios under a new graduated pressure regimen. The pressures and D/S ratios were gradually increased in stages over the 7-week ECP regimen. The patients were divided into three groups based on the pressures applied and the resulting average D/S ratios (Low, Mid, and High). In the Low D/S ratio group (average D/S ratio 0.7:1), all-cause mortality in the year following ECP treatment was only 1.85% (one of 54 patients), whereas over the same time period in the Mid D/S ratio group (average D/S ratio 1.08:1), all-cause mortality was 7.69% (three of 39 patients) and in the High D/S ratio group (average D/S ratio 1.32:1), all-cause mortality was 8.82% (three of 34 patients). For the Low, Mid, and High D/S ratio groups, respectively: 1) average left ventricular ejection fractions increased 23.0%, 20.1%, and 17.5%; 2) NYHA class declined 36.6%, 29.6%, and 29.6%; and 3) all-cause hospitalizations, including terminal admissions, were reduced 85.7%, 82.6%, and 57.1% in the year following ECP therapy from the prior year. There were no adverse effects or withdrawals from the ECP therapy and no significant difference in sex-based outcomes. Consequently, ECP applied at low pressures and average D/S ratios of 0.7:1 under the new graduated pressure regimen is safe and effective in the treatment of CHF and produces a significant reduction in mortality, compared with the 8.5% annualized mortality of the Multicenter Automatic Defibrillator Implantation Trial II (MADIT II) (N=1232) of NYHA class II-III CHF and the 12.2% annual mortality of the Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) study (N=595) of NYHA class III-IV CHF. Lower pressures improve patient comfort and may encourage more CHF patients to seek treatment. The reduction in hospitalizations should significantly reduce the cost of treating CHF.

Clinical and Economic Implications of the Multicenter Automatic Defibrillator Implantation Trial-II

The Multicenter Automatic Defibrillator Implantation Trial (MADIT)-II demonstrated that implantable cardioverter defibrillators (ICDs) save lives when used in patients with a history of myocardial infarction (MI) and an ejection fraction of 0.3 or less. To investigate the cost-effectiveness of implanting ICDs in patients who met MADIT-II eligibility criteria and were enrolled in the Duke Cardiovascular Database between 1 January 1986 and 31 December 2001. Cost-effectiveness analysis. Published literature, databases owned by Duke University Medical Center, and Medicare data. Adults with a history of MI and an ejection fraction of 0.3 or less. Lifetime. Societal. ICD therapy versus conventional medical therapy. Cost per life-year gained and incremental cost-effectiveness. Compared with conventional medical therapy, ICDs are projected to result in an increase of 1.80 discounted years in life expectancy and an incremental cost-effectiveness ratio of 50,500 dollars per life-year gained. Cost-effectiveness varied dramatically with changes in time horizon: The cost-effectiveness ratio increased to 67,800 dollars per life-year gained, 79,900 dollars per life-year gained, 100,000 dollars per life-year gained, 167,900 dollars per life-year gained, and 367,200 dollars per life-year gained for 15-year, 12-year, 9-year, 6-year, and 3-year time horizons, respectively. Changing the frequency of follow-up visits, complication rates, and battery replacements had less of an effect on the cost-effectiveness ratios than reducing the cost of ICD placement and leads. The study was limited by the completeness of the data, referral bias, difference in medical therapy between the Duke cohort and the MADIT-II cohort, and not addressing potential upgrades to biventricular devices. The economic expense of defibrillator implantation in all patients who meet MADIT-II eligibility criteria is substantial. However, in the range of survival benefit observed in MADIT-II, ICD therapy for these patients is economically attractive by conventional standards.

The Clinical Implications of Cumulative Right Ventricular Pacing in the Multicenter Automatic Defibrillator Trial II

This study was designed to assess whether right ventricular pacing in the implantable cardioverter defibrillator (ICD) arm of the Multicenter Automatic Defibrillator Implantation Trial (MADIT) II was associated with an unfavorable outcome. Data on the number of ventricular paced beats were available in 567 (76%) of 742 MADIT II patients with ICDs. The number of ventricular paced beats over the total number of beats showed a bimodal distribution with patients being predominantly paced or nonpaced. Therefore, patients were dichotomized at 0-50% and 51-100% of cumulative pacing with median pacing rate 0.2% and 95.6%, respectively. Endpoints included new or worsening heart failure, appropriate ICD therapy for VT/VF, and the combined endpoint of heart failure or death. Clinical features associated with frequent ventricular pacing included age >or=65 years, advanced NYHA heart failure class, LVEF < 0.25, first degree AV and bundle branch block, and amiodarone use. During follow-up, 119 patients (21%) had new or worsened heart failure, 130 (23%) had new or worsened heart failure or death, and 142 (25%) had appropriate therapy for VT/VF. In comparison to patients with infrequent pacing, those with frequent pacing had significantly higher risk of new or worsened heart failure (hazard ratio = 1.93; P = 0.002) and VT/VF requiring ICD therapy (HR = 1.50; P = 0.02). Patients in MADIT II who were predominantly paced had a higher rate of new or worsened heart failure and were more likely to receive therapy for VT/VF. These results suggest the deleterious consequences of RV pacing, particularly in the setting of severe LV dysfunction.

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

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

Are the MADIT II Criteria for ICD Implantation Appropriate for Japanese Patients?

The Multicenter Automatic Defibrillator Implantation Trial (MADIT) II investigators concluded that prophylactic use of an implantable cardioverter defibrillator (ICD) improved survival in patients with prior myocardial infarction (MI) and reduced the left ventricular ejection fraction (LVEF). However, it is unclear whether MADIT II criteria for ICD implantation are appropriate for Japanese patients. During the period 1997 to 2001 90 (M/F: 75/15; mean age: 65+/-9 years) of the 3,258 patients who underwent elective cardiac catheterization met MADIT II criteria (Q-wave MI more than 4 weeks prior; LVEF <or=0.30; >21 years of age; electrophysiologic testing not required) and were selected in this retrospective study of patient prognosis after catheterization. During the 37+/-12-month follow-up period, 15 patients died of congestive heart failure (n=9), sudden cardiac death (n=2), acute MI (n=1), or noncardiac causes (n=3). The survival rate in the present series was comparable with that in the MADIT II defibrillator group, but higher than that in the MADIT II conventional therapy group. A significantly greater percentage of the present patients were found to be in New York Heart Association class I and have undergone percutaneous coronary intervention than in MADIT II. These results suggest that it may be inappropriate to apply MADIT II criteria to Japanese patients.

The Economics of ICDs

On September 28, 2004, the Centers for Medicare and Medicaid Services (CMS) proposed new reimbursement guidelines for implantable cardioverter–defibrillators (ICDs) used for the prevention of sudden death from cardiac causes. The new guidelines dramatically increase the number of patients for whom prophylactic implantation of an ICD would be covered by Medicare. Among other things, the CMS dispensed with the controversial “QRS restriction” on patients like those who participated in the second Multicenter Automatic Defibrillator Implantation Trial — so-called MADIT-II patients. In this trial, which was reported in the Journal in 2002, ICD therapy conferred a striking survival benefit as compared . . .