Arrhythmic Mortality Research Articles

Effectiveness of prophylactic implantation of cardioverter-defibrillators without cardiac resynchronization therapy in patients with ischaemic or non-ischaemic heart disease: a systematic review and meta-analysis

AimsMuch controversy exists concerning the efficacy of primary prophylactic implantable cardioverter-defibrillators (ICDs) in patients with low ejection fraction due to coronary artery disease (CAD) or dilated cardiomyopathy (DCM). This is also related to the bias created by function improving interventions added to ICD therapy, e.g. resynchronization therapy. The aim was to investigate the efficacy of ICD-only therapy in primary prevention in patients with CAD or DCM.Methods and resultsPublic domain databases, MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials, were searched from 1980 to 2009 for randomized clinical trials of ICD vs. conventional therapy. Two investigators independently abstracted the data. Pooled estimates were calculated using both fixed-effects and random-effects models. Eight trials were included in the final analysis (5343 patients). Implantable cardioverter-defibrillators significantly reduced the arrhythmic mortality [relative risk (RR): 0.40; 95% confidence interval (CI): 0.27–0.67] and all-cause mortality (RR: 0.73; 95% CI: 0.64–0.82). Regardless of aetiology of heart disease, ICD benefit was similar for CAD (RR: 0.67; 95% CI: 0.51–0.88) vs. DCM (RR: 0.74; 95% CI: 0.59–0.93).ConclusionsThe results of this meta-analysis provide strong evidence for the beneficial effect of ICD-only therapy on the survival of patients with ischaemic or non-ischaemic heart disease, with a left ventricular ejection fraction ≤35%, if they are 40 days from myocardial infarction and ≥3 months from a coronary revascularization procedure.

Drug-Induced Arrhythmia

Prolongation of the QTc interval has been associated with proarrhythmia resulting from a potentially fatal form of polymorphic ventricular tachycardia called torsades de pointes (TdP). Genetic forms of the long-QT syndrome (LQTS) associated with high arrhythmic risk have been causally related to mutations in ion channels responsible for the cardiac action potential; genetic factors associated with milder degrees of QTc prolongation and arrhythmic risk have also been described. Acquired forms of QTc prolongation and proarrhythmia, particularly related to drug therapy, are frequently related to drug effects on the same ion channels involved in genetic forms of LQTS. As is true for genetic forms of LQTS, there is a wide spectrum of potential drug effects on the QTc interval ranging from trivial to potentially lethal. Drug-induced QTc prolongation is a complicated phenomenon related not just to the properties or dose of a particular drug but also to drug-drug interactions and a variety of patient factors, including age, gender, the presence and severity of underlying heart disease, and genetic predisposition. Additionally, drug effects on other ion channels, including blockade of sodium channels (causing prolongation of the QRS interval rather than the QTc interval), are an important cause of drug-induced proarrhythmia. The purpose of this review is to summarize the available data related to acquired forms of LQTS, with particular focus on drug-related LQTS and proarrhythmia. A brief summary is presented here of genetic LQTS because the relevant genes and proteins form the basis for an understanding of the causes of acquired LQTS, and in any given patient, the QTc is determined by genetic, substrate, and environmental factors. Emphasis is placed on practical strategies for clinicians, with the goal of minimizing the risk of dangerous proarrhythmia related to the use of both cardiac and noncardiac drugs with the potential for QTc prolongation. Genetic …

Fragmented QRS and Mortality Risk in Patients With Left Ventricular Dysfunction

Fragmented QRS (fQRS) has been shown to predict cardiac events in select patient populations. Whether fQRS improves patient selection for primary prevention patients eligible for implantable cardioverter-defibrillator (ICD) therapy remains unknown. In a prospective, multisite cohort of 842 patients with left ventricular dysfunction (ejection fraction < or =35%) representing both ischemic and nonischemic etiology, the presence of fQRS on ECG was assessed using standardized criteria. The association between fQRS and all-cause and arrhythmic mortality was evaluated overall and stratified by ICD status using multivariable Cox regression models, adjusted for demographic, clinical, and treatment variables. Fragmented QRS was present in 274 (32.5%) patients, and there were 191 (22.7%) deaths during a mean follow-up of 40+/-17 months. Rates of all-cause mortality did not differ between the fQRS+ (19.7%) and fQRS- (24.1%) groups; adjusted hazard ratio, 0.88; 95% confidence interval, 0.63-1.22; P=0.43. Additionally, rates of arrhythmic mortality were similar between the fQRS+ (9.9%) and fQRS- (12.7%) groups: adjusted hazard ratio, 0.77; 95% confidence interval, 0.49-1.31; P=0.38. Subgroup analyses found no association between fQRS and mortality when the cohort was further stratified by ICD status, etiology of left ventricular dysfunction, wide (>/=120 ms) versus narrow (<120 ms) QRS duration, or fQRS myocardial territory. In this prospective, multisite cohort of primary prevention patients with left ventricular dysfunction, the presence of fQRS on ECG was not associated with a higher risk of either all-cause or arrhythmic mortality. These findings do not provide evidence that fQRS would be effective in risk stratifying primary prevention patients eligible for ICD therapy.

Prognostic Importance of Defibrillator Shocks in Survivors of Sudden Cardiac Death

Implantable cardioverter-de fi brillator (ICD) implantation is standard of care for patients who have survived life threatening ventricular tachyarrhythmias (LTVA). ICD shocks predict future adverse events in patients with ICD implantation for primary prevention. However, the role of ICD shocks in prediction of adverse events in a secondary prevention population is unknown. The Antiarrhythmics Versus ICDs (AVID) Trial (n=1016) was a randomized controlled trial comparing ICD (n=507) and antiarrhythmic drugs (n=509) in the treatment of patients with LTVA. Mean follow-up duration was 916 ± 471 days. We analyzed the ICD arm of the AVID trial using the NHLBI limited access dataset. ICD shocks were categorized as appropriate if underlying rhythm triggering the shock was ventricular tachycardia or ventricular fibrillation. All other ICD shocks were considered as inappropriate. Data on ICD therapy was available for 420 patients. Any shock (n=380), any appropriate (n=296) or any inappropriate (n=72) shock was not associated with increased all cause, cardiac or arrhythmic mortality. However any appropriate shock was associated with increased LTVA. In conclusion, ICD shocks do not confer increased risk of death on follow up in LTVA survivors. Use of ICD shocks as surrogate marker for adverse outcomes is not viable in secondary prevention patients.

Implantable Cardioverter Defibrillator in Patients with Coronary Artery Disease.

Patients with ischemic left ventricular dysfunction are at a high risk for ventricular tachyarrhythmias and sudden cardiac death. Randomized clinical trials have demonstrated that pharmacologic management with antiarrhythmic drugs has limited efficacy for the prevention of arrhythmic mortality in this high-risk population, whereas the implantable cardioverter defibrillator (ICD) has significant life-saving benefit in primary and secondary prevention trials. However, secondary analyses of these studies have identified some limitations of the ICD in subsets of patients with coronary artery disease, including limited defibrillator efficacy early after coronary revascularization and acute myocardial infarction. We review current knowledge from primary and secondary prevention clinical trials regarding the benefit and limitations of the ICD in high-risk patients with coronary artery disease.

Fragmented QRS on twelve-lead electrocardiogram predicts arrhythmic events in patients with ischemic and nonischemic cardiomyopathy

Myocardial scar is a substrate for reentrant ventricular arrhythmias and is associated with poor prognosis. Fragmented QRS (fQRS) on 12-lead ECG represents myocardial conduction delays due to myocardial scar in patients with coronary artery disease (CAD). The purpose of this study was to determine whether fQRS is associated with increased ventricular arrhythmic event and mortality in patients with CAD and nonischemic dilated cardiomyopathy (DCM). Arrhythmic events and mortality were studied in 361 patients (91% male, age 63.3 +/- 11.4 years, mean follow-up 16.6 +/- 10.2 months) with CAD and DCM who received an implantable cardioverter-defibrillator for primary or secondary prophylaxis. fQRS included various RSR' patterns (QRS duration <120 ms), such as > or =1 R prime or notching of the R wave or S wave present on at least two contiguous leads of those representing anterior (V(1)-V(5)), lateral (I, aVL, V(6)), or inferior (II, III, aVF) myocardial segments. fQRS was present in 84 (23%) patients (fQRS group) and absent in 100 (28%) patients (non-fQRS group). Wide QRS (wQRS; QRS duration > or =120 ms) was present in 177 (49%) patients. Kaplan-Meier analysis revealed that event-free survival for an arrhythmic event (implantable cardioverter-defibrillator shock or antitachycardia pacing) was significantly lower in the fQRS group than in the non-fQRS and wQRS groups (P <.001 and P <.019, respectively). fQRS was an independent predictor of an arrhythmic event but not of death. fQRS on 12-lead ECG is a predictor of arrhythmic events in patients with CAD and DCM. fQRS is associated with a significantly decreased time to first arrhythmic event compared with non-fQRS and wQRS.

Arrhythmic death in implantable cardioverter defibrillator patients: a long-term study over a 10 year implantation period

Evaluation of cause-specific mortality in a large cohort of unselected implantable cardioverter defibrillator (ICD) recipients. Causes of death of consecutive ICD recipients implanted over a 10 year period were analysed. Overall 822 patients (age 63 +/- 11 years, 80% male, EF 34 +/- 14%, secondary prevention 65%) were followed for 43 +/- 30 months during which time 225 patients died (annual mortality 7.6%). Causes of death were cardiac arrhythmic in 16%, cardiac non-arrhythmic in 39%, non-cardiac vascular in 4%, non-cardiovascular in 27%, and unknown in 13%. Advanced age [relative risk (RR) 1.23 per decades, 95% confidence interval (CI) 1.06-1.43], NYHA class >II (RR 2.27, 95% CI 1.51-3.41), renal failure (RR 1.57, 95% CI 1.15-2.14), use of amiodarone (RR 2.56, 95% CI 1.91-3.43), digitalis (RR 1.87, 95% CI 1.40-2.49), diuretics (RR 1.89, 95% CI 1.35-2.66) were independent predictors of all-cause mortality. Predictors for arrhythmic mortality were NYHA class >II (RR 12, 95% CI 3.69-37.5), spontaneous or inducible VT as indication for ICD therapy (RR 2.53, 95% CI 1.06-6.05), and use of amiodarone (RR 3.95, 95% CI 2.02-7.75). In this unselected group of ICD recipients, at least 16% of patients died from arrhythmic causes. Risk factors associated with arrhythmic mortality were a history of spontaneous or inducible VT, higher NYHA class, and amiodarone use.

The Challenge of Predicting and Preventing Sudden Cardiac Death Immediately After Myocardial Infarction

Risk stratification methodsshould provide information about the likelihood of SCD andnon-SCD to identify potentially effective interventions, suchas implantable cardioverter-defibrillator (ICD) therapy thatprevents SCD and reduces mortality. LVEF has been estab-lished as a useful marker of increased mortality after MI, butit does not identify patients at increased risk of arrhythmicdeath relative to total mortality. Among the risk stratificationtechniques evaluated alone or in conjunction with LVEF toidentify patients at high risk for arrhythmic mortality arespontaneous or induced ventricular arrhythmias, the signal-averaged electrocardiography, QT interval dispersion, micro-volt T-wave alternans, increased QRS duration, baroreceptorsensitivity, and heart rate variability and turbulence.

Omacor® (prescription omega-3-acid ethyl esters 90): From severe rhythm disorders to hypertriglyceridemia

Despite progress made in post-myocardial infarction (MI) revascularization and background therapy for the failing heart, the prevention of adverse cardiac remodeling associated with severe rhythm disorders remains an important drug target. Part of the remodeling can be counteracted by modulating the activity of ion channels and exchangers by omega-3 acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). In the GISSI-Prevenzione and GISSI-HF trials, omega-3 fatty acids were administered as ethyl esters (Omacor Solvay Pharmaceuticals) and not as triglycerides present in fish oil. Ethyl esters result in a sustained intestinal absorption of EPA and DHA and require various purification steps during production, thereby minimizing the content of environmental toxins. Also the rather high (38%) DHA content of Omacor should not be ignored since in rats with low dose intake of omega-3 acids, DHA but not EPA inhibited ischemia-induced arrhythmias. In patients on multiple tablets, 840 mg EPA+DHA in one capsule is preferred to increase compliance. It is not justified to refer to Omacor as "n-3 polyunsaturated fatty acid supplementation" or even "fish oil" and, based on controlled clinical trials, there is no evidence that fish oil could be a substitute of Omacor. To avoid further confusion, guidelines should be precise and refer to the medication, eg, as in NICE guideline CG48: "Omega-3-acid ethyl esters treatment licensed for secondary prevention post-MI." The anti-arrhythmogenic action of Omacor should be seen in the context of implantable cardioverter-defibrillator trials (DINAMIT, IRIS) where non-sudden death was increased and total mortality unaltered. However, Omacor administered in the GISSI-HF trial reduced the incidence of severe arrhythmic events and mortality. Also in the GISSI-Prevenzione trial, arrhythmic death and mortality were reduced. At higher dosages (daily, 3-4 g) Omacor exhibits more pronounced cardiovascular benefits and, as a licensed indication, improves hypertriglyceridemia and related lipid parameters.

Early mortality in implantable cardioverter defibrillator patients: from randomized controlled trials to real life

The implantable cardioverter defibrillator (ICD) has been a story of success over the last three decades. The defibrillator has proven highly effective in termination of ventricular tachyarrhythmias. A plethora of clinical trials have shown survival benefit for patients at risk for life-threatening arrhythmias, resulting in a steady increase in the use of ICDs.1,2 Implantable cardioverter defibrillator guidelines are updated frequently reflecting widening indications. Nevertheless, the reduction in mortality related to ICD depends only on the termination of tachyarrhythmias, regardless of the clinical condition or specific circumstances that may contribute to overall mortality. Most patients at risk for sudden cardiac death suffer from impaired ventricular function and have increased risk of heart failure-related mortality. As resources are limited and cost-effectiveness has to be proven, especially in expensive therapies such as ICD, it is critical to identify patients who will benefit most from the device. In daily routine, some patients could either be managed safely by alternative therapies or might be too sick to benefit from ICD therapy. Prediction of this benefit remains one of the major issues. Presently, only limited data are available reporting predictive variables for either arrhythmic events or mortality from non-arrhythmic events and heart failure in ICD patients. Stein et al. 3 reported a large prospective multicenter follow-up of an unselected cohort of new single or dual-chamber ICD recipients. Over 20 parameters in over 1700 patients from 128 US centres were evaluated to establish the survival benefit during the first year after implantation. Such registries provide further information … *Corresponding author. Tel: +49 251 834 7687, Fax: +49 251 834 9965, Email: l.eckardt{at}uni-muenster.de

Is Anyone Too Old for an Implantable Cardioverter-Defibrillator?

Implantable cardioverter-defibrillators (ICDs) are one of the few interventions where we can be reasonably confident that a patient did or did not benefit from the treatment. If one is to benefit from an ICD, then the person must survive long enough to have an arrhythmic event and receive therapy from the device. Thus, the patients who benefit the most are those with a high rate of arrhythmic death and a low rate of nonarrhythmic death. Indeed the enrollment criteria for clinical trials of ICDs were designed to optimize these 2 rates. Accordingly, the patients enrolled in the primary prevention ICD trials were much younger and had less comorbidity than the community heart failure population.1 Article see p 16 On the basis of trial results, we now have guidelines for ICDs that limit them to patients with an ejection fraction below 35% if symptomatic (New York Heart Association Class II or III) or <30% if asymptomatic (New York Heart Association Class I) and expected survival of at least one year.2 However, the clinician is frequently confronted with a patient who meets the primary prevention ICD criteria yet has other characteristics (advanced age or multiple comorbidities) that create legitimate concern that the patient will not benefit from the device. Payers, policy makers, and society warn that even if there is a benefit in these patients, it may be too small to justify the cost. In other words, they question whether an ICD has value in the elderly and those with multiple comorbidities. Although no threshold for value has been widely accepted, many consider a cost per life year (or quality-adjusted life year) gained below $50 000 to $100 000 to …

Implantable Cardioverter Defibrillator Efficacy and Chronic Kidney Disease: Competing Risks of Arrhythmic and Nonarrhythmic Mortality

Implantable Cardioverter Defibrillator Efficacy and Chronic Kidney Disease: Competing Risks of Arrhythmic and Nonarrhythmic Mortality

Role of Microvolt T-Wave Alternans in Assessment of Arrhythmia Vulnerability Among Patients With Heart Failure and Systolic Dysfunction

Background— Sudden cardiac death remains a leading cause of mortality despite advances in medical treatment for the prevention of ischemic heart disease and heart failure. Recent studies showed a benefit of implantable cardioverter defibrillator implantation, but appropriate shocks for ventricular tachyarrhythmias were noted only in a minority of patients during 4 to 5 years of follow-up. Accordingly, better risk stratification is needed to optimize patient selection. In this regard, microvolt T-wave alternans (TWA) has emerged as a potentially useful measure of arrhythmia vulnerability, but it has not been evaluated previously in a prospective, randomized trial of implantable cardioverter defibrillator therapy. Methods and Results— This investigation was a prospective substudy of the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) that included 490 patients at 37 clinical sites. TWA tests were classified by blinded readers as positive (37%), negative (22%), or indeterminate (41%) by standard criteria. The composite primary end point was the first occurrence of any of the following events: sudden cardiac death, sustained ventricular tachycardia/fibrillation, or appropriate implantable cardioverter defibrillator discharge. During a median follow-up of 30 months, no significant differences in event rates were found between TWA-positive or -negative patients (hazard ratio 1.24, 95% confidence interval 0.60 to 2.59, P =0.56) or TWA-negative and nonnegative (positive and indeterminate) subjects (hazard ratio 1.28, 95% confidence interval 0.65 to 2.53, P =0.46). Similar results were obtained with the inclusion or exclusion of patients randomized to amiodarone in the analyses. Conclusions— TWA testing did not predict arrhythmic events or mortality in SCD-HeFT, although a small reduction in events (20% to 25%) among TWA-negative patients cannot be excluded given the sample size of this study. Accordingly, these results suggest that TWA is not useful as an aid in clinical decision making on implantable cardioverter defibrillator therapy among patients with heart failure and left ventricular systolic dysfunction.

Does Microvolt T-Wave Alternans Testing Predict Ventricular Tachyarrhythmias in Patients With Ischemic Cardiomyopathy and Prophylactic Defibrillators?: The MASTER (Microvolt T Wave Alternans Testing for Risk Stratification of Post-Myocardial Infarction Patients) Trial

The purpose of this trial was to determine whether microvolt T-wave alternans (MTWA) predicts ventricular tachyarrhythmic events (VTEs) in post-myocardial infarction patients with left ventricular ejection fraction (LVEF) < or =30%.Previous studies have established MTWA as a predictor for total and arrhythmic mortality, but its ability to identify prophylactic implantable cardioverter-defibrillator (ICD) recipients most likely to experience VTEs remains uncertain.This prospective trial was conducted at 50 U.S. centers. Patients were eligible if they met MADIT-II (Multicenter Automatic Defibrillator Implantation Trial II) indications for device implant. All patients underwent MTWA testing followed by ICD implantation, with pre-specified programming to minimize the likelihood of therapies for non-life-threatening VTE. Minimum follow-up was 2 years with annual MTWA testing. Initially indeterminate MTWA tests were repeated.Analyses were conducted on 575 patients (84% male; average age +/- SD = 65 +/- 11 years; average LVEF +/- SD = 0.24 +/- 0.05). The final distribution of MTWA results were: MTWA positive in 293 (51%), MTWA negative in 214 (37%), and indeterminate in 68 patients (12%). Over an average follow-up of 2.1 +/- 0.9 years, there were 70 VTEs. A VTE occurred in 48 of 361 (13%, 6.3%/year) MTWA non-negative and 22 of 214 (10%, 5.0%/year) MTWA negative patients. A non-negative MTWA test result was not associated with VTE (hazard ratio: 1.26; 95% confidence interval: 0.76 to 2.09; p = 0.37), although total mortality was significantly increased (hazard ratio: 2.04; 95% confidence interval: 1.10 to 3.78; p = 0.02).In MADIT-II-indicated ICD-treated patients, the risk of VTE does not differ according to MTWA classification, despite differences in total mortality. (MASTER I-Microvolt T Wave Alternans Testing for Risk Stratification of Post MI Patients; NCT00305240).

Abstract 5695: Arrhythmogenic Cardiac Death in Implantable Cardioverter Defibrillator Recipients: A Long-term Study of 783 Consecutive Patients

Introduction: Long-term mortality and cause of mortality of ICD recipients who are not enrolled in controlled clinical trials are not well known. This study seeked to determine cause-specific mortality in a large sample of unselected ICD recipients. Methods: Consecutive ICD recipients followed at a tertiary referral center at regular 3-month intervals were included. In cases of missed visits, pts, their relatives and their family physicians were contacted. Based on all available evidence, causes of death were classified as cardiac arrhythmic (C–A), cardiac non-arrhythmic (C-NA), non cardial (non-C) and unknown. Results: A total of 783 pts (primary prevention of sudden death in 252, secondary prevention in 531) were followed for 43 ± 30 months, during which time 193 pts died (24.7%, annual mortality 6.7%). Causes of death are shown in the figure . Cox regression analysis revealed that all-cause morality was significantly affected by age (odds ratio 1.03, 95% confidence interval 1.01–1.05), LVEF (0.98, 0.96 – 0.99), NYHA &gt; II (2.1, 1.35–3.26) at baseline, while ICD indication and development of electrical storm had no independent impact on all cause mortality. Predictors for arrhythmic mortality were LVEF (0.96, 0.91– 0.99), NYHA &gt; II (5.3, 1.4 –19.6) spontaneous VT (9.9, 2.1– 45.2) or inducible VT (9.5, 2.0 – 44.2) as indication for ICD therapy. Conclusion: In this unselected group of ICD recipients the mortality over 3.5 years was 25 %. Despite device therapy, at least 14% of patients died from presumably arrhythmic causes. Risk factors associated with arrhythmic mortality were a history of spontaneous or inducible monomorphic ventricular tachycardia, LVEF and higher NYHA class.

Spatial QRS-T angle in peritoneal dialysis patients: association with carotid artery atherosclerosis, coronary artery calcification and troponin T

Abnormal values of the spatial angle between the directions of ventricular depolarization and repolarization (QRS-T) predict potently arrhythmic events and mortality in various patients groups. The study was designed to estimate QRS-T in a group of peritoneal dialysis (PD) patients, and to assess the possible association between QRS-T and coronary artery calcification (CAC), atherosclerosis, and some biochemical measurements. The angular differences between the maximum spatial QRS and T vectors were reconstructed from ECGs in 57 selected PD patients and in 54 controls. In patients CAC score was performed by using multi-row computed tomography. Atherosclerotic disease was assessed by measuring carotid arteries' intima-media thickness (IMT) and plaque score (sum of the maximum thicknesses in mm of all plaques on both sides) by using an ultrasound scanner. QRS-T was higher in patients compared with controls (34.79% B111.97 and 14.95% B17.87 respectively; P < 0.001). Median CAC score equalled 104.5 Agatson units (Au) (range, 0-2478). IMT was 0.832% B10.208, and atherosclerotic plaques were detected in 82.5% of patients. The plaque score was 7.97% B14.49. QRS-T was higher in patients with CAC score >400 Au compared with patients with CAC score <400 Au (P = 0.011). The results of univariate linear regression analysis showed correlation between QRT-T and dialysis duration (r = 0.305, P = 0,020), LVMI (r = 0.311, P = 0.017), HDL (r = -0.361, P = 0.006), cTnT (r = 0.442, P < 0.001), plaque score (r = 0.403, P = 0.001) and CAC score (r = 0.451, P < 0.001). On multivariate analysis, CAC score, plaque score and troponine T were found to be independent predictors of QRS-T values. QRS-T is high in PD patients and is mainly associated with coronary artery calcium burden, atherosclerosis and troponin T elevation. The possible clinical importance of the higher QRS-T in PD patients remains to be confirmed in further studies.

Office and out of office heart rate measurements: which clinical value?

Office and out of office heart rate measurements: which clinical value?

The Ability of Heart Rate Recovery To Predict Arrhythmic vs. Non-Arrhythmic Mortality in Patients with Heart Failure

The Ability of Heart Rate Recovery To Predict Arrhythmic vs. Non-Arrhythmic Mortality in Patients with Heart Failure

Sex differences in outcome after implantable cardioverter defibrillator implantation in nonischemic cardiomyopathy

Women have been underrepresented in randomized trials of implantable cardioverter defibrillator (ICD) therapy, and limited data suggest that women may not benefit from prophylactic ICD implantation to the same extent as men. In the Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) trial, a reduction in all-cause mortality was seen in men (P = .018) but not for women (P = .76). Sex-specific cumulative probabilities of event-free survival from total, arrhythmic, and noncardiac mortality as well as appropriate shocks were calculated, and log-rank tests were performed. Interaction terms in multivariable Cox proportional hazards models were used to test the hypothesis that the effectiveness of the ICD differed between men and women. Among 458 patients (326 men and 132 women) with nonischemic cardiomyopathy enrolled in the DEFINITE trial, the test for an interaction between sex and ICD treatment on total mortality was not significant in unadjusted (P = .11) or in multivariable adjusted (P = .18) analyses. When we examined cause-specific mortality, we found no sex difference in the incidence of arrhythmic death. Instead, we documented a relative excess of noncardiac death among women randomized to the ICD (P = .02) as compared with women randomized to standard medical therapy. With respect to device use, there was a trend for women to have fewer appropriate ICD shocks after multivariable adjustment (P = .06). Among patients with nonischemic cardiomyopathy enrolled in DEFINITE, we found no conclusive evidence for a sex difference in the effectiveness of the ICD; however, the trial was not adequately powered to detect such interaction effects. Larger studies are required to definitively address whether the benefit of ICD therapy differs between men and women.

T-Wave Alternans and Sudden Cardiac Death

Sudden cardiac death (SCD) is the leading cause of mortality in patients with ischemic heart disease and left ventricular dysfunction. The majority of SCD are due to ventricular tachyarrhythmias. SCD strikes many asymptomatic patients and often is the first manifestation of heart disease. Thus, reliable determination of arrhythmic risk is warranted to guide preventive therapy. To highlight the prognostic value of microvolt-level electrical alternans of the T-wave (MTWA) in patients at risk for SCD, most of the pertinent published articles in the Medline, Scopus, and EBSCO Host research databases have been reviewed. MTWA has been proposed to be a strong and independent predictor of all-cause and arrhythmic mortality. The high predictive value of MTWA in patient with cardiomyopathy varies significantly depending on the population studied. Combining with other indices or having serial MTWA readings could overcome MTWA limitations. Redefining MTWA readings may expand its prognostic utility.