Sudden Cardiac Death In Heart Failure Research Articles

Sudden Death in Men Versus Women with Heart Failure.

Sudden cardiac death (SCD) represents the most feared complication of heart failure (HF). This review intends to provide insight on our current knowledge of sex differences in SCD mechanisms, prevention, and management in HF patients. Women with HF present a better prognosis than men and have a lower incidence of SCD, irrespective of the presence of ischemic heart disease and age. The influence of sex hormones, sex differences in intracellular calcium handling, and a differential myocardial remodeling may explain such a gap between men and women. Both HF drugs and ventricular arrhythmias ablation seems also useful for the management of women at risk of SCD, but special care must be taken with the use of antiarrhythmic QT-prolonging drugs. However, implantable cardioverter defibrillator (ICD) use has not been shown to be equally effective in women than men. Sex-specific recommendations regarding SCD in HF are still lacking due to the scarcity of information and the under-representation of women in clinical trials. Further investigation is required to provide specific risk stratification models in women. Cardiac magnetic resonance imaging, genetics development, and personalized medicine will probably play an increasing role in this evaluation.

Association of obesity with heart failure outcomes in 11 Asian regions: A cohort study.

BackgroundAsians are predisposed to a lean heart failure (HF) phenotype. Data on the ‘obesity paradox’, reported in Western populations, are scarce in Asia and have only utilised the traditional classification of body mass index (BMI). We aimed to investigate the association between obesity (defined by BMI and abdominal measures) and HF outcomes in Asia.Methods and findingsUtilising the Asian Sudden Cardiac Death in Heart Failure (ASIAN-HF) registry (11 Asian regions including Taiwan, Hong Kong, China, India, Malaysia, Thailand, Singapore, Indonesia, Philippines, Japan, and Korea; 46 centres with enrolment between 1 October 2012 and 6 October 2016), we prospectively examined 5,964 patients with symptomatic HF (mean age 61.3 ± 13.3 years, 26% women, mean BMI 25.3 ± 5.3 kg/m2, 16% with HF with preserved ejection fraction [HFpEF; ejection fraction ≥ 50%]), among whom 2,051 also had waist-to-height ratio (WHtR) measurements (mean age 60.8 ± 12.9 years, 24% women, mean BMI 25.0 ± 5.2 kg/m2, 7% HFpEF). Patients were categorised by BMI quartiles or WHtR quartiles or 4 combined groups of BMI (low, <24.5 kg/m2 [lean], or high, ≥24.5 kg/m2 [obese]) and WHtR (low, <0.55 [thin], or high, ≥0.55 [fat]). Cox proportional hazards models were used to examine a 1-year composite outcome (HF hospitalisation or mortality). Across BMI quartiles, higher BMI was associated with lower risk of the composite outcome (ptrend < 0.001). Contrastingly, higher WHtR was associated with higher risk of the composite outcome. Individuals in the lean-fat group, with low BMI and high WHtR (13.9%), were more likely to be women (35.4%) and to be from low-income countries (47.7%) (predominantly in South/Southeast Asia), and had higher prevalence of diabetes (46%), worse quality of life scores (63.3 ± 24.2), and a higher rate of the composite outcome (51/232; 22%), compared to the other groups (p < 0.05 for all). Following multivariable adjustment, the lean-fat group had higher adjusted risk of the composite outcome (hazard ratio 1.93, 95% CI 1.17–3.18, p = 0.01), compared to the obese-thin group, with high BMI and low WHtR. Results were consistent across both HF subtypes (HFpEF and HF with reduced ejection fraction [HFrEF]; pinteraction = 0.355). Selection bias and residual confounding are potential limitations of such multinational observational registries.ConclusionsIn this cohort of Asian patients with HF, the ‘obesity paradox’ is observed only when defined using BMI, with WHtR showing the opposite association with the composite outcome. Lean-fat patients, with high WHtR and low BMI, have the worst outcomes. A direct correlation between high WHtR and the composite outcome is apparent in both HFpEF and HFrEF.Trial registrationAsian Sudden Cardiac Death in HF (ASIAN-HF) Registry ClinicalTrials.gov Identifier: NCT01633398

March 2019 at a glance: epidemiology and clinical trials.

March 2019 at a glance: epidemiology and clinical trials.

Impact of diabetes and sex in heart failure with reduced ejection fraction patients from the ASIAN-HF registry.

To examine sex differences in clinical characteristics, echocardiographic features, quality of life and 1-year death or heart failure (HF) hospitalization outcomes in patients with/without diabetes mellitus (DM). Utilizing the Asian Sudden Cardiac Death in HF (ASIAN-HF) registry, 5255 patients (mean age 59.6 ± 13.1, 78% men) with symptomatic HF with reduced ejection fraction (HFrEF) were stratified by DM status to address the research aims. Despite similar prevalence of DM between Asian men (43%) and women (42%), the odds of DM increased at lower body mass index in women vs. men (≥ 23 vs. ≥ 27.5 kg/m2 , Pinteraction = 0.014). DM was more strongly related to chronic kidney disease in women vs. men [adjusted odds ratio (OR) 1.85, 95% confidence interval (CI) 1.33-2.57 vs. OR 1.32, 95% CI 1.11-1.56, Pinteraction = 0.009]. Sex also modified the relationship between DM and left ventricular geometry (Pinteraction = 0.003), whereby DM was associated with a more concentric left ventricular geometry in women than men. Women had lower quality of life than men (P < 0.001), in both DM and non-DM groups. DM was associated with worse composite outcomes at 1 year in women vs. men [hazard ratio (HR) 1.79, 95% CI 1.24-2.60 vs. HR 1.32, 95% CI 1.12-1.56; Pinteraction = 0.005). Asian women with HFrEF were more likely to have DM despite a lean body mass index, a greater burden of chronic kidney disease and more concentric left ventricular geometry, compared to men. Furthermore, DM confers worse quality of life, irrespective of sex, and a greater risk of adverse outcomes in women than men. These data underscore the need for sex-specific approaches to diabetes in patients with HF.

Development and validation of warning system of ventricular tachyarrhythmia in patients with heart failure with heart rate variability data.

Implantable-cardioverter defibrillators (ICD) detect and terminate life-threatening ventricular tachyarrhythmia with electric shocks after they occur. This puts patients at risk if they are driving or in a situation where they can fall. ICD’s shocks are also very painful and affect a patient’s quality of life. It would be ideal if ICDs can accurately predict the occurrence of ventricular tachyarrhythmia and then issue a warning or provide preventive therapy. Our study explores the use of ICD data to automatically predict ventricular arrhythmia using heart rate variability (HRV). A 5 minute and a 10 second warning system are both developed and compared. The participants for this study consist of 788 patients who were enrolled in the ICD arm of the Sudden Cardiac Death–Heart Failure Trial (SCD-HeFT). Two groups of patient rhythms, regular heart rhythms and pre-ventricular-tachyarrhythmic rhythms, are analyzed and different HRV features are extracted. Machine learning algorithms, including random forests (RF) and support vector machines (SVM), are trained on these features to classify the two groups of rhythms in a subset of the data comprising the training set. These algorithms are then used to classify rhythms in a separate test set. This performance is quantified by the area under the curve (AUC) of the ROC curve. Both RF and SVM methods achieve a mean AUC of 0.81 for 5-minute prediction and mean AUC of 0.87–0.88 for 10-second prediction; an AUC over 0.8 typically warrants further clinical investigation. Our work shows that moderate classification accuracy can be achieved to predict ventricular tachyarrhythmia with machine learning algorithms using HRV features from ICD data. These results provide a realistic view of the practical challenges facing implementation of machine learning algorithms to predict ventricular tachyarrhythmia using HRV data, motivating continued research on improved algorithms and additional features with higher predictive power.

β2 adrenergic receptor activation governs cardiac repolarization and arrhythmogenesis in a guinea pig model of heart failure.

β2-AR activation increases the risk of sudden cardiac death (SCD) in heart failure (HF) patients. Non-selective β-AR blockers have greater benefits on survival than selective β1-AR blockers in chronic HF patients, indicating that β2-AR activation contributes to SCD in HF. This study investigated the role of β2-AR activation on repolarization and ventricular arrhythmia (VA) in the experimental HF model. The guinea pig HF was induced by descending aortic banding. The effective refractoriness period (ERP), corrected QT (QTc) and the incidence of VA were examined using Langendorff and programmed electrical stimulation. Ikr and APD were recorded by the whole cell patch clamp. Selective β2-AR agonist salbutamol significantly increased the incidence of VA, prolonged QTc and shortened ERP. These effects could be prevented by the selective β2-AR antagonist, ICI118551. Salbutamol prolonged APD90 and reduced Ikr in guinea pig HF myocytes. The antagonists of cAMP (Rp-cAMP) and PKA (KT5720) attenuated Ikr inhibition and APD prolongation induced by salbutamol. However, the antagonists of Gi protein (PTX) and PDE III (amrinone) showed opposite effects. This study indicates that β2-AR activation increases the incidence of VA in the experimental HF model via activation of Gs/cAMP/PKA and/or inhibition of Gi/PDE pathways.

Long-term Follow-up in the Sudden Cardiac Death Heart Failure Trial (SCD-HEFT)

Background: Sudden Cardiac Death Heart Failure Trial (SCD-HeFT) began in 1997 and remains the only placebo-controlled implantable cardioverter-defibrillator (ICD) trial, testing amiodarone vs placebo and single-lead shock-only ICD therapy vs placebo for the prevention of death in congestive heart failure. A total of 2521 patients were randomized on a 1:1:1 basis in the 3 arms. Initial follow-up ended October 31, 2003. Amiodarone was shown to be unhelpful, and ICD therapy provided a 23% survival advantage over a median 45.5-month follow-up period.

Thromboembolism and Antithrombotic Therapy in Patients With Heart Failure in Sinus Rhythm

Heart failure (HF) represents a major and growing public health problem because of its prevalence, incidence, morbidity, mortality, and economic costs. The prevalence of HF is 2% to 3% of the general population.1 Five million Americans are affected, with >550 000 cases diagnosed each year.2 The mortality rate from severe HF remains >60% within 5 years of diagnosis, and 50% of hospitalized patients with HF require readmission within 6 months of discharge. In the US estimated costs amount to > $35 billion per year.3 Although several therapies (eg, β-blockers, angiotensin-converting enzyme [ACE] inhibitors, and cardiac resynchronization therapy) have been proven effective in improving HF outcomes, many unanswered questions about optimal treatment remain. One area of ongoing uncertainty is the appropriate role for antithrombotic therapy in patients with HF. Observational data suggest that patients with HF have an increased venous thromboembolism (VTE) risk (deep venous thromboembolism [DVT], pulmonary embolism [PE], peripheral arterial thromboembolism, and stroke).4 These epidemiological findings are supported by multiple mechanisms that can contribute to a hypercoagulable state in patients with HF. Despite this increased risk of VTE, the role of antithrombotic therapy remains unclear. In this article, we provide an overview of epidemiology, pathophysiology, clinical trial data, and therapeutic recommendations for prevention of thromboembolism in HF. We searched PubMed for articles published between 1958 and 2010 using the following search terms: epidemiology of heart failure , thromboembolism and heart failure , thrombogenesis and heart failure , anticoagulation in heart failure , antiplatelet agent and heart failure , aspirin and heart failure , bleeding risk and anticoagulation , and aspirin and angiotensin-converting enzyme inhibitors . We also studied abstracts from national and international cardiovascular meetings to identify unpublished studies using the key words anticoagulation and dilated cardiomyopathy . Data from published observational studies and secondary …

Combining Shock Reduction Strategies to Enhance ICD Therapy: A Role for Computer Modeling

To develop a computer model to test shock reduction strategies such as antitachycardia pacing and shock withholding for supraventricular rhythms, oversensing, and nonsustained ventricular tachycardia. While the implantable cardioverter defibrillator (ICD) can reduce mortality, inappropriate ICD shocks remain a limitation. Randomized trials provide evidence of efficacy, but they are not always practical. Computer models provide an alternative approach, and are particularly useful when evaluating multiple interventions. A computer model was developed using clinical data and validated in a large ICD data set (EMPIRIC). After validation, the model was applied to 736 adjudicated clinical episodes from the ICD arm of Sudden Cardiac Death Heart Failure Trial (SCD-HeFT). The shock reduction strategies hypothetically reduced the number of VT/VF shocked episodes in SCD-HeFT by an estimated 59% (from 952 observed to 395 modeled shocks, probability of >0.999) at detection duration settings (18 of 24 intervals). The percentage of patients experiencing inappropriate shocks over 5 years was decreased by 15% (23.5-8.4%), and the number of shocks for non-VT/VF episodes was decreased from 423 to 77 (82% reduction). The percentage of patients receiving shocks for VT/VF was reduced from 30.7% (SCD-HeFT) to 26.1% with the addition of ATP. Extended detection (24 of 32 or 30 of 40 intervals) showed modest additional improvement compared to 18 of 24 intervals. Computer modeling is able to predict the results of a known clinical trial and demonstrate that shock reduction strategies have the potential to significantly reduce inappropriate and unnecessary ICD shocks versus the mandated programming used in SCD-HeFT.

Usefulness of the Duke Sudden Cardiac Death Risk Score for Predicting Sudden Cardiac Death in Patients With Angiographic (>75% Narrowing) Coronary Artery Disease

The currently available sudden cardiac death (SCD) risk prediction tools fail to identify most at-risk patients and cannot delineate a specific patient's SCD risk. We sought to develop a tool to improve the risk stratification of patients with coronary artery disease. Clinical, demographic, and angiographic characteristics were evaluated among 37,258 patients who had undergone coronary angiography from January 1, 1985 to May 31, 2005, and who were found to have at least one native coronary artery stenosis of > or =75%. After a median follow-up of 6.2 years, SCD had occurred in 1,568 patients, 14,078 patients had died from other causes, and 21,612 patients remained alive. A Cox proportional hazards model identified 10 independent patient characteristic variables significantly associated with SCD. A simplified model accounting for 97% of the predictive capacity of the full model included the following 7 variables: depressed left ventricular ejection fraction, number of diseased coronary arteries, diabetes mellitus, hypertension, heart failure, cerebrovascular disease, and tobacco use. The Duke SCD risk score was created from the simplified model to predict the likelihood of SCD among patients with coronary artery disease. It was internally validated with bootstrapping (c-index = 0.75, chi-square = 1,220.8) and externally validated in patients with ischemic cardiomyopathy from the Sudden Cardiac Death Heart Failure Trial (SCD-HeFT) database (c-index = 0.64, chi-square = 14.1). In conclusion, the Duke SCD risk score represents a simple, validated method for predicting the risk of SCD among patients with coronary artery disease and might be useful for directing treatment strategies designed to mitigate the risk of SCD.

Clinical Summaries

Clinical Summaries

Indications for ICD and cardiac resynchronization therapy for prevention of sudden cardiac death

The implantable cardioverter–defibrillator (ICD) is used for primary and secondary prophylaxis of sudden cardiac death in high-risk patients. While several trials have demonstrated the superiority of ICD over standard medical therapy or antiarrhythmic medication in this population, a few trials have not shown survival benefit. The Multicenter Automatic Defibrillator Implant Trial II study revealed that ICD reduces mortality in patients with ischemic cardiomyopathy. The Sudden Cardiac Death-Heart Failure Trial demonstrated that the ICD prevents sudden cardiac death and all-cause mortality in high-risk patients with moderate ischemic and nonischemic cardiomyopathy and heart failure. The ICD is also recommended for high-risk patients with inherited arrhythmia or cardiomyopathy. Cardiac resynchronization therapy reduces mortality and heart failure class as compared with optimal medical therapy in advanced heart failure. The high economic cost of widespread ICD use must also be considered. Therefore, it is prudent to identify a high-risk population who will benefit most from these devices.

Abstract 4357: Soluble ST-2 Concentrations to Predict Sudden Cardiac Death in Stable Heart Failure Patients

Background &amp; Aim: The soluble form of the ST2 receptor (sST2) is released, like B-natriopeptides, by cardiomyocytes in response to mechanical overload. sST2 has been shown useful for predicting short- and long-term risk in heart failure (HF). Sudden cardiac death (SCD) is a poorly predictable HF-complication; we previously showed that NT-proBNP and left atrial size (LA) were prognostic of SCD in a cohort of stable HF patients. Since NT-proBNP and sST2 share some common features, we evaluated the role of sST2 to predict SCD in HF. Patients &amp; Methods: A 1:2 case:control design was used. Ninety-nine stable HF patients were included and followed during 3 years (942±323 days); 36 suffered SCD (Cases) and 63 survived (Controls). Cases and Controls were matched by age (66±11 years), sex (83% male) and LVEF (mean: 29%). NT-proBNP and sST2 were measured by immunoassays in serum/ plasma samples collected at inclusion; clinical information was recorded at inclusion and during follow-up. Results: Cases had more often prior history of ischemic disease (72 vs 44%) and AMI (64 vs 41%), lower eGFR (54 vs 64 mL/min) and higher NYHA class (50 vs 22% in class III), LA (27 vs 23 mm/m 2 ) and NT-proBNP (2873 vs 966 ng/L) than Controls (all variables, p&lt;0.05). sST2 was higher in Cases (0.232 vs 0.121 ng/L, p=0.002) and unrelated to eGFR. ROC analysis of sST2 and NT-proBNP showed optimal cut-points to predict SCD of 0.152 and 2005 ng/L, respectively. sST2 values &gt; 0.152 ng/L were found in 78% of Cases and 44% of Controls (p&lt;0.001). In multivariable analysis sST2, NT-proBNP, eGFR and LA were independent predictors of SCD. When sST2 and NT-proBNP concentrations (dichotomized by the set cut-points) were analyzed combined as a single variable the OR to predict SCD raised to 21.857 (95% CI: 2.655–179.909, p=0.004). eGFR and indexed LA size were weaker predictors of SCD (OR: 1.665 and 1.157, respectively). The area under ROC of the combined variable to predict SCD was 0.869 (95% CI: 0.798 – 0.940). Conclusions: sST2 is a novel biomarker for SCD prediction in stable HF patients. A multimarker approach using sST2 and NT-proBNP improves the identification of HF patients at high risk of SCD.

Syncope Predicts the Outcome of Cardiomyopathy Patients: Analysis of the SCD-HeFT Study

The outcome of congestive heart failure (CHF) patients with syncope is understood incompletely.We analyzed data from patients enrolled in the SCD-HeFT (Sudden Cardiac Death Heart Failure Trial) to determine whether syncope predicted outcomes in patients with CHF.We compared outcomes (and associated clinical characteristics) in patients with and without syncope enrolled in SCD-HeFT.In SCD-HeFT, 162 (6%) patients had syncope before randomization, 356 (14%) had syncope after randomization (similar incidence in each randomized arm), and 46 (2%) had syncope before and after randomization. A QRS duration >or=120 ms and absence of beta-blocker use predicted syncope during follow-up (hazard ratio [HR] 1.30 and 95% confidence interval [CI] 1.06 to 1.61, p = 0.014 and HR 1.25, 95% CI 1.01 to 1.56, p = 0.048, respectively). Syncope recurrence did not differ by randomization arm. However, in the implantable cardioverter-defibrillator (ICD) arm, syncope, before and after randomization, was associated with appropriate ICD discharges (HR 1.75, 95% CI 1.10 to 2.80, p = 0.019 and HR 2.91, 95% CI 1.89 to 4.47, p = 0.001, respectively). Post-randomization syncope predicted total and cardiovascular death (HR 1.41, 95% CI 1.13 to 1.76, p = 0.002 and HR 1.55, 95% CI 1.19 to 2.02, p = 0.001, respectively). The elevated relative risk of mortality for syncope versus non-syncope patients did not vary significantly across treatment arms (ICD, HR 1.54, 95% CI 1.04 to 2.27; amiodarone, HR 1.33, 95% CI 0.91 to 1.93; and placebo, HR 1.39, 95% CI 0.96 to 2.02, test for difference p = 0.86).For CHF patients with ICDs, syncope was associated with appropriate ICD activations. Syncope was associated with increased mortality risk in SCD-HeFT regardless of treatment arm (placebo, amiodarone, or ICD).

Value of Microvolt T-Wave Alternans for Predicting Patients Who Would Benefit from Implantable Cardioverter–Defibrillator Therapy

Despite considerable progress in the management of coronary artery disease and dilated cardiomyopathy, a substantial proportion of patients remains at the risk of life-threatening arrhythmic events. The Multicenter Automatic Defibrillator Implantation II and Sudden Cardiac Death Heart Failure studies have conclusively demonstrated that prophylactic implantable cardioverter-defibrillator (ICD) therapy reduces mortality among subjects with ischemic and nonischemic cardiomyopathy but at the expense of potentially unnecessary ICD implantation in a large percentage of patients. Microvolt T-wave alternans (MTWA), with a negative predictive value greater than 90%, holds promise for selecting the patients who would likely and patients not likely to benefit from ICD implantation. Accurate identification of high-risk patients by noninvasive MTWA may allow for improved widespread screening for sudden death prevention in the general population.

Implantable cardiac arrhythmia devices—Part II: Implantable cardioverter defibrillators and implantable loop recorders

Implantable cardiac devices have become firmly entrenched as important therapeutic tools for a variety of cardiac conditions. The second part of this two-part review discusses the contemporary use and follow-up of implantable cardioverter defibrillators (ICD) and the implantable loop recorder. The ICD has become the standard therapy for protecting patients against sudden cardiac death. Two recent trials, the Multicenter Automatic Defibrillator Trial II (MADIT II) and the Sudden Cardiac Death Heart Failure Trial (SCD-HEFT), demonstrated that the ICD is associated with a significant survival benefit for patients with reduced ejection fraction (< 0.30-0.35), particularly if heart failure symptoms are present. The ICD has an important role in the management of other conditions associated with a high risk for sudden death, such as hypertrophic cardiomyopathy, long QT syndrome, and Brugada syndrome. The implantable loop recorder has become an important diagnostic tool for the patient with unexplained syncope.

AB19-3: Failure of spironolactone to reduce mortality or the need for an ICD in chronic moderate heart failure: Observations from the sudden cardiac death heart failure trial

Aldosterone blockade in severe heart failure (HF) and post-infarction HF reduces mortality and strongly reduces sudden cardiac death (SCD). Its benefit in chronic moderate HF and in those moderate HF patients with an implantable defibrillator (ICD) is unknown.

Beyond Heart Rhythms: New Directions for Implantable Devices

Implantable cardiac devices have become firmly entrenched as important therapeutic tools for a variety of conditions. Pacemakers are the only available treatment for symptomatic bradycardia not due to reversible causes. Large randomized studies have demonstrated a small but statistically significant reduction in atrial fibrillation associated with pacing modes that maintain atrioventricular synchrony. In contrast, pacing mode appears to have a less dramatic effect in patients with atrioventricular block. Cardiac resynchronization with specialized left ventricular leads has been shown to reduce symptoms and improve survival in patients with symptomatic heart failure, systolic dysfunction, and widened QRS complexes. The implantable cardioverter defibrillator has become the standard therapy for protecting patients against sudden cardiac death. Two recent trials, Multicenter Automatic Defibrillator Trial II (MADIT II) and the Sudden Cardiac Death Heart Failure Trial (SCD-HEFT), demonstrated that the ICD is associated with a significant survival benefit for patients with reduced ejection fraction (< 0.30-0.35) particularly if heart failure symptoms are present. Finally the implantable loop recorder has become an important diagnostic tool for the patient with unexplained syncope. This brief overview summarizes the indications and follow-up of the wide array of implantable cardiac devices available to the clinical cardiologist.

The role of prophylactic implantable cardioverter defibrillators in heart failure: Recent trials usher in a new era of device therapy

Sudden cardiac death (SCD) manifested as ventricular fibrillation or sustained ventricular tachycardia has been a major focus of cardiovascular research for more than three decades. Although mortality in patients with heart failure (HF) caused by left ventricular systolic dysfunction has declined in recent years through effective pharmacotherapeutic strategies, SCD remains the major cause of death in symptomatic HF, with little improvement by drug therapy. Although it is clear that the implantable cardioverter defibrillator (ICD) is efficacious and should be used to prevent a recurrence of sustained ventricular arrhythmia (secondary prevention) in most patients, the guidelines for prophylactic use of ICDs (primary prevention) are less well defined. The results of recent clinical trials examining the efficacy of prophylactic ICD therapy in HF patients have clarified the role of ICD treatment in this population. This article reviews these trials and summarizes our current approach to the prevention of SCD in HF.

Current role of device therapy to reduce sudden cardiac death in heart failure

Sudden cardiac death (SCD) continues to be a major contributor to mortality in patients with heart failure (HF) despite recent advances in medical therapy. Device therapy, including the implantable cardioverter defibrillator (ICD) and cardiac resynchronization therapy (CRT), serves as an adjunct in reducing HF mortality. Several clinical trials support the prophylactic use of the ICD in reducing mortality in certain HF populations and have established the clinical benefits of CRT in advanced HF. More recently, the Comparison of Medical Therapy Pacing and Defibrillation in Heart Failure trial was the first study to demonstrate a survival benefit of CRT alone or in conjunction with an ICD. This article reviews the most pertinent data regarding the role of device therapy in reducing SCD in HF and addresses future challenges faced by device manufacturers and clinicians.