Reduction In Sudden Cardiac Death Research Articles

Omega-3 Fatty Acids and Arrhythmias.

The pro- and antiarrhythmic effects of omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been extensively studied in preclinical and human trials. Despite early evidence of an antiarrhythmic role of n-3 PUFA in the prevention of sudden cardiac death and postoperative and persistent atrial fibrillation (AF), subsequent well-designed randomized trials have largely not shown an antiarrhythmic benefit. Two trials that tested moderate and high-dose n-3 PUFA demonstrated a reduction in sudden cardiac death, but these findings have not been widely replicated, and the potential of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) to reduce arrhythmic death in combination, or as monotherapy, remains uncertain. The accumulated clinical evidence does not support supplementation of n-3 PUFA for postoperative AF or secondary prevention of AF. Several large, contemporary, randomized controlled trials of high-dose n-3 PUFA for primary or secondary cardiovascular prevention have demonstrated a small, significant, dose-dependent increased risk of incident AF compared with mineral oil or corn oil comparator. These findings were reproduced with both icosapent ethyl monotherapy and a mixed EPA+DHA formulation. The proarrhythmic mechanism of increased AF in contemporary cohorts exposed to high-dose n-3 PUFA is unknown. EPA and DHA and their metabolites have pleiotropic cardiometabolic and pro- and antiarrhythmic effects, including modification of the lipid raft microenvironment; alteration of cell membrane structure and fluidity; modulation of sodium, potassium, and calcium currents; and regulation of gene transcription, cell proliferation, and inflammation. Further characterization of the complex association between EPA, EPA+DHA, and DHA and AF is needed. Which formulations, dose ranges, and patient subgroups are at highest risk, remain unclear.

Development of the NOCSAE Standard to Reduce the Risk of Commotio Cordis.

Commotio cordis, sudden cardiac death (SCD) caused by relatively innocent impact to the chest, is one of the leading causes of SCD in sports. Commercial chest protectors have not been demonstrated to mitigate the risk of these SCDs. To develop a standard to assess chest protectors, 4 phases occurred. A physiological commotio cordis model was utilized to assess variables that predicted for SCD. Next, a surrogate model was developed based on data from the physiological model, and the attenuation in risk was assessed. In the third phase, this model was calibrated and validated. Finally, National Operating Committee on Standards for Athletic Equipment adopted the standard and had an open review process with revision of the standard over 3 years. Of all variables, impact force was the most robust at predicting SCD. Chest wall protectors which could reduce the force of impact to under thresholds were predicted to reduce the risk of SCD. The correlation between the experimental model and the mechanical surrogate ranged from 0.783 with a lacrosse ball at 30 mph to 0.898 with a baseball at 50 mph. The standard was licensed to National Operating Committee on Standards for Athletic Equipment which initially adopted the standard in January 2018, and finalized in July 2021. An effective mechanical surrogate based on physiological data from a well-established model of commotio cordis predicts the reduction in SCD with chest protectors. A greater reduction in force provides a great degree of protection from commotio cordis. This new National Operating Committee on Standards for Athletic Equipment standard for chest protectors should result in a significant reduction in the risk of commotio cordis on the playing field.

Abstract 12506: Implantable Cardioverter Defibrillators for Primary Prevention in Patients With Ischemic and Non Ischemic Cardiomyopathy: A Meta-Analysis of 15 Randomized Controlled Trial

Background: The evidence to support implantable cardioverter defibrillator (ICD) in patients with ischemic and nonischemic cardiomyopathy for prevention of sudden cardiac death (SCD) is not robust, with conflicting results in randomized controlled trials. Objective: We aim to evaluate the impact of ICD therapy with conventional care for the primary prevention of death of various causes in adults with ischemic and nonischemic cardiomyopathy. Methods: We performed a systematic literature search on the electronic database for relevant articles from inception until 15th May 2022. Results: A total of 15 randomized controlled trials involving 9,999 patients: 9 (6523 patients) addressed ischemic cardiomyopathy, and 6 studies (3476 patients) reported nonischemic cardiomyopathy. The mean follow-up duration was 3.02 years. Pooled analysis showed that ICD therapy significantly reduced the risk of ACM (HR, 0.75(95%CI: 0.64-0.88), P<0.001) from the control group. The magnitude of reduction was similar with ischemic (HR, 0.75(95%CI: 0.58-0.96), P=0.02), nonischemic (HR, 0.76(95%CI: 0.64-0.90), P<0.01). There was 67% reduction in SCD among ICD therapy group (OR, 0.33(95%CI: 0.25-0.44), P<0.00001) compared to the control, a similar trend was observed in both ischemic (OR, 0.39(95%CI: 0.28-0.56), P<0.00001), and nonischemic cardiomyopathy (OR, 0.24(95%CI: 0.15-0.38), P<0.00001). The ICD therapy group had a significant reduction of 65% reduction in arrhythmia-related death compared to control in ischemic cardiomyopathy (OR, 0.35(95%CI: 0.19-0.64), P<0.001). However, there was a trend of 23% in cardiovascular mortality in the ICD group (OR, 0.77(95%CI: 0.58-1.02), P=0.07) but unable to reach statistical significance. Conclusion: Overall, primary prevention with ICD therapy reduced the incidence of all-cause mortality and sudden cardiac death among ischemic and nonischemic cardiomyopathy patients.

The athlete's ECG : What is normal or abnormal?

The electrocardiogram (ECG) has become amobile and cost-effective routine assessment tool to risk stratify leisure-time and professional athletes during preparticipation screening. A central goal is the reduction of sudden cardiac death in sports through early recognition of the most prevalent underlying cardiac pathologies, e.g., hereditary cardiomyopathies or primary arrhythmias. Continuous evolution of the first ECG criteria for athletes, presented in 2010 by the European Society of Cardiology (ESC), has helped to improve the specificity of the criteria to both detect cardiac pathologies in early stages and differentiate from physiologic adaptation of the athlete's heart. Thus, the risk of false-positive findings and erroneous stigmatizations of athletes has been successfully reduced. This review article intends to trace back the changes of the ECG criteria in the light of agrowing body of scientific evidence over the last 15years, to present the key messages of the current International ECG criteria from 2017 and to identify some of the remaining challenges that wait to be answered by physicians in the field of sports medicine and sports cardiology.

The Impact of Angiotensin Receptor-Neprilysin Inhibitors on Arrhythmias in Patients with Heart Failure: A Systematic Review and Meta-analysis.

Angiotensin receptor–neprilysin inhibitor (ARNI) use has become increasingly popular. Current guidelines recommend using ARNI therapy for heart failure with reduced (HFrEF) and preserved ejection fraction (HFpEF). As therapies become more widely available, heart failure-associated burdens such as ventricular arrhythmias and sudden cardiac death (SCD) will become increasingly prevalent. We conducted a systematic review and meta-analysis to assess the impact of ARNI therapy on HFrEF and HFpEF pertaining to arrhythmogenesis and SCD. We performed a search of MEDLINE (PubMed), the Cochrane Library, and ClinicalTrials.gov for relevant studies. The odds ratios (ORs) of SCD, ventricular tachycardia (VT), ventricular fibrillation (VF), atrial fibrillation/flutter (AF), supraventricular tachycardia (SVT), and implantable cardioverter-defibrillator (ICD) shocks were calculated. A total of 10 studies, including 6 randomized controlled trials and 4 observational studies, were included in the analysis. A total of 18,548 patients from all studies were included, with 9,328 patients in the ARNI arm and 9,220 patients in the angiotensin-converting enzyme inhibitor (ACEI)/angiotensin II receptor blocker (ARB) arm, with a median follow-up time of 15 months. There was a significant reduction in the composite outcomes of SCD and ventricular arrhythmias in patients treated with ARNIs compared to those treated with ACEIs/ARBs (OR, 0.71; 95% confidence interval, 0.54–0.93; P = .01; I2 = 17%; P = .29). ARNI therapy was also associated with a significant reduction in ICD shocks. There was no significant reduction in the VT, VF, AF, or SVT incidence rate in the ARNI group compared to the ACEI/ARB group. In conclusion, the use of ARNIs confers a reduction in composite outcomes of SCD and ventricular arrhythmias among patients with heart failure. These outcomes were mainly driven by SCD reduction in patients treated with ARNIs.

Prevention of sudden death in heart failure with reduced ejection fraction: do we still needan implantable cardioverter-defibrillator for primary prevention?

Sudden death is a devastating complication of heart failure (HF). Current guidelines recommend an implantable cardioverter-defibrillator (ICD) for prevention of sudden death in patients with HF and reduced ejection fraction (HFrEF) specifically those with a left ventricular ejection fraction ≤35% after at least 3 months of optimized HF treatment. The benefit of ICD in patients with symptomatic HFrEF caused by coronary artery disease has been well documented; however, the evidence for a benefit of prophylactic ICD implantation in patients with HFrEF of non-ischaemic aetiology is less strong. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, beta-blockers (BB), and mineralocorticoid receptor antagonists (MRA) block the deleterious actions of angiotensin II, norepinephrine, and aldosterone, respectively. Neprilysin inhibition potentiates the actions of endogenous natriuretic peptides that mitigate adverse ventricular remodelling. BB, MRA, angiotensin receptor-neprilysin inhibitor (ARNI) have a favourable effect on reduction of sudden cardiac death in HFrEF. Recent data suggest a beneficial effect of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in reducing serious ventricular arrhythmias and sudden cardiac death in patients with HFrEF. So, in the current era of new drugs for HFrEF and with the optimal use of disease-modifying therapies (BB, MRA, ARNI and SGLT2i), we might need to reconsider the need and timing for use of ICD as primary prevention of sudden death, especially in HF of non-ischaemic aetiology.

Neglected Tropical Diseases and Sudden Cardiac Death: The NET-Heart Project.

Sudden cardiac death (SCD) is responsible for approximately 6% of global mortality and 25% of cardiovascular (CV) deaths. SCD has been traditionally linked to coronary artery disease, valvular heart disease, cardiomyopathies, and genetic arrhythmia disorders. However, advancements in care for these diseases have not translated to a proportional reduction in SCD. This suggests an important role of underrecognized contributing pathologies. Neglected tropical diseases (NTDs) are a group of illnesses prevalent in tropical and sub-tropical regions which have been understudied partially due to their high prevalence in marginalized populations. The relationship between SCD and Chagas disease has been well-established, though emerging literature suggests that other NTDs with CV involvement may lead to fatal arrhythmias. Additionally, specific therapies for a subset of NTDs put patients at increased risk of malignant arrhythmias and other cardiac complications. This review aims to summarize the association between a group of selected NTDs and SCD.

HF-567-02 SACUBITRIL-VALSARTAN AND BURDEN OF VENTRICULAR ARRHYTHMIA: A META-ANALYSIS

PARADIGM-HF showed a reduction in sudden cardiac death with Sacubitril-Valsartan (SV) use compared to enalapril in patients with heart failure with reduced ejection fraction (HFrEF). However, it is not clear if there is significant reduction in ventricular arrhythmias due to SV.

Prevalence of Arrhythmic Events in Paediatric Patients with Congenital Heart Disease-A Retrospective Study

Introduction: Various types of arrhythmias occur in patients with Congenital Heart Disease (CHD) and are the leading cause of morbidity and mortality. Knowledge regarding arrhythmias in CHD is important for safe and effective management of arrhythmia and in reduction of sudden cardiac deaths. Aim: To assess the profile of various arrhythmic events in children with CHD. Materials and Methods: A retrospective study was conducted over the period of three years (January 2018 to December 2020). Data were collected from the Department of Paediatrics of a tertiary care hospital in Durgapur, West Bengal, India. A total of 232 children of the age group 0-18 years, diagnosed with CHD were included in this study. Children who underwent cardiac intervention were excluded from the study. Age, sex, age at diagnosis, nature of CHD, clinical findings, Electrocardiogram (ECG) findings were recorded. Data analysis was performed using Fisher’s-exact test on Statistical Package for the Social Sciences (SPSS) 27.0 A p-value <0.05 was considered as statistically significant. Results: A 20.3% children of 0-18 years of age with CHD had conduction abnormalities. Statistically significant association was found between atrial septal defect with Atrial Fibrillation (AF) (p-value <0.001) and atrial flutter (p-value=0.008), Ventricular Septal Defect (VSD) with Premature Ventricular Contractions (PVC) (p-value=0.0001), Atrioventricular (AV) canal defect with first degree AV block with (p-value=0.0004), Tetralogy Of Fallot (TOF) with Ventricular Tachycardia (VT) (p-value=0.021), L-Transposition of Great Vessels (L-TGA) with complete AV block (p-value=0.012), Ebstein’s anomaly with Supraventricular Tachycardia (SVT) (p-value <0.001). Conclusion: Specific conduction abnormalities are significantly associated with specific CHD. These results demand attention for effective management of arrhythmia and reduction of sudden cardiac death in children with CHD.

LEFT VENTRICULAR LEAD IMPLANTATION FOR DETECTION OF VENTRICULAR ARRHYTHMIAS IN PATIENT WITH IMPLANTABLE CARDIOVERTER DEFIBRILLATOR AND LOW R WAVE IN RIGHT VENTRICLE

Dilated cardiomyopathy (DCM) is a disease characterised as left ventricular (LV) or biventricular dilatation with impaired systolic function. Regardless of underlying cause patients with DCM have a propensity to ventricular arrhythmias and sudden cardiac death. Implantable Cardioverter Defibrillator (ICD) implantation for these patients results in significant reduction of sudden cardiac death [1-3]. ICD devices may be limited by right ventricle (RV) sensing dysfunction with low RV sensing amplitude. We present a clinical case of patient with DCM, implanted ICD and low R wave sensing on RV lead.

Effect of icosapent ethyl on susceptibility to ventricular arrhythmias in postinfarcted rat hearts: Role of GPR120-mediated connexin43 phosphorylation.

The ω‐3 fatty acids exert as an antioxidant via the G protein‐coupled receptor 120 (GPR120). Icosapent ethyl, a purified eicosapentaenoic acid, showed a marked reduction in sudden cardiac death. Connexin43 is sensitive to redox status. We assessed whether icosapent ethyl attenuates fatal arrhythmias after myocardial infarction, a status of high oxidative stress, through increased connexin43 expression and whether the GPR120 signalling is involved in the protection. Male Wistar rats after ligating coronary artery were assigned to either vehicle or icosapent ethyl for 4 weeks. The postinfarction period was associated with increased oxidative‐nitrosative stress. In concert, myocardial connexin43 levels revealed a significant decrease in vehicle‐treated infarcted rats compared with sham. These changes of oxidative‐nitrosative stress and connexin43 levels were blunted after icosapent ethyl administration. Provocative arrhythmias in the infarcted rats treated with icosapent ethyl were significantly improved than vehicle. Icosapent ethyl significantly increased GPR120 compared to vehicle after infarction. The effects of icosapent ethyl on superoxide and connexin43 were similar to GPR120 agonist GW9508. Besides, the effects of icosapent ethyl on oxidative‐nitrosative stress and connexin43 phosphorylation were abolished by administering AH‐7614, an inhibitor of GPR120. SIN‐1 abolished the Cx43 phosphorylation of icosapent ethyl without affecting GPR120 levels. Taken together, chronic use of icosapent ethyl after infarction is associated with up‐regulation of connexin43 phosphorylation through a GPR120‐dependent antioxidant pathway and thus plays a beneficial effect on arrhythmogenic response to programmed electrical stimulation.

GPR120‐mediated Connexin43 Phosphorylation is Implicated in Antiarrhythmic Effects of Icosapent Ethyl in Post‐infarcted Rat Hearts

AimsThe w‐3 fatty acids exert as an antioxidant via the G protein‐coupled receptor 120 (GPR120). Icosapent ethyl, a highly purified ethyl ester of eicosapentaenoic acid, showed a marked reduction in sudden cardiac death. Connexin43 is sensitive to redox status. We assessed whether icosapent ethyl attenuates fatal arrhythmias after myocardial infarction, a status of high oxidative stress, through increased connnexin43 expression and whether the GPR120 signaling is involved in the protection.Methods and resultsMale Wistar rats after ligating coronary artery were randomized to either vehicle or icosapent ethyl for 4 weeks. The postinfarction period was associated with increased oxidative‐nitrosative stress, as measured by myocardial superoxide, nitrotyrosine, and dihydroethidium fluorescent staining. In concert, myocardial connnexin43 levels revealed a significant decrease in vehicle‐treated infarcted rats compared with sham. These changes of oxidative‐nitrosative stress and connnexin43 levels were blunted after icosapent ethyl administration. Provocative arrhythmias in the infarcted rats treated with icosapent ethyl were significantly improved than vehicle. Icosapent ethyl significantly increased GPR120 compared to vehicle after infarction. The effects of icosapent ethyl on superoxide and connnexin43 were similar to GPR120 agonist GW9508. Besides, the effects of icosapent ethyl on oxidative‐nitrosative stress and connnexin43 phosphorylation were abolished by administering AH‐7614, an inhibitor of GPR120. SIN‐1 abolished the Cx43 phosphorylation of IPE without affecting GPR120 levels.ConclusionsChronic use of icosapent ethyl after infarction is associated with up‐regulation of connnexin43 phosphorylation through a GPR120‐dependent antioxidant pathway and thus plays a role in the beneficial effect on arrhythmogenic response to programmed electrical stimulation.Support or Funding InformationThis work was supported by the grants of China Medical University (DMR‐108‐035) and Ministry of Science and Technology (MOST‐108‐2622‐B‐039‐002‐CC3), Taiwan.

Changes in causes of death and influence of therapeutic improvement over time in patients with heart failure and reduced ejection fraction.

In patients with heart failure and reduced ejection fraction (HFrEF), several therapies have been proven to reduce mortality in clinical trials. However, there are few data on the effect of the use of evidence-based therapies on causes of death in clinical practice. This study included 2351 outpatients with HFrEF (< 40%) from 2 multicenter prospective registries: MUSIC (n=641, period: 2003-2004) and REDINSCOR I (n=1710, period: 2007-2011). Variables were recorded at inclusion and all patients were followed-up for 4 years. Causes of death were validated by an independent committee. Patients in REDINSCOR I more frequently received beta-blockers (85% vs 71%; P <.001), mineralocorticoid antagonists (64% vs 44%; P <.001), implantable cardioverter-defibrillators (19% vs 2%; P <.001), and resynchronization therapy (7.2% vs 4.8%; P=.04). In these patients, sudden cardiac death was less frequent than in those in MUSIC (6.8% vs 11.4%; P <.001). After propensity score matching, we obtained 2 comparable populations differing only in treatments (575 vs 575 patients). In patients in REDINSCOR I, we found a lower risk of total mortality (HR, 0.70; 95%CI, 0.57-0.87; P=.001) and sudden cardiac death (sHR, 0.46; 95%CI, 0.30-0.70; P <.001), and a trend toward lower mortality due to end-stage HF (sHR, 0.73; 95%CI, 0.53-1.01; P=.059), without differences in other causes of death (sHR, 1.17; 95%CI, 0.78-1.75; P=.445), regardless of functional class. In ambulatory patients with HFrEF, implementation of evidence-based therapies was associated with a lower risk of death, mainly due to a significant reduction in sudden cardiac death.

Cambio en la causa de muerte e influencia de la mejora terapéutica con el tiempo en pacientes con insuficiencia cardiaca y fracción de eyección reducida

Introduction and objectivesIn patients with heart failure and reduced ejection fraction (HFrEF), several therapies have been proven to reduce mortality in clinical trials. However, there are few data on the effect of the use of evidence-based therapies on causes of death in clinical practice. MethodsThis study included 2351 outpatients with HFrEF (< 40%) from 2 multicenter prospective registries: MUSIC (n=641, period: 2003-2004) and REDINSCOR I (n=1710, period: 2007-2011). Variables were recorded at inclusion and all patients were followed-up for 4 years. Causes of death were validated by an independent committee. ResultsPatients in REDINSCOR I more frequently received beta-blockers (85% vs 71%; P <.001), mineralocorticoid antagonists (64% vs 44%; P <.001), implantable cardioverter-defibrillators (19% vs 2%; P <.001), and resynchronization therapy (7.2% vs 4.8%; P=.04). In these patients, sudden cardiac death was less frequent than in those in MUSIC (6.8% vs 11.4%; P <.001). After propensity score matching, we obtained 2 comparable populations differing only in treatments (575 vs 575 patients). In patients in REDINSCOR I, we found a lower risk of total mortality (HR, 0.70; 95%CI, 0.57-0.87; P=.001) and sudden cardiac death (sHR, 0.46; 95%CI, 0.30-0.70; P <.001), and a trend toward lower mortality due to end-stage HF (sHR, 0.73; 95%CI, 0.53-1.01; P=.059), without differences in other causes of death (sHR, 1.17; 95%CI, 0.78-1.75; P=.445), regardless of functional class. ConclusionsIn ambulatory patients with HFrEF, implementation of evidence-based therapies was associated with a lower risk of death, mainly due to a significant reduction in sudden cardiac death.

Heart failure as a substrate and trigger for ventricular tachycardia.

Heart failure (HF) is a major cause of morbidity and mortality with more than 5.1 million individuals affected in the USA. Ventricular tachyarrhythmias (VAs) including ventricular tachycardia and ventricular fibrillation are common in patients with heart failure. The pathophysiology of these mechanisms as well as the contribution of heart failure to the genesis of these arrhythmias is complex and multifaceted. Myocardial hypertrophy and stretch with increased preload and afterload lead to shortening of the action potential at early repolarization and lengthening of the action potential at final repolarization which can result in re-entrant ventricular tachycardia. Myocardial fibrosis and scar can create the substrate for re-entrant ventricular tachycardia. Altered calcium handling in the failing heart can lead to the development of proarrhythmic early and delayed after depolarizations. Various medications used in the treatment of HF such as loop diuretics and angiotensin converting enzyme inhibitors have not demonstrated a reduction in sudden cardiac death (SCD); however, beta-blockers (BB) are effective in reducing mortality and SCD. Amongst patients who have HF with reduced ejection fraction, the angiotensin receptor-neprilysin inhibitor (sacubitril/valsartan) has been shown to reduce cardiovascular mortality, specifically by reducing SCD, as well as death due to worsening HF. Implantable cardioverter-defibrillator (ICD) implantation in HF patients reduces the risk of SCD; however, subsequent mortality is increased in those who receive ICD shocks. Prophylactic ICD implantation reduces death from arrhythmia but does not reduce overall mortality during the acute post-myocardial infarction (MI) period (less than 40days), for those with reduced ejection fraction and impaired autonomic dysfunction. Furthermore, although death from arrhythmias is reduced, this is offset by an increase in the mortality from non-arrhythmic causes. This article provides a review of the aforementioned mechanisms of arrhythmogenesis in heart failure; the role and impact of HF therapy such as cardiac resynchronization therapy (CRT), including the role, if any, of CRT-P and CRT-D in preventing VAs; the utility of both non-invasive parameters as well as multiple implant-based parameters for telemonitoring in HF; and the effect of left ventricular assist device implantation on VAs.

Wearable Cardioverter-Defibrillator Therapy for the Prevention of SuddenCardiac Death: A Systematic Review and Meta-Analysis.

This study sought to synthesize the available evidence on the use of the wearable cardioverter-defibrillator (WCD). Observational WCD studies for the prevention of sudden cardiac death have provided conflicting data. The VEST (Vest Prevention of Early Sudden Death) trial was the first randomized controlled trial (RCT) showing no reduction in sudden cardiac death as compared to medical therapy only. We searched PubMed, EMBASE, and Google Scholar for studies reporting on the outcomes of patients wearing WCDs from January 1, 2001, through March 20, 2018. Rates of appropriate and inappropriate WCD therapies were pooled. Estimates were derived using DerSimonian and Laird's method. Twenty-eight studies were included (N = 33,242; 27 observational, 1 RCT-WCD arm). The incidence of appropriate WCD therapy was 5 per 100 persons over 3 months (95% confidence interval [CI]: 3.0 to 6.0, I2= 93%). In studies on ischemic cardiomyopathy, the appropriate WCD therapy incidence was lower in the VEST trial (1 per 100 persons over 3 months; 95% CI: 1.0 to 2.0) as compared with observational studies (11 per 100 persons over 3 months; 95% CI: 11.0 to 20.0; I2= 93%). The incidence of inappropriate therapy was 2 per 100 persons over 3 months (95% CI: 1.0 to 3.0; I2= 93%). Mortality while wearing WCD was rare at 0.7 per 100 persons over 3 months (95% CI: 0.3 to 1.7; I2= 94%). The rate of appropriately treated WCD patients over 3 months of follow-up was substantial; higherin-observational studies as compared with the VEST trial. There was significant heterogeneity. More RCTs areneeded to justify continued use of WCD in primary prevention.

Implantable cardioverter defibrillator in nonischemic cardiomyopathy: A systematic review and meta-analysis.

The evidence to support implantable cardioverter defibrillator (ICD) in subjects with nonischemic cardiomyopathy (NICM) for primary prevention of sudden cardiac death (SCD) is not robust. This meta‐analysis intends to assess the impact of routine ICD implantation for primary prevention of mortality due to SCD in NICM based on all the published randomized clinical trials (RCTs). Six RCTs were selected using PubMed/Medline, EMBASE, and CENTRAL from inception to December 2016. Outcomes were calculated as random‐effects relative risk (RR) and risk difference (RD) with 95% confidence interval (CI). Patients were randomized to ICD arm and control arm (usual care, medical treatment, and anti‐arrhythmic drugs). ICD significantly reduced all‐cause mortality in NICM patients (RR, 0.74, 95% CI, 0.56‐0.97, P = .03, I2 = 40). Mortality benefit was achieved due to a significant reduction in sudden cardiac death (SCD) (RR, 0.47, 95% CI, 0.30‐0.73, P < .001, I2 = 0). There were no statistical differences between two groups with regard to risk of noncardiac mortality, non‐SCD, cardiac arrest, cardiac transplant, sustained ventricular tachycardia (VT), and VT requiring medical treatment. Our results support efficacy of ICDs at reducing all‐cause mortality due to a reduction in SCD.

Prediction of sudden and non-sudden cardiac death in post-infarction patients with reduced left ventricular ejection fraction by periodic repolarization dynamics: MADIT-II substudy.

AimsTo test the value of Periodic Repolarization Dynamics (PRD), a recently validated electrocardiographic marker of sympathetic activity, as a novel approach to predict sudden cardiac death (SCD) and non-sudden cardiac death (N-SCD) and to improve identification of patients that profit from ICD-implantation.Methods and resultsWe included 856 post-infarction patients with left-ventricular ejection fraction (LVEF) ≤30% of the MADIT-II trial in sinus rhythm. Of these, 507 and 348 patients were randomized to ICD or conventional treatment. PRD was assessed from multipolar 10-min baseline ECGs. Primary and secondary endpoints were total mortality, SCD and N-SCD. Multivariable analyses included treatment group, QRS-duration, New York Heart Association classification, blood-urea nitrogen, diabetes mellitus, beta-blocker therapy and LVEF. During follow-up of 20.4 months, 119 patients died (53 SCD and 36 N-SCD). On multivariable analyses, increased PRD was a significant predictor of mortality (standardized coefficient 1.37[1.19–1.59]; P < 0.001) and SCD (1.40 [1.13–1.75]; P = 0.003) but also predicted N-SCD (1.41[1.10–1.81]; P = 0.006). While increased PRD predicted SCD in conventionally treated patients (1.61[1.23–2.11]; P < 0.001), it was predictive of N-SCD (1.63[1.28–2.09]; P < 0.001) and adequate ICD-therapies (1.20[1.03–1.39]; P = 0.017) in ICD-treated patients. ICD-treatment substantially reduced mortality in the lowest three PRD-quartiles by 53% (P = 0.001). However, there was no effect in the highest PRD-quartile (mortality increase by 29%; P = 0.412; P < 0.001 for difference) as the reduction of SCD was compensated by an increase of N-SCD.ConclusionIn post-infarction patients with impaired LVEF, PRD is a significant predictor of SCD and N-SCD. Assessment of PRD is a promising tool to identify post-MI patients with reduced LVEF who might benefit from intensified treatment.

Prophylactic implantable cardioverter defibrillator in heart failure: the growing evidence for all or Primum non nocere for some?

Heart failure (HF) is a common health problem and has reached epidemic in many western countries. Despite the current era of HF treatment, the risk of sudden cardiac death (SCD) in HF remains significant. Implantable cardioverter defibrillator (ICD) support has been shown to reduce the risk of SCD in patients with HF and impaired left ventricular function. Prophylactic ICD implantation in HF patients seems a logical step to reduce mortality through a reduction in SCD. However, ICD implantation is an invasive procedure, and both short- and long-term complications can occur. This needs to be carefully considered when evaluating the risk-benefit ratio of ICD implantation for individual patients. As the severity of HF increases, the proportion of SCD compared with HF-related deaths decreases. The challenge lies in identifying patients with HF who are at significant risk of SCD and who would most benefit from an ICD in addition to other anti-arrhythmic strategies. This review offers insight on the applicability and practicability of ICD for this growing population.

Programmed Ventricular Stimulation to Risk Stratify for Early Cardioverter-Defibrillator Implantation to Prevent Tachyarrhythmias following Acute Myocardial Infarction (PROTECT-ICD): Trial Protocol, Background and Significance.

The 'Programmed Ventricular Stimulation to Risk Stratify for Early Cardioverter-Defibrillator Implantation to Prevent Tachyarrhythmias following Acute Myocardial Infarction' (PROTECT-ICD) trial is an Australian-led multicentre randomised controlled trial targeting prevention of sudden cardiac death in patients who have at least moderately reduced cardiac function following a myocardial infarct (MI). The primary objective of the trial is to assess whether electrophysiological study to guide prophylactic implantation of an implantable cardioverter-defibrillator (ICD) early following MI (first 40 days) will lead to a significant reduction in sudden cardiac death and non-fatal arrhythmia. The secondary objective is to assess the utility of cardiac MRI (CMR) in assessing early myocardial characteristics, and its predictive value for both inducible ventricular tachycardia (VT) at EPS and SCD/ non-fatal arrhythmia at follow-up.