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Patients with tetralogy of Fallot are at risk for ventricular arrhythmias and sudden cardiac death. These abnormalities are associated with pulmonary regurgitation, right ventricular enlargement, and a substrate of discrete, slowly-conducting isthmuses. Although these arrhythmic events are rare, their prediction is challenging. This review will address contemporary risk assessment and prevention strategies. Numerous variables have been proposed to predict who would benefit from an implantable cardioverter-defibrillator. Current risk stratification models combine independently associated factors into risk scores. Cardiac magnetic resonance imaging, QRS fragmentation assessment, and electrophysiology testing in selected patients may refine some of these models. Interaction between right and left ventricular function is emerging as a critical factor in our understanding of disease progression and risk assessment. Multicenter studies evaluating risk factors and risk mitigating strategies such as pulmonary valve replacement, ablative strategies, and use of implantable cardiac-defibrillators are needed moving forward.

Recent publications have raised serious concerns regarding the safety of digoxin for atrial fibrillation (AF). However, the subgroup of patients with reduced ejection fraction and AF have been speculated to derive clinical benefit from digoxin. We aimed to assess the impact of digoxin on mortality and cardiovascular hospitalizations in the Atrial Fibrillation and Congestive Heart Failure (AF-CHF) trial since all AF-CHF patients had an ejection fraction ≤35% and AF.Using marginal structural modeling, a contemporary statistical method that overcomes limitations of traditional modeling techniques and reduces bias, we assessed the impact of digoxin on the pre-specified primary and secondary outcomes of the AF-CHF trial, i.e., all-cause, cardiac and arrhythmic death as well as cardiovascular hospitalization. Among 1376 patients, 869 (65%) were on digoxin at one-year follow-up. Over a mean (SD) follow-up of 37 (19) months (maximum 74 months), 445 (32%) patients died, 357 (26%) from cardiovascular causes and 159 (12%) from arrhythmic death. Digoxin was significantly associated with all-cause, cardiac, and arrhythmic death, with estimated hazard ratios (HR) of 1.39 (95% confidence interval [CI] 1.11-1.73, P = 0.004), 1.44 (95% CI 1.13-1.82, P = 0.003), and 2.03 (95% CI 1.63-2.54, P 0.0001), respectively. Digoxin was not associated with cardiovascular hospitalizations [HR 1.12 (95% CI 0.91-1.37), P = 0.29].Digoxin is associated with increased all-cause mortality among patients with combined heart failure with reduced ejection fraction and AF, which is predominantly driven by arrhythmic deaths. In contrast, cardiovascular hospitalizations were not impacted by digoxin.

Background:People living with human immunodeficiency virus (HIV+) have greater risk for sudden arrhythmic death than HIV-uninfected (HIV–) individuals. HIV-associated abnormal cardiac repolarization may contribute to this risk. We investigated whether HIV serostatus is associated with ventricular repolarization lability by using the QT variability index (QTVI), defined as a log measure of QT-interval variance indexed to heart rate variance.Methods:We studied 1123 men (589 HIV+ and 534 HIV–) from MACS (Multicenter AIDS Cohort Study), using the ZioXT ambulatory electrocardiography patch. Beat-to-beat analysis of up to 4 full days of electrocardiographic data per participant was performed using an automated algorithm (median analyzed duration [quartile 1–quartile 3]: 78.3 [66.3–83.0] hours/person). QTVI was modeled using linear mixed-effects models adjusted for demographics, cardiac risk factors, and HIV-related and inflammatory biomarkers.Results:Mean (SD) age was 60.1 (11.9) years among HIV– and 54.2 (11.2) years among HIV+ participants (PConclusions:HIV+ men have greater beat-to-beat variability in QT interval (QTVI) than HIV– men, especially in the setting of HIV viremia and heightened inflammation. Among HIV+ men, higher QTVI suggests ventricular repolarization lability, which can increase susceptibility to arrhythmias, whereas lower heart rate variability signals a component of autonomic dysfunction.

Risk stratification of patients with inherited arrhythmia syndromes (IASs) can be challenging. Recent guidelines acknowledge a place for considering the implantable loop recorder (ILR) to outrule malignant arrhythmia as a cause of syncope in certain inherited arrhythmia patients who are at low risk of sudden cardiac death. In this comprehensive literature review, we evaluate the available evidence for the use of the ILR in the IASs and in relatives of victims of sudden arrhythmic death syndrome.

Funding Acknowledgements Type of funding sources: None. Background Although I-123 meta-iodobenzylguanidine (mIBG) has been applied to patients with chronic heart failure (CHF), a diagnostic tool for differential prediction of fatal arrhythmic events (ArE) and heart-failure death (HFD) has been pursued. Purpose The aim of this study was to create a calculator of mortality risk for differentiating mode of cardiac death using a machine learning (ML) method, and to test the accuracy in a new cohort of patients with CHF. Methods A total of 529 patients with CHF was used as the training database for ML. The ArE group consisted of patients with arrhythmic death, sudden cardiac death and appropriate therapy by implantable cardioverter defibrillator. A heart-to-mediastinum ratio (H/M) standardized to the medium-energy collimator condition was calculated with a planar anterior mIBG scintigram. The best classifier models for predicting HFD and ArE were determined by four-fold cross validation. Input variables included age, sex, New York Heart Association (NYHA) functional class, left ventricular ejection fraction, ischemic etiology, mIBG H/M and washout rate, and b-type natriuretic peptide (BNP) or NT Pro BNP, estimated glomerular filtration rate, hemoglobin, and complications such as diabetes and hypertension. After creating the ML-based model, the constructed classifier functions for ArE, HFD, and survival were exported for subsequent use. A new cohort of patients (n = 312, age 67 ± 13 years, 2015 or later) was used to test the ML-based model. Results The training database included 141 events (27%) with ArE (7%) and HFD (20%). Receiver-operating characteristic analysis by four-fold validation showed area under the curve value of 0.90 for HFD and 0.73 for ArE. Among various ML methods, the logistic regression method demonstrated the most stable calculation of the probability of ArE followed by random forest and gradient boosted tree methods. Therefore, the logistic-regression method was used for calculating both HFD and ArE probabilities. In the test cohort, patients with a high HFD probability >8% resulted in 6.3-fold higher HFD than those with low probability (≤ 8%). Patients with high ArE probability >8% showed 2.5-fold higher ArE than those with low probability (≤ 8%). Conclusion The ML-based mortality risk calculator could be used for stratifying patients at high and low risks, which might be useful for estimating appropriate treatment strategy.

Background Sudden cardiac death (SCD) in the young (age 1-35) is commonly attributed to structural and arrhythmogenic syndromes, for which there is often an underlying genetic basis. Expert recommendation emphasises the importance of genetic testing in such cases, however to date this remains the first and only national programme in Europe to facilitate this. Aim To review detection rates of genetic variants in samples tested via the SADS BioBank and possibly demonstrate the merits of this novel resource for primary prevention for family members. Methods Family screening and consent for genetic testing was carried out in the Family Heart Screening Clinic. Result analysis of samples sent for molecular autopsy via the BioBank from its induction in January 2015 was performed. Genetic analysis was conducted via the same internationally accredited next generation sequencing lab. Results From January 2015 to July 2019, 161 samples had been stored in the SADS BioBank following confirmed SADS death on autopsy; 33% female and 67% male. Of these, 24 (14.9%) samples were sent for genetic testing: 21 for a 380 gene molecular autopsy and 3 for a targeted hypertrophic cardiomyopathy panel (173 genes). Of 24 samples tested, 10 (42%) yielded positive genetic variants: 4 American College of Medical Genetics (ACMG) Class IV or V mutations considered pathogenic, and 6 ACMG class III variants of uncertain significance (VUS). Familial cascade screening following confirmed pathogenic mutations resulted in detection of 3 (33.3%) positive genotypes in 9 first-degree relatives. Screening of relatives of Class III positive probands resulted in diagnosis of an Inherited Cardiac Condition (ICC) in 25% of first-degree relatives. 8.2% of first-degree relatives of probands with negative gene testing were given an ICC diagnosis following clinical screening. Conclusions This short study demonstrates the unique potential the SADS BioBank has to offer in terms of identifying those most at risk and optimising prevention strategies for relatives, thus highlighting the role for such a resource in terms of preventative screening in the future. Pathogenic Variant (ACMG Class IV & V) Variant of Uncertain Significance(ACMG Class III) No Gene Variant Identified Number Detected (n = 24) 4 6 14 1st Degree Relatives Screened (n = 86) 17 20 49 2nd Degree Relatives Screened (n = 46) 4 23 19 Genotype Detected (n = 4) 3 1 0 Phenotype Detected (n = 10) 1 5 4 Breakdown of clinical and genetic results of family screening by ACMG class. Abstract Figure.

ObjectiveUnlike for patients with other forms of cardiomyopathies, those with severe ventricular dysfunction due to Duchenne muscular dystrophy (DMD) are not offered implantable cardioverter-defibrillator (ICD) therapy routinely. This prospective study aimed to determine the views of DMD-patients and their carers about discussing sudden death risk and their acceptance of ICDs.Design and settingAdults with DMD (n=9) and parents/carers (n=9) participated in audio-recorded, 60–90 min focus group sessions (patients 2; parents/carers 2) conducted through either a face-to-face session at a neutral venue or a videoconference. Sessions were facilitated by a clinical psychologist, experienced in conducting focus group research. All participants understood the rationale for the study and the nature of ICD therapy. The same predefined themes were explored with each group. Recordings were transcribed, analysed thematically by two researchers, working independently and then agreed. Differences in responses between patient and carer groups were also studied and compared. Participants all provided informed written consent and the study had ethical approval.ResultsThree main themes emerged: (1) access to/quality of information provided by professionals and patient engagement with them; (2) decision-making about ICDs; (3) individuals’ own ‘lived experience’ of DMD.ConclusionsThe main findings were: (1) patients with DMD want to have their risk of sudden arrhythmic death discussed, when relevant and (2) if ICD therapy were established as beneficial, they would welcome an individualised discussion about its appropriateness for them.

The risk of sudden cardiac death (SCD) is high in heart failure (HF) patients. Sudden arrhythmic death (SAD) is a frequent cause of exit in HF patients at the lower end of the HF spectrum, and implantable cardioverter–defibrillators have been recommended to prevent these life-threatening rhythm disturbances in select patients. However, less is known regarding the cause of SCD in patients at the upper end of the HF spectrum, despite the fact that the majority of out-of-hospital SCD victims have unknown or near-normal/normal left ventricular ejection fraction (LVEF). In this review, we report the epidemiology, summarize the mechanisms, discuss the diagnostic challenges, and propose a stepwise approach for the prevention of SAD in HF with near-normal/normal LVEF.

BACKGROUND: Although highly effective in preventing arrhythmic death, there is a high prevalence of anxiety, depression and reduced quality of life among patients who have received an implantable cardioverter defibrillator (ICD). Whether mortality, ICD shock and readmission are predicted by patient-reported outcomes is unknown.AIM: The aim of this study was to describe patient-reported outcomes among patients with ICDs compared by: ICD indication and generator type (ICD or cardiac resynchronisation therapy ICD), and to determine whether patient-reported outcomes at discharge predict mortality, ICD therapy and readmission.METHODS: A national cross-sectional survey at hospital discharge ( n=998) with register follow-up. Patient-reported outcomes included the Hospital Anxiety and Depression Scale, Short Form-12, HeartQoL, EQ-5D and Edmonton Symptom Assessment Scale. Register data: ICD therapy, readmissions and mortality within one year following discharge.RESULTS: Patients with primary prevention ICDs had significantly worse patient-reported outcomes at discharge than patients with secondary prevention ICDs. Likewise, patients with cardiac resynchronisation therapy ICDs had significantly worse patient-reported outcomes at discharge than patients without cardiac resynchronisation therapy. One-year mortality was predicted by patient-reported outcomes, with the highest hazard ratio (HR) being anxiety (HR 2.02; 1.06-3.86), but was not predicted by indication or cardiac resynchronisation therapy. ICD therapy and ventricular tachycardia/ventricular fibrillation were not predicted by patient-reported outcomes, indication or cardiac resynchronisation therapy. Overall, patient-reported outcomes predicted readmissions, e.g. symptoms of anxiety and depression predicted all readmissions within 3 months (HR 1.50; 1.13-1.98) and 1.47 (1.07-2.03), respectively).CONCLUSION: Patients with primary indication ICDs and cardiac resynchronisation therapy ICDs report worse patient-reported outcomes than patients with secondary indication and no cardiac resynchronisation therapy. Patient-reported outcomes such as mental health, quality of life and symptom burden predict one-year mortality and acute and planned hospital readmissions.

Background The wearable cardioverter defibrillator (WCD) is an important approach for better risk stratification, applied to patients considered to be at high risk of sudden arrhythmic death. Patients with implanted pacemakers may also become candidates for use of the WCD. However, there is a potential risk that pacemaker signals may mislead the WCD detection algorithm and cause inappropriate WCD shock delivery. The aim of the study was to test the impact of different types of pacing, various right ventricular (RV) lead positions, and pacing modes for potential misleading of the WCD detection algorithm. Methods Sixty patients with implanted pacemakers received the WCD for a short time and each pacing mode (AAI, VVI, and DDD) was tested for at least 30 seconds in unipolar and bipolar pacing configuration. In case of triggering the WCD detection algorithm and starting the sequence of arrhythmia alarms, shock delivery was prevented by pushing of the response buttons. Results In six of 60 patients (10%), continuous unipolar pacing in DDD mode triggered the WCD detection algorithm. In no patient, triggering occurred with bipolar DDD pacing, unipolar and bipolar AAI, and VVI pacing. Triggering was independent of pacing amplitude, RV pacing lead position, and pulse generator implantation site. Conclusion Unipolar DDD pacing bears a high risk of false triggering of the WCD detection algorithm. Other types of unipolar pacing and all bipolar pacing modes do not seem to mislead the WCD detection algorithm. Therefore, patients with no reprogrammable unipolar DDD pacing should not become candidates for the WCD.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is one of the leading causes of sudden arrhythmic death in the young. The QT interval in CPVT patients is typically within the normal range. However, those with prolonged QT interval have often been diagnosed with mutation‐negative long QT syndrome (LQTS). We report three CPVT patients with prolonged QT interval. Case 1 and 2 were diagnosed as LQTS at first. Genetic test using next‐generation sequencing (NGS) revealed RyR2 mutations. We should consider genetic test using NGS to identify the genes responsible for CPVT in mutation‐negative LQTS.

Aims To determine whether the combination of standard electrocardiographic (ECG) markers reflecting domains of arrhythmic risk improves sudden and/or arrhythmic death (SAD) risk stratification in patients with coronary heart disease (CHD). Methods and results The association between ECG markers and SAD was examined in a derivation cohort (PREDETERMINE; N = 5462) with adjustment for clinical risk factors, left ventricular ejection fraction (LVEF), and competing risk. Competing outcome models assessed the differential association of ECG markers with SAD and competing mortality. The predictive value of a derived ECG score was then validated (ARTEMIS; N = 1900). In the derivation cohort, the 5-year cumulative incidence of SAD was 1.5% [95% confidence interval (CI) 1.1–1.9] and 6.2% (95% CI 4.5–8.3) in those with a low- and high-risk ECG score, respectively (P for Δ Conclusion For patients with CHD, an externally validated ECG score enriched for both absolute and proportional SAD risk and significantly improved risk stratification compared to standard clinical risk factors including LVEF. Clinical Trial Registration https://clinicaltrials.gov/ct2/show/NCT01114269. ClinicalTrials.gov ID NCT01114269.

Conventional definitions of sudden cardiac death (SCD) presume cardiac cause. We studied the World Health Organization-defined SCDs autopsied in the POST SCD study (Postmortem Systematic Investigation of SCD) to determine whether premortem characteristics could identify autopsy-defined sudden arrhythmic death (SAD) among presumed SCDs.Between January 2, 2011, and January 4, 2016, we prospectively identified all 615 World Health Organization-defined SCDs (144 witnessed) 18 to 90 years in San Francisco County for medical record review and autopsy via medical examiner surveillance. Autopsy-defined SADs had no extracardiac or acute heart failure cause of death. We used 2 nested sets of premortem predictors-an emergency medical system set and a comprehensive set adding medical record data-to develop Least Absolute Selection and Shrinkage Operator models of SAD among witnessed and unwitnessed cohorts.Of 615 presumed SCDs, 348 (57%) were autopsy-defined SAD. For witnessed cases, the emergency medical system model (area under the receiver operator curve 0.75 [0.67-0.82]) included presenting rhythm of ventricular tachycardia/fibrillation and pulseless electrical activity, while the comprehensive (area under the receiver operator curve 0.78 [0.70-0.84]) added depression. If only ventricular tachycardia/fibrillation witnessed cases (n=48) were classified as SAD, sensitivity was 0.46 (0.36-0.57), and specificity was 0.90 (0.79-0.97). For unwitnessed cases, the emergency medical system model (area under the receiver operator curve 0.68 [0.64-0.73]) included black race, male sex, age, and time since last seen normal, while the comprehensive (area under the receiver operator curve 0.75 [0.71-0.79]) added use of β-blockers, antidepressants, QT-prolonging drugs, opiates, illicit drugs, and dyslipidemia. If only unwitnessed cases1 hour (n=59) were classified as SAD, sensitivity was 0.18 (0.13-0.22) and specificity was 0.95 (0.90-0.97).Our models identify premortem characteristics that can better specify autopsy-defined SAD among presumed SCDs and suggest the World Health Organization definition can be improved by restricting witnessed SCDs to ventricular tachycardia/fibrillation or nonpulseless electrical activity rhythms and unwitnessed cases to1 hour since last normal, at the cost of sensitivity.

Background We aimed to determine the mutation yield and clinical applicability of “molecular autopsy” following sudden arrhythmic death syndrome (SADS) by validating and utilizing low-cost high-throughput technologies: Fluidigm Access Array PCR-enrichment with Illumina HiSeq 2000 next generation sequencing (NGS). Methods We validated and optimized the NGS platform with a subset of 46 patients by comparison with Sanger sequencing of coding exons of major arrhythmia risk-genes (KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2, RYR2). A combined large multi-ethnic international SADS cohort was sequenced utilizing the NGS platform to determine overall molecular yield; rare variants identified by NGS were subsequently reconfirmed by Sanger sequencing. Results The NGS platform demonstrated 100% sensitivity for pathogenic variants as well as 87.20% sensitivity and 99.99% specificity for all substitutions (optimization subset, n = 46). The positive predictive value (PPV) for NGS for rare substitutions was 16.0% (27 confirmed rare variants of 169 positive NGS calls in 151 additional cases). The overall molecular yield in 197 multi-ethnic SADS cases (mean age 22.6 ± 14.4 years, 68% male) was 5.1% (95% confidence interval 2.0–8.1%), representing 10 cases carrying pathogenic or likely pathogenic risk-mutations. Conclusions Molecular autopsy with Fluidigm Access Array and Illumina HiSeq NGS utilizing a selected panel of LQTS/BrS and CPVT risk-genes offers moderate diagnostic yield, albeit requiring confirmatory Sanger-sequencing of mutational variants. Electronic supplementary material The online version of this article (10.1186/s12872-019-1154-8) contains supplementary material, which is available to authorized users.

It is generally accepted that the current guidelines for the primary prevention of sudden arrhythmic death, which are based on ejection fraction, do not allow the optimal selection of patients with low left ventricular ejection fraction of ischemic and nonischemic etiology for implantation of a cardioverter-defibrillator. Ejection fraction alone is limited in both sensitivity and specificity. An analysis of the risk of sudden arrhythmic death with a combination of multiple tests (ejection fraction associated with one or more arrhythmic risk markers) could partially compensate for these limitations. We propose a polyparametric approach for defining the risk of sudden arrhythmic death using ejection fraction in combination with other clinical and arrhythmic risk markers (i.e. late gadolinium enhancement cardiac magnetic resonance, T-wave alternans, programmed ventricular stimulation, autonomic tone, and genetic testing) that have been validated in nonrandomized trials. In this article, we examine these approaches to identify three subsets of patients who cannot be comprehensively assessed by the current guidelines: patients with ejection fraction of 35% or less and a relatively low risk of sudden arrhythmic death despite the ejection fraction value; patients with ejection fraction of 35% or less and high competitive risk of death due to evolution of heart failure or noncardiac causes; and patients with ejection fraction between 35 and 45% with relatively high risk of sudden arrhythmic death despite the ejection fraction value.

Purpose of review We aim to report on the current status of cardiovascular screening of athletes worldwide and review the up-to-date evidence for its efficacy in reducing sudden cardiac death in young athletes. Recent findings A large proportion of sudden cardiac death in young individuals and athletes occurs during rest with sudden arrhythmic death syndrome being recognised as the leading cause. The international recommendations for ECG interpretation have reduced the false-positive ECG rate to 3% and reduced the cost of screening by 25% without compromising the sensitivity to identify serious disease. There are some quality control issues that have been recently identified including the necessity for further training to guide physicians involved in screening young athletes. Summary Improvements in our understanding of young sudden cardiac death and ECG interpretation guideline modification to further differentiate physiological ECG patterns from those that may represent underlying disease have significantly improved the efficacy of screening to levels that may make screening more attractive and feasible to sporting organisations as a complementary strategy to increased availability of automated external defibrillators to reduce the overall burden of young sudden cardiac death.

The wearable cardioverter defibrillator can be used to protect against sudden cardiac arrhythmic death in at risk children. The wearable cardioverter defibrillator provides clinicians with multiple types of information such as activity level while wearing the device. The current study examined physical activity in pediatric populations while wearing the wearable cardioverter defibrillator and compared age, sex, and diagnostic groups in activity levels. The study sample included 231 children, aged 8–17, who wore a wearable cardioverter defibrillator between 2009 and 2017. All device based information and activity counts were retrieved from the data sent via remote monitoring. Pediatric patients were active for 73 min per day, with a median step count of 7361. These data were collected during their average of 39 days of wear time over an average of 21 h daily. There were no associations between sex, diagnostic groups, or end of use reason and wear time or activity; however, age was negatively associated with changes in activity level for patients aged 8–11. Results indicated significant increases in step count over the first three weeks of wear in all ages χF2 (3, n = 50) = 34.27, p

Viral vector delivery of microRNA-199a after myocardial infarction in pigs can stimulate endogenous myocardial repair mechanisms and improve cardiac function; however, persistent expression of the miRNA leads to sudden arrhythmic death.

Background— J-wave ECG patterns are associated with an increased risk of sudden arrhythmic death, and experimental evidence supports a transient outward current (I to )-mediated mechanism of J-wave formation. This study aimed to determine the frequency of genetic mutations in genes encoding the I to in patients with J waves on ECG. Methods and Results— Comprehensive mutational analysis was performed on I to -encoding KCNA4 , KCND2 , and KCND3 genes, as well as the previously described J-wave–associated KCNJ8 gene, in 51 unrelated patients with ECG evidence defining a J-wave syndrome. Only patients with a resuscitated cardiac arrest or type 1 Brugada ECG pattern were included for analysis. A rare genetic mutation of the KCND2 gene, p.D612N, was identified in a single patient. Co-expression of mutant and wild-type KCND2 with KChIP2 in HEK293 cells demonstrated a gain-of-function phenotype, including an increase in peak I to density of 48% ( P to resulted in loss of the epicardial action potential dome, predicting an increased ventricular transmural I to gradient. The previously described KCNJ8 -S422L mutation was not identified in this cohort of patients with ECG evidence of J-wave syndrome. Conclusions— These findings are the first to implicate the KCND2 gene as a novel cause of J-wave syndrome associated with sudden cardiac arrest. However, genetic defects in I to -encoding genes seem to be an uncommon cause of sudden cardiac arrest in patients with apparent J-wave syndromes.

Sudden cardiac deaths (SCD) are most often caused by ventricular arrhythmias (VA). Among all cause mortality in the elderly, the rate of SCD due to VA is decreasing. The choice of antiarrhythmic drug in elderly patients is not different according to younger patients. Treatment goals, patient compliance, drug interaction risk, liver and kidney function should be considered in the selection of antiarrhythmic drugs. ICD implantation provides mortality reduction in the elderly when appropriate patient selection is made. In older people with minimal comorbid disease and at high risk for arrhythmic death, the ICD has a higher benefit rate.

Defibrillation testing (DT) does not improve shock efficacy or reduce the risk for arrhythmic death in patients undergoing routine transvenous implantable cardioverter-defibrillator (ICD) placement and is no longer compulsory for left pectoral transvenous ICDs [(1)][1]. The subcutaneous ICD (S-ICD)

HIV+ persons have higher rates of CVD but the incidence of actual sudden arrhythmic deaths (SAD) in HIV remains unknown. Between 2011-2016, we prospectively identified all incident deaths attributable to cardiac arrest and presumed SCDs by World Health Organization (WHO) criteria among HIV+ persons

Inferolateral early repolarization (ER) patterns on standard electrocardiogram (ECG) are associated with increased risk for cardiac and arrhythmic death in general adult population cohorts. We sought to determine the prevalence of inferolateral ER on surface ECG in multiracial pre- and postadolescent populations and to analyze its association with age, race, gender, and ST-segment patterns. A retrospective review was conducted of all ECGs recorded from preadolescent (aged 8-12 years, n = 719) and postadolescent (aged 21-25 years, n = 755) patients seen at a large academic medical center between January 1, 2009, and December 31, 2010. The overall prevalence of inferolateral ER was similar in the preadolescent and postadolescent populations (17% vs 16%, NS). The prevalence of ER increased after puberty in male patients (16% to 25%, p0.001) and decreased in female patients (18% to 9%, p0.001). Prevalence of ascending early repolarization (benign variant) also increased in males after puberty (15% to 23%, p0.004) and decreased in females (11% to 4%, p0.001). There were no differences in the prevalence of the risk-associated horizontal/descending pattern (3% in both groups). Subgroup analysis was performed on ECGs from the cohort of outpatients without cardiac disease, and the statistical trends remained the same. In conclusion, the overall prevalence of inferolateral ER was higher in pre- and postadolescent populations than in adult populations. However, the prevalence of the risk-associated horizontal/descending ST-segment pattern was only 3%, comparable to prevalence rates in the adult population. The variations in prevalence by gender and age suggest a possible influence of reproductive hormones.

We present the case of a 68-year-old man with coronary artery disease and a history of recurrent myocardial infarctions, having left ventricular ejection fraction 25% in NYHA functional class III. The patient received a biventricular cardioverter-defibrillator (ICD) Biotronik Lumax 340 HF-T in November 2008 from the primary prophylactic indication. Remote monitoring using the Biotronik Home Monitoring™ (HM) system was activated since device implantation. Up to April 2012 the patient received five shocks including 3 appropriate VF therapies and 2 inappropriate ICD shocks (due to T-wave oversensing and atrial flutter degenerating to VF after ATPs). All arrhythmic events were promptly detected by the HM system with a rapid consequent pharmacological and non-pharmacological intervention (radiofrequency catheter ablation of atrial arrhythmia and reprogramming the device). This case points out that prophylactic ICD implantation is a justifiable method for the prevention of arrhythmic death in high-risk patients and HM significantly helps in the early recognition of inappropriate ICD therapy.

Background— Sudden cardiac death (SCD) is a major cause of mortality in adults with congenital heart disease (CHD). The aim of this study was to determine the adult CHD population at risk of SCD and the clinical parameters associated with SCD. Methods and Results— We performed a multicenter case-control study. Patients who died suddenly as a result of proven or presumed arrhythmia were included (cases). For each case, 2 controls matched on diagnosis, type of surgical intervention, age, and gender were included. From 3 databases including 25 790 adults with CHD, 1189 deaths (5%) were identified, of whom 213 patients (19%) died suddenly. Arrhythmic death occurred in 171 of 1189 patients. The underlying cardiac lesions were mild, moderate, and severe CHD in 12%, 33%, and 55% of the SCD cases, respectively. Clinical variables associated with SCD were supraventricular tachycardia (odds ratio [OR], 3.5; 95% confidence interval [CI], 1.5–7.9; P= 0.004), moderate to severe systemic ventricular dysfunction (OR, 3.4; 95% CI, 1.1–10.4; P= 0.034), moderate to severe subpulmonary ventricular dysfunction (OR, 3.4; 95% CI, 1.1–10.2; P= 0.030), increased QRS duration (OR, 1.34 [per 10-ms increase]; 95% CI, 1.10–1.34; P =0.008), and QT dispersion (OR, 1.22 [per 10-ms increase]; 95% CI, 1.22–1.48; P =0.008). Conclusions— The clinical parameters found to be associated with SCD in adults with a broad spectrum of CHD, including systemic right ventricles, are similar to those in ischemic heart disease. Moreover, even those patients with mild cardiac lesions are potentially at risk for SCD. This highlights the need for further prospective studies as well as vigilant ongoing follow-up of the adult with CHD.

The decision-making process around initial implantation of an Implantable Cardioverter Defibrillator (ICD) is well studied, guided by randomized clinical trials which have translated into widely accepted clinical guidelines. For patients who out-live their first device and are eligible for a generator exchange (GE) the indications to replace the battery is much less well-defined. In this latter case, the clinician needs to make the decision based on persistent indications for primary prevention ICD, risk of future arrhythmic death in the absence of ongoing indications for primary prevention, competing causes of non-arrhythmic death and the patient's overall goals of care.

Remote monitoring is useful for management of implantable cardioverter defibrillator (ICD) patients regarding detection of arrhythmias and probable device or lead failure. We report the case of a patient who died suddenly while being on remote monitoring. The ICD was not retrieved postmortem. Even though clinical circumstances were suspicious of an arrhythmic death, this was excluded due to a distinctive manufacturer feature of the system.

Background: Patients receiving implantable cardioverter-defibrillators (ICDs) often have severely impaired left ventricular function and a poor prognosis. Having an ICD in situ effectively denies them the possibility of a quick, arrhythmic death. It is still unclear if and when the end of life and device deactivation should be discussed with patients and how much patients want to know prior to ICD implantation. Methods: Patients with an active ICD for chronic heart failure were interviewed regarding their attitude toward the ICD, their recollection of the consent procedure, and how they felt the end of life should be discussed with ICD patients (n = 54). Patients who had received ICD therapies (n = 25) were reviewed as a subgroup with extended questions regarding attitudes toward device deactivation. Results: Fifty-four patients were recruited. Most patients were not aware that the ICD could be deactivated. The vast majority of patients (84%) wanted to be involved in the deactivation decision; 40% felt this discussion should be prior to ICD implantation but others felt the discussion should only occur if the patient was terminally ill (16%) or in the last few days of life (5%). Conclusion: Patients with ICDs are routinely counseled about the benefits of ICDs, but options for device deactivation are not well understood by patients. Most patients would like to be involved in deactivation decisions and we feel this should be discussed well in advance. (PACE 2011; 34:1628–1633)

Sudden arrhythmic death syndrome (SADS) accounts for approximately 500 deaths in England and Wales per year. Clinical screening of the surviving first-degree relatives can identify an inherited cardiovascular condition in up to half of families, permitting lifestyle modification and confirmed effective prophylactic therapies to prevent further sudden deaths. Mechanisms for molecular autopsy are available to improve the diagnostic yield but practical barriers to its successful implementation exist. This article reviews the clinical screening of the first-degree relatives of SADS patients, molecular autopsy of probands and the broader implications of national recommendations for the investigation of sudden cardiac death.

Left ventricular noncompaction has been classified as a primary cardiomyopathy with a genetic origin. This condition is morphologically characterized by a thickened, two-layered myocardium with numerous prominent trabeculations and deep, intertrabecular recesses. Recently, it has become clear that these pathological characteristics extend across a continuum with left ventricular hypertrabeculation at one end of the spectrum. The histological findings include areas of interstitial fibrosis. We present a case of left ventricular hypertrabeculation which presented as sudden infant death syndrome. Histologically areas of subendocardial fibrosis was prominent and we propose that this entity may be a hidden cause of arrhythmic death in some infants presenting as sudden infant death syndrome., with areas of subendocardial fibrosis as possible arrhythmogenic foci.

The wearable cardioverter defibrillator (WCD) was introduced into clinical practice about 8 years ago as an alternative approach to protect patients with a temporary high risk of sudden arrhythmic death. The WCD has the characteristics of an implantable defibrillator (ICD) but does not need to be implanted, and it has similarities with an external defibrillator, but does not require a bystander to apply lifesaving shocks when necessary. Based on current clinical experience, the WCD is not an alternative to the ICD, but a device that will contribute to better selection of patients for ICD therapy and may be indicated in case of interrupted protection by an already implanted ICD, temporary inability to implant an ICD, or refusal of an indicated ICD.

To describe the occurrence of arrhythmic death among survivors of acute myocardial infarction (AMI) and the availability of a primary implantable cardioverter defibrillator (ICD).Consecutive patients who fulfilled the criteria for AMI admitted to the Sahlgrenska University Hospital during 21 months were prospectively followed for 2 years with a focus on echocardiography and mode of death.Among the 471 patients, for whom information on ejection fraction (EF) was available and who survived the first week, 10 patients died between days 7 and 30 - of whom one had an arrhythmic death. Among the 461 survivors on day 30, 34 patients (7.4%) had an EF of 30% or less. Among these, 24 were judged to be available for ICD implantation, of whom one died an arrhythmic death during follow-up. Among the remaining 10 patients who were excluded from ICD indication because of either high age and/or severe comorbidity, two patients died an arrhythmic death. Among the remaining 427 patients who had an EF greater than 30%, six died an arrhythmic death. Thus, 10 patients, with EF assessed, died an arrhythmic death between day 7 and 2 years after AMI, but only one would have received an ICD according to the Multicenter Automatic Defibrillator Implantation Trial II criteria and clinical judgement.Of the 471 consecutive survivors of AMI, 10 (2%) died an arrhythmic death, of whom only one would have received an ICD according to current guidelines and clinical judgement. Predictors of subsequent arrhythmic death after an AMI, useful on a per patient basis, remain an unmet need.

Sudden cardiac death (SCD) is widespread and the most serious of the cardiac diseases, accounting for over half of cardiovascular mortality in adults in the United States, and nearly 1 in 3 of these patients does not report symptoms of cardiac disease before the sudden death. Quantifying the left ventricular ejection fraction is currently the best way to risk-stratify patients for SCD and identify those who are most likely to benefit from the insertion of an implantable cardiac defibrillator (ICD). The strategy of systemically placing ICDs in patients at risk of SCD is expensive and leads to substantial psychological hardship. However, noninvasive electrocardiographic indices of depolarization and repolarization may better identify patients who are at an increased risk of SCD. Therefore, developing an approach to identify electrocardiographic changes associated with the highest risk of arrhythmic death could markedly improve patient selection for ICD therapy. This report describes electrocardiographic parameters that may be useful in identifying patients at risk of SCD. The state of the science currently suggests that it is unlikely that a single electrocardiographic parameter will predict SCD, but rather a risk stratification algorithm based on a combination of electrocardiographic parameters may yield the best result.

Mutations that disrupt the coding sequence of Nav1.5, the cardiac Na+ channel encoded by SCN5A, cause inherited arrhythmias and cardiomyopathy. Changes in Nav1.5 splice isoforms, localization and function have also been associated with prognosis in acquired heart disease. However, the role of genetic variants in SCN5A gene regulatory sequences (e.g. those modulating expression) remains poorly understood. MicroRNAs (miRs) have emerged as vital gene regulators in heart, having roles in cardiogenesis, contractile function, and disease. These small non-coding RNAs are loaded into Argonaute proteins to direct post-transcriptional gene suppression by base-pairing with target transcripts, and genetic variants altering miR binding sequences may influence disease. Here, we used high-throughput biochemical means (HITS-CLIP) to generate the first transcriptome-wide map of miR binding events in human heart (4000 sites across >2200 genes). Our query of the data uncovered >500 common SNPs residing in or nearby miR target sites. Among these, we identified a synonymous SNP (rs1805126, T/C) which alters a conserved miR-24 binding site in the terminal coding exon of SCN5A. We hypothesized that this SNP affects Nav1.5 expression and contributes to clinical outcomes in heart failure. In vitro experiments showed that miR-24 suppresses Na+ current on patch clamp analysis (~5-fold; p1800 subjects with EFs≤30% and implantable cardioverter defibrillators (ICDs) from GRADE, a prospective multicenter study of genetic modulators of heart failure outcomes. We found that CC homozygotes had worse survival rates than T-allele carriers (HR=1.5, p=0.001), but no change in appropriate ICD shocks, a surrogate for sudden death. Together, these data reveal a novel miR-24:SCN5A:SNP regulatory axis that points to a surprising link between cardiac Na+ channel levels and non-arrhythmic death in heart failure. Overall, this work represents a key advance in exploring the interface of cardiac miRs with genetics and disease, perhaps signifying a broader functional relevance for “silent” SNPs.

This editorial refers to ‘Significance of electrocardiogram recording in high intercostal spaces in patients with early repolarization syndrome’, by T. Kamakura et al., on page doi:10.1093/eurheartj/ehv369. Electrophysiologists and cardiologists interested in sudden cardiac death have been very lucky over the past decades. Many improvements in our knowledge about the causes of cardiac death have allowed better recognition and proper protection of patients at risk. Until the 1980s, a significant number of patients were left undiagnosed after a documented episode of sudden cardiac death. We used to use the term ‘idiopathic ventricular fibrillation’ to classify these patients. It was a clear recognition of our inability to understand why these patients presented with malignant arrhythmias. However, the effort, curiosity and perseverance of many investigators led to the description of new, unsuspected causes of arrhythmic death. Genetics knowledge and the development of powerful tools to study human DNA variability opened a completely new era in the investigation of sudden cardiac death in the structurally normal heart. Long QT, Brugada,1 short QT or early repolarization syndromes are some examples of newly described diseases that have benefited from advances in basic genetics research. Progress in our understanding of these monogenic diseases has allowed the description of rather novel pathogenic mechanisms and dissemination of the knowledge to increase awareness in the medical …

Prior to the implantable cardioverter–defibrillator (ICD), life-threatening ventricular arrhythmias were treated using anti-arrhythmic drugs. The concept of an implantable defibrillator to prevent sudden arrhythmic death was first published by Michel Mirowski in 1970. Despite critical opinions by leading physicians, Michel Mirowski continued development of his vision. Hallmarks in the development of the ICD include the following: internal–external defibrillator used during surgery on humans in 1971/1972; fully implantable defibrillator tested in canines in 1975; defibrillator successfully implanted in a 57-year-old woman in 1980; second generation devices introduced in 1982; US Food and Drug Administration device approved in 1985. Today it is hard to imagine modern medicine without ICD therapy. This article provides the reader a history of the development of the ICD.

Implantable cardioverter-defibrillators (ICDs) reduce mortality in selected high-risk populations by reducing the risk of sudden death. No clinical trial examining ICD efficacy has focused specifically on benefits and risks in the elderly, but all trials have included substantial numbers of older patients. The author addresses several issues: Is the risk of sudden death different for the elderly than in younger patients? Is ICD implantation feasible in the elderly? Is there evidence that ICD use in the elderly improves survival? The author's research indicates that while total mortality is higher for the elderly, there does not appear to be a specific predilection for arrhythmic death. Recent reports indicate that while ICDs can be implanted in a Medicare population, ICD implantation is associated with significant mortality (0.9%), as well as periprocedural complications (10.8%). In spite of the risks, both secondary and primary prevention trials demonstrate that the survival benefit associated with ICD use in the study populations was at least as great for elderly patients as for younger persons. Thus, published data support judicious ICD use in elderly patients at high risk for sudden death.

All patients with hypertrophic cardiomyopathy (HCM) should have five aspects of care addressed. An attempt should be made to detect the presence or absence of risk factors for sudden arrhythmic death. If the patient appears to be at high risk, discussion of the benefits and risks of ICD are indicated, and many such patients will be implanted. Symptoms are appraised and treated. Bacterial endocarditis prophylaxis is recommended. Patients are advised to avoid athletic competition and extremes of physical exertion. First degree family members should be screened with echocardiography and ECG.