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.

[Catecholaminergic polymorphic ventricular tachycardia (CPVT): an insidious disease that can often lead to sudden cardiac death in young people]. / Die katecholaminerge polymorphe ventrikuläre Tachykardie (CPVT) : Eine tückische Erkrankung, die bei jungen Menschen zum plötzlichen Herztod führen kann.

The first symptoms of catecholaminergic polymorphic ventricular tachycardia (CPVT) usually occur in childhood and adolescence. 60% of patients experience syncope before the age of 40. Sudden cardiac death (SCD) is the first symptom of the disease in 30-50% of patients with CPVT. Early diagnosis is therefore crucial for the patient's prognosis. The diagnosis of CPVT is confirmed by a normal resting ECG, exclusion of structural heart disease, detection of bidirectional or polymorphic ventricular tachycardia (VT) in the stress ECG and/or detection of a pathogenic mutant in a gene associated with CPVT. Up to 60% of CPVT patients carry changes in the RYR2 gene. This gene encodes the cardiac ryanodine receptor, the most important Ca2+-releasing channel of the sarcoplasmic reticulum, which plays a central role in the contraction and relaxation of the heart muscle. If the function of the ryanodine receptor is impaired, too much calcium enters the cells, which triggers life-threatening arrhythmias. The overactive ryanodine receptor is therefore the main target for gene therapy methods. Even though the development of gene therapy is progressing, there is still no causal therapy available and it is all the more important to make a diagnosis as early as possible, which enables appropriate behavior and adequate symptomatic therapy. The decisive factor here is the evaluation of the genetic analysis in the context of the clinical findings. Based on this, recommendations can be made for preventive measures and the avoidance of specific triggers that could lead to life-threatening arrhythmias.

Catheter ablation as first-line treatment for ventricular tachycardia in patients with structural heart disease and preserved left ventricular ejection fraction: a systematic review and meta-analysis.

In this systematic review and meta-analysis, we aim to evaluate the efficacy and safety of catheter ablation as the first-line treatment of ventricular tachycardia (VT) in patients with structural heart disease (SHD) and preserved left ventricular ejection fraction (LVEF). Patients with SHD are particularly susceptible to VT, a condition that increases the risk of sudden cardiac death (SCD). Implantable cardioverter-defibrillators (ICDs) can terminate VT and prevent SCD but do not prevent VT recurrence. The efficacy and safety of CA as a first-line treatment in SHD patients with preserved LVEF remain unclear. We searched PubMed/Medline, EMBASE, Web of Science, and Cochrane CENTRAL for studies reporting the outcomes of CA therapy in patients with VT and preserved LVEF, published up to January 19, 2023. The primary outcome was the incidence of SCD following catheter ablation as the first-line treatment of VT in patients with SHD and preserved LVEF. Secondary outcomes included all-cause mortality, VT recurrence, procedural complications, CA success rate, and ICD implantation after catheter ablation. We included seven studies in the meta-analysis, encompassing a total of 920 patients. The pooled success rate of catheter ablation was 84.6% (95% CI 67.2-93.6). Complications occurred in 6.4% (95% CI 4.0-9.9) of patients, and 13.9% (95% CI 10.1-18.8) required ICD implantation after ablation. VT recurrence was observed in 23.2% (95% CI 14.8-34.6) of patients, while the rate of sudden cardiac death (SCD) was 3.1% (95% CI 1.7-5.6). The overall prevalence of all-cause mortality in this population was 5% (95% CI 1.8-13). CA appears promising as a first-line VT treatment in patients with SHD and preserved LVEF, especially for monomorphic hemodynamically tolerated VT. However, due to the lack of direct comparisons with ICDs and anti-arrhythmic drugs, further research is needed to confirm these findings.

Sudden death after a mountain bike race.

Presented case study deals with the sudden death of a 47 years old male, shortly after a mountain bike race after reported nausea and chest pain followed by loss of consciousness and resuscitation. Cardiopulmonary resuscitation was unsuccessful. An autopsy was enacted due to the sudden death in a seemingly healthy person. An acute infarction of the anterior cardiac wall on the basis of stenosis of the anterior interventricular branch of the left coronary artery with histopathological findings of eosinophilic coronary periarteritis was assessed. Sudden death during sport activities represents a complex problem which forensic physicians have to face. An external and internal examination of the body is not always sufficient. It is crucial for the forensic physician to have sufficient knowledge and enough information about the circumstances of the death and anamnestic records. Eosinophilic coronary periarteritis occurs rarely, predominantly in males and with uncertain etiology.

[Bibliometrics Analysis of Studies on Hypertrophic Cardiomyopathy From 2018 to 2022].

Objective To analyze the research progress and hot topics in hypertrophic cardiomyopathy from 2018 to 2022.Methods The publications in the field of hypertrophic cardiomyopathy from January 1,2018 to December 31,2022 were retrieved from Web of Science core collection database and included for a bibliometric analysis.Results A total of 6355 publications were included,with an average citation frequency of 7 times.The year 2021 witnessed the most publications (1406).The analysis with VOSviewer showed that the research on sudden death related to hypertrophic cardiomyopathy,especially the predictive value of late gadolinium-enhanced cardiac MRI in sudden death,was a hot topic.In addition,gene detection and the new drug mavacamten became hot research topics.The United States was the country with the largest number of publications and the highest citation frequency in this field.Chinese scholars produced the second largest number of publications,which,however,included few high-quality research results.Conclusions Risk stratification and prevention of sudden death is still an important and hot research content in the field of hypertrophic cardiomyopathy.Chinese scholars should carry out multi-center cooperation in the future to improve the research results.

Atrial fibrillation and risk of sudden cardiac arrest in young adults.

AIMS: Evidence of an association between atrial fibrillation (AF) and sudden cardiac arrest (SCA) in young adults is limited. In this study, we aim to evaluate this association in a general population aged between 20 and 39 years. METHODS AND RESULTS: Young adults who underwent health check-ups between 2009 and 2012 were screened from a nationwide healthcare database in South Korea. A history of AF diagnosis before the health check-ups was identified based on the relevant International Classification of Diseases, 10th edition codes reported in the database. Associations between an established diagnosis of AF and the risk of SCA during follow-up were examined. A total of 6 345 162 young people were analysed with a mean follow-up duration of 9.4 years. The mean age was 30.9 ± 5.0 years, and 5875 (0.09%) individuals were diagnosed with AF. During follow-up, SCA occurred in 5352 (0.08%) individuals, and the crude incidence was 0.56 and 0.09 events per 1000 person-years for participants with and without AF, respectively. Individuals with AF had a 3.0-fold higher risk in a multivariate model adjusted for age, sex, lifestyle, anthropometric data, and medical comorbidities (adjusted hazard ratio 2.96, 95% confidence interval 1.99-4.41, P < 0.001). Both incident and prevalent AFs were associated with an increased risk of SCA, with no significant differences between the two groups. CONCLUSION: Atrial fibrillation was associated with a significantly higher risk of SCA developing in healthy young adults. Whether the rate or rhythm control influences the risk of SCA in young patients with AF remains to be examined.

[Cardiac channelopathies in the context of hereditary arrhythmia syndromes]. / Kardiale Kanalopathien im Kontext hereditärer Arrhythmiesyndrome.

Genetic arrhythmia disorders are rare diseases; however, they are a common cause of sudden cardiac death in children, adolescents, and young adults. In principle, a distinction can be made between channelopathies and cardiomyopathies in the context of genetic diseases. This paper focuses on the channelopathies long and short QT syndrome, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia (CPVT). Early diagnosis of these diseases is essential, as drug therapy, behavioral measures, and if necessary, implantation of a cardioverter defibrillator can significantly improve the prognosis and quality of life of patients. This paper highlights the pathophysiological and genetic basis of these channelopathies, describes their clinical manifestations, and comments on the principles of diagnosis, risk stratification and therapy.

Sudden cardiac arrest in patients with cancer in the general population: insights from the Paris-SDEC registry.

BACKGROUND: Data on the management of patients with cancer presenting with sudden cardiac arrest (SCA) are scarce. We aimed to assess the characteristics and outcomes of SCA according to cancer history. METHODS: Prospective, population-based registry including every out-of-hospital SCA in adults in Paris and its suburbs, between 2011 and 2019, with a specific focus on patients with cancer. RESULTS: Out of 4069 patients who had SCA admitted alive in hospital, 207 (5.1%) had current or past medical history of cancer. Patients with cancer were older (69.2 vs 59.3 years old, p<0.001), more often women (37.2% vs 28.0%, p=0.006) with more frequent underlying cardiovascular disease (41.1% vs 32.5%, p=0.01). SCA happened more often with a non-shockable rhythm (62.6% vs 43.1%, p<0.001) with no significant difference regarding witness presence and cardiopulmonary resuscitation (CPR) performed. Cardiac causes were less frequent among patients with cancer (mostly acute coronary syndromes, 25.5% vs 46.8%, p<0.001) and had more respiratory causes (pulmonary embolism and hypoxaemia in 34.2% vs 10.8%, p<0.001). Still, no difference regarding in-hospital survival was found after SCA in patients with cancer versus other patients (26.2% vs 29.8%, respectively, p=0.27). Public location, CPR by witness and shockable rhythm were independent predictors of in-hospital survival after SCA in the cancer group. CONCLUSIONS: One in 20 SCA occurs in patients with a history of cancer, yet with fewer cardiac causes than in patients who are cancer-free. Still, in-hospital outcomes remain similar even in patients with known cancer. Cancer history should therefore not compromise the initiation of resuscitation in the context of SCA.

A case of Williams syndrome with Wolff-Parkinson-White syndrome.

INTRODUCTION: Williams syndrome (WS) cases have been reported to have with 25-100 times greater increased risk of sudden cardiac death (SCD). SCD has been reported in cases without any evidence of structural cardiovascular anomalies. Wolff-Parkinson-White (WPW) syndrome is characterized by short PR interval and delta wave. Ventricular preexcitations can develop paroxysmal reentrant tachycardia through Kent bundle or less frequent atrial fibrillation and in some cases with accessory pathway effective refractory period (APERP) under 250 ms considered as risky and may lead to SCD. WS associated with WPW has not been reported before. CASE REPORT: An 11-year-old male who had been followed up with WS was referred to pediatric cardiology outpatient clinic with the complaint of palpitation. Electrocardiographic examination showed short PR interval and delta wave in the ECG consistent with WPW. He underwent electrophysiological study (EPS). Basic measurements were performed, and APERP was found at 280 ms cycle atrial pacing. RF energy was delivered using a 4 mm tip nonirrigated radiofrequency (RF) ablation catheter where the best ventriculoatrial (VA) signals were received and the AP was abolished within few seconds. DISCUSSION AND CONCLUSIONS: Although, WPW cases are usually asymptomatic or related to SVT, the risk of SCD should not be ignored. Thus, all patients with WPW deserve an EPS for assessing the AP conduction properties. Due to the increased risk of SCD in patients with WS compared to general population, in the presence of concomitant WPW, these patients should be evaluated with EPS even if they do not have symptoms.

Evaluating the Association between Anomalous Aortic Origin of the Right Coronary Artery from the Left Sinus with Interarterial Course at Coronary CT Angiography and Sudden Cardiac Death.

Purpose To investigate the association between the anomalous aortic origin of the right coronary artery (R-AAOCA) from the left coronary sinus with interarterial course (IAC) found at coronary CT angiography and sudden cardiac death using a large data set from five university hospitals. Materials and Methods From a total of 89 314 CCTA scans (January 2009 to December 2016) that were retrospectively collected, 316 patients with R-AAOCA from the left sinus with IAC were retrospectively collected. After excluding patients with less than 2 years of follow-up, patients who had already undergone cardiovascular surgery or intervention, and patients with arrhythmia or heart failure before undergoing coronary CT angiography, 224 patients were analyzed. Follow-up was terminated upon the occurrence of major adverse cardiovascular events (MACE). Logistic regression was used to identify clinical and radiologic information as independent predictors of MACE. Results The period prevalence of R-AAOCA from the left sinus with IAC was 0.354%. The mean age was 62.03 years, with a male-to-female ratio of 182:134. During follow-up, 19 of 224 patients (8.5%) experienced MACE, but none had sudden cardiac death. Of these cases, only seven (3.13%) were suspected of being due to R-AAOCA from the left sinus with IAC and all of them had unstable angina. Coronary artery disease was significantly associated with MACE (P < .001), while no significant correlation was observed with radiologic features. Conclusion Sudden cardiac death was not associated with R-AAOCA from the left sinus with IAC found at coronary CT angiography. The occurrence of MACE was low, with coronary artery disease being the sole significant predictor of a patient's prognosis. Keywords: Anomalous Aortic Origin of the Right Coronary Artery, Left Coronary Sinus with Interarterial Course, Coronary CT Angiography, Sudden Cardiac Death Supplemental material is available for this article. © RSNA, 2024.

Machine Learning in Hypertrophic Cardiomyopathy: Nonlinear Model From Clinical and CMR Features Predicting Cardiovascular Events.

BACKGROUND: The cumulative burden of hypertrophic cardiomyopathy (HCM) is significant, with a noteworthy percentage (10%-15%) of patients with HCM per year experiencing major adverse cardiovascular events (MACEs). A current risk stratification scheme for HCM had only limited accuracy in predicting sudden cardiac death (SCD) and failed to account for a broader spectrum of adverse cardiovascular events and cardiac magnetic resonance (CMR) parameters. OBJECTIVES: This study sought to develop and evaluate a machine learning (ML) framework that integrates CMR imaging and clinical characteristics to predict MACEs in patients with HCM. METHODS: A total of 758 patients with HCM (67% male; age 49 ± 14 years) who were admitted between 2010 and 2017 from 4 medical centers were included. The ML model was built on the internal discovery cohort (533 patients with HCM, admitted to Fuwai Hospital, Beijing, China) by using the light gradient-boosting machine and internally evaluated using cross-validation. The external test cohort consisted of 225 patients with HCM from 3 medical centers. A total of 14 CMR imaging features (strain and late gadolinium enhancement [LGE]) and 23 clinical variables were evaluated and used to inform the ML model. MACEs included a composite of arrhythmic events, SCD, heart failure, and atrial fibrillation-related stroke. RESULTS: MACEs occurred in 191 (25%) patients over a median follow-up period of 109.0 months (Q1-Q3: 73.0-118.8 months). Our ML model achieved areas under the curve (AUCs) of 0.830 and 0.812 (internally and externally, respectively). The model outperformed the classic HCM Risk-SCD model, with significant improvement (P < 0.001) of 22.7% in the AUC. Using the cubic spline analysis, the study showed that the extent of LGE and the impairment of global radial strain (GRS) and global circumferential strain (GCS) were nonlinearly correlated with MACEs: an elevated risk of adverse cardiovascular events was observed when these parameters reached the high enough second tertiles (11.6% for LGE, 25.8% for GRS, -17.3% for GCS). CONCLUSIONS: ML-empowered risk stratification using CMR and clinical features enabled accurate MACE prediction beyond the classic HCM Risk-SCD model. In addition, the nonlinear correlation between CMR features (LGE and left ventricular pressure gradient) and MACEs uncovered in this study provides valuable insights for the clinical assessment and management of HCM.

Vigorous Exercise in Patients With Congenital Long QT Syndrome: Results of the Prospective, Observational, Multinational LIVE-LQTS Study.

BACKGROUND: Whether vigorous exercise increases risk of ventricular arrhythmias for individuals diagnosed and treated for congenital long QT syndrome (LQTS) remains unknown. METHODS: The National Institutes of Health-funded LIVE-LQTS study (Lifestyle and Exercise in the Long QT Syndrome) prospectively enrolled individuals 8 to 60 years of age with phenotypic and/or genotypic LQTS from 37 sites in 5 countries from May 2015 to February 2019. Participants (or parents) answered physical activity and clinical events surveys every 6 months for 3 years with follow-up completed in February 2022. Vigorous exercise was defined as ≥6 metabolic equivalents for >60 hours per year. A blinded Clinical Events Committee adjudicated the composite end point of sudden death, sudden cardiac arrest, ventricular arrhythmia treated by an implantable cardioverter defibrillator, and likely arrhythmic syncope. A National Death Index search ascertained vital status for those with incomplete follow-up. A noninferiority hypothesis (boundary of 1.5) between vigorous exercisers and others was tested with multivariable Cox regression analysis. RESULTS: Among the 1413 participants (13% <18 years of age, 35% 18-25 years of age, 67% female, 25% with implantable cardioverter defibrillators, 90% genotype positive, 49% with LQT1, 91% were treated with beta-blockers, left cardiac sympathetic denervation, and/or implantable cardioverter defibrillator), 52% participated in vigorous exercise (55% of these competitively). Thirty-seven individuals experienced the composite end point (including one sudden cardiac arrest and one sudden death in the nonvigorous group, one sudden cardiac arrest in the vigorous group) with overall event rates at 3 years of 2.6% in the vigorous and 2.7% in the nonvigorous exercise groups. The unadjusted hazard ratio for experience of events for the vigorous group compared with the nonvigorous group was 0.97 (90% CI, 0.57-1.67), with an adjusted hazard ratio of 1.17 (90% CI, 0.67-2.04). The upper 95% one-sided confidence level extended beyond the 1.5 boundary. Neither vigorous or nonvigorous exercise was found to be superior in any group or subgroup. CONCLUSIONS: Among individuals diagnosed with phenotypic and/or genotypic LQTS who were risk assessed and treated in experienced centers, LQTS-associated cardiac event rates were low and similar between those exercising vigorously and those not exercising vigorously. Consistent with the low event rate, CIs are wide, and noninferiority was not demonstrated. These data further inform shared decision-making discussions between patient and physician about exercise and competitive sports participation. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02549664.

First human safety and effectiveness study of defibrillation with a novel patch wearable cardioverter-defibrillator.

AIMS: Wearable cardioverter-defibrillators (WCDs) are indicated in patients at risk of sudden cardiac arrest who are not immediate candidates for implantable defibrillator therapy. Limitations of existing WCDs include poor compliance and high false alarm rates. The Jewel is a novel patch-WCD (P-WCD) that addresses these limitations with an adhesive-based design for near-continuous wear and a machine learning algorithm designed to minimize inappropriate detections. This was a first-in-human study of the Jewel P-WCD conducted in an electrophysiology (EP) lab to determine the safety and effectiveness of the device in terminating ventricular tachycardia/ventricular fibrillation (VT/VF) with a single shock. The aim was to evaluate the safety and effectiveness of terminating VT/VF with a single shock using the Jewel P-WCD. METHODS AND RESULTS: This was a first-in-human, prospective, single-arm, single-centre study in patients scheduled for an EP procedure in which VT/VF was expected to either spontaneously occur or be induced. The Jewel P-WCD was placed on consented patients; upon confirmation of VT/VF, a single shock (150 J) was delivered via the device. A group sequential design and Pocock alpha spending function was used to measure the observed proportion of successful VT/VF single-shock terminations. The endpoint was achieved if the lower confidence limit exceeded the performance goal of 62%, using a one-sided lower 97.4% exact confidence bound. Of 18 eligible subjects, 16 (88.9%, 97.4% confidence bound: 65.4%) were successfully defibrillated with a single shock, exceeding the primary endpoint performance goal with no adverse events. CONCLUSION: This first-in-human evaluation of the Jewel P-WCD demonstrated the safety and effectiveness of terminating VT/VF. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov/; Unique identifier: NCT05490459.

Histological evaluation of cardiac remodelling in equine athletes.

Approximately 1-2 per 100,000 young athletes die from sudden cardiac death (SCD) and extreme exercise may be associated with myocardial scar and arrhythmias. Racehorses have a high prevalence of atrial fibrillation (AF) and SCD but the presence of myocardial scar and inflammation has not been evaluated. Cardiac tissues from the left (LAA) and right (RAA) atrial appendages, left ventricular anterior (LVAPM) and posterior (LVPPM) papillary muscles, and right side of the interventricular septum (IVS-R) were harvested from racehorses with sudden cardiac death (SCD, n = 16) or other fatal injuries (OFI, n = 17), constituting the athletic group (ATH, n = 33), and compared to sedentary horses (SED, n = 10). Horses in the ATH group had myocyte hypertrophy at all sites; increased fibrosis at all sites other than the LAA; increased fibroblast infiltration but a reduction in the overall extracellular matrix (ECM) volume in the RAA, LVAPM, and IVS-R compared to SED horses. In this horse model, athletic conditioning was associated with myocyte hypertrophy and a reduction in ECM. There was an excess of fibrocyte infiltration and focal fibrosis that was not present in non-athletic horses, raising the possibility of an exercise-induced pro-fibrotic substrate.

Recent epidemiology of sudden cardiac death.

We accessed the US CDC online database Wonder, which provides nationwide statistics on causes of death between the years 2018-2022. The crude mortality rate for sudden cardiac death (SCD) increased in parallel with age in both sexes, reaching the highest value in subjects aged 85 years or older. In all age groups, the crude death rate was always significantly higher in men than in women. Despite the cumulative number of officially recorded SCDs may be higher between the ages of 60 and 69 years, the risk of dying from SCD appears to increase with population age, peaking after the age of 85.

Predictors of Shock-Reduction Programming and Its Impact on Implantable Cardioverter-Defibrillator Therapies and Mortality: The CERTITUDE Registry.

BACKGROUND: Shock-reduction implantable cardioverter-defibrillator programming (SRP) was associated with fewer therapies and improved survival in randomized controlled trials, but real-world studies investigating SRP and associated outcomes are limited. METHODS AND RESULTS: The BIOTRONIK CERTITUDE registry was linked with the Medicare database. We included all patients with an implantable cardioverter-defibrillator implanted between August 22, 2012 and September 30, 2021 in the United States. SRP was defined as programming to either a therapy rate cutoff ≥188 beats per minute or number of intervals to detection ≥30/40 for treatment. Among 6781 patients (mean 74±9 years; 27% women), 3393 (50%) had SRP. Older age, secondary prevention indication, and device implantation in the southern or western United States were associated with lower use of SRP. The cumulative incidence rate of implantable cardioverter-defibrillator shocks was lower in the SRP group (5.1% shocks/patient year) compared with the non-SRP group (7.2% shocks/patient year) (adjusted hazard ratio [HR], 0.83 [95% CI, 0.73-0.96]; P=0.005). Over a median follow-up of 2.9 years, 739 deaths occurred in the SRP group and 822 deaths occurred in the non-SRP group (adjusted HR, 0.97 [95% CI, 0.88-1.07]; P=0.569). SRP was associated with a lower all-cause mortality among patients without ischemic heart disease compared with patients with ischemic heart disease (adjusted HR, 0.64 [95% CI, 0.48-0.87] versus adjusted HR, 1.02 [95% CI, 0.92-1.14]; Pinteraction=0.004). CONCLUSIONS: Adoption of SRP is low in real-world clinical practice. Age, clinical variables, and geographic factors are associated with use of SRP. In this study, SRP-associated decrease in mortality was limited to patients without ischemic heart disease.