Sudden Cardiac Death Group Research Articles

Evaluation of Incidence and Risk Factors of Sudden Cardiac Death in Patients with Chronic Coronary Syndrome Attending Physical Training.

Regular physical activity is recommended topatients with chronic coronary syndrome (CCS). However, vigorous physical exercise occurs as a risk factor of sudden cardiac death (SCD). The effect of short-term and irregular exercise is controversial. The aim of this research is to assess the role of regular training in the incidence of SCD and to identify risk factors among patientswith CCS participating in a long-term training program. Data of risk factors, therapy, and participation were collected retrospectively for a 10-year period, assessing the length and regularity of participation. The incidence of SCD and related mortality was registered. ANOVA, χ2 test, and multinominal logistic regression and stepwise analysis were performed. The Incidence of chronic kidney disease (CKD) was higher (p < 0.01) and taking beta-blockers (BBs) was lower (p = 0.04) in the SCD group. Irregular training, lack of BBs, smoking, and CKD increased the risk of SCD, while female sex, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers (ACEI/ARBs), and BBs decreased the risk of SCD. Taking ACEI/ARBs and BBs proved to be a protective factor, emphasizing the use of optimal medical therapy. Assessment of cardiac risk factors and control of comorbidities also proved to be important. The occurrence of SCD was connected to irregular physical activity, probably relating to the adverse effects of ad hoc exercising.

The value of cardiac MRI in the risk stratification in patients with hypertrophic cardiomyopathy

Objective: To explore the value of cardiac magnetic resonance imaging (CMR) in the risk stratification of hypertrophic cardiomyopathy (HCM). Methods: HCM patients who underwent CMR examination in Fuwai Hospital between March 2012 and May 2013 were retrospectively enrolled. Baseline clinical and CMR data were collected and patient follow-up was performed using telephone contact and medical record. The primary composite endpoint was sudden cardiac death (SCD) or and equivalent event. The secondary composite endpoint was all-cause death and heart transplant. Patients were divided into SCD and non-SCD groups. Cox regression was used to explore risk factors of adverse events. Receiver operating characteristic (ROC) curve analysis was used to assess the performance and the optimal cut-off of late gadolinium enhancement percentage (LGE%) for the prediction of endpoints. Kaplan-Meier and log-rank tests were used to compare survival differences between groups. Results: A total of 442 patients were enrolled. Mean age was (48.5±12.4) years and 143(32.4%) were female. At (7.6±2.5) years of follow-up, 30 (6.8%) patients met the primary endpoint including 23 SCD and 7 SCD equivalent events, and 36 (8.1%) patients met the secondary endpoint including 33 all-cause death and 3 heart transplant. In multivariate Cox regression, syncope(HR=4.531, 95%CI 2.033-10.099, P<0.001), LGE% (HR=1.075, 95%CI 1.032-1.120, P=0.001) and left ventricular ejection fraction (LVEF) (HR=0.956, 95%CI 0.923-0.991, P=0.013) were independent risk factors for primary endpoint; Age (HR=1.032, 95%CI 1.001-1.064, P=0.046), atrial fibrillation (HR=2.977, 95%CI 1.446-6.131, P=0.003),LGE% (HR=1.075, 95%CI 1.035-1.116, P<0.001) and LVEF (HR=0.968, 95%CI 0.937-1.000, P=0.047) were independent risk factors for secondary endpoint. ROC curve showed the optimal LGE% cut-offs were 5.1% and 5.8% for the prediction of primary and secondary endpoint, respectively. Patients were further divided into LGE%=0, 0<LGE%<5%, 5%≤LGE%<15% and LGE%≥15% groups. There were significant survival differences between these 4 groups whether for primary endpoint or secondary endpoint (all P<0.001) and the accumulated incidence of primary endpoint was 1.2% (2/161), 2.2% (2/89), 10.5% (16/152) and 25.0% (10/40), respectively. Conclusion: LGE is an independent risk factor for SCD events as well as all-cause death and heart transplant. LGE is of important value in the risk stratification in patients with HCM.

Clinical Presentation and Medium-Term Outcomes of Children With Anomalous Aortic Origin of the Left Coronary Artery: High-Risk Features Beyond Interarterial Course

Anomalous aortic origin of the left coronary artery (AAOLCA) confers a rare, but significant, risk of sudden cardiac death in children. Surgery is recommended for interarterial AAOLCA, and other subtypes considered benign. We aimed to determine the clinical characteristics and outcomes of 3 AAOLCA subtypes. All patients with AAOLCA <21 years old were prospectively enrolled (December 2012-November 2020), including group 1: AAOLCA from the right aortic sinus with interarterial course, group 2: AAOLCA from the right aortic sinus with intraseptal course, and group 3: AAOLCA with a juxtacommissural origin between the left and noncoronary aortic sinus. Anatomic details were assessed using computed tomography angiography. Provocative stress testing (exercise stress testing and stress perfusion imaging) was performed in patients >8 years old or younger if concerning symptoms. Surgery was recommended for group 1 and in select cases in group 2 and group 3. We enrolled 56 patients (64% males) with AAOLCA (group 1, 27; group 2, 20; group 3, 9) at median age of 12 years (interquartile range, 6-15). Intramural course was common in group 1 (93%) compared with group 3 (56%) and group 2 (10%). Seven (13%) presented with aborted sudden cardiac death (group 1, 6/27; group 3, 1/9); 1 (group 3) with cardiogenic shock. Fourteen/42 (33%) had inducible ischemia on provocative testing (group 1, 32%; group 2, 38%; group 3, 29%). Surgery was recommended in 31/56 (56%) patients (group 1, 93%; group 2, 10%; and group 3, 44%). Surgery was performed in 25 patients at a median age 12 (interquartile range, 7-15) years; all have been asymptomatic and free from exercise restrictions at median follow-up of 4 (interquartile range, 1.4-6.3) years. Inducible ischemia was noted in all 3 AAOLCA subtypes while most aborted sudden cardiac deaths occurred in interarterial AAOLCA (group 1). Aborted sudden cardiac death and cardiogenic shock may occur in AAOLCA with left/nonjuxtacommissural origin and intramural course, thus also deemed high-risk. A systematic approach is essential to adequately risk stratify this population.

Galectin-3 Is Associated with Cardiac Fibrosis and an Increased Risk of Sudden Death.

Myocardial fibrosis is a common postmortem finding among individuals with Sudden Cardiac Death (SCD). Numerous in vivo and in vitro studies have shown that increased galectin-3 (gal3) expression into the myocardium is associated with higher incidence of fibrosis. Although elevated gal3 expression is linked with myocardial fibrosis, its role in predicting the risk of SCD is unknown. We reviewed the clinical datasets and post-mortem examination of 221 subjects who had died suddenly. We examined myocardial pathology including the extent of cardiac hypertrophy, fibrosis, and the degree of coronary atherosclerosis in these subjects. In a select group of SCD subjects, we studied myocardial gal3 and periostin expression using immunohistochemistry. To further examine if a higher level of circulating gal3 can be detected preceding sudden death, we measured serum gal3 in a porcine model of subtotal coronary artery ligation which shows an increased tendency to develop lethal cardiac arrhythmias, including ventricular tachycardia or fibrillation. Of the total 1314 human subjects screened, 12.7% had SCD. Comparison of age-matched SCD with non-SCD subjects showed that SCD groups had excessive myocardial fibrosis involving both the left ventricular free wall and interventricular septum. In pigs with subtotal coronary artery ligation and SCD, we detected significantly elevated circulating gal3 levels approximately 10 days preceding the SCD event. Immunohistochemistry showed increased myocardial gal3 and periostin expression in pigs that died suddenly, compared to the controls. Our study shows that increased gal3 is associated with a higher risk of myocardial fibrosis and the risk of SCD. This supports the importance of larger translational studies to target gal3 to prevent cardiac fibrosis and attenuate the risk of SCD.

Significance of postmortem biomarkers and multimarker strategy in sudden cardiac death

The most common cause in the etiology of sudden cardiac death (SCD) is ischemic heart disease due to atherosclerosis. Postmortem diagnosis can be made by histopathological examinations, but routine histopathological examinations are limited, especially in the early period of postmortem ischemia. For this reason, many methods are being investigated for the postmortem diagnosis of ischemia, and postmortem biochemical studies are promising. In our study, we evaluated the biochemical markers; hs-cTnT, NT-proBNP, H-FABP, pentraxin-3, copeptin, ischemic modified albumin (IMA), and PAPP-A in postmortem serums. In forensic pathology practice, it was investigated whether it would be useful to go to the diagnosis by measuring more than one marker in a single biological fluid in SCD cases. The study included 35 sudden cardiac death cases and 24 control cases and as a result of our study, hs-cTnT, NT-proBNP, and H-FABP values were found to be significantly higher in the SCD group than in the control group. Within the scope of the multi-marker strategy, models were tried to be developed in which the markers were used together, and it was concluded that the model consisting of the myocardial ischemia marker hs-cTnT, the myocardial stress marker NT-proBNP, and the inflammation marker pentraxin 3 was the most accurate combination by correctly classifying the cases at a rate of 94.9%. As a result, it was thought that it would be appropriate to use the multi-marker strategy which is widely used in clinical applications, also in forensic medicine applications.

Using QRS loop descriptors to characterize the risk of sudden cardiac death in patients with structurally normal hearts.

The predictive value of non-invasive electrocardiographic examination findings for the risk of sudden cardiac death (SCD) in populations with structurally normal hearts remains unclear. This study aimed to investigate the characteristics of the QRS vectorcardiography of surface electrocardiography in patients with structurally normal hearts who experienced SCD. We consecutively enrolled patients who underwent vectorcardiography between March 2017 and December 2018 in a tertiary referral medical center. These patients didn't have structural heart diseases, histories of congestive heart failure, or reduced ejection fraction, and they were classified into SCD (with aborted SCD history and cerebral performance category score of 1) and control groups (with an intervention for atrioventricular node reentrant tachycardia and without SCD history). A total of 162 patients (mean age, 54.3±18.1 years; men, 75.9%), including 59 in the SCD group and 103 in the control group, underwent propensity analysis. The baseline demographic variables, underlying diseases, QRS loop descriptors (the percentage of the loop area, loop dispersion, and inter-lead QRS dispersion), and other electrocardiographic parameters were compared between the two groups. In the univariate and multivariate analyses, a smaller percentage of the loop area (odds ratio, 0.0003; 95% confidence interval, 0.00-0.02; p<0.001), more significant V4-5 dispersion (odds ratio, 1.04; 95% confidence interval, 1.02-1.07; p = 0.002), and longer QRS duration (odds ratio, 1.05; 95% confidence interval, 1.00-1.10; p = 0.04) were associated with SCD. In conclusion, the QRS loop descriptors of surface electrocardiography could be used as non-invasive markers to identify patients experiencing aborted SCD from a healthy population. A decreased percentage of loop area and elevated V4-5 QRS dispersion values assessed using vectorcardiography were associated with an increased risk of SCD in patients with structurally normal hearts.

Methylation of F2RL3, CDKN2A genes and sudden cardiac death

The aim of the study was to evaluate the association of methylation of the F2RL3, CDKN2A gene with sudden cardiac death (SCD). Material and methods. Case-control study design. The SCD group included 150 deceased men (mean age 46.7 ± 9.2 years) with the main pathological diagnoses of acute circulatory failure, acute coronary insufficiency, which meets the SCD criteria of the European Society of Cardiology. The control group included 150 men who died suddenly, but not due to cardiovascular pathology (mean age 42.6 ± 1.2 years). DNA was isolated by phenol-chloroform extraction from myocardial tissue in both groups. The methylation status of the F2RL3 gene (19: 16890405-16890606, GRCh38.p13) and the CDKN2A gene (9: 21974726-21974877, GRCh38.p13) was assessed by methyl-specific polymerase chain reaction. Results. In the SCD group, 17.3 % (26/150) had the F2RL3 gene completely methylated (MM); in 6.0 % (9/150) it is completely unmethylated (UU); 76.7 % (115/150) had both methylated and unmethylated F2RL3 (MU) gene. In the control group, 16 % (24/150) had the F2RL3 gene completely methylated (MM); in 5.3 % (8/150), it is completely unmethylated (UU); 78.7 % (118/150) had both methylated and unmethylated F2RL3 (MU) gene. When comparing the groups, there were no statistically significant differences in the methylation status of the F2RL3 gene between the groups (p &gt; 0.05). In all subjects in the SCD group and the control group, the CDKN2A gene is completely unmethylated. Conclusions. Methylation of genes F2RL3, CDKN2A is not associated with sudden cardiac death.

Abstract 10541: Clinical Risk Factors and Myocardial Fibrosis in Subjects Who Died Suddenly: Pilot Data from A 10-Year Post-Mortem Data Registry

Introduction: Sudden cardiac death (SCD) is responsible for approximately 380,000 deaths per year. One third of the patients dying of heart disease present with SCD as the first manifestation. There are limited data on the clinico-pathological determinants of SCD. Hypothesis: We hypothesized that, compared to overall deaths, silent coronary atherosclerosis and myocardial fibrosis could be associated with increased frequency of SCDs. Methods: We reviewed the post-mortem data registry from two tertiary care hospitals located at the Buffalo-Niagara Region. Of the 1,314 subjects that underwent comprehensive post-mortem analysis, we identified 187 subjects that died suddenly. For this initial pilot data analysis protocol, we compared the demographic, clinical, electrocardiographic and coronary vascular and myocardial histopathological characteristics of 109 subjects with sudden death vs. 34 age-matched controls with non-sudden death. Results: We found that, of the total 1,314 subjects screened, 14% had SCD. Comparison of age-matched SCD with non-SCD subjects (age in years, SCD: 60±14; non-SCD: 61±20) showed that SCD groups had larger cardiac size (heart weight in grams, SCD: 550±150; non-SCD: 480±117, P=0.03), increased wall thickness (posterior wall thickness in cm, SCD: 1.7±0.4; non-SCD: 1.5±0.2, P=0.01), but reduced LV function reported before the event (LV ejection fraction in %, SCD: 41±17; non-SCD: 58±9, P=0.007). In addition, SCD groups had higher frequency of coronary atherosclerosis (SCD, 76% vs., non-SCD, 52%, P=0.007), and myocardial fibrosis involving both left ventricular free wall (SCD, 47% vs., non-SCD, 26%, P=0.03), and interventricular septum (SCD, 29% vs., non-SCD, 3%, P=0.02). There were no differences on serum electrolytes, circulating biomarkers and the extent of right ventricular fibrosis. Conclusions: The subjects that died suddenly had larger cardiac size, reduced contractile function with myocardial interstitial fibrosis, and silent coronary atherosclerosis. Further studies are in progress to fully examine the clinico-pathological correlates of SCD in our longitudinal study cohorts.

Abstract P113: Underestimation Of Sudden Death Due To Restrictive Sudden Cardiac Death Criteria

Background: Efforts to prevent sudden death may be hampered by restrictive case definitions impairing accurate estimates of incidence and risk factors of sudden death. Sudden cardiac death (SCD) definitions include requirements for presence of comorbid coronary artery disease (CAD) and various time criteria since onset of symptoms or when victims were last seen well. We compared prevalence of three SCD definitions within a registry of all-cause natural, sudden deaths. Hypothesis: We assessed the hypothesis that the restrictive criteria of three SCD definitions underestimate sudden death and exclude populations with increased medical comorbidities. Methods: Using a registry of 399 adjudicated sudden death cases among adults aged 18-64 in Wake County, North Carolina in 2013-2015, we included 271 cases after excluding for missing values, chronic kidney disease, or heart failure. Time since last seen alive was classified as less than one hour or 24 hours from scene reports. Presence of CAD and co-morbidities were defined from clinical or autopsy records. Prevalence of SCD using criteria defined by Atherosclerosis Risk in Communities (ARIC), the World Health Organization (WHO), and the Oregon Sudden Unexpected Death (SUD) registry were calculated. Prevalence of SCD risk factors were calculated for the 3 SCD subgroups and compared to the original 271 victims using two-sample t-test and Fisher’s exact test for continuous and categorical variables. Results: Among the 271 cases, criteria were met for the three SCD definitions for n (%): ARIC 28 (10%), WHO 54 (20%), and SUD 90 (33%) (Table 1). ARIC and WHO-defined SCD cases were younger than the original 271 cases. There were no significant differences in sociodemographic and clinical factors by any SCD group compared to the original 271 cases. Conclusion: Restrictive SCD definitions that require the presence of CAD or a specific time frame of identification of death underestimate the incidence of sudden death and hinder effective prevention efforts for sudden death.

Association of single-­nucleotide polymorphisms rs10867772, rs4700290 with sudden cardiac death

The aim of the research is to verify the association with sudden cardiac death (SCD) of single nucleotide polymorphisms rs10867772 and rs4700290, identified as new molecular genetic markers of SCD in the own genome-wide pooled allelotyping.Material and methods. Case-control study. The SCD group is formed using the criteria of the European Society of Cardiology from the DNA bank of suddenly deceased residents of the Oktyabrsky district of Novosibirsk (n = 437, average age—53.1 ± 9.0 years, men — 73.5%, women — 26.5%) The control group (n = 405, average age 53.2 ± 9.2 years, men — 70.0%, women — 30.0%) is formed from the DNA bank of participants of MONICA and HAPIEE projects. DNA was isolated by phenol-­chloroform extraction from myocardial tissue in the SCD group and venous blood in the control group. Genotyping was performed by the PCR-RFLP method.Results. No statistical significance was found in allele and genotype frequencies of rs10867772 and rs4700290 between groups, even in separating in sex and age (p&gt; 0.05). Conclusion. Single nucleotide polymorphism rs10867772 and rs4700290 are not associated with SCD.

Clinical Associations between Serial Electrocardiography Measurements and Sudden Cardiac Death in Patients with End-Stage Renal Disease Undergoing Hemodialysis.

The rate of sudden cardiac death (SCD) for hemodialysis (HD) patients is significantly higher than that observed in the general population and have the highest risk for arrhythmogenic death. In this multi-center study, patients starting hemodialysis in each hospital were enrolled; they underwent regular check-ups in an open-patient clinic. We examined serial electrocardiography (ECG) data in patients undergoing HD and determined their associations with the occurrence of SCD. Of 678 enrolled subjects who underwent serial ECG before and after hemodialysis, 291 died and 39 developed SCD. In all subjects, the QT peak-to-end (QTpe) interval at all leads and QRS duration were shortened after hemodialysis. The SCD group showed a significant change in the QTpe interval of the inferior, anterior, and lateral leads before and after hemodialysis compared with the survivor group (p < 0.001). In the pre-hemodialysis ECG, SCD patients had significantly longer QTpe intervals in all leads (p < 0.001) and a longer QRS duration (92.6 ± 14.0 vs. 100.6 ± 14.9 ms, p = 0.015) than survivors. In conclusion, patients with a longer QTpe interval before hemodialysis and large changes in ECG parameters after hemodialysis might be at a higher risk of SCD. Therefore, changes in the ECG before and after hemodialysis could help to predict SCD.

The Use of Gas Chromatography Coupled with High-Resolution Mass Spectrometry-Based Untargeted Metabolomics to Discover Metabolic Changes and Help in the Determination of Complex Causes of Death: A Preliminary Study

The determination of cause of death (COD) is one of the most important tasks in forensic practice and is mainly based on macroscopical and microscopical morphological signatures. However, some CODs are hard to determine because the significant morphological signatures can be nonspecific, variable, subjective, or even absent in the real world. In this study, gas chromatography coupled with high-resolution mass spectrometry (GC–HRMS)-based untargeted metabolomics was employed to obtain plasma metabolic profiles of rats that died from anaphylactic shock (AS), mechanical asphyxia (MA), or sudden cardiac death (SCD). The metabolic alterations of each COD group compared to the control group were investigated using a principal component analysis, partial least-squares discriminant analysis, the Wilcoxon test, and fold change analysis. A range of differential features was screened, and 11, 8, and 7 differential metabolites were finally verified for the AS, MA, and SCD groups, respectively. We proposed some explanations that may account for these metabolic differences, including glucose metabolism, the tricarboxylic acid cycle, glycolysis, lipid metabolism, creatinine catabolism, and purine metabolism. Next, for each COD, we used its differential metabolites, which were obtained through comparisons of each COD group to the control group and represented the metabolic changes of the individual COD, to perform a receiver operating characteristic (ROC) analysis to preliminarily evaluate their ability to discriminate each COD group from the other COD groups. We found that creatinine in the AS group and malic acid and uric acid in the MA group might represent some specific metabolic changes for the relevant COD with high areas under the curve in the ROC curve analysis. Moreover, the combination panel for AS or MA also showed a good ability to discriminate it from the others. However, SCD had fewer metabolic signatures and was relatively harder to discriminate from the other CODs in our work. The preliminary study demonstrates the feasibility of GC–HRMS-based untargeted metabolomics as a promising tool to reveal metabolic changes in different death processes and to determine the complex CODs.

ABCA1 gene promoter methylation and sudden cardiac death

Aim . A study of the association of the methylation of the promoter of the ABCA1 gene with sudden cardiac death (SCD). Materials and methods . The study design is based on the case-control principle. The SCD group included 150 men (mean age (46.7 ± 9.2) years) who died of sudden cardiac death according to forensic medical examination data (the main pathological diagnoses are acute circulatory failure, acute coronary insufficiency). The control group included 150 men (mean age (42.6 ± 1.2) years) who died suddenly, but not due to cardiovascular pathology. DNA was isolated by phenol-chloroform extraction from myocardial tissue. The methylation status of the ABCA1 gene promoter was assessed by methyl-specific polymerase chain reaction. The results obtained were statistically processed in SPSS 16.0 using Pearson’s test and Fisher’s test with Yates’ correction for continuity. P &lt; 0.05 was used as a level of significance. Results . Comparing the groups revealed statistically significant differences in the methylation status of the gene promoter ( p = 0.015). In the SCD group, the proportion of individuals whose ABCA1 gene promoter is methylated is statistically significantly higher compared to the control group ( p = 0.020; OR = 5.86; 95% CI (1.28–26.89)). Conclusion. Methylation of the promoter of the ABCA1 gene is associated with sudden cardiac death.

Next generation sequencing in sudden cardiac death (pilot study)

Aim.To search for causal mutations in candidate genes responsible for the development of sudden cardiac death (SCD) in men who died under the age of 45.Materialandmethods.The SCD group (n=37) was formed using the criteria the World Health Organization and the European Society of Cardiology. Autopsy material was collected from men who died suddenly outside medical institutions and underwent forensic medical examination according to the standard protocol. Autopsy revealed no morphological changes that could explain sudden death. The mean age was 32,4±6,4 years. Genomic DNA was isolated from myocardial tissue using phenol-chloroform extraction. Clinical exome sequencing was performed. At first, we analyzed the results of sequencing of 24 genes, mutations in which lead to cardiovascular diseases associated with an increased risk of SCD:KCNQ1,KCNH2,SCN5A,AKAP9,ANK2,CACNA1C,CALM1,CALM2,CAV3,KCNE1,KNCJNE2,KCNE2,SCN4B,SNTA1,MYH2,APOB,KCNA5,TGFB3,NEB,PDX1,FLNC,PLEC,KCND3.Results.Of 37 samples, we revealed 13 probable pathogenic missense mutations in 9 samples (24,3%). Of 13 probable pathogenic variants, 5 were new.Conclusion.This pilot study provides following conclusions: it is necessary to continue molecular autopsy research in Russia; to increase the effectiveness of detecting causal mutations, it is necessary to reduce the age of patients with SCD included in the study; studying the families of deceased; cooperation of experienced specialists — forensic pathologist, laboratory geneticist, cardiologist.

Re-print: Maintenance (r) Alpha Lipoic Acid Reduces Sudden Cardiac Death in Geriatric Diabetes Mellitus II Patients

Background: Diabetes carries a two-fold risk of Sudden Cardiac Death (SCD). Diabetic Autonomic Neuropathy (DAN), often progressing to Cardiovascular Autonomic Neuropathy (CAN, critically low parasympathetic tone [P]), increases death 3.5-fold over 5 years, half sudden or non- renal. Oxidative stress is a major cause of DAN. Also, increased sympathetic tone (S), High Sympathovagal Balance [SB&gt;2.5] increases SCD risk. Objective: Dysautonomic diabetic II patients were treated with the antioxidant (r) Alpha Lipoic Acid (ALA), autonomic function followed, and Sudden Death (SD) compared to untreated patients. Methods: 133 patients (mean age 66y/o) with DAN or CAN, diagnosed using the ANX 3.0 Autonomic Monitor (Physio PS, Inc., Atlanta, GA) was offered (r)-ALA: 83 agreed (Group 1), and 50 refused (Group 2). P and S were re- measured up to 3 times/yr (mean f/u 6.31 yrs); SCDs were recorded. Results: A 43% Relative Risk Reduction (RRR) in SCD occurred with (r)- ALA (25% SCD Group 1 vs. 44% SCD Group 2, p=0.0076). Initial to final patients with high SB or CAN were 21.7%-12% (p=0.010), 10.8%- 15.7% (p=0.045), Group 1 vs. 24%-22% (p=ns), 6%-12% (p=0.083), Group 2. Only Group 1 survivors increased mean resting P. The progressive increase in P’s decline, increasing CAN risk, in the other patients correlated with mortality (p&lt;0.001) and (r) ALA dose. Initially, Group 1 had insignificantly less high SB (p=0.449) and significantly more CAN (p=0.013) vs. Group 2. Finally, Group 1 had significantly less high SB (p=0.0967) vs. Group 2, also improving to insignificantly more CAN (p=0.261). Conclusion: (r)-ALA was associated with a 43% RRR of SCD and favorable P and S changes.

Non-invasive detection of exercise-induced cardiac conduction abnormalities in sudden cardiac death survivors in the inherited cardiac conditions.

Rate adaptation of the action potential ensures spatial heterogeneities in conduction across the myocardium are minimized at different heart rates providing a protective mechanism against ventricular fibrillation (VF) and sudden cardiac death (SCD), which can be quantified by the ventricular conduction stability (V-CoS) test previously described. We tested the hypothesis that patients with a history of aborted SCD due to an underlying channelopathy or cardiomyopathy have a reduced capacity to maintain uniform activation following exercise. Sixty individuals, with (n = 28) and without (n = 32) previous aborted-SCD event underwent electro-cardiographic imaging recordings following exercise treadmill test. These included 25 Brugada syndrome, 13 hypertrophic cardiomyopathy, 12 idiopathic VF, and 10 healthy controls. Data were inputted into the V-CoS programme to calculate a V-CoS score that indicate the percentage of ventricle that showed no significant change in ventricular activation, with a lower score indicating the development of greater conduction heterogeneity. The SCD group, compared to those without, had a lower median (interquartile range) V-CoS score at peak exertion [92.8% (89.8-96.3%) vs. 97.3% (94.9-99.1%); P < 0.01] and 2 min into recovery [95.2% (91.1-97.2%) vs. 98.9% (96.9-99.5%); P < 0.01]. No significant difference was observable later into recovery at 5 or 10 min. Using the lowest median V-CoS scores obtained during the entire recovery period post-exertion, SCD survivors had a significantly lower score than those without for each of the different underlying aetiologies. Data from this pilot study demonstrate the potential use of this technique in risk stratification for the inherited cardiac conditions.

Maintenance (r) Alpha Lipoic Acid Reduces Sudden Cardiac Death in Geriatric Diabetes Mellitus II Patients

Background: Diabetes carries a two-fold risk of Sudden Cardiac Death (SCD). Diabetic Autonomic Neuropathy (DAN), often progressing to Cardiovascular Autonomic Neuropathy (CAN, critically low parasympathetic tone [P]), increases death 3.5-fold over 5 years, half sudden or non-renal. Oxidative stress is a major cause of DAN. Also, increased sympathetic tone (S), High Sympathovagal Balance [SB&gt;2.5] increases SCD risk. Objective: Dysautonomic diabetic II patients were treated with the antioxidant (r) Alpha Lipoic Acid (ALA), autonomic function followed, and Sudden Death (SD) compared to untreated patients. Methods: 133 patients (mean age 66y/o) with DAN or CAN, diagnosed using the ANX 3.0 Autonomic Monitor (Physio PS, Inc., Atlanta, GA) was offered (r)-ALA: 83 agreed (Group 1), and 50 refused (Group 2). P and S were re-measured up to 3 times/yr (mean f/u 6.31 yrs); SCDs were recorded. Results: A 43% Relative Risk Reduction (RRR) in SCD occurred with (r)-ALA (25% SCD Group 1 vs. 44% SCD Group 2, p=0.0076). Initial to final patients with high SB or CAN were 21.7%-12% (p=0.010), 10.8%-15.7% (p=0.045), Group 1 vs. 24%-22% (p=ns), 6%-12% (p=0.083), Group 2. Only Group 1 survivors increased mean resting P. The progressive increase in P’s decline, increasing CAN risk, in the other patients correlated with mortality (p&lt;0.001) and (r) ALA dose. Initially, Group 1 had insignificantly less high SB (p=0.449) and significantly more CAN (p=0.013) vs. Group 2. Finally, Group 1 had significantly less high SB (p=0.0967) vs. Group 2, also improving to insignificantly more CAN (p=0.261). Conclusion: (r)-ALA was associated with a 43% RRR of SCD and favorable P and S changes.

Circadian rhythm dynamics on multiscale entropy identifies autonomic dysfunction associated with risk of ventricular arrhythmias and near syncope in chronic kidney disease

BackgroundA discordant biological clock could potentially induce sudden cardiac death (SCD). We aimed to evaluate the circadian change of heart rate variability (HRV) and its relationship to the risks of ventricular arrhythmia (VA) and near syncope in patients with chronic kidney disease (CKD). MethodsIn this retrospective study, non-CKD and CKD patients were enrolled and underwent a 24-hour Holter examination for linear and nonlinear HRV analyses. The multiscale entropy (MSE) method was selected for nonlinear HRV analyses. The documented VAs or episodes of near syncope were classified as high-risk SCD group (n=8) and others as low-risk SCD group (n=21). ResultsIn linear analyses, time and frequency domains revealed no significant difference between groups. In nonlinear analyses with MSE, MSE5, MSE6–20, and MSEslope 5 were significantly lower (p=0.002, p<0.0001, and p=0.013) in the high-risk SCD group, compared to those in the low-risk SCD group, respectively. Comparing between daytime and nighttime within each group, the MSE5 revealed no difference in the high-risk SCD group (p=0.128), whereas the daytime was significantly higher in the low-risk SCD group (p=0.048). The area under the curve (AUC) analysis revealed MSE6–20 has the best predictive power associated with VAs and near syncope with a cut-off value of ≤24.64 (p<0.001). ConclusionsNonlinear analysis with MSE demonstrated the loss of circadian change in CKD patients and was associated with a higher risk for VAs and near syncope. The MSE method demonstrated the diurnal change of rhythm dynamics which identifies potential autonomic dysfunction leading to poor prognosis.

1228 New predictors of sudden cardiac death in hypertrophic cardiomyopathy

Abstract BACKGROUND Hypertrophic cardiomyopathy (HCM) is a heart disease characterized by hypertrophy of the left ventricular myocardium. HCM is the most common cause of sudden cardiac death (SCD) in young people and competitive athletes due to fatal ventricular arrhythmias. However, in most patients, HCM has a benign course. That is why it is of utmost importance to properly evaluate patients and identify those who would benefit from a cardioverter-defibrillator (ICD) implantation. The HCM SCD-Risk Calculator is a useful tool for estimating the risk of SCD. The parameters included in the model at evaluation are: age, maximum left ventricular (LV) wall thickness, left atrial (LA) dimension, maximum gradient in left ventricular outflow tract, family history of SCD, non-sustained ventricular tachycardia (nsVT) and unexplained syncope. Nevertheless, there is potential to improve and optimize the effectiveness of this tool in clinical practice. Therefore, the following new risk factors are proposed: LV global longitudinal strain (GLS), LV average strain (ASI) and LA volume index (LAVI). GLS and ASI are sensitive and noninvasive methods of assessing LV function. LAVI more accurately characterizes the size of the left atrium in comparison to the LA dimension. METHODS 252 HCM patients (aged 20-88 years, of which 49,6% were men) treated in our Department from 2005 to 2018, were examined. The follow-up period was 0-13 years (average: 3.8 years). SCD was defined as sudden cardiac arrest (SCA) or an appropriate ICD intervention. All patients underwent an echocardiographic examination. The medical and family histories were collected and ICD examinations were performed. RESULTS 76 patients underwent an ICD implantation during the follow-up period. 20 patients have reached an SCD end-point. 1 patient died due to SCA and 19 had an appropriate ICD intervention. There were statistically significant differences of GLS and ASI values between SCD and non-SCD groups; p = 0.026389 and p = 0.006208, respectively. The average GLS in the SCD group was -12.4% ± 3.4%, and -15.1% ± 3.5% in the non-SCD group. The average ASI values were -9.9% ± 3.8% and -12.4% ± 3.5%, respectively. There was a statistically significant difference between LAVI values in SCD and non-SCD groups; p = 0.005343. The median LAVI value in the SCD group was 45.7 ml/m2 and 37.6 ml/m2 in the non-SCD group. The ROC curves showed the following cut-off points for GLS, ASI and LAVI: -13.8%, -13.7% and 41 ml/m2, respectively. Cox’s proportional hazards model for the parameters used in the Calculator was at the borderline of significance; p = 0.04385. The model with new variables (GLS and LAVI instead of LA dimension) was significant; p = 0.00094. The important factors were LAVI; p = 0.000075 and nsVT; p = 0.012267. CONCLUSIONS The proposed new SCD risk factors were statistically significant in the study population and should be taken into account when considering ICD implantation.

Evaluation of Agonal Cardiac Function for Sudden Cardiac Death in Forensic Medicine with Postmortem Brain Natriuretic Peptide (BNP) and NT-proBNP: A Meta-analysis.

Sudden cardiac death (SCD) is an unexpected death caused by a sudden loss of cardiac function, which is currently a global public health problem. Evaluation of the agonal cardiac function of the deceased is a quite important task for the diagnosis of SCD in forensic medicine. Brain natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are currently considered as significant biomarkers for the diagnosis of heart failure in both clinical and forensic practices. To investigate the postmortem evaluation roles of postmortem BNP and NT-proBNP levels for SCD, the present study meta-analyzed eight related studies from Embase, Cochrane Library, PubMed, China Biomedical Literature Database, China National Knowledge Infrastructure, and Wanfang Data. Newcastle-Ottawa Quality Assessment Scale was used to assess the quality of the included literature, and the meta-analysis was performed by RevMan 5.3.5 software. Postmortem NT-proBNP in pericardial fluid showed higher levels in the SCD group than that of the non-SCD group with the weighted mean difference=3665.74, 95% confidence interval: 1812.89-5518.59, and p=0.0001. However, postmortem levels of BNP in pericardial fluid and NT-proBNP in serum revealed no statistical difference between SCD and non-SCD subjects. The results of present meta-analysis demonstrated that postmortem NT-proBNP in the pericardial fluid could be used as an ancillary indicator for evaluation of agonal cardiac function in forensic medicine.