Increased Risk Of Sudden Cardiac Death Research Articles

The Interplay of Type 2 Diabetes Status, Cardiorespiratory Fitness Level, and Sudden Cardiac Death: A Prospective Cohort Study

BackgroundTo evaluate the individual and joint effects of type 2 diabetes (T2D) status and cardiorespiratory fitness (CRF) level with sudden cardiac death (SCD) risk. MethodsPrevalent T2D was defined based on guideline recommendations, and CRF level was assessed using a respiratory gas-exchange analyzer during exercise testing at baseline, in 2308 men aged 42-61 years. T2D status was classified as either “Yes” or “No,” and CRF level was classified as low, medium, or high. Cox regression analysis was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for SCD. ResultsA total of 264 SCDs occurred during a median follow-up of 28.1 years. Comparing Yes vs No history of T2D, the multivariable-adjusted HR (95% CI) for SCD was 1.79 (1.19-2.72). Comparing low vs high CRF levels, the corresponding adjusted HR (95% CI) for SCD was 1.77 (1.21-2.58). The HRs persisted when T2D status was further adjusted for CRF level, and vice versa. Compared with No-T2D & medium-high CRF level, men with No-T2D & low CRF and those with Yes-T2D & low CRF had an increased SCD risk: (HR = 1.87, 95% CI, 1.38-2.55) and (HR = 3.34, 95% CI, 2.00-5.57), respectively. No significant association occurred between men with Yes-T2D & medium-high CRF and SCD risk (HR = 1.46, 95% CI, 0.46-4.65). Modest evidence indicated the presence of additive and multiplicative interactions between T2D status and CRF level, in relation to SCD. ConclusionsAn interplay exists between T2D status, CRF level, and SCD risk in middle-aged and older men. Higher CRF levels may mitigate the increased SCD risk observed in men with T2D.

Evaluating the predictive value of late gadolinium enhancement assessed by cardiac magnetic resonance on sudden cardiac death in patients selected for implantable cardioverter defibrillator and cardiac resynchronization therapy implantation: a systematic review and meta-analysis.

Late gadolinium enhancement (LGE) assessed by cardiovascular magnetic resonance (CMR) can evaluate myocardial scar associated with a higher risk of sudden cardiac death (SCD), which can guide the selection between cardiac resynchronization therapy with or without a defibrillator (CRT-P/CRT-D). Our aim was to investigate the association between LGE and SCD risk in patients with CRT using the LGE-CMR technique. We performed a systematic literature search using four databases. The target population was CRT candidates. The primary endpoint was SCD. The risk of bias was assessed using the QUIPS tool. Fifteen eligible articles were included with a total of 2494 patients, of whom 27%, 56%, and 19% had an implantable cardioverter defibrillator (ICD), CRT-D, and CRT-P, respectively. Altogether, 54.71% of the cohort was LGE positive, who had a 72% higher risk for SCD (HR 1.72; 95% CI 1.18-2.50) compared to LGE negatives. In non-ischemic patients, the proportion of LGE positivity was 46.6%, with a significantly higher risk for SCD as compared to LGE negatives (HR 2.42; 95% CI 1.99-2.94). The subgroup of CRT-only patients showed no difference between the LGE-positive vs. negative candidates (HR 1.17; 95% CI 0.82-1.68). Comparable SCD risk was observed between articles with short- (OR 7.47; 95% CI 0.54-103.12) vs. long-term (OR 6.15; 95% CI 0.96-39.45) follow-up time. LGE-CMR positivity was associated with an increased SCD risk; however, in CRT candidates, the difference in risk reduction between LGE positive vs. negative patients was statistically not significant, suggesting a role of reverse remodeling. LGE-CMR before device implantation could be crucial in identifying high-risk patients even in non-ischemic etiology.

Prolonged mHealth-Based Arrhythmia Monitoring in Patients With Hypertrophic Cardiomyopathy (HCM-PATCH): Protocol for a Single-Center Cohort Study.

Patients with hypertrophic cardiomyopathy (HCM) are at increased risk of sudden cardiac death (SCD) due to ventricular arrhythmias and other arrhythmias. Screening for arrhythmias is mandatory to assess the individual SCD risk, but long-term electrocardiography (ECG) is rarely performed in routine clinical practice. Intensified monitoring may increase the detection rate of ventricular arrhythmias and identify more patients with an increased SCD risk who are potential candidates for the primary prophylactic implantation of an implantable cardioverter-defibrillator. To date, reliable data on the clinical benefit of prolonged arrhythmia monitoring in patients with HCM are rare. This prospective study aims to measure the prevalence of ventricular arrhythmias in patients with HCM observed by mobile health (mHealth)-based continuous rhythm monitoring over 14 days compared to standard practice (a 24- and 48-h long-term ECG). The frequency of ventricular arrhythmias in this 14-day period is compared with the frequency in the first 24 or 48 hours for the same patient (intraindividual comparison). Following the sample size calculation, 34 patients with a low or intermediate risk for SCD, assessed by the HCM Risk-SCD calculator, will need to be recruited in this single-center cohort study between June 2023 and February 2024. All patients will receive an ECG patch that records their heart activity over 14 days. In addition, cardiac magnetic resonance imaging and genetic testing data will be integrated into risk stratification. All patients will be asked to complete questionnaires about their symptoms; previous therapy; family history; and, at the end of the study, their experience with the ECG patch-based monitoring. The Hypertrophic Cardiomyopathy: Clinical Impact of a Prolonged mHealth-Based Arrhythmia Monitoring by Single-Channel ECG (HCM-PATCH) study investigates the prevalence of nonsustained ventricular tachycardia (ie, ≥3 consecutive ventricular beats at a rate of 120 beats per minute, lasting for <30 seconds) in low- to intermediate-risk patients with HCM (according to the HCM Risk-SCD calculator) with additional mHealth-based prolonged rhythm monitoring. The study was funded by third-party funding from the Department of Cardiology and Intensive Care Medicine, University Hospital Ostwestfalen-Lippe of Bielefeld University in June 2023 and approved by the institutional review board in May 2023. Data collection began in June 2023, and we plan to end the study in February 2024. Of the 34 patients, 26 have been recruited. Data analysis has not yet taken place. Publication of the results is planned for the fall of 2024. Prolonged mHealth-based rhythm monitoring could lead to differences in the prevalence of arrhythmias compared to 24- and 48-hour long-term ECGs. This may lead to improved identification of patients at high risk and trigger therapeutic interventions that may provide better protection from SCD or atrial fibrillation-related complications such as embolic stroke. Deutsches Register Klinischer Studien DRKS00032144; https://tinyurl.com/498bkrx8. DERR1-10.2196/52035.

Abstract 16938: Epicardial Adipose Tissue on the Risk of Lethal Ventricular Arrhythmias in Patients With Nonischemic Cardiomyopathy Receiving Implantable Cardioverter-Defibrillator

Background: The arrhythmic risk stratification in patients with nonischemic cardiomyopathy (NICM) remains challenging. The implication of epicardial adipose tissue (EAT) on incident sudden cardiac death (SCD) is unclear. Objectives: To assess the relationship between EAT and SCD in NICM patients receiving implantable cardioverter-defibrillators (ICD) and compare this risk to patients with ischemic cardiomyopathy (ICM). Methods: A total of 421 patients scheduled for primary or secondary prevention ICD implantation underwent CMR at 1.5 or 3T, including cine and late gadolinium enhancement (LGE) imaging. EAT volume surrounding both ventricles was quantified with manual delineation on cine short-axis images and calculated by summation of EAT volume of each slice using the modified Simpson rule. LGE was semiautomatically quantified by adjusting a grayscale threshold. The primary endpoint was a composite of ICD therapy, including anti-tachycardia pacing and SCD. Results: We identified 265 NICM patients (mean age 54 years, 73% men), with LGE present in 152 patients (57%), including 85 patients (32%) with secondary prevention ICD. During the median follow-up of 2.9 years, 42 patients (16%) experienced the endpoint. Low EAT was associated with an increased risk of SCD in NICM patients (HR ad per 10ml decrease, 1.54; 95%CI, 1.19-1.96, p&lt;0.001), even after adjustment for other relevant disease variables. A continuous relationship was evident between EAT and subsequent ICD therapies (p=0.001). Even when considering 85 patients with secondary prevention ICD as theoretically having an SCD event, the risk of EAT in predicting SCD remained essentially unchanged. In contrast, EAT was not associated with increased SCD risk in ICM patients. Conclusions: Low EAT was associated with increased SCD risk in NICM patients receiving ICD implantation, especially primary prevention ICD. These data suggest a potential role of EAT in identifying NICM patients at risk of SCD.

Abstract 16793: The Impact of Late Gadolinium Enhancement on Sudden Death Risk Stratification in Older Patients With Hypertrophic Cardiomyopathy

Background: Extensive late gadolinium enhancement (LGE) is now recognized as a risk factor for sudden cardiac death (SCD) in patients with hypertrophic cardiomyopathy (HCM). However, risk for SCD is very low in older (≥60 years) HCM patients, and therefore utility of assessing LGE for risk stratification in this subgroup of patients is uncertain. Objectives: We assessed the relationship between LGE and SCD in older HCM patients and compared this risk to younger patients. Methods: A total of 1735 HCM patients undergoing cardiovascular magnetic resonance (CMR) for initial evaluation from 4 medical centers were followed up for a median of 3.7 years. LGE was semiautomatically quantified by manually adjusting a grayscale threshold. Results: We identified 638 HCM patients ≥60 years of age (up to 90 years), with LGE present in 337 patients (53%), including 28 patients (4%) with extensive LGE occupying ≥15% of left ventricular mass. Neither the presence nor extent of LGE was associated with increased risk for SCD events (HR ad , 1.13; 95%CI, 0.20-6.44, p=0.89 and HR ad per 10% increase, 1.49; 95%CI, 0.46-3.28, p=0.38, respectively), even after adjustment for other relevant disease variables. The risk for SCD at five years was 4% in older HCM patients with extensive LGE ≥15%, and not different compared to older patients with less LGE (1.0%, p=0.25). The performance of the AHA/ACC SCD risk model was not enhanced in older HCM patients by the addition of LGE (continuous net reclassification index, 0.25; 95%CI, -0.35-0.85, p=0.42). In contrast, the extent of LGE was associated with increased SCD risk in patients &lt;60 years, with extensive LGE associated with a 3-fold greater risk. Conclusions: The extent of LGE was not associated with increased SCD risk in HCM patients ≥60 years, even in the presence of other risk markers. These data suggest a limited role for CMR with LGE in older HCM patients to inform SCD risk stratification.

Being Underweight Is Associated with Increased Risk of Sudden Cardiac Death in People with Diabetes Mellitus.

Diabetes mellitus (DM) can cause various atherosclerotic cardiovascular disease including sudden cardiac death (SCD). The impact of being underweight on the risk of SCD in people with DM remains to be revealed. We aimed to evaluate the risk of SCD according to body-mass index (BMI; kg/m2) level in DM population. We used a nationwide healthcare insurance database to conduct this study. We identified people with DM among those who underwent nationwide health screening during 2009 to 2012. Medical follow-up data was available until December 2018. A total of 2,602,577 people with DM with a 17,851,797 person*year follow-up were analyzed. The underweight group (BMI < 18.5) showed 2.4-fold increased risk of SCD during follow-up (adjusted-hazard ratio [HR] = 2.40; 95% confidence interval [CI] = 2.26-2.56; p < 0.001). When normal-BMI group (18.5 ≤ BMI < 23) was set as a reference, underweight group (adjusted-HR = 2.01; 95% CI = 1.88-2.14) showed even higher risk of SCD compared with the obesity group (BMI ≥ 30; adjusted-HR = 0.89; 95% CI = 0.84-0.94). When BMI was stratified by one unit, BMI and SCD risk showed a U-curve association with the highest risk observed at low BMI levels. The lowest risk was observed in 27 ≤ BMI < 28 group. The association between being underweight and increased SCD risk in DM people was maintained throughout various subgroups. Being underweight is significantly associated with an increased risk of SCD in the DM population. A steep rise in the risk of SCD was observed as the BMI level decreased below 23. The lowest risk of SCD was observed in 27 ≤ BMI < 28 group.

Abstract 11634: Fatty Acid Length Dictates Association of Sphingomyelins With Sudden Cardiac Death

Background: Sudden cardiac death (SCD) is a leading cause of mortality worldwide and is precipitated primarily by ventricular tachyarrhythmias related to coronary artery disease. Sphingolipids, composed of ceramides and sphingomyelins, may influence the pathophysiology and risk of SCD through multiple biological activities. Whether the length of the fatty acid conjugated to the sphingolipid species is associated with SCD risk is not known. Methods and Results: Among 4612 Cardiovascular Health Study participants, we identified 215 patients who experienced SCD over a median follow up of 10.2 years. We examined 8 sphingolipids: ceramide and sphingomyelin species containing palmitic acid and species containing, respectively, the very-long-chain saturated fatty acids (VLSFA) arachidic, behenic, and lignoceric acids. In adjusted Cox regression analyses, ceramides and sphingomyelins with palmitic acid were associated with increased SCD risk per standard deviation log difference (ceramide with palmitic acid: hazard ratio 1.34, 95% CI 1.12-1.59; sphingomyelin with palmitic acid: hazard ratio 1.37, 95% CI 1.12-1.67). In contrast, one sphingomyelin with a VLSFA trended towards an association with reduced SCD risk (sphingomyelin with arachidic acid: hazard ratio 0.83, 95% CI 0.71-0.98). Associations were weakened when adjusted for C-reactive protein (CRP), B-type natriuretic peptide, and troponin-T, but did not differ significantly by age, sex, race, body-mass index, or history of coronary heart disease. In comparison, ceramide with palmitic acid was associated with higher risk of nonfatal myocardial infarction, and ceramide with the VLSFA lignoceric acid trended towards lower risk. Conclusions: Our results suggest associations between sphingolipid species and SCD, differing by the length of the acylated saturated fatty acid. Palmitic acid-containing sphingolipids were strongly associated with increased SCD risk, whereas VLSFA-containing sphingomyelins trended toward reduced SCD risk. The study indicates that plasma sphingolipids may influence the risk of SCD, independent of traditional cardiovascular risk factors. Our findings may provide further insight into the pathogenesis of SCD and enhance risk stratification tools.

Deceleration and acceleration capacities of heart rate in patients with hypertrophic cardiomyopathy: results of a five-year prospective study

Aim. To study the features of deceleration capacity (DC) and acceleration capacity (AC) in patients with hypertrophic cardiomyopathy (HCM) and assess the correlation of these indicators with known complications and risk factors for sudden cardiac death (SCD).Material and methods. A total of 50 patients with HCM were examined. Comparable by sex and age, the control group included 50 individuals without cardiovascular diseases. All patients underwent 24-hour electrocardiographic monitoring with the determination of DC and AC. The follow-up period lasted 5 years. Lethal outcomes were recorded in 6%, including SCD — 4%.Results. Patients with HCM were characterized by significantly lower mean DC — 5,5 [3,7; 7,4] vs 7,8 [7,1; 8,5] ms (p=0,0001) and significantly higher AC– -7,4 [-8,9; -5,8] vs -9,3 [-10,0; -8,6] ms (p=0,001) compared with the control group. In 36% of patients with HCM, pathological values of DC ≤4,5 ms were detected, while in all individuals in the control group, DC corresponded to a favorable prognosis (p=0,001). In patients with and without nonsustained ventricular tachycardia (NSVT), a decrease in DC was detected in 56% and 25,5% (p=0,043), respectively, while with and without heart failure (HF) — in 78% and 27% (p=0,016), respectively. In patients with HF (p=0,003) and paroxysmal atrial fibrillation (p=0,023), mean DC values were significantly lower than in patients without these complications. HF was an independent predictor of DC reduction. DC decrease was not associated with an increase in SCD risk estimated using the HCM Risk-SCD calculator.Conclusion. Patients with HCM compared with healthy individuals are characterized by lower DC and higher AC values. Among patients with HCM, a decrease in DC is typical for patients with a more severe disease course (HF, AF, NSVT). However, the rationale for using this indicator in SCD risk stratification needs to be clarified.

Cardiorespiratory Fitness, Inflammation, and Risk of Sudden Cardiac Death in Middle-Aged Men

Inflammation and cardiorespiratory fitness (CRF) are each independently related to the risk of sudden cardiac death (SCD). The interplay between CRF, inflammation and SCD is not well understood. We aimed to study the separate and joint associations of inflammation (high-sensitivity C-reactive protein [hsCRP]) and CRF with SCD risk in a cohort of Caucasian men. In 1,749 men aged 42 to 61 years without a history of coronary heart disease at baseline, serum hsCRP was measured using an immunometric assay, and CRF was assessed using a respiratory gas exchange analyzer during exercise testing. hsCRP was categorized as normal and high (≤3 and >3 mg/L, respectively) and CRF as low and high (median cutoff). A total of 148 SCD events occurred during a median follow-up of 28.9 years. Comparing high versus normal hsCRP, the multivariable-adjusted hazard ratio (95% confidence interval) for SCD was 1.65 (1.11 to 2.45), which remained similar on further adjustment for CRF 1.62 (1.09 to 2.40). Comparing high versus low CRF, the multivariable-adjusted hazard ratio for SCD was 0.61 (0.42 to 0.89), which remained persistent after adjustment for hsCRP 0.64 (0.44 to 0.93). Compared with normal hsCRP-low CRF, normal hsCRP-high CRF was associated with a decreased SCD risk of 0.65 (0.43 to 0.99), high hsCRP-low CRF was associated with an increased SCD risk of 1.72 (1.10 to 2.69), with no evidence of a relationship between high hsCRP-high CRF and SCD risk 0.86 (0.39 to 1.88). Positive additive and multiplicative interactions were found between hsCRP and CRF. In a middle-aged Finnish male population, both hsCRP and CRF are independently associated with SCD risk. However, high CRF levels appear to offset the increased SCD risk related to high hsCRP levels.

Metabolic Syndrome, Gamma-Glutamyl Transferase, and Risk of Sudden Cardiac Death.

Background: Metabolic syndrome is associated with a significantly increased risk of sudden cardiac death (SCD). However, whether temporal changes in the metabolic syndrome status are associated with SCD is unknown. We aimed to determine whether metabolic syndrome and gamma-glutamyl transferase (ɣ-GTP), including their temporal changes, are associated with the risk of SCD. Methods: We performed a nationwide population-based analysis using the Korean National Health Insurance Service. People who underwent a national health check-up in 2009 and 2011 were enrolled. The influence of metabolic syndrome and ɣ-GTP on SCD risk was evaluated. Results: In 2009, 4,056,423 (848,498 with metabolic syndrome) people underwent health screenings, 2,706,788 of whom underwent follow-up health screenings in 2011. Metabolic syndrome was associated with a 50.7% increased SCD risk (adjusted hazard ratio (aHR) = 1.507; p < 0.001). The SCD risk increased linearly as the metabolic syndrome diagnostic criteria increased. The ɣ-GTP significantly impacted the SCD risk; the highest quartile had a 51.9% increased risk versus the lowest quartile (aHR = 1.519; p < 0.001). A temporal change in the metabolic syndrome status and ɣ-GTP between 2009 and 2011 was significantly correlated with the SCD risk. Having metabolic syndrome in 2009 or 2011 indicated a lower SCD risk than having metabolic syndrome in 2009 and 2011 but a higher risk than having no metabolic syndrome. People with a ≥20-unit increase in ɣ-GTP between 2009 and 2011 had an 81.0% increased SCD risk versus those with a change ≤5 units (aHR = 1.810; p < 0.001). Conclusions: Metabolic syndrome and ɣ-GTP significantly correlated with an increased SCD risk. SCD was also influenced by temporal changes in the metabolic syndrome status and ɣ-GTP, suggesting that appropriate medical treatment and lifestyle modifications may reduce future SCD risk.

Kidney function and the risk of sudden cardiac death in the general population.

ABSTRACTBackgroundChronic kidney disease increases sudden cardiac death (SCD) risk, but the association between kidney function and SCD in a general population is largely unknown. Therefore, we investigated the association between kidney function and SCD in a general middle-aged and elderly population.MethodsWe included individuals aged ≥45 years from a prospective population-based cohort study. The association between kidney function assessments [estimated glomerular filtration rate based on serum creatinine (eGFRcreat), cystatin C (eGFRcys) or both (eGFRcreat-cys)] and SCD was investigated using Cox proportional-hazards and joint models. Absolute 10-year risks were computed using competing risk analyses. Mediation analyses were performed using a four-way decomposition method.ResultsWe included 9687 participants (median follow-up 8.9 years; mean age 65.3 years; 56.7% women; 243 SCD cases). Lower eGFRcys and eGFRcreat-cys were associated with increased SCD risk [hazard ratio (HR) 1.23, 95% confidence interval (CI) 1.12–1.34 and HR 1.17, 95% CI 1.06–1.29, per 10 mL/min/1.73 m2 eGFR decrease]. A significant trend (P = 0.001) across eGFRcys categories was found, with an HR of 2.11 (95% CI 1.19–3.74) for eGFRcys <60 compared with eGFRcys >90 mL/min/1.73 m2. Comparing eGFRcys of 90 to 60 mL/min/1.73 m2, absolute 10-year risk increased from 1.0% to 2.5%. Identified subgroups at increased risk included older participants and participants with atrial fibrillation. The associations were not mediated by coronary heart disease, hypertension or diabetes.ConclusionsReduced kidney function is associated with increased SCD risk in the general population, especially with eGFRcys. eGFRcys could be added to prediction models and screening programmes for SCD prevention.

Prevention of Sudden Cardiac Death in Persons Living with HIV Infection.

Persons living with HIV infection (PLWH) have been recognized to have an increased risk of sudden cardiac death (SCD). Prevention of this risk should theoretically be included in their long-term management. However, only a few approaches have been proposed to optimize such interventions. Targeting detection of the commonly associated conditions such as coronary artery disease, left ventricular dysfunction, heart failure, QT interval prolongation and ventricular arrhythmias is the first step of this prevention. However, although detection of the risk of SCD is a suitable challenge in PLWH, it remains uncertain whether optimized treatment of the identified risks would unequivocally translate into a decrease in SCD rates.

Abstract 12408: Fragmented QRS is Independently Predictive of Long-Term Adverse Clinical Outcomes in Asian Patients Hospitalized for Heart Failure: A Retrospective Cohort Study

Introduction: Fragmented QRS (fQRS) results from myocardial scarring and predicts cardiovascular mortality and ventricular arrhythmia (VA). We evaluated the prevalence and prognostic value of fQRS in Asian patients hospitalized for heart failure. Hypothesis: fQRS is predictive of adverse clinical outcomes. Methods: This was a retrospective cohort study of adult patients hospitalized for heart failure between 1st January 2000 and 31st December 2019 at a tertiary center in Hong Kong. The baseline ECG was analysed. QRS complexes (&lt;120 ms) with fragmented morphology in ≥2 contiguous leads were defined as fQRS. The primary outcome was a composite of cardiovascular mortality, VA, and sudden cardiac death (SCD). The secondary outcomes were the components of the primary outcome, myocardial infarction, and new-onset atrial fibrillation. Results: In total, 2192 patients were included, of whom 179 (8.20%) exhibited fQRS. The follow-up duration was 5.63±4.09 years. fQRS in any leads was associated with a higher risk of the primary outcome (adjusted hazard ratio (HR) 1.541 [1.185, 2.004], p=0.001; Figure A), but not myocardial infarction or new-onset atrial fibrillation. fQRS in &gt;2 contiguous leads was an independent predictor of the primary outcome (HR 1.841 [1.119, 3.029], p=0.016; Figure B), driven by a higher risk of SCD (adjusted HR 2.679 [1.252, 5.729], p=0.011). In patients without ischaemic heart disease (N=1396), fQRS in any leads remained predictive of VA and SCD (adjusted HR 3.336 [1.343, 8.282], p=0.009, and 1.928 [1.135, 3.278], p=0.015, respectively), but not cardiovascular mortality (adjusted HR 1.049 [0.662, 1.662], p=0.839). Conclusions: fQRS is an independent predictor of cardiovascular mortality, VA, and SCD. Higher fQRS burden increased SCD risk. The implications of fQRS in heart failure patients without ischaemic heart disease require further studies.

Fragmented QRS Is Independently Predictive of Long-Term Adverse Clinical Outcomes in Asian Patients Hospitalized for Heart Failure: A Retrospective Cohort Study.

Background: Fragmented QRS (fQRS) results from myocardial scarring and predicts cardiovascular mortality and ventricular arrhythmia (VA). We evaluated the prevalence and prognostic value of fQRS in Asian patients hospitalized for heart failure.Methods and Results: This was a retrospective cohort study of adult patients hospitalized for heart failure between 1st January 2010 and 31st December 2016 at a tertiary center in Hong Kong. The baseline ECG was analyzed. QRS complexes (<120 ms) with fragmented morphology in ≥2 contiguous leads were defined as fQRS. The primary outcome was a composite of cardiovascular mortality, VA, and sudden cardiac death (SCD). The secondary outcomes were the components of the primary outcome, myocardial infarction, and new-onset atrial fibrillation. In total, 2,182 patients were included, of whom 179 (8.20%) had fQRS. The follow-up duration was 5.63 ± 4.09 years. fQRS in any leads was associated with a higher risk of the primary outcome (adjusted hazard ratio (HR) 1.428 [1.097, 1.859], p = 0.001), but not myocardial infarction or new-onset atrial fibrillation. fQRS in >2 contiguous leads was an independent predictor of SCD (HR 2.679 [1.252, 5.729], p = 0.011). In patients without ischaemic heart disease (N = 1,396), fQRS in any leads remained predictive of VA and SCD (adjusted HR 3.526 [1.399, 8.887], p = 0.008, and 1.873 [1.103, 3.181], p = 0.020, respectively), but not cardiovascular mortality (adjusted HR 1.064 [0.671, 1.686], p = 0.792).Conclusion: fQRS is an independent predictor of cardiovascular mortality, VA, and SCD. Higher fQRS burden increased SCD risk. The implications of fQRS in heart failure patients without ischaemic heart disease require further studies.

Prognostic significance of flat T-waves in the lateral leads in general population

BackgroundNegative T-waves are associated with sudden cardiac death (SCD) risk in the general population. Whether flat T-waves also predict SCD is not known. The aim of the study was to examine the clinical characteristics and risk of SCD in general population subjects with flat T-waves. MethodsWe examined the electrocardiograms of 6750 Finnish general population adults aged ≥30 years and classified the subjects into 3 groups: 1) negative T-waves with an amplitude ≥0.1 mV in ≥2 of the leads I, II, aVL, V4–V6, 2) negative or positive low amplitude T-waves with an amplitude <0.1 mV and the ratio of T-wave and R-wave <10% in ≥2 of the leads I, II, aVL, V4–V6, and 3) normal positive T-waves (not meeting the aforesaid criteria). The association between T-wave classification and SCD was assessed during a 10-year follow-up. ResultsA total of 215 (3.2%) subjects had negative T-waves, 856 (12.7%) flat T-waves, and 5679 (84.1%) normal T-waves. Flat T-wave subjects were older and had more often cardiovascular morbidities compared to normal T-wave subjects, while negative T-wave subjects were the oldest and had most often cardiovascular morbidities. After adjusting for multiple factors, both flat T-waves (hazard ratio [HR] 1.81; 95% confidence interval [CI] 1.13–2.91) and negative T-waves (HR 3.27; 95% CI 1.85–5.78) associated with SCD. ConclusionsCardiovascular risk factors and disease are common among subjects with flat T-waves, but these minor T-wave abnormalities are also independently associated with increased SCD risk.

HIV Infection and the Risk of World Health Organization-Defined Sudden Cardiac Death.

BackgroundPeople living with HIV have higher sudden cardiac death (SCD) rates compared with the general population. Whether HIV infection is an independent SCD risk factor is unclear.Methods and ResultsThis study evaluated participants from the Veterans Aging Cohort Study, an observational, longitudinal cohort of veterans with and without HIV infection matched 1:2 on age, sex, race/ethnicity, and clinical site. Baseline for this study was a participant's first clinical visit on or after April 1, 2003. Participants were followed through December 31, 2014. Using Cox proportional hazards regression, we assessed whether HIV infection, CD4 cell counts, and/or HIV viral load were associated with World Health Organization (WHO)–defined SCD risk. Among 144 336 participants (30% people living with HIV), the mean (SD) baseline age was 50.0 years (10.6 years), 97% were men, and 47% were of Black race. During follow‐up (median, 9.0 years), 3035 SCDs occurred. HIV infection was associated with increased SCD risk (hazard ratio [HR], 1.14; 95% CI, 1.04–1.25), adjusting for possible confounders. In analyses with time‐varying CD4 and HIV viral load, people living with HIV with CD4 counts <200 cells/mm3 (HR, 1.57; 95% CI, 1.28–1.92) or viral load >500 copies/mL (HR, 1.70; 95% CI, 1.46–1.98) had increased SCD risk versus veterans without HIV. In contrast, people living with HIV who had CD4 cell counts >500 cells/mm3 (HR, 1.03; 95% CI, 0.90–1.18) or HIV viral load <500 copies/mL (HR, 0.97; 95% CI, 0.87–1.09) were not at increased SCD risk.ConclusionsHIV infection is associated with increased risk of WHO‐defined SCD among those with elevated HIV viral load or low CD4 cell counts.

Heartbeat: sudden cardiac death risk predicted by simple ECG measures

Sudden cardiac death (SCD) accounts for 10%–20% of all deaths in high-income countries, with about 50% of victims having no prior history of heart disease. Currently, primary prevention of SCD...

P6588Impact of age and sex on the long-term prognosis associated with early repolarization in the general population

Abstract Background Early repolarization (ER) in the electrocardiogram (ECG) has been associated with increased sudden cardiac death (SCD) risk in the general population. However, controversy remains about the risk associated with ER in different population subgroups. Purpose We evaluated whether age and sex affect the prognostic significance of ER in general population subjects. Methods The study population consisted of Finnish general population subjects aged over 30 years participating in the Mini-Finland Health Survey in 1978–80. Subjects underwent extensive baseline health examinations including a resting 12-lead ECG and were followed for 24±10 years. After excluding ECGs with QRS duration &gt;110ms, the presence of ER (J-point elevation ≥0.1 mV in ≥2 inferior/lateral leads) was assessed from the remaining 6,631 subjects. The association between ER and SCD risk was analysed in subgroups according to age (&lt;50 years or ≥50 years) and sex by using the Cox proportional hazards model. Effect modification of ER by age group and by sex was tested using the Wald test. Results ER was present in 250 (15.7%) of the 1,592 male subjects aged &lt;50 years, 117 (6.8%) of the 1,713 female subjects aged &lt;50 years, 182 (13.4%) of the 1,362 male subjects aged ≥50 years, and 244 (12.4%) of the 1,964 female subjects aged ≥50 years. There was a significant interaction between age group and ER (p=0.011). Among subjects aged &lt;50 years, ER was associated with SCD risk after adjusting for age, sex, blood pressure, body mass index, serum cholesterol, coronary artery disease, diabetes, and active smoking (hazard ratio [HR] 1.79; 95% confidence interval [CI] 1.09–2.92; p=0.021), whereas in subjects aged ≥50 years ER was not associated with increased risk of SCD. Particularly female subjects aged &lt;50 years with ER had a high risk of SCD (HR 4.85; 95% CI 1.65–14.29; p=0.004) in the multivariate analysis, whereas among &lt;50-year-old male subjects ER was not associated with SCD (p=0.024 for interaction between sex and ER). Conclusion Our results suggest that among adults &lt;50 years old, and especially among &lt;50-year-old women, ER is associated with increased SCD risk, whereas among older subjects ER is not associated with SCD. Future research should focus on identifying the factors accounting for the difference between the age groups and to improve the risk stratification in the younger female patient populations with ER. Acknowledgement/Funding Aarne Koskelo foundation and Paavo Ilmari Ahvenainen Foundation

The evolving risk of sudden cardiac death after heart transplant. An analysis of the ISHLT Thoracic Transplant Registry.

Sudden cardiac death (SCD) is responsible for ~10% of post-heart transplant deaths. We conducted a retrospective analysis of the ISHLT registry evaluating the risk of post-transplant SCD. Adult heart transplant recipients (2004-2014) surviving the first year were included. We used multivariable multistate competing risk survival analysis to evaluate the impact of history of treated rejection and cardiac allograft vasculopathy (CAV) on SCD risk. We used a probabilistic analytical model and Monte Carlo simulation to estimate the impact of CAV severity and graft dysfunction on SCD. We included 25242 recipients. During a median follow-up of 4.7 (2.3-7.0) years, 582 patients died suddenly. Treated rejection (HR 1.76, 95% CI 1.36-2.31) and CAV (HR 3.32, 95% CI 2.73-4.03) were important risk factors for SCD. The estimated SCD risk in patients with severe CAV without and with graft dysfunction was 3.2% (95% CI 2.0-4.6) and 5.4% (95% CI 3.8-7.0), respectively, at 2years from the CAV diagnosis, and 4.9% (95% CI 3.4-6.5) and 8.0% (95% CI 6.1-10.0), respectively, in those who also had treated rejection. These results provide evidence that recipients with severe CAV and graft dysfunction or treated rejection are at clinically significant increased SCD risk. The benefit of ICD post-transplant remains uncertain.

The relationship between anemia and sudden cardiac death in severe aortic stenosis

BackgroundAortic stenosis (AS) affects, and is associated with significant comorbidity and mortality, including sudden cardiac death (SCD) from unknown mechanisms. However, it is difficult to predict which patients with AS will suffer a SCD event. Anemia and low iron are known risk factors for mortality in heart failure populations and AS. We hypothesized that anemia in patients with AS is associated with increased risk of SCD.PurposeUnderstand the relationship and prognostic implications between anemia and SCD in patients with severe AS.Methods and ResultsWe selected 8,144 of 10,850 patients with severe AS (mean transvalvular gradient ≥40 mmHg or peak velocity ≥4 m/s or calculated valve area &lt; 1 cm2) from the Mayo Clinic Aortic Stenosis Registry, which includes all consecutive patients with severe AS over the time period January 1st, 1983 to September 30th, 2015. Subjects in this analysis (median age 76 years and 57% male) were diagnosed starting in 1995 and had hemoglobin (Hb) measurements within one year of diagnosis and prior to intervention. The mean Hb level was 12.8 (± 1.9) g/dL. The prevalence of anemia (Hb&lt;13.0g/dL for men, &lt;12.0g/dL for women) was 40%, 14% microcytic, 20% macrocytic, with the remainder normocytic. Of the 8,144 patients, a total of 4,440 died (10‐year survival 39%; and 240 were confirmed as SCD events [10 year cumulative incidence 4%]). Anemia was associated with increased all‐cause mortality (HR 1.87, 95% CI 1.76–1.99, P=&lt;0.001) and increased SCD events (HR 1.58, 95% CI 1.22–2.06, P=&lt;0.001) in patients with severe AS. Every SD decrease in Hb (1.9 g/dL) was associated with an increased risk of SCD (HR 1.42, 95% CI 1.24–1.62, P&lt;0.001).ConclusionsAnemia is highly prevalent in patients with severe aortic stenosis and is independently associated with increased all‐cause mortality, and more specifically with increased SCD risk. Possible mechanisms include anemia aggrevating myocardial hypoxia, increasing propensity for arrhythmia and abnormal Bezold‐Jarisch reflex mismatch. Anemia may be a useful prognostic marker and a potential therapeutic target in patients with severe AS.Support or Funding InformationCAAC is supported by AHA17POST33400211 and NIH HL134885. This study was supported by a grant from the Department of Cardiovascular Medicine, Mayo Clinic Rochester.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.