Jaliparthy, Keerthi

Background Sudden cardiac arrest is the leading mode of death in the United States. Epilepsy affects 1% of Americans; yet epidemiological data show a prevalence of 4% in cases of sudden cardiac arrest. Sudden unexpected death in epilepsy (SUDEP) may share features with sudden cardiac arrest. The objective of this study was to report autopsy and genomic findings in a large cohort of SUDEP cases. Methods and Results Mayo Clinic Sudden Death Registry containing cases (ages 0–90 years) of sudden unexpected and unexplained deaths 1960 to present was queried. Exome sequencing performed on decedent cases. From 13 687 cases of sudden death, 656 (4.8%) had a history of seizures, including 368 confirmed by electroencephalography, 96 classified as SUDEP, 58 as non‐SUDEP, and 214 as unknown (insufficient records). Mean age of death in SUDEP was 37 (±19.7) years; 56 (58.3%) were male; 65% of deaths occurred at night; 54% were found in bed; and 80.6% were prone. Autopsies were obtained in 83 cases; bystander coronary artery disease was frequently reported as cause of death; nonspecific fibrosis was seen in 32.6% of cases, in structurally normal hearts. There were 4 cases of Dravet syndrome with pathogenic variants in SCN1A gene. Using whole exome sequencing in 11 cases, 18 ultrarare nonsynonymous variants were identified in 6 cases including CACNB2, RYR2, CLNB, CACNA1H, and CLCN2 . Conclusions This study examined one of the largest single‐center US series of SUDEP cases. Several cases were reclassified as SUDEP, 15% had an ECG when alive, and 11 (11.4%) had blood for whole exome sequencing analysis. The most frequent antemortem genetic finding was pathogenic variants in SCN1A ; postmortem whole exome sequencing identified 18 ultrarare variants.

Introduction: Idiopathic Dilated (DCM) and hypertrophic cardiomyopathies (HCM) are leading causes of sudden cardiac death. The incidence and prevalence of both DCM and HCM were originally estimated in Olmsted County, MN over 1975-1984. Incidence was 6.0 and prevalence was 36.5 per 100,000 person-years, for DCM; with incidence and prevalence rates of 2.5 and 19.7 per 100,000 person-years for HCM. This study aims to determine the incidence and mortality rates of individuals diagnosed with HCM and DCM in Olmsted County, MN from 1984 to 2016. Methods: The Rochester Epidemiology Project is a validated long term medical record linkage system that collects and links medical information for the approximately 145000 residents of Olmsted County, Minnesota. Using this database and the Electronic Health Record systems at Mayo Clinic and Olmsted Medical Center in Rochester, MN, we manually reviewed and validated the medical records of 4440 patients. This cohort includes all patients with any mention of a cardiomyopathy based on ICD and HICDA codes during the period 1984 to 2016. Data were summarized with mean and standard deviation, frequency and percentage and compared between groups using two sample t-test for continuous data and chi-square for proportions. Survival was computed using Kaplan-Meier methods and compared to expected survival based on age and gender. Incidence was computed using Olmsted County population numbers during the time period and adjusted to the US 1980 white population to allow for comparison with the previous study. Results: The calculated crude incidence rate for DCM and HCM are 10.1 and 7.8 per 100,000 respectively. Incidence rates adjusted for comparison to US 1980 white population (age and sex adjusted) are 10.4 (95% CI: 9.3-11.4) and 8.0 (95% CI: 7.1-8.8) per 100,000 person-years, respectively. The observed number of deaths in this cohort (HCM and DCM) was 420 vs 194 expected. Conclusions: Calculated incidence, both crude and adjusted rates are higher than previously estimated rates. The crude incidence rate for HCM is almost 4-fold higher than that for DCM is 2.4 times higher than the original estimate by Codd et al. Individuals with cardiomyopathies were found to have a higher overall mortality rate than the general population with an observed to expected hazard ratio of 1.73 (95% CI 1.49-2.01, p<0.001) for DCM and 1.44 (95% CI 1.21-1.71, p<0.001) for HCM. Our findings suggest that previous studies may have underestimated the true burden of HCM and DCM in the population which has important implications for healthcare provision and cost.

Abstract Introduction Cardiopulmonary exercise testing (CPET) has an established role in the clinical evaluation of exercise intolerance and in the risk stratification of patients with heart failure. There is limited data assessing its prognostic utility in the evaluation of patients with Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC). The predisposition of patients with ARVC for ventricular arrhythmias and sudden cardiac death has led to recommendations for exercise restrictions and limits our understanding of how the impairment in oxygen extraction and cardiac output impact disease progression and outcomes in these patients. Purpose We examined the association between CPET indices and event free survival (time to mortality or cardiac transplantation) in patients with Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC). Methods Patients with definite ARVC based on 2010 task force criteria and genetically positive were enrolled into our institutional ARVC registry. 43 patients underwent CPET and have been included in our analyses. Indications for testing included: Evaluation of exercise-induced palpitations/arrhythmias or syncope (37%), pharmacotherapy optimization (28%), heart failure evaluation (19%), and ARVC management decisions (16%). CPET data (peak oxygen consumption (pVO2), respiratory exchange ratio (RER), and ventilatory efficiency (VE/VCO2) were assessed in patients at time of initial evaluation. Median follow-up time was 4.9 years (IQR 9 years). Results 126 patients were studied (age 43.7+ 15 yrs; 41% women; LVEF 57+ 11%; 15% with LVEF &lt;50%) and 43 underwent CPET evaluation. 41 patients (95%) performed at near maximal effort (RER &gt;1) and no fatal events were reported during testing. During the follow up period, the outcome (death or cardiac transplantation) occurred in 31 patients. On Kaplan Meier analysis, pVO2 ≤14 mL/kg/min was associated with worse outcomes (unadjusted p&lt;0.001). Peak oxygen consumption (pVO2) ≤14 mL/kg/min and ventilatory efficiency (VE/VCO2) &gt;34 were associated with shorter event free survival (HR 5.58, p=0.002 and HR 5.56 p=0.005, respectively). After adjusting for age, sex, and right ventricular function, the association between peak oxygen consumption (pVO2) and event free survival remained significant (p=0.02). Conclusions In patients with ARVC, peak oxygen consumption (pVO2) was a prognostic indicator of worse outcomes. Our findings suggest a potential role for pVO2 in disease surveillance and early assessment for advanced heart failure therapies. Figure 1. KM plot pVO2 & event free survival Funding Acknowledgement Type of funding source: Other. Main funding source(s): Mayo Clinic

SummaryObjectiveWe aimed to determine the frequency of probable obstructive sleep apnea (pOSA) in refractory epilepsy monitoring unit inpatients and clinical features associated with pOSA, including risk for sudden unexpected death in epilepsy (SUDEP).MethodsWe prospectively recruited 49 consecutive adult patients admitted to the Mayo Clinic Epilepsy Monitoring Unit with focal, generalized, or unclassified epilepsy syndromes. pOSA was identified using oximetric oxyhemoglobin desaturation index (ODI) and the Sleep Apnea–Sleep Disorders Questionnaire (SA‐SDQ) and STOP‐BAG screening tools. Revised SUDEP Risk Inventory (rSUDEP‐7) scores were calculated, and epilepsy patients with and without pOSA were compared with Wilcoxon signed‐rank tests. Correlation and regression analyses were utilized to determine relationships between pOSA and rSUDEP‐7 scores.ResultsThirty‐five percent of patients had pOSA, with a mean ODI of 11.3 ± 5.1/h (range = 5.1‐22.8). Patients with pOSA were older and heavier, and more frequently had a focal epilepsy syndrome and longer epilepsy duration, with higher SA‐SDQ and STOP‐BAG scores (all P < 0.05). Median rSUDEP‐7 score was 3 ± 1.4 (range = 0‐6). Higher rSUDEP‐7 scores were positively correlated with higher ODI (P = 0.036). rSUDEP‐7 score ≥ 5 was associated with pOSA by ODI, SA‐SDQ, and STOP‐BAG questionnaire criteria (P < 0.05).SignificanceOur pilot study identified a high frequency of pOSA in refractory epilepsy monitoring patients, finding that pOSA patients were older and heavier, with higher screening symptoms for sleep apnea and more frequent focal seizures with a longer epilepsy duration. We also found a possible association between OSA and SUDEP risk. Identification and treatment of OSA in patients with epilepsy could conceivably provide a novel approach toward preventing the risk of SUDEP. Future studies with polysomnography are needed to confirm predictive features for OSA in epilepsy populations, and to determine whether OSA is associated with SUDEP risk.