Background

Sudden cardiac death (SCD) remains a major public health problem. Current established criteria identifying those at risk of sudden arrhythmic death, and likely to benefit from implantable cardioverter defibrillators (ICDs), are neither sensitive nor specific. Exercise electrocardiogram (ECG) testing was traditionally used for information concerning patients' symptoms, exercise capacity, cardiovascular function, myocardial ischemia detection, and hemodynamic responses during activity in patients with hypertrophic cardiomyopathy.

Methods

We conducted a systematic review of MEDLINE on the utility of exercise ECG testing in SCD risk stratification.

Results

Exercise testing can unmask suspected primary electrical diseases in certain patients (catecholaminergic polymorphic ventricular tachycardia or concealed long QT syndrome) and can be effectively utilized to risk stratify patients at an increased (such as early repolarization syndrome and Brugada syndrome) or decreased risk of SCD, such as the loss of preexcitation on exercise testing in asymptomatic Wolff-Parkinson-White syndrome.

Conclusions

Exercise ECG testing helps in SCD risk stratification in patients with and without arrhythmogenic hereditary syndromes.

Intracardiac device electrograms demonstrating differing VF sensing performance between two manufacturer ICD generators.

Background Heart failure (HF) admissions in adults with congenital heart disease (CHD) are becoming more common. We compared in-hospital and readmission events among adults with and without CHD admitted for HF. Methods and Results We identified all admissions with the primary diagnosis of HF among adults in the California State Inpatient Database between January 1, 2005 and January 1, 2012. International Classification of Disease (ICD) codes identified the type of CHD lesion, comorbidities, and in-hospital and 30-day readmissions events. Adjusted odds ratio (AOR, 95% CI) was calculated after adjusting for admission year, age, sex, race, household income, primary payor, and Charlson comorbidity index. Of 203 759 patients admitted for HF, 539 had CHD other than atrial septal defect. Compared with patients admitted for HF without CHD, those with CHD were younger, more often male, and had fewer comorbidities as determined by Charlson comorbidity index. On multivariate analysis, CHD patients admitted for HF had higher odds of length of stay ≥7 days (AOR 2.5 [95% CI 2.0-3.1]), incident arrhythmias (AOR 2.8 [95% CI 1.7-4.5]), and in-hospital mortality (AOR 1.9 [95% CI 1.1-3.1]). Also, CHD patients had lower odds of readmission for HF (AOR 0.6 [95% CI 0.3-0.9]), but similar odds of other 30-day readmission events. Complex CHD patients had higher odds of length of stay ≥7 days (AOR 1.9 [95% CI 1.1-3.3]) than patients with noncomplex CHD lesions, but similar odds of all other clinical outcomes. Conclusions Among patients admitted with the primary diagnosis of HF in California, adults with CHD have substantially higher odds of longer length of stay, incident arrhythmias, and in-hospital mortality compared with non-CHD patients. These results suggest a need for HF risk stratification strategies and management protocols specific for patients with CHD.

Objective

To determine the definite and potential frequency of seizures and epilepsy as a cause of death (COD) and how often this goes unrecognized.

Methods

Prospective determination of seizures or epilepsy and final COD for individuals aged 18-90 years with out-of-hospital sudden cardiac deaths (SCDs) from the population-based San Francisco POST SCD Study. We compared prospective seizure or epilepsy diagnosis and final COD as adjudicated by a multidisciplinary committee (pathologists, electrophysiologists, and a vascular neurologist) vs retrospective adjudication by 2 epileptologists with expertise in seizure-related mortality.

Results

Of 541 SCDs identified during the 37-month study period (mean age 62.8 years, 69% men), 525 (97%) were autopsied; 39/525 (7.4%) had seizures or epilepsy (mean age: 58 years, range: 27-92; 67% men), comprising 17% of 231 nonarrhythmic sudden deaths. The multidisciplinary team identified 15 cases of epilepsy, 6 sudden unexpected deaths in epilepsy (SUDEPs), and no deaths related to acute symptomatic seizures. The epileptologists identified 25 cases of epilepsy and 8 definite SUDEPs, 10 possible SUDEPs, and 5 potential cases of acute symptomatic seizures as a COD.

Conclusions

Among the 25 patients identified with epilepsy by the epileptologists, they found definite or possible SUDEP in 72% (18/25) vs 24% (6/25) by the multidisciplinary group (6/15 cases they identified with epilepsy). The epileptologists identified acute symptomatic seizures as a potential COD in 5/14 patients with alcohol-related seizures. Epilepsy is underdiagnosed among decedents. Among patients with seizures and epilepsy who die suddenly, seizures and SUDEP often go unrecognized as a potential or definite COD.

Objective

Since cardic fibrosis was previously found more frequently in patients with sudden unexpected death in epilepsy (SUDEP) than control cases, we compared blinded and quantitative reviews of cardiac pathology in SUDEP to multiple control groups.

Methods

We adjudicated causes of death in epilepsy patients as part of consecutive out-of-hospital sudden cardiac deaths (SCDs) from the Postmortem Systematic Investigation of Sudden Cardiac Death (POSTSCD) study. Blinded cardiac gross and microscopic examinations were performed by forensic and cardiac pathologists.

Results

Of 541 SCDs over 37 months (mean age 62.8 years, 69% male), 525 (97%) were autopsied; 25/525 (4.8%) had epilepsy (mean age 56.4 years ± 15.4, range 27-92; 67% male). The 25 epilepsy patients died of definite SUDEP/definite SUDEP-plus (n = 8), possible SUDEP (n = 10), or other causes (n = 7). Comparison groups included autopsy-defined sudden arrhythmic death (SAD; n = 285) and trauma (n = 104) and we adjusted for age, sex, HIV, coronary artery disease, congestive heart failure, and cardiomyopathy in the analyses. Compared to SAD cases, SUDEP cases had less gross and histologic evidence of cardiac pathology; significant for cardiac mass (p < 0.0011), coronary artery disease (p < 0.0024), total cardiac fibrosis (CF) (p = 0.022), and interstitial CF (p = 0.013). Compared to trauma cases, SUDEP cases had similar cardiac pathology including CF.

Conclusion

Among SUDEP cases, cardiac pathology was less severe than in SAD cases but similar to trauma and epilepsy controls. Our data do not support prior studies finding elevated rates of CF among SUDEP cases compared to controls. Larger studies including molecular analyses would further our understanding of cardiac changes associated with SUDEP.

[Figure: see text].

Background

In the POST SCD study, the authors autopsied all World Health Organization (WHO)-defined sudden cardiac deaths (SCDs) and found that only 56% had an arrhythmic cause; resuscitated sudden cardiac arrests (SCAs) were excluded because they did not die suddenly. They hypothesized that causes underlying resuscitated SCAs would be similarly heterogeneous.

Objectives

The aim of this study was to determine the causes and outcomes of resuscitated SCAs.

Methods

The authors identified all out-of-hospital cardiac arrests (OHCAs) from February 1, 2011, to January 1, 2015, of patients aged 18 to 90 years in San Francisco County. Resuscitated SCAs were OHCAs surviving to hospitalization and meeting WHO criteria for suddenness. Underlying cause was determined by comprehensive record review.

Results

The authors identified 734 OHCAs over 48 months; 239 met SCA criteria, 133 (55.6%) were resuscitated to hospitalization, and 47 (19.7%) survived to discharge. Arrhythmic causes accounted for significantly more resuscitated SCAs overall (92 of 133, 69.1%), particularly among survivors (43 of 47, 91.5%), than WHO-defined SCDs in POST SCD (293 of 525, 55.8%; p < 0.004 for both). Among resuscitated SCAs, arrhythmic cause, ventricular tachycardia/fibrillation initial rhythm, and white race were independent predictors of survival. None of the resuscitated SCAs due to neurologic causes survived.

Conclusions

In this 4-year countywide study of OHCAs, only one-third were sudden, of which one-half were resuscitated to hospitalization and 1 in 5 survived to discharge. Arrhythmic cause predicted survival and nearly one-half of nonsurvivors had nonarrhythmic causes, suggesting that SCA survivors are not equivalent to SCDs. Early identification of nonarrhythmic SCAs, such as neurologic emergencies, may be a target to improve OHCA survival.

Background

Abnormal calcium handling plays a crucial role in arrhythmias, sudden cardiac arrest (SCA), and congestive heart failure (CHF). Calsequestrin 2 (CASQ2) mutations affect calcium release and initiate malignant ventricular arrhythmias (VAs) and SCA syndromes. Common single nucleotide polymorphisms (SNPs) in CASQ2 may be associated with SCA in patients with coronary artery disease (CAD).

Objective

The purpose of this study was to examine the association of common CASQ2 SNPs with the risk of SCA in patients with CAD.

Methods

CASQ2 SNPs (n = 14) were genotyped and analyzed in a case control study comparing 114 patients with CAD and SCA due to VA to 311 CAD controls without VA or SCA.

Results

Multivariate logistic regression adjusting for age and CHF status identified an association between rs7521023 with SCA (odds ratio [OR] 2.72, 95% confidence interval [CI] 1.44-5.13, P = .002). The substantial impact of CHF on SCA in the model (OR 26.6, 95% CI 13.40-52.70, P <.001) led us to further examine the relationship between CHF, SCA, and CASQ2 SNPs. We identified 2 CASQ2 variants (rs7521023: OR 0.4, 95% CI 0.25-0.76, P = .003; rs6684209: OR 19.8, 95% CI 3.63-108.2, P <.001) associated with CHF after adjusting for SCA, age, gender, and hypertension.

Conclusion

We observed association between a CASQ2 polymorphism and SCA due to VA in patients with CAD adjusting for CHF and independent associations between CASQ2 SNPs and CHF adjusting for SCA. Further investigation in independent cohorts is needed to confirm these findings.

Objective

To characterize the frequency of and risk factors for out-of-hospital sudden neurologic deaths.

Methods

During the initial 25 months (February 1, 2011-March 1, 2013) of the San Francisco Postmortem Systematic Investigation of Sudden Cardiac Death Study, we captured incident WHO criteria sudden cardiac deaths (SCDs) through active surveillance of consecutive out-of-hospital deaths, which must be reported to the medical examiner by law. All cases were referred for full autopsy with detailed examination of the heart and cranial vault, toxicology, and histology. A multidisciplinary committee adjudicated a final cause of death.

Results

Of 352 incident SCDs, 335 (95%) underwent systematic evaluation including full autopsy. Of these 335 cases, 18 (5.4%) were sudden neurologic deaths (mean age 60.6 years [SD 17.6, range 27-87]; 67.7% female), which accounted for 14.9% of the 121 noncardiac sudden deaths. The risk of sudden neurologic death compared to non-neurologic SCD was lower in male and white participants (p < 0.01). Neurologic causes included intracranial hemorrhage (8), sudden unexpected death in epilepsy (6, including 2 with juvenile myoclonic epilepsy), aneurysmal subarachnoid hemorrhage (2), acute ischemic stroke (1), and aspiration from Huntington disease (1). Most deaths were unwitnessed (16; 89%) with asystole at presentation (17; 94%). Prior stroke/TIA was not associated with risk of stroke (odds ratio [OR] 1.4 [95% confidence interval (CI) 0.18-11.8], p = 0.73), but antithrombotic medication use was (OR 3.9 [95% 1.01-15.5], p = 0.05).

Conclusions

Sudden neurologic death is an important cause of out-of-hospital apparent SCDs. Low prevailing autopsy rates may result in systematic misclassification of apparent SCDs and underestimation of the incidence of sudden neurologic death.

We report a case of sudden death in a clinically stable adult with l-transposition of the great arteries (l-TGA). Sudden death has been reported to be the leading cause of death in l-TGA and is often attributed to arrhythmias in the absence of another identifiable cause. However, the contribution of nonarrhythmic causes to the burden of sudden death in this population is unknown. Comprehensive postmortem investigation, including autopsy and pacemaker interrogation, demonstrated that the cause of death was massive pulmonary hemorrhage due to stenosis of the patient's mechanical tricuspid (systemic AV) valve. This report highlights the important contribution of nonarrhythmic causes of sudden death in this population and the value of autopsy and device interrogation in determining true cause of death.