Fine particulate matter-sudden death association modified by ventricular hypertrophy and inflammation: a case-crossover study.

Background: Sudden death accounts for approximately 10% of deaths among working-age adults and is associated with poor air quality. Objectives: To identify high-risk groups and potential modifiers and mediators of risk, we explored previously established associations between fine particulate matter (PM2.5) and sudden death stratified by potential risk factors. Methods: Sudden death victims in Wake County, NC, from 1 March 2013 to 28 February 2015 were identified by screening Emergency Medical Systems reports and adjudicated (n = 399). Daily PM2.5 concentrations for Wake County from the Air Quality Data Mart were linked to event and control periods. Potential modifiers included greenspace metrics, clinical conditions, left ventricular hypertrophy (LVH), and neutrophil-to-lymphocyte ratio (NLR). Using a case-crossover design, conditional logistic regression estimated the OR (95%CI) for sudden death for a 5 µg/m3 increase in PM2.5 with a 1-day lag, adjusted for temperature and humidity, across risk factor strata. Results: Individuals having LVH or an NLR above 2.5 had PM2.5 associations of greater magnitude than those without [with LVH OR: 1.90 (1.04, 3.50); NLR > 2.5: 1.25 (0.89, 1.76)]. PM2.5 was generally less impactful for individuals living in areas with higher levels of greenspace. Conclusion: LVH and inflammation may be the final step in the causal pathway whereby poor air quality and traditional risk factors trigger arrhythmia or myocardial ischemia and sudden death. The combination of statistical evidence with clinical knowledge can inform medical providers of underlying risks for their patients generally, while our findings here may help guide interventions to mitigate the incidence of sudden death.

High-output heart failure due to a giant left circumflex coronary aneurysm with a left atrial fistula and atrial septal defect: a case report.

Background: A coronary artery aneurysm is a rare cardiac anomaly that may be incidentally detected on echocardiography. When associated with a coronary cameral fistula, an aneurysm can become symptomatic. We present a unique case of a giant left circumflex coronary aneurysm with a fistula to the left atrium and a large atrial septal defect causing acute heart failure in a young woman during the peripartum period. Case summary: A 32 year-old woman who presented with hypoxia after the delivery of her fourth child was found to have heart failure with severe mitral regurgitation and multiple abnormal intracardiac shunts. Echocardiography showed a large circular structure with Doppler color flow into the left atrium and between the atria. Cardiac computed tomography showed multiple dilated coronary arteries including a left circumflex coronary artery aneurysm measuring >10 cm in diameter with fistulous communication to the left atrium and a large atrial septal defect. A right heart catheterization was performed, and the patient was diagnosed with high-output heart failure. Surgical closure of the coronary cameral fistula was deferred due to the risk of worsening pressure in the coronary aneurysm, and the patient was referred for cardiac transplantation. Discussion: This case illustrates severe heart failure as a complication of a giant coronary artery aneurysm with fistulization to the left atrium and subsequent shunting through a large atrial defect. Echocardiography allows for the detection of a coronary aneurysm and shunting, and cardiac computed tomography provides detailed visualization of a coronary cameral fistula.

Percutaneous Coronary Interventions in Women.

PURPOSEOF REVIEW: Cardiovascular disease is the leading cause of morbidity and mortality among women globally. Numerous studies show ongoing disparities in diagnosis, management, and outcomes of ischemic heart disease in women compared to men. We aim to review the factors contributing to sex-based differential outcomes of percutaneous coronary interventions in women. RECENT FINDINGS: Hormonal influence on coronary arteries and progression of atherosclerosis in women results in distinct coronary plaque characteristics and unique pathological process such as spontaneous coronary artery dissection and myocardial infarction with non-obstructive coronary arteries. During the presentation of acute coronary syndromes, women are older and have higher burden of comorbidities, with higher short- and long-term mortality. Awareness of differences in vascular biology and unique risk factors for cardiovascular disease in women is essential for sustained improvement in cardiovascular mortality. Better representation of women in trials is crucial to address the gaps in knowledge and allow for individualized treatment approaches in women.

Characteristics of sudden death by clinical criteria.

Sudden death is a leading cause of deaths nationally. Definitions of sudden death vary greatly, resulting in imprecise estimates of its frequency and incomplete knowledge of its risk factors. The degree to which time-based and coronary artery disease (CAD) criteria impacts estimates of sudden death frequency and risk factors is unknown. Here, we apply these criteria to a registry of all-cause sudden death to assess its impact on sudden death frequency and risk factors. The sudden unexpected death in North Carolina (SUDDEN) project is a registry of out of-hospital, adjudicated, sudden unexpected deaths attended by Emergency Medical Services. Deaths were not excluded by time since last seen or alive or by prior symptoms or diagnosis of CAD. Common criteria for sudden death based on time since last seen alive (both 24 hours and 1 hour) and prior diagnosis of CAD were applied to the SUDDEN case registry. The proportion of cases satisfying each of the 4 criteria was calculated. Characteristics of victims within each restrictive set of criteria were measured and compared to the SUDDEN registry. There were 296 qualifying sudden deaths. Application of 24 hour and 1 hour timing criteria compared to no timing criteria reduced cases by 25.0% and 69.6%, respectively. Addition of CAD criteria to each timing criterion further reduced qualifying cases, for a total reduction of 81.8% and 90.5%, respectively. However, characteristics among victims meeting restrictive criteria remained similar to the unrestricted population. Timing and CAD criteria dramatically reduces estimates of the number of sudden deaths without significantly impacting victim characteristics.

The Selective 5-HT1A Agonist SR57746A Protects Intestinal Epithelial Cells and Enteric Glia Cells and Promotes Mucosal Recovery in Experimental Colitis.

BACKGROUND: Neurotrophic growth factors can stabilize the intestinal barrier by preventing the apoptosis of enteric glial cells (EGCs) and enterocytes. We reasoned that a selective 5-HT1A receptor agonist may have neuroprotective properties in the gut and that topical application of SR57746A might be an effective treatment strategy in inflammatory bowel disease (IBD). METHODS: The therapeutic potential of 5-HT1A receptor agonist SR57746A in IBD was evaluated in vitro (nontransformed NCM460 colonic epithelial cells, SW480 colorectal carcinoma cells) and in vivo (murine dextran sulfate sodium [DSS] colitis and CD4-T-cell transfer colitis). In vitro, we analyzed the effect of SR57746A on apoptosis in intestinal epithelial cells (IECs) and EGCs, and upon proliferation, migration, and intracellular signaling in IECs. In vivo, the effect of topical application of SR57746 on disease activity and on histological and endoscopic findings was compared with intraperitoneal infliximab and placebo, respectively. RESULTS: The SR57746A activates PI3-K/AKT- and ERK-signaling in IECs. Depending on ERK- and AKT activation, SR57746A potently prevents apoptosis of IECs without inducing proliferation or migration in these cells. Moreover, SR57746A prevented apoptosis in EGCs in vitro. Topical SR57746A treatment significantly reduced mucosal injury in 2 experimental murine colitis models and was as effective as intraperitoneal infliximab treatment. CONCLUSIONS: Treatment with SR57746A prevents inflammatory cell damage and apoptosis in IECs and EGCs, similar to the neurotrophic effects of EGCs on IECs. Topical treatment with SR57746A could be a candidate for clinical evaluation in the treatment of IBD.

Missed Opportunities for Prevention of Sudden Death.

BACKGROUND: We assessed patterns of health care utilization to further characterize chronic comorbidities prior to sudden death. METHOD: From March 1, 2013, through February 28, 2015, all out-of-hospital deaths aged 18-64 reported by emergency medical services in Wake County, North Carolina, were screened to adjudicate 399 sudden death victims. Retrospective analysis of clinical records on victims determined health care utilization. Health care utilization frequency was assessed by latent growth curve analysis. RESULTS: Medical records were available for 264 victims (aged 53.5 ± 9.2) who were predominantly male (65%) and white (64%). Of these, 210 (80%) victims had at least one visit within two years of death and 73 (28%) had a visit within one month of death. Over the two years prior to death, there was an increasing frequency of doctor visits (P < .001). Victims averaged 3.7 ± 4.6 yearly visits and were categorized into low (0.4 visits/year), medium (3.3 visits/year), and high (11.4 visits/year) tiers of visit frequency. The high visit tier had a greater prevalence of coronary artery disease (38%), hypertension (80%), diabetes (58%), depression (74%), anxiety (64%), and substance misuse (46%) (P < .001). LIMITATIONS: Those who were non-free-living, minors, without formal medical records, and adults aged 65 and older were excluded from the analysis. CONCLUSIONS: A majority of sudden death victims utilized health care within two years prior to death and had comorbidities that may have contributed to their unexpected death. The increasing frequency of visits prior to death provided an opportunity for health care providers to address potential victims' chronic medical conditions to potentially prevent death.

High Prevalence of Diabetes Mellitus and Mental Illness Among Victims of Sudden Death.

OBJECTIVES: Diabetes mellitus (DM) increases the risk of cardiovascular disease and is associated with sudden death. Mental illness among individuals with DM may confound medical care. This study assessed the association of mental illness with DM and poorly controlled DM in sudden death victims. METHODS: We screened out-of-hospital deaths ages 18 to 64 years in Wake County, North Carolina from 2013 to 2015 to adjudicate sudden deaths. We abstracted demographics and clinical characteristics from health records. Mental illness included anxiety, schizophrenia, bipolar disorder, or depression. Poorly controlled DM was defined as a hemoglobin A1c >8 or taking ≥3 medications for glycemic control. Logistic regression assessed the association between DM and mental illness. RESULTS: Among victims with available records, 109 (29.4%) had DM. Of those, 62 (56.9%) had mental illness. Mental illness was present in 53.42% and 63.89% of victims with mild and poorly controlled DM, respectively. Mental illness was associated with DM (adjusted odds ratio 2.46, 95% confidence interval 1.57-3.91). Victims with poorly controlled DM were more likely to have mental illness (adjusted odds ratio 2.66, 95% confidence interval 1.14-6.18). CONCLUSIONS: DM is a common comorbid condition in sudden death victims. Among victims, mental illness is associated with the control of DM. Early management of comorbid mental illnesses may improve the care of patients with DM and reduce the incidence of sudden death.

Mental Disorders, Substance Use Disorders, and Psychotropic Medication Use Among Sudden-Death Victims.

OBJECTIVE: The authors sought to estimate the prevalence of mental and substance use disorders and psychotropic medication prescriptions among working-age sudden-death victims. METHODS: Using a written protocol, the authors screened for sudden deaths attended by emergency medical services (EMS) in a large metropolitan county in North Carolina from March 1, 2013, to February 28, 2015. Sudden-death cases were adjudicated by three cardiologists. Mental health and chronic disease diagnoses and treatments were abstracted from EMS, medical examiner, toxicology, and autopsy reports and from clinical records for the past 5 years before death. RESULTS: Sudden death was identified for 399 adults ages 18-64 years, 270 of whom had available medical records. Most sudden-death victims were White (63%) and male (65%), had a comorbid condition such as hypertension or respiratory disease, and had a mean±SD age of death of 53.6±8.8 years. Most victims (59%) had at least one mental health or substance use disorder documented in a recent medical record; 76%-78% of victims with a mental disorder had a documented psychotropic medication prescription. However, fewer than one-half (41%) had a documented referral to a mental health professional. The most common diagnostic categories were depressive, anxiety, and alcohol-related disorders. Almost one-half (46%) of the victims had a recent psychotropic prescription, most commonly antidepressants (29%) and benzodiazepines (19%). CONCLUSIONS: Mental illness, substance use disorders, and psychotropic medication prescriptions were prevalent among sudden-death victims. The health care needs of these individuals may be better addressed by collaborative care for general medical and mental disorders.

Coronary Artery Disease and Atherosclerotic Risk Factors in a Population-Based Study of Sudden Death.

BACKGROUND: Sudden death is a public health problem with major impact on society. Coronary artery disease (CAD) is believed to underlie 60-80% of these deaths. While deaths from CAD have decreased in the recent decades, sudden death rates remain unacceptably high. OBJECTIVE: We aimed to assess the prevalence of CAD and its risk factors among 18-64-year-old adults in a population-based case registry of sudden deaths and compare them to a living population from the same geographical area. DESIGN: From 2013 to 2015, all sudden deaths among 18-64-year-old adults in Wake County, NC, were identified (n = 371). A comparison group was formed by randomly selecting individuals from an electronic health record repository of a major healthcare system in the area (N = 4218). MAIN MEASURES: Prevalence of CAD and its risk factors among cases of sudden death and living population across sex and age groups. Odds of sudden death associated with atherosclerotic risk factors and comorbidities. KEY RESULTS: CAD was present in 14.8% of sudden death cases. Among sudden death victims, most risk factors and comorbidities were more common in the older age group, except for obesity which was more common in younger cases, and diabetes which was equally prevalent in younger and older cases. Compared to living population, sudden death cases had higher prevalence of atherosclerotic risk factors across all gender and age groups. Sudden death cases had a numerically higher number of risk factors compared to living population, regardless of age group or presence of CAD. CONCLUSIONS: Coronary artery disease is not common among sudden death cases, but risk factors and comorbidities are prevalent. Our findings support the changing etiology of sudden death. In the absence of clinically diagnosed CAD, use of novel imaging modalities and biomarkers may identify high-risk individuals and lead to prevention of sudden death.

A case-crossover analysis of the relationship of air pollution with out-of-hospital sudden unexpected death in Wake County, North Carolina (2013-2015).

Out-of-hospital sudden unexpected deaths are non-accidental deaths that occur without obvious underlying causes and may account for 10% of natural deaths before age 65. Short-term exposure to ambient air pollution is associated with all-cause (non-accidental) and cause-specific (e.g., cardiovascular) mortality, and with immediate exposures often yielding the highest magnitude risk estimates. Few studies have focused on short-term exposure to air pollution and sudden unexpected deaths. Using the University of North Carolina Sudden Unexpected Death in North Carolina population, we examine associations between short-term criteria air pollutant exposures with sudden unexpected deaths using a time-stratified case-crossover design, with data on criteria air pollutants from the Environmental Protection Agency's Air Quality System. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression with air pollutant exposures scaled to roughly inter-quartile ranges; models were adjusted for average temperature and relative humidity on event day and preceding 3 days. Potential for confounding by co-pollutants were examined in two pollutant models. ORs for PM2.5 at lag day 1 were elevated (adjusted OR for 5 µg/m3 increase: 1.17 (0.98, 1.40)), and were robust to co-pollutant adjustment. Elevated odds were observed for SO2 at lag day 0, and reduced odds for O3 at lag day 0; however, these associations were somewhat attenuated toward the null (SO2) or were not robust (O3) to co-pollutant adjustment. This analysis in a racially and socioeconomically diverse cohort, with a more inclusive definition of sudden unexpected death than is typically employed offers evidence that PM2.5 may be a clinically relevant trigger of sudden unexpected deaths in susceptible individuals.