Search

Noradrenergic afferents to hypothalamic corticotropin releasing hormone (CRH) neurons provide a major excitatory drive to the hypothalamic-pituitary-adrenal (HPA) axis via α1 adrenoreceptor activation. Noradrenergic afferents are recruited preferentially by somatic, rather than psychological, stress stimuli. Stress-induced glucocorticoids feed back onto the hypothalamus to negatively regulate the HPA axis, providing a critical autoregulatory constraint that prevents glucocorticoid overexposure and neuropathology. Whether negative feedback mechanisms target stress modality-specific HPA activation is not known. Here, we describe a desensitization of the α1 adrenoreceptor activation of the HPA axis following acute stress in male mice that is mediated by rapid glucocorticoid regulation of adrenoreceptor trafficking in CRH neurons. Glucocorticoid-induced α1 receptor trafficking desensitizes the HPA axis to a somatic but not a psychological stressor. Our findings demonstrate a rapid glucocorticoid suppression of adrenergic signaling in CRH neurons that is specific to somatic stress activation, and they reveal a rapid, stress modality-selective glucocorticoid negative feedback mechanism., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: We investigated the impact of the COVID-19 crisis on mental health of professionals working in the intensive care unit (ICU) according to the intensity of the epidemic in France., Methods: This cross-sectional survey was conducted in 77 French hospitals from April 22 to May 13 2020. All ICU frontline healthcare workers were eligible. The primary endpoint was the mental health, assessed using the 12-item General Health Questionnaire. Sources of stress during the crisis were assessed using the Perceived Stressors in Intensive Care Units (PS-ICU) scale. Epidemic intensity was defined as high or low for each region based on publicly available data from Santé Publique France. Effects were assessed using linear mixed models, moderation and mediation analyses., Results: In total, 2643 health professionals participated; 64.36% in high-intensity zones. Professionals in areas with greater epidemic intensity were at higher risk of mental health issues (p < 0.001), and higher levels of overall perceived stress (p < 0.001), compared to low-intensity zones. Factors associated with higher overall perceived stress were female sex (B = 0.13; 95% confidence interval [CI] = 0.08-0.17), having a relative at risk of COVID-19 (B = 0.14; 95%-CI = 0.09-0.18) and working in high-intensity zones (B = 0.11; 95%-CI = 0.02-0.20). Perceived stress mediated the impact of the crisis context on mental health (B = 0.23, 95%-CI = 0.05, 0.41) and the impact of stress on mental health was moderated by positive thinking, b = - 0.32, 95% CI = - 0.54, - 0.11., Conclusion: COVID-19 negatively impacted the mental health of ICU professionals. Professionals working in zones where the epidemic was of high intensity were significantly more affected, with higher levels of perceived stress. This study is supported by a grant from the French Ministry of Health (PHRC-COVID 2020).

Background: Implantable cardioverter defibrillators (ICDs) reduce mortality in patients at risk for life-threatening arrhythmias. Implantation of ICDs in rural or economically disadvantaged populations is suspected to be low. This study examined Out of Hospital Premature Natural Death (OHPND) and electronic medical record (EMR) data to identify rates of non-implantation of ICDs among decedents in eastern North Carolina., Methods: OHPND cases in 2016 were identified using mortality data and matched with EMRs. Those meeting criteria for ICD implantation based on chart review were adjudicated by two electrophysiologists to determine whether they qualified for implantation. Comorbidity burden was established using Charlson's Comorbidity Index (CCI)., Results: Out of 1316 OHPND cases, 967 (73.4%) had EMR records. Chart review identified 70 (7.2%) potential ICD candidates with a LVEF ≤35 of which 5 (7.1%) did not meet criteria because LVEF subsequently improved. Of the remaining 65 patients, 32 (49.2%) already received an ICD, and 33 patients (50.7%) met criteria but had not received one. Reasons for non-implantation included: limited life expectancy secondary to comorbidities, principally chronic kidney disease (CKD) (N = 11, 17%), physician non-adherence to guidelines (N = 9, 14%), loss to follow-up (N = 7, 11%), patient refusal (N = 5, 8%), and death before commencing medical therapy (N = 1, 2%). Among our cohort of 967 individuals who died unexpectedly, nine (0.9%) patients may have avoided death with an ICD., Conclusion: This study using decedent data shows low rates of ICD-underutilization in a rural population and emphasizes the role of advanced comorbidities such as CKD in ICD-underutilization., (© 2021 Wiley Periodicals LLC.)

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.

Three-dimensional (3 D) hydrogel scaffolds are an attractive option for tissue regeneration applications because they allow for cell migration, fluid exchange, and can be synthesized to closely mimic the physical properties of the extracellular matrix environment. The material properties of hydrogels play a vital role in cellular migration and differentiation. In light of this, in-depth understanding of material properties is required before such scaffolds can be used to study their influence on cells. Herein, various blends and thicknesses of poly (ethylene glycol) dimethacrylate (PEGDMA) hydrogels were synthesized, flash frozen, and dried by lyophilization to create scaffolds with multiscale porosity. Environmental scanning electron microscopy (ESEM) images demonstrated that lyophilization induced microporous voids in the PEGDMA hydrogels while swelling studies show the hydrogels retain their innate swelling properties. Change in pore size was observed between drying methods, polymer blend, and thickness when imaged in the hydrated state. Human adipose-derived stem cells (hASCs) were seeded on lyophilized and non-lyophilized hydrogels to determine if the scaffolds would support cell attachment and proliferation of a clinically relevant cell type. Cell attachment and morphology of the hASCs were evaluated using fluorescence imaging. Qualitative observations in cell attachment and morphology of hASCs on the surface of the different hydrogel spatial configurations indicate these multiscale porosity hydrogels create a suitable scaffold for hASC culture. These findings offer another factor of tunability in creating biomimetic hydrogels for various tissue engineering applications including tissue repair, regeneration, wound healing, and controlled release of growth factors.

Objective: To determine the association between serum lipid measurements and the occurrence of out-of-hospital sudden unexpected death (OHSUD)., Patients and Methods: We compared 139 OHSUD cases (43 female patients [30.9%]) and 968 controls (539 female patients [55.7%]) from Wake County, North Carolina, from March 1, 2013, through February 28, 2015. Individuals were included if they were aged 18 to 64 years and had lipid measurements in the 5 years before their death (cases) or the most recent health care encounter (controls). Covariates were abstracted from medical records for all subjects, and those with triglyceride (TG) levels greater than 400 mg/dL (to convert to mmol/L, multiply by 0.0259) were excluded for low-density lipoprotein (LDL)-related analyses., Results: By linear regression using age- and sex-adjusted models, cases of OHSUD had lower adjusted mean total cholesterol (170.3±52.2 mg/dL vs 188.9±39.7 mg/dL; P <.001), LDL cholesterol (90.9±39.6 mg/dL vs 109.6±35.2 mg/dL; P <.001), and non-high-density lipoprotein (HDL) (121.6±49.8 mg/dL vs 134.3±39.6 mg/dL; P <.001) levels and a higher adjusted TG/HDL-C ratio (4.7±7 vs 3±2.7; P <.001) than did controls. By logistic regression using age- and sex-adjusted models, the odds of OHSUD were elevated per unit increase in TG/HDL-C ratio (1.08; 95% CI, 1.03-1.12)., Conclusion: Out-of-hospital sudden unexpected death cases had more favorable levels of total cholesterol, LDL cholesterol, and non-HDL, possibly indicating a lack of association between traditional lipid cardiovascular risk factors and sudden unexpected death. A comparatively elevated TG/HDL-C ratio in cases may corroborate an evolving hypothesis of how vasoactive and prothrombotic remnant-like lipoprotein particles contribute to sudden unexpected death.

The incidence of out-of-hospital sudden unexpected death (OHSUD) in a racially and socioeconomically diverse population has been inadequately studied. We collated all OHSUDs over a 24-month period among 18- to 64-year olds in Wake County, North Carolina, to investigate geographic and socioeconomic disparity in incidence of OHSUD. An electronic query of Wake County Emergency Medical Services (EMS) identified all EMS attended out-of-hospital deaths. After excluding trauma, expected deaths, and deaths occurring in non-free-living subjects, medical records and medical examiner's reports were reviewed by a committee of cardiologists to make the determination of OHSUD. Victims were geocoded to census tracts, and demographic and socioeconomic data were obtained from the 2014 American Community Survey and 2010 US Census. Incidence was examined by sociodemographic group with univariate analysis and multivariable regression. There were 397 OHSUDs, and 53% of census tracts had >1 event. The incidence of OHSUD was 64 of 100,000; 107 of 100,000 among blacks; and 60 of 100,000 among whites. Census tracts with >1 OHSUD had a higher population of blacks, a greater proportion unmarried, a lower median household income, and a greater proportion residing in a rural area. Only median household income remained a significant predictor of OHSUD after adjustment in multivariable analysis. Low median household income of a community portends a higher incidence of sudden death. In conclusion, interventions to reduce the incidence of sudden death need to be developed with these specific communities in mind., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: In this manuscript, we estimate the incidence and identify risk factors for sudden unexpected death in a socioeconomically and racially diverse population in one county in North Carolina. Estimates of the incidence and risk factors contributing to sudden death vary widely. The Sudden Unexpected Death in North Carolina (SUDDEN) project is a population-based investigation of the incidence and potential causes of sudden death., Methods: From 3 March 2013 to 2 March 2014, all out-of-hospital deaths in Wake County, North Carolina, were screened to identify presumed sudden unexpected death among free-living residents between the ages of 18 and 64 years. Death certificate, public and medical records were reviewed and adjudicated to confirm sudden unexpected death cases., Results: Following adjudication, 190 sudden unexpected deaths including 122 men and 68 women were identified. Estimated incidence was 32.1 per 100 000 person-years overall: 42.7 among men and 22.4 among women. The majority of victims were white, unmarried men over age 55 years, with unwitnessed deaths at home. Hypertension and dyslipidaemia were common in men and women. African-American women dying from sudden unexpected death were over-represented. Women who were under age 55 years with coronary disease accounted for over half of female participants with coronary artery disease., Conclusions: The overall estimated incidence of sudden unexpected death may account for approximately 10% of all deaths classified as 'natural'. Women have a lower estimated incidence of sudden unexpected death than men. However, we found no major differences in age or comorbidities between men and women. African-Americans and young women with coronary disease are at risk for sudden unexpected death.

Background: It can be challenging to convince asymptomatic to minimally symptomatic patients to pursue treatment of their atrial fibrillation (AF). We hypothesized that once in sinus rhythm, asymptomatic to minimally symptomatic patients would realize they were compensating for moderate symptoms, and that we could quantify this via the Canadian Cardiovascular Society Severity of AF (CCS-SAF) score., Methods: All patients in our study come from the Symptom Mitigation in Atrial Fibrillation (SMART) study. Upon enrollment all patients were assigned a CCS-SAF score. Patients receiving a CCS-SAF score of 0 or 1 that elected to pursue intervention were contacted by phone and asked about their symptoms post-intervention as compared to pre-intervention. Paired t-test was used for analysis., Results: Out of 800 patients in the SMART study to date, 48 patients have qualified for our phone survey and presented for follow-up in our clinic. In our cohort, the revised pre-intervention CCS-SAF score was 1.69 ± 1.36 and the post-intervention CCS-SAF score was 0.52 ± 0.80. Thirty-seven patients reported symptom improvement; those who improved were on average 72.4% improved from baseline., Conclusions: We conclude asymptomatic to minimally symptomatic AF patients benefit from therapy and should be offered intervention despite lack of symptoms.

Background: Atrial fibrillation (AF) guidelines recommend that symptom relief be a primary goal in management. However, patient perception of their prevailing rhythm is often inaccurate, complicating symptom-targeted treatment., Objective: The purpose of this study was to evaluate the accuracy of patient perception of their prevailing rhythm and identify factors that predict inaccuracies., Methods: Demographic and health status data were captured by questionnaires for 458 outpatients with documented AF. AF burden (%) was captured by 1-week continuous heart monitors. Patients estimated the length and frequency of their AF episodes by completing the AF Symptom Severity questionnaire. Patient reports were compared to AF burden, and outliers were identified and broken into 2 groups: patients with AF burden <10% who indicated near-continuous AF (overestimators) and patients with AF burden >90% who estimated little to no AF (underestimators). Multinomial logistic regression was used to identify predictors of inaccuracies (over- or underestimators)., Results: By continuous monitor, 15% of patients were found to be over- or underestimators. Persistent AF, female sex, older age, anxiety, and depression were predictive of inaccurate patient perception. Persistent AF, female sex, and older age were predictive of underestimating, while mood disorders (anxiety and depression) were predictive of overestimating. The prevalence of underestimators was nearly twice that of overestimators., Conclusion: Sex, age, and mood disorders are among factors that lead to inaccurate patient perception of their prevailing rhythm in patients with AF. Such modulating factors should be considered when evaluating treatment strategies. Consideration should be given to more liberal use of heart monitors in these patient populations to better target therapy., (Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

The goal of treatment for atrial fibrillation (AF) is often to control symptoms. It remains unclear whether targets for treatment such as AF rate or AF burden are correlated with AF symptom severity. Two hundred eighty-six patients completed a questionnaire of their general health and well-being, including a detailed AF symptom assessment immediately followed by a 7-day continuous monitor. AF characteristics assessed from the monitor included AF burden, AF rate, sinus rhythm rate, frequency and severity of pauses, and premature atrial contraction or premature ventricular contraction burden. Characteristics were analyzed separately for patients with paroxysmal or persistent AF. Symptom severity was assessed using the University of Toronto Atrial Fibrillation Severity Scale. Monitor characteristics were compared with AF symptom severity. The mean age of the cohort was 61.8 years and the majority of subjects were male (65.4%). Co-morbidities included hypertension (64.5%), sleep apnea (38.4%), congestive heart failure (19.6%), and diabetes (16.4%). In those with persistent or paroxysmal AF, there were no significant predictors of AF symptom severity. Specifically, heart rate in AF or sinus rhythm, AF burden, or premature atrial contraction or premature ventricular contraction burden was not predictive of AF symptom severity. After adjusting for potential cofounders (including age, gender, and co-morbidities), these findings persisted. In conclusion, there is no value in using AF monitor characteristics to predict symptoms in patients with AF., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Symptoms attributed to atrial fibrillation (AF) are nonspecific, and it remains unclear what influences perception of symptoms. Anxiety or depression may be important in modulating perception of AF symptoms. However, few longitudinal studies have addressed this effect., Methods: A total of 378 patients with AF completed anxiety and depression severity questionnaires as well as AF symptom and frequency severity questionnaires. Patients were offered treatment strategies including catheter ablation or antiarrhythmic or rate-controlling medications. Patients were followed at 3-month intervals and completed follow-up questionnaires including repeat assessment of anxiety, depression, and AF symptoms. A method of generalized estimating equations was used for longitudinal analyses., Results: Analysis revealed that increased anxiety or depression was associated with increased AF symptom severity (AFSS), after adjusting for potential confounders. In both unadjusted and adjusted follow-up analyses, antiarrhythmic drug therapy or catheter ablation reduced AFSS (P < 0.001). However, none of anxiety severity, depression severity, or the perception of AF frequency severity improved significantly with AF treatment., Conclusions: Our results extend previous studies demonstrating that anxiety and depression are associated with worsened AFSS. Antiarrhythmic drug therapy or catheter ablation reduces AFSS but does not affect depression and anxiety symptoms. To achieve more comprehensive AF symptom relief, treatment of both AF and psychological comorbidities may be beneficial., (©2013, The Authors. Journal compilation ©2013 Wiley Periodicals, Inc.)

Background: Displacement of ECG leads can result in unwarranted findings. We assessed the frequency of Brugada-type patterns in athletes when precordial leads were purposely placed upward., Methods: Four hundred ninety-one collegiate athletes underwent two ECGs: one with standard leads, one with V1 and V2 along the 2nd intercostal space. A positive Brugada-type pattern was defined as ST elevation in V1 or V2 consistent with a Type 1, 2, or 3 pattern in the high-lead ECG. A control group was comprised of 181 outpatients., Results: No Type 1 patterns were seen. In 58 athletes (11.8%), a Brugada-type 2 or 3 pattern was observed. Those with Brugada-type 2 or 3 patterns were more likely male, taller, and heavier. In the control group, 18 (9.9%) had Brugada-type 2 or 3 patterns and were more likely male., Conclusions: Proper lead positioning is essential to avoid unwarranted diagnosis of a Brugada-type ECG, especially in taller, heavier male athletes., (© 2013.)

Background: Pectus excavatum is a skeletal abnormality that may have cardiac manifestations., Objective: To determine whether pectus excavatum is associated with lone atrial fibrillation (AF)., Methods: The pectus severity index (PSI) is the ratio of the lateral diameter of the chest to the distance between the sternum and the spine on computed tomography scan. A normal PSI is ≤2.5 whereas patients with severe pectus excavatum have a PSI >3.25. We calculated the PSI of 220 consecutive patients with AF who underwent radiofrequency catheter ablation from September 2008 to 2012 and compared this to the PSI of 225 controls without a history of AF undergoing chest computed tomography., Results: Mean PSI was higher in patients with lone AF (2.72 ± 0.07) compared to patients with nonlone AF (2.25 ± 0.03) or controls (2.26 ± 0.03) (P < .001). The likelihood of mild, moderate, or severe pectus excavatum was higher in patients with lone AF compared to patients with nonlone AF and controls (P < .001). Patients with lone AF were more than 5 times as likely to have severe pectus excavatum compared to patients with nonlone AF or controls (P < .001) even after adjustment for potential confounders., Conclusions: Nearly two-thirds of the patients with lone AF have at least mild pectus excavatum and 17% have severe pectus, which is significantly higher than in patients with nonlone AF or controls. This association suggests a potential genetic or mechanical abnormality may be common to the 2 disorders. Our study may provide insight into the pathogenesis of lone AF., (Copyright © 2013 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Atherosclerosis development is a complex process, with inflammation, indicated by elevated high-sensitivity C-reactive protein (hs-CRP), as a potential mediator. Obesity, physical activity, and depression have all been reported to affect hs-CRP. However, these factors are interconnected, and their relative individual importance remains unclear. From a separate prospective cohort study, 289 patients were selected for the present substudy. We assessed the relation of a variety of potential predictors and hs-CRP. Obesity, physical activity, and depression, in addition to several other potential factors, were analyzed in bivariate and multivariate linear regression models, adjusting for potential confounders. In unadjusted analyses, mild-to-moderate and severe depression were associated with increased hs-CRP compared to no or minimal depression. Vigorous physical activity was associated with decreased hs-CRP compared to no physical activity. All classes of obesity were associated with increased hs-CRP. In addition, attaining a college or graduate degree was associated with decreased hs-CRP compared to high school or less educational attainment. On multivariate analysis, depression was no longer associated with increased hs-CRP. Physical activity remained associated with decreased hs-CRP but only at vigorous levels. Educational attainment also remained associated but only at the collegiate or professional education level. Ultimately, obesity remained the greatest absolute predictor of elevated hs-CRP. In conclusion, in analyses of multiple factors potentially predictive of elevated hs-CRP in a large population of patients with subclinical coronary heart disease, we found the most important predictor to be obesity., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Catheter ablation is an effective treatment for medically refractory, disabling atrial fibrillation (AF). Ablation success may be limited in patients with persistent or long-standing persistent AF. A pericardioscopic, hybrid epicardial-endocardial technique for AF ablation may be a preferred approach for such patients. Limited data are available using such an approach., Objective: To evaluate 1-year outcomes of a hybrid technique for AF ablation., Methods: A cohort of 101 patients underwent AF ablation using a transdiaphragmatic pericardioscopic, hybrid epicardial-endocardial technique. Patients were followed with 24-hour Holter monitors at 3-, 6-, and 12-month intervals. Symptom severity was assessed at baseline and follow-up by using the Canadian Cardiovascular Society Severity of Atrial Fibrillation scale., Results: Mean AF duration was 5.9 years; 47% were persistent and 37% were long-standing persistent. Mean left atrial size was 5.1 cm (range 3.3-7 cm). Overall, 12-month arrhythmia-free survival was 66.3% after a single ablation procedure and 70.5% including repeat ablation. Repeat ablation was required in 6% of the patients and antiarrhythmic drug therapy in 37% of the patients. Quality of life improved significantly and was durable over 12-month follow-up. There were 2 deaths, which occurred in the early postoperative period: one due to atrioesophageal fistula and the second due to sudden cardiac death without apparent cause by autopsy., Conclusions: We report the largest series to date of a hybrid epicardial-endocardial, stand-alone ablation procedure using a pericardioscopic technique for the treatment of AF. While respecting the identified complications, our results demonstrate a high potential for successful treatment in a challenging patient population with AF., (Copyright © 2013 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Introduction: Owing to the very great age and the polypathology of the patients in geriatrics, we are often confronted to the palliative care decision., Purpose: The purposes of this retrospective study were both to define the criteria leading to palliative care and to analyse the evolution of patients., Method: We analysed 40 files of patients hospitalised in Geriatric internal medicine or Geriatric rehabilitation departments over 11 months., Results: Mean age was 85.4 years and 62.5% of patients were females. Infections, heart failure, general weakness, orthopaedic affections, strokes and cancers were the main causes of hospitalisation. Patients had 3 medical or surgical histories of chronic or cured serious diseases and a MMSE average value of 17.7. The rate of malnutrition was 92% and 90% of patients were very dependent. Severe infections, cancers, heart failure and severe pressure ulcers were the main affections for decision of palliative care. The latter was always decided by the staff with patients or families taking part in 8 cases and being informed in other cases. The palliative care lasted 7 days on average. Morphine was used in 31 cases. No artificial nutrition was introduced., Conclusion: The decision of palliative care is very complex since great age, polypathology, great dependence and high prevalence of cognitive disorders are frequent in this population.