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Chronic psychological stress is a recognized, yet understudied risk factor for heart disease, with potential sex-specific effects. We investigated whether chronic stress triggers sex-dependent cardiac dysfunction in isolated Wistar rat hearts subjected to ischemia-reperfusion injury. The experimental cohort underwent 1 h of daily restraint stress for 4 wk versus matched controls, followed by euthanasia (sodium pentobarbital) and heart excision for ex vivo perfusion. Blood analysis revealed sex-specific alterations in stress hormones and inflammatory markers. When compared with controls, chronic restraint stress (CRS) males displayed decreased plasma brain-derived neurotrophic factor (BDNF) levels (P < 0.05), whereas CRS females exhibited elevated plasma adrenocorticotropic hormone (ACTH) (P < 0.01) and reduced corticosterone (P < 0.001) alongside lower serum estradiol (P < 0.001) and estradiol/progesterone ratio (P < 0.01). Of note, CRS females showed increased serum cardiac troponin T (P < 0.05) and tumor necrosis factor-α (TNF-α) (P < 0.01) with suppressed interleukin (IL)-1α, IL-1β, IL-6, and IL-10 levels (P < 0.05) when compared with controls. Ex vivo Langendorff perfusions revealed that CRS female hearts displayed impaired postischemic functional recovery for baseline stroke volume (SV, P < 0.01), work performance (P < 0.05), aortic output (AO, P < 0.05), coronary flow (CF, P < 0.01), and overall cardiac output (CO, P < 0.01) when compared with matched controls and CRS males (P < 0.05). Our findings reveal intriguing sex-specific responses at both the systemic and functional levels in stressed hearts. Here, the dysregulation of stress hormones, proinflammatory state, and potential underlying cardiomyopathy in females following the stress protocol renders them more prone to damage following myocardial ischemia. This study emphasizes the importance of incorporating sex as a biological variable in cardiac research focusing on stress-related cardiomyopathy. NEW & NOTEWORTHY: Although chronic psychological stress is a risk factor for cardiovascular diseases, the underlying mechanisms remain poorly understood. This study revealed that chronic restraint stress resulted in systemic changes (dysregulated stress hormones, proinflammatory state) and potential cardiomyopathy in females versus controls and their male counterparts. The stressed female hearts also displayed reduced functional recovery following ex vivo ischemia-reperfusion. This highlights the importance of incorporating sex as a biological variable in cardiac research. [ABSTRACT FROM AUTHOR]

Cardiac conditions are the leading cause of pregnancy-related deaths and disproportionately affect non-Hispanic Black people. Multidisciplinary maternal mortality review committees have found that most people who died from cardiac conditions during pregnancy or postpartum were not diagnosed with a cardiovascular disease before death and that more than 80% of all pregnancy-related deaths, regardless of cause, were preventable. In addition, other obstetric complications, such as preeclampsia and gestational diabetes, are associated with future cardiovascular disease risk. Those with cardiac risk factors and those with congenital and acquired heart disease require specialized care during pregnancy and postpartum to minimize risk of preventable morbidity and mortality. This bundle provides guidance for health care teams to develop coordinated, multidisciplinary care for pregnant and postpartum people with cardiac conditions and to respond to cardio-obstetric emergencies. This bundle is one of several core patient safety bundles developed by the Alliance for Innovation on Maternal Health that provide condition- or event-specific clinical practices for implementation in appropriate care settings. The Cardiac Conditions in Obstetric Care bundle is organized into five domains: 1) Readiness , 2) Recognition and Prevention , 3) Response , 4) Reporting and Systems Learning , and 5) Respectful Care . This bundle is the first by the Alliance to be developed with the fifth domain of Respectful Care . The Respectful Care domain provides essential best practices to support respectful, equitable, and supportive care to all patients. Further health equity considerations are integrated into elements in each domain.

BACKGROUND: Cardiac device infection (CDI) can occur in up to 2.2% of patients after device placement, with mortality rates exceeding 15%. Although device removal is standard management, the COVID-19 pandemic has been associated with resource diversion and decreased patient presentation for cardiovascular disease. We ascertained the association of the COVID-19 pandemic with outcomes and resource utilization after admission for CDI. METHODS: The 2016-2020 National Inpatient Sample was used to retrospectively study all adult admissions for CDI. Patients admitted between March and December, 2020 were classified as the pandemic cohort, with the rest pre-pandemic. The primary outcome was major adverse events (MAE), with secondary outcomes of overall length of stay (LOS), post-device removal LOS, time to device replacement, and hospitalization costs. MAE was a combination of in-hospital mortality and select complications. Multivariable regression models were developed to determine the relationship between the pandemic and the aforementioned outcomes. RESULTS: Of an estimated 190,160 patients, 14.3% comprised the pandemic cohort; 2.4% of these patients were COVID-19 positive. The pandemic cohort was older, less commonly female, and had higher rates of congestive heart failure. After adjustment, the pandemic was not associated with altered odds of MAE, device removal, or subsequent device replacement. The pandemic was, however, associated with decreased adjusted overall LOS (β -0.38 days) and days to device replacement (β -0.83 days). The pandemic was likewise associated with $2,000 increased adjusted hospitalization costs. CONCLUSION: The pandemic did not have a significant impact on clinical outcomes in patients admitted for CDI, despite higher hospitalization costs and decreased length of stay.

IntroductionAlthough the physiological role of the C-terminal hydrolase domain of the soluble epoxide hydrolase (sEH-H) is well investigated, the function of its N-terminal phosphatase activity (sEH-P) remains unknown.ObjectivesThis study aimed to assess in vivo the physiological role of sEH-P.MethodsCRISPR/Cas9 was used to generate a novel knock-in (KI) rat line lacking the sEH-P activity.ResultsThe sEH-P KI rats has a decreased metabolism of lysophosphatidic acids to monoacyglycerols. KI rats grew almost normally but with less weight and fat mass gain while insulin sensitivity was increased compared to wild-type rats. This lean phenotype was more marked in males than in female KI rats and mainly due to decreased food consumption and enhanced energy expenditure. In fact, sEH-P KI rats had an increased lipolysis allowing to supply fatty acids as fuel to potentiate brown adipose thermogenesis under resting condition and upon cold exposure. The potentiation of thermogenesis was abolished when blocking PPARγ, a nuclear receptor activated by intracellular lysophosphatidic acids, but also when inhibiting simultaneously sEH-H, showing a functional interaction between the two domains. Furthermore, sEH-P KI rats fed a high-fat diet did not gain as much weight as the wild-type rats, did not have increased fat mass and did not develop insulin resistance or hepatic steatosis. In addition, sEH-P KI rats exhibited enhanced basal cardiac mitochondrial activity associated with an enhanced left ventricular contractility and were protected against cardiac ischemia-reperfusion injury.ConclusionOur study reveals that sEH-P is a key player in energy and fat metabolism and contributes together with sEH-H to the regulation of cardiometabolic homeostasis. The development of pharmacological inhibitors of sEH-P appears of crucial importance to evaluate the interest of this promising therapeutic strategy in the management of obesity and cardiac ischemic complications.

Introduction: heart disease is the leading cause of death in the world for both men and women. The presentation of ischemic heart disease varies depending on multiple factors, including gender. Materials and method: observational, cross-sectional study with an analytical component of all patients admitted with ACS at the Comandante Manuel Fajardo Clinical-Surgical Teaching Hospital, between January 2016 and December 2020. Results: female patients had a median age of 73 (IQR: 62-80) significantly higher than the male gender; with a higher prevalence of arterial hypertension and diabetes mellitus (n = 353 and n = 143 respectively and p < 0.01). Age, creatinine value, and STEACS were identified as triggering factors for cardiac complications (RR: 1.01; 95% CI: 1.00-1.07; p = 0.03; RR: 1.01; 95% CI: 1.00-1.02; p = 0.01; and RR: 2.77; 95% CI: 1.31-5.87; p = 0.02 respectively). Conclusions: women with ACS were older than men, with a higher prevalence of arterial hypertension and diabetes mellitus, while the predictive variables of intrahospital cardiovascular complications identified were age, serum creatinine value, and ACS with ST elevation. [ABSTRACT FROM AUTHOR]

BackgroundRacial differences in metabolomic profiles may reflect underlying differences in social determinants of health by self-reported race and may be related to racial disparities in coronary heart disease (CHD) among women in the United States. However, the magnitude of differences in metabolomic profiles between Black and White women in the United States has not been well-described. It also remains unknown whether such differences are related to differences in CHD risk.MethodsPlasma metabolomic profiles were analyzed using liquid chromatography-tandem mass spectrometry in the WHI-OS (Women's Health Initiative-Observational Study; 138 Black and 696 White women), WHI-HT trials (WHI-Hormone Therapy; 156 Black and 1138 White women), MESA (Multi-Ethnic Study of Atherosclerosis; 114 Black and 219 White women), JHS (Jackson Heart Study; 1465 Black women with 107 incident CHD cases), and NHS (Nurses' Health Study; 2506 White women with 136 incident CHD cases). First, linear regression models were used to estimate associations between self-reported race and 472 metabolites in WHI-OS (discovery); findings were replicated in WHI-HT and validated in MESA. Second, we used elastic net regression to construct a racial difference metabolomic pattern (RDMP) representing differences in the metabolomic patterns between Black and White women in the WHI-OS; the RDMP was validated in the WHI-HT and MESA. Third, using conditional logistic regressions in the WHI (717 CHD cases and 719 matched controls), we examined associations of metabolites with large differences in levels by race and the RDMP with risk of CHD, and the results were replicated in Black women from the JHS and White women from the NHS.ResultsOf the 472 tested metabolites, levels of 259 (54.9%) metabolites, mostly lipid metabolites and amino acids, significantly differed between Black and White women in both WHI-OS and WHI-HT after adjusting for baseline characteristics, socioeconomic status, lifestyle factors, baseline health conditions, and medication use (false discovery rate

BackgroundHeart disease is the leading cause of death for women and men in the United States. Yet, little is known about the motivation for care-seeking behavior for heart attack and the perception of self-risk of a heart attack in individuals, especially those at high risk for developing type 2 diabetes.ObjectivesThis study aimed to describe knowledge and awareness of heart attacks and perceived risk for future heart attacks and evaluate factors associated with a low perceived risk of a heart attack in adults with a high risk for type 2 diabetes.MethodsIn this secondary data, cross-sectional study, the screening/baseline data of 80 adults participating in the mobile phone-based diabetes prevention program trial were analyzed. Validated measures assessed knowledge, self-efficacy, and heart attack risk perception were used. Logistic regressions were performed.ResultsThe mean (standard deviation) age of participants was 55.4 (9.0) years. 32.5% of the sample failed to identify any heart attack symptoms. Half of the sample did not perceive their risk of having a heart attack in their lifetime. Older age, lower body mass index, not having a family history of heart attack, and current smokers were significantly associated with a lower perceived risk of heart attack (P < .05).ConclusionsHealthcare providers need to assess the discrepancies between the individual's risk perception and the presence of actual risk factors of a heart attack in adults with a high risk for type 2 diabetes.

Primary cardiac involvement is one of the leading causes of mortality in systemic sclerosis (SSc), but little is known regarding circulating biomarkers for cardiac SSc. Here, we aimed to investigate potential associations between cardiac SSc and candidate serum markers. Serum samples from patients of the Oslo University SSc cohort and 100 healthy controls were screened against two custom-made candidate marker panels containing molecules deemed relevant for cardiopulmonary and/or fibrotic diseases. Left (LV) and right ventricular (RV) dysfunction was assessed by protocol echocardiography, performed within three years from serum sampling. Patients suspected of pulmonary hypertension underwent right heart catheterization. Vital status at study end was available for all patients. Descriptive analyses, logistic and Cox regressions were conducted to assess associations between cardiac SSc and candidate serum markers. The 371 patients presented an average age of 57.2 (± 13.9) years. Female sex (84%) and limited cutaneous SSc (73%) were predominant. Association between LV diastolic dysfunction and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) (OR 0.41, 95% CI 0.21-0.78, p = 0.007) was identified. LV systolic dysfunction defined by global longitudinal strain was associated with angiopoietin 2 (ANGPT2) (OR 3.42, 95% CI 1.52-7.71, p = 0.003) and osteopontin (OPN) (OR 1.95, 95% CI 1.08-3.52, p = 0.026). RV systolic dysfunction, measured by tricuspid annular plane systolic excursion, was associated to markers of LV dysfunction (ANGPT2, OPN, and TRAIL) (OR 1.67, 95% CI 1.11-2.50, p = 0.014, OR 1.86, 95% CI 1.25-2.77, p = 0.002, OR 0.32, 95% CI 0.15-0.66, p = 0.002, respectively) and endostatin (OR 1.86, 95% CI 1.22-2.84, p = 0.004). In conclusion, ANGPT2, OPN and TRAIL seem to be circulating biomarkers associated with both LV and RV dysfunction in SSc.

BackgroundWe sought to evaluate the association of metabolic syndrome (MetS) and computed tomography (CT)-derived cardiometabolic biomarkers (non-alcoholic fatty liver disease [NAFLD] and epicardial adipose tissue [EAT] measures) with long-term risk of major adverse cardiovascular events (MACE) in asymptomatic individuals.MethodsThis was a post-hoc analysis of the prospective EISNER (Early-Identification of Subclinical Atherosclerosis by Noninvasive Imaging Research) study of participants who underwent baseline coronary artery calcium (CAC) scoring CT and 14-year follow-up for MACE (myocardial infarction, late revascularization, or cardiac death). EAT volume (cm3) and attenuation (Hounsfield units [HU]) were quantified from CT using fully automated deep learning software (

Background: Younger women with chronic disease (

Hydroxychloroquine has been widely prescribed to treat patients with COVID-19 pneumonia. A 73-year-0ld woman with COVID-19 pneumonia was treated with dexamethasone and hydroxychloroquine. Her home medications, citalopram and donepezil, were continued. The ECG prior to starting hydroxychloroquine showed normal sinus rhythm with prolonged corrected QT (QTc) of 497 ms, due to citalopram and donepezil therapy. Repeat ECG on days 3 and 4 of hydroxychloroquine therapy showed significantly prolonged QTc of 557 ms and 538 ms, respectively, despite normal serum electrolytes. All QT-prolonging medications including hydroxychloroquine were discontinued on day 4; however, she suffered a transient torsades de pointes lasting for about 15 s, which resolved before any intervention. QTc improved to 477 ms, after discontinuation of QT-prolonging medications. The patient had QTc prolongation and torsades de pointes due to therapy with multiple QT-prolonging medications. Medicine reconciliation and careful monitoring of QTc may help prevent cardiac complications in patients with COVID-19 treated with hydroxychloroquine.

BackgroundA limitation of the Agatston coronary artery calcium (CAC) score is that it does not use all of the calcium density information in the computed tomography scan such that many individuals have a score of zero. We examined the predictive validity for incident coronary heart disease (CHD) events of the spatially weighted coronary calcium score (SWCS), an alternative scoring method for CAC that assigns scores to individuals with Agatston CAC=0.MethodsThe MESA (Multi-Ethnic Study of Atherosclerosis) is a longitudinal study that conducted a baseline exam from 2000 to 2002 in 6814 participants including computed tomography scanning for CAC. Subsequent exams and systematic follow-up of the cohort for outcomes were performed. Statistical models were adjusted using the MESA risk score based on age, sex, race/ethnicity, systolic blood pressure, use of hypertension medications, diabetes, total and HDL (high-density lipoprotein) cholesterol, use of lipid-lowering medications, smoking status, and family history of heart attack.ResultsIn the 3286 participants with Agatston CAC=0 at baseline and for whom SWCS was computed, 98 incident CHD events defined as definite or probably myocardial infarction or definite CHD death occurred during a median follow-up of 15.1 years. In this group, SWCS predicted incident CHD events after multivariable adjustment (hazard ratio=1.30 per SD of natural logarithm [SWCS] [95% CI, 1.04-1.60]; P=0.005); and progression from Agatston CAC=0 at baseline to CAC>0 at subsequent exams (multivariable-adjusted incidence rate difference per SD of natural logarithm [SWCS] per 100 person-years 1.68 [95% CI, 1.03-2.33]; P0 at repeat computed tomography scanning at later exams. SWCS has predictive validity as a subclinical phenotype and marker of CHD risk in individuals with Agatston CAC=0.

BackgroundInvestigators conducting studies that include potentially suicidal individuals are obligated to develop a suicide risk management (SRM) protocol. There is little available in the literature to guide researchers in SRM protocol development.ObjectivesThe aim of the study was to describe an SRM protocol developed for a randomized controlled trial (RCT) currently enrolling cardiac patients who report moderate to severe levels of hopelessness.MethodsThe SRM protocol identifies suicidal ideation and measures ideation severity through use of the Columbia-Suicide Severity Rating Scale risk factor questions. Based on responses, study participants are deemed safe or at low, moderate, or high risk for suicide. The SRM protocol guides research staff through a plan of action based on risk level. The protocol further guides staff through a plan over the course of this prospective study-from hospital enrollment to home-based visits.ResultsResearch staff are well trained to identify suicidal ideation risk factors, initiate specific questioning about suicidal intent, determine level of risk, identify protective factors and a safe environment, and make referrals if needed. Of the 51 patients hospitalized with cardiac disease who reported moderate to severe hopelessness, 43 scored at a safe suicide risk level and 8 scored at low risk. Thirty-five of the 51 patients enrolled in the RCT. Of the 35 participants who received home visits to date, there have been three instances of low and one instance of moderate suicide risk. The SRM protocol has been consistently and accurately used by research personnel in both hospital and home settings. One modification has been made to the protocol since study activation, namely, the addition of an assessment of counseling history and encouragement of continued counseling. Booster training sessions of research staff will continue throughout the course of the RCT.DiscussionUse of the SRM protocol identifies study participants who are safe or at risk for suicide in both hospital and home settings, and research staff can refer participants accordingly.ConclusionThe SRM protocol developed for this RCT can serve as a model in the development of SRM protocols for future research in acute care, community, or home-based settings.

Many crucial cardiovascular adaptations occur in the body during pregnancy to ensure successful gestation. Maladaptation of the cardiovascular system during pregnancy can lead to complications that promote cardiac dysfunction and may lead to heart failure (HF). About 12% of pregnancy-related deaths in the USA have been attributed to HF and the detrimental effects of cardiovascular complications on the heart can be long-lasting, pre-disposing the mother to HF later in life. Indeed, cardiovascular complications such as gestational diabetes mellitus, preeclampsia, gestational hypertension, and peripartum cardiomyopathy have been shown to induce cardiac metabolic dysfunction, oxidative stress, fibrosis, apoptosis, and diastolic and systolic dysfunction in the hearts of pregnant women, all of which are hallmarks of HF. The exact etiology and cardiac pathophysiology of pregnancy-related complications is not yet fully deciphered. Furthermore, diagnosis of cardiac dysfunction in pregnancy is often made only after clinical symptoms are already present, thus necessitating the need for novel diagnostic and prognostic biomarkers. Mounting data demonstrates an altered expression of maternal circulating miRNAs during pregnancy affected by cardiovascular complications. Throughout the past decade, miRNAs have become of growing interest as modulators and biomarkers of pathophysiology, diagnosis, and prognosis in cardiac dysfunction. While the association between pregnancy-related cardiovascular complications and cardiac dysfunction or HF is becoming increasingly evident, the roles of miRNA-mediated regulation herein remain poorly understood. Therefore, this review will summarize current reports on pregnancy-related cardiovascular complications that may lead to cardiac dysfunction and HF during and after pregnancy in previously healthy women, with a focus on the pathophysiological role of miRNAs.

The prognostic power of circulating cardiac biomarkers, their utility, and pattern of release in coronavirus disease 2019 (COVID-19) patients have not been clearly defined. In this multicentered retrospective study, we enrolled 3219 patients with diagnosed COVID-19 admitted to 9 hospitals from December 31, 2019 to March 4, 2020, to estimate the associations and prognostic power of circulating cardiac injury markers with the poor outcomes of COVID-19. In the mixed-effects Cox model, after adjusting for age, sex, and comorbidities, the adjusted hazard ratio of 28-day mortality for hs-cTnI (high-sensitivity cardiac troponin I) was 7.12 ([95% CI, 4.60-11.03] P

Assessing thromboembolic risk is crucial for proper management of patients with atrial fibrillation. Left atrial volume is a promising predictor of cardiac thrombosis. To determine whether left atrial volume can predict left atrial appendage thrombus in patients with atrial fibrillation, we conducted a prospective study of 73 patients. Left atrial and ventricular volumes were evaluated by cardiac computed tomography with retrospective electrocardiographic gating and then indexed to body surface area. Left atrial appendage thrombus was confirmed or excluded by cardiac computed tomography with delayed enhancement. Seven patients (9.6%) had left atrial appendage thrombus; 66 (90.4%) did not. Those with thrombus had a significantly higher mean left atrial end-systolic volume index (139 ± 55 vs 101 ± 35 mL/m2; P =0.0097) and mean left atrial end-diastolic volume index (122 ± 45 vs 84 ± 34 mL/m2; P =0.0077). On multivariate logistic regression analysis, left atrial end-systolic volume index (per 10 mL/m2 increase) was significantly associated with left atrial appendage thrombus (odds ratio [OR]=1.24; 95% CI, 1.03-1.50; P =0.02); so too was the left atrial end-diastolic volume index (per 10 mL/m2 increase) (OR=1.29; 95% CI, 1.05-1.60; P =0.02). These findings suggest that increased left atrial volume increases the risk of left atrial appendage thrombus. Therefore, patients with atrial fibrillation and an enlarged left atrium should be considered for cardiac computed tomography with delayed enhancement to confirm whether thrombus is present.

BackgroundThe left atrial end-systolic volume index (LAESVI) is a predictor of cardiovascular outcomes and is the recommended measurement of left atrial size. The left atrial end-diastolic volume index (LAEDVI), representing the minimum or residual left atrial volume, has not been fully evaluated as a predictor of cardiovascular events. This study evaluated the predictive power of LAEDVI compared with LAESVI for heart failure (HF) hospitalizations, a composite of HF hospitalizations, myocardial infarction, stroke, and heart disease death, and all-cause mortality.MethodsWe measured LAESVI and LAEDVI in subjects without atrial fibrillation or flutter or significant mitral valve disease. Using Cox proportional-hazard models, the association of LAESVI and LAEDVI with the stated outcomes was examined.ResultsAfter a mean of 7.3±2.6 years of follow-up, there were 147 HF hospitalizations, 118 myocardial infarctions, 45 strokes, 96 heart disease deaths, and 351 deaths from all causes in 938 subjects. When comparing the highest and the lowest quartiles of LAEDVI, there was a near 6-fold increase in the hazard ratio (HR) for HF hospitalization (HR, 5.96; P

BACKGROUND: The National Comprehensive Cancer Network and American Society of Clinical Oncology recommend consideration of the use of echocardiography 6 to 12 months after completion of anthracycline-based chemotherapy in at-risk populations. Assessment of BNP (B-type natriuretic peptide) has also been suggested by the American College of Cardiology/American Heart Association/Heart Failure Society of America for the identification of Stage A (at risk) heart failure patients. The real-world frequency of the use of these tests in patients after receipt of anthracycline therapy, however, has not been studied previously. METHODS AND RESULTS: In this retrospective study, using administrative claims data from the OptumLabs Data Warehouse, we identified 31 447 breast cancer and lymphoma patients (age ≥18 years) who were treated with an anthracycline in the United States between January 1, 2008 and January 31, 2018. Continuous medical and pharmacy coverage was required for at least 6 months before the initial anthracycline dose and 12 months after the final dose. Only 36.1% of patients had any type of cardiac surveillance (echocardiography, BNP, or cardiac imaging) in the year following completion of anthracycline therapy (29.7% echocardiography). Surveillance rate increased from 37.5% in 2008 to 42.7% in 2018 (25.6% in 2008 to 40.5% echocardiography in 2018). Lymphoma patients had a lower likelihood of any surveillance compared with patients with breast cancer (odds ratio, 0.79 [95% CI, 0.74-0.85]; P50% rate of surveillance. CONCLUSIONS: The majority of survivors of breast cancer and lymphoma who have received anthracycline-based chemotherapy do not undergo cardiac surveillance after treatment, including those with a history of cardiovascular comorbidities, such as heart failure.

BackgroundExposure to household air pollution (HAP) from cooking with biomass fuel affects billions of people. We hypothesized that HAP from woodsmoke, compared to other household fuels, was associated with adverse cardiovascular outcomes, of which there have been few studies.MethodsA cross-sectional study was completed in 299 females aged 40-70 years in Kaski District, Nepal, during 2017-18. All participants underwent a standard 12-lead ECG, ankle and brachial systolic blood pressure measurement, and 2D color and Doppler echocardiography. Current stove type was confirmed by inspection. Blood pressure, height, and weight were measured using a standardized protocol. Hypertension was defined as ≥140/90 mmHg or prior diagnosis. Hemoglobin A1c (HbA1c) was obtained, with diabetes mellitus defined as a prior diagnosis or HbA1C ≥ 6.5%. We used adjusted linear and logistic multivariable regressions to examine the relationship of stove type with cardiac structure and function.ResultsThe majority of women primarily used liquified petroleum gas (LPG) stoves (65%), while 12% used biogas, and 23% used wood-burning cook-stoves. Prevalence of major cardiovascular risk factors was 35% with hypertension, 19% with diabetes mellitus, and 15% current smokers. After adjustment, compared to LPG, wood stove use was associated with increased indexed left atrial volume (β = 3.15, 95% CI 1.22 to 5.09) and increased indexed left ventricular end diastolic volume (β = 7.97, 95% CI 3.11 to 12.83). There was no association between stove type and systemic hypertension, left ventricular mass, systolic dysfunction, diastolic dysfunction, pulmonary hypertension, abnormal ankle-brachial index, or clinically significant ECG abnormalities.ConclusionBiomass fuel use was associated with increased indexed left atrial volume and increased indexed left ventricular diastolic volume in Nepali women, suggesting subclinical adverse cardiac remodeling from HAP in this cross-sectional study. We did not find evidence of an association with hypertension or typical cardiac sequelae of hypertension. Future studies to confirm these results are needed.

BackgroundCarfilzomib improves survival in patients with recurrent myeloma. Given the strict eligibility criteria in clinical trials, the actual frequency of cardiac adverse events (CAEs) and pulmonary adverse events (PAEs) and the risk factors associated with these AEs in the general population need to be established.MethodsThe authors extracted myeloma cases in the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database from 2000 through 2013 and corresponding claims through 2014. They then identified patients who received carfilzomib during their disease course. Subsequently, the International Classification of Diseases, Ninth Revision (ICD-9) was used to identify all the codes for CAEs, PAEs, and respiratory infections associated with carfilzomib use. Preexisting diagnoses corresponding to the CAEs and PAEs of interest were excluded to distinguish toxicity from comorbidity. Multivariate Cox regression was performed to determine those variables independently associated with the development of CAEs and PAEs.ResultsOf the 635 patients analyzed, the median age was 72 years (range, 36-94 years); 55% of the patients were male and 79% were white. The median duration of carfilzomib treatment was 58 days (range, 1-716 days). Overall, approximately 66% of the patients had codes for either CAEs or PAEs. In terms of CAEs, approximately 22% of patients developed hypertension, 15% developed peripheral edema, and 14% experienced heart failure. With regard to PAEs, approximately 28% of patients developed dyspnea, 15% developed cough, and 15% developed pneumonia. Only chronic obstructive pulmonary disease (COPD) was found to be independently associated with the development of CAEs. Patients with preexisting COPD were found to have a 40% increase in their hazard of developing CAEs (adjusted hazard ratio, 1.40; 95% CI, 1.03-1.90).ConclusionsIn older adults with myeloma who are undergoing treatment with carfilzomib, new cardiac and pulmonary diagnoses were common. Patients with preexisting COPD were found to be at an increased risk of developing CAEs.

BACKGROUND: Cardiac adverse events are common among patients presenting with acute stroke and contribute to overall morbidity and mortality. Prophylactic measures for the reduction of cardiac adverse events in hospitalized stroke patients have not been well understood. We sought to investigate the effect of early initiation of high-dose intravenous magnesium sulfate on cardiac adverse events in stroke patients. METHODS: This is a secondary analysis of the prehospital Field Administration of Stroke Therapy-Magnesium (FAST-MAG) randomized phase-3 clinical trial, conducted from 2005-2013. Consecutive patients with suspected acute stroke and a serum magnesium level within 72 hours of enrollment were selected. Twenty grams of magnesium sulfate or placebo was administered in the ambulance starting with a 15-minute loading dose intravenous infusion followed by a 24-hour maintenance infusion in the hospital. RESULTS: Among 1126 patients included in the analysis of this study, 809 (71.8%) patients had ischemic stroke, 277 (24.6%) had hemorrhagic stroke, and 39 (3.5%) with stroke mimics. The mean age was 69.5 (SD13.4) and 42% were female. 565 (50.2%) received magnesium treatment, and 561 (49.8%) received placebo. 254 (22.6%) patients achieved the target, and 872 (77.4%) did not achieve the target, regardless of their treatment group. Among 1126 patients, 159 (14.1%) had at least one CAE. Treatment with magnesium was not associated with fewer cardiac adverse events. A multivariate binary logistic regression for predictors of CAEs showed a positive association of older age and frequency of CAEs (R = 1.04, 95% CI 1.03-1.06, p < 0.0001). Measures of early and 90-day outcomes did not differ significantly between the magnesium and placebo groups among patients who had CAEs. CONCLUSION: Treatment of acute stroke patients with magnesium did not result in a reduction in the number or severity of cardiac serious adverse events.

Macronutrient intake, the proportion of calories consumed from carbohydrate, fat, and protein, is an important risk factor for metabolic diseases with significant familial aggregation. Previous studies have identified two genetic loci for macronutrient intake, but incomplete coverage of genetic variation and modest sample sizes have hindered the discovery of additional loci. Here, we expanded the genetic landscape of macronutrient intake, identifying 12 suggestively significant loci (P

BackgroundSyncope is a common chief complaint among older adults in the Emergency Department (ED), and orthostatic vital signs are often a part of their evaluation. We assessed whether abnormal orthostatic vital signs in the ED are associated with composite 30-day serious outcomes in older adults presenting with syncope.MethodsWe performed a secondary analysis of a prospective, observational study at 11 EDs in adults ≥ 60 years who presented with syncope or near syncope. We excluded patients lost to follow up. We used the standard definition of abnormal orthostatic vital signs or subjective symptoms of lightheadedness upon standing to define orthostasis. We determined the rate of composite 30-day serious outcomes, including those during the index ED visit, such as cardiac arrhythmias, myocardial infarction, cardiac intervention, new diagnosis of structural heart disease, stroke, pulmonary embolism, aortic dissection, subarachnoid hemorrhage, cardiopulmonary resuscitation, hemorrhage/anemia requiring transfusion, with major traumatic injury from fall, recurrent syncope, and death) between the groups with normal and abnormal orthostatic vital signs.ResultsThe study cohort included 1974 patients, of whom 51.2% were male and 725 patients (37.7%) had abnormal orthostatic vital signs. Comparing those with abnormal to those with normal orthostatic vital signs, we did not find a difference in composite 30-serious outcomes (111/725 (15.3%) vs 184/1249 (14.7%); unadjusted odds ratio, 1.05 [95%CI, 0.81-1.35], p = 0.73). After adjustment for gender, coronary artery disease, congestive heart failure (CHF), history of arrhythmia, dyspnea, hypotension, any abnormal ECG, physician risk assessment, medication classes and disposition, there was no association with composite 30-serious outcomes (adjusted odds ratio, 0.82 [95%CI, 0.62-1.09], p = 0.18).ConclusionsIn a cohort of older adult patients presenting with syncope who were able to have orthostatic vital signs evaluated, abnormal orthostatic vital signs did not independently predict composite 30-day serious outcomes.

PURPOSE: Cardiovascular adverse events (CVAEs) can occur during proteasome inhibitor (PI) therapy. We conducted a prospective, observational, multi-institutional study to define risk factors and outcomes in patients with multiple myeloma (MM) receiving PIs. PATIENTS AND METHODS: Patients with relapsed MM initiating carfilzomib- or bortezomib-based therapy underwent baseline assessments and repeated assessments at regular intervals over 6 months, including cardiac biomarkers (troponin I or T, brain natriuretic peptide [BNP], and N-terminal proBNP), ECG, and echocardiography. Monitoring occurred over 18 months for development of CVAEs. RESULTS: Of 95 patients enrolled, 65 received carfilzomib and 30 received bortezomib, with median 25 months of follow-up. Sixty-four CVAEs occurred, with 55% grade 3 or greater in severity. CVAEs occurred in 51% of patients treated with carfilzomib and 17% of those treated with bortezomib (P = .002). Median time to first CVAE from treatment start was 31 days, and 86% occurred within the first 3 months. Patients receiving carfilzomib-based therapy with a baseline elevated BNP level higher than 100 pg/mL or N-terminal proBNP level higher than 125 pg/mL had increased risk for CVAE (odds ratio, 10.8; P < .001). Elevated natriuretic peptides occurring mid-first cycle of treatment with carfilzomib were associated with a substantially higher risk of CVAEs (odds ratio, 36.0; P < .001). Patients who experienced a CVAE had inferior progression-free survival (log-rank P = .01) and overall survival (log-rank P < .001). PI therapy was safely resumed in 89% of patients, although 41% required chemotherapy modifications. CONCLUSION: CVAEs are common during PI therapy for relapsed MM, especially with carfilzomib, particularly within the first 3 months of therapy. CVAEs were associated with worse overall outcomes, but usually, discontinuation of therapy was not required. Natriuretic peptides were highly predictive of CVAEs; however, validation of this finding is necessary before uniform incorporation into the routine management of patients receiving carfilzomib.

Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n = 321,223) and offspring birth weight (n = 230,069 mothers), we identified 190 independent association signals (129 of which are novel). We used structural equation modeling to decompose the contributions of direct fetal and indirect maternal genetic effects, then applied Mendelian randomization to illuminate causal pathways. For example, both indirect maternal and direct fetal genetic effects drive the observational relationship between lower birth weight and higher later blood pressure: maternal blood pressure-raising alleles reduce offspring birth weight, but only direct fetal effects of these alleles, once inherited, increase later offspring blood pressure. Using maternal birth weight-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring blood pressure, indicating that the inverse birth weight-blood pressure association is attributable to genetic effects, and not to intrauterine programming.

ObjectiveResistin is a hormone that has been associated with metabolic syndrome and cardiovascular disease. The role of resistin in patients with peripheral artery disease (PAD) has not been fully explored. This study seeks to understand the relationship between serum resistin, vascular function, and cardiovascular outcomes in patients with PAD.MethodsThere were 106 patients with PAD who were recruited between 2011 and 2016. Patients attended a baseline visit during which a comprehensive vascular physiology assessment including medical and surgical history, radial artery tonometry, and flow mediated-vasodilation (FMD) was completed. A blood sample was drawn, and serum resistin was assayed using enzyme-linked immunosorbent assay kits. Using the time of study enrollment as the time of origin, incident major adverse cardiac events (MACEs) were identified by subsequent chart review and defined as a composite end point of myocardial infarction, coronary revascularization, transient ischemic attack, stroke, or death from a cardiac cause.ResultsPatients had a mean age of 68 ± 8 years, were largely white (75%), and had comorbidities commonly associated with PAD including hypertension (92%), hyperlipidemia (87%), coronary artery disease (37%), and diabetes mellitus (38%). After stratification by resistin quartile, higher resistin quartiles were significantly associated with an older age, a greater number of pack-years smoked, and a lower estimated glomerular filtration rate. Despite similar comorbidities and medication use, endothelial function, as measured by FMD, was significantly lower with increasing resistin quartile (I, 9.1% ± 3.3%; II, 7.1% ± 3.5%; III, 5.8% ± 4.0%; IV, 5.6% ± 3.5%; P = .002). In multivariable linear regression, higher resistin quartiles (III and IV) were associated with lower FMD relative to quartile I after adjusting for several patient characteristics, medications, and comorbidities (III, -2.26 [95% confidence interval (CI), -4.51 to -0.01; P = .05]; IV, -2.53 [95% CI, -4.87 to -0.20; P = .03]). During a median follow-up period of 36 months (interquartile range, 29-45 months), 21 patients experienced the primary end point. In a Cox proportional hazards model adjusted for smoking status, coronary artery disease, and age, each 1 ng/mL increase in resistin was associated with a 10% increased risk of MACEs (hazard ratio, 1.10; 95% CI, 1.00-1.20; P = .04).ConclusionsIn patients with PAD, higher levels of resistin were associated with impaired endothelial function and an increased rate of MACEs. These results suggest that resistin may be a marker or effector of impaired vascular physiology and adverse cardiac outcomes in patients with PAD. Further research is needed to determine the potential mechanisms by which resistin may impair endothelial function and increase MACEs in this population.

ObjectivesPediatric cardiac ICUs should be adept at treating both critical medical and surgical conditions for patients with cardiac disease. There are no case-mix adjusted quality metrics specific to medical cardiac ICU admissions. We aimed to measure case-mix adjusted cardiac ICU medical mortality rates and assess variation across cardiac ICUs in the Pediatric Cardiac Critical Care Consortium.DesignObservational analysis.SettingPediatric Cardiac Critical Care Consortium clinical registry.PatientsAll cardiac ICU admissions that did not include cardiac surgery.InterventionsNone.Measurements and main resultsThe primary endpoint was cardiac ICU mortality. Based on multivariable logistic regression accounting for clustering, we created a case-mix adjusted model using variables present at cardiac ICU admission. Bootstrap resampling (1,000 samples) was used for model validation. We calculated a standardized mortality ratio for each cardiac ICU based on observed-to-expected mortality from the fitted model. A cardiac ICU was considered a statistically significant outlier if the 95% CI around the standardized mortality ratio did not cross 1. Of 11,042 consecutive medical admissions from 25 cardiac ICUs (August 2014 to May 2017), the observed mortality rate was 4.3% (n = 479). Final model covariates included age, underweight, prior surgery, time of and reason for cardiac ICU admission, high-risk medical diagnosis or comorbidity, mechanical ventilation or extracorporeal membrane oxygenation at admission, and pupillary reflex. The C-statistic for the validated model was 0.87, and it was well calibrated. Expected mortality ranged from 2.6% to 8.3%, reflecting important case-mix variation. Standardized mortality ratios ranged from 0.5 to 1.7 across cardiac ICUs. Three cardiac ICUs were outliers; two had lower-than-expected (standardized mortality ratio 1) mortality.ConclusionsWe measured case-mix adjusted mortality for cardiac ICU patients with critical medical conditions, and provide the first report of variation in this quality metric within this patient population across Pediatric Cardiac Critical Care Consortium cardiac ICUs. This metric will be used by Pediatric Cardiac Critical Care Consortium cardiac ICUs to assess and improve outcomes by identifying high-performing (low-mortality) centers and engaging in collaborative learning.

The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)-pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D-pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P

BackgroundDonor-specific HLA antibodies (DSA) are associated with increased rates of rejection and of graft failure in cardiac transplantation. The goal of this study was to determine the association of preformed and posttransplant development of newly detected DSA (ndDSA) with antibody-mediated rejection (AMR) and characterize the clinical relevance of complement-activating DSA in heart allograft recipients.MethodsThe study included 128 adult and 48 pediatric heart transplant patients transplanted between 2010 and 2013. Routine posttransplant HLA antibody testing was performed by IgG single-antigen bead test. The C3d single-antigen bead assay was used to identify complement-activating antibodies. Rejection was diagnosed using International Society for Heart and Lung Transplantation criteria.ResultsIn this study, 22 patients were transplanted with preexisting DSA, and 43 patients developed ndDSA posttransplant. Pretransplant (P < 0.05) and posttransplant (P < 0.001) ndDSA were associated with higher incidence of AMR. Patients with C3d + DSA had significantly higher incidence of AMR compared with patients with no DSA (P < 0.001) or patients with C3d-DSA (P = 0.02). Nine (36%) of 25 patients with AMR developed transplant coronary artery disease compared with 17 (15.9%) of 107 patients without AMR (P < 0.05). Among the 47 patients who received ventricular assistant device (VAD), 7 of 9 VAD+ patients with preformed DSA experienced AMR compared with 7 of 38 VAD+ patients without preformed DSA, indicating presensitization to donor HLA significantly increased the risk of AMR (P < 0.01).ConclusionsPreformed and posttransplant ndDSA were associated with AMR. C3d + DSA correlates with complement deposition on the graft and higher risk of AMR which may permit the application of personalized immunotherapy targeting the complement pathway.

Rationale & objectiveAbnormal cardiac structure and function are common in chronic kidney disease (CKD) and end-stage renal disease (ESRD) and linked with mortality and heart failure. We examined changes in echocardiographic measures during the transition from CKD to ESRD and their associations with post-ESRD mortality.Study designProspective study.Setting & participantsWe studied 417 participants with CKD in the Chronic Renal Insufficiency Cohort (CRIC) who had research echocardiograms during CKD and ESRD.PredictorWe measured change in left ventricular mass index, left ventricular ejection fraction (LVEF), diastolic relaxation (normal, mildly abnormal, and moderately/severely abnormal), left ventricular end-systolic (LVESV), end-diastolic (LVEDV) volume, and left atrial volume from CKD to ESRD.OutcomesAll-cause mortality after dialysis therapy initiation.Analytical approachCox proportional hazard models were used to test the association of change in each echocardiographic measure with postdialysis mortality.ResultsOver a mean of 2.9 years between pre- and postdialysis echocardiograms, there was worsening of mean LVEF (52.5% to 48.6%; P

This randomized, open-label, phase 2b study (NCT01565668) evaluated the efficacy and safety of 2 dosing regimens of quizartinib monotherapy in patients with relapsed/refractory (R/R) FLT3-internal tandem duplication (ITD)-mutated acute myeloid leukemia (AML) who previously underwent transplant or 1 second-line salvage therapy. Patients (N = 76) were randomly assigned to 30- or 60-mg/day doses (escalations to 60 or 90 mg/day, respectively, permitted for lack/loss of response) of single-agent oral quizartinib dihydrochloride. Allelic frequency of at least 10% was defined as FLT3-ITD-mutated disease. Coprimary endpoints were composite complete remission (CRc) rates and incidence of QT interval corrected by Fridericia's formula (QTcF) of more than 480 ms (grade 2 or greater). Secondary endpoints included overall survival (OS), duration of CRc, bridge to transplant, and safety. CRc rates were 47% in both groups, similar to earlier reports with higher quizartinib doses. Incidence of QTcF above 480 ms was 11% and 17%, and QTcF above 500 ms was 5% and 3% in the 30- and 60-mg groups, respectively, which is less than earlier reports with higher doses of quizartinib. Median OS (20.9 and 27.3 weeks), duration of CRc (4.2 and 9.1 weeks), and bridge to transplant rates (32% and 42%) were higher in the 60-mg groups than in the 30-mg group. Dose escalation occurred in 61% and 14% of patients in the 30- and 60-mg groups, respectively. This high clinical activity of quizartinib at the evaluated doses is consistent with previous reports with an improved safety profile. Need to dose-escalate more than half of patients who received quizartinib 30 mg also supports further investigation of treatment with quizartinib 60 mg/day.

BACKGROUND:The objective of this study was to examine the use of preoperative cardiac stress testing (PCST) in the Southern California Vascular Outcomes Improvement Collaborative (So Cal VOICe). METHODS:A retrospective review was performed on data in all modules of the So Cal VOICe from September 2012 through May 2016. PCST was defined as stress echocardiogram or nuclear stress test. A new postoperative myocardial infarction (MI) was defined as troponin elevation and/or electrocardiogram/imaging changes with or without ischemic symptoms. Only elective cases in patients with asymptomatic cardiac status were included in the study. RESULTS:During the study period, 3,063 procedures meeting the inclusion criteria were performed in 7 registries: carotid endarterectomy (CEA), carotid artery stent, thoracic endovascular aneurysm repair, infrainguinal bypass (Infra), endovascular aneurysm repair (EVAR), suprainguinal bypass (Supra), and open abdominal aortic aneurysm repair (OAAA). PCST varied across registries from 17% in PVI to 62% in OAAA. PCST in CEA varied across 9 institutions from 10% to 79%. PCST in EVAR varied across 7 institutions from 14% to 83%. PCST in Infra varied across 4 institutions from 10% to 57%. Of the 12 patients across all registries who had a new MI, 6 had PCST, one of which was abnormal. CONCLUSIONS:The incidence of PCST varies widely across registries and institutions in the So Cal VOICe. Despite the wide variation, the incidence of new postoperative MI is exceptionally low. Further studies should evaluate the cost-effectiveness of the PCST practices and future quality improvement efforts should focus on standardization of indications for PCST.

BackgroundCardiac rehabilitation is strongly recommended after myocardial infarction, percutaneous coronary intervention, or coronary artery bypass surgery, but it is historically underused. We sought to evaluate variation in cardiac rehabilitation participation across the United States.MethodsFrom administrative data from the Veterans Affairs (VA) healthcare system and a 5% Medicare sample, we used International Classification of Diseases, 9th Revision codes to identify patients hospitalized for myocardial infarction, percutaneous coronary intervention, or coronary artery bypass surgery from 2007 to 2011. After excluding patients who died in ≤30 days of hospitalization, we calculated the percentage of patients who participated in ≥1 outpatient visits for cardiac rehabilitation during the 12 months after hospitalization. We estimated adjusted and standardized rates of participation in cardiac rehabilitation by state using hierarchical logistic regression models.ResultsOverall, participation in cardiac rehabilitation was 16.3% (23 403/143 756) in Medicare and 10.3% (9123/88 826) in VA. However, participation rates varied widely across states, ranging from 3.2% to 41.8% in Medicare and 1.2% to 47.6% in VA. Similar regional variation was observed in both populations. Patients in the West North Central region (Iowa, Kansas, Minnesota, Missouri, Nebraska, North Dakota, and South Dakota) had the highest participation, whereas those in the Pacific region (Alaska, California, Hawaii, Oregon, and Washington) had the lowest participation in both Medicare (33.7% versus 10.6%) and VA (16.6% versus 5.1%) populations. Significant hospital-level variation was also present, with participation ranging from 3% to 75% in Medicare and 1% to 43% in VA.ConclusionsCardiac rehabilitation participation remains low overall in both Medicare and VA populations. However, remarkably similar regional variation exists, with some regions and hospitals achieving high rates of participation in both populations. This provides an opportunity to identify best practices from higher performing hospitals and regions that could be used to improve cardiac rehabilitation participation in lower performing hospitals and regions.

Adolescents with single ventricle heart disease (SVHD) show autonomic, mood, and cognitive deficits, indicating aberrations in brain areas that regulate these functions. However, the gray matter integrity in autonomic, mood, and cognitive control sites is unclear. We examined regional brain gray matter changes, using high-resolution T1-weighted images (3.0-T magnetic resonance scanner) with voxel based morphometry procedures, as well as mood and cognitive functions in SVHD (n=18; age, 15.7±1.1years; male, 10) and controls (n=31; age, 16.0±1.1years; male, 17). High-resolution T1-weighted images were realigned, gray matter tissue type partitioned, normalized to a common space, smoothed, and compared between groups (analysis of covariance; covariates, age and gender). The mood and cognitive scores were compared between groups using independent samples t-tests. SVHD subjects showed significantly altered mood and cognitive functions over controls. Significantly reduced gray matter emerged in multiple brain areas, including the thalamus, caudate nuclei, putamen, insula, prefrontal, post-central and precentral gyrus, occipital gyrus, para-hippocampal gyrus, temporal gyrus, and cerebellar sites in SVHD over controls. SVHD subjects show compromised gray matter integrity in autonomic, mood and cognitive control sites. The findings indicate that frequent deficits found in SVHD subjects have a brain structural basis in the condition.

Patients with end stage renal disease (ESRD) suffer high mortality from arrhythmias linked to fibrosis, but are contraindicated to late gadolinium enhancement magnetic resonance imaging (MRI). We present a quantitative method for gadolinium-free cardiac fibrosis imaging using magnetization transfer (MT) weighted MRI, and probe correlations with widely used surrogate markers including cardiac structure and contractile function in patients with ESRD. In a sub-group of patients who returned for follow-up imaging after one year, we examine the correlation between changes in fibrosis and ventricular structure/function. Quantification of changes in MT revealed significantly greater fibrotic burden in patients with ESRD compared to a healthy age matched control cohort. Ventricular mechanics, including circumferential strain and diastolic strain rate were unchanged in patients with ESRD. No correlation was observed between fibrotic burden and concomitant measures of either circumferential or longitudinal strains or strain rates. However, among patients who returned for follow up examination a strong correlation existed between initial fibrotic burden and subsequent loss of contractile function. Gadolinium-free myocardial fibrosis imaging in patients with ESRD revealed a complex and longitudinal, not contemporary, association between fibrosis and ventricular contractile function.

INTRODUCTION:Left atrial appendage closure (LAAC) with LARIAT offers an alternative to oral anticoagulation (OAC) for patients with atrial fibrillation. The aim of this study was to present long-term clinical outcomes of LAAC in these patients (AF). MATERIAL AND METHODS:A prospective, single-center study was performed in 139 patients undergoing LAAC with Lariat. Thromboembolic events, severe bleeding and mortality rate were recorded. The reduction in risk of thromboembolism and bleeding after LAAC was calculated. RESULTS:The mean CHADS2-score was 1.8 ± 1.0, mean CHA2DS2-VASc score was 2.9 ± 1.6 and HAS-BLED score was 3.1 ± 1.1. After 428.4 patient-years of follow-up (mean 4.2±1.0 years), the thromboembolism rate was 0.6% with a calculated thromboembolism risk reduction of 81%. The severe bleeding rate was 0.8%; calculated bleeding risk reduction was 78%. The overall mortality rate was 1.6%. CONCLUSIONS:Long-term outcomes show that LAAC with Lariat is a safe and effective treatment for stroke prevention and bleeding risk reduction in AF patients with a high level of underlying risk.

BackgroundChildren with heart disease may require repeated X-Ray cardiac catheterization procedures, are more radiosensitive, and more likely to survive to experience oncologic risks of medical radiation. Cardiovascular magnetic resonance (CMR) is radiation-free and offers information about structure, function, and perfusion but not hemodynamics. We intend to perform complete radiation-free diagnostic right heart catheterization entirely using CMR fluoroscopy guidance in an unselected cohort of pediatric patients; we report the feasibility and safety.MethodsWe performed 50 CMR fluoroscopy guided comprehensive transfemoral right heart catheterizations in 39 pediatric (12.7 ± 4.7 years) subjects referred for clinically indicated cardiac catheterization. CMR guided catheterizations were assessed by completion (success/failure), procedure time, and safety events (catheterization, anesthesia). Pre and post CMR body temperature was recorded. Concurrent invasive hemodynamic and diagnostic CMR data were collected.ResultsDuring a twenty-two month period (3/2015 - 12/2016), enrolled subjects had the following clinical indications: post-heart transplant 33%, shunt 28%, pulmonary hypertension 18%, cardiomyopathy 15%, valvular heart disease 3%, and other 3%. Radiation-free CMR guided right heart catheterization attempts were all successful using passive catheters. In two subjects with septal defects, right and left heart catheterization were performed. There were no complications. One subject had six such procedures. Most subjects (51%) had undergone multiple (5.5 ± 5) previous X-Ray cardiac catheterizations. Retained thoracic surgical or transcatheter implants (36%) did not preclude successful CMR fluoroscopy heart catheterization. During the procedure, two subjects were receiving vasopressor infusions at baseline because of poor cardiac function, and in ten procedures, multiple hemodynamic conditions were tested.ConclusionsComprehensive CMR fluoroscopy guided right heart catheterization was feasible and safe in this small cohort of pediatric subjects. This includes subjects with previous metallic implants, those requiring continuous vasopressor medication infusions, and those requiring pharmacologic provocation. Children requiring multiple, serial X-Ray cardiac catheterizations may benefit most from radiation sparing. This is a step toward wholly CMR guided diagnostic (right and left heart) cardiac catheterization and future CMR guided cardiac intervention.Trial registrationClinicalTrials.gov NCT02739087 registered February 17, 2016.

Chronic consumption of Western‐type diet (WD) induces cardiac structural and functional abnormalities. Previously, we have shown that WD consumption in male ATM (ataxia‐telangiectasia mutated kinase) deficient mice associates with accelerated body weight (BW) gain, cardiac systolic dysfunction with increased preload, and exacerbation of hypertrophy, apoptosis, and inflammation. This study investigated the role of ATM deficiency in WD‐induced changes in functional and biochemical parameters of the heart in female mice. Six‐week‐old wild‐type (WT) and ATM heterozygous knockout (hKO) female mice were placed on WD or NC (normal chow) for 14 weeks. BW gain, fat accumulation, and cardiac functional and biochemical parameters were measured 14 weeks post‐WD. WD‐induced subcutaneous and total fat contents normalized to body weight were higher in WT‐WD versus hKO‐WD. Heart function measured using echocardiography revealed decreased percent fractional shortening and ejection fraction, and increased LV end systolic diameter and volume in WT‐WD versus WT‐NC. These functional parameters remained unchanged in hKO‐WD versus hKO‐NC. Myocardial fibrosis, myocyte hypertrophy, and apoptosis were higher in WT‐WD versus WT‐NC. However, apoptosis was significantly lower and hypertrophy was significantly higher in hKO‐WD versus WT‐WD. MMP‐9 and Bax expression, and Akt activation were higher in WT‐WD versus WT‐NC. PARP‐1 (full‐length) expression and mTOR activation were lower in WT‐WD versus hKO‐WD. Thus, ATM deficiency in female mice attenuates fat weight gain, preserves heart function, and associates with decreased cardiac cell apoptosis in response to WD. [ABSTRACT FROM AUTHOR]

BackgroundIn 2014, Joint Commission recommended palliative care (PC) engagement in ventricular assist device (VAD) implantation as destination therapy. Limited information is available on established PC protocols in the mechanical circulatory support (MCS) population.MeasuresThe goals of our PC consultation were to document advance care planning (ACP) discussions and designate a surrogate decision maker (SDM) before MCS implantation. A retrospective analysis compared the frequency of PC consults, ACP discussion, and SDM before and after protocol implementation.InterventionA protocol was developed to conduct interdisciplinary PC consultations for the MCS population.OutcomesThe percentage of PC consults placed before MCS implantation increased from 11 (17.2%) before protocol to 56 (96.6%) after protocol (P

Background and purposeCase-control studies suggest that acute infection transiently increases the risk of childhood arterial ischemic stroke. We hypothesized that an unbiased pathogen discovery approach utilizing MassTag-polymerase chain reaction would identify pathogens in the blood of childhood arterial ischemic stroke cases.MethodsThe multicenter international VIPS study (Vascular Effects of Infection in Pediatric Stroke) enrolled arterial ischemic stroke cases, and stroke-free controls, aged 29 days through 18 years. Parental interview included questions on recent infections. In this pilot study, we used MassTag-polymerase chain reaction to test the plasma of the first 161 cases and 34 controls enrolled for a panel of 28 common bacterial and viral pathogens.ResultsPathogen DNA was detected in no controls and 14 cases (8.7%): parvovirus B19 (n=10), herpesvirus 6 (n=2), adenovirus (n=1), and rhinovirus 6C (n=1). Parvovirus B19 infection was confirmed by serologies in all 10; infection was subclinical in 8. Four cases with parvovirus B19 had underlying congenital heart disease, whereas another 5 had a distinct arteriopathy involving a long-segment stenosis of the distal internal carotid and proximal middle cerebral arteries.ConclusionsUsing MassTag-polymerase chain reaction, we detected parvovirus B19-a virus known to infect erythrocytes and endothelial cells-in some cases of childhood arterial ischemic stroke. This approach can generate new, testable hypotheses about childhood stroke pathogenesis.

BackgroundCocaine is a well-known risk factor for acute cardiac events, but the effects in users outside of acute events are less clear. We investigated a possible association between cocaine use and the concentration of a novel biomarker for cardiac stress and heart failure, ST2.MethodsA case-control study was conducted to compare ST2 concentrations by the presence of cocaine in patients presenting for care, but not cardiac care, at an urban safety net hospital.ResultsIn samples taken from 100 cocaine-positive and 100 cocaine-negative patients, the presence of cocaine was associated with ST2 concentrations>35ng/mL. Serum concentrations of benzoylecgonine, a major cocaine metabolite, were significantly correlated with ST2 concentrations.ConclusionsCocaine use is associated with subclinical cardiac stress and damage outside of acute cardiac events. This information could add to better stratification of cocaine users with elevated ST2 concentrations who may be at higher risk for developing heart failure and other cardiac complications.

ObjectiveThe aim of the study was to compare knowledge and awareness of heart attacks/heart disease and perceived risk for future heart attack in Asian/Pacific Islander women, compared to other racial and ethnic groups.Materials and methodsIn this cross-sectional study, 318 women enrolled in a mobile phone-based physical activity education trial were analyzed. Heart attack knowledge, self-efficacy for recognizing and responding to heart attack symptoms, and perceived risk for a future heart attack were measured. Analyses were conducted using logistic, proportional odds, and linear regression models, depending on the outcome and adjusting for age. Pairwise differences between Asian/Pacific Islanders and the other four groups were assessed using a Bonferroni correction (p

BackgroundEwing sarcoma survivors (ESSs) are at increased risk for treatment-related complications. The incidence of treatment-related morbidity and late mortality with aging is unknown.MethodsThis study reports survival probabilities, estimated with the Kaplan-Meier method, and the cumulative incidence of cause-specific mortality and chronic conditions among ESSs in the Childhood Cancer Survivor Study who were treated between 1970 and 1986. Piecewise exponential models were used to estimate relative rates (RRs) and 95% confidence intervals (CIs) for these outcomes. Chronic conditions were graded with the Common Terminology Criteria for Adverse Events (version 4.03).ResultsAmong 404 5-year ESSs (median age at last follow-up, 34.8 years; range, 9.1-54.8 years), the 35-year survival rate was 70% (95% CI, 66%-74%). Late recurrence (cumulative incidence at 35 years, 15.1%) was the most common cause of death, and it was followed by treatment-related causes (11.2%). There were 53 patients with subsequent neoplasms (SNs; cumulative incidence at 35 years, 24.0%), and 38 were malignant (14.3% at 35 years). The standardized incidence ratios were 377.1 (95% CI, 172.1-715.9) for osteosarcoma, 28.9 (95% CI, 3.2-104.2) for acute myeloid leukemia, 14.9 (95% CI, 7.9-25.5) for breast cancer, and 13.1 (95% CI, 4.8-28.5) for thyroid cancer. Rates of chronic conditions were highest for musculoskeletal (RR, 18.1; 95% CI, 12.8-25.7) and cardiac complications (RR, 1.8; 95% CI, 1.4-2.3). Thirty-five years after the diagnosis, the cumulative incidences of any chronic conditions and 2 or more chronic conditions were 84.6% (95% CI, 80.4%-88.8%) and 73.8% (95% CI, 67.8%-79.9%), respectively.ConclusionsWith extended follow-up, ESSs' risk for late mortality and SNs does not plateau. Treatment-related chronic conditions develop years after therapy, and this supports the need for lifelong follow-up. Cancer 2017;123:2551-60. © 2017 American Cancer Society.

A 12-year-old spayed female miniature Poodle presented for coughing, respiratory distress, and anorexia. After thoracentesis for pleural effusion, radiography revealed an enlarged cardiac silhouette with a bulge in the area of the body of the right atrium. Echocardiography revealed an anechoic chamber-like cavity lateral to the right atrium that communicated with the right atrium through a 13 mm defect in the right atrial free wall. Contrast echocardiography and color flow Doppler were used to prove that the cavity communicated with the right atrium. The cavity was diagnosed as a giant right atrial diverticulum.

BackgroundUnderstanding the genetic architecture of cardiac structure and function may help to prevent and treat heart disease. This investigation sought to identify common genetic variations associated with inter-individual variability in cardiac structure and function.MethodsA GWAS meta-analysis of echocardiographic traits was performed, including 46,533 individuals from 30 studies (EchoGen consortium). The analysis included 16 traits of left ventricular (LV) structure, and systolic and diastolic function.ResultsThe discovery analysis included 21 cohorts for structural and systolic function traits (n = 32,212) and 17 cohorts for diastolic function traits (n = 21,852). Replication was performed in 5 cohorts (n = 14,321) and 6 cohorts (n = 16,308), respectively. Besides 5 previously reported loci, the combined meta-analysis identified 10 additional genome-wide significant SNPs: rs12541595 near MTSS1 and rs10774625 in ATXN2 for LV end-diastolic internal dimension; rs806322 near KCNRG, rs4765663 in CACNA1C, rs6702619 near PALMD, rs7127129 in TMEM16A, rs11207426 near FGGY, rs17608766 in GOSR2, and rs17696696 in CFDP1 for aortic root diameter; and rs12440869 in IQCH for Doppler transmitral A-wave peak velocity. Findings were in part validated in other cohorts and in GWAS of related disease traits. The genetic loci showed associations with putative signaling pathways, and with gene expression in whole blood, monocytes, and myocardial tissue.ConclusionThe additional genetic loci identified in this large meta-analysis of cardiac structure and function provide insights into the underlying genetic architecture of cardiac structure and warrant follow-up in future functional studies.FundingFor detailed information per study, see Acknowledgments.

PurposeSurvival following ovarian cancer diagnosis is generally low; understanding factors related to prognosis could be important to optimize treatment. The role of previously diagnosed comorbidities and use of medications for those conditions in relation to prognosis for ovarian cancer patients has not been studied extensively, particularly according to histological subtype.MethodsUsing pooled data from fifteen studies participating in the Ovarian Cancer Association Consortium, we examined the associations between history of hypertension, heart disease, diabetes, and medications taken for these conditions and overall survival (OS) and progression-free survival (PFS) among patients diagnosed with invasive epithelial ovarian carcinoma. We used Cox proportional hazards regression models adjusted for age and stage to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) overall and within strata of histological subtypes.ResultsHistory of diabetes was associated with increased risk of mortality (n = 7,674; HR = 1.12; 95% CI = 1.01-1.25). No significant mortality associations were observed for hypertension (n = 6,482; HR = 0.95; 95% CI = 0.88-1.02) or heart disease (n = 4,252; HR = 1.05; 95% CI = 0.87-1.27). No association of these comorbidities was found with PFS in the overall study population. However, among patients with endometrioid tumors, hypertension was associated with lower risk of progression (n = 339, HR = 0.54; 95% CI = 0.35-0.84). Comorbidity was not associated with OS or PFS for any of the other histological subtypes. Ever use of beta blockers, oral antidiabetic medications, and insulin was associated with increased mortality, HR = 1.20; 95% CI = 1.03-1.40, HR = 1.28; 95% CI = 1.05-1.55, and HR = 1.63; 95% CI = 1.20-2.20, respectively. Ever use of diuretics was inversely associated with mortality, HR = 0.71; 95% CI = 0.53-0.94.ConclusionsHistories of hypertension, diabetes, and use of diuretics, beta blockers, insulin, and oral antidiabetic medications may influence the survival of ovarian cancer patients. Understanding mechanisms for these observations could provide insight regarding treatment.

BackgroundUnderstanding the relationship between alcohol abuse, a common and theoretically modifiable condition, and the most common cause of death in the world, cardiovascular disease, may inform potential prevention strategies.ObjectivesThe study sought to investigate the associations among alcohol abuse and atrial fibrillation (AF), myocardial infarction (MI), and congestive heart failure (CHF).MethodsUsing the Healthcare Cost and Utilization Project database, we performed a longitudinal analysis of California residents ≥21 years of age who received ambulatory surgery, emergency, or inpatient medical care in California between 2005 and 2009. We determined the risk of an alcohol abuse diagnosis on incident AF, MI, and CHF. Patient characteristics modifying the associations and population-attributable risks were determined.ResultsAmong 14,727,591 patients, 268,084 (1.8%) had alcohol abuse. After multivariable adjustment, alcohol abuse was associated with an increased risk of incident AF (hazard ratio [HR]: 2.14; 95% confidence interval [CI]: 2.08 to 2.19; p < 0.0001), MI (HR: 1.45; 95% CI: 1.40 to 1.51; p < 0.0001), and CHF (HR: 2.34; 95% CI: 2.29 to 2.39; p

Nuclear shape defects are a distinguishing characteristic in laminopathies, cancers, and other pathologies. Correlating these defects to the symptoms, mechanisms, and progression of disease requires unbiased, quantitative, and high-throughput means of quantifying nuclear morphology. To accomplish this, we developed a method of automatically segmenting fluorescently stained nuclei in 2D microscopy images and then classifying them as normal or dysmorphic based on three geometric features of the nucleus using a package of Matlab codes. As a test case, cultured skin-fibroblast nuclei of individuals possessing LMNA splice-site mutation (c.357-2A>G), LMNA nonsense mutation (c.736 C>T, pQ246X) in exon 4, LMNA missense mutation (c.1003C>T, pR335W) in exon 6, Hutchinson-Gilford Progeria Syndrome, and no LMNA mutations were analyzed. For each cell type, the percentage of dysmorphic nuclei, and other morphological features such as average nuclear area and average eccentricity were obtained. Compared to blind observers, our procedure implemented in Matlab codes possessed similar accuracy to manual counting of dysmorphic nuclei while being significantly more consistent. The automatic quantification of nuclear defects revealed a correlation between in vitro results and age of patients for initial symptom onset. Our results demonstrate the method's utility in experimental studies of diseases affecting nuclear shape through automated, unbiased, and accurate identification of dysmorphic nuclei.

BackgroundSocioeconomic differences in health in Brazil are largely driven by differences in educational attainment. In this paper, we assess whether educational gradients in chronic disease prevalence have narrowed in Brazil from 1998 to 2013, a period of a booming economy accompanied by major investments in public health in the country.MethodsIndividual-level data came from the 1998, 2003 and 2008 Brazilian National Household Survey and the 2013 National Health Survey. We first evaluate age-standardized prevalence rates of chronic disease by education and second, we predict the estimated prevalence rate between those in low vs. high education to assess if relative changes in chronic disease have narrowed over time. Third, we estimate the slope index of inequality (SII) that evaluates the absolute change in the predicted prevalence of a disease between those in low vs. high education. Finally, we tested for statistically significant time trends in adult chronic disease inequalities by education.ResultsPrevalence of diabetes and hypertension have increased over the period, whereas the prevalence of heart disease decreased. Brazilian adults with no education had higher levels of diabetes, hypertension and heart disease than those with some college or more. Adjusted prevalence for hypertension and heart disease indicate some progress in reducing educational disparities over time. However, for diabetes, adjusted results show a continuously increasing educational disparity from 1998 to 2013. By 2013, individuals with no education had about two times higher diabetes prevalence than those with higher education with larger disparity among women.ConclusionsResults confirm findings from previous work that educational inequalities in health are large in Brazil but also provide evidence suggesting some improvement in narrowing these differentials in recent times. Recent policies aiming at reducing the prevalence of obesity, smoking and alcohol consumption, and increasing physical activity and consumption of fruits and vegetables may increase the overall health and wellbeing of the Brazilian population. These programs are likely to be more effective if they target those with low socioeconomic status, as they appeared to be at a higher risk of developing chronic conditions, and promote educational opportunities.