Coronary artery endothelial function and aging in people with HIV and HIV-negative individuals.

Coronary artery disease (CAD) is a common comorbidity in people with human immunodeficiency virus (HIV) (PWH) and impaired coronary endothelial function (CEF) plays a central role in the pathogenesis of CAD. Age-related impaired CEF among PWH, however, is not well characterized. We investigated the association between CEF and age in males and females with and without HIV using 3-T magnetic resonance imaging (MRI). We measured the changes in coronary cross-sectional area (CSA) and coronary blood flow during isometric handgrip exercise (IHE), an established endothelial-dependent stressor with smaller increases in CSA and coronary blood flow indicative of impaired CEF. We included 106 PWH and 82 individuals without HIV. Differences in demographic and clinical characteristics between PWH and individuals without HIV were explored using Pearson's χ2 test for categorical variables and Welch's t test for continuous variables. Linear regression models were used to examine the association between CEF and age. CEF was significantly lower in PWH as compared with individuals without HIV. Coronary endothelial dysfunction was also present at younger ages in PWH than in the individuals without HIV and there were significant differences in CEF between the PWH and individuals without HIV across age groups. Among the individuals without HIV, the percent changes in CSA were inversely related to age in unadjusted and adjusted models. There was no significant association between CEF and age in PWH. To the best of our knowledge, this is the first study to examine the relationship between age and CEF in PWH, and our results suggest that factors other than age significantly impair CEF in PWH across the life span.NEW & NOTEWORTHY This is the first study to examine the relationship between age and coronary endothelial function (CEF) in people with human immunodeficiency virus (HIV) (PWH). CEF was assessed using magnetic resonance imaging (MRI) in people with and without HIV. Although age and CEF were significantly inversely related in individuals without HIV, there was no association between age and CEF in PWH.

Association of Depression and Poor Mental Health With Cardiovascular Disease and Suboptimal Cardiovascular Health Among Young Adults in the United States.

Background Depression is a nontraditional risk factor for cardiovascular disease (CVD). Data on the association of depression and poor mental health with CVD and suboptimal cardiovascular health (CVH) among young adults are limited. Methods and Results We used data from 593 616 young adults (aged 18-49 years) from the 2017 to 2020 Behavioral Risk Factor Surveillance System, a nationally representative survey of noninstitutionalized US adults. Exposures were self-reported depression and poor mental health days (PMHDs; categorized as 0, 1-13, and 14-30 days of poor mental health in the past 30 days). Outcomes were self-reported CVD (composite of myocardial infarction, angina, or stroke) and suboptimal CVH (≥2 cardiovascular risk factors: hypertension, hypercholesterolemia, overweight/obesity, smoking, diabetes, physical inactivity, and inadequate fruit and vegetable intake). Using logistic regression, we investigated the association of depression and PMHDs with CVD and suboptimal CVH, adjusting for sociodemographic factors (and cardiovascular risk factors for the CVD outcome). Of the 593 616 participants (mean age, 34.7±9.0 years), the weighted prevalence of depression was 19.6% (95% CI, 19.4-19.8), and the weighted prevalence of CVD was 2.5% (95% CI, 2.4-2.6). People with depression had higher odds of CVD than those without depression (odds ratio [OR], 2.32 [95% CI, 2.13-2.51]). There was a graded association of PMHDs with CVD. Compared with individuals with 0 PMHDs, the odds of CVD in those with 1 to 13 PMHDs and 14 to 30 PHMDs were 1.48 (95% CI, 1.34-1.62) and 2.29 (95% CI, 2.08-2.51), respectively, after adjusting for sociodemographic and cardiovascular risk factors. The associations did not differ significantly by sex or urban/rural status. Individuals with depression had higher odds of suboptimal CVH (OR, 1.79 [95% CI, 1.65-1.95]) compared with those without depression, with a similar graded relationship between PMHDs and suboptimal CVH. Conclusions Depression and poor mental health are associated with premature CVD and suboptimal CVH among young adults. Although this association is likely bidirectional, prioritizing mental health may help reduce CVD risk and improve CVH in young adults.

The Relationship Between Impaired Coronary Endothelial Function and Systemic Markers of Inflammation in People Living With HIV.

BACKGROUND: People with HIV (PWH) are at an increased risk of cardiovascular disease, partially believed to be related to chronically elevated systemic inflammation. Abnormal systemic endothelial function (SEF) and coronary endothelial function (CEF) develop early in atherogenesis and predict adverse events. It is unknown whether abnormal CEF is related to systemic inflammation in PWH. METHODS: In this substudy of a prior randomized controlled trial in PWH without prior clinical coronary artery disease suppressed on antiretroviral therapy with CEF as a primary end point (N = 82), we investigated the associations between baseline serum markers of inflammation and adhesion and baseline CEF, assessed by noninvasive MRI measures of percentage changes in coronary blood flow and cross-sectional area during isometric handgrip exercise, and SEF using brachial ultrasound for flow-mediated dilation. We also evaluated whether baseline marker levels were associated with CEF after 8 weeks in the placebo group (N = 40). RESULTS: CEF measures were abnormal at baseline, based on trial entry criteria. A higher value of CEF was directly associated with levels of interleukin 10, whereas CEF at baseline was inversely associated with E-selectin. Worse CEF at 8 weeks was directly associated with baseline tumor necrosis factor alpha, intercellular adhesion molecule 1, C-reactive protein, interferon gamma and sICAM-3. SEF at baseline or 8 weeks was not associated with any baseline markers. CONCLUSION: Coronary but not systemic endothelial dysfunction was significantly associated with select markers of inflammation and adhesion in PWH. Furthermore, CEF but not SEF at 8 weeks was associated with baseline levels of inflammation. Our findings suggest that abnormal CEF and systemic markers of inflammation are linked in PWH.

Longitudinal Prediction of Ventricular Arrhythmic Risk in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy.

BACKGROUND: The arrhythmogenic right ventricular cardiomyopathy (ARVC) risk calculator stratifies risk for incident sustained ventricular arrhythmias (VA) at the time of ARVC diagnosis. However, included risk factors change over time, and how well the ARVC risk calculator performs at follow-up is unknown. METHODS: This was a retrospective analysis of patients with definite ARVC and without prior sustained VA. Risk factors for VA including age, nonsustained ventricular tachycardia, premature ventricular complex burden, T-wave inversions on electrocardiogram, cardiac syncope, right ventricular function, therapeutic medication use, and exercise intensity were assessed at the time of 2010 Task Force Criteria based ARVC diagnosis and upon repeat evaluations. Changes in these risk factors were analyzed over 5-year follow-up. The 5-year risk of VA was predicted longitudinally using (1) the baseline ARVC risk calculator prediction, (2) the ARVC risk prediction calculated using updated risk factors, and (3) time-varying Cox regression. Discrimination and calibration were assessed in comparison to observed VA event rates. RESULTS: Four hundred eight patients with ARVC experiencing 132 primary VA events were included. Matched comparison of risk factors at baseline versus at 5 years of follow-up revealed decreased burdens of premature ventricular complexes (-1200/day) and nonsustained ventricular tachycardia (-14%). Presence of significant right ventricular dysfunction and number of T-wave inversions on electrocardiogram were unchanged. Observed risk for VA decreased by 13% by 5 years follow-up. The baseline ARVC risk calculator's ability to predict 5-year VA risk worsened during follow-up (C statistics, 0.83 at diagnosis versus 0.68 at 5 years). Both the updated ARVC risk calculator (C statistics of 0.77) and time-varying Cox regression model (C statistics, 0.77) had strong discrimination. The updated ARVC risk calculator overestimated 5-year VA risk by an average of +6%. CONCLUSIONS: Risk factors for VA in ARVC are dynamic, and overall risk for incident sustained VA decreases during follow-up. Up-to-date risk factor assessment improves VA risk stratification.

Deterioration in myocardial work indices precedes changes in global longitudinal strain following anthracycline chemotherapy.

BACKGROUND: Left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) have conventionally been used for surveillance of cardiac function after cancer therapy, but indices of myocardial work (MW) are potentially superior for this purpose because they take into account both myocardial deformation and loading conditions. OBJECTIVES: We aimed to investigate the usefulness of MW in the follow-up of children and young adults following anthracycline chemotherapy. METHODS: Conventional markers of LV function (LV fractional shortening [LVFS], LVEF, GLS) and MW indices (global work index [GWI], global constructive work [GCW], global wasted work [GWW], and global work efficiency [GWE]) were obtained from 2342 echocardiographic examinations in 598 patients (354 male, 12.2 [4.7-17.3] years at initiation of chemotherapy). RESULTS: GWI, GCW, GLS, LVFS, and LVEF all deteriorated significantly during and after anthracycline chemotherapy, while GWW decreased and GWE was preserved. On multivariable analysis, MW indices were correlated with conventional markers of LV function and with clinical information relating to underlying malignancy and chemotherapy. Cox regression analysis revealed that similar levels of deterioration in GWW, GWI, and GCW preceded those in GLS, LFS, and LVEF. CONCLUSIONS: Non-invasive MW indices correlate well with conventional markers of LV function. Indices of MW appear to provide an earlier and more sensitive marker of progression towards chemotherapy-related cardiac dysfunction. Future studies are warranted to validate whether the incorporation of non-invasive MW into the routine clinical surveillance in patients after chemotherapy would improve outcomes.

Unsupervised machine learning demonstrates the prognostic value of TAPSE/PASP ratio among hospitalized patients with COVID-19.

BACKGROUND: The ratio of tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (PASP) is a validated index of right ventricular-pulmonary arterial (RV-PA) coupling with prognostic value. We determined the predictive value of TAPSE/PASP ratio and adverse clinical outcomes in hospitalized patients with COVID-19. METHODS: Two hundred and twenty-nine consecutive hospitalized racially/ethnically diverse adults (≥18 years of age) admitted with COVID-19 between March and June 2020 with clinically indicated transthoracic echocardiograms (TTE) that included adequate tricuspid regurgitation (TR) velocities for calculation of PASP were studied. The exposure of interest was impaired RV-PA coupling as assessed by TAPSE/PASP ratio. The primary outcome was in-hospital mortality. Secondary endpoints comprised of ICU admission, incident acute respiratory distress syndrome (ARDS), and systolic heart failure. RESULTS: One hundred and seventy-six patients had both technically adequate TAPSE measurements and measurable TR velocities for analysis. After adjustment for age, sex, BMI, race/ethnicity, diabetes mellitus, and smoking status, log(TAPSE/PASP) had a significantly inverse association with ICU admission (p = 0.015) and death (p = 0.038). ROC analysis showed the optimal cutoff for TAPSE/PASP for death was 0.51 mm mmHg-1 (AUC = 0.68). Unsupervised machine learning identified two groups of echocardiographic function. Of all echocardiographic measures included, TAPSE/PASP ratio was the most significant in predicting in-hospital mortality, further supporting its significance in this cohort. CONCLUSION: Impaired RV-PA coupling, assessed noninvasively via the TAPSE/PASP ratio, was predictive of need for ICU level care and in-hospital mortality in hospitalized patients with COVID-19 suggesting utility of TAPSE/PASP in identification of poor clinical outcomes in this population both by traditional statistical and unsupervised machine learning based methods.

Racial Disparities in Prevalence of Gestational Diabetes by Maternal Nativity and Length of US Residence in an Urban Low-Income Population in the United States.

Background: Gestational diabetes mellitus (GDM) is associated with increased risk of cardiovascular disease (CVD). Racial/ethnic differences in GDM prevalence have been described, but disparities by nativity and duration of US residence are not well studied. Methods: We analyzed data from 6088 women (mean age: 27.5 years [standard deviation: 6.3 years]) from the Boston Birth Cohort who self-identified as non-Hispanic Black (NHB; n = 2697), Hispanic (n = 2395), or non-Hispanic White (NHW; n = 996). Using multivariable logistic regression, we examined the cross-sectional association of nativity and duration of US residence (< 10 vs ≥ 10 years) with GDM within each race/ethnicity group. Results: Foreign-born NHB, NHW, and Hispanic women with a duration of US residence of < 10 years had a lower prevalence of CVD risk factors than those with US residence of ≥ 10 years, respectively, as follows: smoking (NHB: 1.7% vs 3.1%; NHW: 5.7% vs 8.1%; Hispanic: 0.4% vs 2.6%); obesity (NHB: 17.1% vs 23.4%; NHW: 3.8% vs 15.6%; Hispanic: 10.9% vs 22.7%); and severe stress (NHB: 8.7% vs 11.9%; NHW: 5.7% vs 28.1%; Hispanic: 3.8% vs 7.3%). In analyses adjusting for sociodemographic characteristics and CVD risk factors, foreign-born NHB women with a duration of US residence of < 10 years had higher odds of having GDM (adjusted odds ratio: 1.60, 95% confidence interval: 0.99-2.60), compared with their US-born counterparts, whereas foreign-born Hispanic women with a duration of US residence of < 10 years had lower odds of having GDM (adjusted odds ratio: 0.54, 95% confidence interval: 0.32-0.91). The odds of having GDM in Hispanic and NHB women with a duration of US residence of ≥ 10 years were not significantly different from those of their US-born counterparts. Conclusions: The "healthy immigrant effect" and its waning with longer duration of US residence apply to the prevalence of GDM among Hispanic women but not NHB women. Further research on the intersectionality of race and nativity-based disparities is needed.

Introduction: Le diabète sucré gestationnel (DSG) est associé à l'augmentation du risque de maladies cardiovasculaires (MCV). Les différences raciales/ethniques dans la prévalence du DSG ont été décrites, mais les disparités selon le lieu de naissance et la durée de résidence aux É.-U font l'objet de peu d'études. Méthodes: Nous avons analysé les données de 6 088 femmes (âge moyen : 27,5 ans [écart type : 6,3 ans]) de la Boston Birth Cohort qui ont déclaré être noires non hispaniques (NNH; n = 2 697), hispaniques (n = 2 395) ou blanches non hispaniques (BNH; n = 996). À l'aide de la régression logistique multivariée, nous avons examiné l'association transversale entre le lieu de naissance et la durée de résidence aux É.-U. (< 10 vs ≥ 10 ans), et le DSG dans chaque groupe racial/ethnique. Résultats: Les femmes NNH, BNH et hispaniques nées à l'étranger qui avaient une durée de résidence aux É.-U. de < 10 ans avaient une prévalence plus faible des facteurs de risque de MCV que celles qui avaient une résidence aux É.-U. de ≥ 10 ans, et ce, de façon respective comme suit : le tabagisme (NNH : 1,7 % vs 3,1 %; BNH : 5,7 % vs 8,1 %; hispaniques : 0,4 % vs 2,6 %); l'obésité (NNH : 17,1 % vs 23,4 %; BNH : 3,8 % vs 15,6 %; hispaniques : 10,9 % vs 22,7 %); le stress important (NNH : 8,7 % vs 11,9 %; BNH : 5,7 % vs 28,1 %; hispaniques : 3,8 % vs 7,3 %). Lors de l'ajustement des caractéristiques sociodémographiques et des facteurs de risque de MCV, les femmes NNH nées à l'étranger qui avaient une durée de résidence aux É.-U. de < 10 ans montraient une plus grande probabilité d'avoir le DSG (rapport de cotes ajusté : 1,60, intervalle de confiance à 95 % : 0,99-2,60) que leurs homologues nées aux É.-U., alors que les femmes hispaniques nées à l'étranger qui avaient une durée de résidence aux É.-U. de < 10 ans montraient une plus faible probabilité d'avoir le DSG (rapport de cotes ajusté : 0,54, intervalle de confiance à 95 % : 0,32-0,91). La probabilité que les femmes hispaniques et NNH qui avaient une durée de résidence aux É.-U. de ≥ 10 ans aient le DSG n'était pas significativement différente de celles de leurs homologues nées aux É.-U. Conclusions: L'« effet de l'immigrant en bonne santé ¼ et son déclin associé à la plus longue durée de résidence aux É.-U. s'appliquent à la prévalence du DSG chez les femmes hispaniques, mais non chez les femmes NNH. D'autres recherches sur l'intersectionnalité entre la race et les disparités selon le lieu de naissance sont nécessaires.

A Systematic Review and Meta-Analysis of the Association Between Polycystic Ovary Syndrome and Coronary Artery Calcification.

Background: Polycystic ovary syndrome (PCOS) is a common endocrine pathology affecting women of reproductive age characterized by chronic anovulation, hyperandrogenism, and polycystic ovaries. Coronary artery calcification (CAC) is a marker of subclinical atherosclerosis and prognostic of cardiovascular disease (CVD) risk. Some studies have shown that women with PCOS have a greater risk of CAC; however, a few others report contrary findings. The objective of this study is to examine and quantify the association between PCOS and CAC. Materials and Methods: We searched EMBASE, Google Scholar, PubMed, and Web of Science from inception to November 2021 to identify studies that provided information on PCOS and CAC. We used a random-effects model to aggregate the odds ratios (ORs) for CAC (score >0) among women with PCOS compared with controls adjusted for sociodemographic characteristics and CVD risk factors. Results: From the 36 articles reviewed, 3 prospective cohort and 4 cross-sectional studies met the inclusion criteria with a total of 2341 participants. Six studies used CAC > 0 as an outcome and were included in the pooled analysis. Using the Hartung-Knapp-Sidik-Jonkman method, the pooled adjusted ORs for the associations between PCOS and the presence of CAC were 2.48 (95% confidence interval: 2.11-2.84) with no significant heterogeneity (I2 = 0.10%, p = 0.97) for the cohort studies and 1.88 (0.71-3.06) with no significant heterogeneity (I2 = 13.95%, p = 0.87) for the cross-sectional studies. Conclusion: In pooled analyses, women with PCOS had approximately twofold greater odds of having CAC compared with women without PCOS. However, additional prospective studies will be needed to further understand the relationship between PCOS and CAC.

Nativity-Related Disparities in Preterm Birth and Cardiovascular Risk in a Multiracial U.S. Cohort.

INTRODUCTION: Having a preterm birth is associated with future cardiovascular risk. Non-Hispanic Black women have higher rates of preterm birth than non-Hispanic White and Hispanic women, but nativity-related disparities in preterm birth are not well understood. METHODS: Data from 6,096 women in the Boston Birth Cohort: non-Hispanic Black (2,699), non-Hispanic White (997), or Hispanic (2,400), were analyzed in June 2021. Differences in cardiovascular risk factors were assessed. The association of preterm birth with nativity and duration of U.S. residence were investigated using multivariable logistic regression. RESULTS: U.S.-born women in all 3 racial-ethnic groups had a higher prevalence of obesity, smoking, and severe stress than foreign-born women. Foreign-born non-Hispanic Black and Hispanic women had lower odds of preterm birth than U.S.-born counterparts (non-Hispanic Black: AOR=0.79, 95% CI=0.65, 0.97; Hispanic: AOR=0.72, 95% CI=0.56, 0.93). In all the 3 groups, foreign-born women with shorter (<10 years) duration of U.S. residence had lower odds of preterm birth than the U.S.-born women (non-Hispanic Black: AOR=0.57, 95% CI=0.43, 0.75; Hispanic: AOR=0.72, 95% CI=0.55, 0.94; non-Hispanic White: AOR=0.46, 95% CI=0.25, 0.85), whereas the odds of preterm birth in foreign-born women with ≥10 years of residence were not significantly different. CONCLUSIONS: Foreign-born women had better cardiovascular risk profiles in all groups and lower odds of preterm birth in non-Hispanic Black and Hispanic groups. In all the 3 groups, a shorter duration of U.S. residence was associated with lower odds of preterm birth. Further studies are needed to understand the biological and social determinants underlying these nativity-related disparities and the impact of acculturation.

Multimodality Evaluation of Aortic Insufficiency and Aortitis in Rheumatologic Diseases.

Aortic insufficiency is commonly observed in rheumatologic diseases such as ankylosing spondylitis, systemic lupus erythematosus, antiphospholipid syndrome, Behçet's disease, granulomatosis with polyangiitis, and Takayasu arteritis. Aortic insufficiency with an underlying rheumatologic disease may be caused by a primary valve pathology (leaflet destruction, prolapse or restriction), annular dilatation due to associated aortitis or a combination of both. Early recognition of characteristic valve and aorta morphology on cardiac imaging has both diagnostic and prognostic importance. Currently, echocardiography remains the primary diagnostic tool for aortic insufficiency. Complementary use of computed tomography, cardiac magnetic resonance imaging and positron emission tomography in these systemic conditions may augment the assessment of underlying mechanism, disease severity and identification of relevant non-valvular/extracardiac pathology. We aim to review common rheumatologic diseases associated with aortic insufficiency and describe their imaging findings that have been reported in the literature.

Multimodality Imaging in the Evaluation and Prognostication of Cardiac Amyloidosis.

Cardiac amyloidosis (CA) is an infiltrative cardiomyopathy resulting from deposition of misfolded immunoglobulin light chains (AL-CA) or transthyretin (ATTR-CA) proteins in the myocardium. Survival varies between the different subtypes of amyloidosis and degree of cardiac involvement, but accurate diagnosis is essential to ensure initiation of therapeutic interventions that may slow or potentially prevent morbidity and mortality in these patients. As there are now effective treatment options for CA, identifying underlying disease pathogenesis is crucial and can be guided by multimodality imaging techniques such as echocardiography, magnetic resonance imaging, and nuclear scanning modalities. However, as use of cardiac imaging is becoming more widespread, understanding optimal applications and potential shortcomings is increasingly important. Additionally, certain imaging modalities can provide prognostic information and may affect treatment planning. In patients whom imaging remains non-diagnostic, tissue biopsy, specifically endomyocardial biopsy, continues to play an essential role and can facilitate accurate and timely diagnosis such that appropriate treatment can be started. In this review, we examine the multimodality imaging approach to the diagnosis of CA with particular emphasis on the prognostic utility and limitations of each imaging modality. We also discuss how imaging can guide the decision to pursue tissue biopsy for timely diagnosis of CA.

Multimodality Imaging in Arrhythmogenic Right Ventricular Cardiomyopathy.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare, heritable myocardial disease associated with the development of ventricular arrhythmias, heart failure, and sudden cardiac death in early adulthood. Multimodality imaging is a central component in the diagnosis and evaluation of ARVC. Diagnostic criteria established by an international task force in 2010 include noninvasive parameters from echocardiography and cardiac magnetic resonance imaging. These criteria identify right ventricular structural abnormalities, chamber and outflow tract dilation, and reduced right ventricular function as features of ARVC. Echocardiography is a widely available and cost-effective technique, and it is often selected for initial evaluation. Beyond fulfillment of diagnostic criteria, features such as abnormal tricuspid annular plane excursion, increased right ventricular basal diameter, and abnormal strain patterns have been described. 3-dimensional echocardiography may also expand opportunities for structural and functional assessment of ARVC. Cardiac magnetic resonance has the ability to assess morphological and functional cardiac features of ARVC and is also a core modality in evaluation, however, tissue characterization of the right ventricle is limited by spatial resolution and low specificity for detection of pathological changes. Nonetheless, the ability of cardiac magnetic resonance to identify left ventricular involvement, offer high negative predictive value, and provide a reproducible structural evaluation of the right ventricle enhance the ability and scope of the modality. In this review, the prognostic significance of multimodality imaging is outlined, including the supplemental value of multidetector computed tomography and nuclear imaging. Strengths and weaknesses of imaging techniques, as well as future direction of multimodality assessment, are also described.

A comparative analysis of premature heart disease- and cancer-related mortality in women in the USA, 1999-2018.

AIMS: To compare premature heart disease- and cancer-related deaths in women in the USA. METHODS AND RESULTS: We analysed the US national database of death certificates of women aged <65 from the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research database between 1999 and 2018. We measured annual percentage changes (APCs) in age-adjusted mortality rates (AAMRs) and years of potential life lost per 100 000 persons due to heart disease and cancer. Overall, cancer was a more prevalent cause of premature death compared with heart disease. Between 1999 and 2018, the AAMRs decreased for both cancer (61.9/100 000 to 45.6/100 000) and heart disease (29.2/100 000 to 22.6/100 000). However, while APC in AAMR for cancer declined consistently over time, after an initial decline, APC in AAMR for heart disease increased between 2010 and 2018 [0.53 95% confidence interval (0.18-0.89)], with a significant rise in Midwest, medium/small metros, and rural areas after 2008. Compared with cancer, APC in AAMR for heart disease increased in women aged 25-34 years [2.24 (0.30-4.22); 2013-18) and 55-64 years [0.46 (0.13-0.80); 2009-13], as well as Non-Hispanic (NH) Whites [APC, 0.79 (0.46-1.13); 2009-18] and NH American Indian/Alaskan Native [2.71 (0.59-4.87); 2011-2018]. Consequently, the mortality gap between cancer and heart disease has narrowed from an AAMR of 32.7/100 000 to 23.0/100 000. CONCLUSIONS: The mortality gap between cancer and heart disease is decreasing among women <65 years. Intensive cardiovascular health interventions are required focusing on vulnerable young demographic subgroups and underserved regional areas to meet the American Heart Association's Impact Goal and Million Hearts Initiative.

Nativity-Related Disparities in Preeclampsia and Cardiovascular Disease Risk Among a Racially Diverse Cohort of US Women.

Importance: Preeclampsia is an independent risk factor for future cardiovascular disease and disproportionally affects non-Hispanic Black women. The association of maternal nativity and duration of US residence with preeclampsia and other cardiovascular risk factors is well described among non-Hispanic Black women but not among women of other racial and ethnic groups. Objective: To examine differences in cardiovascular risk factors and preeclampsia prevalence by race and ethnicity, nativity, and duration of US residence among Hispanic, non-Hispanic Black, and non-Hispanic White women. Design, Setting, and Participants: This cross-sectional analysis of the Boston Birth Cohort included a racially diverse cohort of women who had singleton deliveries at the Boston Medical Center from October 1, 1998, to February 15, 2016. Participants self-identified as Hispanic, non-Hispanic Black, or non-Hispanic White. Data were analyzed from March 1 to March 31, 2021. Exposures: Maternal nativity and duration of US residence (<10 vs ≥10 years) were self-reported. Main Outcome and Measures: Diagnosis of preeclampsia, the outcome of interest, was retrieved from maternal medical records. Results: A total of 6096 women (2400 Hispanic, 2699 non-Hispanic Black, and 997 non-Hispanic White) with a mean (SD) age of 27.5 (6.3) years were included in the study sample. Compared with Hispanic and non-Hispanic White women, non-Hispanic Black women had the highest prevalence of chronic hypertension (204 of 2699 [7.5%] vs 65 of 2400 [2.7%] and 28 of 997 [2.8%], respectively), obesity (658 of 2699 [24.4%] vs 380 of 2400 [15.8%] and 152 of 997 [15.2%], respectively), and preeclampsia (297 of 2699 [11.0%] vs 212 of 2400 [8.8%] and 71 of 997 [7.1%], respectively). Compared with their counterparts born outside the US, US-born women in all 3 racial and ethnic groups had a significantly higher prevalence of obesity (Hispanic women, 132 of 556 [23.7%] vs 248 of 1844 [13.4%]; non-Hispanic Black women, 444 of 1607 [27.6%] vs 214 of 1092 [19.6%]; non-Hispanic White women, 132 of 776 [17.0%] vs 20 of 221 [9.0%]), smoking (Hispanic women, 98 of 556 [17.6%] vs 30 of 1844 [1.6%]; non-Hispanic Black women, 330 of 1607 [20.5%] vs 53 of 1092 [4.9%]; non-Hispanic White women, 382 of 776 [49.2%] vs 42 of 221 [19.0%]), and severe stress (Hispanic women, 76 of 556 [13.7%] vs 85 of 1844 [4.6%]; non-Hispanic Black women, 231 of 1607 [14.4%] vs 120 of 1092 [11.0%]; non-Hispanic White women, 164 of 776 [21.1%] vs 26 of 221 [11.8%]). After adjusting for sociodemographic and cardiovascular risk factors, birth status outside the US (adjusted odds ratio [aOR], 0.74 [95% CI, 0.55-1.00]) and shorter duration of US residence (aOR, 0.62 [95% CI, 0.41-0.93]) were associated with lower odds of preeclampsia among non-Hispanic Black women. However, among Hispanic and non-Hispanic White women, maternal nativity (aOR for Hispanic women, 1.07 [95% CI, 0.72-1.60]; aOR for non-Hispanic White women, 0.98 [95% CI, 0.49-1.96]) and duration of US residence (aOR for Hispanic women <10 years, 1.04 [95% CI, 0.67-1.59]; aOR for non-Hispanic White women <10 years, 1.20 [95% CI, 0.48-3.02]) were not associated with preeclampsia. Conclusions and Relevance: Nativity-related disparities in preeclampsia persisted among non-Hispanic Black women but not among Hispanic and non-Hispanic White women after adjusting for sociodemographic and cardiovascular risk factors. Further research is needed to explore the interplay of factors contributing to nativity-related disparities in preeclampsia, particularly among non-Hispanic Black women.

Acute Hemodynamic Effects and Tolerability of Phosphodiesterase-1 Inhibition With ITI-214 in Human Systolic Heart Failure.

BACKGROUND: PDE1 (phosphodiesterase type 1) hydrolyzes cyclic adenosine and guanosine monophosphate. ITI-214 is a highly selective PDE1 inhibitor that induces arterial vasodilation and positive inotropy in larger mammals. Here, we assessed pharmacokinetics, hemodynamics, and tolerability of single-dose ITI-214 in humans with stable heart failure with reduced ejection fraction. METHODS: Patients with heart failure with reduced ejection fraction were randomized 3:1 to 10, 30, or 90 mg ITI-214 single oral dose or placebo (n=9/group). Vital signs and electrocardiography were monitored predose to 5 hours postdose and transthoracic echoDoppler cardiography predose and 2-hours postdose. RESULTS: Patient age averaged 54 years; 42% female, and 60% Black. Mean systolic blood pressure decreased 3 to 8 mm Hg (P<0.001) and heart rate increased 5 to 9 bpm (P≤0.001 for 10, 30 mg doses, RM-ANCOVA). After 4 hours, neither blood pressure or heart rate significantly differed among cohorts (supine or standing). ITI-214 increased mean left ventricular power index, a relatively load-insensitive inotropic index, by 0.143 Watts/mL2·104 (P=0.03, a +41% rise; 5-71 CI) and cardiac output by 0.83 L/min (P=0.002, +31%, 13-49 CI) both at the 30 mg dose. Systemic vascular resistance declined with 30 mg (-564 dynes·s/cm-5, P<0.001) and 90 mg (-370, P=0.016). Diastolic changes were minimal, and no parameters were significantly altered with placebo. ITI-214 was well-tolerated. Five patients had mild-moderate hypotension or orthostatic hypotension recorded adverse events. There were no significant changes in arrhythmia outcome and no serious adverse events. CONCLUSIONS: Single-dose ITI-214 is well-tolerated and confers inodilator effects in humans with heart failure with reduced ejection fraction. Further investigations of its therapeutic utility are warranted. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03387215.

Current State and Future Directions of Multimodality Imaging in Cardiac Sarcoidosis.

Cardiac sarcoidosis (CS) is an increasingly recognized cause of heart failure and arrhythmia. Historically challenging to identify, particularly in the absence of extracardiac sarcoidosis, diagnosis of CS has improved with advancements in cardiac imaging. Recognition as well as management may require interpretation of multiple imaging modalities. Echocardiography may serve as an initial screening study for cardiac involvement in patients with systemic sarcoidosis. Cardiac magnetic resonance imaging (CMR) provides information on diagnosis as well as risk stratification, particularly for ventricular arrhythmia in the setting of late gadolinium enhancement. More recently, 18F-fluorodeoxyglucose position emission tomography (FDG-PET) has assumed a valuable role in the diagnosis and longitudinal management of patients with CS, allowing for the assessment of response to treatment. Hybrid FDG-PET/CT may also be used in the evaluation of extracardiac inflammation, permitting the identification of biopsy sites for diagnostic confirmation. Herein we examine the approach to diagnosis and management of CS using multimodality imaging via a case-based review.

Right Ventricular Strain Predicts Structural Disease Progression in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy.

Background Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited condition associated with ventricular arrhythmias and myocardial dysfunction; however, limited data exist on identifying patients at highest risk. The purpose of the study was to determine whether measures of right ventricular (RV) dysfunction on echocardiogram including RV strain were predictive of structural disease progression in ARVC. Methods and Results A retrospective analysis of serial echocardiograms from 40 patients fulfilling 2010 task force criteria for ARVC was performed to assess structural progression defined by an increase in proximal RV outflow tract dimensions (parasternal short or long axis) or decrease in RV fractional area change. Echocardiograms were analyzed for RV free-wall peak longitudinal systolic strain using 2-dimensional speckle tracking. Risk of structural progression and 5-year change in RV outflow tract measurements were compared with baseline RV strain. Of the 40 ARVC patients, 61% had structural progression with an increase in the mean parasternal short-axis RV outflow tract dimension from 36.2 to 38.5 mm (P=0.022) and 68% by increase in parasternal long-axis RV outflow tract dimension from 36.1 to 39.2 mm (P=0.001). RV fractional area change remained stable over time. Baseline RV strain was significantly associated with the risk of structural progression and 5-year rate of change. Patients with an RV strain more positive than -20% had a higher risk (odds ratio: 18.4; 95% CI, 2.7-125.8; P=0.003) of structural progression. Conclusions RV free wall strain is associated with the rate of structural progression in patients with ARVC. It may be a useful marker in determining which patients require closer follow-up and treatment.

Endogenous Sex Hormones and Endothelial Function in Postmenopausal Women and Men: The Multi-Ethnic Study of Atherosclerosis.

Background: The relationship of endogenous sex hormones (SH) with vascular endothelial function and with cardiovascular disease (CVD) is incompletely understood. We examined the associations between SH and endothelial function measured by brachial artery flow-mediated dilation (FMD). Materials and Methods: We included 1368 postmenopausal women and 1707 men, free of clinical CVD, participating in MESA Visit 1 (2000-2002). Serum SH [total testosterone, SH binding globulin (SHBG), dehydroepiandrosterone (DHEA), estradiol] were measured; free testosterone was calculated. The percent FMD difference (%FMD) was measured by high-resolution ultrasound. Using multivariable-adjusted linear regression, we tested the cross-sectional associations of SH (log transformed, compared per one SD increment) with %FMD. Results: The mean age of women and men were 64.2 and 61.4 years, respectively. Among women, after adjusting for demographics, CVD risk factors, and hormone therapy, higher SHBG was associated with greater %FMD [ß = 0.215% (95% CI 0.026-0.405)], whereas higher free testosterone was associated with a smaller %FMD [-0.209% (-0.402, -0.017)]. Estradiol and DHEA were not associated with %FMD in women after multivariable adjustment. There was an age interaction, with higher free testosterone and lower SHBG associated with worse FMD in women <65 years of age, but not in those ≥65 years (p = 0.04). We did not see similar associations in men. Conclusions: A more androgenic SH profile of higher free testosterone and lower SHBG was associated with worse %FMD in postmenopausal women. Changes in SH with aging and menopause may result in vascular changes in women. Further studies are needed to assess longitudinal changes in SH levels and their association with vascular function.