<div><h4>Association Between Omega-3 Fatty Acid Intake and Dyslipidemia: A Continuous Dose-Response Meta-Analysis of Randomized Controlled Trials.</h4><i>Wang T, Zhang X, Zhou N, Shen Y, ... Chen BE, Li X</i><br /><AbstractText><br /><b>Background:</b><br/>Previous results provide supportive but not conclusive evidence for the use of omega-3 fatty acids to reduce blood lipids and prevent events of atherosclerotic cardiovascular disease, but the strength and shape of dose-response relationships remain elusive. Methods and Results This study included 90 randomized controlled trials, reported an overall sample size of 72 598 participants, and examined the association between omega-3 fatty acid (docosahexaenoic acid, eicosapentaenoic acid, or both) intake and blood lipid changes. Random-effects 1-stage cubic spline regression models were used to study the mean dose-response association between daily omega-3 fatty acid intake and changes in blood lipids. Nonlinear associations were found in general and in most subgroups, depicted as J-shaped dose-response curves for low-/high-density lipoprotein cholesterol. However, we found evidence of an approximately linear dose-response relationship for triglyceride and non-high-density lipoprotein cholesterol among the general population and more evidently in populations with hyperlipidemia and overweight/obesity who were given medium to high doses (>2 g/d). <br /><b>Conclusions:</b><br/>This dose-response meta-analysis demonstrates that combined intake of omega-3 fatty acids near linearly lowers triglyceride and non-high-density lipoprotein cholesterol. Triglyceride-lowering effects might provide supportive evidence for omega-3 fatty acid intake to prevent cardiovascular events.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 02 Jun 2023:e029512; epub ahead of print</small></div>

<div><h4>Obstructive Sleep Apnea-Induced Hypertension Is Associated With Increased Gut and Neuroinflammation.</h4><i>Ayyaswamy S, Shi H, Zhang B, Bryan RM, Durgan DJ</i><br /><AbstractText><br /><b>Background:</b><br/>Obstructive sleep apnea (OSA) is an independent risk factor for the development of hypertension. We have demonstrated that OSA induces gut dysbiosis, and this dysbiotic microbiota contributes to hypertension. However, the mechanisms linking gut dysbiosis to blood pressure regulation remain unclear. Recent studies demonstrate that gut dysbiosis can induce a proinflammatory response of the host resulting in peripheral and neuroinflammation, key factors in the development of hypertension. We hypothesized that OSA induces inflammation in the gut that contributes to neuroinflammation and hypertension. Methods and Results OSA was induced in 8-week-old male rats. After 2 weeks of apneas, lymphocytes were isolated from aorta, brain, cecum, ileum, mesenteric lymph node, and spleen for flow cytometry. To examine the role of interleukin-17a, a monoclonal antibody was administered to neutralize interleukin-17a. Lymphocytes originating from the gut were tracked by labeling with carboxyfluorescein succinimidyl ester dye. OSA led to a significant decrease in T regulatory cells along with an increase in T helper (T<sub>H</sub>) 17 cells in the ileum, cecum, and brain. Interleukin-17a neutralization significantly reduced blood pressure, increased T regulatory cells, and decreased T<sub>H</sub>1 cells in the ileum, cecum, and brain of OSA rats. T<sub>H</sub>1, T<sub>H</sub>2, and T<sub>H</sub>17 cells from the gut were found to migrate to the mesenteric lymph node, spleen, and brain with increased frequency in rats with OSA. <br /><b>Conclusions:</b><br/>OSA induces a proinflammatory response in the gut and brain that involves interleukin-17a signaling. Gut dysbiosis may serve as the trigger for gut and neuroinflammation, and treatments to prevent or reverse gut dysbiosis may prove useful in reducing neuroinflammation and hypertension.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 01 Jun 2023:e029218; epub ahead of print</small></div>

<div><h4>Evolving Management of Low-Density Lipoprotein Cholesterol: A Personalized Approach to Preventing Atherosclerotic Cardiovascular Disease Across the Risk Continuum.</h4><i>Wilkinson MJ, Lepor NE, Michos ED</i><br /><AbstractText>Management of elevated low-density lipoprotein cholesterol (LDL-C) is central to preventing atherosclerotic cardiovascular disease (ASCVD) and key to reducing the risk of ASCVD events. Current guidelines on the management of blood cholesterol recommend statins as first-line therapy for LDL-C reduction according to an individual\'s ASCVD risk and baseline LDL-C levels. The addition of nonstatin lipid-lowering therapy to statins to achieve intensive LDL-C lowering is recommended for patients at very high risk of ASCVD events, including patients with familial hypercholesterolemia who have not achieved adequate LDL-C lowering with statins alone. Despite guideline recommendations and clinical trial evidence to support the use of lipid-lowering therapies for ASCVD risk reduction, most patients at high or very high risk do not meet LDL-C thresholds. This review explores the challenges associated with LDL-C lowering in contemporary clinical practice and proposes a framework for rethinking the binary definition of ASCVD, shifting from \"primary\" versus \"secondary\" prevention to a \"continuum of risk.\" The approach considers the role of plaque burden and progression in subclinical disease and emphasizes the importance of early risk assessment and treatment for preventing first cardiovascular events. Patients at high risk of ASCVD events who require significant LDL-C lowering should be considered for combination therapies comprising statin and nonstatin agents. Practical guidance for the pharmacological management of elevated LDL-C, both now and in the future, is provided.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 01 Jun 2023:eJAHA2022028892; epub ahead of print</small></div>

<div><h4>Rationale and Design of the ORCCA (Outcomes Registry for Cardiac Conditions in Athletes) Study.</h4><i>Moulson N, Petek BJ, Ackerman MJ, Churchill TW, ... Baggish AL, Drezner JA</i><br /><AbstractText><br /><b>Background:</b><br/>Clinical practice recommendations for participation in sports and exercise among young competitive athletes with cardiovascular conditions at risk for sudden death are based largely on expert consensus with a paucity of prospective outcomes data. Recent guidelines have taken a more permissive approach, using a shared decision-making model. However, the impact and outcomes of this strategy remain unknown. Methods The ORCCA (Outcomes Registry for Cardiac Conditions in Athletes) study is a prospective, multicenter, longitudinal, observational cohort study designed to monitor clinical outcomes in athletes with potentially life-threatening cardiovascular conditions. The study will assess sports eligibility decision-making, exercise habits, psychosocial well-being, and long-term cardiovascular outcomes among young competitive athletes with cardiovascular conditions. Competitive athletes aged 18 to <35 years diagnosed with a confirmed cardiovascular condition or borderline finding with potential increased risk of major adverse cardiovascular events are eligible. Outcomes will be monitored for an initial 5-year follow-up period or until age 35, and metrics of psychosocial well-being and composite adverse cardiovascular events including arrhythmias, sudden cardiac arrest/sudden cardiac death, and evidence of disease progression will be compared among athletes who continue versus discontinue competitive sports participation. <br /><b>Conclusions:</b><br/>The ORCCA study aims to assess the process and results of return to sport decision-making and to monitor major adverse cardiovascular events, exercise habits, and the psychosocial well-being among young competitive athletes diagnosed with confirmed cardiovascular conditions or borderline findings with potential increased risk of major adverse cardiovascular events. The results of this work will generate an evidence base to inform future guidelines.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 01 Jun 2023:e029052; epub ahead of print</small></div>

<div><h4>Risk of Cardiovascular Disease in Women With a History of Hyperemesis Gravidarum, With and Without Preeclampsia.</h4><i>Cécile B, Potter BJ, Lewin A, Healy-Profitós J, Brousseau É, Auger N</i><br /><AbstractText><br /><b>Background:</b><br/>Hyperemesis gravidarum is associated with preeclampsia, but it is unclear whether hyperemesis gravidarum is a risk factor for cardiovascular disease. We assessed the long-term risk of cardiovascular disease in women who experienced hyperemesis gravidarum with or without preeclampsia. Methods and Results We analyzed a longitudinal cohort of 1 413 166 pregnant women in Quebec between 1989 and 2021. Women were followed from their first pregnancy up to 3 decades later. We computed hazard ratios (HRs) and 95% CIs for the association of hyperemesis gravidarum, preeclampsia, or both conditions with subsequent risk of cardiovascular hospitalization using Cox regression models adjusted for baseline characteristics. Among 1 413 166 women, 16 288 (1.2%) had hyperemesis gravidarum only, 69 645 (4.9%) preeclampsia only, and 1103 (0.08%) had both conditions. After 32 years of follow-up, cardiovascular disease incidence was 17.7 per 100 women with hyperemesis gravidarum only, 28.2 per 100 women with preeclampsia only, 30.9 per 100 women with both exposures, and 14.0 per 100 women with neither exposure. Compared with no exposure, women with both hyperemesis and preeclampsia had the greatest risk of cardiovascular hospitalization (HR, 3.54 [95% CI, 3.03-4.14]), followed by women with preeclampsia only (HR, 2.58 [95% CI, 2.51-2.64]) and hyperemesis only (HR, 1.46 [95% CI, 1.38-1.54]). Having both hyperemesis gravidarum and preeclampsia was strongly associated with valve disease (HR, 3.38 [95% CI, 1.69-6.75]), heart failure (HR, 3.43 [95% CI, 1.79-6.59]), and cardiomyopathy (HR, 4.17 [95% CI, 1.99-8.76]). <br /><b>Conclusions:</b><br/>Hyperemesis gravidarum is associated with the development of cardiovascular disease, whether preeclampsia is present or not.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 01 Jun 2023:e029298; epub ahead of print</small></div>

<div><h4>Congenitally Corrected Transposition of the Great Arteries: Fetal Diagnosis, Associations, and Postnatal Outcome: A Fetal Heart Society Research Collaborative Study.</h4><i>Cohen J, Arya B, Caplan R, Donofrio MT, ... Thakur V, Srivastava S</i><br /><AbstractText><br /><b>Background:</b><br/>Fetal diagnosis of congenitally corrected transposition of the great arteries (ccTGA) has been increasingly reported; however, predictors of clinical outcomes remain underexplored. We undertook a multicenter, retrospective study to investigate natural history, associated anomalies, and outcomes of fetal ccTGA. Methods and Results Fetuses with ccTGA diagnosed from January 2004 to July 2020 within 20 North American programs were included. Fetuses with severe ventricular hypoplasia thought to definitively preclude biventricular repair were excluded. We included 205 fetuses diagnosed with ccTGA at a median gestational age of 23 (interquartile range, 21-27) weeks. Genetic abnormalities were found in 5.9% tested, with extracardiac anomalies in 6.3%. Associated cardiac defects were diagnosed in 161 (78.5%), with atrioventricular block in 23 (11.3%). On serial fetal echocardiogram, 39% demonstrated a functional or anatomic change, most commonly increased tricuspid regurgitation (6.7%) or pulmonary outflow obstruction (11.1%). Of 194 fetuses with follow-up, 26 were terminated, 3 experienced fetal death (2 with atrioventricular block), and 165 were live-born. Of 158 with postnatal data (median follow-up 3.7 years), 10 (6.6%) had death/transplant before 1 year. On univariable analysis, fetal factors associated with fetal death or death/transplant by 1 year included ≥ mild tricuspid regurgitation, pulmonary atresia, aortic obstruction, fetal arrhythmia, and worsening hemodynamics on serial fetal echocardiogram (defined as worse right ventricular function, tricuspid regurgitation, or effusion). <br /><b>Conclusions:</b><br/>Associated cardiac lesions and arrhythmias are common in fetal ccTGA, and functional changes commonly occur through gestation. Worse outcomes are associated with fetal tricuspid regurgitation (≥mild), any arrhythmia, pulmonary atresia, aortic obstruction, and worsening hemodynamics on serial echocardiograms. These findings can inform prenatal counseling and perinatal management planning.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 01 Jun 2023:e029706; epub ahead of print</small></div>

<div><h4>Omega-3 Fatty Acids and Heart Rhythm, Rate, and Variability in Atrial Fibrillation.</h4><i>Baumgartner P, Reiner MF, Wiencierz A, Coslovsky M, ... Beer JH, SWISS‐AF Investigators</i><br /><AbstractText><br /><b>Background:</b><br/>Previous randomized control trials showed mixed results concerning the effect of omega-3 fatty acids (n-3 FAs) on atrial fibrillation (AF). The associations of n-3 FA blood levels with heart rhythm in patients with established AF are unknown. The goal of this study was to assess the associations of total and individual n-3 FA blood levels with AF type (paroxysmal versus nonparoxysmal), heart rate (HR), and HR variability in patients with AF. Methods and Results Total n-3 FAs, eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid, and alpha-linolenic acid blood levels were determined in 1969 patients with known AF from the SWISS-AF (Swiss Atrial Fibrillation cohort). Individual and total n-3 FAs were correlated with type of AF, HR, and HR variability using standard logistic and linear regression, adjusted for potential confounders. Only a mild association with nonparoxysmal AF was found with total n-3 FA (odds ratio [OR], 0.97 [95% CI, 0.89-1.05]) and docosahexaenoic acid (OR, 0.93 [95% CI, 0.82-1.06]), whereas other individual n-3 FAs showed no association with nonparoxysmal AF. Higher total n-3 FAs (estimate 0.99 [95% CI, 0.98-1.00]) and higher docosahexaenoic acid (0.99 [95% CI, 0.97-1.00]) tended to be associated with slower HR in multivariate analysis. Docosapentaenoic acid was associated with a lower HR variability triangular index (0.94 [95% CI, 0.89-0.99]). <br /><b>Conclusions:</b><br/>We found no strong evidence for an association of n-3 FA blood levels with AF type, but higher total n-3 FA levels and docosahexaenoic acid might correlate with lower HR, and docosapentaenoic acid with a lower HR variability triangular index.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 01 Jun 2023:e027646; epub ahead of print</small></div>

<div><h4>Heart Failure Impairs Bone Marrow Hematopoietic Stem Cell Function and Responses to Injury.</h4><i>Marvasti TB, Alibhai FJ, Yang GJ, Li SH, ... Yau T, Li RK</i><br /><AbstractText><br /><b>Background:</b><br/>Heart failure (HF) is a clinical syndrome associated with a progressive decline in myocardial function and low-grade systemic inflammation. Chronic inflammation can have lasting effects on the bone marrow (BM) stem cell pool by impacting cell renewal and lineage differentiation. However, how HF affects BM stem/progenitor cells remains largely unexplored. Methods and Results EGFP<sup>+</sup> (Enchanced green fluorescent protein) mice were subjected to coronary artery ligation, and BM was collected 8 weeks after myocardial infarction. Transplantation of EGFP<sup>+</sup> BM into wild-type mice revealed reduced reconstitution potential of BM from mice subjected to myocardial infarction versus BM from sham mice. To study the effects HF has on human BM function, 71 patients, HF (n=20) and controls (n=51), who were scheduled for elective cardiac surgery were consented and enrolled in this study. Patients with HF exhibited more circulating blood myeloid cells, and analysis of patient BM revealed significant differences in cell composition and colony formation potential. Human CD34<sup>+</sup> cell reconstitution potential was also assessed using the NOD-SCID-IL2rγ<sup>null</sup> mouse xenotransplant model. NOD-SCID-IL2rγ<sup>null</sup> mice reconstituted with BM from patients with HF had significantly fewer engrafted human CD34<sup>+</sup> cells as well as reduced lymphoid cell production. Analysis of tissue repair responses using permanent left anteriordescending coronary artery ligation demonstrated reduced survival of HF-BM reconstituted mice as well as significant differences in human (donor) and mouse (host) cellular responses after MI. <br /><b>Conclusions:</b><br/>HF alters the BM composition, adversely affects cell reconstitution potential, and alters cellular responses to injury. Further studies are needed to determine whether restoring BM function can impact disease progression or improve cellular responses to injury.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 01 Jun 2023:e027727; epub ahead of print</small></div>

<div><h4>Impaired Distensibility of the Proximal Aorta in Fetuses With Tetralogy of Fallot.</h4><i>Zhou D, Xu R, Zhou J, Liu M, ... Hou M, Zeng S</i><br /><AbstractText><br /><b>Background:</b><br/>Increased aortic wall stiffness, which even persists after repair, has been reported in patients with tetralogy of Fallot (TOF). We aimed to observe the distensibility of the ascending aorta and descending aorta in fetuses with TOF and explore its relation with aortic blood flow volume and aortic and pulmonary annular size. Methods and Results Twenty-three fetuses with TOF and 23 gestational age-matched normal fetuses were included in this prospective cross-sectional study. The distensibilities of the ascending aorta and descending aorta were assessed by aortic strain (AS), which was defined as follows: 100×(maximum internal diameter in the systolic phase-minimum internal diameter in the diastolic phase)/minimum internal diameter in the diastolic phase. The maximum internal diameter in the systolic phase and minimum internal diameter in the diastolic phase of the ascending aorta and descending aorta were measured by M-mode echocardiography. Associations between AS and aortic blood flow volume and aortic and pulmonary valve diameters were assessed in both groups. AS of the ascending aorta in TOF group was lower than that in controls (20.48%±4.19% versus 28.17%±4.54%; <i>P</i><0.001), whereas there was no significant difference in the descending aorta. The multivariate regression model demonstrated that AS was significantly related to aortic valve size (<i>P</i>=0.014) and aortic blood flow volume (<i>P</i>=0.022) in fetuses with TOF, whereas only aortic blood flow volume was significantly correlated with AS in the control group (<i>P</i>=0.01). No significant association was found between AS and pulmonary valve size. <br /><b>Conclusions:</b><br/>Impaired distensibility of proximal aorta was observed in fetuses with TOF. Both intrinsic abnormalities of the aortic wall and aortic volume overload probably play roles in the altered aortic distensibility.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 01 Jun 2023:e028499; epub ahead of print</small></div>

<div><h4>Plasma Pro-Enkephalin A and Incident Cognitive Impairment: The Reasons for Geographic and Racial Differences in Stroke Cohort.</h4><i>Short SAP, Wilkinson K, Schulte J, Renteria MA, ... Howard VJ, Cushman M</i><br /><AbstractText><br /><b>Background:</b><br/>Cardiovascular disease is a risk factor for cognitive impairment. Evidence links both lower and higher concentration of the circulating opioid pro-enkephalin A (PENK-A) with stroke risk. We studied the association of plasma PENK-A with incident cognitive impairment. Methods and Results REGARDS (Reasons for Geographic and Racial Differences in Stroke) is a prospective cohort study of 30 239 adults enrolled from 2003 to 2007. Baseline PENK-A was measured in a nested case-control study of 462 participants who developed cognitive impairment over 4.7 years, and 556 controls. Logistic regression and spline plots adjusted for confounders estimated odds ratios (ORs) of cognitive impairment by baseline PENK-A. Interaction terms tested for differences in associations by age, sex, and race. Baseline PENK-A was comparable between cases and controls. There were significant differences in the association of PENK-A with cognitive impairment by sex and age (adjusted <i>P</i>=0.003 and 0.06, respectively). In women but not men, spline plots showed that higher and lower PENK-A were associated with decreased odds of cognitive impairment (ORs for 10th and 90th percentiles versus median, 0.65 [95% CI, 0.43-0.96] and 0.64 [95% CI, 0.41-0.99]), with no difference by age. In men ≥65 years of age but not younger men, higher PENK-A was associated with decreased odds for cognitive impairment (OR for fourth versus first quartile 0.47 [95% CI, 0.22-0.99]); this pattern was not confirmed with spline plotting. <br /><b>Conclusions:</b><br/>High and low levels of circulating opioid PENK-A were associated with decreased odds of future cognitive impairment in specific subgroups. Additional research is warranted to understand the biology underlying this association and the observed differences by sex.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 01 Jun 2023:e029081; epub ahead of print</small></div>

<div><h4>Exercise Capacity and Ventilatory Efficiency in Patients With Pulmonary Arterial Hypertension.</h4><i>Tobita K, Goda A, Teruya K, Nishida Y, ... Satoh T, Soejima K</i><br /><AbstractText><br /><b>Background:</b><br/>The symptom for identification of pulmonary arterial hypertension (PAH) is dyspnea on exertion, with a concomitant decrease in exercise capacity. Even patients with hemodynamically improved PAH may have impaired exercise tolerance; however, the effect of central and peripheral factors on exercise tolerance remains unclear. We explored the factors contributing to exercise capacity and ventilatory efficiency in patients with hemodynamically normalized PAH after medical treatment. Methods and Results In total, 82 patients with PAH (age: median 46 [interquartile range, 39-51] years; male:female, 23:59) and mean pulmonary arterial pressure ≤30 mm Hg at rest were enrolled. The exercise capacity, indicated by the 6-minute walk distance and peak oxygen consumption, and the ventilatory efficiency, indicated by the minute ventilation versus carbon dioxide output slope, were assessed using cardiopulmonary exercise testing with a right heart catheter. The mean pulmonary arterial pressure was 21 (17-25) mm Hg, and the 6-minute walk distance was 530 (458-565) m, whereas the peak oxygen consumption was 18.8 (14.8-21.6) mLꞏmin<sup>-1</sup>ꞏkg<sup>-1</sup>. The multivariate model that best predicted 6-minute walk distance included peak arterial mixed venous oxygen content difference (β=0.46, <i>P</i><0.001), whereas the best peak oxygen consumption predictors included peak cardiac output (β=0.72, <i>P</i><0.001), peak arterial mixed venous oxygen content difference (β=0.56, <i>P</i><0.001), and resting mean pulmonary arterial pressure (β=-0.25, <i>P</i>=0.026). The parameter that best predicted minute ventilation versus carbon dioxide output slope was the resting mean pulmonary arterial pressure (β=0.35, <i>P</i>=0.041). Quadriceps muscle strength was moderately correlated with exercise capacity (6-minute walk distance; ρ=0.57, <i>P</i><0.001; peak oxygen consumption: ρ=0.56, <i>P</i><0.001) and weakly correlated with ventilatory efficiency (ρ<i>=</i>-0.32, <i>P</i>=0.007). <br /><b>Conclusions:</b><br/>Central and peripheral factors are closely related to impaired exercise tolerance in patients with hemodynamically normalized PAH.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 01 Jun 2023:e026890; epub ahead of print</small></div>

<div><h4>Neonatal Depression Is Associated With 1-Year Mortality in Critical Congenital Heart Disease.</h4><i>Miles KG, Liu J, Tseng SY, DeFranco EA, ... Ollberding NJ, Cnota JF</i><br /><AbstractText><br /><b>Background:</b><br/>Low 5-minute Apgar scores (AS) are predictive of term and preterm neonatal mortality but have not been well studied in the critical congenital heart disease (CCHD) population. We analyzed US national vital statistics data to evaluate the association between neonatal depression (AS 0-3) and 1-year mortality in CCHD. Methods and Results We performed a retrospective cohort study using 2014 to 2018 Centers for Disease Control and Prevention cohort-linked birth certificate and infant death records. Five-minute AS were categorized as ≤3, 4 to 6, or ≥7. We calculated birth rates and associated mortality rates by AS group in infants with and without CCHD. Multivariable logistic regression analyzed neonatal, maternal, and pregnancy-related risk factors for neonatal depression and 1-year mortality. Of 11 642 neonates with CCHD (0.06% of all births), the 5.8% with AS 0 to 3 accounted for 23.3% of all 1-year CCHD mortality, with 69.9% of deaths occurring within 1 month of life. Gestational age at birth, growth restriction, extracardiac defects, race, and low maternal education were associated with an increased odds of AS 0 to 3 in neonates with CCHD relative to those with AS 7 to 10 on multivariable analysis. AS 0 to 3 was associated with 1-year CCHD mortality after adjusting for these factors, prenatal care, and delivery location (adjusted odds ratio, 14.57 [95% CI, 11.73-18.10]). <br /><b>Conclusions:</b><br/>The AS is a routine clinical measure providing important prognostic information in CCHD. These findings suggest that prenatal and perinatal factors, beyond those included in current risk stratification tools, are important for CCHD outcomes. Multidisciplinary collaboration to understand the pathophysiology underlying neonatal depression may help identify interventions to improve CCHD mortality rates.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 01 Jun 2023:e028774; epub ahead of print</small></div>

<div><h4>Subclinical Cardiovascular Disease in US Adults With and Without Diabetes.</h4><i>Fang M, Wang D, Tang O, McEvoy JW, ... Christenson RH, Selvin E</i><br /><AbstractText><br /><b>Background:</b><br/>We characterized the burden and prognostic value of subclinical cardiovascular disease (CVD) assessed by cardiac biomarkers among adults with and without diabetes in the general US population. Methods and Results We measured hs-cTnT (high-sensitivity cardiac troponin T) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) in stored serum samples from the 1999 to 2004 National Health and Nutrition Examination Survey. Among US adults without a history of CVD (n=10 304), we estimated the prevalence of elevated hs-cTnT (≥14 ng/L) and NT-proBNP (≥125 pg/mL) in those with and without diabetes. We examined the associations between elevated hs-cTnT and NT-proBNP with all-cause and CVD mortality after adjustment for demographics and traditional CVD risk factors. The crude prevalence of subclinical CVD (elevated hs-cTnT or NT-proBNP) was ≈2 times higher in adults with (versus without) diabetes (33.4% versus 16.1%). After age adjustment, elevated hs-cTnT, but not elevated NT-proBNP, was more common in those with diabetes, overall and across age, sex, race and ethnicity, and weight status. The prevalence of elevated hs-cTnT was significantly higher in those with longer diabetes duration and worse glycemic control. In persons with diabetes, elevated hs-cTnT and NT-proBNP were independently associated with all-cause mortality (adjusted hazard ratio [HR], 1.77 [95% CI, 1.33-2.34] and HR, 1.78 [95% CI, 1.26-2.51]) and CVD mortality (adjusted HR, 1.54 [95% CI, 0.83-2.85] and HR, 2.46 [95% CI, 1.31-4.60]). <br /><b>Conclusions:</b><br/>Subclinical CVD affects ≈1 in 3 US adults with diabetes and confers substantial risk for mortality. Routine testing of cardiac biomarkers may be useful for assessing and monitoring risk in persons with diabetes.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 31 May 2023:e029083; epub ahead of print</small></div>

<div><h4>Ten-Year Cardiovascular Disease Risk Score and Cognitive Function Among Older Adults: The National Health and Nutrition Examination Survey 2011 to 2014.</h4><i>Wei J, Xu H, Liese AD, Merchant AT, ... Wang T, Friedman DB</i><br /><AbstractText><br /><b>Background:</b><br/>The Framingham 10-year cardiovascular disease risk score, which is based on age, sex, smoking, total cholesterol, high-density lipoprotein-cholesterol, blood pressure, and diabetes, has been found to be associated with cognitive health, but these findings have not been validated in a representative sample in the United States. We aimed to examine the associations of Framingham risk score with cognitive function among older adults in a nationally representative sample, as well as by race or ethnicity, education, and family income. Methods and Results A total of 2254 older adults ≥60 years (57% female, 79% non-Hispanic White) in the National Health and Nutrition Examination Survey 2011 to 2014 were included in the final sample for analysis. All components of the Framingham risk score were obtained with questionnaire or measured in the laboratory. Cognitive function was examined using the Consortium to Establish a Registry for Alzheimer\'s Disease Word List Memory Task (immediate and delayed memory), Digit Symbol Substitution Test, and Animal Fluency Test. Multivariable linear regression models were used to assess the associations between Framingham risk score and test-specific and global cognition <i>Z</i> scores. Each incremental 5% in Framingham 10-year cardiovascular disease risk was associated with lower <i>Z</i> scores for Digit Symbol Substitution Test (β=-0.06 [95% CI, -0.09 to -0.03]), delayed memory (β=-0.05 [95% CI, -0.08 to -0.01]), immediate memory (β=-0.07 [95% CI, -0.10 to -0.03]), and global cognition (β=-0.05 [95% CI, -0.09 to -0.02]). Socioeconomic status, particularly race or ethnicity and monthly income levels, were strong effect measure modifiers of the associations. <br /><b>Conclusions:</b><br/>Lower cardiovascular risk factors are associated with better cognitive function.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 30 May 2023:e028527; epub ahead of print</small></div>

<div><h4>Reducing Long-Term Mortality Post Transcatheter Aortic Valve Replacement Requires Systemic Differentiation of Patient-Specific Coronary Hemodynamics.</h4><i>Khodaei S, Garber L, Abdelkhalek M, Maftoon N, Emadi A, Keshavarz-Motamed Z</i><br /><AbstractText><br /><b>Background:</b><br/>Despite the proven benefits of transcatheter aortic valve replacement (TAVR) and its recent expansion toward the whole risk spectrum, coronary artery disease is present in more than half of the candidates for TAVR. Many previous studies do not focus on the longer-term impact of TAVR on coronary arteries, and hemodynamic changes to the circulatory system in response to the anatomical changes caused by TAVR are not fully understood. Methods and Results We developed a multiscale patient-specific computational framework to examine the effect of TAVR on coronary and cardiac hemodynamics noninvasively. Based on our findings, TAVR might have an adverse impact on coronary hemodynamics due to the lack of sufficient coronary blood flow during diastole phase (eg, maximum coronary flow rate reduced by 8.98%, 16.83%, and 22.73% in the left anterior descending, left circumflex coronary artery, and right coronary artery, respectively [N=31]). Moreover, TAVR may increase the left ventricle workload (eg, left ventricle workload increased by 2.52% [N=31]) and decrease the coronary wall shear stress (eg, maximum time averaged wall shear stress reduced by 9.47%, 7.75%, 6.94%, 8.07%, and 6.28% for bifurcation, left main coronary artery, left anterior descending, left circumflex coronary artery, and right coronary artery branches, respectively). <br /><b>Conclusions:</b><br/>The transvalvular pressure gradient relief after TAVR might not result in coronary flow improvement and reduced cardiac load. Optimal revascularization strategy pre-TAVR and progression of coronary artery disease after TAVR could be determined by noninvasive personalized computational modeling.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 26 May 2023:e029310; epub ahead of print</small></div>

<div><h4>NT-proBNP and All-Cause and Cardiovascular Mortality in US Adults: A Prospective Cohort Study.</h4><i>Echouffo-Tcheugui JB, Zhang S, Daya N, McEvoy JW, ... Christenson RH, Selvin E</i><br /><AbstractText><br /><b>Background:</b><br/>NT-proBNP (N-terminal pro-B-type natriuretic peptide) is strongly associated with mortality in patients with heart failure. Prior studies, primarily in middle-aged and older populations, have suggested that NT-proBNP has prognostic value in ambulatory adults. Methods and Results We conducted a prospective cohort analysis of adults, aged ≥20 years, in the nationally representative 1999 to 2004 National Health and Nutrition Examination Survey, to characterize the association of NT-proBNP with mortality in the general US adult population overall and by age, race and ethnicity, and body mass index. We used Cox regression to characterize associations of NT-proBNP with all-cause and cardiovascular disease (CVD) mortality through 2019, adjusting for demographics and cardiovascular risk factors. We included 10 645 individuals (mean age, 45.7 years; 50.8% women; 72.8% White adults; 8.5% with a self-reported history of CVD). There were 3155 deaths (1009 CVD-related) over a median 17.3 years of follow-up. Among individuals without prior CVD, elevated NT-proBNP (≥75th percentile [81.5 pg/mL] versus <25th percentile [20.5 pg/mL]) was associated with a significantly higher risk of all-cause (hazard ratio [HR], 1.67 [95% CI, 1.39-2.00]) and CVD mortality (HR, 2.87 [95% CI, 1.61-5.11]). Associations of NT-proBNP with all-cause and CVD mortality were generally similar across subgroups defined by age, sex, race and ethnicity, or body mass index (all <i>P</i> interaction >0.05). <br /><b>Conclusions:</b><br/>In a representative sample of the US adult population, NT-proBNP was an important independent risk factor for all-cause and CVD mortality. NT-proBNP may be useful for monitoring risk in the general adult population.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 26 May 2023:e8386; epub ahead of print</small></div>

<div><h4>Association of Cardiovascular Health Assessed by the New Life\'s Essential 8 Metrics With Years Lived Without Cardiovascular Disease.</h4><i>Xia X, Chen S, Tian X, Xu Q, ... Lin L, Wang A</i><br /><AbstractText><br /><b>Background:</b><br/>The American Heart Association recently proposed an updated definition of cardiovascular health (CVH) named as Life\'s Essential 8. We aimed to explore the association between this latest published CVH measurement and years lived without cardiovascular disease (CVD) among the Chinese population. Methods and Results We included 89 755 adults free of CVD at baseline from the Kailuan study. The CVH of each participant was scored (from 0 point to 100 points) and classified (low [0-49 points], moderate [50-79 points], and high [80-100 points]) according to Life\'s Essential 8, which incorporated 8 components covering health behaviors and health factors. Incident CVD was documented through follow-ups from baseline (June 2006 to October 2007) until December 31, 2020. CVD-free life years from age 30 to 80 years associated with different CVH scores were estimated using flexible parametric survival models. A total of 9977 incident CVDs were recorded. We observed a gradient relationship between CVH score and years lived without CVD. The age- and sex-adjusted CVD-free life years (95% CI) were 40.7 (40.3-41.0) years for low CVH, 43.3 (43.0-43.5) years for moderate CVH, and 45.5 (45.1-45.9) years for high CVH. Similar trends were noted when individual subtypes of CVD were investigated, and high CVH evaluated by health behaviors and health factors was also related to longer CVD-free life years. <br /><b>Conclusions:</b><br/>A higher CVH evaluated by the updated Life\'s Essential 8 metrics was significantly associated with a greater number of life years without CVD, indicating the importance of promoting CVH for healthy aging in China.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 26 May 2023:e029241; epub ahead of print</small></div>

<div><h4>Heart Rate Variability Parameter Changes in Patients With Acute Ischemic Stroke Undergoing Intravenous Thrombolysis.</h4><i>Qu Y, Sun YY, Abuduxukuer R, Si XK, ... Yang Y, Guo ZN</i><br /><AbstractText><br /><b>Background:</b><br/>Autonomic dysfunction has been revealed in patients with acute ischemic stroke and is associated with poor prognosis. However, autonomic nervous system function assessed by heart rate variability (HRV) and its relationship with clinical outcomes in patients undergoing intravenous thrombolysis (IVT) remain unknown. Methods and Results Patients who did and did not undergo IVT between September 2016 and August 2021 were prospectively and consecutively recruited. HRV values were measured at 1 to 3 and 7 to 10 days after stroke to assess autonomic nervous system function. A modified Rankin scale score ≥2 at 90 days was defined as an unfavorable outcome. Finally, the analysis included 466 patients; 224 underwent IVT (48.1%), and 242 did not (51.9%). Linear regression showed a positive correlation of IVT with parasympathetic activation-related HRV parameters at 1 to 3 days (high frequency: <i>β</i>=0.213, <i>P</i>=0.002) and with both sympathetic (low frequency: <i>β</i>=0.152, <i>P</i>=0.015) and parasympathetic activation-related HRV parameters (high frequency: <i>β</i>=0.153, <i>P</i>=0.036) at 7 to 10 days after stroke. Logistic regression showed HRV values and autonomic function within 1 to 3 and 7 to 10 days after stroke were independently associated with 3-month unfavorable outcomes after adjusting for confounders in patients who underwent IVT (all <i>P</i><0.05). Furthermore, addition of HRV parameters to conventional risk factors significantly improved risk-predictive ability of 3-month outcome (the area under the receiver operating characteristic curve significantly improved from 0.784 [0.723-0.846] to 0.855 [0.805-0.906], <i>P</i>=0.002). <br /><b>Conclusions:</b><br/>IVT positively affected HRV and autonomic nervous system activity, and autonomic function assessed by HRV in acute stroke phase was independently associated with unfavorable outcomes in patients undergoing IVT.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 26 May 2023:e028778; epub ahead of print</small></div>

<div><h4>Inequities in Treatments and Outcomes Among Patients Hospitalized With Hypertrophic Cardiomyopathy in the United States.</h4><i>Johnson DY, Waken RJ, Fox DK, Hammond G, Joynt Maddox KE, Cresci S</i><br /><AbstractText><br /><b>Background:</b><br/>Hypertrophic cardiomyopathy (HCM) is the most common heritable cardiac disease. In small studies, sociodemographic factors have been associated with disparities in septal reduction therapy, but little is known about the association of sociodemographic factors with HCM treatments and outcomes more broadly. Methods and Results Using the National Inpatient Survey from 2012 to 2018, HCM diagnoses and procedures were identified by <i>International Classification of Diseases, Ninth/Tenth Revision, Clinical Modification</i> (<i>ICD-9-CM</i> and <i>ICD-10-CM</i>) codes. Logistic regression was used to determine the association of sociodemographic risk factors with HCM procedures and in-hospital death, adjusting for clinical comorbidities and hospital characteristics. Of 53 117 patients hospitalized with HCM, 57.7% were women, 20.5% were Black individuals, 27.7% lived in the lowest zip income quartile, and 14.7% lived in rural areas. Among those with obstruction (45.2%), compared with White patients, Black patients were less likely to undergo septal myectomy (adjusted odds ratio [aOR], 0.52 [95% CI, 0.40-0.68]), or alcohol septal ablation (aOR, 0.60 [95% CI, 0.42-0.86]). Patients with Medicaid were less likely to undergo each procedure (aOR, 0.78 [95% CI, 0.61-0.99] for myectomy; aOR, 0.54 [95% CI, 0.36-0.83] for ablation). Women (aOR, 0.66 [95% CI, 0.58-0.74]), patients with Medicaid (aOR, 0.78 [95% CI, 0.65-0.93]), and patients from low-income areas (aOR, 0.77 [95% CI, 0.65-0.93]) were less likely to receive implantable cardioverter-defibrillators. Women (aOR, 1.23 [95% CI, 1.10-1.37]) and patients from towns (aOR, 1.16 [95% CI, 1.03-1.31]) or rural areas (aOR, 1.57 [95% CI, 1.30-1.89]) had higher odds of in-hospital death. <br /><b>Conclusions:</b><br/>Among 53 117 patients hospitalized with HCM, race, sex, social, and geographic risk factors were associated with disparities in HCM outcomes and treatment. Further research is required to identify and address the sources of these inequities.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 26 May 2023:e029930; epub ahead of print</small></div>

<div><h4>Red Blood Cell Transfusions Are Not Associated With Incident Complications or Poor Outcomes in Patients With Intracerebral Hemorrhage.</h4><i>Carvalho Poyraz F, Boehme A, Cottarelli A, Eisler L, ... Hod EA, Roh DJ</i><br /><AbstractText><br /><b>Background:</b><br/>Anemia is associated with poor intracerebral hemorrhage (ICH) outcomes, yet the relationship of red blood cell (RBC) transfusions to ICH complications and functional outcomes remains unclear. We investigated the impact of RBC transfusion on hospital thromboembolic and infectious complications and outcomes in patients with ICH. Methods and Results Consecutive patients with spontaneous ICH enrolled in a single-center, prospective cohort study from 2009 to 2018 were assessed. Primary analyses assessed relationships of RBC transfusions on incident thromboembolic and infectious complications occurring after the transfusion. Secondary analyses assessed relationships of RBC transfusions with mortality and poor discharge modified Rankin Scale score 4 to 6. Multivariable logistic regression models adjusted for baseline demographics and medical disease severity (Acute Physiology and Chronic Health Evaluation II), and ICH severity (ICH score).Of 587 patients with ICH analyzed, 88 (15%) received at least one RBC transfusion. Patients receiving RBC transfusions had worse medical and ICH severity. Though patients receiving RBC transfusions had more complications at any point during the hospitalization (64.8% versus 35.9%), we found no association between RBC transfusion and incident complications in our regression models (adjusted odds ratio [aOR], 0.71 [95% CI, 0.42-1.20]). After adjusting for disease severity and other relevant covariates, we found no significant association between RBC transfusion and mortality (aOR, 0.87 [95% CI, 0.45-1.66]) or poor discharge modified Rankin Scale score (aOR, 2.45 [95% CI, 0.80-7.61]). <br /><b>Conclusions:</b><br/>In our cohort with ICH, RBC transfusions were expectedly given to patients with higher medical and ICH severity. Taking disease severity and timing of transfusions into account, RBC transfusion was not associated with incident hospital complications or poor clinical ICH outcomes.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 26 May 2023:e028816; epub ahead of print</small></div>

<div><h4>Is There a Sex Difference in the Prognosis of Hypertrophic Cardiomyopathy? A Systematic Review and Meta-Analysis.</h4><i>Zhao H, Tan Z, Liu M, Yu P, ... Zhu W, Liu X</i><br /><AbstractText><br /><b>Background:</b><br/>It is still unclear whether there is a sex difference in the prognosis of patients with hypertrophic cardiomyopathy (HCM). Therefore, we performed a meta-analysis to elucidate the association between sex and adverse outcomes in patients with HCM. Methods and Results The PubMed, Cochrane Library, and Embase databases were used to search for studies on sex differences in prognosis in patients with HCM up to August 17, 2021. Summary effect sizes were calculated using a random effects model. The protocol was registered in PROSPERO (International prospective register of systematic reviews) (registration number- CRD42021262053). A total of 27 cohorts involving 42 365 patients with HCM were included. Compared with male subjects, female subjects had a higher age at onset (mean difference=5.61 [95% CI, 4.03-7.19]), a higher left ventricular ejection fraction (standard mean difference=0.09 [95% CI, 0.02-0.15]) and a higher left ventricular outflow tract gradient (standard mean difference=0.23 [95% CI, 0.18-0.29]). The results showed that compared with male subjects with HCM, female subjects had higher risks of HCM-related events (risk ratio [RR]=1.61 [95% CI, 1.33-1.94], <i>I</i><sup>2</sup>=49%), major cardiovascular events (RR=3.59 [95% CI, 2.26-5.71], <i>I</i><sup>2</sup>=0%), HCM-related death (RR=1.57 [95% CI, 1.34-1.82], <i>I</i><sup>2</sup>=0%), cardiovascular death (RR=1.55 [95% CI, 1.05-2.28], <i>I</i><sup>2</sup>=58%), noncardiovascular death (RR=1.77 [95% CI, 1.46-2.13], <i>I</i><sup>2</sup>=0%) and all-cause mortality (RR=1.43 [95% CI, 1.09-1.87], <i>I</i><sup>2</sup>=95%), but not atrial fibrillation (RR=1.13 [95% CI, 0.95-1.35], <i>I</i><sup>2</sup>=5%), ventricular arrhythmia (RR=0.88 [95% CI, 0.71-1.10], <i>I</i><sup>2</sup>=0%), sudden cardiac death (RR=1.04 [95% CI, 0.75-1.42], <i>I</i><sup>2</sup>=38%) or composite end point (RR=1.24 [95% CI, 0.96-1.60], <i>I</i><sup>2</sup>=85%). <br /><b>Conclusions:</b><br/>Based on current evidence, our results show significant sex-specific differences in the prognosis of HCM. Future guidelines may emphasize the use of a sex-specific risk assessment for the diagnosis and management of HCM.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 26 May 2023:e026270; epub ahead of print</small></div>

<div><h4>Neurovascular Uncoupling Is Linked to Microcirculatory Dysfunction in Regions Outside the Ischemic Core Following Ischemic Stroke.</h4><i>Staehr C, Giblin JT, Gutiérrez-Jiménez E, Guldbrandsen HØ, ... Boas DA, Matchkov VV</i><br /><AbstractText><br /><b>Background:</b><br/>Normal brain function depends on the ability of the vasculature to increase blood flow to regions with high metabolic demands. Impaired neurovascular coupling, such as the local hyperemic response to neuronal activity, may contribute to poor neurological outcome after stroke despite successful recanalization, that is, futile recanalization. Methods and Results Mice implanted with chronic cranial windows were trained for awake head-fixation before experiments. One-hour occlusion of the anterior middle cerebral artery branch was induced using single-vessel photothrombosis. Cerebral perfusion and neurovascular coupling were assessed by optical coherence tomography and laser speckle contrast imaging. Capillaries and pericytes were studied in perfusion-fixed tissue by labeling lectin and platelet-derived growth factor receptor β. Arterial occlusion induced multiple spreading depolarizations over 1 hour associated with substantially reduced blood flow in the peri-ischemic cortex. Approximately half of the capillaries in the peri-ischemic area were no longer perfused at the 3- and 24-hour follow-up (45% [95% CI, 33%-58%] and 53% [95% CI, 39%-66%] reduction, respectively; <i>P</i><0.0001), which was associated with contraction of an equivalent proportion of peri-ischemic capillary pericytes. The capillaries in the peri-ischemic cortex that remained perfused showed increased point prevalence of dynamic flow stalling (0.5% [95% CI, 0.2%-0.7%] at baseline, 5.1% [95% CI, 3.2%-6.5%] and 3.2% [95% CI, 1.1%-5.3%] at 3- and 24-hour follow-up, respectively; <i>P</i>=0.001). Whisker stimulation at the 3- and 24-hour follow-up led to reduced neurovascular coupling responses in the sensory cortex corresponding to the peri-ischemic region compared with that observed at baseline. <br /><b>Conclusions:</b><br/>Arterial occlusion led to contraction of capillary pericytes and capillary flow stalling in the peri-ischemic cortex. Capillary dysfunction was associated with neurovascular uncoupling. Neurovascular coupling impairment associated with capillary dysfunction may be a mechanism that contributes to futile recanalization. Hence, the results from this study suggest a novel treatment target to improve neurological outcome after stroke.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 26 May 2023:e029527; epub ahead of print</small></div>

<div><h4>What Is the Optimal Mitral Valve Repair for Isolated Posterior Leaflet Prolapse to Achieve Long-Term Durability?</h4><i>Kakuta T, Fukushima S, Minami K, Kainuma S, ... Saiki Y, Fujita T</i><br /><AbstractText><br /><b>Background:</b><br/>This study assessed risk factors for mitral regurgitation (MR) recurrence or functional mitral stenosis during long-term follow-up in patients undergoing mitral valve repair for isolated posterior mitral leaflet prolapse. Methods and Results We assessed a consecutive series of 511 patients who underwent primary mitral valve repair for isolated posterior leaflet prolapse between 2001 and 2021. Annuloplasty using a partial band was selected in 86.3%. The leaflet resection technique was used in 83.0%, whereas the chordal replacement without resection was used in 14.5%. Risk factors were analyzed for MR recurrence ≥grade 2 or functional mitral stenosis with mean transmitral pressure gradient ≥5 mm Hg using a multivariable Fine-Gray regression model. The 1-, 5-, and 10-year cumulative incidence of MR ≥grade 2 was 7.8%, 22.7%, and 30.1%, respectively, whereas that of mean transmitral pressure gradient ≥5 mm Hg was 8.1%, 20.6%, and 29.3%, respectively. Risk factors for MR ≥grade 2 included chordal replacement without resection (hazard ratio [HR], 2.50, <i>P</i><0.001) and larger prosthesis size (HR, 1.13, <i>P</i>=0.023), whereas factors for functional mitral stenosis were use of a full ring (partial band versus full ring, HR, 0.53, <i>P</i>=0.013), smaller prosthesis size (HR, 0.74, <i>P</i><0.001), and larger body surface area (HR, 3.03, <i>P</i>=0.045). Both MR ≥grade 2 and mean transmitral pressure gradient ≥5 mm Hg at 1 year post surgery were significantly associated with the long-term incidence of reoperation. <br /><b>Conclusions:</b><br/>Leaflet resection with a large partial band may be an optimal strategy for isolated posterior mitral valve prolapse.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 26 May 2023:e028607; epub ahead of print</small></div>

<div><h4>Relationship Between Endothelial Dysfunction and the Outcomes After Atrial Fibrillation Ablation.</h4><i>Okawa K, Sogo M, Morimoto T, Tsushima R, ... Ozaki M, Takahashi M</i><br /><AbstractText><br /><b>Background:</b><br/>Endothelial dysfunction (ED) is associated with cardiovascular events in patients with atrial fibrillation (AF). However, the utility of ED as a prognostic marker after AF ablation supplementary to the CHA<sub>2</sub>DS<sub>2</sub>-VASc score is unclear. This study aimed to investigate the relationship between ED and 5-year cardiovascular events in patients undergoing AF ablation. Methods and Results We conducted a prospective cohort study of patients who underwent a first-time AF ablation and for whom the endothelial function was assessed by the peripheral vascular reactive hyperemia index (RHI) before ablation. We defined ED as an RHI of <2.1. Cardiovascular events included strokes, heart failure requiring hospitalization, arteriosclerotic disease requiring treatment, venous thromboses, and ventricular arrhythmias or sudden cardiac death. We compared the 5-year incidence of cardiovascular events after AF ablation between those with and without ED. Among the 1040 patients who were enrolled, 829 (79.7%) had ED, and the RHI value was found to be associated with the CHA<sub>2</sub>DS<sub>2</sub>-VASc score (<i>P</i>=0.004). The 5-year incidence of cardiovascular events was higher among patients with ED than those without ED (98 [11.8%] versus 13 [6.2%]; log-rank <i>P</i>=0.014). We found ED to be an independent predictor of cardiovascular events after AF ablation (hazard ratio [HR], 1.91 [95% CI, 1.04-3.50]; <i>P</i>=0.036) along with a CHA<sub>2</sub>DS<sub>2</sub>-VASc score of ≥2 (≥3 for women) (HR, 3.68 [95% CI, 1.89-7.15]; <i>P</i><0.001). <br /><b>Conclusions:</b><br/>The prevalence of ED among patients with AF was high. Assessing the endothelial function could enable the risk stratification of cardiovascular events after AF ablation.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 26 May 2023:e028482; epub ahead of print</small></div>

<div><h4>Impact of Preoperative Quantitative Flow Ratio of the Left Anterior Descending Artery on Internal Mammary Artery Graft Patency and Midterm Patient Outcomes After Coronary Artery Bypass Grafting.</h4><i>Wang C, Hu Z, Hou Z, Wang Y, ... Feng W, Zhang Y</i><br /><AbstractText><br /><b>Background:</b><br/>In coronary artery bypass grafting, grafting a target vessel with nonsignificant stenosis increases the risk of graft failure. The present study aims to investigate the impact of preoperative quantitative flow ratio (QFR), a novel functional assessment of the coronary artery, on internal mammary artery graft failure rate and midterm patient outcomes. Methods and Results Between January 2016 and January 2020, we retrospectively included 419 patients who underwent coronary artery bypass grafting who had received preoperative angiography and postoperative coronary computed tomographic angiography in our center. QFR of the left anterior descending (LAD) artery was computed based on preoperative angiograms. The primary end point was the failure of the graft on the LAD artery assessed by coronary computed tomographic angiography at 1 year, and the secondary end point was major adverse cardiac and cerebrovascular events including death from any cause, myocardial infarction, stroke, or repeat revascularization. Grafts on functionally nonsignificant LAD arteries (QFR >0.80) had a significantly higher failure rate than those on functionally significant LAD arteries (31.4% versus 7.2%, <i>P</i><0.001). QFR outperforms degree of stenosis in discriminating graft failure (C statistic, 0.76 versus 0.58). Clinical follow-up (3.6 years, interquartile range [3.3-4.1]) was accomplished in 405 patients, and the rate of major adverse cardiac and cerebrovascular events was significantly higher among patients with functionally nonsignificant LAD arteries (10.1% versus 4.2%; adjusted hazard ratio, 3.08 [95% CI, 1.18-8.06]; <i>P</i>=0.022). <br /><b>Conclusions:</b><br/>In patients receiving internal mammary artery to LAD artery coronary artery bypass grafting, preoperative QFR of the LAD artery of >0.80 was associated with a higher graft failure rate at 1 year and worse patient outcomes at the 3.6-year follow-up.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 26 May 2023:e029134; epub ahead of print</small></div>

<div><h4>Association of Arterial Stiffness and Atherosclerotic Burden With Brain Structural Changes Among Japanese Men.</h4><i>Azahar NM, Yano Y, Kadota A, Shiino A, ... Miura K, SESSA Research Group</i><br /><AbstractText><br /><b>Background:</b><br/>Little is known regarding whether arterial stiffness and atherosclerotic burden are each independently associated with brain structural changes. Simultaneous assessments of both arterial stiffness and atherosclerotic burden in associations with brain could provide insights into the mechanisms of brain structural changes. Methods and Results Using data from the SESSA (Shiga Epidemiological Study of Subclinical Atherosclerosis), we analyzed data among 686 Japanese men (mean [SD] age, 67.9 [8.4] years; range, 46-83 years) free from history of stroke and myocardial infarction. Brachial-ankle pulse wave velocity and coronary artery calcification on computed tomography scans were measured between March 2010 and August 2014. Brain volumes (total brain volume, gray matter, Alzheimer disease signature and prefrontal) and brain vascular damage (white matter hyperintensities) were quantified using brain magnetic resonance imaging from January 2012 through February 2015. In multivariable adjustment models including mean arterial pressure, when brachial-ankle pulse wave velocity and coronary artery calcification were entered into the same models, the β (95% CI) for Alzheimer disease signature volume for each 1-SD increase in brachial-ankle pulse wave velocity was -0.33 (-0.64 to -0.02), and the unstandardized β (95% CI) for white matter hyperintensities for each 1-unit increase in coronary artery calcification was 0.68 (0.05-1.32). Brachial-ankle pulse wave velocity and coronary artery calcification were not statistically significantly associated with total brain and gray matter volumes. <br /><b>Conclusions:</b><br/>Among Japanese men, higher arterial stiffness was associated with lower Alzheimer disease signature volumes, whereas higher atherosclerotic burden was associated with brain vascular damage. Arterial stiffness and atherosclerotic burden may be independently associated with brain structural changes via different pathways.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 26 May 2023:e028586; epub ahead of print</small></div>

<div><h4>Midterm Outcomes in Patients With Aortic Stenosis Treated With Contemporary Balloon-Expandable and Self-Expanding Valves: Does Valve Size Have an Impact on Outcome?</h4><i>Kalogeras K, Jabbour RJ, Pracon R, Kabir T, ... Dalby M, Panoulas V</i><br /><AbstractText><br /><b>Background:</b><br/>No data currently exist comparing the contemporary iterations of balloon-expandable (BE) Edwards SAPIEN 3/Ultra and the self-expanding (SE) Medtronic Evolut PRO/R34 valves. The aim of the study was the comparison of these transcatheter heart valves with emphasis on patients with small aortic annulus. Methods and Results In this retrospective registry, periprocedural outcomes and midterm all-cause mortality were analyzed. A total of 1673 patients (917 SE versus 756 BE) were followed up for a median of 15 months. A total of 194 patients died (11.6%) during follow-up. SE and BE groups showed similar survival at 1 (92.6% versus 90.6%) and 3 (80.3% versus 85.2%) years (<i>P</i><sub>log-rank</sub>=0.136). Compared with the BE group, patients treated with the SE device had lower peak (16.3±8 mm Hg SE versus 21.9±8 mm Hg BE) and mean (8.8±5 mm Hg SE versus 11.5±5 mm Hg BE) gradients at discharge. Conversely, the BE group demonstrated lower rates of at least moderate paravalvular regurgitation postoperatively (5.6% versus 0.7% for SE and BE valves, respectively; <i>P</i><0.001). In patients treated with small transcatheter heart valves (≤26 mm for SE and ≤23 mm for BE; N=284 for SE and N=260 for BE), survival was higher among patients treated with SE valves at both 1 (96.7% SE versus 92.1% BE) and 3 (91.8% SE versus 82.2% BE) years (<i>P</i><sub>log-rank</sub>=0.042). In propensity-matched patients treated with small transcatheter heart valve, there remained a trend for higher survival among the SE group at both 1 (97% SE versus 92.3% BE) and 3 years (91.8% SE versus 78.7% BE), <i>P</i><sub>log-rank</sub>=0.096). <br /><b>Conclusions:</b><br/>Real-world comparison of the latest-generation SE and BE devices demonstrated similar survival up to 3 years\' follow-up. In patients with small transcatheter heart valves, there may be a trend for improved survival among those treated with SE valves.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 26 May 2023:e028038; epub ahead of print</small></div>

<div><h4>Associations of Menstrual Cycle Regularity and Length With Cardiovascular Diseases: A Prospective Study From UK Biobank.</h4><i>Huang C, Lin B, Yuan Y, Li K, ... Huang Y, Zhang H</i><br /><AbstractText><br /><b>Background:</b><br/>The association between menstrual cycle characteristics and cardiovascular outcomes remains unclear. This study was undertaken to evaluate whether menstrual cycle regularity and length throughout the life course are associated with cardiovascular outcomes. Methods and Results This cohort study included 58 056 women who had no cardiovascular disease (CVD) at baseline and reported their menstrual cycle regularity and length. Hazard ratios (HRs) and 95% CIs for CVD events were estimated using Cox proportional hazards models. During the median 11.8 years of follow-up, 1623 incident CVD cases were documented, including 827 incident cases of coronary heart disease, 199 myocardial infarctions, 271 strokes, 174 cases of heart failure, and 393 cases of atrial fibrillations. Compared with women with regular menstrual cycles, the HRs for women with irregular menstrual cycles were 1.19 (95% CI, 1.07-1.31) for CVD events and 1.40 (95% CI, 1.14-1.72) for atrial fibrillation. The multivariable-adjusted HRs for short (≤21 days) or long (35 days) menstrual cycles during follow-up were 1.29 (95% CI, 1.11-1.50) and 1.11 (95% CI, 0.98-1.56) for CVD events, respectively. Similarly, long or short cycle length were more likely to be associated with increased risk of atrial fibrillation (HR, 1.30 [95% CI, 1.01-1.66]; and HR, 1.38 [95% CI, 1.02-1.87]), and short cycle length was more likely to be associated with increased risk of coronary heart disease and myocardial infarction. However, these associations for stroke and heart failure were not significant. <br /><b>Conclusions:</b><br/>Long or short menstrual cycle length was associated with increased risks of CVD and atrial fibrillation but not myocardial infarction, heart failure, or stroke. Short cycle length was associated with a greater risk of coronary heart disease and myocardial infarction.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 24 May 2023:e029020; epub ahead of print</small></div>

<div><h4>Decreased Muscle Strength in Children With Repaired Tetralogy of Fallot: Relation With Exercise Capacity.</h4><i>Eshuis G, van Duinen H, Lelieveld OTHM, Hegeman AK, ... du Marchie Sarvaas GJ, Berger RMF</i><br /><AbstractText><br /><b>Background:</b><br/>The aim of this study is to describe muscle strength in pediatric patients with repaired tetralogy of Fallot compared with healthy peers and to analyze the correlation between muscle strength and peak oxygen uptake, exercise capacity (mL/min). Methods and Results A prospective, cross-sectional study was carried out in the University Medical Center Groningen between March 2016 and December 2019, which included 8 -to-19-year-old patients with repaired tetralogy of Fallot. Exclusion criteria comprised the following: Down syndrome, unstable pulmonary disease and severe scoliosis affecting pulmonary function, neuromuscular disease, and mental or physical limitations that prohibit the execution of the functional tests. Muscle strength was compared with 2 healthy pediatric cohorts from the Northern Netherlands. Handgrip strength, maximal voluntary isometric contraction, and dynamic muscle strength in correlation with peak oxygen uptake, exercise capacity (mL/min) were the main outcomes of the study. The 67 patients with repaired tetralogy of Fallot (42% female; aged 12.9 [interquartile range, 10.0-16.3] years old) were compared with healthy children. The patients showed reduced grip strength (<i>z</i>-score [mean±SD] -1.5±1.2, <i>P</i><0.001), and total muscle strength (<i>z</i>-score -0.9±1.3, <i>P</i><0.001). Dynamic strength (Bruininks-Oseretsky test) was significantly reduced (<i>z</i>-score -0.3±0.8, <i>P</i>=0.001), but running, speed, and agility were normal (<i>z</i>-score 0.1±0.7, <i>P</i>=0.4). Univariate correlation analyses showed strong correlations between absolute peak oxygen uptake, exercise capacity (mL/min), and muscle strength (grip strength <i>r</i>=0.83, total muscle strength <i>r</i>=0.88; <i>P</i><0.001). In multivariate analyses, including correction for age and sex, total muscle strength (B 0.3; <i>P</i>=0.009), and forced vital capacity (B 0.5; <i>P</i>=0.02) correlated with peak oxygen uptake, exercise capacity (mL/min), independent of conventional cardiovascular parameters. <br /><b>Conclusions:</b><br/>Children with repaired tetralogy of Fallot show reduced muscle strength, which strongly correlated with their exercise performance.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 23 May 2023:e027937; epub ahead of print</small></div>

<div><h4>Identification of White Matter Hyperintensities in Routine Emergency Department Visits Using Portable Bedside Magnetic Resonance Imaging.</h4><i>de Havenon A, Parasuram NR, Crawford AL, Mazurek MH, ... Kimberly WT, Sheth KN</i><br /><AbstractText><br /><b>Background:</b><br/>White matter hyperintensity (WMH) on magnetic resonance imaging (MRI) of the brain is associated with vascular cognitive impairment, cardiovascular disease, and stroke. We hypothesized that portable magnetic resonance imaging (pMRI) could successfully identify WMHs and facilitate doing so in an unconventional setting. Methods and Results In a retrospective cohort of patients with both a conventional 1.5 Tesla MRI and pMRI, we report Cohen\'s kappa (κ) to measure agreement for detection of moderate to severe WMH (Fazekas ≥2). In a subsequent prospective observational study, we enrolled adult patients with a vascular risk factor being evaluated in the emergency department for a nonstroke complaint and measured WMH using pMRI. In the retrospective cohort, we included 33 patients, identifying 16 (49.5%) with WMH on conventional MRI. Between 2 raters evaluating pMRI, the interrater agreement on WMH was strong (κ=0.81), and between 1 rater for conventional MRI and the 2 raters for pMRI, intermodality agreement was moderate (κ=0.66, 0.60). In the prospective cohort we enrolled 91 individuals (mean age, 62.6 years; 53.9% men; 73.6% with hypertension), of which 58.2% had WMHs on pMRI. Among 37 Black and Hispanic individuals, the Area Deprivation Index was higher (versus White, 51.8±12.9 versus 37.9±11.9; <i>P</i><0.001). Among 81 individuals who did not have a standard-of-care MRI in the preceding year, we identified WMHs in 43 of 81 (53.1%). <br /><b>Conclusions:</b><br/>Portable, low-field imaging could be useful for identifying moderate to severe WMHs. These preliminary results introduce a novel role for pMRI outside of acute care and the potential role for pMRI to reduce disparities in neuroimaging.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 23 May 2023:e029242; epub ahead of print</small></div>

<div><h4>Effect of Adapted Mindfulness Training in Participants With Elevated Office Blood Pressure: The MB-BP Study: A Randomized Clinical Trial.</h4><i>Loucks EB, Schuman-Olivier Z, Saadeh FB, Scarpaci MM, ... Britton WB, Kronish IM</i><br /><AbstractText><br /><b>Background:</b><br/>Hypertension is a leading risk factor for cardiovascular disease. Despite availability of effective lifestyle and medication treatments, blood pressure (BP) is poorly controlled in the United States. Mindfulness training may offer a novel approach to improve BP control. The objective was to evaluate the effects of Mindfulness-Based Blood Pressure Reduction (MB-BP) versus enhanced usual care control on unattended office systolic BP. Methods and Results Methods included a parallel-group phase 2 randomized clinical trial conducted from June 2017 to November 2020. Follow-up time was 6 months. Outcome assessors and data analyst were blinded to group allocation. Participants had elevated unattended office BP (≥120/80 mm Hg). We randomized 201 participants to MB-BP (n=101) or enhanced usual care control (n=100). MB-BP is a mindfulness-based program adapted for elevated BP. Loss-to-follow-up was 17.4%. The primary outcome was change in unattended office systolic BP at 6 months. A total of 201 participants (58.7% women; 81.1% non-Hispanic White race and ethnicity; mean age, 59.5 years) were randomized. Results showed that MB-BP was associated with a 5.9-mm Hg reduction (95% CI, -9.1 to -2.8 mm Hg) in systolic BP from baseline and outperformed the control group by 4.5 mm Hg at 6 months (95% CI, -9.0 to -0.1 mm Hg) in prespecified analyses. Plausible mechanisms with evidence to be impacted by MB-BP versus control were sedentary activity (-350.8 sitting min/wk [95% CI, -636.5 to -65.1] sitting min/wk), Dietary Approaches to Stop Hypertension diet (0.32 score [95% CI, -0.04 to 0.67]), and mindfulness (7.3 score [95% CI, 3.0-11.6]). <br /><b>Conclusions:</b><br/>A mindfulness-based program adapted for individuals with elevated BP showed clinically relevant reductions in systolic BP compared with enhanced usual care. Mindfulness training may be a useful approach to improve BP. Registration URL: https://www.clinicaltrials.gov; Unique identifiers: NCT03256890 and NCT03859076.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 23 May 2023:e028712; epub ahead of print</small></div>

<div><h4>Long-Term High Level of Insulin Resistance Is Associated With an Increased Prevalence of Coronary Artery Calcification: The CARDIA Study.</h4><i>Ke Z, Huang R, Xu X, Liu W, ... Zhuang X, Zhen L</i><br /><AbstractText><br /><b>Background:</b><br/>Coronary artery calcification (CAC) is a crucial indicator of subclinical atherosclerotic cardiovascular disease. The relationship between long-term insulin resistance (IR) trajectory and CAC has been explored in few studies. Therefore, this study aimed to investigate whether the long-term IR time series of young adults are associated with the incidence of CAC in midlife. Methods and Results In a cohort study comprising 2777 participants from the CARDIA (Coronary Artery Risk Development in Young Adults) study, the homeostasis model assessment for IR was used to measure IR levels, and group-based trajectory modeling was used to fit three 25-year homeostasis model assessments for IR trajectories. Logistic regression was used to estimate the association between the 3 homeostasis model assessments for IR trajectories and CAC events at year 25. The results showed that among 2777 participants (mean age, 50.10±3.58 years; 56.2% women; 46.4% Black), there were 780 incident CAC events after a 25-year follow-up. After full adjustment, the prevalence of CAC was higher in the moderate- (odds ratio [OR], 1.40 [1.10-1.76]) and the high-level homeostasis model assessments for IR trajectories (OR, 1.84 [1.21-2.78]) than in the low-level trajectory. This association was observed in obese individuals despite the negative interaction between IR and different types of obesity (all <i>P</i> interactions >0.05). <br /><b>Conclusions:</b><br/>Our study revealed that young adults with a higher level of IR were more likely to develop CAC in middle age. Furthermore, this association persisted in obese individuals. These findings highlight the importance of identifying subclinical cardiovascular risk factors and implementing primary prevention measures.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 23 May 2023:e028985; epub ahead of print</small></div>

<div><h4>Branched-Chain Amino Acids in Computed Tomography-Defined Adipose Depots and Coronary Artery Disease: A PROMISE Trial Biomarker Substudy.</h4><i>Zhao E, Giamberardino SN, Pagidipati NJ, Voora D, ... Foldyna B, Shah SH</i><br /><AbstractText><br /><b>Background:</b><br/>The interplay between branched-chain amino acid (BCAA) metabolism, an important pathway in adiposity and cardiometabolic disease, and visceral adipose depots such as hepatic steatosis (HS) and epicardial adipose tissue is unknown. We leveraged the PROMISE clinical trial with centrally adjudicated coronary computed tomography angiography imaging to determine relationships between adipose depots, BCAA dysregulation, and coronary artery disease (CAD). Methods and Results The PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) trial randomized 10 003 outpatients with stable chest pain to computed tomography angiography versus standard-of-care diagnostics. For this study, we included 1798 participants with available computed tomography angiography data and biospecimens. Linear and logistic regression were used to determine associations between a molar sum of BCAAs measured by nuclear magnetic resonance spectroscopy with body mass index, adipose traits, and obstructive CAD. Mendelian randomization was then used to determine if BCAAs are in the causal pathway for adipose depots or CAD. The study sample had a mean age of 60 years (SD, 8.0), body mass index of 30.6 (SD, 5.9), and epicardial adipose tissue volume of 57.3 (SD, 21.3) cm<sup>3</sup>/m<sup>2</sup>; 27% had HS, and 14% had obstructive CAD. BCAAs were associated with body mass index (multivariable beta 0.12 per SD increase in BCAA [95% CI, 0.08-0.17]; <i>P</i>=4×10<sup>-8</sup>). BCAAs were also associated with HS (multivariable odds ratio [OR], 1.46 per SD increase in BCAAs [95% CI, 1.28-1.67]; <i>P</i>=2×10<sup>-8</sup>), but BCAAs were associated only with epicardial adipose tissue volume (odds ratio, 1.18 [95% CI, 1.07-1.32]; <i>P</i>=0.002) and obstructive CAD (OR, 1.18 [95% CI, 1.04-1.34]; <i>P</i>=0.009) in univariable models. Two-sample Mendelian randomization did not support the role of BCAAs as within the causal pathways for HS or CAD. <br /><b>Conclusions:</b><br/>BCAAs have been implicated in the pathogenesis of cardiometabolic diseases, and adipose depots have been associated with the risk of CAD. Leveraging a large clinical trial, we further establish the role of dysregulated BCAA catabolism in HS and CAD, although BCAAs did not appear to be in the causal pathway of either disease. This suggests that BCAAs may serve as an independent circulating biomarker of HS and CAD but that their association with these cardiometabolic diseases is mediated through other pathways.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 23 May 2023:e028410; epub ahead of print</small></div>

<div><h4>Sexual Minority Status Disparities in Life\'s Essential 8 and Life\'s Simple 7 Cardiovascular Health Scores: A French Nationwide Population-Based Study.</h4><i>Deraz O, Caceres B, Streed CG, Beach LB, ... Zins M, Empana JP</i><br /><AbstractText><br /><b>Background:</b><br/>A higher burden of cardiovascular disease risk factors has been reported in sexual minority populations. Primordial prevention may therefore be a relevant preventative strategy. The study\'s objectives are to estimate the associations of Life\'s Essential 8 (LE8) and Life\'s Simple 7 (LS7) cardiovascular health scores with sexual minority status. Methods and Results The CONSTANCES is a nationwide French epidemiological cohort study that recruited randomly selected participants older than 18 years in 21 cities. Sexual minority status was based on self-reported lifetime sexual behavior and categorized as lesbian, gay, bisexual, or heterosexual. The LE8 score includes nicotine exposure, diet, physical activity, body mass index, sleep health, blood glucose, blood pressure, and blood lipids. The previous LS7 score included 7 metrics without sleep health. The study included 169 434 cardiovascular disease-free adults (53.64% women; mean age, 45.99 years). Among 90 879 women, 555 were lesbian, 3149 were bisexual, and 84 363 were heterosexual. Among 78 555 men, 2421 were gay, 2748 were bisexual, and 70 994 were heterosexual. Overall, 2812 women and 2392 men declined to answer. In multivariable mixed effects linear regression models, lesbian (β=-0.95 [95% CI, -1.89 to -0.02]) and bisexual (β=-0.78 [95% CI, -1.18 to -0.38]) women had a lower LE8 cardiovascular health score compared with heterosexual women. Conversely, gay (β=2.72 [95% CI, 2.25-3.19]) and bisexual (β=0.83 [95% CI, 0.39-1.27]) men had a higher LE8 cardiovascular health score compared with heterosexual men. The findings were consistent, although of smaller magnitudes for the LS7 score. <br /><b>Conclusions:</b><br/>Cardiovascular health disparities exist in sexual minority adults, particularly lesbian and bisexual women, who may represent a priority population for primordial cardiovascular disease prevention.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 17 May 2023:e028429; epub ahead of print</small></div>

<div><h4>Hospital Procedural Volume and Clinical Outcomes Following Septal Reduction Therapy in Obstructive Hypertrophic Cardiomyopathy.</h4><i>Altibi AM, Ghanem F, Zhao Y, Elman M, ... Song HK, Masri A</i><br /><AbstractText><br /><b>Background:</b><br/>Prior national data showed a substantial in-hospital mortality in septal myectomy (SM) with an inverse volume-outcomes relationship. This study sought to assess the contemporary outcomes of septal reduction therapy and volume-outcome relationship in obstructive hypertrophic cardiomyopathy. Methods and Results All septal reduction therapy admissions between 2010 to 2019 in the United States were analyzed using the National Readmission Databases. Hospitals were stratified into tertiles of low-, medium-, and high-volume based on annualized procedural volume of alcohol septal ablation and SM. Of 19 007 patients with obstructive hypertrophic cardiomyopathy who underwent septal reduction therapy, 12 065 (63%) had SM. Two-thirds of hospitals performed ≤5 SM or alcohol septal ablation annually. In all SM encounters, 482 patients (4.0%) died in-hospital post-SM. In-hospital mortality was <1% in 1505 (88.4%) hospitals, 1% to 10% in 30 (1.8%) hospitals, and ≥10% in 167 (9.8%) hospitals. There were 63 (3.7%) hospitals (averaging 2.2 SM cases/year) with 100% in-hospital mortality. Post-SM (in low-, medium-, and high-volume centers, respectively), in-hospital mortality (5.7% versus 3.9% versus 2.4%, <i>P</i>=0.003; adjusted odds ratio [aOR], 2.86 [95% CI, 1.70-4.80], <i>P</i>=0.001), adverse in-hospital events (21.30% versus 18.0% versus 12.6%, <i>P</i>=0.001; aOR, 1.88 [95% CI, 1.45-2.43], <i>P</i>=0.001), and 30-day readmission (17.1% versus 12.9% versus 9.7%, <i>P</i>=0.001; adjusted hazard ratio, 1.53 [95% CI, 1.27-1.96], <i>P</i>=0.001) were significantly higher in low- versus high-volume hospitals. For alcohol septal ablation, the incidence of in-hospital death and all other outcomes did not differ by hospital volume. <br /><b>Conclusions:</b><br/>In-hospital SM mortality was 4% with an inverse volume-mortality relationship. Mortality post-alcohol septal ablation was similar across all volume tertiles. Morbidity associated with SM was substantial across all volume tertiles.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 16 May 2023; 12:e028693</small></div>

<div><h4>Cost Implications of Left Atrial Appendage Occlusion During Cardiac Surgery: A Cost Analysis of the LAAOS III Trial.</h4><i>Eqbal A, Tong W, Lamy A, Belley-Cote E, ... Whitlock RP, LAAOS III Investigators</i><br /><AbstractText><br /><b>Background:</b><br/>The LAAOS III (Left Atrial Appendage Occlusion Study) clinical trial demonstrated that concomitant left atrial appendage (LAA) occlusion leads to a lower risk of ischemic stroke or systemic embolism compared with no occlusion in participants with atrial fibrillation and a CHA<sub>2</sub>DS<sub>2</sub>-VASc score of ≥2 undergoing cardiac surgery for another indication. We report the cost implications of concomitant LAA occlusion during cardiac surgery. Methods and Results Using LAAOS III data, we compared the costs (in US dollars) associated with LAA occlusion to no occlusion from the perspective of the Centers for Medicare and Medicaid Services. We calculated the average cost per participant during the trial by applying Medicare reimbursement costs to cardiovascular events for all trial participants. We conducted sensitivity analyses, varying the cost of stroke ±25% and occlusion technique use. Cost neutrality was defined as a mean cost difference within ±5% of the cost per participant in the no-occlusion group. Total study cost per participant was $3878 in the LAA occlusion group and $4490 in the no-occlusion group, a mean difference of -$612 (95% CI, -$1276 to $45). The main drivers of cost savings were fewer stroke events during the trial (mean difference of -$1021). In sensitivity analyses, LAA occlusion was cost saving for suture and stapler techniques but more expensive with closure device. <br /><b>Conclusions:</b><br/>Concomitant LAA occlusion was cost saving for participants in LAAOS III. Our findings support concomitant LAA occlusion as an economically dominant strategy for patients with atrial fibrillation and a CHA<sub>2</sub>DS<sub>2</sub>-VASc score of ≥2 undergoing cardiac surgery.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 16 May 2023; 12:e028716</small></div>

<div><h4>Risk Factor Interactions, Non-High-Density Lipoprotein Cholesterol to Apolipoprotein B Ratio, and Severity of Coronary Arteriosclerosis in South Asian Individuals: An Observational Cohort Study.</h4><i>Molina CR, Mathur A, Soykan C, Sathe A, Kunhiraman L</i><br /><AbstractText><br /><b>Background:</b><br/>South Asian individuals are at higher risk for arteriosclerotic cardiovascular disease and diabetes. The factors associated with arteriosclerotic cardiovascular disease severity and their interactions are unknown. Methods and Results This is a retrospective cohort study of the first 1162 South Asian participants enrolled in the South Asian Heart Center\'s AIM to Prevent Program who completed noncontrast coronary computed tomography scans. Using machine-learning algorithms, we identified and modeled the interaction of predictor variables with coronary artery calcification (CAC) severity in South Asian individuals. Anthropometric, laboratory, demographic, and lifestyle predictor variables were analyzed using continuous boosted regression trees to model the relationship with and in between predictor variables and CAC. Participants with CAC were older, predominately men, had smoking history, had personal histories of diabetes, hypertension, and hypercholesterolemia, and had family histories of coronary artery disease. Insulin, body mass index, blood pressure, fasting blood sugar, hemoglobin A1c, and waist-to-height ratio were associated with CAC but not low-density lipoprotein cholesterol or lipoprotein (a). The arteriosclerotic cardiovascular disease score failed to classify individuals. Only age, body mass index, non-high-density lipoprotein cholesterol/apolipoprotein B ratio, smoking risk, fasting blood sugar, and diastolic blood pressure were predictive, explaining 30.3% of CAC severity. A non-high-density lipoprotein cholesterol/apolipoprotein B ratio of 1.4 or less markedly increased coronary calcification. <br /><b>Conclusions:</b><br/>Our findings highlight factors associated with dysmetabolism and cholesterol-depleted non-high-density lipoprotein cholesterol particles with coronary arteriosclerosis, possibly explaining the dual epidemics of diabetes and arteriosclerotic cardiovascular disease in this population. Markers of glucose dysmetabolism and the non-high-density lipoprotein cholesterol to apolipoprotein B ratio should become the focus of assessment for cardiovascular risk in South Asian individuals, with prevention strategies directed at improving glucose metabolic health.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 16 May 2023; 12:e027697</small></div>

<div><h4>Feasibility of Lipid Screening During First Trimester of Pregnancy to Identify Women at Risk of Severe Dyslipidemia.</h4><i>Golwala S, Dolin CD, Nemiroff R, Soffer D, ... Jacoby D, Lewey J</i><br /><AbstractText><br /><b>Background:</b><br/>Dyslipidemia is an important risk factor for atherosclerotic cardiovascular disease, especially when disease presents at a young age. Despite national screening guidelines to perform a lipid profile test in children and young adults, many reproductive-age women have not undergone lipid screening. Our objective was to assess the feasibility of lipid screening during the first trimester of pregnancy as a strategy to increase lipid screening rates among women receiving prenatal care. Methods and Results A nonfasting lipid panel was incorporated into routine prenatal care among obstetricians at a single academic clinic. Educational materials and a clinical referral pathway were developed for patients with abnormal results. Over 6 months, 445 patients had a first prenatal care visit. Of the 358 patients who completed laboratory testing, 236 (66%) patients completed lipid testing. Overall, 59 (25%) patients had abnormal results. One patient with previously undiagnosed suspected familial hypercholesterolemia was identified. Barriers to ordering lipid tests included the burden of reviewing additional laboratory results and uncertainty about patient counseling. <br /><b>Conclusions:</b><br/>Implementation of nonfasting lipid screening as part of routine prenatal care during the first trimester is feasible and may play a crucial role in timely diagnosis and management of lipid disorders in women of reproductive age. Future work should focus on optimizing health system workflow to minimize burden on clinical staff and facilitate follow-up with appropriate specialists.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 16 May 2023; 12:e028626</small></div>

<div><h4>Impact of Diabetes on Outcomes in Patients Hospitalized With Acute Myocardial Infarction: Insights From the Atherosclerosis Risk in Communities Study Community Surveillance.</h4><i>Jain V, Qamar A, Matsushita K, Vaduganathan M, ... Arora S, Caughey MC</i><br /><AbstractText><br /><b>Background:</b><br/>Diabetes is associated with increased risk of acute myocardial infarction (AMI). The demographic trends, clinical presentation, management, and outcomes of patients with diabetes who are hospitalized with AMI have not been recently reported. Methods and Results The ARIC (Atherosclerosis Risk in Communities) study conducted hospital surveillance of AMI in 4 US communities. AMI was classified by physician review using a validated algorithm. Medications and procedures were abstracted from the medical record. From 2000 to 2014, 21 094 weighted hospitalizations for AMI were sampled. The prevalence of diabetes steadily increased, from 35% to 41% to 43% (<i>P</i>-trend<0.0001) across 2000 to 2004, 2005 to 2009, and 2010 to 2014, respectively. Patients with diabetes were older (61 versus 59 years of age), more often Black (44% versus 31%), and more commonly women (42% versus 34%). The burden of cardiovascular comorbidities was higher with diabetes and increased temporally. Patients with diabetes less often presented with ST-segment elevation (9% versus 17%) or acute chest pain (72% versus 80%), and had higher mean GRACE (Global Registry of Acute Coronary Syndrome) score (123 versus 109), Thrombolysis in Myocardial Ischemia (TIMI) score (4.3 versus 4.0), and Killip class (1.9 versus 1.5). Patients with diabetes had a lower adjusted probability of receiving aspirin (relative probability, 0.95 [95% CI, 0.91-0.99]), nonaspirin antiplatelets (0.93 [95% CI, 0.86-0.99]), coronary angiography (0.85 [95% CI, 0.78-0.92]), and coronary revascularization (0.85 [95% CI, 0.76-0.92]). Diabetes was associated with a 52% higher hazard of all-cause 1-year mortality (hazard ratio, 1.52 [95% CI, 1.23-1.89]). <br /><b>Conclusions:</b><br/>Diabetes is associated with higher risk of death in patients hospitalized with AMI, highlighting the need for adherence to evidence-based therapies in this high-risk population.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 16 May 2023; 12:e028923</small></div>

<div><h4>Association Between Postresuscitation 12-Lead ECG Features and Early Mortality After Out-of-Hospital Cardiac Arrest: A Post Hoc Subanalysis of the PEACE Study.</h4><i>Gentile FR, Baldi E, Klersy C, Schnaubelt S, ... Auricchio A, Savastano S</i><br /><AbstractText><br /><b>Background:</b><br/>Once the return of spontaneous circulation after out-of-hospital cardiac arrest is achieved, a 12-lead ECG is strongly recommended to identify candidates for urgent coronary angiography. ECG has no apparent role in mortality risk stratification. We aimed to assess whether ECG features could be associated with 30-day survival in patients with out-of-hospital cardiac arrest. Methods and Results All the post-return of spontaneous circulation ECGs from January 2015 to December 2018 in 3 European centers (Pavia, Lugano, and Vienna) were collected. Prehospital data were collected according to the Utstein style. A total of 370 ECGs were collected: 287 men (77.6%) with a median age of 62 years (interquartile range, 53-70 years). After correction for the return of spontaneous circulation-to-ECG time, age >62 years (hazard ratio [HR], 1.78 [95% CI, 1.21-2.61]; <i>P</i>=0.003), female sex (HR, 1.5 [95% CI, 1.05-2.13]; <i>P</i>=0.025), QRS wider than 120 ms (HR, 1.64 [95% CI, 1.43-1.87]; <i>P</i><0.001), the presence of a Brugada pattern (HR, 1.49 [95% CI, 1.39-1.59]; <i>P</i><0.001), and the presence of ST-segment elevation in >1 segment (HR, 1.75 [95% CI, 1.59-1.93]; <i>P</i><0.001) were independently associated with 30-day mortality. A score ranging from 0 to 26 was created, and by dividing the population into 3 tertiles, 3 classes of risk were found with significantly different survival rate at 30 days (score 0-4, 73%; score 5-7, 66%; score 8-26, 45%). <br /><b>Conclusions:</b><br/>The post-return of spontaneous circulation ECG can identify patients who are at high risk of mortality after out-of-hospital cardiac arrest earlier than other forms of prognostication. This provides important risk stratification possibilities in postcardiac arrest care that could help to direct treatments and improve outcomes in patients with out-of-hospital cardiac arrest.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 16 May 2023; 12:e027923</small></div>

<div><h4>Magnetic Resonance Imaging and Computed Tomography for the Noninvasive Assessment of Arterial Aging: A Review by the VascAgeNet COST Action.</h4><i>Bianchini E, Lønnebakken MT, Wohlfahrt P, Piskin S, ... Alastruey J, Guala A</i><br /><AbstractText>Magnetic resonance imaging and computed tomography allow the characterization of arterial state and function with high confidence and thus play a key role in the understanding of arterial aging and its translation into the clinic. Decades of research into the development of innovative imaging sequences and image analysis techniques have led to the identification of a large number of potential biomarkers, some bringing improvement in basic science, others in clinical practice. Nonetheless, the complexity of some of these biomarkers and the image analysis techniques required for their computation hamper their widespread use. In this narrative review, current biomarkers related to aging of the aorta, their founding principles, the sequence, and postprocessing required, and their predictive values for cardiovascular events are summarized. For each biomarker a summary of reference values and reproducibility studies and limitations is provided. The present review, developed in the COST Action VascAgeNet, aims to guide clinicians and technical researchers in the critical understanding of the possibilities offered by these advanced imaging modalities for studying the state and function of the aorta, and their possible clinically relevant relationships with aging.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 16 May 2023; 12:e027414</small></div>

<div><h4>Lipoprotein(a) Genotype Influences the Clinical Diagnosis of Familial Hypercholesterolemia.</h4><i>Olmastroni E, Gazzotti M, Averna M, Arca M, ... Casula M, LIPIGEN Study Group *</i><br /><AbstractText><br /><b>Background:</b><br/>Evidence suggests that <i>LPA</i> risk genotypes are a possible contributor to the clinical diagnosis of familial hypercholesterolemia (FH). This study aimed at determining the prevalence of <i>LPA</i> risk variants in adult individuals with FH enrolled in the Italian LIPIGEN (Lipid Transport Disorders Italian Genetic Network) study, with (FH/M+) or without (FH/M-) a causative genetic variant. Methods and Results An lp(a) [lipoprotein(a)] genetic score was calculated by summing the number risk-increasing alleles inherited at rs3798220 and rs10455872 variants. Overall, in the 4.6% of 1695 patients with clinically diagnosed FH, the phenotype was not explained by a monogenic or polygenic cause but by genotype associated with high lp(a) levels. Among 765 subjects with FH/M- and 930 subjects with FH/M+, 133 (17.4%) and 95 (10.2%) were characterized by 1 copy of either rs10455872 or rs3798220 or 2 copies of either rs10455872 or rs3798220 (lp(a) score ≥1). Subjects with FH/M- also had lower mean levels of pretreatment low-density lipoprotein cholesterol than individuals with FH/M+ (<i>t</i> test for difference in means between FH/M- and FH/M+ groups <0.0001); however, subjects with FH/M- and lp(a) score ≥1 had higher mean (SD) pretreatment low-density lipoprotein cholesterol levels (223.47 [50.40] mg/dL) compared with subjects with FH/M- and lp(a) score=0 (219.38 [54.54] mg/dL for), although not statistically significant. The adjustment of low-density lipoprotein cholesterol levels based on lp(a) concentration reduced from 68% to 42% the proportion of subjects with low-density lipoprotein cholesterol level ≥190 mg/dL (or from 68% to 50%, considering a more conservative formula). <br /><b>Conclusions:</b><br/>Our study supports the importance of measuring lp(a) to perform the diagnosis of FH appropriately and to exclude that the observed phenotype is driven by elevated levels of lp(a) before performing the genetic test for FH.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 16 May 2023; 12:e029223</small></div>

<div><h4>Positive Airway Pressure Adherence and Health Care Resource Utilization in Patients With Obstructive Sleep Apnea and Heart Failure With Reduced Ejection Fraction.</h4><i>Malhotra A, Cole KV, Malik AS, Pépin JL, ... Somers VK, medXcloud group *</i><br /><AbstractText><br /><b>Background:</b><br/>Obstructive sleep apnea (OSA) is a common comorbidity in patients with heart failure, although current evidence is equivocal regarding the potential benefits of treating OSA with positive airway pressure (PAP) therapy in patients with heart failure. This study assessed the impact of adherence to PAP therapy on health care resource utilization in patients with OSA and heart failure with reduced ejection fraction. Methods and Results Administrative insurance claims data linked with objective PAP therapy use data from patients with OSA and heart failure with reduced ejection fraction were used to determine associations between PAP adherence and a composite outcome of hospitalizations and emergency room visits. One-year PAP adherence was based on an adapted US Medicare definition. Propensity score methods were used to create groups with similar characteristics across PAP adherence levels. The study cohort included 3182 patients (69.9% male, mean age 59.7 years); 39% were considered adherent to PAP therapy (29% intermediate adherent, 31% nonadherent). One year after PAP initiation, adherent patients had fewer composite visits than matched nonadherent patients, driven by a 24% reduction in emergency room visits for adherent patients. Composite visit costs were lower in adherent versus nonadherent patients ($3500 versus $5879, <i>P</i>=0.031), although total health care costs were not statistically different ($13 028 versus $14 729, <i>P</i>=0.889). <br /><b>Conclusions:</b><br/>PAP therapy adherence in patients with OSA with heart failure with reduced ejection fraction was associated with a reduction in health care resource utilization. This suggests that greater emphasis should be placed on diagnosing and effectively treating OSA with PAP in patients with heart failure with reduced ejection fraction.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 16 May 2023; 12:e028732</small></div>

<div><h4>Association Between Spotty Calcification in Nonstenosing Extracranial Carotid Artery Plaque and Ipsilateral Ischemic Stroke.</h4><i>Homssi M, Vora A, Zhang C, Baradaran H, Kamel H, Gupta A</i><br /><AbstractText><br /><b>Background:</b><br/>Small spotty calcifications in the coronary arteries are associated with an increased risk of myocardial infarction. We examined the association between spotty calcifications near the carotid bifurcations and ipsilateral ischemic stroke in patients with <50% luminal stenosis of the extracranial carotid arteries. Methods and Results We used data from the CAESAR (Cornell Acute Stroke Academic Registry), a prospective registry of all patients with acute ischemic stroke admitted to our institution. We included patients who met criteria for cryptogenic stroke and underwent computed tomography angiography and brain magnetic resonance imaging. Patients with extracranial carotid artery stenosis ≥50% and patients with posterior or bilateral anterior circulation infarcts were excluded. We examined the carotid bifurcations for spotty calcifications, defined as ≥1 contiguous regions of luminal calcification ≤3 mm along the long axis of the vessel. We also measured low-density plaque and maximum plaque thickness. The eligible cohort consisted of 117 patients with a mean age of 66.7±1.65 years with a median National Institute of Health Stroke Scale stroke at the time of arrival of 6 (range, 3-13). The number of spotty calcifications present within a low-density plaque was significantly associated with ipsilateral infarction (0.3±0.8 versus 0.1±0.4, <i>P</i>=0.02). Maximum plaque thickness was also significantly associated with ipsilateral infarction (1.4 mm ±1.5 versus 1.0 mm ±1.1, <i>P</i>=0.004). <br /><b>Conclusions:</b><br/>Spotty calcifications associated with low-density plaque and maximum plaque thickness were associated with ipsilateral ischemic stroke in patients with nonstenotic carotid atherosclerosis, suggesting a role as imaging markers of high-risk plaque.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 16 May 2023; 12:e028525</small></div>

<div><h4>Identification of Optical Coherence Tomography-Defined Coronary Plaque Erosion by Preprocedural Computed Tomography Angiography.</h4><i>Nagamine T, Hoshino M, Yonetsu T, Sugiyama T, ... Sasano T, Kakuta T</i><br /><AbstractText><br /><b>Background:</b><br/>A previous coronary computed tomography (CT) angiographic study failed to discriminate optical coherence tomography-defined intact fibrous cap culprit lesions (IFC group) from those with ruptured fibrous caps (RFC group) in patients with coronary artery disease. This study aimed to evaluate the diagnostic efficacy of preprocedural coronary CT imaging in identifying subsequently performed optical coherence tomography-defined plaque rupture or erosion at culprit lesions in patients with non-ST-segment-elevation acute myocardial infarction. Methods and Results This study used data from 2 recently published studies that tested the hypothesis that coronary CT angiography (CCTA) before percutaneous coronary intervention may provide diagnostic information on the high-risk atherosclerotic burden in patients with non-ST-segment-elevation acute myocardial infarction. In the analysis of 186 patients, optical coherence tomography identified 106 RFC plaques and 80 IFC plaques as the culprit lesions. On CT, the prevalence of low-attenuation plaque, positive remodeling, napkin-ring sign, and spotty calcification were all significantly lower in the IFC group. The culprit vessel pericoronary adipose tissue inflammation and coronary artery calcium scores were significantly lower in the IFC group than in the RFC group. The absence of low-attenuation plaque, napkin-ring sign, zero coronary artery calcium, and low pericoronary adipose tissue inflammation were independent predictors of IFC. When stratified into 5 subgroups according to the number of these 4 CT factors, the prevalence of IFC was 8.3%, 20.8%, 44.6%, 75.6%, and 100% (<i>P</i><0.001), respectively. <br /><b>Conclusions:</b><br/>Preprocedural comprehensive coronary CT imaging, including coronary artery calcium and pericoronary adipose tissue inflammation assessment, can accurately and noninvasively identify optical coherence tomography-defined IFC or RFC culprit lesions.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 16 May 2023; 12:e029239</small></div>

<div><h4>Association of Normal Serum Uric Acid Level and Cardiovascular Disease in People Without Risk Factors for Cardiac Diseases in China.</h4><i>Tian X, Wang P, Chen S, Zhang Y, ... Wu S, Wang A</i><br /><AbstractText><br /><b>Background:</b><br/>Healthy individuals with normal level of serum uric acid (SUA) may not be truly at the lowest risk of cardiovascular disease (CVD). This study aimed to assess the association of SUA levels with CVD and its subtypes in people without CVD risk factors and determine a suitable target of SUA to prevent CVD. Methods and Results We enrolled 25 284 participants who were free of CVD, absent of CVD risk factors, and with an SUA level between 180 and 359 μmol/L (3-6 mg/dL) at baseline from the Kailuan study. Cox proportional hazards models were applied to calculated adjusted hazard ratio (HR) and 95% CI for the risk of CVD and its subtypes. During a median follow-up of 12.97 years (interquartile range, 12.68-13.16 years), we identified 1007 cases of CVD. There was an increase in the risk of incident CVD with increasing SUA levels (<i>P</i><sub>trend</sub>=0.0011). Compared with participants with SUA levels of 180 to 239 μmol/L (3-4 mg/dL), the HR of CVD was 1.12 (95% CI, 0.96-1.31) and 1.28 (95% CI, 1.08-1.52) for SUA levels of 240 to 299 μmol/L (4-5 mg/dL) and 300 to 359 μmol/L (5-6 mg/dL), respectively. A multivariable-adjusted spline regression model showed a J-shaped association between SUA and the risk of CVD. Similar results were observed for stroke and myocardial infarction. <br /><b>Conclusions:</b><br/>The risk of incident CVD increased with elevating SUA levels among individuals without hyperuricemia or other traditional CVD risk factors. These findings highlighted the importance of primordial prevention for SUA level increase along with other traditional CVD risk factors.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 16 May 2023; 12:e029633</small></div>

<div><h4>Hemodynamic Effects of Ketone Bodies in Patients With Pulmonary Hypertension.</h4><i>Nielsen R, Christensen KH, Gopalasingam N, Berg-Hansen K, ... Bøtker HE, Mellemkjær S</i><br /><AbstractText><br /><b>Background:</b><br/>Pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) are debilitating diseases with a high mortality. Despite emerging treatments, pulmonary vascular resistance frequently remains elevated. However, the ketone body 3-hydroxybutyrate (3-OHB) may reduce pulmonary vascular resistance in these patients. Hence, the aim was to assess the hemodynamic effects of 3-OHB in patients with PAH or CTEPH. Methods and Results We enrolled patients with PAH (n=10) or CTEPH (n=10) and residual pulmonary hypertension. They received 3-OHB infusion and placebo (saline) for 2 hours in a randomized crossover study. Invasive hemodynamic and echocardiography measurements were performed. Furthermore, we investigated the effects of 3-OHB on the right ventricle of isolated hearts and isolated pulmonary arteries from Sprague-Dawley rats. Ketone body infusion increased circulating 3-OHB levels from 0.5±0.5 to 3.4±0.7 mmol/L (<i>P</i><0.001). Cardiac output improved by 1.2±0.1 L/min (27±3%, <i>P</i><0.001), and right ventricular annular systolic velocity increased by 1.4±0.4 cm/s (13±4%, <i>P</i>=0.002). Pulmonary vascular resistance decreased by 1.3±0.3 Wood units (18%±4%, <i>P</i><0.001) with no significant difference in response between patients with PAH and CTEPH. In the rat studies, 3-OHB administration was associated with decreased pulmonary arterial tension compared with saline administration (maximal relative tension difference: 12±2%, <i>P</i><0.001) and had no effect on right ventricular systolic pressures (<i>P</i>=0.63), whereas pressures rose at a slower pace (dP/dtmax, <i>P</i>=0.02). <br /><b>Conclusions:</b><br/>In patients with PAH or CTEPH, ketone body infusion improves cardiac output and decreases pulmonary vascular resistance. Experimental rat studies support that ketone bodies relax pulmonary arteries. Long-term studies are warranted to assess the clinical role of hyperketonemia. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04615754.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 16 May 2023; 12:e028232</small></div>

<div><h4>Sodium-Glucose Cotransporter-2 Inhibitor Prevents Stroke in Patients With Diabetes and Atrial Fibrillation.</h4><i>Chang SN, Chen JJ, Huang PS, Wu CK, ... Hwang JJ, Tsai CT</i><br /><AbstractText><br /><b>Background:</b><br/>Atrial fibrillation (AF) is associated with increasing risk of thromboembolic or ischemic stroke. The CHA<sub>2</sub>DS<sub>2</sub>-VASc score is a well-established predictor of AF stroke. Patients with AF have an increased risk of stroke if they have diabetes. Use of sodium-glucose cotransporter-2 inhibitor (SGLT2i) has been shown to be associated with favorable cardiovascular outcomes in patients with diabetes. It was unknown whether use of SGLT2i decreased stroke risk in patients with AF who have diabetes. Methods and Results A total of 9116 patients with AF and diabetes from the National Taiwan University historical cohort were longitudinally followed up for 5 years (January 2016-December 2020). The risk of stroke related to SGLT2i use was evaluated by Cox model, adjusting CHA<sub>2</sub>DS<sub>2</sub>-VASc score in the propensity score-matched population with 474 SGLT2i users and 3235 nonusers. Adverse thromboembolic end points during follow-up were defined as ischemic stroke. The mean age was 73.2±10.5 years, and 61% of patients were men. There were no significant differences of baseline characteristics between users and nonusers of SGLT2i, including CHA<sub>2</sub>DS<sub>2</sub>-VASc score in the propensity score-matched population. The stroke rate was 3.4% (95% CI, 2.8-4.2) patient-years in SGLT2i users and 4.3% (95% CI, 4.0-4.6) in nonusers (<i>P</i>=0.021). SGLT2i users had a 20% reduction of stroke (hazard ratio, 0.80 [95% CI, 0.64-0.99]; <i>P</i>=0.043) after adjustment for the CHA<sub>2</sub>DS<sub>2</sub>-VASc score. <br /><b>Conclusions:</b><br/>Use of SGLT2i was associated with a lower stroke risk in patients with diabetes and AF, and it may be considered to escalate SGLT2i to the first-line treatment in patients with diabetes and AF.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 16 May 2023; 12:e027764</small></div>

<div><h4>Progressive Cardiac Metabolic Defects Accompany Diastolic and Severe Systolic Dysfunction in Spontaneously Hypertensive Rat Hearts.</h4><i>Li J, Minczuk K, Huang Q, Kemp BA, ... Kundu BK, Keller SR</i><br /><AbstractText><br /><b>Background:</b><br/>Cardiac metabolic abnormalities are present in heart failure. Few studies have followed metabolic changes accompanying diastolic and systolic heart failure in the same model. We examined metabolic changes during the development of diastolic and severe systolic dysfunction in spontaneously hypertensive rats (SHR). Methods and Results We serially measured myocardial glucose uptake rates with dynamic 2-[<sup>18</sup>F] fluoro-2-deoxy-d-glucose positron emission tomography in vivo in 9-, 12-, and 18-month-old SHR and Wistar Kyoto rats. Cardiac magnetic resonance imaging determined systolic function (ejection fraction) and diastolic function (isovolumetric relaxation time) and left ventricular mass in the same rats. Cardiac metabolomics was performed at 12 and 18 months in separate rats. At 12 months, SHR hearts, compared with Wistar Kyoto hearts, demonstrated increased isovolumetric relaxation time and slightly reduced ejection fraction indicating diastolic and mild systolic dysfunction, respectively, and higher (versus 9-month-old SHR decreasing) 2-[<sup>18</sup>F] fluoro-2-deoxy-d-glucose uptake rates (Ki). At 18 months, only few SHR hearts maintained similar abnormalities as 12-month-old SHR, while most exhibited severe systolic dysfunction, worsening diastolic function, and markedly reduced 2-[<sup>18</sup>F] fluoro-2-deoxy-d-glucose uptake rates. Left ventricular mass normalized to body weight was elevated in SHR, more pronounced with severe systolic dysfunction. Cardiac metabolite changes differed between SHR hearts at 12 and 18 months, indicating progressive defects in fatty acid, glucose, branched chain amino acid, and ketone body metabolism. <br /><b>Conclusions:</b><br/>Diastolic and severe systolic dysfunction in SHR are associated with decreasing cardiac glucose uptake, and progressive abnormalities in metabolite profiles. Whether and which metabolic changes trigger progressive heart failure needs to be established.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 16 May 2023; 12:e026950</small></div>

<div><h4>Maternal and Fetal Outcomes in Pregnant Patients With Mechanical and Bioprosthetic Heart Valves.</h4><i>Ng AP, Verma A, Sanaiha Y, Williamson CG, Afshar Y, Benharash P</i><br /><AbstractText><br /><b>Background:</b><br/>Guidelines for choice of prosthetic heart valve in people of reproductive age are not well established. Although biologic heart valves (BHVs) have risk of deterioration, mechanical heart valves (MHVs) require lifelong anticoagulation. This study aimed to characterize the association of prosthetic valve type with maternal and fetal outcomes in pregnant patients. Methods and Results Using the 2008 to 2019 National Inpatient Sample, we identified all adult patients hospitalized for delivery with prior heart valve implantation. Multivariable regressions were used to analyze the primary outcome, major adverse cardiovascular events, and secondary outcomes, including maternal and fetal complications, length of stay, and costs. Among 39 871 862 birth hospitalizations, 4152 had MHVs and 874 had BHVs. Age, comorbidities, and cesarean birth rates were similar between patients with MHVs and BHVs. The presence of a prosthetic valve was associated with over 22-fold increase in likelihood of major adverse cardiovascular events (MHV: adjusted odds ratio, 22.1 [95% CI, 17.3-28.2]; BHV: adjusted odds ratio, 22.5 [95% CI, 13.9-36.5]) as well as increased duration of stay and hospitalization costs. However, patients with MHVs and BHVs had no significant difference in the odds of any maternal outcome, including major adverse cardiovascular events, hypertensive disease of pregnancy, and ante/postpartum hemorrhage. Similarly, fetal complications were more likely in patients with valve prostheses, including a 4-fold increase in odds of stillbirth, but remained comparable between MHVs and BHVs. <br /><b>Conclusions:</b><br/>Patients hospitalized for delivery with prior valve replacement carry substantial risk of adverse maternal and fetal events, regardless of valve type. Our findings reveal comparable outcomes between MHVs and BHVs.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 16 May 2023; 12:e028653</small></div>

<div><h4>Association Between Life\'s Simple 7 and Biomarkers of Cardiovascular Disease: Aldosterone, Interleukin-6, C-Reactive Protein.</h4><i>Yuan YE, Haas AV, Williams GH, Taylor H, Seely EW, Adler GK</i><br /><AbstractText><br /><b>Background:</b><br/>To promote ideal cardiovascular health, the American Heart Association recommends adhering to Life\'s Simple 7 (LS7)-achieving healthy targets for body mass index, physical activity, dietary intake, blood pressure, fasting plasma glucose, and cholesterol, along with smoking abstinence. Poorer achievement of LS7 (lower score) has been associated with the development of hypertension and cardiovascular disease. However, less is known about the associations between LS7 and specific biomarkers linked to cardiovascular health: aldosterone, CRP (C-reactive protein), and IL-6 (interleukin-6). Methods and Results We analyzed 379 individuals (age 18-66 years) from the HyperPATH (International Hypertensive Pathotype), who were maintained on ≥200 mEq of sodium daily for 1 week. We calculated a 14-point summative LS7 score according to participants\' baseline data. Based on the range of LS7 score in this population (3-14), we classified participants as \"inadequate\" (3-6), \"average\" (7-10), and \"optimal\" (11-14). Regression analyses found that a higher LS7 score group was associated with lower levels of serum and urinary aldosterone (<i>P</i><sub>trend</sub><0.001 and <i>P</i><sub>trend</sub>=0.001, respectively), lower plasma renin activity (<i>P</i><sub>trend</sub><0.001), and a blunted increase in serum aldosterone with angiotensin II infusion (<i>P</i><sub>trend</sub>=0.023). Being in the \"optimal\" LS7 score group was associated with lower serum CRP (<i>P</i><sub>trend</sub>=0.001) and IL-6 (<i>P</i><sub>trend</sub>=0.001). <br /><b>Conclusions:</b><br/>A higher LS7 score was associated with a lower activity of the renin-angiotensin-aldosterone system and lower levels of the inflammatory markers CRP and IL-6. These findings offer a possible link between ideal cardiovascular health targets and biomarkers known to play a central role in the development of cardiovascular disease.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 09 May 2023:e028718; epub ahead of print</small></div>

<div><h4>Peptidase Inhibitor 16 Attenuates Left Ventricular Injury and Remodeling After Myocardial Infarction by Inhibiting the HDAC1-Wnt3a-β-Catenin Signaling Axis.</h4><i>Wang L, Du A, Lu Y, Zhao Y, ... Sun W, Kong X</i><br /><AbstractText><br /><b>Background:</b><br/>Myocardial infarction (MI) is a cardiovascular disease with high morbidity and mortality. PI16 (peptidase inhibitor 16), as a secreted protein, is highly expressed in heart diseases such as heart failure. However, the functional role of PI16 in MI is unknown. This study aimed to investigate the role of PI16 after MI and its underlying mechanisms. Methods and Results PI16 levels after MI were measured by enzyme-linked immunosorbent assay and immunofluorescence staining, which showed that PI16 was upregulated in the plasma of patients with acute MI and in the infarct zone of murine hearts. PI16 gain- and loss-of-function experiments were used to investigate the potential role of PI16 after MI. In vitro, PI16 overexpression inhibited oxygen-glucose deprivation-induced apoptosis in neonatal rat cardiomyocytes, whereas knockdown of PI16 exacerbated neonatal rat cardiomyocyte apoptosis. In vivo, left anterior descending coronary artery ligation was performed on PI16 transgenic mice, PI16 knockout mice, and their littermates. PI16 transgenic mice showed decreased cardiomyocyte apoptosis at 24 hours after MI and improved left ventricular remodeling at 28 days after MI. Conversely, PI16 knockout mice showed aggravated infract size and remodeling. Mechanistically, PI16 downregulated Wnt3a (wingless-type MMTV integration site family, member 3a)/β-catenin pathways, and the antiapoptotic role of PI16 was reversed by recombinant Wnt3a in oxygen-glucose deprivation-induced neonatal rat cardiomyocytes. PI16 also inhibited HDAC1 (class I histone deacetylase) expression, and overexpression HDAC1 abolished the inhibition of apoptosis and Wnt signaling of PI16. <br /><b>Conclusions:</b><br/>In summary, PI16 protects against cardiomyocyte apoptosis and left ventricular remodeling after MI through the HDAC1-Wnt3a-β-catenin axis.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 09 May 2023:e028866; epub ahead of print</small></div>

<div><h4>Rising and Falling High-Sensitivity Cardiac Troponin in Diagnostic Algorithms for Patients With Suspected Myocardial Infarction.</h4><i>Haller PM, Sörensen NA, Hartikainen TS, Goßling A, ... Westermann D, Neumann JT</i><br /><AbstractText><br /><b>Background:</b><br/>High-sensitivity cardiac troponin (hs-cTn)-based diagnostic algorithms are recommended for the management of patients with suspected myocardial infarction (MI) without ST elevation. Although mirroring different phases of myocardial injury, falling and rising troponin patterns (FPs and RPs, respectively) are equally considered by most algorithms. We aimed to compare the performance of diagnostic protocols for RPs and FPs, separately. Methods and Results We pooled 2 prospective cohorts of patients with suspected MI and stratified patients to stable, FP, and RP during serial sampling separately for hs-cTnI and hs-cTnT and applied the European Society of Cardiology 0/1- and 0/3-hour algorithms comparing the positive predictive values to rule in MI. Overall, 3523 patients were included in the hs-cTnI study population. The positive predictive value for patients with an FP was significantly reduced compared with patients with an RP (0/1-hour: FP, 53.3% [95% CI, 45.0-61.4] versus RP, 76.9 [95% CI, 71.6-81.7]; 0/3-hour: FP, 56.9% [95% CI, 42.2-70.7] versus RP, 78.1% [95% CI, 74.0-81.8]). The proportion of patients in the observe zone was larger in the FP using 0/1-hour (31.3% versus 55.8%) and 0/3-hour (14.6% versus 38.6%) algorithms. Alternative cutoffs did not improve algorithm performances. Compared with stable hs-cTn, the risk for death or MI was highest in those with an FP (adjusted hazard ratio [HR], hs-cTnI 2.3 [95% CI, 1.7-3.2]; RP adjusted HR, hs-cTnI 1.8 [95% CI, 1.4-2.4]). Findings were similar for hs-cTnT tested in 3647 patients overall. <br /><b>Conclusions:</b><br/>The positive predictive value to rule in MI by the European Society of Cardiology 0/1- and 0/3-hour algorithms is significantly lower in patients with FP than RP. These are at highest risk for incident death or MI. <b>REGISTRATION:</b> URL: https://www.clinicaltrials.gov; Unique identifiers: NCT02355457, NCT03227159.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 09 May 2023:e027166; epub ahead of print</small></div>

<div><h4>Significant Delayed Activation on the Right Ventricular Outflow Tract Represents Complete Right Bundle-Branch Block Pattern in Brugada Syndrome.</h4><i>Morimoto Y, Morita H, Ejiri K, Mizuno T, ... Nakamura K, Ito H</i><br /><AbstractText><br /><b>Background:</b><br/>The appearance of complete right bundle-branch block (CRBBB) in Brugada syndrome (BrS) is associated with an increased risk of ventricular fibrillation. The pathophysiological mechanism of CRBBB in patients with BrS has not been well established. We aimed to clarify the significance of a conduction delay zone associated with arrhythmias on CRBBB using body surface mapping in patients with BrS. Methods and Results Body surface mapping was recorded in 11 patients with BrS and 8 control patients both with CRBBB. CRBBB in control patients was transiently exhibited by unintentional catheter manipulation (proximal RBBB). Ventricular activation time maps were constructed for both of the groups. We divided the anterior chest into 4 areas (inferolateral right ventricle [RV], RV outflow tract [RVOT], intraventricular septum, and left ventricle) and compared activation patterns between the 2 groups. Excitation propagated to the RV from the left ventricle through the intraventricular septum with activation delay in the entire RV in the control group (proximal RBBB pattern). In 7 patients with BrS, excitation propagated from the inferolateral RV to the RVOT with significant regional activation delay. The remaining 4 patients with BrS showed a proximal RBBB pattern with the RVOT activation delay. The ventricular activation time in the inferolateral RV was significantly shorter in patients with BrS without a proximal RBBB pattern than in control patients. <br /><b>Conclusions:</b><br/>The CRBBB morphology in patients with BrS consisted of 2 mechanisms: (1) significantly delayed conduction in the RVOT and (2) proximal RBBB with RVOT conduction delay. Significant RVOT conduction delay without proximal RBBB resulted in CRBBB morphology in patients with BrS.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 09 May 2023:e028706; epub ahead of print</small></div>

<div><h4>Heterogeneity in Cardiovascular Disease Risk Factors Among Latino Immigrant Subgroups: Evidence From the 2010 to 2018 National Health Interview Survey.</h4><i>Elias S, Turkson-Ocran RA, Koirala B, Byiringiro S, ... Himmelfarb CR, Commodore-Mensah Y</i><br /><AbstractText><br /><b>Background:</b><br/>The Latino population is a growing and diverse share of the US population. Previous studies have examined Latino immigrants as a homogenous group. The authors hypothesized that there would be heterogeneity in cardiovascular disease risk factors among Latino immigrant subgroups (from Mexico, Puerto Rico, Cuba, Dominican Republic, Central America, or South America) compared with non-Latino White adults. Methods and Results A cross-sectional analysis of the 2010 to 2018 National Health Interview Survey (NHIS) among 548 739 individuals was performed. Generalized linear models with Poisson distribution were fitted to compare the prevalence of self-reported hypertension, overweight/obesity, diabetes, high cholesterol, physical inactivity, and current smoking, adjusting for known confounders. The authors included 474 968 non-Latino White adults and 73 771 Latino immigrants from Mexico (59%), Puerto Rico (7%), Cuba (6%), Dominican Republic (5%), Central America (15%), and South America (9%). Compared with White adults, Mexican immigrants had the highest prevalence of overweight/obesity (prevalence ratio [PR], 1.17 [95% CI, 1.15-1.19]); Puerto Rican individuals had the highest prevalence of diabetes (PR, 1.63 [95% CI, 1.45-1.83]); individuals from Central America had the highest prevalence of high cholesterol (PR, 1.16 [95% CI, 1.04-1.28]); and individuals from the Dominican Republic had the highest prevalence of physical inactivity (PR, 1.25 [95% CI, 1.18-1.32]). All Latino immigrant subgroups were less likely to be smokers than White adults. <br /><b>Conclusions:</b><br/>The authors observed advantages and disparities in cardiovascular disease risk factors among Latino immigrants. Aggregating data on Latino individuals may mask differences in cardiovascular disease risk and hinder efforts to reduce health disparities in this population. Study findings provide Latino group-specific actionable information and targets for improving cardiovascular health.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 09 May 2023:e027433; epub ahead of print</small></div>

<div><h4>Racial and Ethnic Differences in Cardiac Surveillance Evaluation of Patients Treated With Anthracycline-Based Chemotherapy.</h4><i>DeRemer DL, Nguyen NK, Guha A, Ahmad FS, ... Fradley MG, Gong Y</i><br /><AbstractText><br /><b>Background:</b><br/>Anthracyclines remain a key treatment for many malignancies but can increase the risk of heart failure or cardiomyopathy. Specific guidelines recommend echocardiography and serum cardiac biomarkers such as BNP (B-type natriuretic peptide) or NT-proBNP (N-terminal proBNP) evaluation before and 6 to 12 months after treatment. Our objective was to evaluate associations between racial and ethnic groups in cardiac surveillance of survivors of cancer after exposure to anthracyclines. Methods and Results Adult patients in the OneFlorida Consortium without prior cardiovascular disease who received at least 2 cycles of anthracyclines were included in the analysis. Multivariable logistic regression was performed to estimate the odds ratios (ORs) and 95% CIs for receiving cardiac surveillance at baseline before anthracycline therapy, 6 months after, and 12 months after anthracycline exposure among different racial and ethnic groups. Among the entire cohort of 5430 patients, 63.4% had a baseline echocardiogram, with 22.3% receiving an echocardiogram at 6 months and 25% at 12 months. Non-Hispanic Black (NHB) patients had a lower likelihood of receiving a baseline echocardiogram than Non-Hispanic White (NHW) patients (OR, 0.75 [95% CI, 0.63-0.88]; <i>P</i>=0.0006) or any baseline cardiac surveillance (OR, 0.76 [95% CI, 0.64-0.89]; <i>P</i>=0.001). Compared with NHW patients, Hispanic patients received significantly less cardiac surveillance at the 6-month (OR, 0.84 [95% CI, 0.72-0.98]; <i>P</i>=0.03) and 12-month (OR, 0.85 [95% CI, 0.74-0.98]; <i>P</i>=0.03) time points, respectively. <br /><b>Conclusions:</b><br/>There were significant racial and ethnic differences in cardiac surveillance among survivors of cancer at baseline and following anthracycline-based treatment in NHB and Hispanic cohorts. Health care providers need to be cognizant of these social inequities and initiate efforts to ensure recommended cardiac surveillance occurs following anthracyclines.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 09 May 2023:e027981; epub ahead of print</small></div>

<div><h4>Treatment With Small Molecule Inhibitors of Advanced Glycation End-Products Formation and Advanced Glycation End-Products-Mediated Collagen Cross-Linking Promotes Experimental Aortic Aneurysm Progression in Diabetic Mice.</h4><i>Li Y, Zheng X, Guo J, Samura M, ... Xu B, Dalman RL</i><br /><AbstractText><br /><b>Background:</b><br/>Although diabetes attenuates abdominal aortic aneurysms (AAAs), the mechanisms by which diabetes suppresses AAAs remain incompletely understood. Accumulation of advanced glycation end- (AGEs) reduces extracellular matrix (ECM) degradation in diabetes. Because ECM degradation is critical for AAA pathogenesis, we investigated whether AGEs mediate experimental AAA suppression in diabetes by blocking AGE formation or disrupting AGE-ECM cross-linking using small molecule inhibitors. Methods and Results Male C57BL/6J mice were treated with streptozotocin and intra-aortic elastase infusion to induce diabetes and experimental AAAs, respectively. Aminoguanidine (AGE formation inhibitor, 200 mg/kg), alagebrium (AGE-ECM cross-linking disrupter, 20 mg/kg), or vehicle was administered daily to mice from the last day following streptozotocin injection. AAAs were assessed via serial aortic diameter measurements, histopathology, and in vitro medial elastolysis assays. Treatment with aminoguanidine, not alagebrium, diminished AGEs in diabetic AAAs. Treatment with both inhibitors enhanced aortic enlargement in diabetic mice as compared with vehicle treatment. Neither enhanced AAA enlargement in nondiabetic mice. AAA enhancement in diabetic mice by aminoguanidine or alagebrium treatment promoted elastin degradation, smooth muscle cell depletion, mural macrophage accumulation, and neoangiogenesis without affecting matrix metalloproteinases, C-C motif chemokine ligand 2, or serum glucose concentration. Additionally, treatment with both inhibitors reversed suppression of diabetic aortic medial elastolysis by porcine pancreatic elastase in vitro. <br /><b>Conclusions:</b><br/>Inhibiting AGE formation or AGE-ECM cross-linking enhances experimental AAAs in diabetes. These findings support the hypothesis that AGEs attenuate experimental AAAs in diabetes. These findings underscore the potential translational value of enhanced ECM cross-linking as an inhibitory strategy for early AAA disease.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 09 May 2023:e028081; epub ahead of print</small></div>

<div><h4>Antihypertensive Medication Regimens Used by US Adults With Hypertension and the Potential for Fixed-Dose Combination Products: The National Health and Nutrition Examination Surveys 2015 to 2020.</h4><i>Derington CG, Bress AP, Herrick JS, Jacobs JA, ... Cushman WC, King JB</i><br /><AbstractText><br /><b>Background:</b><br/>Fixed-dose combination (FDC) antihypertensive products improve blood pressure control and adherence among patients with hypertension. It is unknown to what degree commercially available FDC products meet the current hypertension management prescription patterns in the United States. Methods and Results This cross-sectional analysis of the National Health and Nutrition Examination Surveys 2015 to March 2020 included participants with hypertension taking ≥2 antihypertensive medications (N=2451). After constructing each participant\'s regimen according to antihypertensive classes used, we estimated the extent to which the 7 class-level FDC regimens available in the United States as of January 2023 would match the regimens used. Among a weighted population of 34.1 million US adults (mean age, 66.0 years; 52.8% women; 69.1% non-Hispanic White race and ethnicity), the proportions using 2, 3, 4, and ≥5 antihypertensive classes were 60.6%, 28.2%, 9.1%, and 1.6%, respectively. The 7 FDC regimens were among 189 total regimens used (3.7%), and 39.2% of the population used one of the FDC regimens (95% CI, 35.5%-43.0%; 13.4 million US adults); 60.8% of the population (95% CI, 57.0%-64.5%; 20.7 million US adults) were using a regimen not available as a class-equivalent FDC product. <br /><b>Conclusions:</b><br/>Three in 5 US adults with hypertension taking ≥2 antihypertensive classes are using a regimen that is not commercially available as a class-equivalent FDC product as of January 2023. To maximize the potential benefit of FDCs to improve medication adherence (and thus blood pressure control) among patients taking multiple antihypertensive medications, use of FDC-compatible regimens and improvements in the product landscape are needed.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 09 May 2023:e028573; epub ahead of print</small></div>

<div><h4>Ethnic Variations in Cardiovascular and Renal Outcomes From Newer Glucose-Lowering Drugs: A Meta-Analysis of Randomized Outcome Trials.</h4><i>Tang H, Chen W, Bian J, O\'Neal LJ, ... Schatz DA, Guo J</i><br /><AbstractText><br /><b>Background:</b><br/>Hispanic populations are more likely to develop diabetes and its related diseases than non-Hispanic White populations. Little evidence exists to support whether the cardiovascular and renal benefits of sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists are generalizable to the Hispanic populations. Methods and Results We included the cardiovascular and renal outcome trials (up to March 2021) that reported the major adverse cardiovascular events (MACEs), cardiovascular death/hospitalization for heart failure, and composite renal outcomes by ethnicity in individuals with type 2 diabetes (T2D), calculated pooled hazard ratios (HRs) with 95% CIs using fixed-effects models, and tested the differences between Hispanic and non-Hispanic populations (<i>P</i> for interaction [<i>P</i><sub>interaction</sub>]). In 3 sodium-glucose cotransporter 2 inhibitor trials, there was a statistically significant difference between Hispanic (HR, 0.70 [95% CI, 0.54-0.91]) and non-Hispanic (HR, 0.96 [95% CI, 0.86-1.07]) groups in treatment effects on MACE risk (<i>P</i><sub>interaction</sub>=0.03), except for risks of cardiovascular death/hospitalization for heart failure (<i>P</i><sub>interaction</sub>=0.46) and composite renal outcome (<i>P</i><sub>interaction</sub>=0.31). In 5 glucagon-like peptide-1 receptor agonist trials, there was no statistically significant difference in treatment effect on MACE risk between Hispanic (HR, 0.82 [95% CI, 0.70-0.96]) and non-Hispanic (HR, 0.92 [95% CI, 0.84-1.00]) populations (<i>P</i><sub>interaction</sub>=0.22). In 3 dipeptidyl peptidase-4 inhibitor trials, the HR for MACE risk appeared greater in Hispanic (HR, 1.15 [95% CI, 0.98-1.35]) than non-Hispanic (HR, 0.96 [95% CI, 0.88-1.04]) populations (<i>P</i><sub>interaction</sub>=0.045). <br /><b>Conclusions:</b><br/>Compared with non-Hispanic individuals, Hispanic individuals with T2D appeared to obtain a greater benefit of lowered MACE risk with sodium-glucose cotransporter 2 inhibitors.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 09 May 2023:e026791; epub ahead of print</small></div>

<div><h4>Factors Impacting Treatment of Out-of-Hospital Cardiac Arrest: A Qualitative Study of Emergency Responders.</h4><i>Missel AL, Dowker SR, Dzierwa D, Krein SL, ... Hunt N, Friedman CP</i><br /><AbstractText><br /><b>Background:</b><br/>Of the more than 250 000 emergency medical services-treated out-of-hospital cardiac arrests that occur each year in the United States, only about 8% survive to hospital discharge with good neurologic function. Treatment for out-of-hospital cardiac arrest involves a system of care that includes complex interactions among multiple stakeholders. Understanding the factors inhibiting optimal care is fundamental to improving outcomes. Methods and Results We conducted group interviews with emergency responders including 911 telecommunicators, law enforcement officers, firefighters, and transporting emergency medical services personnel (ie, emergency medical technicians and paramedics) who responded to the same out-of-hospital cardiac arrest incident. We used the American Heart Association System of Care as the framework for our analysis to identify themes and their contributory factors from these interviews. We identified 5 themes under the structure domain, which included workload, equipment, prehospital communication structure, education and competency, and patient attitudes. In the process domain, 5 themes were identified focusing on preparedness, field response and access to patient, on-scene logistics, background information acquisition, and clinical interventions. We identified 3 system themes including emergency responder culture; community support, education, and engagement; and stakeholder relationships. Three continuous quality improvement themes were identified, which included feedback provision, change management, and documentation. <br /><b>Conclusions:</b><br/>We identified structure, process, system, and continuous quality improvement themes that may be leveraged to improve outcomes for out-of-hospital cardiac arrest. Interventions or programs amenable to rapid implementation include improving prearrival communication between agencies, appointing patient care and logistical leadership on-scene, interstakeholder team training, and providing more standardized feedback to all responder groups.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 09 May 2023:e027756; epub ahead of print</small></div>

<div><h4>Rapid Improvements in Physical Activity and Sedentary Behavior in Patients With Acute Myocardial Infarction Immediately Following Hospital Discharge.</h4><i>van Bakel BMA, de Koning IA, Bakker EA, Pop GAM, ... Thijssen DHJ, Eijsvogels TMH</i><br /><AbstractText><br /><b>Background:</b><br/>Little is known about changes in physical activity (PA) and sedentary behavior (SB) patterns in the acute phase of a myocardial infarction (MI). We objectively assessed PA and SB during hospitalization and the first week after discharge. Methods and Results Consecutively admitted patients hospitalized with an MI were approached to participate in this prospective cohort study. SB, light-intensity PA, and moderate-vigorous intensity PA were objectively assessed for 24 h/d during hospitalization and up to 7 days after discharge in 165 patients. Changes in PA and SB from the hospital to home phase were evaluated using mixed-model analyses, and outcomes were stratified for predefined subgroups based on patient characteristics. Patients (78% men) were aged 65±10 years and diagnosed with ST-segment-elevation MI (50%) or non-ST-segment-elevation MI (50%). Sedentary time was high during hospitalization (12.6 [95% CI, 11.8-13.7] h/d) but substantially decreased following transition to the home environment (-1.8 [95% CI, -2.4 to -1.3] h/d). Furthermore, the number of prolonged sedentary bouts (≥60 minutes) decreased between hospital and home (-1.6 [95% CI, -2.0 to -1.2] bouts/day). Light-intensity PA (1.1 [95% CI, 0.8-1.6] h/d) and moderate-vigorous intensity PA (0.2 [95% CI, 0.1-0.3] h/d) were low during hospitalization but significantly increased following transition to the home environment (light-intensity PA: 1.8 [95% CI, 1.4-2.3] h/d; moderate-vigorous intensity PA: 0.4 [95% CI, 0.3-0.5] h/d; both <i>P</i><0.001). Improvements in PA and SB were similar across groups, except for patients who underwent coronary artery bypass grafting and who did not improve their PA patterns after discharge. <br /><b>Conclusions:</b><br/>Patients with MI demonstrate high levels of SB and low PA volumes during hospitalization, which immediately improved following discharge at the patient\'s home environment. Registration URL: trialsearch.who.int/; Unique identifier: NTR7646.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 09 May 2023:e028700; epub ahead of print</small></div>

<div><h4>Association of Degree of Urbanization and Survival in Out-of-Hospital Cardiac Arrest.</h4><i>Gregers MCT, Møller SG, Kjoelbye JS, Jakobsen LK, ... Ersbøll AK, Folke F</i><br /><AbstractText><br /><b>Background:</b><br/>Survival from out-of-hospital cardiac arrest (OHCA) varies across regions. The aim of this study was to evaluate the association between urbanization (rural, suburban, and urban areas), bystander interventions (cardiopulmonary resuscitation and defibrillation), and 30-day survival from OHCAs in Denmark. Methods and Results We included OHCAs not witnessed by ambulance staff in Denmark from January 1, 2016, to December 31, 2020. Patients were divided according to the Eurostat Degree of Urbanization Tool in rural, suburban, and urban areas based on the 98 Danish municipalities. Poisson regression was used to estimate incidence rate ratios. Logistic regression (adjusted for ambulance response time) tested differences between the groups with respect to bystander interventions and survival, according to degree of urbanization. A total of 21 385 OHCAs were included, of which 8496 (40%) occurred in rural areas, 7025 (33%) occurred in suburban areas, and 5864 (27%) occurred in urban areas. Baseline characteristics, as age, sex, location of OHCA, and comorbidities, were comparable between groups. The annual incidence rate ratio of OHCA was higher in rural areas (1.54 [95% CI, 1.48-1.58]) compared with urban areas. Odds for bystander cardiopulmonary resuscitation were lower in suburban (0.86 [95% CI, 0.82-0.96]) and urban areas (0.87 [95% CI, 0.80-0.95]) compared with rural areas, whereas bystander defibrillation was higher in urban areas compared with rural areas (1.15 [95% CI, 1.01-1.31]). Finally, 30-day survival was higher in suburban (1.13 [95% CI, 1.02-1.25]) and urban areas (1.17 [95% CI, 1.05-1.30]) compared with rural areas. <br /><b>Conclusions:</b><br/>Degree of urbanization was associated with lower rates of bystander defibrillation and 30-day survival in rural areas compared with urban areas.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 09 May 2023:e8322; epub ahead of print</small></div>

<div><h4>New Hypertension After Pregnancy in Patients With Heart Disease.</h4><i>Siu SC, Lee DS, Fang J, Austin PC, Silversides CK</i><br /><AbstractText><br /><b>Background:</b><br/>After pregnancy, patients with preexisting heart disease are at high risk for cardiovascular complications. The primary objective was to compare the incidence of new hypertension after pregnancy in patients with and without heart disease. Methods and Results This was a retrospective matched-cohort study comparing the incidence of new hypertension after pregnancy in 832 patients who are pregnant with congenital or acquired heart disease to a comparison group of 1664 patients who are pregnant without heart disease; matching was by demographics and baseline risk for hypertension at the time of the index pregnancy. We also examined whether new hypertension was associated with subsequent death or cardiovascular events. The 20-year cumulative incidence of hypertension was 24% in patients with heart disease, compared with 14% in patients without heart disease (hazard ratio [HR], 1.81 [95% CI, 1.44-2.27]). The median follow-up time at hypertension diagnosis in the heart disease group was 8.1 years (interquartile range, 4.2-11.9 years). The elevated rate of new hypertension was observed not only in patients with ischemic heart disease, but also in those with left-sided valve disease, cardiomyopathy, and congenital heart disease. Pregnancy risk prediction methods can further stratify risk of new hypertension. New hypertension was associated with an increased rate of subsequent death or cardiovascular events (HR, 1.54 [95% CI, 1.05-2.25]). <br /><b>Conclusions:</b><br/>Patients with heart disease are at higher risk for developing hypertension in the decades after pregnancy when compared with those without heart disease. New hypertension in this young cohort is associated with adverse cardiovascular events highlighting the importance of systematic and lifelong surveillance.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 09 May 2023:e029260; epub ahead of print</small></div>

<div><h4>Evidence-Based Optimal Medical Therapy and Mortality in Patients With Acute Myocardial Infarction After Percutaneous Coronary Intervention.</h4><i>Lee K, Han S, Lee M, Kim DW, ... Park GM, Park MW</i><br /><AbstractText><br /><b>Background:</b><br/>The secondary prevention with pharmacologic therapy is essential for preventing recurrent cardiovascular events in patients experiencing acute myocardial infarction. Guideline-based optimal medical therapy (OMT) for patients with acute myocardial infarction consists of antiplatelet therapy, angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, β-blockers, and statins. We aimed to determine the prescription rate of OMT use at discharge and to evaluate the impact of OMT on long-term clinical outcomes in patients with acute myocardial infarction who underwent percutaneous coronary intervention in the drug-eluting stent era using nationwide cohort data. Methods and Results Using the National Health Insurance claims data in South Korea, patients with acute myocardial infarction who had undergone percutaneous coronary intervention with a drug-eluting stent between July 2013 and June 2017 were enrolled. A total of 35 972 patients were classified into the OMT and non-OMT groups according to the post-percutaneous coronary intervention discharge medication. The primary end point was all-cause death, and the 2 groups were compared using a propensity-score matching analysis. Fifty-seven percent of patients were prescribed OMT at discharge. During the follow-up period (median, 2.0 years [interquartile range, 1.1-3.2 years]), OMT was associated with a significant reduction in the all-cause mortality (adjusted hazard ratio [aHR], 0.82 [95% CI, 0.76-0.90]; <i>P</i><0.001) and composite outcome of death or coronary revascularization (aHR, 0.89 [95% CI, 0.85-0.93]; <i>P</i><0.001). <br /><b>Conclusions:</b><br/>OMT was prescribed at suboptimal rates in South Korea. However, our nationwide cohort study showed that OMT has a benefit for long-term clinical outcomes on all-cause mortality and composite outcome of death or coronary revascularization after percutaneous coronary intervention in the drug-eluting stent era.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 09 May 2023:e024370; epub ahead of print</small></div>

<div><h4>Culprit-Only Versus Immediate Multivessel Percutaneous Coronary Intervention in Patients With Acute Myocardial Infarction Complicating Advanced Cardiogenic Shock Requiring Venoarterial-Extracorporeal Membrane Oxygenation.</h4><i>Choi KH, Yang JH, Park TK, Lee JM, ... Kang TS, Gwon HC</i><br /><AbstractText><br /><b>Background:</b><br/>Despite the benefit of culprit-only percutaneous coronary intervention (PCI) in the CULPRIT-SHOCK (Culprit Lesion Only PCI Versus Multi-vessel PCI in Cardiogenic Shock) trial, the optimal revascularization strategy for refractory cardiogenic shock (CS) requiring mechanical circulatory support devices remains controversial. This study aimed to compare clinical outcomes between the culprit-only and immediate multivessel PCI strategies in patients with acute myocardial infarction complicated by CS who underwent venoarterial-extracorporeal membrane oxygenation before revascularization. Methods and Results This study included patient-pooled data from the RESCUE (Retrospective and Prospective Observational Study to Investigate Clinical Outcomes and Efficacy of Left Ventricular Assist Devices for Korean Patients With Cardiogenic Shock) and SMC-ECMO (Samsung Medical Center-Extracorporeal Membrane Oxygenation) registries. A total of 315 patients with acute myocardial infarction with multivessel disease who underwent venoarterial-extracorporeal membrane oxygenation before revascularization attributable to refractory CS were included in this analysis. The study population was classified into culprit-only versus immediate multivessel PCI according to nonculprit lesion treatment strategies. The primary end point was 30-day mortality or renal-replacement therapy, and the key secondary end point was 12-month follow-up mortality. Among the study population, 175 (55.6%) underwent culprit-only PCI and 140 (44.4%) underwent immediate multivessel PCI. Compared with culprit-only PCI, immediate multivessel PCI was associated with significantly lower risks of 30-day mortality or renal-replacement therapy (68.0% versus 54.3%; <i>P</i>=0.018) and all-cause mortality during 12 months of follow-up (59.5% versus 47.5%; hazard ratio [HR], 0.689 [95% CI, 0.506-0.939]; <i>P</i>=0.018) in patients with acute myocardial infarction and CS who underwent venoarterial-extracorporeal membrane oxygenation before revascularization. These results were also consistent in the 99 pairs of propensity score-matched population (60.6% versus 43.6%; HR, 0.622 [95% CI, 0.420-0.922]; <i>P</i>=0.018). <br /><b>Conclusions:</b><br/>Among patients with acute myocardial infarction with multivessel disease complicated by advanced CS requiring venoarterial-extracorporeal membrane oxygenation before revascularization, immediate multivessel PCI was associated with lower incidences of 30-day mortality or renal replacement therapy and 12-month follow-up mortality, compared with culprit-only PCI. Registration Information clinicaltrials.gov. Identifier: NCT02985008.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 09 May 2023:e029792; epub ahead of print</small></div>

<div><h4>Clinical Profile, Health Care Costs, and Outcomes of Patients Hospitalized for Heart Failure With Severely Reduced Ejection Fraction.</h4><i>Harrington J, Sun JL, Fonarow GC, Heitner SB, ... Felker GM, Greene SJ</i><br /><AbstractText><br /><b>Background:</b><br/>Many patients with heart failure (HF) have severely reduced ejection fraction but do not meet threshold for consideration of advanced therapies (ie, stage D HF). The clinical profile and health care costs associated with these patients in US practice is not well described. Methods and Results We examined patients hospitalized for worsening chronic heart failure with reduced ejection fraction ≤40% from 2014 to 2019 in the GWTG-HF (Get With The Guidelines-Heart Failure) registry, who did not receive advanced HF therapies or have end-stage kidney disease. Patients with severely reduced EF defined as EF ≤30% were compared with those with EF 31% to 40% in terms of clinical profile and guideline-directed medical therapy. Among Medicare beneficiaries, postdischarge outcomes and health care expenditure were compared. Among 113 348 patients with EF ≤40%, 69% (78 589) had an EF ≤30%. Patients with severely reduced EF ≤30% tended to be younger and were more likely to be Black. Patients with EF ≤30% also tended to have fewer comorbidities and were more likely to be prescribed guideline-directed medical therapy (\"triple therapy\" 28.3% versus 18.2%, <i>P</i><0.001). At 12-months postdischarge, patients with EF ≤30% had significantly higher risk of death (HR, 1.13 [95% CI, 1.08-1.18]) and HF hospitalization (HR, 1.14 [95% CI, 1.09-1.19]), with similar risk of all-cause hospitalizations. Health care expenditures were numerically higher for patients with EF ≤30% (median US$22 648 versus $21 392, <i>P</i>=0.11). <br /><b>Conclusions:</b><br/>Among patients hospitalized for worsening chronic heart failure with reduced ejection fraction in US clinical practice, most patients have severely reduced EF ≤30%. Despite younger age and modestly higher use of guideline-directed medical therapy at discharge, patients with severely reduced EF face heightened postdischarge risk of death and HF hospitalization.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 09 May 2023:e028820; epub ahead of print</small></div>

<div><h4>Geographic Disparities in Case Fatality and Discharge Disposition Among Patients With Primary Intracerebral Hemorrhage.</h4><i>Bako AT, Potter T, Pan A, Tannous J, ... Britz G, Vahidy FS</i><br /><AbstractText><br /><b>Background:</b><br/>We evaluate nationwide trends and urban-rural disparities in case fatality (in-hospital mortality) and discharge dispositions among patients with primary intracerebral hemorrhage (ICH). Methods and Results In this repeated cross-sectional study, we identified adult patients (≥18 years of age) with primary ICH from the National Inpatient Sample (2004-2018). Using a series of survey design Poisson regression models, with hospital location-time interaction, we report the adjusted risk ratio (aRR), 95% CI, and average marginal effect (AME) for factors associated with ICH case fatality and discharge dispositions. We performed a stratified analysis of each model among patients with extreme loss of function and minor to major loss of function. We identified 908 557 primary ICH hospitalizations (overall mean age [SD], 69.0 [15.0] years; 445 301 [49.0%] women; 49 884 [5.5%] rural ICH hospitalizations). The crude ICH case fatality rate was 25.3% (urban hospitals: 24.9%, rural hospitals:32.5%). Urban (versus rural) hospital patients had a lower likelihood of ICH case fatality (aRR, 0.86 [95% CI, 0.83-0.89]). ICH case fatality is declining over time; however, it is declining faster in urban hospitals (AME, -0.049 [95% CI, -0.051 to -0.047]) compared with rural hospitals (AME, -0.034 [95% CI, -0.040 to -0.027]). Conversely, home discharge is increasing significantly among urban hospitals (AME, 0.011 [95% CI, 0.008-0.014]) but not significantly changing in rural hospitals (AME, -0.001 [95% CI, -0.010 to 0.007]). Among patients with extreme loss of function, hospital location was not significantly associated with ICH case fatality or home discharge. <br /><b>Conclusions:</b><br/>Improving access to neurocritical care resources, particularly in resource-limited communities, may reduce the ICH outcomes disparity gap.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 09 May 2023:e027403; epub ahead of print</small></div>

<div><h4>Repeat Mitral Transcatheter Edge-to-Edge Repair for Recurrent Significant Mitral Regurgitation.</h4><i>Shechter A, Lee M, Kaewkes D, Koren O, ... Makkar RR, Siegel RJ</i><br /><AbstractText><br /><b>Background:</b><br/>There are limited data on repeat mitral transcatheter edge-to-edge repair for recurrent significant mitral regurgitation (MR). Methods and Results We conducted a single-center, retrospective analysis of consecutive patients referred to a second mitral transcatheter edge-to-edge repair after a technically successful first procedure. Clinical, laboratory, and echocardiographic measures were assessed up to 1 year after the intervention. The composite of all-cause death or heart failure (HF) hospitalizations constituted the primary outcome. A total of 52 patients (median age, 81 [interquartile range, 76-87] years, 29 [55.8%] men, 26 [50.0%] with functional MR) met the inclusion criteria. MR recurrences were mostly related to progression of the underlying cardiac pathology. All procedures were technically successful. At 1 year, most patients with available records (n=24; 96.0%) experienced improvement in MR severity or New York Heart Association functional class that was statistically significant but numerically modest. Fourteen (26.9%) patients died or were hospitalized due to HF. These were higher-risk cases with predominantly functional MR who mostly underwent an urgent procedure and exhibited more severe HF indices before the intervention, as well as an attenuated 1-month clinical and echocardiographic response. Overall, 1-year course was comparable to that experienced by patients who underwent only a first transcatheter edge-to-edge repair at our institution (n=902). Tricuspid regurgitation of greater than moderate grade was the only baseline parameter to independently predict the primary outcome. <br /><b>Conclusions:</b><br/>Repeat mitral transcatheter edge-to-edge repair is feasible, safe, and clinically effective, especially in non-functional MR patients without concomitant significant tricuspid regurgitation.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 29 Apr 2023:e028654; epub ahead of print</small></div>

<div><h4>Hypertension, Blood Pressure Variability, and Acute Kidney Injury in Hospitalized Children.</h4><i>Nugent JT, Ghazi L, Yamamoto Y, Bakhoum C, Wilson FP, Greenberg JH</i><br /><AbstractText><br /><b>Background:</b><br/>Although hypertensive blood pressure measurements are common in hospitalized children, the degree of inpatient hypertension and blood pressure variability (BPV) associated with end organ complications like acute kidney injury (AKI) is unknown. Methods and Results All analyses are based on a retrospective cohort of children aged 1 to 17 years with ≥2 creatinine measurements during admission from 2014 to 2018. We used time-updated Cox models to evaluate the association between BPV and hypertension with AKI. Time-varying BPV and hypertension were based on blood pressure in the preceding 72 hours. For the analysis of hypertension and AKI, we excluded patients on vasopressors to ensure comparison between hypertensive and normotensive patients. During 5425 pediatric encounters, 258 430 blood pressure measurements were recorded (median [interquartile range] 22 [11-47] readings per encounter). Among all measurements, 32.7% were ≥95th percentile and 18.9% were ≥99th percentile for age, sex, and height. AKI occurred in 389 (7.2%) encounters. We observed a U-shaped relationship between mean blood pressure and incident AKI. BPV was associated with AKI, with the largest effect sizes in the systolic and mean arterial pressure variability measures. Multiple hypertension thresholds were associated with AKI after controlling for confounders. In an additional multivariable model adjusted for BPV, the association between hypertension and AKI was attenuated but remained significant for hypertension defined as three stage 2 measurements in 1 day (hazard ratio, 1.43 [95% CI, 1.01-2.01]). <br /><b>Conclusions:</b><br/>Hypertension and BPV are associated with AKI in hospitalized children. Future studies are needed to determine how pharmacologic and nonpharmacologic interventions modify AKI risk in pediatric inpatients with hypertension.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 29 Apr 2023:e029059; epub ahead of print</small></div>

<div><h4>Catestatin Protects Against Diastolic Dysfunction by Attenuating Mitochondrial Reactive Oxygen Species Generation.</h4><i>Qiu Z, Fan Y, Wang Z, Huang F, ... Jin W, Chen Y</i><br /><AbstractText><br /><b>Background:</b><br/>Catestatin has been reported as a pleiotropic cardioprotective peptide. Heart failure with preserved ejection fraction (HFpEF) was considered a heterogeneous syndrome with a complex cause. We sought to investigate the role of catestatin in HFpEF and diastolic dysfunction. <br /><b>Methods and results:</b><br/>Administration of recombinant catestatin (1.5 mg/kg/d) improved diastolic dysfunction and left ventricular chamber stiffness in transverse aortic constriction mice with deoxycorticosterone acetate pellet implantation, as reflected by Doppler tissue imaging and pressure-volume loop catheter. Less cardiac hypertrophy and myocardial fibrosis was observed, and transcriptomic analysis revealed downregulation of mitochondrial electron transport chain components after catestatin treatment. Catestatin reversed mitochondrial structural and respiratory chain component abnormality, decreased mitochondrial proton leak, and reactive oxygen species generation in myocardium. Excessive oxidative stress induced by Ru360 abolished catestatin treatment effects on HFpEF-like cardiomyocytes in vitro, indicating the beneficial role of catestatin in HFpEF as a mitochondrial ETC modulator. The serum concentration of catestatin was tested among 81 patients with HFpEF and 76 non-heart failure controls. Compared with control subjects, serum catestatin concentration was higher in patients with HFpEF and positively correlated with E velocity to mitral annular e\' velocity ratio, indicating a feedback compensation role of catestatin in HFpEF. <br /><b>Conclusions:</b><br/>Catestatin protects against diastolic dysfunction in HFpEF through attenuating mitochondrial electron transport chain-derived reactive oxygen species generation. Serum catestatin concentration is elevated in patients with HFpEF, probably as a relatively insufficient but self-compensatory mechanism.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 29 Apr 2023:e029470; epub ahead of print</small></div>

<div><h4>Effects of Dapagliflozin in Chronic Kidney Disease, With and Without Other Cardiovascular Medications: DAPA-CKD Trial.</h4><i>Chertow GM, Correa-Rotter R, Vart P, Jongs N, ... Heerspink HJL, DAPA‐CKD Trial Committees and Investigators</i><br /><AbstractText><br /><b>Background:</b><br/>The DAPA-CKD (Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease) trial (NCT03036150) demonstrated that dapagliflozin reduced the risk of kidney and cardiovascular events in patients with chronic kidney disease and albuminuria with and without type 2 diabetes. We aimed to determine whether baseline cardiovascular medication use modified the dapagliflozin treatment effect. Methods and Results We randomized 4304 adults with baseline estimated glomerular filtration rate 25 to 75 mL/min per 1.73 m<sup>2</sup> and urinary albumin:creatinine ratio 200 to 5000 mg/g to dapagliflozin 10 mg or placebo once daily. The primary end point was a composite of ≥50% estimated glomerular filtration rate decline, end-stage kidney disease, and kidney or cardiovascular death. Secondary end points included a kidney composite end point (primary composite end point without cardiovascular death), a cardiovascular composite end point (hospitalized heart failure or cardiovascular death), and all-cause mortality. We categorized patients according to baseline cardiovascular medication use/nonuse. Patients were required by protocol to receive a stable (and maximally tolerated) dose of a renin-angiotensin-aldosterone system inhibitor. We observed consistent benefits of dapagliflozin relative to placebo, irrespective of baseline use/nonuse of renin-angiotensin-aldosterone system inhibitors (98.1%), calcium channel blockers (50.7%), β-adrenergic antagonists (39.0%), diuretics (43.7%), and antithrombotic (47.4%), and lipid-lowering (15.0%) agents. Use of these drugs in combination with dapagliflozin did not increase the number of serious adverse events. <br /><b>Conclusions:</b><br/>The safety profile and efficacy of dapagliflozin on kidney and cardiovascular end points in patients with chronic kidney disease were consistent among patients treated and not treated at baseline with a range of cardiovascular medications. Registration Information clinicaltrials.gov. Identifier: NCT03036150.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 29 Apr 2023:e028739; epub ahead of print</small></div>

<div><h4>Longitudinal Study of Left Ventricular Mass Index Trajectories and Risk of Mortality in Hypertension: A Cohort Study.</h4><i>Zhou D, Huang Y, Cai A, Yan M, ... Nie Z, Feng Y</i><br /><AbstractText><br /><b>Background:</b><br/>Left ventricular mass index (LVMI) has been extensively studied for its relationship with mortality but has been typically assessed at a single time point. We, therefore, describe the trajectory of LVMI in a population with hypertension over 6 years to study the subsequent risk of mortality. Methods and Results We assessed LVMI that was collected during annual health examinations in round 1 (2010-2012), round 2 (2013-2014), and round 3 (2015-2016) with 2 allometric scalings, height<sup>2.7</sup>, and body surface area, in a cohort of participants with hypertension to identify 6-year trajectories of LVMI by latent class trajectory modeling. We followed up with participants for mortality by latent trajectory from the last echocardiographic examination (September 17, 2014-December 8, 2016) to December 31, 2018. We calculated mortality hazard ratios by assigned trajectory using Cox proportional hazards models. We obtained data for LVMI from 2453 participants (mean age, 61.80 [SD, 12.14] years, 1428 [58.2%] female). We identified 3 trajectories of LVM/H<sup>2.7</sup>, characterized by maintained low stable (1298 [52.9%]); moderate stable (935 [38.1%]); high stable (220 [9.0%]), as well as 3 trajectories by LVM/body surface area. During a median follow-up of 2.15 years, 167 participants developed all-cause mortality, and 71 were cardiovascular mortality. Only the high stable trajectory was associated with a higher risk of all-cause mortality compared with the low stable trajectory by LVM/H<sup>2.7</sup> or LVM/body surface area (all <i>P</i><0.05). In Kaplan-Meier survival analysis, the trajectory with high stable LVM/body surface area had significantly lower survival probability. <br /><b>Conclusions:</b><br/>In community hypertension, the individuals with high stable LVMI trajectory had the highest risk of all-cause mortality. The individuals in the moderate stable trajectory had a similar risk for mortality as those in the low stable trajectory.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 29 Apr 2023:e028568; epub ahead of print</small></div>

<div><h4>Aortic Dissection During Pregnancy and Puerperium: Contemporary Incidence and Outcomes in the United States.</h4><i>Wang Y, Yin K, Datar Y, Mohnot J, ... Reardon MJ, Dobrilovic N</i><br /><AbstractText><br /><b>Background:</b><br/>Aortic dissection (AD) during pregnancy and puerperium is a rare catastrophe with devastating consequences for both parent and fetus. Population-level incidence trends and outcomes remain relatively undetermined. Methods and Results We queried a US population-based health care database, the National Inpatient Sample, and identified all patients with a pregnancy-related AD hospitalization from 2002 to 2017. In total, 472 pregnancy-related AD hospitalizations (mean age, 30.9±0.6 years) were identified from 68 514 000 pregnancy-related hospitalizations (0.69 per 100 000 pregnancy-related hospitalizations), with 107 (22.7%) being type A and 365 (77.3%) being type B. The incidence of AD appeared to increase over the 16-year study period but was not statistically significant (<i>P</i> for trend >0.05). Marfan syndrome, primary hypertension, and preeclampsia/eclampsia were found in 21.9%, 14.4%, and 11.5%, respectively. On multivariable logistic regression analysis, Marfan syndrome was associated with the highest risk of developing AD during pregnancy and puerperium (adjusted odds ratio, 3469.36 [95% CI, 1767.84-6831.75]; <i>P</i><0.001). The in-hospital mortalities of AD, type A AD, and type B AD were 7.3%, 4.3%, and 8.1%, respectively. Length of hospital stay for the AD, type A AD, and type B AD groups were 7.7±0.8, 10.4±1.9, and 6.9±0.9 days, respectively. <br /><b>Conclusions:</b><br/>We quantified population-level incidence and in-hospital mortality in the United States and observed an increase in the incidence of pregnancy-related AD. In contrast, its in-hospital mortality appears lower than that of non-pregnancy-related AD.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 29 Apr 2023:e028436; epub ahead of print</small></div>

<div><h4>Aortic Stenosis and Outcomes in Patients With Atrial Fibrillation: A Nationwide Cohort Study.</h4><i>Teppo K, Airaksinen KEJ, Biancari F, Jaakkola J, ... Aro AL, Lehto M</i><br /><AbstractText><br /><b>Background:</b><br/>Patients with aortic stenosis (AS) have been underrepresented in the trials evaluating direct oral anticoagulants (DOACs) in atrial fibrillation (AF). We aimed to assess whether AS impacts outcomes in patients with AF and estimate the effects of DOACs versus warfarin in patients with AF and AS. Methods and Results The registry-based FinACAF (Finnish Anticoagulation in Atrial Fibrillation) study covered all patients with AF diagnosed during 2007 to 2018 in Finland. Hazard ratios (HRs) of first-ever gastrointestinal bleeding, intracranial bleeding, any bleeding, ischemic stroke, and death were estimated with cause-specific hazards regression adjusted for anticoagulant exposure variables. We identified 183 946 patients (50.5% women; mean age, 71.7 [SD, 13.5] years) with incident AF without prior bleeding or ischemic stroke, of whom 5231 (2.8%) had AS. The crude incidence rate of all outcomes was higher in patients with AS than in patients without AS. After propensity score matching, AS was associated with the hazard of any bleeding, gastrointestinal bleeding, and death but not with intracranial bleeding or ischemic stroke (adjusted HRs, 1.36 [95% CI, 1.25-1.48], 1.63 [95% CI, 1.43-1.86], 1.32 [95% CI, 1.26-1.38], 0.96 [95% CI, 0.78-1.17], and 1.11 [95% CI, 0.99-1.25], respectively). Among patients with AS, DOACs were associated with a lower risk of ischemic stroke when compared with warfarin, while bleeding and mortality did not differ between DOACs and warfarin. <br /><b>Conclusions:</b><br/>AS is associated with substantially higher risk of gastrointestinal bleeding in patients with AF. DOACs may be more effective in preventing ischemic stroke than warfarin in patients with AF and AS. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04645537.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 29 Apr 2023:e029337; epub ahead of print</small></div>

<div><h4>Contemporary Homozygous Familial Hypercholesterolemia in the United States: Insights From the CASCADE FH Registry.</h4><i>Cuchel M, Lee PC, Hudgins LC, Duell PB, ... Wilemon K, McGowan MP</i><br /><AbstractText><br /><b>Background:</b><br/>Homozygous familial hypercholesterolemia (HoFH) is a rare, treatment-resistant disorder characterized by early-onset atherosclerotic and aortic valvular cardiovascular disease if left untreated. Contemporary information on HoFH in the United States is lacking, and the extent of underdiagnosis and undertreatment is uncertain. Methods and Results Data were analyzed from 67 children and adults with clinically diagnosed HoFH from the CASCADE (Cascade Screening for Awareness and Detection) FH Registry. Genetic diagnosis was confirmed in 43 patients. We used the clinical characteristics of genetically confirmed patients with HoFH to query the Family Heart Database, a US anonymized payer health database, to estimate the number of patients with similar lipid profiles in a \"real-world\" setting. Untreated low-density lipoprotein cholesterol levels were lower in adults than children (533 versus 776 mg/dL; <i>P</i>=0.001). At enrollment, atherosclerotic cardiovascular disease and supravalvular and aortic valve stenosis were present in 78.4% and 43.8% and 25.5% and 18.8% of adults and children, respectively. At most recent follow-up, despite multiple lipid-lowering treatment, low-density lipoprotein cholesterol goals were achieved in only a minority of adults and children. Query of the Family Heart Database identified 277 individuals with profiles similar to patients with genetically confirmed HoFH. Advanced lipid-lowering treatments were prescribed for 18%; 40% were on no lipid-lowering treatment; atherosclerotic cardiovascular disease was reported in 20%; familial hypercholesterolemia diagnosis was uncommon. <br /><b>Conclusions:</b><br/>Only patients with the most severe HoFH phenotypes are diagnosed early. HoFH remains challenging to treat. Results from the Family Heart Database indicate HoFH is systemically underdiagnosed and undertreated. Earlier screening, aggressive lipid-lowering treatments, and guideline implementation are required to reduce disease burden in HoFH.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 29 Apr 2023:e029175; epub ahead of print</small></div>

<div><h4>All-Cause, Cardiovascular, and Stroke Mortality Among Foreign-Born Versus US-Born Individuals of African Ancestry.</h4><i>Looti AL, Ovbiagele B, Markovic D, Towfighi A</i><br /><AbstractText><br /><b>Background:</b><br/>Little is known about the effect of region of origin on all-cause mortality, cardiovascular mortality, and stroke mortality among Black individuals. We examined associations between nativity and mortality (all-cause, cardiovascular, and stroke) in Black individuals in the United States. Methods and Results Using the National Health Interview Service 2000 to 2014 data and mortality-linked files through 2015, we identified participants aged 25 to 74 years who self-identified as Black (n=64 717). Using a Cox regression model, we examined the association between nativity and all-cause, cardiovascular, and stroke mortality. We recorded 4329 deaths (205 stroke and 932 cardiovascular deaths). In the model adjusted for age and sex, compared with US-born Black individuals, all-cause (hazard ratio [HR], 0.44 [95% CI, 0.37-0.53]) and cardiovascular mortality (HR, 0.66 [95% CI, 0.44-0.87]) rates were lower among Black individuals born in the Caribbean, South America, and Central America, but stroke mortality rates were similar (HR, 1.01 [95% CI, 0.52-1.94]). African-born Black individuals had lower all-cause mortality (HR, 0.43 [95% CI, 0.27-0.69]) and lower cardiovascular mortality (HR, 0.42 [95% CI, 0.18-0.98]) but comparable stroke mortality (HR, 0.48 [95% CI, 0.11-2.05]). When the model was further adjusted for education, income, smoking, body mass index, hypertension, and diabetes, the difference in mortality between foreign-born Black individuals and US-born Black individuals was no longer significant. Time since migration did not significantly affect mortality outcomes among foreign-born Black individuals. <br /><b>Conclusions:</b><br/>In the United States, foreign-born Black individuals had lower all-cause mortality, a difference that was observed in recent and well-established immigrants. Foreign-born Black people had age- and sex-adjusted lower cardiovascular mortality than US-born Black people.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 29 Apr 2023:e026331; epub ahead of print</small></div>

<div><h4>US Initiative to Eliminate Racial and Ethnic Disparities in Health: The Impact on the Outcomes of ST-Segment-Elevation Myocardial Infarction in New Jersey.</h4><i>Bhatia N, Vakil D, Zinonos S, Cabrera J, ... Moreyra AE, Myocardial Infarction Data Acquisition System (MIDAS 44) Study Group *</i><br /><AbstractText><br /><b>Background:</b><br/>In 1998, President Clinton launched a federal initiative to eliminate racial and ethnic health disparities. The impact on the outcomes of ST-segment-elevation myocardial infarction has not been well studied. Methods and Results ST-segment-elevation myocardial infarction outcomes from 1994 to 2015 were studied in 7942 Black, 27 665 Hispanic, and 88 727 White patients with first admission of ST-segment-elevation myocardial infarction using the Myocardial Infarction Data Acquisition System. Logistic regressions were used to assess mortality adjusting for demographics, comorbidities, and interventional procedures. There was an overall rise from 1994 to 2015 in the use of percutaneous coronary interventions in all 3 groups. Before 1998, White patients received more percutaneous coronary interventions compared with Black and Hispanic patients (<i>P</i><0.05). After 1998, the disparity in use of percutaneous coronary interventions in Black and Hispanic patients was greatly reduced compared with White patients, and the difference reversed in favor of Hispanic patients after 2005 (<i>P</i><0.05). There was an overall downward trend of in-hospital mortality without evidence of disparity among Black, Hispanic, and White patients. A linear regression model was used with a change point in 1998. Before 1998, the slope of 1-year all-cause and cardiovascular mortality was not statistically significant. After 1998, the mortality showed negative slopes for all 3 groups, however, with lower overall crude mortality for Hispanic patients compared with Black and White patients (<i>P</i><0.0001). <br /><b>Conclusions:</b><br/>The initiative launched in 1998 may have contributed to a reduction in percutaneous coronary intervention usage disparity in patients with ST-segment-elevation myocardial infarction. Short- and long-term mortality decreased in all 3 groups, but more in the Hispanic population.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 29 Apr 2023:e026954; epub ahead of print</small></div>

<div><h4>Survey and Evaluation of Hypertension Machine Learning Research.</h4><i>du Toit C, Tran TQB, Deo N, Aryal S, ... Joe B, Padmanabhan S</i><br /><AbstractText><br /><b>Background:</b><br/>Machine learning (ML) is pervasive in all fields of research, from automating tasks to complex decision-making. However, applications in different specialities are variable and generally limited. Like other conditions, the number of studies employing ML in hypertension research is growing rapidly. In this study, we aimed to survey hypertension research using ML, evaluate the reporting quality, and identify barriers to ML\'s potential to transform hypertension care. Methods and Results The Harmonious Understanding of Machine Learning Analytics Network survey questionnaire was applied to 63 hypertension-related ML research articles published between January 2019 and September 2021. The most common research topics were blood pressure prediction (38%), hypertension (22%), cardiovascular outcomes (6%), blood pressure variability (5%), treatment response (5%), and real-time blood pressure estimation (5%). The reporting quality of the articles was variable. Only 46% of articles described the study population or derivation cohort. Most articles (81%) reported at least 1 performance measure, but only 40% presented any measures of calibration. Compliance with ethics, patient privacy, and data security regulations were mentioned in 30 (48%) of the articles. Only 14% used geographically or temporally distinct validation data sets. Algorithmic bias was not addressed in any of the articles, with only 6 of them acknowledging risk of bias. <br /><b>Conclusions:</b><br/>Recent ML research on hypertension is limited to exploratory research and has significant shortcomings in reporting quality, model validation, and algorithmic bias. Our analysis identifies areas for improvement that will help pave the way for the realization of the potential of ML in hypertension and facilitate its adoption.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 29 Apr 2023:e027896; epub ahead of print</small></div>

<div><h4>Incremental Value of Exercise ECG to Myocardial Perfusion Single-Photon Emission Computed Tomography for Prediction of Cardiac Events.</h4><i>Kraen M, Akil S, Hedén B, Berg J, ... Arheden H, Engblom H</i><br /><AbstractText><br /><b>Background:</b><br/>Both myocardial perfusion single-photon emission computed tomography (MPS) and exercise ECG (Ex-ECG) carry prognostic information in patients with stable chest pain. However, it is not fully understood if combining the findings of MPS and Ex-ECG improves risk prediction. Current guidelines no longer recommend Ex-ECG for diagnostic evaluation of chronic coronary syndrome, but Ex-ECG could still be of incremental prognostic importance. Methods and Results This study comprised 908 consecutive patients (age 63.3±9.4 years, 49% male) who performed MPS with Ex-ECG. Subjects were followed for 5 years. The end point was a composite of cardiovascular death, acute myocardial infarction, unstable angina, and unplanned percutaneous coronary intervention. National registry data and medical charts were used for end point allocation. Combining the findings of MPS and Ex-ECG resulted in concordant evidence of ischemia in 72 patients or absence of ischemia in 634 patients. Discordant results were found in 202 patients (MPS-/Ex-ECG+, n=126 and MPS+/Ex-ECG-, n=76). During follow-up, 95 events occurred. Annualized event rates significantly increased across groups (MPS-/Ex-ECG- =1.3%, MPS-/Ex-ECG+ =3.0%, MPS+/Ex-ECG- =5.1% and MPS+/Ex-ECG+ =8.0%). In multivariable analyses MPS was the strongest predictor regardless of Ex-ECG findings (MPS+/Ex-ECG-, hazard ratio [HR], 3.0, <i>P</i>=0.001 or MPS+/Ex-ECG+, HR,4.0, <i>P</i><0.001). However, an abnormal Ex-ECG almost doubled the risk in subjects with normal MPS (MPS-/Ex-ECG+, HR, 1.9, <i>P</i>=0.04). <br /><b>Conclusions:</b><br/>In patients with chronic coronary syndrome, combining the results from MPS and Ex-ECG led to improved risk prediction. Even though MPS is the stronger predictor, there is an incremental value of adding data from Ex-ECG to MPS, especially in patients with normal MPS.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 29 Apr 2023:e028313; epub ahead of print</small></div>

<div><h4>Circulating Ectonucleotidases Signal Impaired Myocardial Perfusion at Rest and Stress.</h4><i>Kroll RG, Powell C, Chen J, Snider NT, ... Murthy VL, Sutton NR</i><br /><AbstractText><br /><b>Background:</b><br/>Ectonucleotidases maintain vascular homeostasis by metabolizing extracellular nucleotides, modulating inflammation and thrombosis, and potentially, myocardial flow through adenosine generation. Evidence implicates dysfunction or deficiency of ectonucleotidases CD39 or CD73 in human disease; the utility of measuring levels of circulating ectonucleotidases as plasma biomarkers of coronary artery dysfunction or disease has not been previously reported. Methods and Results A total of 529 individuals undergoing clinically indicated positron emission tomography stress testing between 2015 and 2019 were enrolled in this single-center retrospective analysis. Baseline demographics, clinical data, nuclear stress test, and coronary artery calcium score variables were collected, as well as a blood sample. CD39 and CD73 levels were assessed as binary (detectable, undetectable) or continuous variables using ELISAs. Plasma CD39 was detectable in 24% of White and 8% of Black study participants (<i>P</i>=0.02). Of the clinical history variables examined, ectonucleotidase levels were most strongly associated with underlying liver disease and not other traditional coronary artery disease risk factors. Intriguingly, detection of circulating ectonucleotidase was inversely associated with stress myocardial blood flow (2.3±0.8 mL/min per g versus 2.7 mL/min per g±1.1 for detectable versus undetectable CD39 levels, <i>P</i><0.001) and global myocardial flow reserve (Pearson correlation between myocardial flow reserve and log(CD73) -0.19, <i>P</i><0.001). A subanalysis showed these differences held true independent of liver disease. <br /><b>Conclusions:</b><br/>Vasodilatory adenosine is the expected product of local ectonucleotidase activity, yet these data support an inverse relationship between plasma ectonucleotidases, stress myocardial blood flow (CD39), and myocardial flow reserve (CD73). These findings support the conclusion that plasma levels of ectonucleotidases, which may be shed from the endothelial surface, contribute to reduced stress myocardial blood flow and myocardial flow reserve.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 29 Apr 2023:e027920; epub ahead of print</small></div>

<div><h4>Blood Pressure Variability in Clinical Practice: Past, Present and the Future.</h4><i>Sheikh AB, Sobotka PA, Garg I, Dunn JP, ... McDonnell BJ, Fudim M</i><br /><AbstractText>Recent advances in wearable technology through convenient and cuffless systems will enable continuous, noninvasive monitoring of blood pressure (BP), heart rate, and heart rhythm on both longitudinal 24-hour measurement scales and high-frequency beat-to-beat BP variability and synchronous heart rate variability and changes in underlying heart rhythm. Clinically, BP variability is classified into 4 main types on the basis of the duration of monitoring time: very-short-term (beat to beat), short-term (within 24 hours), medium-term (within days), and long-term (over months and years). BP variability is a strong risk factor for cardiovascular diseases, chronic kidney disease, cognitive decline, and mental illness. The diagnostic and therapeutic value of measuring and controlling BP variability may offer critical targets in addition to lowering mean BP in hypertensive populations.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 29 Apr 2023:e029297; epub ahead of print</small></div>

<div><h4>Association of Multitrajectories of Lipid Indices With Premature Cardiovascular Disease: A Cohort Study.</h4><i>Tian X, Chen S, Wang P, Zhang Y, ... Wu S, Wang A</i><br /><AbstractText><br /><b>Background:</b><br/>The multitrajectory model can identify joint longitudinal patterns of different lipids simultaneously, which might help better understand the heterogeneous risk of premature cardiovascular disease (CVD) and facilitate targeted prevention programs. This study aimed to investigate the associations between multitrajectories of lipids with premature CVD. Methods and Results The study enrolled 78 526 participants from the Kailuan study, a prospective cohort study in Tangshan, China. Five distinct multitrajectories of triglyceride, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol over 6-year exposure were identified on the basis of Nagin\'s criteria, using group-based multitrajectory modeling. During a median follow-up of 6.75 years (507 645.94 person-years), 665 (0.85%) premature CVDs occurred. After adjustment for confounders, the highest risk of premature CVD was observed in group 4 (the highest and increasing triglyceride, optimal and decreasing LDL-C, low and decreasing high-density lipoprotein cholesterol) (hazard ratio [HR], 2.13 [95% CI, 1.36-3.32]), followed by group 5 (high and decreasing triglyceride, optimal and increasing LDL-C, low and decreasing high-density lipoprotein cholesterol) (HR, 2.07 [95% CI, 1.45-2.98]), and group 3 (optimal and increasing triglyceride, borderline high and increasing LDL-C, optimal and decreasing high-density lipoprotein cholesterol) (HR, 1.90 [95% CI, 1.32-2.73]). <br /><b>Conclusions:</b><br/>Our results showed that the residual risk of premature CVD caused by increasing triglyceride levels remained high despite the fact that LDL-C levels were optimal or declining over time. These findings emphasized the importance of assessing the joint longitudinal patterns of lipids and undertaking potential interventions on triglyceride lowering to reduce the residual risk of premature CVD, even among individuals with optimal LDL-C levels.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 29 Apr 2023:e029173; epub ahead of print</small></div>

<div><h4>Sex Differences in Midterm Prognostic Implications of High Platelet Reactivity After Percutaneous Coronary Intervention With Drug-Eluting Stents in East Asian Patients: Results From the PTRG-DES (Platelet Function and Genotype-Related Long-Term Prognosis in Drug-Eluting Stent-Treated Patients With Coronary Artery Disease) Consortium.</h4><i>Kim SJ, Her AY, Jeong YH, Kim BK, ... Shin ES, PTRG‐DES Consortium Investigators</i><br /><AbstractText><br /><b>Background:</b><br/>Although high platelet reactivity (HPR) on clopidogrel is associated with higher ischemic events and lower bleeding events in patients who have undergone percutaneous coronary intervention with drug-eluting stents, the differential risk of HPR in East Asian women versus men is unknown. Methods and Results We compared 11 714 patients enrolled in the PTRG-DES (Platelet Function and Genotype-Related Long-Term Prognosis in Drug-Eluting Stent-Treated Patients With Coronary Artery Disease) Consortium according to sex and the presence/absence of HPR on clopidogrel (defined as ≥252 P2Y12 reactivity units). The primary study end point was major adverse cardiac and cerebrovascular events (MACCEs; comprising all-cause mortality, myocardial infarction, cerebrovascular accident, and stent thrombosis). HPR was more common in women (46.7%) than in men (28.1%). In propensity-adjusted models, HPR was an independent predictor of MACCEs (men with HPR: hazard ratio [HR], 1.60 [95% CI, 1.20-2.12]; women with HPR: HR, 0.99 [95% CI, 0.69-1.42]) and all-cause mortality (men with HPR: HR, 1.61 [95% CI, 1.07-2.44]; women with HPR: HR, 0.92 [95% CI, 0.57-1.50]) in men, although those associations were insignificant among women. In addition, a significant interaction between sex was noted in the associations between HPR and MACCE (<i>P</i><sub>interaction</sub>=0.013) or all-cause mortality (<i>P</i><sub>interaction</sub>=0.025). <br /><b>Conclusions:</b><br/>In this study, HPR was a differential risk factor for 1-year MACCEs and all-cause mortality in women and men. And it was an independent predictor of 1-year MACCEs and all-cause mortality in men but not in women. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04734028. Registered July 9, 2003, https://clinicaltrials.gov/ct2/show/NCT04734028.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 29 Apr 2023:e027804; epub ahead of print</small></div>

<div><h4>A New Clinical Prediction Rule for Infective Endocarditis in Emergency Department Patients With Fever: Definition and First Validation of the CREED Score.</h4><i>Covino M, De Vita A, d\'Aiello A, Ravenna SE, ... Massetti M, Franceschi F</i><br /><AbstractText><br /><b>Background:</b><br/>Infective endocarditis (IE) could be suspected in any febrile patients admitted to the emergency department (ED). This study was aimed at assessing clinical criteria predictive of IE and identifying and prospectively validating a sensible and easy-to-use clinical prediction score for the diagnosis of IE in the ED. Methods and Results We conducted a retrospective observational study, enrolling consecutive patients with fever admitted to the ED between January 2015 and December 2019 and subsequently hospitalized. Several clinical and anamnestic standardized variables were collected and evaluated for the association with IE diagnosis. We derived a multivariate prediction model by logistic regression analysis. The identified predictors were assigned a score point value to obtain the Clinical Rule for Infective Endocarditis in the Emergency Department (CREED) score. To validate the CREED score we conducted a prospective observational study between January 2020 and December 2021, enrolling consecutive febrile patients hospitalized after the ED visit, and evaluating the association between the CREED score values and the IE diagnosis. A total of 15 689 patients (median age, 71 [56-81] years; 54.1% men) were enrolled in the retrospective cohort, and IE was diagnosed in 267 (1.7%). The CREED score included 12 variables: male sex, anemia, dialysis, pacemaker, recent hospitalization, recent stroke, chest pain, specific infective diagnosis, valvular heart disease, valvular prosthesis, previous endocarditis, and clinical signs of suspect endocarditis. The CREED score identified 4 risk groups for IE diagnosis, with an area under the receiver operating characteristic curve of 0.874 (0.849-0.899). The prospective cohort included 13 163 patients, with 130 (1.0%) IE diagnoses. The CREED score had an area under the receiver operating characteristic curve of 0.881 (0.848-0.913) in the validation cohort, not significantly different from the one calculated in the retrospective cohort (<i>P</i>=0.578). <br /><b>Conclusions:</b><br/>In this study, we propose and prospectively validate the CREED score, a clinical prediction rule for the diagnosis of IE in patients with fever admitted to the ED. Our data reflect the difficulty of creating a meaningful tool able to identify patients with IE among this general and heterogeneous population because of the complexity of the disease and its low prevalence in the ED setting.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 29 Apr 2023:e027650; epub ahead of print</small></div>

<div><h4>Age-Related Macular Degeneration With Visual Disability Is Associated With Cardiovascular Disease Risk in the Korean Nationwide Cohort.</h4><i>Jung W, Han K, Kim B, Hwang S, ... Lim DH, Shin DW</i><br /><AbstractText><br /><b>Background:</b><br/>Age-related macular degeneration (AMD) is the leading cause of visual disability. AMD shares some risk factors with the pathogenesis of cardiovascular disease (CVD). However, previous studies examining the association between AMD and the risk of CVD provide conflicting results. Hence, we investigated the association between AMD, visual disability, and the risk of CVD. Methods and Results This is a nationwide cohort study using data from the Korean National Health Insurance System database (2009-2019) on subjects who underwent a national health screening program in 2009. A total of 3 789 963 subjects were categorized by the presence of AMD and visual disability. Visual disability was defined as a best-corrected visual acuity of ≤20/100 by validated documentation from a specialist physician. Cox regression hazard model was used to examine the hazard ratios (HRs) of CVD, including myocardial infarction and ischemic stroke, after adjusting for potential confounders. During a mean 9.77 years of follow-up, AMD was associated with a 5% higher risk of myocardial infarction (adjusted HR [aHR], 1.05 [95% CI, 1.01-1.10]) but not associated with increased risk of overall CVD (aHR, 1.02 [95% CI, 1.00-1.05]) or ischemic stroke (aHR, 1.02 [95% CI, 0.98-1.06]). However, when AMD was accompanied by visual disability, there was increased risk of CVD (aHR, 1.17 [95% CI, 1.06-1.29]), myocardial infarction (aHR, 1.18 [95% CI, 1.01-1.37]), and ischemic stroke (aHR, 1.20 [95% CI, 1.06-1.35]). These trends were more evident in women and subjects with cardiometabolic comorbidities. <br /><b>Conclusions:</b><br/>AMD with visual disability, but not all AMD, was associated with an increased risk of CVD. Patients with AMD who have visual disability should be targeted for CVD prevention.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 29 Apr 2023:e028027; epub ahead of print</small></div>

<div><h4>BNT162b2 or CoronaVac Vaccinations Are Associated With a Lower Risk of Myocardial Infarction and Stroke After SARS-CoV-2 Infection Among Patients With Cardiovascular Disease.</h4><i>Ye X, Yan VKC, Yiu HHE, Shami JJP, ... Wong ICK, Chan EW</i><br /><AbstractText><br /><b>Background:</b><br/>COVID-19 vaccines have demonstrated effectiveness against SARS-CoV-2 infection, hospitalization, and mortality. The association between vaccination and risk of cardiovascular complications shortly after SARS-CoV-2 infection among patients with cardiovascular disease remains unknown. Methods and Results A case-control study was conducted with cases defined as patients who had myocardial infarction or stroke within 28 days after SARS-CoV-2 infection between January 1, 2022 and August 15, 2022. Controls were defined as all other patients who attended any health services and were not cases. Individuals without history of cardiovascular disease were excluded. Each case was randomly matched with 10 controls according to sex, age, Charlson comorbidity index, and date of hospital admission. Adjusted odds ratio with 95% CI was estimated using conditional logistic regression. We identified 808 cases matched with 7771 controls among all patients with cardiovascular disease. Results showed that vaccination with BNT162b2 or CoronaVac was associated with a lower risk of myocardial infarction or stroke after SARS-CoV-2 infection with a dose-response relationship. For BNT162b2, risk decreased from 0.49 (95% CI, 0.29-0.84) to 0.30 (95% CI, 0.20-0.44) and 0.17 (95% CI, 0.08-0.34) from 1 to 3 doses, respectively. Similar trends were observed for CoronaVac, with risk decreased from 0.69 (95% CI, 0.57-0.85) to 0.42 (95% CI, 0.34-0.52) and 0.32 (95% CI, 0.21-0.49) from 1 to 3 doses, respectively. <br /><b>Conclusions:</b><br/>Vaccination with BNT162b2 or CoronaVac is associated with a lower risk of myocardial infarction or stroke after SARS-CoV-2 infection among patients with cardiovascular disease.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 29 Apr 2023:e029291; epub ahead of print</small></div>

<div><h4>Cardiovascular Magnetic Resonance in Survivors of Critical Illness: Cardiac Abnormalities Are Associated With Acute Kidney Injury.</h4><i>Isaak A, Pomareda I, Mesropyan N, Kravchenko D, ... Kreyer S, Luetkens JA</i><br /><AbstractText><br /><b>Background:</b><br/>The objective of this study was to investigate cardiac abnormalities in intensive care unit (ICU) survivors of critical illness and to determine whether temporary acute kidney injury (AKI) is associated with more pronounced findings on cardiovascular magnetic resonance. Methods and Results There were 2175 patients treated in the ICU (from 2015 until 2021) due to critical illness who were screened for study eligibility. Post-ICU patients without known cardiac disease were prospectively recruited from March 2021 to May 2022. Participants underwent cardiovascular magnetic resonance including assessment of cardiac function, myocardial edema, late gadolinium enhancement, and mapping including extracellular volume fraction. Student <i>t</i> test, Mann-Whitney <i>U</i> test, and χ<sup>2</sup> tests were used. There were 48 ICU survivors (46±15 years of age, 28 men, 29 with AKI and continuous kidney replacement therapy, and 19 without AKI) and 20 healthy controls who were included. ICU survivors had elevated markers of myocardial fibrosis (T1: 995±31 ms versus 957±21 ms, <i>P</i><0.001; extracellular volume fraction: 24.9±2.5% versus 22.8±1.2%, <i>P</i><0.001; late gadolinium enhancement: 1% [0%-3%] versus 0% [0%-0%], <i>P</i><0.001), more frequent focal late gadolinium enhancement lesions (21% versus 0%, <i>P</i>=0.03), and an impaired left ventricular function (eg, ejection fraction: 57±6% versus 60±5%, <i>P</i>=0.03; systolic longitudinal strain: 20.3±3.7% versus 23.1±3.5%, <i>P</i>=0.004) compared with healthy controls. ICU survivors with AKI had higher myocardial T1 (1002±33 ms versus 983±21 ms; <i>P</i>=0.046) and extracellular volume fraction values (25.6±2.6% versus 23.9±1.9%; <i>P</i>=0.02) compared with participants without AKI. <br /><b>Conclusions:</b><br/>ICU survivors of critical illness without previously diagnosed cardiac disease had distinct abnormalities on cardiovascular magnetic resonance including signs of myocardial fibrosis and systolic dysfunction. Findings were more abnormal in participants who experienced AKI with necessity of continuous kidney replacement therapy during their ICU stay. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT05034588.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 29 Apr 2023:e029492; epub ahead of print</small></div>

<div><h4>Evaluation of Quantitative Decision-Making for Rhythm Management of Atrial Fibrillation Using Tabular Q-Learning.</h4><i>Barrett CD, Suzuki Y, Hussein S, Garg L, ... Banaei-Kashani F, Rosenberg MA</i><br /><AbstractText><br /><b>Background:</b><br/>Rhythm management is a complex decision for patients with atrial fibrillation (AF). Although clinical trials have identified subsets of patients who might benefit from a given rhythm-management strategy, for individual patients it is not always clear which strategy is expected to have the greatest mortality benefit or durability. Methods and Results In this investigation 52 547 patients with a new atrial fibrillation diagnosis between 2010 and 2020 were retrospectively identified. We applied a type of artificial intelligence called tabular Q-learning to identify the optimal initial rhythm-management strategy, based on a composite outcome of mortality, change in treatment, and sustainability of the given treatment, termed the reward function. We first applied an unsupervised learning algorithm using a variational autoencoder with K-means clustering to cluster atrial fibrillation patients into 8 distinct phenotypes. We then fit a Q-learning algorithm to predict the best outcome for each cluster. Although rate-control strategy was most frequently selected by treating providers, the outcome was superior for rhythm-control strategies across all clusters. Subjects in whom provider-selected treatment matched the Q-table recommendation had fewer total deaths (4 [8.5%] versus 473 [22.4%], odds ratio=0.32, <i>P</i>=0.02) and a greater reward (<i>P</i>=4.8×10<sup>-6</sup>). We then demonstrated application of dynamic learning by updating the Q-table prospectively using batch gradient descent, in which the optimal strategy in some clusters changed from cardioversion to ablation. <br /><b>Conclusions:</b><br/>Tabular Q-learning provides a dynamic and interpretable approach to apply artificial intelligence to clinical decision-making for atrial fibrillation. Further work is needed to examine application of Q-learning prospectively in clinical patients.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 29 Apr 2023:e028483; epub ahead of print</small></div>

<div><h4>Workplace Discrimination and Risk of Hypertension: Findings From a Prospective Cohort Study in the United States.</h4><i>Li J, Matthews TA, Clausen T, Rugulies R</i><br /><AbstractText><br /><b>Background:</b><br/>Mounting evidence has demonstrated a role of psychosocial stressors such as discrimination in hypertension and cardiovascular diseases. The objective of this study was to provide the first instance of research evidence examining prospective associations of workplace discrimination with onset of hypertension. Methods and Results Data were from MIDUS (Midlife in the United States), a prospective cohort study of adults in the United States. Baseline data were collected in 2004 to 2006, with an average 8-year follow-up period. Workers with self-reported hypertension at baseline were excluded, yielding a sample size of 1246 participants for the main analysis. Workplace discrimination was assessed using a validated 6-item instrument. During follow-up with 9923.17 person-years, 319 workers reported onset of hypertension, and incidence rates of hypertension were 25.90, 30.84, and 39.33 per 1000 person-years among participants with low, intermediate, and high levels of workplace discrimination, respectively. Cox proportional hazards regression analyses demonstrated that workers who experienced high exposure to workplace discrimination, compared with workers with low exposure, had a higher hazard of hypertension (adjusted hazard ratio, 1.54 [95% CI, 1.11-2.13]). Sensitivity analysis excluding more baseline hypertension cases based on additional information on blood pressure plus antihypertensive medication use (N=975) showed slightly stronger associations. A trend analysis showed an exposure-response association. <br /><b>Conclusions:</b><br/>Workplace discrimination was prospectively associated with elevated risk of hypertension among US workers. The adverse impacts of discrimination on cardiovascular disease have major implications for workers\' health and indicate a need for government and employer policy interventions addressing discrimination.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 26 Apr 2023:e027374; epub ahead of print</small></div>

<div><h4>Association of Prenatal Depression With New Cardiovascular Disease Within 24 Months Postpartum.</h4><i>Ackerman-Banks CM, Lipkind HS, Palmsten K, Pfeiffer M, Gelsinger C, Ahrens KA</i><br /><AbstractText><br /><b>Background:</b><br/>Although depression is well established as an independent risk factor for cardiovascular disease (CVD) in the nonpregnant population, this association has largely not been investigated in pregnant populations. We aimed to estimate the cumulative risk of new CVD in the first 24 months postpartum among pregnant individuals diagnosed with prenatal depression compared with patients without depression diagnosed during pregnancy. Methods and Results Our longitudinal population-based study included pregnant individuals with deliveries during 2007 to 2019 in the Maine Health Data Organization\'s All Payer Claims Data. We excluded those with prepregnancy CVD, multifetal gestations, or no continuous health insurance during pregnancy. Prenatal depression and CVD (heart failure, ischemic heart disease, arrhythmia/cardiac arrest, cardiomyopathy, cerebrovascular disease, and chronic hypertension) were identified by <i>International Classification of Diseases, Ninth Revision</i> (<i>ICD-9</i>)/<i>International Classification of Diseases, Tenth Revision</i> (<i>ICD-10</i>) codes. Cox models were used to estimate hazard ratios (HRs), adjusting for potential confounding factors. Analyses were stratified by hypertensive disorder of pregnancy. A total of 119 422 pregnancies were examined. Pregnant individuals with prenatal depression had an increased risk of ischemic heart disease, arrhythmia/cardiac arrest, cardiomyopathy, and new hypertension (adjusted HR [aHR], 1.83 [95% CI, 1.20-2.80], aHR, 1.60 [95% CI, 1.10-2.31], aHR, 1.61 [95% CI, 1.15-2.24], and aHR, 1.32 [95% CI, 1.17-1.50], respectively). When the analyses were stratified by co-occurring hypertensive disorders of pregnancy, several of these associations persisted. <br /><b>Conclusions:</b><br/>The cumulative risk of a new CVD diagnosis postpartum was elevated among individuals with prenatal depression and persists even in the absence of co-occurring hypertensive disorders of pregnancy. Further research to determine the causal pathway can inform postpartum CVD preventive measures.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 19 Apr 2023:e028133; epub ahead of print</small></div>