<div><h4>Acute Myocardial Infarction: Etiologies and Mimickers in Young Patients.</h4><i>Krittanawong C, Khawaja M, Tamis-Holland JE, Girotra S, Rao SV</i><br /><AbstractText>Acute myocardial infarction is an important cause of death worldwide. While it often affects patients of older age, acute myocardial infarction is garnering more attention as a significant cause of morbidity and mortality among young patients (<45 years of age). More specifically, there is a focus on recognizing the unique etiologies for myocardial infarction in these younger patients as nonatherosclerotic etiologies occur more frequently in this population. As such, there is a potential for delayed and inaccurate diagnoses and treatments that can carry serious clinical implications. The understanding of acute myocardial infarction manifestations in young patients is evolving, but there remains a significant need for better strategies to rapidly diagnose, risk stratify, and manage such patients. This comprehensive review explores the various etiologies for acute myocardial infarction in young adults and outlines the approach to efficient diagnosis and management for these unique patient phenotypes.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 19 Sep 2023:e029971; epub ahead of print</small></div>

<div><h4>Insulin-Like Growth Factor 1 Receptor Deficiency Alleviates Angiotensin II-Induced Cardiac Fibrosis Through the Protein Kinase B/Extracellular Signal-Regulated Kinase/Nuclear Factor-κB Pathway.</h4><i>Zhu J, Li Q, Sun Y, Zhang S, ... Sun Z, Zhang L</i><br /><AbstractText><br /><b>Background:</b><br/>The renin-angiotensin system plays a crucial role in the development of heart failure, and Ang II (angiotensin II) acts as the critical effector of the renin-angiotensin system in regulating cardiac fibrosis. However, the mechanisms of cardiac fibrosis are complex and still not fully understood. IGF1R (insulin-like growth factor 1 receptor) has multiple functions in maintaining cardiovascular homeostasis, and low-dose IGF1 treatment is effective in relieving Ang II-induced cardiac fibrosis. Here, we aimed to investigate the molecular mechanism of IGF1R in Ang II-induced cardiac fibrosis. Methods and Results Using primary mouse cardiac microvascular endothelial cells and fibroblasts, in vitro experiments were performed. Using C57BL/6J mice and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9)-mediated IGF1R heterozygous knockout (<i>Igf1r</i><sup>+/-</sup>) mice, cardiac fibrosis mouse models were induced by Ang II for 2 weeks. The expression of IGF1R was examined by quantitative reverse transcription polymerase chain reaction, immunohistochemistry, and Western blot. Mice heart histologic changes were evaluated using Masson and picro sirius red staining. Fibrotic markers and signal molecules indicating the function of the Akt (protein kinase B)/ERK (extracellular signal-regulated kinase)/nuclear factor-κB pathway were detected using quantitative reverse transcription polymerase chain reaction and Western blot. RNA sequencing was used to explore IGF1R-mediated target genes in the hearts of mice, and the association of IGF1R and G-protein-coupled receptor kinase 5 was identified by coimmunoprecipitation. More important, blocking IGF1R signaling significantly suppressed endothelial-mesenchymal transition in primary mouse cardiac microvascular endothelial cells and mice in response to transforming growth factor-β1 or Ang II, respectively. Deficiency or inhibition of IGF1R signaling remarkably attenuated Ang II-induced cardiac fibrosis in primary mouse cardiac fibroblasts and mice. We further observed that the patients with heart failure exhibited higher blood levels of IGF1 and IGF1R than healthy individuals. Moreover, Ang II treatment significantly increased cardiac IGF1R in wild type mice but led to a slight downregulation in <i>Igf1r</i><sup><i>+/-</i></sup> mice. Interestingly, IGF1R deficiency significantly alleviated cardiac fibrosis in Ang II-treated mice. Mechanistically, the phosphorylation level of Akt and ERK was upregulated in Ang II-treated mice, whereas blocking IGF1R signaling in mice inhibited these changes of Akt and ERK phosphorylation. Concurrently, phosphorylated p65 of nuclear factor-κB exhibited similar alterations in the corresponding group of mice. Intriguingly, IGF1R directly interacted with G-protein-coupled receptor kinase 5, and this association decreased ≈50% in <i>Igf1r</i><sup><i>+/-</i></sup> mice. In addition, <i>Grk5</i> deletion downregulated expression of the Akt/ERK/nuclear factor-κB signaling pathway in primary mouse cardiac fibroblasts. <br /><b>Conclusions:</b><br/>IGF1R signaling deficiency alleviates Ang II-induced cardiac fibrosis, at least partially through inhibiting endothelial-mesenchymal transition via the Akt/ERK/nuclear factor-κB pathway. Interestingly, G-protein-coupled receptor kinase 5 associates with IGF1R signaling directly, and it concurrently acts as an IGF1R downstream effector. This study suggests the promising potential of IGF1R as a therapeutic target for cardiac fibrosis.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 18 Sep 2023:e029631; epub ahead of print</small></div>

<div><h4>Repair of Aortic Regurgitation in Young Adults: Sooner Rather Than Later.</h4><i>Barradas-Pires A, Merás P, Constantine A, Costola G, ... Rubio AM, Dimopoulos K</i><br /><AbstractText><br /><b>Background:</b><br/>Establishing surgical criteria for aortic valve replacement (AVR) in severe aortic regurgitation in young adults is challenging due to the lack of evidence-based recommendations. We studied indications for AVR in young adults with severe aortic regurgitation and their outcomes, as well as the relationship between presurgical echocardiographic parameters and postoperative left ventricular (LV) size, function, clinical events, and valve-related complications. Methods and Results Data were collected retrospectively on 172 consecutive adult patients who underwent AVR or repair for severe aortic regurgitation between 2005 and 2019 in a tertiary cardiac center (age at surgery 29 [22-41] years, 81% male). One-third underwent surgery before meeting guideline indications. Postsurgery, 65% achieved LV size and function normalization. LV ejection fraction showed no significant change from baseline. A higher presurgical LV end-systolic diameter correlated with a lack of LV normalization (odds ratio per 1-cm increase 2.81, <i>P</i><0.01). The baseline LV end-systolic diameter cut-off for predicting lack of LV normalization was 43 mm. Pre- and postoperative LV dimensions and postoperative LV ejection fraction predicted clinical events during follow-up. Prosthetic valve-related complications occurred in 20.3% during an average 5.6-year follow-up. Freedom from aortic reintervention was 98%, 96.5%, and 85.4% at 1, 5, and 10 years, respectively. <br /><b>Conclusions:</b><br/>Young adult patients with increased baseline LV end-systolic diameter or prior cardiac surgery are less likely to achieve LV normalization after AVR. Clinicians should carefully balance the long-term benefits of AVR against procedural risks and future interventions, especially in younger patients. Evidence-based criteria for AVR in severe aortic regurgitation in young adults are crucial to improve outcomes.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 18 Sep 2023:e029251; epub ahead of print</small></div>

<div><h4>Sex-Specific Comparison Between Triglyceride Glucose Index and Modified Triglyceride Glucose Indices to Predict New-Onset Hypertension in Middle-Aged and Older Adults.</h4><i>Lee JH, Heo SJ, Kwon YJ</i><br /><AbstractText><br /><b>Background:</b><br/>Triglyceride and glucose (TyG) index and TyG-related indices combined with obesity-related markers are considered important markers of insulin resistance. We aimed to examine the association between the TyG index and modified TyG indices with new-onset hypertension and their predictive ability stratified by sex. Methods and Results We analyzed data from 5414 Korean Genome and Epidemiology Study participants aged 40 to 69 years. Multiple Cox proportional hazard regression analyses were conducted to estimate the hazard ratio (HR) and 95% CI for new-onset hypertension according to sex-specific tertile groups after confounder adjustments. To evaluate the predictive performance of these indices for new-onset hypertension, we calculated Harrell\'s C-index (95% CI). Over a 9.5-year follow-up period, 1014 men and 1012 women developed new-onset hypertension. Compared with the lowest tertile (T) group, the adjusted HR and 95% CI for new-onset hypertension in T3 for TyG, TyG-body mass index, TyG-waist circumference, and TyG-waist-to-height ratio were 1.16 (0.95-1.40), 1.11 (0.84-1.48), 1.77 (1.38-2.27), and 1.68 (1.33-2.13) in men and 1.37 (1.13-1.66), 1.55 (1.16-2.06), 1.43 (1.15-1.79), and 1.64 (1.30-2.07) in women, respectively. The C-indices of TyG-waist-to-height ratio for new-onset hypertension were significantly higher than those of TyG and TyG-body mass index in both men and women. <br /><b>Conclusions:</b><br/>TyG and TyG-body mass index were significantly associated with new-onset hypertension only in women. TyG-waist circumference and TyG-waist-to-height ratio were significantly associated with new-onset hypertension in both men and women. A sex-specific approach is required when using TyG and modified TyG indices to identify individuals at risk of incident hypertension.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 18 Sep 2023:e030022; epub ahead of print</small></div>

<div><h4>Vagus Nerve Stimulation and Inflammation in Cardiovascular Disease: A State-of-the-Art Review.</h4><i>Bazoukis G, Stavrakis S, Armoundas AA</i><br /><AbstractText>Vagus nerve stimulation (VNS) has been found to exert anti-inflammatory effects in different clinical settings and has been associated with improvement of clinical outcomes. However, evidence on the mechanistic link between the potential association of inflammatory status with clinical outcomes following VNS is scarce. This review aims to summarize the existing knowledge linking VNS with inflammation and its potential link with major outcomes in cardiovascular diseases, in both preclinical and clinical studies. Existing data show that in the setting of myocardial ischemia and reperfusion, VNS seems to reduce inflammation resulting in reduced infarct size and reduced incidence of ventricular arrhythmias during reperfusion. Furthermore, VNS has a protective role in vascular function following myocardial ischemia and reperfusion. Atrial fibrillation burden has also been reduced by VNS, whereas suppression of inflammation may be a potential mechanism for this effect. In the setting of heart failure, VNS was found to improve systolic function and reverse cardiac remodeling. In summary, existing experimental data show a reduction in inflammatory markers by VNS, which may cause improved clinical outcomes in cardiovascular diseases. However, more data are needed to evaluate the association between the inflammatory status with the clinical outcomes following VNS.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 18 Sep 2023:e030539; epub ahead of print</small></div>

<div><h4>Prevalence, Associated Factors, and Echocardiographic Estimation of Left Atrial Hypertension in Patients With Atrial Fibrillation.</h4><i>Mukai Y, Nakanishi K, Daimon M, Iwama K, ... Morita H, Komuro I</i><br /><AbstractText><br /><b>Background:</b><br/>Elevated left atrial (LA) pressure predisposes individuals to the initiation and persistence of atrial fibrillation (AF), and LA hypertension is associated with AF recurrence after catheter ablation (CA). However, the exact frequency and factors associated with LA hypertension are unknown, and its noninvasive estimation is challenging. This study aimed to investigate the prevalence and determinants of LA hypertension in patients with AF who underwent first CA. Methods and Results We examined 183 patients with AF who underwent conventional and speckle-tracking echocardiography before CA to assess LA size, reservoir strain, and stiffness. Direct LA pressure was measured at the time of CA, and LA hypertension was defined as mean LA pressure >15 mm Hg. Thirty-three (18.0%) patients exhibited LA hypertension. Patients with LA hypertension had a significantly larger LA volume index (40.2 [28.4-52.1] versus 34.1 [26.9-42.4] mL/m<sup>2</sup>, <i>P</i>=0.025), reduced LA reservoir strain (15.1 [10.4-21.7] versus 22.7 [14.4-32.3] %, <i>P</i>=0.002) and increased LA stiffness (0.69 [0.34-0.99] versus 0.36 [0.24-0.54], <i>P</i><0.001). Multivariable analyses showed that waist circumference, C-reactive protein level, LA reservoir strain, and LA stiffness were independently associated with LA hypertension (all <i>P</i><0.05), while LA volume and E/e\' ratio were not. Among echocardiographic parameters, receiver operating characteristic curve analysis identified LA stiffness as the best predictor of LA hypertension. <br /><b>Conclusions:</b><br/>Approximately 20% of patients with AF who underwent CA had LA hypertension. Central obesity and inflammation might be involved in the pathophysiological mechanisms of LA hypertension, and echocardiography-derived LA stiffness may have clinical utility for the detection of LA hypertension before CA.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 13 Sep 2023:e030325; epub ahead of print</small></div>

<div><h4>Lipoprotein(a) Testing Trends in a Large Academic Health System in the United States.</h4><i>Bhatia HS, Hurst S, Desai P, Zhu W, Yeang C</i><br /><AbstractText><br /><b>Background:</b><br/>Despite its high prevalence and clinical significance, clinical measurement of lipoprotein(a) is rare but has not been systematically quantified. We assessed the prevalence of lipoprotein(a) testing overall, in those with various cardiovascular disease (CVD) conditions and in those undergoing cardiac testing across 6 academic medical centers associated with the University of California, in total and by year from 2012 to 2021. Methods and Results In this observational study, data from the University of California Health Data Warehouse on the number of individuals with unique lipoprotein(a) testing, unique CVD diagnoses (using <i>International Classification of Diseases, Tenth Revision</i> [<i>ICD-10</i>], codes), and other unique cardiac testing were collected. The proportion of total individuals, the proportion of individuals with a given CVD diagnosis, and the proportion of individuals with a given cardiac test and lipoprotein(a) testing any time during the study period were calculated. From 2012 to 2021, there were 5 553 654 unique adults evaluated in the University of California health system, of whom 18 972 (0.3%) had lipoprotein(a) testing. In general, those with lipoprotein(a) testing were more likely to be older, men, and White race, with a greater burden of CVD. Lipoprotein(a) testing was performed in 6469 individuals with ischemic heart disease (2.9%), 836 with aortic stenosis (3.1%), 4623 with family history of CVD (3.3%), 1202 with stroke (1.7%), and 612 with coronary artery calcification (6.1%). For most conditions, the prevalence of testing in the same year as the diagnosis of CVD was relatively stable, with a small upward trend over time. Lipoprotein(a) testing was performed in 10 753 individuals (1.8%) who had lipid panels, with higher rates with more specialized testing, including coronary computed tomography angiography (6.8%) and apolipoprotein B (63.0%). <br /><b>Conclusions:</b><br/>Lipoprotein(a) testing persists at low rates, even among those with diagnosed CVD, and remained relatively stable over the study period.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 13 Sep 2023:e031255; epub ahead of print</small></div>

<div><h4>Long-Term Exposure to Ambient PM and Hospitalizations for Myocardial Infarction Among US Residents: A Difference-in-Differences Analysis.</h4><i>Wang Y, Qiu X, Wei Y, Schwartz JD</i><br /><AbstractText><br /><b>Background:</b><br/>Air pollution has been recognized as an untraditional risk factor for myocardial infarction (MI). However, the MI risk attributable to long-term exposure to fine particulate matter ≤2.5 μm in aerodynamic diameter (PM<sub>2.5</sub>) is unclear, especially in younger populations, and few studies have represented the general population or had power to examine comorbidities. Methods and Results We applied the difference-in-differences approach to estimate the relationship between annual PM<sub>2.5</sub> exposure and hospitalizations for MI among US residents and further identified potential susceptible subpopulations. All hospital admissions for MI in 10 US states over the period 2002 to 2016 were obtained from the Healthcare Cost and Utilization Project State Inpatient Database. In total, 1 914 684 MI hospital admissions from 8106 zip codes were included in this study. We observed a 1.35% (95% CI, 1.11-1.59) increase in MI hospitalization rate for 1-μg/m<sup>3</sup> increase in annual PM<sub>2.5</sub> exposure. The estimate was robust to adjustment for surface pressure, relative humidity, and copollutants. In the population exposed to ≤12 μg/m<sup>3</sup>, there was a larger increment of 2.17% (95% CI, 1.79-2.56) in hospitalization rate associated with 1-μg/m<sup>3</sup> increase in PM<sub>2.5</sub>. Young people (0-34 years of age) and elderly people (≥75 years of age) were the 2 most susceptible age groups. Residents living in more densely populated or poorer areas and individuals with comorbidities were observed to be at a greater risk. <br /><b>Conclusions:</b><br/>This study indicates long-term residential exposure to PM<sub>2.5</sub> could increase risk of MI among the general US population, people with comorbidities, and poorer individuals. The association persists below current standards.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 13 Sep 2023:e029428; epub ahead of print</small></div>

<div><h4>Risk Factors and Outcomes With Progressive Mitral Annular Calcification.</h4><i>Lee HJ, Seo J, Gwak SY, Kim K, ... Ha JW, Shim CY</i><br /><AbstractText><br /><b>Background:</b><br/>Mitral annular calcification (MAC) is a chronic degenerative process that may progress. This study aimed to investigate associating factors and clinical implications of MAC progression. Methods and Results Among 560 patients with MAC identified by transthoracic echocardiography between January 2012 and June 2016, 138 patients (mean±SD age 72.7±10.2 years, 73 women) with mild or moderate MAC who received follow-up examination within 18 to 36 months were retrospectively analyzed. Progressive MAC was defined as hemodynamic or structural profiles that had worsened by more than 1 grade. Hemodynamic features were assessed by the transmitral mean diastolic pressure gradient (MDPG), and structural features were assessed by the MAC angle in the parasternal short-axis view. The clinical outcome was defined as a composite of all-cause mortality, hospitalization for heart failure, and occurrence of ischemic stroke. Forty-three patients (31.2%) showed progressive MAC. Patients with progressive MAC had higher systolic blood pressure, pulse pressure, MAC angle, and MDPG than those with stable MAC. Patients with progressive MAC had smaller left ventricular (LV) end-systolic dimensions and higher LV ejection fractions compared with those with stable MAC. In multivariate analysis, pulse pressure, LV ejection fraction, MAC angle, and MDPG at baseline were significantly associated with MAC progression. During a median of 39.2 months\' follow-up, patients with progressive MAC showed poorer clinical outcomes than those with stable MAC (log-rank <i>P</i>=0.015). <br /><b>Conclusions:</b><br/>MAC progression is not rare and is associated with structural substrate and hemodynamic loads that result in mechanical stress. Patients with progressive MAC have poor outcomes.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 13 Sep 2023:e030620; epub ahead of print</small></div>

<div><h4>Zymosan A Improved Doxorubicin-Induced Ventricular Remodeling by Evoking Heightened Cardiac Inflammatory Responses and Healing in Mice.</h4><i>Xu G, Hao Z, Xiao W, Tan R, ... Xia Y, Liu Y</i><br /><AbstractText><br /><b>Background:</b><br/>Doxorubicin-induced myocardial injury is reflected by the presence of vacuolization in both clinical and animal models. The lack of scar tissue to replace the vacuolizated cardiomyocytes indicates that insufficient cardiac inflammation and healing occurred following doxorubicin injection. Whether improved macrophage activity by zymosan A (zymosan) ameliorates doxorubicin-induced ventricular remodeling in mice is unknown. Methods and Results Mice were intravenously injected with vehicle or doxorubicin (5 mg/kg per week, 4 weeks), and cardiac structure and function were assessed by echocardiography. Two distinct macrophage subsets in hearts following doxorubicin injection were measured at different time points by flow cytometry. Moreover, cardiomyocyte vacuolization, capillary density, collagen content, and ventricular tensile strength were assessed. The therapeutic effect of zymosan (3 mg/kg, single injection) on doxorubicin-induced changes in the aforementioned parameters was determined. At the cellular level, the polarization of monocytes to proinflammatory or reparative macrophages were measured, with or without doxorubicin (0.25 and 0.5 μmol/L). Doxorubicin led to less proinflammatory and reparative macrophage infiltration in the heart in the early phase, with decreased cardiac capillary density and collagen III in the chronic phase. In cell culture, doxorubicin (0.5 μmol/L) repressed macrophage transition toward both proinflammatory and reparative subset. Zymosan enhanced both proinflammatory and reparative macrophage infiltration in doxorubicin-injected hearts, evoking a heightened acute inflammatory response. Zymosan alleviated doxorubicin-induced cardiomyocyte vacuolization in the chronic phase, in parallel with enhanced collagen content, capillary density, and ventricular tensile strength. <br /><b>Conclusions:</b><br/>Zymosan improved cardiac healing and ameliorated doxorubicin-induced ventricular remodeling and dysfunction by activating macrophages at an optimal time.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 13 Sep 2023:e030200; epub ahead of print</small></div>

<div><h4>Association of PCSK9 Inhibitor Initiation on Statin Adherence and Discontinuation.</h4><i>LaFratte C, Peasah SK, Huang Y, Hall D, Patel U, Good CB</i><br /><AbstractText><br /><b>Background:</b><br/>PCSK9is (proprotein convertase subtilisin/kexin type 9 inhibitors) are well tolerated, potently lower cholesterol, and decrease cardiovascular events when added to statins. However, statin adherence may decrease after PCSK9i initiation and alter clinical outcomes. We evaluate the association of PCSK9i initiation on statin discontinuation and adherence. Methods and Results In this retrospective pre-post difference-in-difference analysis, new PCSK9i claims were propensity matched with statin-alone users (April 2017-September 2019). The primary outcomes were statin adherence (proportion of days covered) and statin discontinuation (absence of statin coverage for at least 60 days) 12 months following PCSK9i initiation. Secondary outcomes included low-density lipoprotein cholesterol levels after 1 year. A total of 220 538 statin users and 700 PCSK9i users were identified, from which 178 on PCSK9i were included and matched to 712 on statins alone. At 12 months, mean statin proportion of days covered decreased from 67% to 48% in the PCSK9i group but increased from 68% to 86% in the statin-alone groups (<i>P</i><0.0001). Statin discontinuation rates increased from 11% to 39% in the PCSK9i group and from 7% to 9% in the statin-alone group (<i>P</i>=0.0041). Patients with low-density lipoprotein cholesterol <70 mg/dL increased from 5% to 68% with PCSK9i but increased from 16% to 24% with statins alone (<i>P</i><0.0001). Changes in hospitalization rates were similar between both groups during the follow-up period. <br /><b>Conclusions:</b><br/>PCSK9i initiation was associated with decreased low-density lipoprotein cholesterol, higher statin discontinuation, and reduced statin adherence.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 13 Sep 2023:e029707; epub ahead of print</small></div>

<div><h4> and Are Required in the Endocardial Lineage for Heart Valve Development.</h4><i>Wu B, Wu B, Benkaci S, Shi L, ... Wang Y, Zhou B</i><br /><AbstractText><br /><b>Background:</b><br/>Endocardial cells are a major progenitor population that gives rise to heart valves through endocardial cushion formation by endocardial to mesenchymal transformation and the subsequent endocardial cushion remodeling. Genetic variants that affect these developmental processes can lead to congenital heart valve defects. <i>Crk</i> and <i>Crkl</i> are ubiquitously expressed genes encoding cytoplasmic adaptors essential for cell signaling. This study aims to explore the specific role of <i>Crk</i> and <i>Crkl</i> in the endocardial lineage during heart valve development. Methods and Results We deleted <i>Crk</i> and <i>Crkl</i> specifically in the endocardial lineage. The resultant heart valve morphology was evaluated by histological analysis, and the underlying cellular and molecular mechanisms were investigated by immunostaining and quantitative reverse transcription polymerase chain reaction. We found that the targeted deletion of <i>Crk</i> and <i>Crkl</i> impeded the remodeling of endocardial cushions at the atrioventricular canal into the atrioventricular valves. We showed that apoptosis was temporally increased in the remodeling atrioventricular endocardial cushions, and this developmentally upregulated apoptosis was repressed by deletion of <i>Crk</i> and <i>Crkl</i>. Loss of <i>Crk</i> and <i>Crkl</i> also resulted in altered extracellular matrix production and organization in the remodeling atrioventricular endocardial cushions. These morphogenic defects were associated with altered expression of genes in BMP (bone morphogenetic protein), connective tissue growth factor, and WNT signaling pathways, and reduced extracellular signal-regulated kinase signaling activities. <br /><b>Conclusions:</b><br/>Our findings support that <i>Crk</i> and <i>Crkl</i> have shared functions in the endocardial lineage that critically regulate atrioventricular valve development; together, they likely coordinate the morphogenic signals involved in the remodeling of the atrioventricular endocardial cushions.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 13 Sep 2023:e029683; epub ahead of print</small></div>

<div><h4>Neighborhood Social Vulnerability and Interstage Weight Gain: Evaluating the Role of a Home Monitoring Program.</h4><i>Shustak RJ, Huang J, Tam V, Stagg A, ... Guevara JP, Gardner MM</i><br /><AbstractText><br /><b>Background:</b><br/>Poor interstage weight gain is a risk factor for adverse outcomes in infants with hypoplastic left heart syndrome. We sought to examine the association of neighborhood social vulnerability and interstage weight gain and determine if this association is modified by enrollment in our institution\'s Infant Single Ventricle Management and Monitoring Program (ISVMP). Methods and Results We performed a retrospective single-center study of infants with hypoplastic left heart syndrome before (2007-2010) and after (2011-2020) introduction of the ISVMP. The primary outcome was interstage weight gain, and the secondary outcome was interstage growth failure. Multivariable linear and logistic regression models were used to examine the association between the Social Vulnerability Index and the outcomes. We introduced an interaction term into the models to test for effect modification by the ISVMP. We evaluated 217 ISVMP infants and 111 pre-ISVMP historical controls. The Social Vulnerability Index was associated with interstage growth failure (<i>P</i>=0.001); however, enrollment in the ISVMP strongly attenuated this association (<i>P</i>=0.04). Pre-ISVMP, as well as high- and middle-vulnerability infants gained 4 g/d less and were significantly more likely to experience growth failure than low-vulnerability infants (high versus low: adjusted odds ratio [aOR], 12.5 [95% CI, 2.5-62.2]; middle versus low: aOR, 7.8 [95% CI, 2.0-31.2]). After the introduction of the ISVMP, outcomes did not differ by Social Vulnerability Index tertile. Infants with middle and high Social Vulnerability Index scores who were enrolled in the ISVMP gained 4 g/d and 2 g/d more, respectively, than pre-ISVMP controls. <br /><b>Conclusions:</b><br/>In infants with hypoplastic left heart syndrome, high social vulnerability is a risk factor for poor interstage weight gain. However, enrollment in the ISVMP significantly reduces growth disparities.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 13 Sep 2023:e030029; epub ahead of print</small></div>

<div><h4>Sex-Specific Associations of Obstructive Sleep Apnea Risk With Patient Characteristics and Functional Outcomes After Acute Myocardial Infarction: Evidence From the VIRGO Study.</h4><i>Gupta A, Barthel AB, Mahajan S, Dreyer RP, ... Lichtman JH, Krumholz HM</i><br /><AbstractText><br /><b>Background:</b><br/>Though associations between obstructive sleep apnea (OSA) and cardiovascular outcomes are well described, limited data exist regarding the impact of OSA on sex-specific outcomes after acute myocardial infarction (AMI). Methods and Results The VIRGO (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients) study enrolled 3572 adults aged 18 to 55 years with AMI from the United States and Spain during 2008 to 2012. We included patients for whom the Berlin Questionnaire for OSA was scored at the time of AMI admission (3141; 2105 women, 1036 men). We examined the sex-specific association between baseline OSA risk with functional outcomes including health status and depressive symptoms at 1 and 12 months after AMI. Among both groups, 49% of patients were at high risk for OSA (1040 women; 509 men), but only 4.7% (148) of patients had a diagnosed history of OSA. Though patients with a high OSA risk reported worse physical and mental health status and depression than low-risk patients in both sexes, the difference in these functional outcomes was wider in women than men. Moreover, women with a high OSA risk had worse health status, depression, and quality of life than high-risk men, both at baseline and at 1 and 12 months after AMI. <br /><b>Conclusions:</b><br/>Young women with a high OSA risk have poorer health status and more depressive symptoms than men at the time of AMI, which may place them at higher risk of poorer health outcomes over the year following the AMI. Further, the majority of patients at high risk of OSA are undiagnosed at the time of presentation of AMI.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 13 Sep 2023:e027225; epub ahead of print</small></div>

<div><h4>Association Between Onset of Type 2 Diabetes and Risk of Atrial Fibrillation in New Zealanders With Impaired Glucose Tolerance Over 25 Years.</h4><i>Yu D, Qu B, Osuagwu UL, Pickering K, ... Zhao Z, Simmons D</i><br /><AbstractText><br /><b>Background:</b><br/>The association between the onset of type 2 diabetes (T2D) and atrial fibrillation (AF) risk in individuals with impaired glucose tolerance (IGT) remains unclear. This study aimed to investigate the relationship between the incident onset of T2D and 5- and 10-year (after the landmark period) risks of AF in people with IGT identified in South and West Auckland primary care settings between 1994 and 2019. Methods and Results We compared AF risk in patients with IGT with and without newly diagnosed T2D within a 1- to 5-year exposure window. Tapered matching and landmark analysis (to address immortal bias) were used to control for confounding variables. The cohorts incorporated 785 patients who had T2D newly diagnosed within 5 years from enrollment (landmark date) and 15 079 patients without a T2D diagnosis. Patients progressing to T2D exhibited significantly higher 5-year (after the landmark period) AF risk (hazard ratio [HR], 1.34 [95% CI, 1.10-1.63]) and 10-year (after the landmark period) AF risk (HR, 1.28 [95% CI, 1.02-1.62]) compared with those without incident T2D. The association was more pronounced among men, older patients, socioeconomically deprived individuals, current smokers, those with higher metabolic measures, and lower renal function. New Zealand European ethnicity was associated with a lower 5- and 10-year risk of AF. <br /><b>Conclusions:</b><br/>This study found a mediating effect of T2D on the risk of AF in a population with IGT in New Zealand. The development of risk scores and future replication studies can help identify and guide management of individuals with IGT at the highest risk of AF following incident T2D.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 13 Sep 2023:e030159; epub ahead of print</small></div>

<div><h4>Association of Socioeconomic Status With Life\'s Essential 8 Varies by Race and Ethnicity.</h4><i>Williams A, Nolan TS, Brock G, Garner J, ... Sanchez EJ, Joseph JJ</i><br /><AbstractText><br /><b>Background:</b><br/>The American Heart Association\'s Life\'s Essential 8 (LE8) are 8 risk factors for cardiovascular disease, with poor attainment across all racial, ethnic, and socioeconomic groups. Attainment is lowest among Americans of low socioeconomic status (SES). Evidence suggests the association of SES with LE8 may vary by race and ethnicity. Methods and Results The association of 4 SES categories (education, income-to-poverty line ratio, employment, insurance) with LE8 was computed in age-adjusted linear regression models, with an interaction term for race and ethnicity, using National Health and Nutrition Examination Survey data, years 2011 to 2018. The sample (n=13 529) had a median age of 48 years (51% female) with weighting to be representative of the US population. The magnitude of positive association of college education (relative to ≤high school) with LE8 was greater among non-Hispanic White Americans (NHWA) compared with non-Hispanic Black Americans, Hispanic Americans, and non-Hispanic Asian Americans (all interactions <i>P</i><0.001). NHWA had a greater magnitude of positive association of income-to-poverty line ratio with LE8, compared with non-Hispanic Black Americans, Hispanic Americans, and non-Hispanic Asian Americans (all interactions <i>P</i><0.001). NHWA with Medicaid compared with private insurance had a greater magnitude of negative association with LE8 compared with non-Hispanic Black Americans, non-Hispanic Asian Americans, or Hispanic Americans (all interactions <i>P</i><0.01). NHWA unemployed due to disability or health condition (compared with employed) had a greater magnitude of negative association with LE8 than non-Hispanic Black Americans, non-Hispanic Asian Americans, or Hispanic Americans (all interactions <i>P</i><0.05). <br /><b>Conclusions:</b><br/>The magnitude of association of SES with LE8 is greatest among NHWA. More research is needed on SES\'s role in LE8 attainment in minority group populations.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 13 Sep 2023:e029254; epub ahead of print</small></div>

<div><h4>Association of Magnesium Depletion Score With Cardiovascular Disease and Its Association With Longitudinal Mortality in Patients With Cardiovascular Disease.</h4><i>Ye L, Zhang C, Duan Q, Shao Y, Zhou J</i><br /><AbstractText><br /><b>Background:</b><br/>Dietary magnesium and serum magnesium play an important part in cardiovascular disease (CVD). However, the association between magnesium depletion score (MDS) and CVD development and prognosis remains unclear. This analysis examines the cross-sectional relationship between MDS and CVD, and the longitudinal association between MDS and all-cause and CVD mortality in individuals with CVD. Methods and Results In all, 42 711 individuals were selected from the National Health and Nutrition Examination Survey, including 5015 subjects with CVD. The association between MDS and total and individual CVDs was examined using the survey-weighted multiple logistic regression analysis. Among 5011 patients with CVD, 2285 and 927 participants were recorded with all-cause and CVD deaths, respectively. We applied survey-weighted Cox proportional hazards regression analyses to investigate the impact of MDS on the mortality of individuals with CVD. The CVD group had higher MDS levels than the non-CVD groups. After controlling all confounding factors, individuals with MDS of 2 and ≥3 had higher odds of total CVD and specific CVD than those with MDS of 0. Besides, each 1-unit increase in MDS was strongly related to the risk of total CVD and specific CVD. The relationship between MDS and total CVD was stable and significant in all subgroups. The fully adjusted Cox regression model indicated that high MDS, irrespective of MDS as a categorical or continuous variable, was significantly associated with an elevated risk of all-cause and CVD deaths. <br /><b>Conclusions:</b><br/>MDS is a vital risk factor for the prevalence and mortality of individuals with CVD.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 08 Sep 2023:e030077; epub ahead of print</small></div>

<div><h4>Statin Treatment in Patients With Stroke With Low-Density Lipoprotein Cholesterol Levels Below 70 mg/dL.</h4><i>Kim JT, Lee JS, Kim BJ, Kang J, ... Park KY, Bae HJ</i><br /><AbstractText><br /><b>Background:</b><br/>It is unclear whether statin treatment could reduce the risk of early vascular events when baseline low-density lipoprotein cholesterol (LDL-C) levels are already low, at <70 mg/dL, at the time of the index stroke. Methods and Results This study was an analysis of a prospective, multicenter, nationwide registry of consecutive patients with first-ever acute ischemic stroke with baseline low-density lipoprotein cholesterol levels <70 mg/dL and without statin pretreatment. An inverse probabilities of treatment weights method was applied to control for imbalances in baseline characteristics. The primary outcome was a composite of stroke (either hemorrhagic or ischemic), myocardial infarction, and all-cause death within 3 months. A total of 2850 patients (age, 69.5±13.4 years; men, 63.5%) were analyzed for this study. In-hospital statin treatment was used for 74.2% of patients. The primary composite outcome within 3 months occurred in 21.5% of patients in the nonstatin group and 6.7% of patients in the statin group (<i>P</i><0.001), but the rates of stroke (2.65% versus 2.33%), hemorrhagic stroke (0.16% versus 0.10%), and myocardial infarction (0.73% versus 0.19%) were not significantly different between the 2 groups. After inverse probability of treatment weighting analysis, the primary composite outcome was significantly reduced in patients with statin therapy (weighted hazard ratio [HR], 0.54 [95% CI, 0.42-0.69]). However, statin treatment did not increase the risk of hemorrhagic stroke (weighted HR, 1.11 [95% CI, 0.10-12.28]). <br /><b>Conclusions:</b><br/>Approximately three-quarters of the patients with first-ever ischemic stroke with baseline low-density lipoprotein cholesterol levels <70 mg/dL received in-hospital statin treatment. Statin treatment, compared with no statin treatment, was significantly associated with a reduced risk of the 3-month primary composite outcomes and all-cause death but did not alter the rate of stroke recurrence.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 08 Sep 2023:e030738; epub ahead of print</small></div>

<div><h4>Risk Stratification Tools to Guide a Personalized Approach for Cardiac Monitoring in Embolic Stroke of Undetermined Source.</h4><i>Louka AM, Nagraj S, Adamou AT, Perlepe K, ... Palaiodimos L, Ntaios G</i><br /><AbstractText>Current recommendations support a personalized sequential approach for cardiac rhythm monitoring to detect atrial fibrillation after embolic stroke of undetermined source. Several risk stratification scores have been proposed to predict the likelihood of atrial fibrillation after embolic stroke of undetermined source. This systematic review aimed to provide a comprehensive overview of the field by identifying risk scores proposed for this purpose, assessing their characteristics and the cohorts in which they were developed and validated, and scrutinizing their predictive performance. We identified 11 risk scores, of which 4 were externally validated. The most frequent variables included were echocardiographic markers and demographics. The areas under the curve ranged between 0.70 and 0.94. The 3 scores with the highest area under the curve were the Decryptoring (0.94 [95% CI, 0.88-1.00]), newly diagnosed atrial fibrillation (0.87 [95% CI, 0.79-0.94]), and AF-ESUS (Atrial Fibrillation in Embolic Stroke of Undetermined Source) (0.85 [95% CI, 0.80-0.87]), of which only the latter was externally validated. Risk stratification scores can guide a personalized approach for cardiac rhythm monitoring after embolic stroke of undetermined source.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 08 Sep 2023:e030479; epub ahead of print</small></div>

<div><h4>Decoding Angiotensin Receptors: TOMAHAQ-Based Detection and Quantification of Angiotensin Type-1 and Type-2 Receptors.</h4><i>Cosarderelioglu C, Kreimer S, Plaza-Rodriguez AI, Iglesias PA, ... Walston J, Abadir P</i><br /><AbstractText><br /><b>Background:</b><br/>The renin-angiotensin system plays a crucial role in human physiology, and its main hormone, angiotensin, activates 2 G-protein-coupled receptors, the angiotensin type-1 and type-2 receptors, in almost every organ. However, controversy exists about the location, distribution, and expression levels of these receptors. Concerns have been raised over the low sensitivity, low specificity, and large variability between lots of commercially available antibodies for angiotensin type-1 and type-2 receptors, which makes it difficult to reconciliate results of different studies. Here, we describe the first non-antibody-based sensitive and specific targeted quantitative mass spectrometry assay for angiotensin receptors. Methods and Results Using a technique that allows targeted analysis of multiple peptides across multiple samples in a single mass spectrometry analysis, known as TOMAHAQ (triggered by offset, multiplexed, accurate mass, high resolution, and absolute quantification), we have identified and validated specific human tryptic peptides that permit identification and quantification of angiotensin type-1 and type-2 receptors in biological samples. Several peptide sequences are conserved in rodents, making these mass spectrometry assays amenable to both preclinical and clinical studies. We have used this method to quantify angiotensin type-1 and type-2 receptors in postmortem frontal cortex samples of older adults (n=28) with Alzheimer dementia. We correlated levels of angiotensin receptors to biomarkers classically linked to renin-angiotensin system activation, including oxidative stress, inflammation, amyloid-β load, and paired helical filament-tau tangle burden. <br /><b>Conclusions:</b><br/>These robust high-throughput assays will not only catalyze novel mechanistic studies in the angiotensin research field but may also help to identify patients with an unbalanced angiotensin receptor distribution who would benefit from angiotensin receptor blocker treatment.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 08 Sep 2023:e030791; epub ahead of print</small></div>

<div><h4>A Multicenter Analysis of Abnormal Chromosomal Microarray Findings in Congenital Heart Disease.</h4><i>Landis BJ, Helvaty LR, Geddes GC, Lin JI, ... Hodge JC, Ware SM</i><br /><AbstractText><br /><b>Background:</b><br/>Chromosomal microarray analysis (CMA) provides an opportunity to understand genetic causes of congenital heart disease (CHD). The methods for describing cardiac phenotypes in patients with CMA abnormalities have been inconsistent, which may complicate clinical interpretation of abnormal testing results and hinder a more complete understanding of genotype-phenotype relationships. Methods and Results Patients with CHD and abnormal clinical CMA were accrued from 9 pediatric cardiac centers. Highly detailed cardiac phenotypes were systematically classified and analyzed for their association with CMA abnormality. Hierarchical classification of each patient into 1 CHD category facilitated broad analyses. Inclusive classification allowing multiple CHD types per patient provided sensitive descriptions. In 1363 registry patients, 28% had genomic disorders with well-recognized CHD association, 67% had clinically reported copy number variants (CNVs) with rare or no prior CHD association, and 5% had regions of homozygosity without CNV. Hierarchical classification identified expected CHD categories in genomic disorders, as well as uncharacteristic CHDs. Inclusive phenotyping provided sensitive descriptions of patients with multiple CHD types, which occurred commonly. Among CNVs with rare or no prior CHD association, submicroscopic CNVs were enriched for more complex types of CHD compared with large CNVs. The submicroscopic CNVs that contained a curated CHD gene were enriched for left ventricular obstruction or septal defects, whereas CNVs containing a single gene were enriched for conotruncal defects. Neuronal-related pathways were over-represented in single-gene CNVs, including top candidate causative genes <i>NRXN3</i>, <i>ADCY2</i>, and <i>HCN1</i>. <br /><b>Conclusions:</b><br/>Intensive cardiac phenotyping in multisite registry data identifies genotype-phenotype associations in CHD patients with abnormal CMA.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 08 Sep 2023:e029340; epub ahead of print</small></div>

<div><h4>Prognostic Implications and Efficacy of Catheter Ablation by Atrial Fibrillation Type.</h4><i>Miyama H, Takatsuki S, Ikemura N, Kimura T, ... Fukuda K, Kohsaka S</i><br /><AbstractText><br /><b>Background:</b><br/>Catheter ablation (CA) for atrial fibrillation (AF) is preferred for paroxysmal AF (PAF) but selectively performed in patients with persistent AF (PersAF). This study aimed to investigate the prognostic differences and consequences of CA based on the AF type. Methods and Results Data from a multicenter AF cohort study were analyzed, categorizing patients as PAF or PersAF according to AF duration (≤7 or >7 days, respectively). A composite of all-cause death, heart failure hospitalization, stroke, and bleeding events during 2-year follow-up and changes in the Atrial Fibrillation Effect on Quality-of-life score were compared. Additionally, propensity score matching was performed to compare clinical outcomes of patients with and without CA in both AF types. Among 2788 patients, 51.6% and 48.4% had PAF and PersAF, respectively. Patients with PersAF had a higher incidence of the composite outcome (12.8% versus 7.2%; <i>P</i><0.001) and smaller improvements in Atrial Fibrillation Effect on Quality-of-life scores than those with PAF. After adjusting for baseline characteristics, PersAF was an independent predictor of adverse outcomes (adjusted hazard ratio, 1.35 [95% CI, 1.30-1.78], <i>P</i>=0.031) and was associated with poor improvements in Atrial Fibrillation Effect on Quality-of-life scores. Propensity score matching analysis showed that the CA group had significantly fewer adverse events than the medication group among patients with PAF (odds ratio, 0.31 [95% CI, 0.18-0.68]; <i>P</i>=0.002). Patients with PersAF showed a similar but nonsignificant trend. <br /><b>Conclusions:</b><br/>PersAF is a risk factor for worse clinical outcomes, including patients\' health status. CA is associated with fewer adverse events, although careful consideration is required based on the AF type.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 08 Sep 2023:e029321; epub ahead of print</small></div>

<div><h4>Menstrual Cycle Irregularity in Adolescence Is Associated With Cardiometabolic Health in Early Adulthood.</h4><i>Keenan K, Hipwell AE, Polonsky TS</i><br /><AbstractText><br /><b>Background:</b><br/>Menstrual cycle irregularities are associated with cardiovascular and cardiometabolic disease. We tested associations between age at menarche and cycle irregularity in adolescence and cardiometabolic health in early adulthood in a subsample from the Pittsburgh Girls Study. Methods and Results Data from annual interviews were used to assess age at menarche and cycle irregularity (ie, greater or less than every 27-29 days) at age 15 years. At ages 22 to 25 years, cardiometabolic health was measured in a subsample of the Pittsburgh Girls Study (n=352; 68.2% Black), including blood pressure, waist circumference, and fasting serum insulin, glucose, and lipids. <i>T</i> tests were used for continuous data and odds ratios for dichotomous data to compare differences in cardiometabolic health as a function of onset and regularity of menses. Early menarche (ie, before age 11 years; n=52) was associated with waist circumference (<i>P</i>=0.043). Participants reporting irregular cycles (n=50) in adolescence had significantly higher levels of insulin, glucose, and triglycerides, and higher systolic and diastolic blood pressure (<i>P</i> values range from 0.035 to 0.005) and were more likely to have clinical indicators of cardiometabolic predisease in early adulthood compared with women who reported regular cycles (odds ratios ranged from 1.89 to 2.56). <br /><b>Conclusions:</b><br/>Increasing rates and earlier onset of cardiovascular and metabolic disease among women, especially among Black women, highlights the need for identifying early and reliable risk indices. Menstrual cycle irregularity may serve this purpose and help elucidate the role of women\'s reproductive health in protecting and conferring risk for later cardiovascular and cardiometabolic diseases.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 08 Sep 2023:e029372; epub ahead of print</small></div>

<div><h4>Arginine Vasopressin Plays a Role in Microvascular Dysfunction After ST-Elevation Myocardial Infarction.</h4><i>Al-Atta A, Spray L, Mohammed A, Shmeleva E, Spyridopoulos I</i><br /><AbstractText><br /><b>Background:</b><br/>Coronary microvascular dysfunction (CMD) predicts mortality after ST-elevation-myocardial infarction (STEMI). Arginine vasopressin (AVP) may be implicated, but data in humans are lacking, and no study has investigated the link between arginine vasopressin and invasive measures of CMD. Methods and Results We invasively assessed CMD in 55 patients with STEMI treated with primary percutaneous coronary intervention (PPCI), by measuring the index of microcirculatory resistance after PPCI. In a separate group of 45 patients with STEMI/PPCI, recruited for a clinical trial, we measured infarct size and microvascular obstruction with cardiac magnetic resonance (CMR) imaging at 1 week and 12 weeks post-STEMI. Serum copeptin was measured at 4 time points before and after PPCI in all patients with STEMI. Plasma copeptin levels fell from 92.5 pmol/L before reperfusion to 6.4 pmol/L at 24 hours. Copeptin inversely correlated with diastolic, but not systolic, blood pressure (r=-0.431, <i>P</i>=0.001), suggesting it is released in response to myocardial ischemia. Persistently raised copeptin at 24 hours was correlated with higher index of microcirculatory resistance (r=0.372, <i>P</i>=0.011). Patients with microvascular obstruction on early CMR imaging showed a trend toward higher admission copeptin, which was not statistically significant. Copeptin levels were not associated with infarct size on either early or late CMR. <br /><b>Conclusions:</b><br/>Patients with CMD after STEMI have persistently elevated copeptin at 24 hours, suggesting arginine vasopressin may contribute to microvascular dysfunction. Arginine vasopressin receptor antagonists may represent a novel therapeutic option in patients with STEMI and CMD.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 08 Sep 2023:e030473; epub ahead of print</small></div>

<div><h4>Outcomes of Patients With Takotsubo Syndrome Compared With Type 1 and Type 2 Myocardial Infarction.</h4><i>Khaloo P, Ledesma PA, Nahlawi A, Galvin J, Ptaszek LM, Ruskin JN</i><br /><AbstractText><br /><b>Background:</b><br/>Takotsubo syndrome (TS) and myocardial infarction (MI) share similar clinical and laboratory characteristics but have important differences in causes, demographics, management, and outcomes. Methods and Results In this observational study, the National Inpatient Sample and National Readmission Database were used to identify patients admitted with TS, type 1 MI, or type 2 MI in the United States between October 1, 2017, and December 31, 2019. We compared patients hospitalized with TS, type 1 MI, and type 2 MI with respect to key features and outcomes. Over the 27-month study period, 2 035 055 patients with type 1 MI, 639 075 patients with type 2 MI, and 43 335 patients with TS were identified. Cardiac arrest, ventricular fibrillation, and ventricular tachycardia were more prevalent in type 1 MI (4.02%, 3.2%, and 7.2%, respectively) compared with both type 2 MI (2.8%, 0.8%, and 5.4% respectively) and TS (2.7%, 1.8%, and 5.3%, respectively). Risk of mortality was lower in TS compared with both type 1 MI (3.3% versus 7.9%; adjusted odds ratio [OR], 0.3; <i>P</i><0.001) and type 2 MI (3.3% versus 8.2%; adjusted OR, 0.3; <i>P</i><0.001). Mortality rate (OR, 1.2; <i>P</i><0.001) and cardiac-cause 30-day readmission rate (adjusted OR, 1.7; <i>P</i><0.001) were higher in type 1 MI than in type 2 MI. <br /><b>Conclusions:</b><br/>Patients with type 1 MI had the highest rates of in-hospital mortality and cardiac-cause 30-day readmission. Risk of all-cause 30-day readmission was highest in patients with type 2 MI. The risk of ventricular arrhythmias in patients with TS is lower than in patients with type 1 MI but higher than in patients with type 2 MI.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 08 Sep 2023:e030114; epub ahead of print</small></div>

<div><h4>Cardiovascular Hospitalizations and Resource Use Following Atrial Fibrillation Ablation.</h4><i>Dhande M, Barakat A, Canterbury A, Thoma F, ... Saba S, Jain SK</i><br /><AbstractText><br /><b>Background:</b><br/>Over the next few years, atrial fibrillation (AF)-related morbidity and costs will increase significantly. Thus, it is prudent to examine the impact of AF treatment on health care resource use. This study examined the impact of AF ablation on hospitalization, length of stay, and resource use for patients undergoing AF ablation in a multihospital system. Methods and Results In an observational analysis, outcomes of total, cardiovascular, and AF hospitalizations, emergency department visits, and length of stay were compared for 3417 patients between 12 months before and 24 months following AF ablation. Use of electrical cardioversions and antiarrhythmic use were also compared 1 year before to 2 years after AF ablation. There were fewer total (0.7±1.3 versus 0.3±0.7; <i>P</i><0.001), cardiovascular (0.7±1.2 versus 0.2±0.6; <i>P</i><0.001), and AF (0.6±1.1 versus 0.1±0.3; <i>P</i><0.001) hospitalizations and emergency department visits (0.8±2.1 versus 0.4±0.9; <i>P</i><0.001) per patient-year for the 2 years following AF ablation compared with 1 year before. Average length of stay per patient-year (1.4±7.9 versus 3.6±5.3 days; <i>P</i><0.0001), the percentage of patients on antiarrhythmic therapy (21.2% versus 58.5%; <i>P</i><0.0001), and those undergoing electrical cardioversions (16.1% versus 28.1%; <i>P</i><0.0001) were lower 2 years following AF ablation versus 1 year before. <br /><b>Conclusions:</b><br/>We noted a decrease in total, cardiovascular, and AF hospitalizations and health care resource use during the 2-year period after index AF ablation, compared with the 1 year before. AF ablation may portend a decline in patient morbidity and health care costs.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 08 Sep 2023:e028609; epub ahead of print</small></div>

<div><h4>Long-Term Outcomes of Patients Undergoing Aortic Root Replacement With Mechanical Versus Bioprosthetic Valves: Meta-Analysis of Reconstructed Time-to-Event Data.</h4><i>Sá MP, Tasoudis P, Jacquemyn X, Van den Eynde J, ... Serna-Gallegos D, Sultan I</i><br /><AbstractText><br /><b>Background:</b><br/>An aspect not so clear in the scenario of aortic surgery is how patients fare after composite aortic valve graft replacement (CAVGR) depending on the type of valve (bioprosthetic versus mechanical). We performed a study to evaluate the long-term outcomes of both strategies comparatively. Methods and Results Pooled meta-analysis of Kaplan-Meier-derived time-to-event data from studies with follow-up for overall survival (all-cause death), event-free survival (composite end point of cardiac death, valve-related complications, stroke, bleeding, embolic events, and/or endocarditis), and freedom from reintervention. Twenty-three studies met our eligibility criteria, including 11 428 patients (3786 patients with mechanical valves and 7642 patients with bioprosthetic valve). The overall population was mostly composed of men (mean age, 45.5-75.6 years). In comparison with patients who underwent CAVGR with bioprosthetic valves, patients undergoing CAVGR with mechanical valves presented no statistically significant difference in the risk of all-cause death in the first 30 days after the procedure (hazard ratio [HR], 1.24 [95% CI, 0.95-1.60]; <i>P</i>=0.109), but they had a significantly lower risk of all-cause mortality after the 30-day time point (HR, 0.89 [95% CI, 0.81-0.99]; <i>P</i>=0.039) and lower risk of reintervention (HR, 0.33 [95% CI, 0.24-0.45]; <i>P</i><0.001). Despite its increased risk for the composite end point in the first 6 years of follow-up (HR, 1.41 [95% CI, 1.09-1.82]; <i>P</i>=0.009), CAVGR with mechanical valves is associated with a lower risk for the composite end point after the 6-year time point (HR, 0.46 [95% CI, 0.31-0.67]; <i>P</i><0.001). <br /><b>Conclusions:</b><br/>CAVGR with mechanical valves is associated with better long-term outcomes in comparison with CAVGR with bioprosthetic valves.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 08 Sep 2023:e030629; epub ahead of print</small></div>

<div><h4>Identifying Unique Subgroups of Individuals With Stroke Using Heart Rate and Steps to Characterize Physical Activity.</h4><i>Koffman LJ, Crainiceanu CM, Roemmich RT, French MA</i><br /><AbstractText><br /><b>Background:</b><br/>Low physical activity (PA) is associated with poor health outcomes after stroke. Step counts are a common metric of PA; however, other physiologic signals (eg, heart rate) may help to identify subgroups of individuals poststroke at varying levels of risk of poor health outcomes. Here, we aimed to identify clinically relevant subgroups of individuals poststroke based on PA profiles that leverage multiple data sources, including step count and heart rate data, from wearable devices. Methods and Results Seventy individuals poststroke participated. Participants wore a Fitbit Inspire 2 for 1 year and completed clinical assessments. We defined a group-based steps-per-minute threshold and an individual heart rate threshold to categorize each minute of PA into 1 of 4 states: high steps/high heart rate, low steps/low heart rate, high steps/low heart rate, and low steps/high heart rate. We used the proportion of time spent in each state along with steps per day, sedentary time, mean steps among minutes with high steps and high heart rate, and resting heart rate in a k-means clustering algorithm to identify subgroups and compared Activity Measure for Post-Acute Care Mobility T Score, Stroke Impact Scale, and gait speed among subgroups. We identified 3 subgroups, Active (n=8), Sedentary (n=29), and Deconditioned (n=33), which differed significantly on all clustering variables except resting heart rate. We observed significant differences in Activity Measure for Post-Acute Care Mobility T scores between subgroups, with the Deconditioned subgroup exhibiting the lowest score. <br /><b>Conclusions:</b><br/>Quantifying PA with heart rate and step count using readily available wearable devices can identify clinically meaningful subgroups of individuals poststroke.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 08 Sep 2023:e030577; epub ahead of print</small></div>

<div><h4>Sedentary Bout Patterns and Metabolic Health in the Hispanic Community Health Study/Study of Latino Youth (SOL Youth).</h4><i>Carlson JA, Hibbing PR, Forseth B, Diaz KM, ... Thyfault J, Gallo LC</i><br /><AbstractText><br /><b>Background:</b><br/>There is limited evidence on the potential negative metabolic health impacts of prolonged and uninterrupted sedentary bouts in structurally disadvantaged youth. This study investigated associations between sedentary bout variables and metabolic health markers in the Hispanic Community Health Study/SOL Youth (Study of Latino Youth). Methods and Results SOL Youth was a population-based cohort of 1466 youth (age range, 8-16 years; 48.5% female); 957 youth were included in the analytic sample based on complete data. Accelerometers measured moderate-to-vigorous physical activity (MVPA), total sedentary time, and sedentary bout patterns (daily time spent in sedentary bouts ≥30 minutes, median sedentary bout duration, and number of daily breaks from sedentary time). Clinical measures included body mass index, waist circumference, fasting glucose, glycated hemoglobin, fasting insulin, and the homeostasis model assessment of insulin resistance. After adjusting for sociodemographics, total sedentary time, and MVPA, longer median bout durations and fewer sedentary breaks were associated with a greater body mass index percentile (b<sub>bouts</sub>=0.09 and b<sub>breaks</sub>=-0.18), waist circumference (b<sub>bouts</sub>=0.12 and b<sub>breaks</sub>=-0.20), and fasting insulin (b<sub>bouts</sub>=0.09 and b<sub>breaks</sub>=-0.21). Fewer breaks were also associated with a greater homeostasis model assessment of insulin resistance (b=-0.21). More time in bouts lasting ≥30 minutes was associated with a greater fasting glucose (b=0.18) and glycated hemoglobin (b=0.19). <br /><b>Conclusions:</b><br/>Greater accumulation of sedentary time in prolonged and uninterrupted bouts had adverse associations with adiposity and glycemic control over and above total sedentary time and MVPA. Findings suggest interventions in Hispanic/Latino youth targeting both ends of the activity spectrum (more MVPA and less prolonged/uninterrupted sedentary patterns) may provide greater health benefits than those targeting only MVPA.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 08 Sep 2023:e028495; epub ahead of print</small></div>

<div><h4>Age at Menopause and the Risk of Stroke: Observational and Mendelian Randomization Analysis in 204 244 Postmenopausal Women.</h4><i>Tschiderer L, Peters SAE, van der Schouw YT, van Westing AC, ... Butterworth A, Onland-Moret NC</i><br /><AbstractText><br /><b>Background:</b><br/>Observational studies have shown that women with an early menopause are at higher risk of stroke compared with women with a later menopause. However, associations with stroke subtypes are inconsistent, and the causality is unclear. Methods and Results We analyzed data of the UK Biobank and EPIC-CVD (European Prospective Investigation Into Cancer and Nutrition-Cardiovascular Diseases) study. A total of 204 244 postmenopausal women without a history of stroke at baseline were included (7883 from EPIC-CVD [5292 from the subcohort], 196 361 from the UK Biobank). Pooled mean baseline age was 58.9 years (SD, 5.8), and pooled mean age at menopause was 47.8 years (SD, 6.2). Over a median follow-up of 12.6 years (interquartile range, 11.8-13.3), 6770 women experienced a stroke (5155 ischemic strokes, 1615 hemorrhagic strokes, 976 intracerebral hemorrhages, and 639 subarachnoid hemorrhages). In multivariable adjusted observational Cox regression analyses, the pooled hazard ratios per 5 years younger age at menopause were 1.09 (95% CI, 1.07-1.12) for stroke, 1.09 (95% CI, 1.06-1.13) for ischemic stroke, 1.10 (95% CI, 1.04-1.16) for hemorrhagic stroke, 1.14 (95% CI, 1.08-1.20) for intracerebral hemorrhage, and 1.00 (95% CI, 0.84-1.20) for subarachnoid hemorrhage. When using 2-sample Mendelian randomization analysis, we found no statistically significant association between genetically proxied age at menopause and risk of any type of stroke. <br /><b>Conclusions:</b><br/>In our study, earlier age at menopause was related to a higher risk of stroke. We found no statistically significant association between genetically proxied age at menopause and risk of stroke, suggesting no causal relationship.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 08 Sep 2023:e030280; epub ahead of print</small></div>

<div><h4>Regression of Coronary Fatty Plaque and Risk of Cardiac Events According to Blood Pressure Status: Data From a Randomized Trial of Eicosapentaenoic Acid and Docosahexaenoic Acid in Patients With Coronary Artery Disease.</h4><i>Welty FK, Hariri E, Asbeutah AA, Daher R, ... Alfaddagh A, Malik A</i><br /><AbstractText><br /><b>Background:</b><br/>Residual risk of cardiovascular events and plaque progression remains despite reduction in low-density lipoprotein cholesterol. Factors contributing to residual risk remain unclear. The authors examined the role of eicosapentaenoic acid and docosahexaenoic acid in coronary plaque regression and its predictors. Methods and Results A total of 240 patients with stable coronary artery disease were randomized to eicosapentaenoic acid plus docosahexaenoic acid (3.36 g/d) or none for 30 months. Patients were stratified by regression or progression of coronary fatty plaque measured by coronary computed tomographic angiography. Cardiac events were ascertained. The mean±SD age was 63.0±7.7 years, mean low-density lipoprotein cholesterol level was <2.07 mmol/L, and median triglyceride level was <1.38 mmol/L. Regressors had a 14.9% reduction in triglycerides that correlated with fatty plaque regression (<i>r</i>=0.135; <i>P</i>=0.036). Compared with regressors, progressors had higher cardiac events (5% vs 22.3%, respectively; <i>P</i><0.001) and a 2.89-fold increased risk of cardiac events (95% CI, 1.1-8.0; <i>P</i>=0.034). Baseline non-high-density lipoprotein cholesterol level <2.59 mmol/L (100 mg/dL) and systolic blood pressure <125 mm Hg were significant independent predictors of fatty plaque regression. Normotensive patients taking eicosapentaenoic acid plus docosahexaenoic acid had regression of noncalcified coronary plaque that correlated with triglyceride reduction (<i>r</i>=0.35; <i>P</i>=0.034) and a significant decrease in neutrophil/lymphocyte ratio. In contrast, hypertensive patients had no change in noncalcified coronary plaque or neutrophil/lymphocyte ratio. <br /><b>Conclusions:</b><br/>Triglyceride reduction, systolic blood pressure <125 mm Hg, and non-high-density lipoprotein cholesterol <2.59 mmol/L were associated with coronary plaque regression and reduced cardiac events. Normotensive patients had greater benefit than hypertensive patients potentially due to lower levels of inflammation. Future studies should examine the role of inflammation in plaque regression. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01624727.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 08 Sep 2023:e030071; epub ahead of print</small></div>

<div><h4>Use of the Wearable Cardioverter-Defibrillator Among Patients With Myocarditis and Reduced Ejection Fraction or Ventricular Tachyarrhythmia: Data From a Multicenter Registry.</h4><i>El-Battrawy I, Koepsel K, Tenbrink D, Kovacs B, ... Aweimer A, Beiert T</i><br /><AbstractText><br /><b>Background:</b><br/>Data on the use of the wearable cardioverter-defibrillator (WCD) among patients with myocarditis remain sparse. Consequently, evidence for guideline recommendations in this patient population is lacking. Methods and Results In total, 1596 consecutive patients were included in a multicenter registry from 8 European centers, with 124 patients (8%) having received the WCD due to myocarditis and reduced left ventricular ejection fraction or prior ventricular tachyarrhythmia. The mean age was 51.6±16.3 years, with 74% being male. Patients were discharged after index hospitalization on heart failure medication: Angiotensin-converting enzyme inhibitors (62.5%), angiotensin-receptor-neprilysin inhibitor (22.9%), aldosterone-antagonists (51%), or beta blockers (91.4%). The initial median left ventricular ejection fraction was 30% (22%-45%) and increased to 48% (39%-55%) over long-term follow-up (<i>P</i><0.001). The median BNP (brain natriuretic peptide) level at baseline was 1702 pg/mL (565-3748) and decreased to 188 pg/mL (26-348) over long-term follow-up (<i>P</i>=0.022). The mean wear time was 79.7±52.1 days and 21.0±4.9 hours per day. Arrhythmic event rates documented by the WCD were 9.7% for nonsustained ventricular tachycardia, 6.5% for sustained ventricular tachycardia, and 0% for ventricular fibrillation. Subsequently, 2.4% of patients experienced an appropriate WCD shock. The rate of inappropriate WCD shocks was 0.8%. All 3 patients with appropriate WCD shock had experienced ventricular tachycardia/ventricular fibrillation before WCD prescription, with only 1 patient showing a left ventricular ejection fraction <35%. <br /><b>Conclusions:</b><br/>Patients with myocarditis and risk for occurrence of ventricular tachyarrhythmia may benefit from WCD use. Prior ventricular arrhythmia might appear as a better risk predictor than a reduced left ventricular ejection fraction <35% in this population.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 08 Sep 2023:e030615; epub ahead of print</small></div>

<div><h4>Penalized Model-Based Unsupervised Phenomapping Unravels Distinctive HFrEF Phenotypes With Improved Outcomes Discrimination From Sacubitril/Valsartan Treatment Independent of MAGGIC Score.</h4><i>Sung KT, Chang HY, Hsu NW, Huang WH, ... Yeh HI, Hung CL</i><br /><AbstractText><br /><b>Background:</b><br/>The angiotensin receptor-neprilysin inhibitor (LCZ696) has emerged as a promising pharmacological intervention against renin-angiotensin system inhibitor in reduced ejection fraction heart failure (HFrEF). Whether the therapeutic benefits may vary among heterogeneous HFrEF subgroups remains unknown. Methods and Results This study comprised a pooled 2-center analysis including 1103 patients with symptomatic HFrEF with LCZ696 use and another 1103 independent HFrEF control cohort (with renin-angiotensin system inhibitor use) matched for age, sex, left ventricular ejection fraction, and comorbidity conditions. Three main distinct phenogroup clusterings were identified from unsupervised machine learning using 29 clinical variables: phenogroup 1 (youngest, relatively lower diabetes prevalence, highest glomerular filtration rate with largest left ventricular size and left ventricular wall stress); phenogroup 2 (oldest, lean, highest diabetes and vascular diseases prevalence, lowest highest glomerular filtration rate with smallest left ventricular size and mass), and phenogroup 3 (lowest clinical comorbidity with largest left ventricular mass and highest hypertrophy prevalence). During the median 1.74-year follow-up, phenogroup assignment provided improved prognostic discrimination beyond Meta-Analysis Global Group in Chronic Heart Failure risk score risk score (all net reclassification index <i>P</i><0.05) with overall good calibrations. While phenogroup 1 showed overall best clinical outcomes, phenogroup 2 demonstrated highest cardiovascular death and worst renal end point, with phenogroup 3 having the highest all-cause death rate and HF hospitalization among groups, respectively. These findings were broadly consistent when compared with the renin-angiotensin system inhibitor control as reference group. <br /><b>Conclusions:</b><br/>Phenomapping provided novel insights on unique characteristics and cardiac features among patients with HFrEF with sacubitril/valsartan treatment. These findings further showed potentiality in identifying potential sacubitril/valsartan responders and nonresponders with improved outcome discrimination among patients with HFrEF beyond clinical scoring.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 08 Sep 2023:e028860; epub ahead of print</small></div>

<div><h4>Association Between Alcohol Consumption and Ectopic Fat in the Multi-Ethnic Study of Atherosclerosis.</h4><i>Kazibwe R, Chevli PA, Evans JK, Allison M, ... Shapiro MD, Mongraw-Chaffin M</i><br /><AbstractText><br /><b>Background:</b><br/>The relationship between alcohol consumption and ectopic fat distribution, both known factors for cardiovascular disease, remains understudied. Therefore, we aimed to examine the association between alcohol consumption and ectopic adiposity in adults at risk for cardiovascular disease. Methods and Results In this cross-sectional analysis, we categorized alcohol intake among participants in MESA (Multi-Ethnic Study of Atherosclerosis) as follows (drinks/day): <1 (light drinking), 1 to 2 (moderate drinking), >2 (heavy drinking), former drinking, and lifetime abstention. Binge drinking was defined as consuming ≥5 drinks on 1 occasion in the past month. Visceral, subcutaneous, and intermuscular fat area, pericardial fat volume, and hepatic fat attenuation were measured using noncontrast computed tomography. Using multivariable linear regression, we examined the associations between categories of alcohol consumption and natural log-transformed fat in ectopic depots. We included 6756 MESA participants (62.1±10.2 years; 47.2% women), of whom 6734 and 1934 had chest computed tomography (pericardial and hepatic fat) and abdominal computed tomography (subcutaneous, intermuscular, and visceral fat), respectively. In adjusted analysis, heavy drinking, relative to lifetime abstention, was associated with a higher (relative percent difference) pericardial 15.1 [95% CI, 7.1-27.7], hepatic 3.4 [95% CI, 0.1-6.8], visceral 2.5 [95% CI, -10.4 to 17.2], and intermuscular 5.2 [95% CI, -6.6 to 18.4] fat but lower subcutaneous fat -3.5 [95% CI, -15.5 to 10.2]). The associations between alcohol consumption and ectopic adiposity exhibited a J-shaped pattern. Binge drinking, relative to light-to-moderate drinking, was also associated with higher ectopic fat. <br /><b>Conclusions:</b><br/>Alcohol consumption had a J-shaped association with ectopic adiposity. Both heavy alcohol intake and binge alcohol drinking were associated with higher ectopic fat.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 08 Sep 2023:e030470; epub ahead of print</small></div>

<div><h4>Racial Disparities in Obesity-Related Cardiovascular Mortality in the United States: Temporal Trends From 1999 to 2020.</h4><i>Raisi-Estabragh Z, Kobo O, Mieres JH, Bullock-Palmer RP, ... Breathett K, Mamas MA</i><br /><AbstractText><br /><b>Background:</b><br/>Obesity is a major risk factor for cardiovascular disease, with differential impact across populations. This descriptive epidemiologic study outlines trends and disparities in obesity-related cardiovascular mortality in the US population between 1999 and 2020. Methods and Results The Multiple Cause of Death database was used to identify adults with primary cardiovascular death and obesity recorded as a contributing cause of death. Cardiovascular deaths were grouped into ischemic heart disease, heart failure, hypertensive disease, cerebrovascular disease, and other. Absolute, crude, and age-adjusted mortality rates (AAMRs) were calculated by racial group, considering temporal trends and variation by sex, age, and residence (urban versus rural). Analysis of 281 135 obesity-related cardiovascular deaths demonstrated a 3-fold increase in AAMRs from 1999 to 2020 (2.2-6.6 per 100 000 population). Black individuals had the highest AAMRs. American Indian or Alaska Native individuals had the greatest temporal increase in AAMRs (+415%). Ischemic heart disease was the most common primary cause of death. The second most common cause of death was hypertensive disease, which was most common in the Black racial group (31%). Among Black individuals, women had higher AAMRs than men; across all other racial groups, men had a greater proportion of obesity-related cardiovascular mortality cases and higher AAMRs. Black individuals had greater AAMRs in urban compared with rural settings; the reverse was observed for all other races. <br /><b>Conclusions:</b><br/>Obesity-related cardiovascular mortality is increasing with differential trends by race, sex, and place of residence.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 06 Sep 2023:e028409; epub ahead of print</small></div>

<div><h4>Intensive Statin Therapy Versus Upfront Combination Therapy of Statin and Ezetimibe in Patients With Acute Coronary Syndrome: A Propensity Score Matching Analysis Based on the PL-ACS Data.</h4><i>Lewek J, Niedziela J, Desperak P, Dyrbuś K, ... Gąsior M, Banach M</i><br /><AbstractText><br /><b>Background:</b><br/>We aimed to compare statin monotherapy and upfront combination therapy of statin and ezetimibe in patients with acute coronary syndromes (ACSs). Methods and Results The study included consecutive patients with ACS included in the PL-ACS (Polish Registry of Acute Coronary Syndromes), which is a national, multicenter, ongoing, prospective observational registry that is mandatory for patients with ACS hospitalized in Poland. Data were matched using the Mahalanobis distance within propensity score matching calipers. Multivariable stepwise logistic regression analysis, including all variables, was next used in propensity score matching analysis. Finally, 38 023 consecutive patients with ACS who were discharged alive were included in the analysis. After propensity score matching, 2 groups were analyzed: statin monotherapy (atorvastatin or rosuvastatin; n=768) and upfront combination therapy of statin and ezetimibe (n=768 patients). The difference in mortality between groups was significant during the follow-up and was present at 1 (5.9% versus 3.5%; <i>P</i>=0.041), 2 (7.8% versus 4.3%; <i>P</i>=0.019), and 3 (10.2% versus 5.5%; <i>P</i>=0.024) years of follow-up in favor of the upfront combination therapy, as well as for the overall period. For the treatment, rosuvastatin significantly improved prognosis compared with atorvastatin (odds ratio [OR], 0.790 [95% CI, 0.732-0.853]). Upfront combination therapy was associated with a significant reduction of all-cause mortality in comparison with statin monotherapy (OR, 0.526 [95% CI, 0.378-0.733]), with absolute risk reduction of 4.7% after 3 years (number needed to treat=21). <br /><b>Conclusions:</b><br/>The upfront combination lipid-lowering therapy is superior to statin monotherapy for all-cause mortality in patients with ACS. These results suggest that in high-risk patients, such an approach, rather than a stepwise therapy approach, should be recommended.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 06 Sep 2023:e030414; epub ahead of print</small></div>

<div><h4>Disrupted Lives: Caregivers\' Experiences of In-Hospital Cardiac Arrest Survivors\' Recovery 5 Years Later.</h4><i>Harrod M, Hauschildt K, Kamphuis LA, Korpela PR, ... Nallamothu BK, Iwashyna TJ</i><br /><AbstractText><br /><b>Background:</b><br/>Survivors of in-hospital cardiac arrest (IHCA) experience ongoing physical and cognitive impairments, often requiring support from a caregiver at home afterwards. Caregivers are important in the survivor\'s recovery, yet there is little research specifically focused on their experiences once the survivor is discharged home. In this study, we highlight how caregivers for veteran IHCA survivors described and experienced their caregiver role, the strategies they used to fulfill their role, and the additional needs they still have years after the IHCA event. Methods and Results Between March and July 2019, semistructured telephone interviews were conducted with 12 caregivers for veteran IHCA survivors. Interviews were transcribed, and content analysis was performed. Patterns within the data were further analyzed and grouped into themes. A predominant theme of \"disruption\" was identified across 3 different domains including the following: (1) disruption in caregiver\'s life, (2) disruption in caregiver-patient relationship, and (3) disruption in caregiver\'s well-being. Disruption was associated with both positive and negative caregiver experiences. Strategies caregivers used and resources they felt would have helped them adjust to their caregiver role were also identified. <br /><b>Conclusions:</b><br/>Caregivers for veteran IHCA survivors experienced a disruption in many facets of their lives. Caregivers felt the veterans\' IHCA impacted various aspects of their lives, and they continued to need additional support in order to care for the IHCA survivor and themselves. Although some were able to procure coping strategies, such as counseling and engaging in stress-relieving activities, most indicated additional help and resources were still needed.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 06 Sep 2023:e028746; epub ahead of print</small></div>

<div><h4>Cold Case of Thrombolysis: Cold Recombinant Tissue Plasminogen Activator Confers Enhanced Neuroprotection in Experimental Stroke.</h4><i>Huang Y, Gu S, Han Z, Yang Z, ... Borlongan C, Lu J</i><br /><AbstractText><br /><b>Background:</b><br/>Thrombolysis and endovascular thrombectomy are the primary treatment for ischemic stroke. However, due to the limited time window and the occurrence of adverse effects, only a small number of patients can genuinely benefit from recanalization. Intraarterial injection of rtPA (recombinant tissue plasminogen activator) based on arterial thrombectomy could improve the prognosis of patients with acute ischemic stroke, but it could not reduce the incidence of recanalization-related adverse effects. Recently, selective brain hypothermia has been shown to offer neuroprotection against stroke. To enhance the recanalization rate of ischemic stroke and reduce the adverse effects such as tiny thrombosis, brain edema, and hemorrhage, we described for the first time a combined approach of hypothermia and thrombolysis via intraarterial hypothermic rtPA. Methods and Results We initially established the optimal regimen of hypothermic rtPA in adult rats subjected to middle cerebral artery occlusion. Subsequently, we explored the mechanism of action mediating hypothermic rtPA by probing reduction of brain tissue temperature, attenuation of blood-brain barrier damage, and sequestration of inflammation coupled with untargeted metabolomics. Hypothermic rtPA improved neurological scores and reduced infarct volume, while limiting hemorrhagic transformation in middle cerebral artery occlusion rats. These therapeutic outcomes of hypothermic rtPA were accompanied by reduced brain temperature, glucose metabolism, and blood-brain barrier damage. A unique metabolomic profile emerged in hypothermic rtPA-treated middle cerebral artery occlusion rats characterized by downregulated markers for energy metabolism and inflammation. <br /><b>Conclusions:</b><br/>The innovative use of hypothermic rtPA enhances their combined, as opposed to stand-alone, neuroprotective effects, while reducing hemorrhagic transformation in ischemic stroke.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 01 Sep 2023:e029817; epub ahead of print</small></div>

<div><h4>Causal Effects of YKL-40 on Ischemic Stroke and Its Subtypes: A 2-Sample Mendelian Randomization Study.</h4><i>Xu Q, Sun L, Wang Y, Wang R, ... Zhang Y, Zhu Z</i><br /><AbstractText><br /><b>Background:</b><br/>Chitinase-3 like protein 1 (CHI3L1, YKL-40) was reported to be implicated in the development of ischemic stroke, but whether the association between them was causal remained unclear. We conducted a 2-sample Mendelian randomization study to explore the associations of genetically determined plasma YKL-40 with ischemic stroke and its subtypes (large artery stroke, small vessel stroke, and cardioembolic stroke). Methods and Results Based on genome-wide association study data of 3394 European-descent individuals, we selected 13 single-nucleotide polymorphisms associated with plasma YKL-40 as genetic instruments. Summary data about ischemic stroke and its subtypes were obtained from the Multiancestry Genome-wide Association Study of Stroke Consortium, involving 34 217 ischemic stroke cases and 406 111 controls of European ancestry. We used the inverse-variance weighted method followed by a series of sensitivity analyses to assess the causal associations of plasma YKL-40 with ischemic stroke and its subtypes. The primary analysis showed that genetically determined high YKL-40 levels were associated with increased risks of large artery stroke (odds ratio [OR], 1.08 [95% CI, 1.04-1.12]; <i>P</i>=1.73×10<sup>-4</sup>) and small vessel stroke (OR, 1.05 [95% CI, 1.01-1.09]; <i>P</i>=7.96×10<sup>-3</sup>) but not with ischemic stroke or cardioembolic stroke. Sensitivity analyses further confirmed these associations, and Mendelian randomization-Egger indicated no evidence of genetic pleiotropy. In addition, supplementary analysis based on the summary data from the Olink proximity extension assay cardiovascular I (Olink CVD-I) panel showed that high YKL-40 levels were positively associated with the risks of large artery stroke (OR, 1.15 [95% CI, 1.08-1.22]; <i>P</i>=4.16×10<sup>-6</sup>) but not with small vessel stroke. <br /><b>Conclusions:</b><br/>Genetically determined high plasma YKL-40 levels were causal associated with increased risks of large artery stroke.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 01 Sep 2023:e029000; epub ahead of print</small></div>

<div><h4>Association of SGLT-2 Inhibitors With Treatment Satisfaction and Diabetes-Specific and General Health Status in Adults With Cardiovascular Disease and Type 2 Diabetes.</h4><i>Ding Q, Spatz ES, Bena JF, Morrison SL, ... Combs P, Albert NM</i><br /><AbstractText><br /><b>Background:</b><br/>It is unknown if initiation of a sodium-glucose cotransporter-2 inhibitor (SGLT-2i) is associated with changes in patient-reported health status outside of clinical trials. Methods and Results Using a prospective observational study design, adults with type 2 diabetes and cardiovascular disease were recruited from 14 US hospitals between November 2019 and December 2021 if they were new users of noninsulin antidiabetic medications. The primary outcome was change in 6-month diabetes treatment satisfaction. Secondary outcomes included diabetes-related symptom distress, diabetes-specific quality of life, and general health status for all patients and based on cardiovascular disease type. Inverse probability of treatment weight using propensity score was performed to compare outcome changes based on medication use. Of 887 patients (SGLT-2i: n=242) included in the inverse probability of treatment weight analyses, there was no difference in changes in treatment satisfaction in SGLT-2i users compared with other diabetes medication users (0.99 [95% CI, -0.14 to 2.13] versus 1.54 [1.08 to 2.00], <i>P</i>=0.38). Initiating an SGLT-2i versus other diabetes medications was associated with a greater reduction in ophthalmological symptoms (-3.09 [95% CI, -4.99 to -1.18] versus -0.38 [-1.54 to 0.77], <i>P</i>=0.018) but less improvement in hyperglycemia (1.08 [-2.63 to 4.79] versus -3.60 [-5.34 to -1.86], <i>P</i>=0.026). In subgroup analyses by cardiovascular disease type, SGLT-2i use was associated with a greater reduction in total diabetes symptom burden and neurological sensory symptoms in patients with heart failure. <br /><b>Conclusions:</b><br/>Among patients with type 2 diabetes and cardiovascular disease, initiating an SGLT-2i was not associated with changes in diabetes treatment satisfaction, total diabetes symptoms, diabetes-specific quality of life, or general health status.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 01 Sep 2023:e029058; epub ahead of print</small></div>

<div><h4>New Users of Angiotensin II Receptor Blocker-Versus Angiotensin-Converting Enzyme Inhibitor-Based Antihypertensive Medication Regimens and Cardiovascular Disease Events: A Secondary Analysis of ACCORD-BP and SPRINT.</h4><i>King JB, Berchie RO, Derington CG, Marcum ZA, ... Bress AP, Cohen JB</i><br /><AbstractText><br /><b>Background:</b><br/>Angiotensin II receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) block distinct components of the renin-angiotensin system. Whether this translates into differential effects on cardiovascular disease events remains unclear. <br /><b>Methods and results:</b><br/>We used the ACCORD-BP (Action to Control Cardiovascular Risk in Diabetes-Blood Pressure) trial and the SPRINT (Systolic Blood Pressure Intervention Trial) to emulate target trials of new users of ARBs versus ACEIs on cardiovascular disease events (primary outcome) and death (secondary outcome). We estimated marginal cause-specific hazard ratios (HRs) and treatment-specific cumulative incidence functions with inverse probability of treatment weights. We identified 3298 new users of ARBs or ACEIs (ACCORD-BP: 374 ARB versus 884 ACEI; SPRINT: 727 ARB versus 1313 ACEI). For participants initiating ARBs versus ACEIs, the inverse probability of treatment weight rate of the primary outcome was 3.2 versus 3.5 per 100 person-years in ACCORD-BP (HR, 0.91 [95% CI, 0.63-1.31]) and 1.8 versus 2.2 per 100 person-years in SPRINT (HR, 0.81 [95% CI, 0.56-1.18]). There were no appreciable differences in pooled analyses, except that ARBs versus ACEIs were associated with a lower death rate (HR, 0.56 [95% CI, 0.37-0.85]). ARBs were associated with a lower rate of the primary outcome among subgroups of male versus female participants, non-Hispanic Black versus non-Hispanic White participants, and those randomly assigned to standard versus intensive blood pressure (<i>P</i><sub>interaction</sub>: <0.01, 0.05, and <0.01, respectively). CONCLUSIONS In this secondary analysis of ACCORD-BP and SPRINT, new users of ARB- versus ACEI-based antihypertensive medication regimens experienced similar cardiovascular disease events rates, with important subgroup differences and lower rates of death overall. REGISTRATION URL: https://www.clinicaltrials.gov; Unique identifiers: NCT01206062, NCT00000620.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 30 Aug 2023:e030311; epub ahead of print</small></div>

<div><h4>Prognostic Impact of Mitral Regurgitation Before and After Transcatheter Aortic Valve Replacement in Patients With Severe Low-Flow, Low-Gradient Aortic Stenosis.</h4><i>Ferruzzi GJ, Silverio A, Giordano A, Corcione N, ... Vecchione C, Galasso G</i><br /><AbstractText><br /><b>Background:</b><br/>There is little evidence about the prognostic role of mitral regurgitation (MR) in patients with low-flow, low-gradient aortic stenosis undergoing transcatheter aortic valve replacement (TAVR). The aim of this study was to assess the prevalence and outcome implications of MR severity in patients with low-flow, low-gradient aortic stenosis undergoing TAVR, and to evaluate whether MR improvement after TAVR could influence clinical outcome. Methods and Results This study included consecutive patients with low-flow, low-gradient aortic stenosis undergoing TAVR at 2 Italian high-volume centers. The study population was categorized according to the baseline MR severity and to the presence of MR improvement at discharge. The primary outcome was the composite of all-cause death and hospitalization for worsening heart failure up to 1 year. The study included 268 patients; 57 (21%) patients showed MR >2+. Patients with MR >2+ showed a lower 1-year survival free from the primary outcome (<i>P</i><0.001), all-cause death (<i>P</i><0.001), and heart failure hospitalization (<i>P</i><0.001) compared with patients with MR ≤2+. At multivariable analysis, baseline MR >2+ was an independent predictor of the primary outcome (<i>P</i><0.001). Among patients with baseline MR >2+, MR improvement was reported in 24 (44%) cases after TAVR. The persistence of MR was associated with a significantly reduced survival free from the primary outcome, all-cause death, and heart failure hospitalization up to 1 year. <br /><b>Conclusions:</b><br/>In this study, the presence of moderately severe to severe MR in patients with low-flow, low-gradient aortic stenosis undergoing TAVR portends a worse clinical outcome at 1 year. TAVR may improve MR severity in nearly half of the patients, resulting in a potential outcome benefit after discharge.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 30 Aug 2023:e029553; epub ahead of print</small></div>

<div><h4>Association Between Insomnia, Stress Events, and Other Psychosocial Factors and Incident Atrial Fibrillation in Postmenopausal Women: Insights From the Women\'s Health Initiative.</h4><i>Zhao SX, Tindle HA, Larson JC, Woods NF, ... Stefanick ML, Perez MV</i><br /><AbstractText><br /><b>Background:</b><br/>The association between psychosocial factors and atrial fibrillation (AF) is poorly understood. Methods and Results Postmenopausal women from the Women\'s Health Initiative were retrospectively analyzed to identify incident AF in relation to a panel of validated psychosocial exposure variables, as assessed by multivariable Cox proportional hazard regression and hierarchical cluster analysis. Among the 83 736 women included, the average age was 63.9±7.0 years. Over an average of 10.5±6.2 years follow-up, there were 23 954 cases of incident AF. Hierarchical cluster analysis generated 2 clusters of highly correlated psychosocial variables: the Stress Cluster included stressful life events, depressive symptoms, and insomnia, and the Strain Cluster included optimism, social support, social strain, cynical hostility, and emotional expressiveness. Incident AF was associated with higher values in the Stress Cluster (hazard ratio [HR], 1.07 per unit cluster score [95% CI, 1.05-1.09]) and the Strain Cluster (HR, 1.03 per unit cluster score [95% CI, 1.00-1.05]). Of the 8 individual psychosocial predictors that were tested, insomnia (HR, 1.04 [95% CI, 1.03-1.06]) and stressful life events (HR, 1.02 [95% CI, 1.01-1.04]) were most strongly associated with increased incidence of AF in Cox regression analysis after multivariate adjustment. Subgroup analyses showed that the Strain Cluster was more strongly associated with incident AF in those with lower traditional AF risks (<i>P</i> for interaction=0.02) as determined by the cohorts for heart and aging research in genomic epidemiology for atrial fibrillation score. <br /><b>Conclusions:</b><br/>Among postmenopausal women, 2 clusters of psychosocial stressors were found to be significantly associated with incident AF. Further research is needed to validate these associations.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 30 Aug 2023:e030030; epub ahead of print</small></div>

<div><h4>Differential Treatment and Outcomes for Patients With Heart Attacks in Advantaged and Disadvantaged Communities.</h4><i>Shen YC, Sarkar N, Hsia RY</i><br /><AbstractText><br /><b>Background:</b><br/>Racially and ethnically minoritized groups, people with lower income, and rural communities have worse access to percutaneous coronary intervention (PCI) than their counterparts, but PCI hospitals have preferentially opened in wealthier areas. Our study analyzed disparities in PCI access, treatment, and outcomes for patients with acute myocardial infarction based on the census-derived Area Deprivation Index. Methods and Results We obtained patient-level data on 629 419 patients with acute myocardial infarction in California between January 1, 2006 and December 31, 2020. We linked patient data with population characteristics and geographic coordinates, and categorized communities into 5 groups based on the share of the population in low or high Area Deprivation Index neighborhoods to identify differences in PCI access, treatment, and outcomes based on community status. Risk-adjusted models showed that patients in the most advantaged communities had 20% and 15% greater likelihoods of receiving same-day PCI and PCI during the hospitalization, respectively, compared with patients in the most disadvantaged communities. Patients in the most advantaged communities also had 19% and 16% lower 30-day and 1-year mortality rates, respectively, compared with the most disadvantaged, and a 15% lower 30-day readmission rate. No statistically significant differences in admission to a PCI hospital were observed between communities. <br /><b>Conclusions:</b><br/>Patients in disadvantaged communities had lower chances of receiving timely PCI and a greater risk of mortality and readmission compared with those in more advantaged communities. These findings suggest a need for targeted interventions to influence where cardiac services exist and who has access to them.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 30 Aug 2023:e030506; epub ahead of print</small></div>

<div><h4>Changes in Left Ventricular Global Longitudinal Strain in Patients With Heart Failure and Secondary Mitral Regurgitation: The COAPT Trial.</h4><i>Pio SM, Medvedofsky D, Stassen J, Delgado V, ... Stone GW, Bax JJ</i><br /><AbstractText><br /><b>Background:</b><br/>Left ventricular (LV) global longitudinal strain (GLS) provides incremental prognostic information over LV ejection fraction in patients with heart failure (HF) and secondary mitral regurgitation. We examined the prognostic impact of LV GLS improvement in this population. Methods and Results The COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial randomized symptomatic patients with HF with severe (3+/4+) mitral regurgitation to transcatheter edge-to-edge repair with the MitraClip device plus maximally tolerated guideline-directed medical therapy (GDMT) versus GDMT alone. LV GLS was measured at baseline and 6-month follow-up. The relationship between the improvement in LV GLS from baseline to 6 months and the composite of all-cause death or HF hospitalization between 6- and 24-month follow-up were assessed. Among 383 patients, 174 (45.4%) had improved LV GLS at 6-month follow-up (83/195 [42.6%] with transcatheter edge-to-edge repair+GDMT and 91/188 [48.4%] with GDMT alone; <i>P</i>=0.25). Improvement in LV GLS was strongly associated with reduced death or HF hospitalization between 6 and 24 months (<i>P</i><0.009), with similar risk reduction in both treatment arms (<i>P</i><sub>interaction</sub>=0.40). By multivariable analysis, LV GLS improvement at 6 months was independently associated with a lower risk of death or HF hospitalization (hazard ratio [HR], 0.55 [95% CI, 0.36-0.83]; <i>P</i>=0.009), death (HR, 0.48 [95% CI, 0.29-0.81]; <i>P</i>=0.006), and HF hospitalization (HR, 0.50 [95% CI, 0.31-0.81]; <i>P</i>=0.005) between 6 and 24 months. <br /><b>Conclusions:</b><br/>Among patients with HF and severe mitral regurgitation in the COAPT trial, improvement in LV GLS at 6-month follow-up was associated with improved outcomes after both transcatheter edge-to-edge repair and GDMT alone between 6 and 24 months. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01626079.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 30 Aug 2023:e029956; epub ahead of print</small></div>

<div><h4>Global Burden of Atrial Fibrillation and Flutter by National Income: Results From the Global Burden of Disease 2019 Database.</h4><i>Ohlrogge AH, Brederecke J, Schnabel RB</i><br /><AbstractText><br /><b>Background:</b><br/>Atrial fibrillation (AF) and atrial flutter (AFL) are common conditions that can lead to significant morbidity and death. We aimed to understand the distribution and disparities of the global burden of AF/AFL as well as the underlying risk factors. Methods and Results Data on the AF/AFL burden from the Global Burden of Disease data set were analyzed for the years 1990 to 2019, with countries grouped into low, lower-middle, upper-middle, and high national income classes according to World Bank categories. Data were supplemented with World Health Organization and World Bank information. The prevalence of AF/AFL has more than doubled (+120.7%) since 1990 in all income groups, though with a larger increment in middle-income countries (+146.6% in lower-middle- and +145.2% in upper-middle-income countries). In absolute numbers, 63.4% of AF/AFL cases originate from upper-middle-income countries, although the relative prevalence is highest in high-income countries. Prevalence of AF/AFL appears to be correlated with medical doctor rate and life expectancy. The most relevant AF/AFL risk factors are unevenly distributed among income classes, with elevated blood pressure as the only risk factor that becomes less common with increasing income. The development of these risk factors differed over time. <br /><b>Conclusions:</b><br/>The global burden of AF/AFL is increasing in all income groups and is more pronounced in middle-income countries, with further growth to be expected. Underdiagnosis of AF/AFL in low- and middle-income countries may contribute to lower reported prevalence. The risk factor distribution varies between income groups.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 30 Aug 2023:e030438; epub ahead of print</small></div>

<div><h4>Complications and Outcomes of Impella Treatment in Cardiogenic Shock Patients With and Without Acute Myocardial Infarction.</h4><i>Saito Y, Tateishi K, Toda K, Matsumiya G, Kobayashi Y, J‐PVAD registry study investigators</i><br /><AbstractText><br /><b>Background:</b><br/>In patients with cardiogenic shock (CS), acute myocardial infarction (AMI) is the most common cause, and a percutaneous microaxial ventricular assist device (Impella, Abiomed, Danvers, MA) is a choice for temporary mechanical circulatory support. However, data are limited on complications and outcomes of Impella treatment in patients with CS with and without AMI. Methods and Results Using nationwide prospective registry data in Japan, we included a total of 2047 patients with CS in whom the Impella devices were successfully placed between February 2020 and December 2021. Patients were divided into 2 groups according to the primary indication for the Impella use: AMI versus non-AMI. The primary end point was a composite of in-hospital all-cause death and major complications. Of the 2047 patients, the Impella was indicated for AMI in 1337 (65.3%). In the group without AMI, myocarditis was the leading cause of CS. Patients with AMI-CS were older and more likely to have cardiovascular risk factors than those with non-AMI-CS. The rates of in-hospital mortality (46.0% versus 43.9%, <i>P</i>=0.38) and major complications (35.2% versus 34.7%, <i>P</i>=0.85) were similar between the 2 groups. Overall, multivariable analysis identified older age, higher body mass index, previous transient ischemic attack or stroke, out-of-hospital cardiac arrest, and the Impella 5.0 as factors significantly associated with the primary end point. <br /><b>Conclusions:</b><br/>The use of Impella in patients with and without AMI was related to similar clinical outcomes with high mortality and complication rates. Further studies are needed to identify patients who may benefit from the Impella devices in CS. Registration URL: https://www.umin.ac.jp/english. Identifier: UMIN000033603.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 30 Aug 2023:e030819; epub ahead of print</small></div>

<div><h4>Short-Term Effects of Different Transcatheter Edge-to-Edge Devices on Mitral Valve Geometry.</h4><i>Rosch S, Kösser L, Besler C, Kister T, ... Lurz P, Noack T</i><br /><AbstractText><br /><b>Background:</b><br/>Short-term effects on mitral valve (MV) anatomy after transcatheter edge-to-edge repair using the PASCAL system remain unknown. Precise quantification might allow for an advanced analysis of predictors for mean transmitral gradients. Methods and Results Consecutive patients undergoing transcatheter edge-to-edge repair for secondary mitral regurgitation using PASCAL or MitraClip systems were included. Quantification of short-term MV changes throughout the cardiac cycle was performed using peri-interventional 3-dimensional MV images. Predictors for mean transmitral gradients were identified in univariable and multivariable regression analysis. Long-term results were described during 1-year follow-up. A total of 100 patients undergoing transcatheter edge-to-edge repair using PASCAL (n=50) or MitraClip systems (n=50) were included. Significant reductions of anterior-posterior diameter, annular circumference, and area throughout the cardiac cycle were found in both cohorts (<i>P</i><0.05 for all). Anatomic MV orifice area remained larger in the PASCAL cohort in mid (2.8±1.0 versus 2.4±0.9 cm<sup>2</sup>; <i>P</i>=0.049) and late diastole (2.7±1.1 versus 2.2±0.8 cm<sup>2</sup>; <i>P</i>=0.036) compared with the MitraClip cohort. Besides a device-specific profile of independent predictor of mean transmitral gradients, reduction of middiastolic anatomic MV orifice area was identified as an independent predictor in both the PASCAL (<i>β</i>=-0.410; <i>P</i>=0.001) and MitraClip cohorts (<i>β</i>=-0.318; <i>P</i>=0.028). At follow-up, reduction of mitral regurgitation grade to mild or less was more durable in the PASCAL cohort (90% versus 72%; <i>P</i>=0.035). <br /><b>Conclusions:</b><br/>PASCAL and MitraClip showed comparable short-term effects on MV geometry. However, PASCAL might better preserve MV function and demonstrated more durable mitral regurgitation reduction during follow-up. Identification of independent predictors for mean transmitral gradients might potentially help to guide device selection in the future.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 30 Aug 2023:e030333; epub ahead of print</small></div>

<div><h4>Better Life\'s Essential 8 Is Associated With Lower Risk of Diabetic Kidney Disease: A Community-Based Study.</h4><i>Gao J, Liu Y, Ning N, Wang J, ... Ma Y, Wu S</i><br /><AbstractText><br /><b>Background:</b><br/>Diabetic kidney disease (DKD) is a common diabetic complication and increases the complexity of diabetes management. No prospective study has focused on the association between DKD and Life\'s Essential 8 (LE8). Our study aims to examine the association between LE8 and DKD risk. Methods and Results A total of 7605 participants, aged 54.32±9.77 years, and 4688 participants, aged 56.11±10.38 years, were included in the longitudinal and trajectory analyses, respectively, from 2006 to 2020. The DKD was confirmed using data collected during each follow-up. LE8 was based on 4 health behaviors and 4 health factors. The range of each metric was 0 to 100, and the overall LE8 score was calculated as the unweighted average of all 8 component metric scores. The trajectories of LE8 during 2006 to 2010 were classified using latent mixture models. Cox models and restricted cubic splines were applied. After a median follow-up of 12.41 and 6.71 years in longitudinal and trajectory analyses, respectively, the DKD incidence decreased, with the LE8 level increasing (<i>P</i>-trend<0.05), and the linearity assumption for this relationship (<i>P</i>-nonlinear=0.685) had been satisfied. Adjusted hazard ratios (HRs) for the highest tertile were 0.77 (95% CI, 0.69-0.87) and 0.70 (95% CI, 0.62-0.78) in baseline and time-updated LE8 scores, respectively, compared with the lowest tertile. Adjusted HR was 0.53 (95% CI, 0.41-0.69) for the stable-high pattern compared with the stable-low pattern. <br /><b>Conclusions:</b><br/>Although LE8 is an indicator of cardiovascular health, the beneficial impact of a high LE8 score is also evident in the protection of renal health among patients with diabetes.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 30 Aug 2023:e029399; epub ahead of print</small></div>

<div><h4>Prevention of Cardiovascular Disease in Women With Pregnancy-Related Risk Factors: A Prospective Women\'s Heart Clinic Study.</h4><i>Marschner S, Mukherjee S, Watts M, Min H, ... Tremmel JA, Zaman S</i><br /><AbstractText><br /><b>Background:</b><br/>Hypertensive disorders of pregnancy, gestational diabetes, and having a small-for-gestational-age baby are known to substantially increase a woman\'s risk of cardiovascular disease. Despite this, evidence for models of care that mitigate cardiovascular disease risk in women with these pregnancy-related conditions is lacking. Methods and Results A 6-month prospective cohort study assessed the effectiveness of a multidisciplinary Women\'s Heart Clinic on blood pressure and lipid control in women aged 30 to 55 years with a past pregnancy diagnosis of hypertensive disorders of pregnancy, gestational diabetes, or a small-for-gestational age baby in Melbourne, Australia. The co-primary end points were (1) blood pressure <140/90 mm Hg or <130/80 mm Hg if diabetes and (2) total cholesterol to high-density lipoprotein cholesterol ratio <4.5. The study recruited 156 women with a mean age of 41.0±4.2 years, 3.9±2.9 years from last delivery, 68.6% White, 20.5% South/East Asian, and 80.5% university-educated. The proportion meeting blood pressure target increased (69.2% to 80.5%, <i>P</i>=0.004), with no significant change in lipid targets (80.6% to 83.7%, <i>P</i>=0.182). Systolic blood pressure (-6.9 mm Hg [95% CI, -9.1 to -4.7], <i>P</i><0.001), body mass index (-0.6 kg/m<sup>2</sup> [95% CI, -0.8 to -0.3], <i>P</i><0.001), low-density lipoprotein cholesterol (-4.2 mg/dL [95% CI, -8.2 to -0.2], <i>P</i>=0.042), and total cholesterol (-4.6 mg/dL [95% CI, -9.1 to -0.2] <i>P</i>=0.042) reduced. Heart-healthy lifestyle significantly improved with increased fish/olive oil (36.5% to 51.0%, <i>P</i>=0.012), decreased fast food consumption (33.8% to 11.0%, <i>P</i><0.001), and increased physical activity (84.0% to 92.9%, <i>P</i>=0.025). <br /><b>Conclusions:</b><br/>Women at high risk for cardiovascular disease due to past pregnancy-related conditions experienced significant improvements in multiple cardiovascular risk factors after attending a Women\'s Heart Clinic, potentially improving long-term cardiovascular disease outcomes. Registration URL: https://www.anzctr.org.au; Unique identifier: ACTRN12622000646741.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 29 Aug 2023:e030015; epub ahead of print</small></div>

<div><h4>Differentiating the Prognostic Determinants of Myocardial Steatosis for Heart Failure With Preserved Ejection Fraction by Cardiac Magnetic Resonance Imaging.</h4><i>Lin TT, Lee CK, Huang KC, Wu CK, ... Wang YC, Lin LY</i><br /><AbstractText><br /><b>Background:</b><br/>Myocardial steatosis and fibrosis may play a role in the pathophysiology of heart failure with preserved ejection fraction. We therefore investigated the prognostic significance of epicardial fat (epicardial adipose tissue [EAT]) and myocardial diffuse fibrosis. Methods and Results Myocardial fibrosis, estimated as extracellular volume (ECV), and EAT were measured using cardiac magnetic resonance imaging in 163 subjects with heart failure with preserved ejection fraction. We also evaluated cardiac structure and diastolic and systolic function by echocardiography and cardiac magnetic resonance imaging. After 24 months\' follow-up, 39 (24%) subjects had experienced cardiovascular events, including hospitalization for heart failure, acute coronary syndrome, and cardiovascular death. Median EAT and mean ECV were significantly higher in subjects with cardiovascular events than survivors (EAT, 35 [25-45] versus 31 [21-38], <i>P</i>=0.006 and ECV, 28.9±3.16% versus 27.2±3.56%, <i>P</i>=0.04). Subjects with high EAT (≥42 g) had increased risk of cardiovascular events (hazard ratio [HR], 2.528 [95% CI, 1.704-4.981]; <i>P</i>=0.032). High ECV (>29%) was also significantly associated with poorer outcomes (HR, 1.647 [95% CI, 1.263-2.548]; <i>P</i>=0.013). With respect to secondary end points, high EAT and high ECV were associated with increased risk of the incident acute coronary syndrome (HR, 1.982 [95% CI, 1.008-4.123]; <i>P</i>=0.049) and hospitalization for heart failure (HR, 1.789 [95% CI, 1.102-6.987]; <i>P</i>=0.033), respectively. <br /><b>Conclusions:</b><br/>Our study suggested that increased epicardial fat and ECV detected by cardiac magnetic resonance imaging have an impact on cardiovascular prognosis, in particular acute coronary syndrome and hospitalization for heart failure, respectively.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 29 Aug 2023:e027781; epub ahead of print</small></div>

<div><h4>Disparities in Stroke Incidence Over Time by Sex and Age in Latin America and the Caribbean Region 1997 to 2021: A Systematic Review and Meta-Analysis.</h4><i>Nuñez M, Delfino C, Asenjo-Lobos C, Schilling A, ... Anderson CS, Muñoz Venturelli P</i><br /><AbstractText><br /><b>Background:</b><br/>High-income country studies show unfavorable trends in stroke incidence (SI) in younger populations. We aimed to estimate temporal change in SI disaggregated by age and sex in Latin America and the Caribbean region. Methods and Results A search strategy was used in MEDLINE, WOS, and LILACS databases from 1997 to 2021, including prospective population-based observational studies with first-ever stroke incidence in Latin America. Reports without data broken down by age and sex were excluded. Risk of bias was assessed with The Joanna Briggs Institute\'s guide. The main outcomes were incidence rate ratio and relative temporal trend ratio of SI, comparing time periods before 2010 with after 2010. Pooled relative temporal trend ratios considering only studies with 2 periods in the same population were calculated by random-effects meta-analysis. Meta-regression analysis was used to evaluate incidence rate determinants. From 9242 records identified, 6 studies were selected including 4483 first-ever stroke in 4 101 084 individuals. Crude incidence rate ratio in younger subjects (<55 years) comparing before 2010:after 2010 periods showed an increase in SI in the past decade (incidence rate ratio, 1.37 [95% CI, 1.23-1.50]), in contrast to a decrease in older people during the same period (incidence rate ratio, 0.83 [95% CI, 0.76-0.89]). Overall relative temporal trend ratio (<55:≥55 years) was 1.65 (95 CI%, 1.50-1.80), with higher increase in young women (pooled relative temporal trend ratio, 3.08 [95% CI, 1.18-4.97]; <i>P</i> for heterogeneity <0.001). <br /><b>Conclusions:</b><br/>An unfavorable change in SI in young people, especially in women, was detected in population-based studies in the past decade in Latin America and the Caribbean. Further investigation of the explanatory variables is required to ameliorate stroke prevention and inform local decision-makers. Registration URL: https://www.crd.york.ac.uk/prospero/ Identifier: CRD42022332563.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 29 Aug 2023:e029800; epub ahead of print</small></div>

<div><h4>TRAF Family Member 4 Promotes Cardiac Hypertrophy Through the Activation of the AKT Pathway.</h4><i>Li J, Wang CQ, Xiao WC, Chen Y, ... Deng KQ, Li HP</i><br /><AbstractText><br /><b>Background:</b><br/>Pathological cardiac hypertrophy is a major cause of heart failure morbidity. The complex mechanism of intermolecular interactions underlying the pathogenesis of cardiac hypertrophy has led to a lack of development and application of therapeutic methods. Methods and Results Our study provides the first evidence that TRAF4, a member of the tumor necrosis factor receptor-associated factor (TRAF) family, acts as a promoter of cardiac hypertrophy. Here, Western blotting assays demonstrated that TRAF4 is upregulated in cardiac hypertrophy. Additionally, TRAF4 deletion inhibits the development of cardiac hypertrophy in a mouse model after transverse aortic constriction surgery, whereas its overexpression promotes phenylephrine stimulation-induced cardiomyocyte hypertrophy in primary neonatal rat cardiomyocytes. Mechanistically, RNA-seq analysis revealed that TRAF4 promoted the activation of the protein kinase B pathway during cardiac hypertrophy. Moreover, we found that inhibition of protein kinase B phosphorylation rescued the aggravated cardiomyocyte hypertrophic phenotypes caused by TRAF4 overexpression in phenylephrine-treated neonatal rat cardiomyocytes, suggesting that TRAF4 may regulate cardiac hypertrophy in a protein kinase B-dependent manner. <br /><b>Conclusions:</b><br/>Our results revealed the regulatory function of TRAF4 in cardiac hypertrophy, which may provide new insights into developing therapeutic and preventive targets for this disease.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 29 Aug 2023:e028185; epub ahead of print</small></div>

<div><h4>Long-Term Impact of Additional Ablation After Pulmonary Vein Isolation: Results From EARNEST-PVI Trial.</h4><i>Masuda M, Inoue K, Tanaka N, Watanabe T, ... Sakata Y, Osaka Cardiovascular Conference (OCVC)‐Arrhythmia Investigators</i><br /><AbstractText><br /><b>Background:</b><br/>An optimal strategy for left atrial ablation in addition to pulmonary vein isolation (PVI) in patients with persistent atrial fibrillation (AF) has not been determined. Methods and Results We conducted an extended follow-up of the multicenter randomized controlled EARNEST-PVI (Efficacy of Pulmonary Vein Isolation Alone in Patients With Persistent Atrial Fibrillation) trial, which compared 12-month rhythm outcomes in patients with persistent AF between patients randomized to a PVI-alone strategy (n=248) or PVI-plus strategy (n=248; PVI followed by left atrial additional ablation, including linear ablation or ablation targeting areas with complex fractionated electrograms). The present study extended the follow-up period to 3 years after enrollment. Outcomes were compared not only between randomly allocated groups but also between on-treatment groups categorized by actually created ablation lesions. Recurrence rate of AF or atrial tachycardia (AT) was lower in the randomly allocated to PVI-plus group than the PVI-alone group (29.0% versus 37.5%, <i>P</i>=0.036). On-treatment analysis revealed that patients with PVI+linear ablation (n=205) demonstrated a lower AF/AT recurrence rate than those with PVI only (26.3% versus 37.8%, <i>P</i>=0.007). In contrast, patients with PVI+complex fractionated electrograms ablation (n=37) had an AF/AT recurrence rate comparable to that of patients with PVI only (40.5% versus 37.8%, <i>P</i>=0.76). At second ablation in 126 patients with AF/AT recurrence, ATs excluding common atrial flutter were more frequent in patients with PVI+linear ablation than in those with PVI only (32.6% versus 5.7%, <i>P</i><0.0001). <br /><b>Conclusions:</b><br/>Left atrial ablation in addition to PVI was efficacious during 3-year follow-up. Linear ablation was superior to other ablation strategies but may increase iatrogenic ATs. Registration URL: http://www.umin.ac.jp/ctr/index-j.htm; Unique identifier: UMIN000019449.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 29 Aug 2023:e029651; epub ahead of print</small></div>

<div><h4>Prenatal and Childhood Per- and Polyfluoroalkyl Substance (PFAS) Exposures and Blood Pressure Trajectories From Birth to Late Adolescence in a Prospective US Prebirth Cohort.</h4><i>Zhang M, Aris IM, Lin PD, Rifas-Shiman SL, ... Oken E, Hivert MF</i><br /><AbstractText><br /><b>Background:</b><br/>Evidence is limited regarding the associations of prenatal and childhood per- and polyfluoroalkyl substance (PFAS) exposures with blood pressure (BP) trajectories in children. Methods and Results Participants are from Project Viva, a prospective prebirth cohort in eastern Massachusetts. We measured PFAS in early-pregnancy maternal (median, 9.6 weeks) and midchildhood (median, 7.7 years) plasma samples. We conducted standardized BP measurements at 6 research visits: birth, infancy (median, 6.3 months), early childhood (median, 3.2 years), midchildhood (median, 7.7 years), early adolescence (median, 12.9 years), and late adolescence (median, 17.5 years). We used linear regression to examine associations of individual PFASs with BP at each visit, linear spline mixed-effects regression to model BP trajectories, and a mixture approach to estimate PFAS exposure burden. We included 9036 BP measures from 1506 participants. We observed associations between particular individual prenatal PFASs and child BP at specific time points, for example, prenatal 2-(N-ethyl-perfluorooctane sulfonamido) acetate (EtFOSAA) and 2-(N-methyl-perfluorooctane sulfonamido) acetate (MeFOSAA) with higher systolic BP at birth; prenatal perfluorooctane sulfonate (PFOS) and EtFOSAA with lower diastolic BP in infancy; and prenatal PFOS, perfluorooctanoate (PFOA), and EtFOSAA with higher systolic BP at midchildhood. No prenatal or childhood PFAS was consistently associated with BP across all visits. Diastolic BP trajectories from 0 to 20 years differed slightly by prenatal PFOA, perfluorohexane sulfonate (PFHxS), and perfluorononanoate (PFNA) (<i>P</i> values 0.01-0.09). Diastolic BP trajectories from 6 to 20 years differed slightly by midchildhood PFHxS and MeFOSAA (<i>P</i>-values 0.03-0.08). Prenatal or childhood PFAS mixture burden scores were not associated with BP. <br /><b>Conclusions:</b><br/>We found associations of prenatal and childhood PFAS exposures with BP at specific time points between birth and late adolescence but no consistent associations across all time points or PFAS types.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 29 Aug 2023:e030760; epub ahead of print</small></div>

<div><h4>Risk of Incident Venous Thromboembolism Among Patients With Bullous Pemphigoid or Pemphigus Vulgaris: A Nationwide Cohort Study With Meta-Analysis.</h4><i>Chen TL, Huang WT, Loh CH, Huang HK, Chi CC</i><br /><AbstractText><br /><b>Background:</b><br/>Bullous pemphigoid (BP) and pemphigus vulgaris (PV) share similar pathophysiology with venous thromboembolism (VTE) involving platelet activation, immune dysregulation, and systemic inflammation. Nevertheless, their associations have not been well established. Methods and Results To examine the risk of incident VTE among patients with BP or PV, we performed a nationwide cohort study using Taiwan\'s National Health Insurance Research Database and enrolled 12 162 adults with BP or PV and 12 162 controls. A Cox regression model considering stabilized inverse probability weighting was used to calculate the hazard ratios (HRs) for incident VTE associated with BP or PV. To consolidate the findings, a meta-analysis that incorporated results from the present cohort study with previous literature was also conducted. Compared with controls, patients with BP or PV had an increased risk for incident VTE (HR, 1.87 [95% CI, 1.55-2.26]; <i>P</i><0.001). The incidence of VTE was 6.47 and 2.20 per 1000 person-years in the BP and PV cohorts, respectively. The risk for incident VTE significantly increased among patients with BP (HR, 1.85 [95% CI, 1.52-2.24]; <i>P</i><0.001) and PV (HR, 1.99 [95% CI, 1.02-3.91]; <i>P</i>=0.04). In the meta-analysis of 8 studies including ours, BP and PV were associated with an increased risk for incident VTE (pooled relative risk, 2.17 [95% CI, 1.82-2.62]; <i>P</i><0.001). <br /><b>Conclusions:</b><br/>BP and PV are associated with an increased risk for VTE. Preventive approaches and cardiovascular evaluation should be considered particularly for patients with BP or PV with concomitant risk factors such as hospitalization or immobilization.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 29 Aug 2023:e029740; epub ahead of print</small></div>

<div><h4>Evolutionary Action-Machine Learning Model Identifies Candidate Genes Associated With Early-Onset Coronary Artery Disease.</h4><i>Shapiro D, Lee K, Asmussen J, Bourquard T, Lichtarge O</i><br /><AbstractText><br /><b>Background:</b><br/>Coronary artery disease is a primary cause of death around the world, with both genetic and environmental risk factors. Although genome-wide association studies have linked >100 unique loci to its genetic basis, these only explain a fraction of disease heritability. Methods and Results To find additional gene drivers of coronary artery disease, we applied machine learning to quantitative evolutionary information on the impact of coding variants in whole exomes from the Myocardial Infarction Genetics Consortium. Using ensemble-based supervised learning, the Evolutionary Action-Machine Learning framework ranked each gene\'s ability to classify case and control samples and identified 79 significant associations. These were connected to known risk loci; enriched in cardiovascular processes like lipid metabolism, blood clotting, and inflammation; and enriched for cardiovascular phenotypes in knockout mouse models. Among them, <i>INPP5F</i> and <i>MST1R</i> are examples of potentially novel coronary artery disease risk genes that modulate immune signaling in response to cardiac stress. <br /><b>Conclusions:</b><br/>We concluded that machine learning on the functional impact of coding variants, based on a massive amount of evolutionary information, has the power to suggest novel coronary artery disease risk genes for mechanistic and therapeutic discoveries in cardiovascular biology, and should also apply in other complex polygenic diseases.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 29 Aug 2023:e029103; epub ahead of print</small></div>

<div><h4>Association Between Maternal Factors in Early Pregnancy and Congenital Heart Defects in Offspring: The Japan Environment and Children\'s Study.</h4><i>Kawai S, Pak K, Iwamoto S, Kawakami C, ... Kobayashi T, Japan Environment and Children\'s Study Group</i><br /><AbstractText><br /><b>Background:</b><br/>Many prenatal factors are reported to be associated with congenital heart defects (CHD) in offspring. However, these associations have not been adequately examined using large-scale birth cohorts. Methods and Results We evaluated a data set of the Japan Environmental and Children\'s Study. The primary outcome was a diagnosis of CHD by age 2 years. We defined the following variables as exposures: maternal baseline characteristics, fertilization treatment, maternal history of diseases, socioeconomic status, maternal alcohol intake, smoking, tea consumption, maternal dietary intake, and maternal medications and supplements up to 12 weeks of gestation. We used multivariable logistic regression analysis to assess the associations between various exposures and CHD in offspring. A total of 91 664 singletons were included, among which 1264 (1.38%) had CHD. In multivariable analysis, vitamin A supplements (adjusted odds ratio [aOR], 5.78 [95% CI, 2.30-14.51]), maternal use of valproic acid (aOR, 4.86 [95% CI, 1.51-15.64]), maternal use of antihypertensive agents (aOR, 3.80 [95% CI, 1.74-8.29]), maternal age ≥40 years (aOR, 1.59 [95% CI, 1.14-2.20]), and high maternal hemoglobin concentration in the second trimester (aOR, 1.10 per g/dL [95% CI, 1.03-1.17]) were associated with CHD in offspring. <br /><b>Conclusions:</b><br/>Using a Japanese large-scale birth cohort study, we found 6 maternal factors to be associated with CHD in offspring.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 29 Aug 2023:e029268; epub ahead of print</small></div>

<div><h4>Human Milk Feeding and Direct Breastfeeding Improve Outcomes for Infants With Single Ventricle Congenital Heart Disease: Propensity Score-Matched Analysis of the NPC-QIC Registry.</h4><i>Elgersma KM, Wolfson J, Fulkerson JA, Georgieff MK, ... Uzark K, McKechnie AC</i><br /><AbstractText><br /><b>Background:</b><br/>Infants with single ventricle congenital heart disease undergo 3 staged surgeries/interventions, with risk for morbidity and mortality. We estimated the effect of human milk (HM) and direct breastfeeding on outcomes including necrotizing enterocolitis, infection-related complications, length of stay, and mortality. Methods and Results We analyzed the National Pediatric Cardiology Quality Improvement Collaborative (NPC-QIC) registry (2016-2021), examining HM/breastfeeding groups during stage 1 and stage 2 palliations. We calculated propensity scores for feeding exposures, then fitted Poisson and logistic regression models to compare outcomes between propensity-matched cohorts. Participants included 2491 infants (68 sites). Estimates for all outcomes were better in HM/breastfeeding groups. Infants fed exclusive HM before stage 1 palliation (S1P) had lower odds of preoperative necrotizing enterocolitis (odds ratio [OR], 0.37 [95% CI, 0.17-0.84]; <i>P</i>=0.017) and shorter S1P length of stay (rate ratio [RR], 0.87 [95% CI, 0.78-0.98]; <i>P</i>=0.027). During the S1P hospitalization, infants with high HM had lower odds of postoperative necrotizing enterocolitis (OR, 0.28 [95% CI, 0.15-0.50]; <i>P</i><0.001) and sepsis (OR, 0.29 [95% CI, 0.13-0.65]; <i>P</i>=0.003), and shorter S1P length of stay (RR, 0.75 [95% CI, 0.66-0.86]; <i>P</i><0.001). At stage 2 palliation, infants with any HM (RR, 0.82 [95% CI, 0.69-0.97]; <i>P</i>=0.018) and any breastfeeding (RR, 0.71 [95% CI, 0.57-0.89]; <i>P</i>=0.003) experienced shorter length of stay. <br /><b>Conclusions:</b><br/>Infants with single ventricle congenital heart disease in high-HM and breastfeeding groups experienced multiple significantly better outcomes. Given our findings of improved health, strategies to increase the rates of HM/breastfeeding in these patients should be implemented. Future research should replicate these findings with granular feeding data and in broader congenital heart disease populations, and should examine mechanisms (eg, HM components, microbiome) by which HM/breastfeeding benefits these infants.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 29 Aug 2023:e030756; epub ahead of print</small></div>

<div><h4>Prognostic Value of Hospital Frailty Risk Score and Clinical Outcomes in Patients Undergoing Revascularization for Critical Limb-Threatening Ischemia.</h4><i>Majmundar M, Patel KN, Doshi R, Mehta H, ... Ali A, Gupta K</i><br /><AbstractText><br /><b>Background:</b><br/>The impact of medical record-based frailty assessment on clinical outcomes in patients undergoing revascularization for critical limb-threatening ischemia (CLTI) is unknown. Methods and Results This study included patients with CLTI aged ≥18 years from the nationwide readmissions database 2016 to 2018 who underwent endovascular revascularization (ER) or surgical revascularization (SR). The hospital frailty risk score, a previously validated <i>International Classification of Diseases, Tenth Edition, Clinical Modification (ICD-10-CM</i>) claims-based score, was used to categorize patients into low- (<5), intermediate- (5-15), and high-risk (>15) frailty categories. Primary outcomes were in-hospital mortality and major amputation at 6 months. A total of 64 338 patients were identified who underwent ER (82.3%) or SR (17.7%) for CLTI. The mean (SD) age of the cohort was 69.3 (11.8) years, and 63% of patients were male. This study found a nonlinear association between hospital frailty risk score and in-hospital mortality and 6-month major amputation. In both ER and SR cohorts, the intermediate- and high-risk groups were associated with a significantly higher risk of in-hospital mortality (high-risk group: ER: odds ratio [OR], 7.2 [95% CI, 4.4-11.6], <i>P</i><0.001; SR: OR, 28.6 [95% CI, 3.4-237.6], <i>P</i>=0.002) and major amputation at 6 months (high-risk group: ER: hazard ratio [HR], 1.6 [95% CI, 1.5-1.7], <i>P</i><0.001; SR: HR, 1.7 [95% CI, 1.4-2.2], <i>P</i><0.001) compared with the low-risk group. <br /><b>Conclusions:</b><br/>The hospital frailty risk score, generated from the medical record, can identify frailty and predict in-hospital mortality and 6-month major amputation in patients undergoing ER or SR for CLTI. Further studies are needed to assess if this score can be incorporated into clinical decision-making in patients undergoing revascularization for CLTI.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 29 Aug 2023:e030294; epub ahead of print</small></div>

<div><h4>Clinical and Vessel Characteristics Associated With Hard Outcomes After PCI and Their Combined Prognostic Implications.</h4><i>Yang S, Hwang D, Zhang J, Park J, ... De Bruyne B, Koo BK</i><br /><AbstractText><br /><b>Background:</b><br/>Cardiac death or myocardial infarction still occurs in patients undergoing contemporary percutaneous coronary intervention (PCI). We aimed to identify adverse clinical and vessel characteristics related to hard outcomes after PCI and to investigate their individual and combined prognostic implications. Methods and Results From an individual patient data meta-analysis of 17 cohorts of patients who underwent post-PCI fractional flow reserve measurement after drug-eluting stent implantation, 2081 patients with available clinical and vessel characteristics were analyzed. The primary outcome was cardiac death or target-vessel myocardial infarction at 2 years. The mean age of patients was 64.2±10.2 years, and the mean angiographic percent diameter stenosis was 63.9%±14.3%. Among 11 clinical and 8 vessel features, 4 adverse clinical characteristics (age ≥65 years, diabetes, chronic kidney disease, and left ventricular ejection fraction <50%) and 2 adverse vessel characteristics (post-PCI fractional flow reserve ≤0.80 and total stent length ≥54 mm) were identified to independently predict the primary outcome (all <i>P</i><0.05). The number of adverse vessel characteristics had additive predictability for the primary end point to that of adverse clinical characteristics (area under the curve 0.72 versus 0.78; <i>P</i>=0.03) and vice versa (area under the curve 0.68 versus 0.78; <i>P</i>=0.03). The cumulative event rate increased in the order of none, either, and both of adverse clinical characteristics ≥2 and adverse vessel characteristics ≥1 (0.3%, 2.4%, and 5.3%; <i>P</i> for trend <0.01). <br /><b>Conclusions:</b><br/>In patients undergoing drug-eluting stent implantation, adverse clinical and vessel characteristics were associated with the risk of cardiac death or target-vessel myocardial infarction. Because these characteristics showed independent and additive prognostic value, their integrative assessment can optimize post-PCI risk stratification. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04684043. www.crd.york.ac.uk/prospero/. Unique Identifier: CRD42021234748.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 29 Aug 2023:e030572; epub ahead of print</small></div>

<div><h4>Study Design, Rationale, and Methodology for Promote Weight Loss in Patients With Peripheral Artery Disease Who Also Have Obesity: The PROVE Trial.</h4><i>Whipple MO, Pfammatter AF, Spring B, Rejeski WJ, ... Ambrosius WT, McDermott MM</i><br /><AbstractText><br /><b>Background:</b><br/>Overweight and obesity are associated with adverse functional outcomes in people with peripheral artery disease (PAD). The effects of weight loss in people with overweight/obesity and PAD are unknown. Methods The PROVE (Promote Weight Loss in Obese PAD Patients to Prevent Mobility Loss) Trial is a multicentered randomized clinical trial with the primary aim of testing whether a behavioral intervention designed to help participants with PAD lose weight and walk for exercise improves 6-minute walk distance at 12-month follow-up, compared with walking exercise alone. A total of 212 participants with PAD and body mass index ≥25 kg/m<sup>2</sup> will be randomized. Interventions are delivered using a Group Mediated Cognitive Behavioral intervention model, a smartphone application, and individual telephone coaching. The primary outcome is 12-month change in 6-minute walk distance. Secondary outcomes include total minutes of walking exercise/wk at 12-month follow-up and 12-month change in accelerometer-measured physical activity, the Walking Impairment Questionnaire distance score, and the Patient-Reported Outcomes Measurement Information System mobility questionnaire. Tertiary outcomes include 12-month changes in perceived exertional effort at the end of the 6-minute walk, diet quality, and the Short Physical Performance Battery. Exploratory outcomes include changes in gastrocnemius muscle biopsy measures of mitochondrial cytochrome C oxidase activity, mitochondrial biogenesis, capillary density, and inflammatory markers. <br /><b>Conclusions:</b><br/>The PROVE randomized clinical trial will evaluate the effects of exercise with an intervention of coaching and a smartphone application designed to achieve weight loss, compared with exercise alone, on walking performance in people with PAD and overweight/obesity. Results will inform optimal treatment for the growing number of patients with PAD who have overweight/obesity. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04228978.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 29 Aug 2023:e031182; epub ahead of print</small></div>

<div><h4>Methods of a Study to Assess the Contribution of Cerebral Small Vessel Disease and Dementia Risk Alleles to Racial Disparities in Vascular Cognitive Impairment and Dementia.</h4><i>Sawyer RP, Worrall BB, Howard VJ, Crowe MG, Howard G, Hyacinth HI</i><br /><AbstractText><br /><b>Background:</b><br/>Non-Hispanic Black adults have a higher proportion of vascular cognitive impairment and Alzheimer\'s disease and related dementias compared with non-Hispanic White adults that may be due to differences in the burden of cerebral small vessel disease and risk alleles for Alzheimer\'s disease and related dementias. We describe here the methods of an ancillary study to the REGARDS (Reason for Geographic and and Racial Difference in Stroke) study, which will examine the role of magnetic resonance imaging markers of cerebral small vessel disease and vascular as well as genetic risk factors for Alzheimer\'s disease and related dementias in racial disparity in the prevalence and trajectory of vascular cognitive impairment and dementia in non-Hispanic White and non-Hispanic Black participants. Methods In participants with no prior history of stroke who had an incident stroke or transient ischemic attack after enrollment in the study, magnetic resonance imaging scans will be evaluated using the Standards for Reporting Vascular Changes on Neuroimaging international consensus criteria and automated analysis pipelines for quantification of cerebral small vessel disease. Participants will be genotyped for <i>APOE</i> ε4 and <i>TREM2</i> risk alleles for Alzheimer\'s disease and related dementias. The 6-item screener will define global cognitive function and be the primary cognitive outcome. <br /><b>Conclusions:</b><br/>With at least 426 non-Hispanic Black and 463 non-Hispanic White participants who have at least 2 prior and 2 poststroke or transient ischemic attack cognitive assessments, we will have at least 80% power to detect a minimum effect size of 0.09 SD change in <i>Z</i> score, with correction for as many as 20 tests (ie, at <i>P</i><0.0025, after adjusting for up to 20 covariates) for cognitive decline.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 29 Aug 2023:e030925; epub ahead of print</small></div>

<div><h4>Total and Regional Fat/Muscle Mass Ratio and Risks of Incident Cardiovascular Disease and Mortality.</h4><i>Zhou R, Chen HW, Lin Y, Li FR, ... Huang YN, Wu XB</i><br /><AbstractText><br /><b>Background:</b><br/>To evaluate the sex-specific associations of total and regional fat/muscle mass ratio (FMR) with cardiovascular disease (CVD) incidence and mortality, and to explore the underlying mechanisms driven by cardiometabolites and inflammatory cells. We compared the predictive value of FMRs to body mass index. Methods and Results This population-based, prospective cohort study included 468 885 UK Biobank participants free of CVD at baseline. Fat mass and muscle mass were estimated using a bioelectrical impedance assessment device. FMR was calculated as fat mass divided by muscle mass in corresponding body parts (total body, trunk, arm, and leg). Multivariable Cox proportional hazards models and mediation analyses were used. During 12.5 years of follow-up, we documented 49 936 CVD cases and 4158 CVD deaths. Higher total FMR was associated with an increased risk of incident CVD (hazard ratios [HRs] were 1.63 and 1.83 for men and women, respectively), ischemic heart disease (men: HR, 1.61; women: HR, 1.81), myocardial infarction (men: HR, 1.72; women: HR, 1.49), and congestive heart failure (men: HR, 2.25; women: HR, 2.57). The positive associations of FMRs with mortality from total CVD or its subtypes were significant mainly in trunk and arm for male patients (<i>P</i> for trend <0.05). We also identified 8 cardiometabolites and 5 inflammatory cells that partially mediated FMR-CVD associations. FMRs were modestly better at discriminating cardiovascular mortality risk. <br /><b>Conclusions:</b><br/>Higher total and regional FMRs were associated with an increased risk of CVD and mortality, partly mediated through cardiometabolites and inflammatory cells. Early monitoring of FMR should be considered to alleviate CVD risk. FMRs were superior to body mass index in predicting CVD mortality.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 29 Aug 2023:e030101; epub ahead of print</small></div>

<div><h4>Racial and Ethnic Disparities in Treatment of Critical Limb Ischemia: A National Perspective.</h4><i>Wahood W, Duval S, Takahashi EA, Secemsky EA, Misra S</i><br /><AbstractText><br /><b>Background:</b><br/>Recent guidelines have emphasized the use of medical management, early diagnosis, and a multidisciplinary team to effectively treat patients with critical limb ischemia (CLI). Previous literature briefly highlighted the current racial disparities in its intervention. Herein, we analyze the trend over a 14-year time period to investigate whether the disparities gap in CLI management is closing. Methods and Results The National Inpatient Sample was queried between 2005 and 2018 for hospitalizations involving CLI. Nontraumatic amputations and revascularization were identified. Utilization trends of these procedures were compared between races (White, Black, Hispanic, Asian and Pacific Islander, Native American, and Other). Multivariable regression assessed differences in race regarding procedure usage. There were 6 904 562 admissions involving CLI in the 14-year study period. The rate of admissions in White patients who received any revascularization decreased by 0.23% (<i>P</i><0.001) and decreased by 0.25% (<i>P</i>=0.025) for Asian and Pacific Islander patients. Among all patients, the annual rate of admission in White patients who received any amputation increased by 0.21% (<i>P</i><0.001), increased by 0.19% (<i>P</i>=0.001) for Hispanic patients, and increased by 0.19% (<i>P</i>=0.012) for the Other race patients. Admissions involving Black, Hispanic, Asian and Pacific Islander, or Other race patients had higher odds of receiving any revascularization compared with White patients. All races had higher odds of receiving major amputation compared with White patients. <br /><b>Conclusions:</b><br/>Our analysis highlights disparities in CLI treatment in our nationally representative sample. Non-White patients are more likely to receive invasive treatments, including major amputations and revascularization for CLI, compared with White patients.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 23 Aug 2023:e029074; epub ahead of print</small></div>

<div><h4>Type 2 Diabetes and Atrial Fibrillation: Evaluating Causal and Pleiotropic Pathways Using Mendelian Randomization.</h4><i>Reddy RK, Ardissino M, Ng FS</i><br /><AbstractText><br /><b>Background:</b><br/>Observational associations between type 2 diabetes (T2D) and atrial fibrillation (AF) have been established, but causality remains undetermined. We performed Mendelian randomization (MR) to study causal effects of genetically predicted T2D on AF risk, independent of cardiometabolic risk factors. Methods and Results Instrumental variables included 182 uncorrelated single nucleotide polymorphisms associated with T2D at genome-wide significance (<i>P</i> <5×10<sup>-8</sup>). Genetic association estimates for cardiometabolic exposures were obtained from genome-wide association studies including 188 577 individuals for low-density lipoprotein-C, 694 649 individuals for body mass index, and 757 601 for systolic blood pressure. Two-sample, inverse-variance weighted MR formed the primary analyses. The MR-TRYX approach was used to dissect potential pleiotropic pathways, with multivariable MR performed to investigate cardiometabolic mediation. Genetically predicted T2D associated with increased AF liability in univariable MR (odds ratio [OR], 1.08 [95% CI, 1.02-1.13], <i>P</i>=0.003). Sensitivity analyses indicated potential pleiotropy, with radial MR identifying 4 outlier single nucleotide polymorphisms that were likely contributors. Phenomic scanning on MR-base and subsequent least absolute shrinkage and selection operator regression allowed prioritization of 7 candidate traits. The outlier-adjusted effect estimate remained consistent with the original inverse-variance weighted estimate (OR, 1.07 [95% CI, 1.02-1.12], <i>P</i>=0.008). On multivariable MR, T2D remained associated with increased AF liability after adjustment for low-density lipoprotein-C and body mass index. Following adjustment for systolic blood pressure, the relationship between T2D and AF became nonsignificant (OR, 1.04 [95% CI, 0.95-1.13], <i>P</i>=0.40). <br /><b>Conclusions:</b><br/>These data provide novel genetic evidence that while T2D likely causally associates with AF, mediation via systolic blood pressure exists. Endeavoring to lower systolic blood pressure alongside achieving normoglycemia may provide particular benefit on AF risk in patients with T2D.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 23 Aug 2023:e030298; epub ahead of print</small></div>

<div><h4>Computed Tomography Scan Evidence for Left Atrial Appendage Short-Term Remodeling Following Percutaneous Occlusion: Impact of Device Oversizing.</h4><i>Mahmoudi K, Galea R, Elhadad S, Temperli F, ... Räber L, Amabile N</i><br /><AbstractText><br /><b>Background:</b><br/>The interrelationships between left atrial appendage (LAA) dimensions and device following implantation are unknown. We aimed to analyze the impact of Watchman device implantation on LAA dimensions following its percutaneous closure and potential predictors of remodeling. Methods and Results All consecutive LAA closure procedures performed at 2 centers between November 2017 and December 2020 were included in the WATCH-DUAL (Watchman 2.5 Versus Watchman FLX in a Dual-Center Left Atrial Appendage Closure Cohort) registry. This study included patients who had pre- and postintervention computed tomography scan analysis. The LAA and device dimensions were measured in a centralized core lab by 3-dimensional computed tomography scan reconstruction methods, focusing on the device landing zone. This analysis included 104 patients (age, 76.0 [range, 72.0-83.0] years; 72% men; 53% Watchman FLX; 47% Watchman 2.5). The baseline characteristics were comparable between Watchman 2.5 and Watchman FLX groups, except for the higher use of oversizing in the latter group. The median delay for computed tomography control was 49 (range, 43-64) days. The landing zone area (median, 446 [range, 363-523] versus 290 [222-366] mm<sup>2</sup>; <i>P</i><0.001) and minimal diameter (median, 23.0 [range, 20.7-24.8] versus 16.7 [14.7-19.4] mm; <i>P</i><0.001) significantly increased after implantation. The absolute (median, 157 [range, 98-220] versus 85 [18-148] mm<sup>2</sup>, <i>P</i><0.001) and relative (median, 50% [range, 32%-79%] versus 26% [4%-50%]; <i>P</i><0.001) increases in landing zone area were more pronounced in patients with oversized device. Baseline LAA dimensions were smaller, landing zone eccentricity larger, and oversized device more frequent in patients with significant overexpansion compared with the others. <br /><b>Conclusions:</b><br/>LAA dimensions increased at the site of the Watchman prosthesis after implantation, suggesting a local positive remodeling after the procedure. This phenomenon was more pronounced in the case of oversized devices.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 23 Aug 2023:e030037; epub ahead of print</small></div>

<div><h4>Plasma Serotonin and Cardiovascular Outcomes in Chronic Kidney Disease.</h4><i>Edmonston D, Isakova T, Wolf M, CRIC (Chronic Renal Insufficiency Cohort) Study Investigators *</i><br /><AbstractText><br /><b>Background:</b><br/>Platelet-poor plasma serotonin levels are associated with adverse cardiovascular outcomes. Although plasma serotonin levels increase in chronic kidney disease, the cardiovascular implications remain unknown. Methods and Results In 1114 participants from the prospective CRIC (Chronic Renal Insufficiency Cohort) Study, we evaluated the association between plasma serotonin, categorized as undetectable, intermediate, and high (≥20 ng/mL) levels, and cross-sectional findings on echocardiography, including left ventricular hypertrophy, left ventricular ejection fraction, and pulmonary hypertension. We also analyzed whether serotonin was associated with time-to-event cardiovascular outcomes, including heart failure hospitalization and atherosclerotic cardiovascular disease (ASCVD) events, in addition to mortality. Because selective serotonin reuptake inhibitors decrease plasma serotonin levels, we specifically evaluated the influence of selective serotonin reuptake inhibitor use in the relationship between serotonin and outcomes. Plasma serotonin level inversely correlated with estimated glomerular filtration rate and directly correlated with blood pressure. High plasma serotonin was associated with left ventricular hypertrophy (adjusted odds ratio, 2.74 [95% CI, 1.11-7.41]). In contrast, undetectable plasma serotonin level was associated with the highest risk of heart failure (adjusted hazard ratio [HR], 2.26 [95% CI, 1.40-3.66]) and ASCVD events (adjusted HR, 1.96 [95% CI, 1.15-3.32]). <br /><b>Conclusions:</b><br/>In a large chronic kidney disease cohort, plasma serotonin levels correlated with blood pressure, and elevated serotonin levels were associated with left ventricular hypertrophy. In contrast, undetectable plasma serotonin was associated with the highest risk of heart failure and ASCVD events.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 23 Aug 2023:e029785; epub ahead of print</small></div>

<div><h4>Lifestyle Behaviors and Cardiometabolic Diseases by Race and Ethnicity and Social Risk Factors Among US Young Adults, 2011 to 2018.</h4><i>Shi S, Huang H, Huang Y, Zhong VW, Feng N</i><br /><AbstractText><br /><b>Background:</b><br/>Cardiometabolic health has been worsening among young adults, but the prevalence of lifestyle risk factors and cardiometabolic diseases is unclear. Methods and Results Adults aged 18 to 44 years were included from the National Health and Nutrition Examination Survey, 2011 to 2018. Age-standardized prevalence of lifestyle risk factors and cardiometabolic diseases was estimated overall and by demographic and social risk factors. A set of multivariable logistic regressions was sequentially performed by adjusting for age, sex, social risk factors, and lifestyle factors to determine whether racial and ethnic disparities in the prevalence of cardiometabolic diseases may be attributable to differences in social risk factors and lifestyle factors. Appropriate weights were used to ensure national representativeness of the estimates. A total of 10 405 participants were analyzed (median age, 30.3 years; 50.8% women; 32.3% non-Hispanic White). The prevalence of lifestyle risk factors ranged from 16.3% for excessive drinking to 49.3% for poor diet quality. The prevalence of cardiometabolic diseases ranged from 4.3% for diabetes to 37.3% for dyslipidemia. The prevalence of having ≥2 lifestyle risk factors was 45.2% and having ≥2 cardiometabolic diseases was 22.0%. Racial and ethnic disparities in many cardiometabolic diseases persisted but were attenuated after adjusting for social risk factors and lifestyle factors. <br /><b>Conclusions:</b><br/>The prevalence of lifestyle risk factors and cardiometabolic diseases was high among US young adults and varied by race and ethnicity and social risk factors. Racial and ethnic disparities in the prevalence of cardiometabolic diseases were not fully explained by differences in social risk factors and lifestyle factors.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 23 Aug 2023:e028926; epub ahead of print</small></div>

<div><h4>Elevated Plasma Levels of Ketone Bodies Are Associated With All-Cause Mortality and Incidence of Heart Failure in Older Adults: The CHS.</h4><i>Niezen S, Connelly MA, Hirsch C, Kizer JR, ... Jiang ZG, Mukamal KJ</i><br /><AbstractText><br /><b>Background:</b><br/>Chronic disease, such as heart failure, influences cellular metabolism and shapes circulating metabolites. The relationships between key energy metabolites and chronic diseases in aging are not well understood. This study aims to determine the relationship between main components of energy metabolism with all-cause mortality and incident heart failure. Methods and Results We analyzed the association between plasma metabolite levels with all-cause mortality and incident heart failure among US older adults in the CHS (Cardiovascular Health Study). We followed 1758 participants without heart failure at baseline with hazard ratios (HRs) of analyte levels and metabolic profiles characterized by high levels of ketone bodies for all-cause mortality and incident heart failure. Multivariable Cox analyses revealed a dose-response relationship of 50% increase in all-cause mortality between lowest and highest quintiles of ketone body concentrations (HR, 1.5 [95% CI, 1.0-1.9]; <i>P</i>=0.007). Ketone body levels remained associated with incident heart failure after adjusting for cardiovascular disease confounders (HR, 1.2 [95% CI, 1.0-1.3]; <i>P</i>=0.02). Using K-means cluster analysis, we identified a cluster with higher levels of ketone bodies, citrate, interleukin-6, and B-type natriuretic peptide but lower levels of pyruvate, body mass index, and estimated glomerular filtration rate. The cluster with elevated ketone body levels was associated with higher all-cause mortality (HR, 1.7 [95% CI, 1.1-2.7]; <i>P</i>=0.01). <br /><b>Conclusions:</b><br/>Higher concentrations of ketone bodies predict incident heart failure and all-cause mortality in an older US population, independent of metabolic and cardiovascular confounders. This association suggests a potentially important relationship between ketone body metabolism and aging.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 23 Aug 2023:e029960; epub ahead of print</small></div>

<div><h4>Sex Differences in Clinical Characteristics and Outcomes After Myocardial Infarction With Low Ejection Fraction: Insights From PARADISE-MI.</h4><i>Wang X, Jering KS, Cikes M, Tokmakova MP, ... Pfeffer MA, Solomon SD</i><br /><AbstractText><br /><b>Background:</b><br/>Studies demonstrated sex differences in outcomes following acute myocardial infarction, with women more likely to develop heart failure (HF). Sacubitril/valsartan has been shown to reduce cardiovascular death and HF hospitalizations in patients with HF with reduced ejection fraction. Methods and Results A total of 5661 patients (1363 women [24%]) with acute myocardial infarction complicated by reduced left ventricular ejection fraction (≤40%), pulmonary congestion, or both and ≥1 of 8 risk-augmenting factors were randomized to receive sacubitril/valsartan or ramipril. The primary outcome was cardiovascular death or incident HF. Baseline characteristics, clinical outcomes, and safety events were compared according to sex, a prespecified subgroup. Female participants were older and had more comorbidities. After multivariable adjustment, women and men were at similar risks for cardiovascular death or all-cause death. Women were more likely to have first HF hospitalization (hazard ratio [HR], 1.34 [95% CI, 1.05-1.70]; <i>P</i>=0.02) and total HF hospitalizations (HR, 1.39 [95% CI, 1.05-1.84]; <i>P</i>=0.02). Sex did not significantly modify the treatment effect of sacubitril/valsartan compared with ramipril on the primary outcome (<i>P</i> for interaction=0.11). <br /><b>Conclusions:</b><br/>In contemporary patients who presented with reduced left ventricular ejection fraction, pulmonary congestion, or both, following acute myocardial infarction, women had a higher incidence of HF during follow-up. Sex did not modify the treatment effect of sacubitril/valsartan relative to ramipril. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02924727.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 23 Aug 2023:e028942; epub ahead of print</small></div>

<div><h4>Association of a Healthy Lifestyle, Life\'s Essential 8 Scores With Incident Macrovascular and Microvascular Disease Among Individuals With Type 2 Diabetes.</h4><i>He P, Li H, Ye Z, Liu M, ... Zhang Y, Qin X</i><br /><AbstractText><br /><b>Background:</b><br/>The association of a healthy lifestyle with the prognosis of type 2 diabetes remains uncertain. We aimed to evaluate the associations of a healthy lifestyle and a higher American Heart Association\'s Life\'s Essential 8 score with incident macrovascular and microvascular diseases in type 2 diabetes. Methods and Results A total of 13 543 participants with baseline type 2 diabetes and free of macrovascular and microvascular diseases from the UK Biobank were included. A healthy lifestyle was determined based on body mass index, smoking, alcohol consumption, physical activity, sleep duration, and diet. Life\'s Essential 8 scores were generated from 8 metrics according to the American Heart Association\'s cardiovascular health advisory, ranging from 0 to 100. During a median follow-up of 12.1 years, 3279 (24.2%) incident macrovascular diseases and 2557 (18.9%) microvascular diseases were documented. Compared with those with a poor lifestyle, participants with an ideal lifestyle had significantly lower risks of incident macrovascular disease (hazard ratio [HR], 0.46 [95% CI, 0.36-0.59]) and microvascular disease (HR, 0.60 [95% CI, 0.47-0.77]). Significantly lower risks of macrovascular disease (HR, 0.20 [95% CI, 0.05-0.79]) and microvascular disease (HR, 0.24 [95% CI, 0.06-0.98]) were also found in the high cardiovascular health group (Life\'s Essential 8 scores: 80-100), compared to the low cardiovascular health group (scores: 0-49). Adhering to an ideal lifestyle may prevent 37.0% of macrovascular disease and 24.7% of microvascular disease, and attaining a high cardiovascular health may prevent 71.9% of macrovascular disease and 67.5% of microvascular disease. <br /><b>Conclusions:</b><br/>A healthy lifestyle and a higher Life\'s Essential 8 score were associated with lower risks of macrovascular and microvascular diseases among participants with type 2 diabetes.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 23 Aug 2023:e029441; epub ahead of print</small></div>

<div><h4>Carotid Plaque Score for Stroke and Cardiovascular Risk Prediction in a Middle-Aged Cohort From the General Population.</h4><i>Ihle-Hansen H, Vigen T, Berge T, Walle-Hansen MM, ... Tveit A, Lyngbakken M</i><br /><AbstractText><br /><b>Background:</b><br/>We aimed to explore the predictive value of the carotid plaque score, compared with the Systematic Coronary Risk Evaluation 2 (SCORE2) risk prediction algorithm, on incident ischemic stroke and major adverse cardiovascular events and establish a prognostic cutoff of the carotid plaque score. Methods and Results In the prospective ACE 1950 (Akershus Cardiac Examination 1950 study), carotid plaque score was calculated with ultrasonography at inclusion in 2012 to 2015. The largest plaque diameter in each extracranial segment of the carotid artery on both sides was scored from 0 to 3 points. The sum of points in all segments provided the carotid plaque score. The cohort was followed up by linkage to national registries for incident ischemic stroke and major adverse cardiovascular events (nonfatal ischemic stroke, nonfatal myocardial infarction, and cardiovascular death) throughout 2020. Carotid plaque score was available in 3650 (98.5%) participants, with mean±SD age of 63.9±0.64 years at inclusion. Only 462 (12.7%) participants were free of plaque, and and 970 (26.6%) had a carotid plaque score of >3. Carotid plaque score predicted ischemic stroke (hazard ratio [HR], 1.25 [95% CI, 1.15-1.36]) and major adverse cardiovascular events (HR, 1.21 [95% CI, 1.14-1.27]) after adjustment for SCORE2 and provided strong incremental prognostic information to SCORE2. The best cutoff value of carotid plaque score for ischemic stroke was >3, with positive predictive value of 2.5% and negative predictive value of 99.3%. <br /><b>Conclusions:</b><br/>The carotid plaque score is a strong predictor of ischemic stroke and major adverse cardiovascular events, and it provides incremental prognostic information to SCORE2 for risk prediction. A cutoff score of >3 seems to be suitable to discriminate high-risk subjects. Registration Information clinicaltrials.gov. Identifier: NCT01555411.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 23 Aug 2023:e030739; epub ahead of print</small></div>

<div><h4>Age-Associated Changes in Endothelial Transcriptome and Epigenetic Landscapes Correlate With Elevated Risk of Cerebral Microbleeds.</h4><i>Mohan K, Gasparoni G, Salhab A, Orlich MM, ... Walter J, Nordheim A</i><br /><AbstractText><br /><b>Background:</b><br/>Stroke is a leading global cause of human death and disability, with advanced aging associated with elevated incidences of stroke. Despite high mortality and morbidity of stroke, the mechanisms leading to blood-brain barrier dysfunction and development of stroke with age are poorly understood. In the vasculature of brain, endothelial cells (ECs) constitute the core component of the blood-brain barrier and provide a physical barrier composed of tight junctions, adherens junctions, and basement membrane. Methods and Results We show, in mice, the incidents of intracerebral bleeding increases with age. After isolating an enriched population of cerebral ECs from murine brains at 2, 6, 12, 18, and 24 months, we studied age-associated changes in gene expression. The study reveals age-dependent dysregulation of 1388 genes, including many involved in the maintenance of the blood-brain barrier and vascular integrity. We also investigated age-dependent changes on the levels of CpG methylation and accessible chromatin in cerebral ECs. Our study reveals correlations between age-dependent changes in chromatin structure and gene expression, whereas the dynamics of DNA methylation changes are different. <br /><b>Conclusions:</b><br/>We find significant age-dependent downregulation of the <i>Aplnr</i> gene along with age-dependent reduction in chromatin accessibility of promoter region of the <i>Aplnr</i> gene in cerebral ECs. <i>Aplnr</i> is associated with positive regulation of vasodilation and is implicated in vascular health. Altogether, our data suggest a potential role of the apelinergic axis involving the ligand apelin and its receptor to be critical in maintenance of the blood-brain barrier and vascular integrity.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 23 Aug 2023:e031044; epub ahead of print</small></div>

<div><h4>Effect of Cardiopulmonary Bypass on SARS-CoV-2 Vaccination Antibody Levels.</h4><i>Strobel RJ, Narahari AK, Rotar EP, Young AM, ... Nelson MR, Roeser M</i><br /><AbstractText><br /><b>Background:</b><br/>Adults undergoing heart surgery are particularly vulnerable to respiratory complications, including COVID-19. Immunization can significantly reduce this risk; however, the effect of cardiopulmonary bypass (CPB) on immunization status is unknown. We sought to evaluate the effect of CPB on COVID-19 vaccination antibody concentration after cardiac surgery. Methods and Results This prospective observational clinical trial evaluated adult participants undergoing cardiac surgery requiring CPB at a single institution. All participants received a full primary COVID-19 vaccination series before CPB. SARS-CoV-2 spike protein-specific antibody concentrations were measured before CPB (pre-CPB measurement), 24 hours following CPB (postoperative day 1 measurement), and approximately 1 month following their procedure. Relationships between demographic or surgical variables and change in antibody concentration were assessed via linear regression. A total of 77 participants were enrolled in the study and underwent surgery. Among all participants, mean antibody concentration was significantly decreased on postoperative day 1, relative to pre-CPB levels (-2091 AU/mL, <i>P</i><0.001). Antibody concentration increased between postoperative day 1and 1 month post CPB measurement (2465 AU/mL, <i>P</i>=0.015). Importantly, no significant difference was observed between pre-CPB and 1 month post CPB concentrations (<i>P</i>=0.983). Two participants (2.63%) developed symptomatic COVID-19 pneumonia postoperatively; 1 case of postoperative COVID-19 pneumonia resulted in mortality (1.3%). <br /><b>Conclusions:</b><br/>COVID-19 vaccine antibody concentrations were significantly reduced in the short-term following CPB but returned to pre-CPB levels within 1 month. One case of postoperative COVID 19 pneumonia-specific mortality was observed. These findings suggest the need for heightened precautions in the perioperative period for cardiac surgery patients.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 17 Aug 2023:e029406; epub ahead of print</small></div>

<div><h4>Impact of Marital Stress on 1-Year Health Outcomes Among Young Adults With Acute Myocardial Infarction.</h4><i>Zhu C, Dreyer RP, Li F, Spatz ES, ... Pilote L, Lichtman JH</i><br /><AbstractText><br /><b>Background:</b><br/>Stress experienced in a marriage or committed relationship may be associated with worse patient-reported outcomes after acute myocardial infarction (AMI), but little is known about this association in young adults (≤55 years) with AMI. Methods and Results We used data from VIRGO (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients), an observational cohort study that enrolled individuals aged 18 to 55 years with AMI (2008-2012). Marital stress was self-reported 1 month after AMI using the Stockholm Marital Stress Scale (categorized as absent/mild, moderate, and severe). Outcomes were physical/mental health (Short Form-12<i>)</i>, generic health status (EuroQol-5 Dimensions), cardiac-specific quality of life and angina (Seattle Angina Questionnaire), depressive symptoms (Patient Health Questionnaire-9), and all-cause readmission 1 year after AMI. Regression models were sequentially adjusted for baseline health, demographics (sex, age, race or ethnicity), and socioeconomic factors (education, income, employment, and insurance). Sex and marital stress interaction was also tested. Among 1593 married/partnered participants, 576 (36.2%) reported severe marital stress, which was more common in female than male participants (39.4% versus 30.4%, <i>P</i>=0.001). Severe marital stress was significantly associated with worse mental health (beta=-2.13, SE=0.75, <i>P</i>=0.004), generic health status (beta=-3.87, SE=1.46, <i>P</i>=0.008), cardiac-specific quality of life (beta=-6.41, SE=1.65, <i>P</i><0.001), and greater odds of angina (odds ratio [OR], 1.49 [95% CI, 1.06-2.10], <i>P</i>=0.023) and all-cause readmissions (OR, 1.45 [95% CI, 1.04-2.00], <i>P</i>=0.006), after adjusting for baseline health, demographics, and socioeconomic factors. These associations were similar across sexes (<i>P</i>-interaction all >0.05). <br /><b>Conclusions:</b><br/>The association between marital stress and worse 1-year health outcomes was statistically significant in young patients with AMI, suggesting a need for routine screening and the creation of interventions to support patients with stress recovering from an AMI.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 17 Aug 2023:e030031; epub ahead of print</small></div>

<div><h4>Transcatheter Ductal Stents Versus Surgical Systemic-Pulmonary Artery Shunts in Neonates With Congenital Heart Disease With Ductal-Dependent Pulmonary Blood Flow: Trends and Associated Outcomes From the Pediatric Health Information System Database.</h4><i>Valencia E, Staffa SJ, Kuntz MT, Zaleski KL, ... Maschietto N, Nasr VG</i><br /><AbstractText><br /><b>Background:</b><br/>Surgical systemic-to-pulmonary artery shunts have been the standard approach to establish stable pulmonary blood flow in neonates with congenital heart disease with ductal-dependent pulmonary blood flow. More recently, transcatheter ductal stents have been performed as an alternative, less invasive intervention. We aimed to characterize trends in the utilization of surgical shunts versus ductal stents and compare associated outcomes. Methods and Results Using data from the Pediatric Health Information System, we retrospectively analyzed neonates with congenital heart disease with ductal-dependent pulmonary blood flow who underwent surgical shunt or ductal stent placement between January 2016 and December 2021. Patients were identified by <i>International Classification of Diseases, Tenth Revision</i> (<i>ICD-10</i>) diagnosis and procedure codes. The primary outcome was length of hospital stay. Secondary outcomes were reintervention risk and adjusted hospital costs. Of 936 patients included, 65.2% underwent a surgical shunt over the 6-year period. The proportion who underwent ductal stenting increased from 19% to 53.4% from 2016 to 2021. The median adjusted difference in postintervention length of hospital stay was 11 days greater for the surgical shunt cohort (95% CI, 7.2-14.8; <i>P</i><0.001). The adjusted reintervention risks within 3 (odds ratio [OR], 3.37 [95% CI, 1.91-5.95], <i>P</i><0.001) and 6 months (OR, 2.43 [95% CI, 1.62-3.64], <i>P</i><0.001) were significantly greater in the ductal stent group. Median adjusted index hospital costs were $198 300 ($11 6400-$340 000) versus $120 400 ($81 800-$192 400) for the surgical shunt and ductal stent cohorts, respectively (<i>P</i><0.001). <br /><b>Conclusions:</b><br/>Ductal stenting has become an increasingly utilized palliative approach to secure pulmonary blood flow in neonates with congenital heart disease with ductal-dependent pulmonary blood flow in the United States. Ductal stenting is associated with decreased length of hospital stay and reduced overall cost for the index hospitalization but with a greater reintervention risk than surgical shunting.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 17 Aug 2023:e030528; epub ahead of print</small></div>

<div><h4>Influence of Recent Standing, Moving, or Sitting on Daytime Ambulatory Blood Pressure.</h4><i>Barone Gibbs B, Muldoon MF, Conroy MB, Paley JL, Shimbo D, Perera S</i><br /><AbstractText><br /><b>Background:</b><br/>There are no recommendations for being seated versus nonseated during ambulatory blood pressure (BP) monitoring (ABPM). The authors examined how recent standing or moving versus sitting affect average daytime BP on ABPM. Methods and Results This analysis used baseline assessments from a clinical trial in desk workers with office systolic BP (SBP) 120 to 159 mm Hg or diastolic BP (DBP) 80 to 99 mm Hg. ABPM was measured every 30 minutes with a SunTech Medical Oscar 2 monitor. Concurrent posture (standing or seated) and moving (steps) were measured via a thigh-worn accelerometer. Linear regression determined within-person BP variability explained (<i>R</i><sup>2</sup>) by standing and steps before ABPM readings. Mean daytime BP and the prevalence of mean daytime BP >135/85 mm Hg from readings after sitting (seated) or after recent standing or moving (nonseated) were compared with all readings. Participants (n=266, 59% women; age, 45.2±11.6 years) provided 32.5±3.9 daytime BP readings. Time standing and steps before readings explained variability up to 17% for daytime SBP and 14% for daytime DBP. Using the 5-minute prior interval, seated SBP/DBP was lower (130.8/79.7 mm Hg, <i>P</i><0.001) and nonseated SBP/DBP was higher (137.8/84.3 mm Hg, <i>P</i><0.001) than mean daytime SBP/DBP from all readings (133.9/81.6 mm Hg). The prevalence of mean daytime SBP/DBP ≥135/85 mm Hg also differed: 38.7% from seated readings, 70.3% from nonseated readings, and 52.6% from all readings (<i>P</i><0.05). <br /><b>Conclusions:</b><br/>Daytime BP was systematically higher after standing and moving compared with being seated. Individual variation in activity patterns could influence the diagnosis of high BP using daytime BP readings on ABPM.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 17 Aug 2023:e029999; epub ahead of print</small></div>

<div><h4>Diagnostic Approach for Suspected Acute Myocarditis: Considerations for Standardization and Broadening Clinical Spectrum.</h4><i>Martens P, Cooper LT, Tang WHW</i><br /><AbstractText>Myocarditis is most recognized in patients with moderate to severe, recent-onset heart failure. However, less typical presentations including myocardial infarction with normal coronary arteries and arrhythmias are important manifestations but less commonly recognized to be caused by myocarditis. Most cases of myocarditis can be self-limiting without specific treatment; however, appropriate identification of risk during the diagnostic process of myocarditis and once a diagnosis is established is of primordial importance to identify patients in need for more specific follow-up and management. We propose a flexible, multitiered approach to the diagnostic process, allowing for capturing of the spectrum of myocarditis at an early time-point, individualized use of diagnostic resources through disease severity phenotyping, and providing structured follow-up care once myocarditis is confirmed. Such diagnostic processes allow for identification of specific etiologies with potential therapeutic consequences or allows for the comprehension of disease chronicity by understanding genetic contributions or elements of persistent immune dysregulation and degree of cardiac damage. The article highlights the evolving field of immunophenotyping in myocarditis, generating a potential for the development of targeted therapeutic approaches. Currently long-term follow-up should be titrated to the refined risk assessments of patients with a diagnosis of myocarditis and includes arrhythmia monitoring and imaging when the results will likely impact management. Genetic testing should be considered in selected cases, and histologic diagnosis may be considered in nonresponders even at later stages.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 17 Aug 2023:e031454; epub ahead of print</small></div>

<div><h4>Cardiac Genetic Investigation of Sudden Infant and Early Childhood Death: A Study From Victims to Families.</h4><i>Kotta MC, Torchio M, Bayliss P, Cohen MC, ... Coombs RC, Schwartz PJ</i><br /><AbstractText><br /><b>Background:</b><br/>Sudden infant death syndrome (SIDS) is the leading cause of death up to age 1. Sudden unexplained death in childhood (SUDC) is similar but affects mostly toddlers aged 1 to 4. SUDC is rarer than SIDS, and although cardiogenetic testing (molecular autopsy) identifies an underlying cause in a fraction of SIDS, less is known about SUDC. Methods and Results Seventy-seven SIDS and 16 SUDC cases underwent molecular autopsy with 25 definitive-evidence arrhythmia-associated genes. In 18 cases, another 76 genes with varying degrees of evidence were analyzed. Parents were offered cascade screening. Double-blind review of clinical-genetic data established genotype-phenotype correlations. The yield of likely pathogenic variants in the 25 genes was higher in SUDC than in SIDS (18.8% [3/16] versus 2.6% [2/77], respectively; <i>P</i>=0.03), whereas novel/ultra-rare variants of uncertain significance were comparably represented. Rare variants of uncertain significance and likely benign variants were found only in SIDS. In cases with expanded analyses, likely pathogenic/likely benign variants stemmed only from definitive-evidence genes, whereas all other genes contributed only variants of uncertain significance. Among 24 parents screened, variant status and phenotype largely agreed, and 3 cases positively correlated for cardiac channelopathies. Genotype-phenotype correlations significantly aided variant adjudication. <br /><b>Conclusions:</b><br/>Genetic yield is higher in SUDC than in SIDS although, in both, it is contributed only by definitive-evidence genes. SIDS/SUDC cascade family screening facilitates establishment or dismissal of a diagnosis through definitive variant adjudication indicating that anonymity is no longer justifiable. Channelopathies may underlie a relevant fraction of SUDC. Binary classifications of genetic causality (pathogenic versus benign) could not always be adequate.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 17 Aug 2023:e029100; epub ahead of print</small></div>

<div><h4>High Self-Reported Levels of Pain 1 Year After a Myocardial Infarction Are Related to Long-Term All-Cause Mortality: A SWEDEHEART Study Including 18 376 Patients.</h4><i>Vixner L, Hambraeus K, Äng B, Berglund L</i><br /><AbstractText><br /><b>Background:</b><br/>Pain increases the risk for cardiovascular diseases, including myocardial infarction (MI). However, the impact of pain on mortality after MI has not yet been investigated in large studies with long-term follow-up periods. Thus, we aimed to examine various levels of pain severity 1 year after an MI as a potential risk for all-cause mortality. Methods and Results We collected data from 18 376 patients, aged <75 years, who had a registered MI event during the period from 2004 to 2013 and with measurements of potential cardiovascular risk indicators at hospital discharge from the Swedish quality register SWEDEHEART (Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies). Self-reported levels of experienced pain according to EuroQol-5 dimension instrument were recorded in secondary prevention clinics 1 year after hospital discharge. We collected all-cause mortality data up to 8.5 years (median, 3.4 years) after the 1-year visit. The Cox proportional hazard regression was used to estimate hazard ratio (HR) and 95% CI. Moderate pain and extreme pain were reported by 38.2% and 4.5%, respectively, of included patients. There were 1067 deaths. Adjusted HR was 1.35 (95% CI, 1.18-1.55) and 2.06 (95% CI, 1.63-2.60) for moderate and extreme pain, respectively. Pain was a stronger mortality predictor than smoking. <br /><b>Conclusions:</b><br/>Pain 1 year after MI is highly prevalent, and its effect on mortality 1 year after MI was found to be more pronounced than smoking. Clinicians managing patients after MI should recognize the need to consider experienced pain when making prognosis or treatment decisions.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 16 Aug 2023:e029648; epub ahead of print</small></div>

<div><h4>Plasma Trimethylamine--Oxide and Incident Ischemic Stroke: The Cardiovascular Health Study and the Multi-Ethnic Study of Atherosclerosis.</h4><i>Lemaitre RN, Jensen PN, Wang Z, Fretts AM, ... Hazen SL, Mozaffarian D</i><br /><AbstractText><br /><b>Background:</b><br/>The association of circulating trimethylamine-<i>N</i>-oxide (TMAO) with stroke has received limited attention. To address this gap, we examined the associations of serial measures of plasma TMAO with incident ischemic stroke. Methods and Results We used a prospective cohort design with data pooled from 2 cohorts. The settings were the CHS (Cardiovascular Health Study), a cohort of older adults, and the MESA (Multi-Ethnic Study of Atherosclerosis), both in the United States. We measured plasma concentrations of TMAO at baseline and again during the follow-up using high-performance liquid chromatography and mass spectrometry. We assessed the association of plasma TMAO with incident ischemic stroke using proportional hazards regression adjusted for risk factors. The combined cohorts included 11 785 participants without a history of stroke, on average 73 (CHS) and 62 (MESA) years old at baseline, including 60% (CHS) and 53% (MESA) women. We identified 1031 total incident ischemic strokes during a median 15-year follow-up in the combined cohorts. In multivariable analyses, TMAO was significantly associated with incident ischemic stroke risk (hazard ratios comparing a doubling of TMAO: 1.11 [1.03-1.18], <i>P</i>=0.004). The association was linear over the range of TMAO concentrations and appeared restricted to those without diagnosed coronary heart disease. An association with hemorrhagic stroke was not found. <br /><b>Conclusions:</b><br/>Plasma TMAO levels are associated with incident ischemic stroke in a diverse population. Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT00005133.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 15 Aug 2023; 12:e8711</small></div>

<div><h4>Associations of Oral Contraceptive Use With Cardiovascular Disease and All-Cause Death: Evidence From the UK Biobank Cohort Study.</h4><i>Dou W, Huang Y, Liu X, Huang C, ... Liu C, Zhang H</i><br /><AbstractText><br /><b>Background:</b><br/>The associations of oral contraceptive (OC) use with cardiovascular disease (CVD) and all-cause death remains unclear. We aimed to determine the associations of OC use with incident CVD and all-cause death. Methods and Results This cohort study included 161 017 women who had no CVD at baseline and reported their OC use. We divided OC use into ever use and never use. Cox proportional hazard models were used to calculate hazard ratios and 95% CIs for cardiovascular outcomes and death. Overall, 131 131 (81.4%) of 161 017 participants reported OC use at baseline. The multivariable-adjusted hazard ratios for OC ever users versus never users were 0.92 (95% CI, 0.86-0.99) for all-cause death, 0.91 (95% CI, 0.87-0.96) for incident CVD events, 0.88 (95% CI, 0.81-0.95) for coronary heart disease, 0.87 (95% CI, 0.76-0.99) for heart failure, and 0.92 (95% CI, 0.84-0.99) for atrial fibrillation. However, no significant associations of OC use with CVD death, myocardial infarction, or stroke were observed. Furthermore, the associations of OC use with CVD events were stronger among participants with longer durations of use (<i>P</i> for trend<0.001). <br /><b>Conclusions:</b><br/>OC use was not associated with an increased risk of CVD events and all-cause death in women and may even produce an apparent net benefit. In addition, the beneficial effects appeared to be more apparent in participants with longer durations of use.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 15 Aug 2023; 12:e030105</small></div>

<div><h4>Explainable Machine Learning to Predict Anchored Reentry Substrate Created by Persistent Atrial Fibrillation Ablation in Computational Models.</h4><i>Bifulco SF, Macheret F, Scott GD, Akoum N, Boyle PM</i><br /><AbstractText><br /><b>Background:</b><br/>Postablation arrhythmia recurrence occurs in ~40% of patients with persistent atrial fibrillation. Fibrotic remodeling exacerbates arrhythmic activity in persistent atrial fibrillation and can play a key role in reentrant arrhythmia, but emergent interaction between nonconductive ablation-induced scar and native fibrosis (ie, residual fibrosis) is poorly understood. Methods and Results We conducted computational simulations in pre- and postablation left atrial models reconstructed from late gadolinium enhanced magnetic resonance imaging scans to test the hypothesis that ablation in patients with persistent atrial fibrillation creates new substrate conducive to recurrent arrhythmia mediated by anchored reentry. We trained a random forest machine learning classifier to accurately pinpoint specific nonconductive tissue regions (ie, areas of ablation-delivered scar or vein/valve boundaries) with the capacity to serve as substrate for anchored reentry-driven recurrent arrhythmia (area under the curve: 0.91±0.03). Our analysis suggests there is a distinctive nonconductive tissue pattern prone to serving as arrhythmogenic substrate in postablation models, defined by a specific size and proximity to residual fibrosis. <br /><b>Conclusions:</b><br/>Overall, this suggests persistent atrial fibrillation ablation transforms substrate that favors functional reentry (ie, rotors meandering in excitable tissue) into an arrhythmogenic milieu more conducive to anchored reentry. Our work also indicates that explainable machine learning and computational simulations can be combined to effectively probe mechanisms of recurrent arrhythmia.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 15 Aug 2023; 12:e030500</small></div>

<div><h4>Real-World Evidence on Disparities on the Initiation of Ticagrelor Versus Prasugrel in Patients With Acute Coronary Syndrome.</h4><i>Yildirim M, Mueller-Hennessen M, Milles BR, Biener M, ... Giannitsis E, Salbach C</i><br /><AbstractText><br /><b>Background:</b><br/>Management of patients with non-ST-segment-elevation acute coronary syndrome (NSTE-ACS) is based on 2020 European Society of Cardiology guidelines, which recommend the preferential use of prasugrel over ticagrelor. Because the selection of the respective P<sub>2</sub>Y<sub>12</sub> inhibitor has to consider label restrictions, we sought to evaluate the proportion of patients qualifying for either ticagrelor or prasugrel and reasons for noneligibility in an unselected cohort of patients with acute coronary syndrome. Methods and Results In this retrospective observational study, patients with ST-segment-elevation myocardial infarction (STEMI) or NSTE-ACS presenting consecutively during a 24-month period were enrolled. The eligibility of patients for a dual antiplatelet therapy option was assessed retrospectively. A total of 1502 patients had confirmed acute coronary syndrome (287 STEMI and 1215 NSTE-ACS). Eligibility for ticagrelor and full-dose prasugrel differed significantly for STEMI and NSTE-ACS (93% versus 51%, <i>P</i><0.0001 versus 80% versus 31%, <i>P</i><0.0001). Eligibility remained significantly lower (STEMI 78% versus NSTE-ACS 52%) if low-dose prasugrel was considered. Patients eligible for full-dose prasugrel had lower ischemic risk per GRACE (Global Registry of Acute Coronary Events) score (109 points [90-129 points] versus 121 points [98-146 points], <i>P</i><0.0001) and lower bleeding risk (14 points [13-15 points] versus 20 points [12-29 points], <i>P</i><0.0001) per PRECISE-DAPT (Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy) score. <br /><b>Conclusions:</b><br/>In real life, eligibility for prasugrel in patients requiring dual antiplatelet therapy is considerably lower than for ticagrelor, even in a cohort with high rates of coronary angiography and percutaneous coronary interventions. The recommended use of prasugrel over ticagrelor in current acute coronary syndrome guidelines contrasts with our observations of a substantial disparity on the eligibility. This important aspect has not received appropriate attention yet. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT05774431.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 15 Aug 2023; 12:e030879</small></div>

<div><h4>Cardiac Reversibility and Survival After Transcatheter Aortic Valve Implantation in Patients With Low-Gradient Aortic Stenosis.</h4><i>Sato K, Seo Y, Ishizu T, Albakaa NK, ... Takamura T, Ieda M</i><br /><AbstractText><br /><b>Background:</b><br/>Prognostic implications of transcatheter aortic valve implantation (TAVI) in low-gradient (LG) aortic stenosis (AS) remain controversial. The authors hypothesized that differences in cardiac functional recovery may solve this ongoing controversy. The aim was to evaluate clinical outcomes and the response of left ventricular (LV) function following TAVI in patients with LG AS. Methods and Results This multicenter retrospective study included 1742 patients with severe AS undergoing TAVI between January 2015 and March 2019. Patients were subdivided into low-flow (LF) LG, normal-flow (NF) LG, LF high-gradient, and NF high-gradient AS groups according to the mean gradient of the aortic valve (LG <40 mm Hg) and LV stroke volume index (LF <35 mL/m<sup>2</sup>). Outcomes and changes in echocardiographic parameters after TAVI were compared between the groups. A total of 227 patients (13%) had reduced ejection fraction, and 486 patients (28%) had LG AS (LF-LG 143 [8%]; NF-LG 343 [20%]). During a median follow-up period of 747 days, 301 patients experienced a composite end point of cardiovascular death and rehospitalization for cardiovascular events, which was higher in the LF-LG and NF-LG groups than in the high-gradient groups. LG AS was independently associated with the primary outcome (hazard ratio, 1.69; <i>P</i><0.001). Among 1239 patients with follow-up echocardiography, LG AS showed less improvement in the LV mass index and LV end-diastolic volume compared with high-gradient AS after 1 year, while LV recovery was similar between the LF AS and NF AS groups. <br /><b>Conclusions:</b><br/>LG AS was associated with poorer outcomes and LV recovery, regardless of flow status after TAVI. Careful evaluation of AS severity may be required in LG AS to provide TAVI within the appropriate time and advanced care afterward.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 15 Aug 2023; 12:e029717</small></div>

<div><h4>Prognosis of Right Ventricular Systolic Dysfunction in Patients With Duchenne Muscular Dystrophy.</h4><i>Fayssoil A, Mansencal N, Nguyen LS, Nardi O, ... Annane D, Orlikowski D</i><br /><AbstractText><br /><b>Background:</b><br/>Chronic respiratory failure and heart involvement may occur in Duchenne muscular dystrophy. We aimed to assess the prognostic value of the right ventricular (RV) systolic dysfunction in patients with Duchenne muscular dystrophy. Methods and Results We studied 90 genetically proven patients with Duchenne muscular dystrophy from 2010 to 2019, to obtain respiratory function and Doppler echocardiographic RV systolic function. Prognostic value was assessed in terms of death and cardiac events. The median age was 27.5 years, and median forced vital capacity was at 10% of the predicted value: 83 patients (92%) were on home mechanical ventilation. An RV systolic dysfunction was found in 46 patients (51%). In patients without RV dysfunction at inclusion, a left ventricular systolic dysfunction at inclusion was associated with a higher risk of developing RV dysfunction during follow-up with an odds ratio of 4.5 (<i>P</i>=0.03). RV systolic dysfunction was significantly associated with cardiac events, mainly acute heart failure (62%) and cardiogenic shock (23%). In a multivariable Cox model, the adjusted hazard ratio was 4.96 (95% CI [1.09-22.6]; <i>P</i>=0.04). In terms of death, we found a significant difference between patients with RV dysfunction versus patients without RV dysfunction in the Kaplan-Meier curves (log-rank <i>P</i>=0.045). <br /><b>Conclusions:</b><br/>RV systolic dysfunction is frequently present in patients with Duchenne muscular dystrophy and is associated with increased risk of cardiac events, irrespective of left ventricular dysfunction and mechanical ventilation. Registration URL: https://www.clinicaltrials.org; unique identifier: NCT02501083.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 15 Aug 2023; 12:e027231</small></div>

<div><h4>Performance of Computed Tomographic Angiography-Based Aortic Valve Area for Assessment of Aortic Stenosis.</h4><i>Ash J, Sandhu GS, Arriola-Montenegro J, Agakishiev D, ... Duval S, Nijjar PS</i><br /><AbstractText><br /><b>Background:</b><br/>A total of 40% of patients with severe aortic stenosis (AS) have low-gradient AS, raising uncertainty about AS severity. Aortic valve calcification, measured by computed tomography (CT), is guideline-endorsed to aid in such cases. The performance of different CT-derived aortic valve areas (AVAs) is less well studied. Methods and Results Consecutive adult patients with presumed moderate and severe AS based on echocardiography (AVA measured by continuity equation on echocardiography <1.5 cm<sup>2</sup>) who underwent cardiac CT were identified retrospectively. AVAs, measured by direct planimetry on CT (AVA<sub>CT</sub>) and by a hybrid approach (AVA measured in a hybrid manner with echocardiography and CT [AVA<sub>Hybrid</sub>]), were measured. Sex-specific aortic valve calcification thresholds (≥1200 Agatston units in women and ≥2000 Agatston units in men) were applied to adjudicate severe or nonsevere AS. A total of 215 patients (38.0% women; mean±SD age, 78±8 years) were included: normal flow, 59.5%; and low flow, 40.5%. Among the different thresholds for AVA<sub>CT</sub> and AVA<sub>Hybrid</sub>, diagnostic performance was the best for AVA<sub>CT</sub> <1.2 cm<sup>2</sup> (sensitivity, 85%; specificity, 26%; and accuracy, 72%), with no significant difference by flow status. The percentage of patients with correctly classified AS severity (correctly classified severe AS+correctly classified moderate AS) was as follows; AVA measured by continuity equation on echocardiography <1.0 cm<sup>2</sup>, 77%; AVA<sub>CT</sub> <1.2 cm<sup>2</sup>, 73%; AVA<sub>CT</sub> <1.0 cm<sup>2</sup>, 58%; AVA<sub>Hybrid</sub> <1.2 cm<sup>2</sup>, 59%; and AVA<sub>Hybrid</sub> <1.0 cm<sup>2</sup>, 45%. AVA<sub>CT</sub> cut points of 1.52 cm<sup>2</sup> for normal flow and 1.56 cm<sup>2</sup> for low flow, provided 95% specificity for excluding severe AS. <br /><b>Conclusions:</b><br/>CT-derived AVAs have poor discrimination for AS severity. Using an AVA<sub>CT</sub> <1.2-cm<sup>2</sup> threshold to define severe AS can produce significant error. Larger AVA<sub>CT</sub> thresholds improve specificity.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 15 Aug 2023; 12:e029973</small></div>

<div><h4>Profiling Daily Life Performance Recovery in the Early Subacute Phase After Stroke Using a Graphical Modeling Approach.</h4><i>Veerbeek JM, Hutter C, Ottiger B, Micheletti S, ... Vanbellingen T, Nyffeler T</i><br /><AbstractText><br /><b>Background:</b><br/>Laboratory-based assessments have shown that stroke recovery is heterogeneous between patients and affected domains such as motor and language function. However, laboratory-based assessments are not ecologically valid and do not necessarily reflect patients\' daily life performance. Therefore, we aimed to give an innovative view on stroke recovery by profiling daily life performance recovery across domains in patients with early subacute stroke and determine their interrelatedness, taking stroke localization into account. Methods and Results Daily life performance was observed at neurorehabilitation admission and weekly thereafter until discharge, using a scale containing 7 daily life domains. Graphical modeling was applied to investigate the conditional independence between recovery of these domains depending on stroke localization. There were 592 patients analyzed. Four clusters of interrelated domains were identified within the first 6 weeks poststroke. The first cluster included recovery in learning and applying knowledge, general tasks and demands, and domestic life. The second cluster comprised recovery in self-care and general tasks and demands. The third cluster included recovery in mobility and self-care; it incorporated interpersonal interactions and relationships in left supratentorial stroke, and learning and applying knowledge in right supratentorial stroke. The final cluster included only communication recovery. <br /><b>Conclusions:</b><br/>Daily life recovery dynamics early poststroke show that although impairments in body functions are anatomically determined, their impact on performance is comparable. Second, some, but by no means all, domains show an interrelated recovery. Domains requiring cognitive abilities are especially interrelated and seem to be essential for concomitant recovery in mobility and domestic life.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 15 Aug 2023; 12:e030472</small></div>

<div><h4>Amyloid Transthyretin Cardiomyopathy in Elderly Patients With Aortic Stenosis Undergoing Transcatheter Aortic Valve Implantation.</h4><i>Dobner S, Pilgrim T, Hagemeyer D, Heg D, ... Windecker S, Stortecky S</i><br /><AbstractText><br /><b>Background:</b><br/>The prevalence of calcific aortic stenosis and amyloid transthyretin cardiomyopathy (ATTR-CM) increase with age, and they often coexist. The objective was to determine the prevalence of ATTR-CM in patients with severe aortic stenosis and evaluate differences in presentations and outcomes of patients with concomitant ATTR-CM undergoing transcatheter aortic valve implantation. Methods and Results Prospective screening for ATTR-CM with Technetium<sup>99</sup>-3,3-diphosphono-1,2-propanodicarboxylic acid bone scintigraphy was performed in 315 patients referred with severe aortic stenosis between August 2019 and August 2021. Myocardial Technetium<sup>99</sup>-3,3-diphosphono-1,2-propanodicarboxylic acid tracer uptake was detected in 34 patients (10.8%), leading to a diagnosis of ATTR-CM in 30 patients (Perugini ≥2: 9.5%). Age (85.7±4.9 versus 82.8±4.5; <i>P</i>=0.001), male sex (82.4% versus 57.7%; <i>P</i>=0.005), and prior carpal tunnel surgery (17.6% versus 4.3%; <i>P</i>=0.007) were associated with coexisting ATTR-CM, as were ECG (discordant QRS voltage to left ventricular wall thickness [42% versus 12%; <i>P</i><0.001]), echocardiographic (left ventricular ejection fraction 48.8±12.8 versus 58.4±10.8; <i>P</i><0.001; left ventricular mass index, 144.4±45.8 versus 117.2±34.4g/m<sup>2</sup>; <i>P</i><0.001), and hemodynamic parameters (mean aortic valve gradient, 23.4±12.6 versus 35.5±16.6; <i>P</i><0.001; mean pulmonary artery pressure, 29.5±9.7 versus 25.8±9.5; <i>P</i>=0.037). Periprocedural (cardiovascular death: hazard ratio [HR], 0.71 [95% CI, 0.04-12.53]; stroke: HR, 0.46 [95% CI, 0.03-7.77]; pacemaker implantation: HR, 1.54 [95% CI, 0.69-3.43]) and 1-year clinical outcomes (cardiovascular death: HR, 1.04 [95% CI, 0.37-2.96]; stroke: HR, 0.34 [95% CI, 0.02-5.63]; pacemaker implantation: HR, 1.50 [95% CI, 0.67-3.34]) were similar between groups. <br /><b>Conclusions:</b><br/>Coexisting ATTR-CM was observed in every 10th elderly patient with severe aortic stenosis referred for therapy. While patients with coexisting pathologies differ in clinical presentation and echocardiographic and hemodynamic parameters, peri-interventional risk and early clinical outcomes were comparable up to 1 year after transcatheter aortic valve implantation. REGISTRATION URL: https://www.clinicaltrials.gov. Unique identifier: NCT04061213.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 15 Aug 2023; 12:e030271</small></div>