<div><h4>Percutaneous Coronary Intervention vs Coronary Artery Bypass Graft Surgery for Left Main Disease in Patients With and Without Acute Coronary Syndromes: A Pooled Analysis of 4 Randomized Clinical Trials.</h4><i>Gaba P, Christiansen EH, Nielsen PH, Murphy SA, ... Holm NR, Bergmark BA</i><br /><b>Importance</b><br />Patients with left main coronary artery disease presenting with an acute coronary syndrome (ACS) represent a high-risk and understudied subgroup of patients with atherosclerosis.<br /><b>Objective</b><br />To assess clinical outcomes after PCI vs CABG in patients with left main disease with vs without ACS.<br /><b>Design, setting, and participants</b><br />Data were pooled from 4 trials comparing PCI with drug-eluting stents vs CABG in patients with left main disease who were considered equally suitable candidates for either strategy (SYNTAX, PRECOMBAT, NOBLE, and EXCEL). Patients were categorized as presenting with or without ACS. Kaplan-Meier event rates through 5 years and Cox model hazard ratios were generated, and interactions were tested. Patients were enrolled in the individual trials from 2004 through 2015. Individual patient data from the trials were pooled and reconciled from 2020 to 2021, and the analyses pertaining to the ACS subgroup were performed from March 2022 through February 2023.<br /><b>Main outcomes and measures</b><br />The primary outcome was death through 5 years. Secondary outcomes included cardiovascular death, spontaneous myocardial infarction (MI), procedural MI, stroke, and repeat revascularization.<br /><b>Results</b><br />Among 4394 patients (median [IQR] age, 66 [59-73] years; 3371 [76.7%] male and 1022 [23.3%] female) randomized to receive PCI or CABG, 1466 (33%) had ACS. Patients with ACS were more likely to have diabetes, prior MI, left ventricular ejection fraction less than 50%, and higher SYNTAX scores. At 30 days, patients with ACS had higher all-cause death (hazard ratio [HR], 3.40; 95% CI, 1.81-6.37; P < .001) and cardiovascular death (HR, 3.21; 95% CI, 1.69-6.08; P < .001) compared with those without ACS. Patients with ACS also had higher rates of spontaneous MI (HR, 1.70; 95% CI, 1.25-2.31; P < .001) through 5 years. The rates of all-cause mortality through 5 years with PCI vs CABG were 10.9% vs 11.5% (HR, 0.93; 95% CI, 0.68-1.27) in patients with ACS and 11.3% vs 9.6% (HR, 1.19; 95% CI, 0.95-1.50) in patients without ACS (P = .22 for interaction). The risk of early stroke was lower with PCI vs CABG (ACS: HR, 0.39; 95% CI, 0.12-1.25; no ACS: HR, 0.35; 95% CI, 0.16-0.75), whereas the 5-year risks of spontaneous MI and repeat revascularization were higher with PCI vs CABG (spontaneous MI: ACS: HR, 1.74; 95% CI, 1.09-2.77; no ACS: HR, 3.03; 95% CI, 1.94-4.72; repeat revascularization: ACS: HR, 1.57; 95% CI, 1.19-2.09; no ACS: HR, 1.90; 95% CI, 1.54-2.33), regardless of ACS status.<br /><br /><b>Conclusion:</b><br/>and relevance</b><br />Among largely stable patients undergoing left main revascularization and with predominantly low to intermediate coronary anatomical complexity, those with ACS had higher rates of early death. Nonetheless, rates of all-cause mortality through 5 years were similar with PCI vs CABG in this high-risk subgroup. The relative advantages and disadvantages of PCI vs CABG in terms of early stroke and long-term spontaneous MI and repeat revascularization were consistent regardless of ACS status.<br /><b>Trial registration</b><br />ClinicalTrials.gov Identifiers: NCT00114972, NCT00422968, NCT01496651, NCT01205776.<br /><br /><br /><br /><small>JAMA Cardiol: 31 May 2023; epub ahead of print</small></div>

<div><h4>Association of Circulating Cardiomyocyte Cell-Free DNA With Cancer Therapy-Related Cardiac Dysfunction in Patients Undergoing Treatment for ERBB2-Positive Breast Cancer.</h4><i>Yu AF, Moore ZR, Moskowitz CS, Liu JE, ... Steingart RM, Schmitt AM</i><br /><b>Importance</b><br />Cancer therapy-related cardiac dysfunction (CTRCD) is a potentially serious cardiotoxicity of treatments for ERBB2-positive breast cancer (formerly HER2). Identifying early biomarkers of cardiotoxicity could facilitate an individualized approach to cardiac surveillance and early pharmacologic intervention. Circulating cell-free DNA (cfDNA) of cardiomyocyte origin is present during acute cardiac injury but has not been established as a biomarker of CTRCD.<br /><b>Objective</b><br />To determine whether circulating cardiomyocyte cfDNA is associated with CTRCD in patients with ERBB2-positive breast cancer treated with anthracyclines and ERBB2-targeted therapy.<br /><b>Design, setting, and participants</b><br />A prospective cohort of 80 patients with ERBB2-positive breast cancer enrolled at an academic cancer center between July 2014 and April 2016 underwent echocardiography and blood collection at baseline, after receiving anthracyclines, and at 3 months and 6 months of ERBB2-targeted therapy. Participants were treated with doxorubicin-based chemotherapy followed by trastuzumab (+/- pertuzumab). The current biomarker study includes participants with sufficient biospecimen available for analysis after anthracycline therapy. Circulating cardiomyocyte-specific cfDNA was quantified by a methylation-specific droplet digital polymerase chain reaction assay. Data for this biomarker study were collected and analyzed from June 2021 through April 2022.<br /><b>Main outcomes and measures</b><br />The outcome of interest was 1-year CTRCD, defined by symptomatic heart failure or an asymptomatic decline in left ventricular ejection fraction (≥10% from baseline to less than lower limit of normal or ≥16%). Values for cardiomyocyte cfDNA and high-sensitivity cardiac troponin I (hs-cTnI) measured after patients completed treatment with anthracyclines were compared between patients who later developed CTRCD vs patients who did not using the Wilcoxon rank sum test, and the association of post-anthracycline cardiomyocyte cfDNA level with CTRCD was estimated using logistic regression.<br /><b>Results</b><br />Of 71 patients included in this study, median (IQR) age was 50 (44-58) years, all were treated with dose-dense doxorubicin, and 48 patients underwent breast radiotherapy. Ten of 71 patients (14%) in this analysis developed CTRCD. The level of cardiomyocyte cfDNA at the post-anthracycline time point was higher in patients who subsequently developed CTRCD (median, 30.5 copies/mL; IQR, 24-46) than those who did not (median, 7 copies/mL; IQR, 2-22; P = .004). Higher cardiomyocyte cfDNA level after completion of anthracycline chemotherapy was associated with risk of CTRCD (hazard ratio, 1.02 per 1-copy/mL increase; 95% CI, 1.00-1.03; P = .046).<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />This study found that higher cardiomyocyte cfDNA level after completion of anthracycline chemotherapy was associated with risk of CTRCD. Cardiomyocyte cfDNA quantification shows promise as a predictive biomarker to refine risk stratification for CTRCD among patients with breast cancer receiving cardiotoxic cancer therapy, and its use warrants further validation.<br /><b>Trial registration</b><br />ClinicalTrials.gov Identifier: NCT02177175.<br /><br /><br /><br /><small>JAMA Cardiol: 31 May 2023; epub ahead of print</small></div>

<div><h4>Heterogeneity of Lipoprotein(a) Levels Among Hispanic or Latino Individuals Residing in the US.</h4><i>Joshi PH, Marcovina S, Orroth K, López JAG, ... Schneiderman N, Rodriguez CJ</i><br /><b>Importance</b><br />Lipoprotein(a) (Lp[a]) is a genetically determined risk-enhancing factor for atherosclerotic cardiovascular disease (ASCVD). The Lp(a) distribution among the diverse Hispanic or Latino community residing in the US has not been previously described, to the authors\' knowledge.<br /><b>Objective</b><br />To determine the distribution of Lp(a) levels across a large cohort of diverse Hispanic or Latino adults living in the US and by key demographic groups.<br /><b>Design, setting, and participants</b><br />The Hispanic Community Health Study/Study of Latinos (HCHS/SOL) is a prospective, population-based, cohort study of diverse Hispanic or Latino adults living in the US. At screening, participants aged 18 to 74 years were recruited between 2008 and 2011 from 4 US metropolitan areas (Bronx, New York; Chicago, Illinois; Miami, Florida; San Diego, California). HCHS/SOL included 16 415 noninstitutionalized adults recruited through probability sampling of randomly selected households. The study population represents Hispanic or Latino participants from diverse self-identified geographic and cultural backgrounds: Central American, Cuban, Dominican, Mexican, Puerto Rican, and South American. This study evaluated a subset of HCHS/SOL participants who underwent Lp(a) measurement. Sampling weights and surveys methods were used to account for HCHS/SOL sampling design. Data for this study were analyzed from April 2021 to April 2023.<br /><b>Exposure</b><br />Lp(a) molar concentration was measured by a particle-enhanced turbidimetric assay with minimized sensitivity to apolipoprotein(a) size variation.<br /><b>Main outcome and measure</b><br />Lp(a) quintiles were compared using analysis of variance among key demographic groups, including self-identified Hispanic or Latino background. Median percentage genetic ancestry (Amerindian, European, West African) were compared across Lp(a) quintiles.<br /><b>Results</b><br />Lp(a) molar concentration was measured in 16 117 participants (mean [SD] age, 41 [14.8] years; 9680 female [52%]; 1704 Central American [7.7%], 2313 Cuban [21.1%], 1436 Dominican [10.3%], 6395 Mexican [39.1%], 2652 Puerto Rican [16.6%], 1051 South American [5.1%]). Median (IQR) Lp(a) level was 19.7 (7.4-59.7) nmol/L. Across Hispanic or Latino background groups, there was significant heterogeneity in median Lp(a) levels ranging from 12 to 41 nmol/L in those reporting a Mexican vs Dominican background. Median (IQR) West African genetic ancestry was lowest in the first quintile of Lp(a) level and highest in the fifth quintile (5.5% [3.4%-12.9%] and 12.1% [5.0%-32.5%]; respectively; P < .001), whereas the converse was seen for Amerindian ancestry (32.8% [9.9%-53.2%] and 10.7% [4.9%-30.7%], respectively; P < .001).<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />Results of this cohort study suggest that differences in Lp(a) level distribution across the diverse US Hispanic or Latino population may carry important implications for the use of Lp(a) level in ASCVD risk assessment for this group. Cardiovascular outcomes data are needed to better understand the clinical impact of differences in Lp(a) levels by Hispanic or Latino background.<br /><br /><br /><br /><small>JAMA Cardiol: 24 May 2023; epub ahead of print</small></div>

<div><h4>Safety and Efficacy of Empagliflozin and Diuretic Use in Patients with Heart Failure and Preserved Ejection Fraction: A Post Hoc Analysis of the EMPEROR-Preserved Trial.</h4><i>Butler J, Usman MS, Filippatos G, Ferreira JP, ... Packer M, Anker S</i><br /><b>Importance</b><br />The diuretic effect of sodium-glucose cotransporter 2 inhibitors may result in interaction with background diuretic therapy in patients with heart failure and preserved ejection fraction (HFpEF).<br /><b>Objective</b><br />To assess the safety and efficacy of empagliflozin in combination with background diuretic therapy and the association of empagliflozin with the need for conventional diuretics.<br /><b>Design, setting, and participants</b><br />This was a post hoc analysis of the Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Preserved Ejection Fraction (EMPEROR-Preserved). EMPEROR-Preserved was a phase 3, randomized, placebo-controlled, double-blind clinical trial conducted from March 2017 to April 2021. Patients with class II to IV heart failure and left ventricular ejection fraction greater than 40% were included. Of 5988 patients enrolled, 5815 (97.1%) had baseline data on diuretic use and were included in this analysis, which was conducted from November 2021 to August 2022.<br /><b>Interventions</b><br />Participants in EMPEROR-Preserved were randomized to empagliflozin or placebo. In this analysis, participants were divided into 4 subgroups: no diuretics and furosemide-equivalent diuretic dose of less than 40 mg, 40 mg, and greater than 40 mg at baseline.<br /><b>Main outcomes and measures</b><br />The main outcomes of interest were first hospitalization for heart failure (HHF) or cardiovascular death (CV death) and its components. Association of empagliflozin vs placebo with outcomes by baseline diuretic status (no diuretic vs any dose) and dose (no diuretic, <40 mg, 40 mg, and > 40mg) was assessed. Association of empagliflozin use with changes in diuretic therapy was also studied.<br /><b>Results</b><br />Among 5815 patients (mean [SD] age, 71.9 [9.4] years; 2594 [44.6%] female) with known baseline diuretic use, 1179 (20.3%) were not taking diuretics, 1725 (29.7%) were taking less than 40 mg, 1772 (30.5%) were taking 40 mg, and 1139 (19.6%) were taking greater than 40 mg. In the placebo arm, patients with higher diuretic doses had worse outcomes. Empagliflozin decreased the risk of HHF or CV death, regardless of background diuretic status (hazard ratio [HR], 0.81; 95% CI, 0.70-0.93] for the diuretic group vs HR, 0.72; 95% CI, 0.48-1.06 for the nondiuretic group; P for interaction = .58). Similarly, diuretic status was not associated with changes in improvements in first HHF, total HHF, rate of decline in estimated glomerular filtration rate, and Kansas City Cardiomyopathy Questionnaire 23 clinical summary score with empagliflozin. Findings were consistent when patients were categorized by diuretic dose. Empagliflozin was associated with a decreased likelihood of diuretic dose escalation (HR, 0.74; 95% CI, 0.65-0.84) and an increased likelihood of de-escalation (HR, 1.15; 95% CI, 1.02-1.30). Empagliflozin was associated with an increased risk of volume depletion in patients taking diuretics (HR, 1.34; 95% CI, 1.13-1.59).<br /><b>Conclusion</b><br />In this study, treatment with empagliflozin was similar regardless of diuretic use or dose. Empagliflozin use was associated with decreased conventional diuretic dosing.<br /><b>Trial registration</b><br />ClinicalTrials.gov Identifier: NCT03057951.<br /><br /><br /><br /><small>JAMA Cardiol: 24 May 2023; epub ahead of print</small></div>

<div><h4>Age Dependency of Cardiovascular Outcomes With the Amyloidogenic pV142I Transthyretin Variant Among Black Individuals in the US.</h4><i>Selvaraj S, Claggett BL, Quarta CC, Yu B, ... Falk RH, Solomon SD</i><br /><b>Importance</b><br />Hereditary transthyretin cardiac amyloidosis is an increasingly recognized cause of heart failure (HF) with distinct treatment. The amyloidogenic pV142I (V122I) variant is present in 3% to 4% of Black individuals in the US and increases the risk for atrial fibrillation (AF), HF, and mortality. Since hereditary transthyretin cardiac amyloidosis demonstrates age-dependent anatomic penetrance, evaluation later in life may identify survivors at particularly high risk.<br /><b>Objective</b><br />To estimate age-dependent risks for cardiovascular events with the variant.<br /><b>Design, settings, and participants</b><br />This cohort study analyzed Black participants from the Atherosclerosis Risk in Communities (ARIC) study attending visit 1 (1987-1989) (followed up until 2019; median follow-up, 27.6 years). Data analyses were completed from June 2022 to April 2023.<br /><b>Exposure</b><br />pV142I carrier status.<br /><b>Main outcomes</b><br />The association between the variant and AF, HF hospitalization, mortality, and a composite of HF hospitalization or mortality was modeled by generating 10-year absolute risk differences for each year between ages 53 (the median age at visit 1) and 80 years, adjusting for the first 5 principal components of ancestry and sex. As an example, 5- and 10-year risk differences were specifically estimated for the composite outcome among participants surviving to age 80 years.<br /><b>Results</b><br />Among 3856 Black participants (including 124 carriers) at visit 1, 2403 (62%) were women, 2140 (56%) had hypertension, and 740 (20%) had diabetes, with no differences between groups. The 10-year absolute risk difference between ages 53 and 80 years increased over time for each outcome. Statistical significance for increased 10-year risk difference emerged near ages 65 years for AF, 70 years for HF hospitalization, and 75 years for mortality. Among participants surviving to age 80 years, carriers had a 20% (95% CI, 2%-37%) and 24% (95% CI, 1%-47%) absolute increased risk for HF hospitalization or death at 5 and 10 years, respectively. Thus, at age 80 years, only 4 carriers would need to be identified to attribute 1 HF hospitalization or death over the following decade to the variant.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />In this study, age-specific risks were provided for relevant outcomes with the pV142I variant. Despite a relatively benign course during earlier years, Black individuals who carry the pV142I variant surviving into later life may be particularly vulnerable. These data may inform timing for screening, risk counseling to patients, and potential strategies for early targeted therapy.<br /><br /><br /><br /><small>JAMA Cardiol: 22 May 2023; epub ahead of print</small></div>

<div><h4>Contemporary Use of Sodium-Glucose Cotransporter-2 Inhibitor Therapy Among Patients Hospitalized for Heart Failure With Reduced Ejection Fraction in the US: The Get With The Guidelines-Heart Failure Registry.</h4><i>Pierce JB, Vaduganathan M, Fonarow GC, Ikeaba U, ... Yancy CW, Greene SJ</i><br /><b>Importance</b><br />Clinical guidelines for patients with heart failure with reduced ejection fraction (HFrEF) strongly recommend treatment with a sodium-glucose cotransporter-2 inhibitor (SGLT2i) to reduce cardiovascular mortality or HF hospitalization. Nationwide adoption of SGLT2i for HFrEF in the US is unknown.<br /><b>Objective</b><br />To characterize patterns of SGLT2i use among eligible US patients hospitalized for HFrEF.<br /><b>Design, setting, and participants</b><br />This retrospective cohort study analyzed 49 399 patients hospitalized for HFrEF across 489 sites in the Get With The Guidelines-Heart Failure (GWTG-HF) registry between July 1, 2021, and June 30, 2022. Patients with an estimated glomerular filtration rate less than 20 mL/min/1.73 m2, type 1 diabetes, and previous intolerance to SGLT2i were excluded.<br /><b>Main outcomes and measures</b><br />Patient-level and hospital-level prescription of SGLT2i at hospital discharge.<br /><b>Results</b><br />Of 49 399 included patients, 16 548 (33.5%) were female, and the median (IQR) age was 67 (56-78) years. Overall, 9988 patients (20.2%) were prescribed an SGLT2i. SGLT2i prescription was less likely among patients with chronic kidney disease (CKD; 4550 of 24 437 [18.6%] vs 5438 of 24 962 [21.8%]; P < .001) but more likely among patients with type 2 diabetes (T2D; 5721 of 21 830 [26.2%] vs 4262 of 27 545 [15.5%]; P < .001) and those with both T2D and CKD (2905 of 12 236 [23.7%] vs 7078 vs 37 139 [19.1%]; P < .001). Patients prescribed SGLT2i therapy were more likely to be prescribed background triple therapy with an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor-neprilysin inhibitor, β-blocker, and mineralocorticoid receptor antagonist (4624 of 9988 [46.3%] vs 10 880 of 39 411 [27.6%]; P < .001), and 4624 of 49 399 total study patients (9.4%) were discharged with prescriptions for quadruple medical therapy including SGLT2i. Among 461 hospitals with 10 or more eligible discharges, 19 hospitals (4.1%) discharged 50% or more of patients with prescriptions for SGLT2i, whereas 344 hospitals (74.6%) discharged less than 25% of patients with prescriptions for SGLT2i (including 29 [6.3%] that discharged zero patients with SGLT2i prescriptions). There was high between-hospital variance in the rate of SGLT2i prescription in unadjusted models (median odds ratio, 2.53; 95% CI, 2.36-2.74) and after adjustment for patient and hospital characteristics (median odds ratio, 2.51; 95% CI, 2.34-2.71).<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />In this study, prescription of SGLT2i at hospital discharge among eligible patients with HFrEF was low, including among patients with comorbid CKD and T2D who have multiple indications for therapy, with substantial variation among US hospitals. Further efforts are needed to overcome implementation barriers and improve use of SGLT2i among patients with HFrEF.<br /><br /><br /><br /><small>JAMA Cardiol: 22 May 2023; epub ahead of print</small></div>

<div><h4>Association of Dapagliflozin vs Placebo With Individual Kansas City Cardiomyopathy Questionnaire Components in Patients With Heart Failure With Mildly Reduced or Preserved Ejection Fraction: A Secondary Analysis of the DELIVER Trial.</h4><i>Peikert A, Chandra A, Kosiborod MN, Claggett BL, ... Solomon SD, Vaduganathan M</i><br /><b>Importance</b><br />Dapagliflozin has been shown to improve overall health status based on aggregate summary scores of the Kansas City Cardiomyopathy Questionnaire (KCCQ) in patients with heart failure (HF) with mildly reduced or preserved ejection fraction enrolled in the Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure (DELIVER) trial. A comprehensive understanding of the responsiveness of individual KCCQ items would allow clinicians to better inform patients on expected changes in daily living with treatment.<br /><b>Objective</b><br />To examine the association of dapagliflozin treatment with changes in individual components of the KCCQ.<br /><b>Design, setting, and participants</b><br />This is a post hoc exploratory analysis of DELIVER, a randomized double-blind placebo-controlled trial conducted at 353 centers in 20 countries from August 2018 to March 2022. KCCQ was administered at randomization and 1, 4, and 8 months. Scores of individual KCCQ components were scaled from 0 to 100. Eligibility criteria included symptomatic HF with left ventricular ejection fraction greater than 40%, elevated natriuretic peptide levels, and evidence of structural heart disease. Data were analyzed from November 2022 to February 2023.<br /><b>Main outcomes and measures</b><br />Changes in the 23 individual KCCQ components at 8 months.<br /><b>Interventions</b><br />Dapagliflozin, 10 mg, once daily or placebo.<br /><b>Results</b><br />Baseline KCCQ data were available for 5795 of 6263 randomized patients (92.5%) (mean [SD] age, 71.5 [9.5] years; 3344 male [57.7%] and 2451 female [42.3%]). Dapagliflozin was associated with larger improvements in almost all KCCQ components at 8 months compared with placebo. The most significant improvements with dapagliflozin were observed in frequency of lower limb edema (difference, 3.2; 95% CI, 1.6-4.8; P < .001), sleep limitation by shortness of breath (difference, 3.0; 95% CI, 1.6-4.4; P < .001), and limitation in desired activities by shortness of breath (difference, 2.8; 95% CI, 1.3-4.3; P < .001). Similar treatment patterns were observed in longitudinal analyses integrating data from months 1, 4, and 8. Higher proportions of patients treated with dapagliflozin experienced improvements, and fewer had deteriorations across most individual components.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />In this study of patients with HF with mildly reduced or preserved ejection fraction, dapagliflozin was associated with improvement in a broad range of individual KCCQ components, with the greatest benefits in domains related to symptom frequency and physical limitations. Potential improvements in specific symptoms and activities of daily living might be more readily recognizable and easily communicated to patients.<br /><b>Trial registration</b><br />ClinicalTrials.gov Identifier: NCT03619213.<br /><br /><br /><br /><small>JAMA Cardiol: 20 May 2023; epub ahead of print</small></div>

<div><h4>Titanium-Nitride-Oxide-Coated vs Everolimus-Eluting Stents in Acute Coronary Syndrome: 5-Year Clinical Outcomes of the TIDES-ACS Randomized Clinical Trial.</h4><i>Bouisset F, Sia J, Mizukami T, Karjalainen PP, ... De Bruyne B, TIDES-ACS Study Group</i><br /><b>Importance</b><br />Titanium-nitride-oxide (TiNO)-coated stents show faster strut coverage compared with drug-eluting stents without excessive intimal-hyperplasia observed in bare metal stents. It is important to study long-term clinical outcomes after treatment of patients with an acute coronary syndrome (ACS) by TiNO-coated stents, which are neither drug-eluting stents nor bare metal stents.<br /><b>Objective</b><br />To compare the rate of main composite outcome of cardiac death, myocardial infarction (MI), or ischemia-driven target lesion revascularization at 5 years in patients with ACS randomized to receive either a TiNO-coated stent or a third-generation everolimus-eluting stent (EES).<br /><b>Design, setting, and participants</b><br />This multicenter, randomized, controlled, open-label trial was conducted in 12 clinical sites in 5 European countries and enrolled patients from January 2014 to August 2016. Patients presenting with ACS (ST-segment elevation MI, non-ST-segment elevation MI, and unstable angina) with at least 1 de novo lesion were randomized to receive either a TiNO-coated stent or an EES. The present report analyzes the long-term follow-up for the main composite outcome and its individual components. Analysis took place between November 2022 to March 2023.<br /><b>Main outcome</b><br />The primary end point was a composite of cardiac death, MI, or target lesion revascularization at 12-month follow-up.<br /><b>Results</b><br />A total of 1491 patients with ACS were randomly assigned to receive either TiNO-coated stents (989 [66.3%]) or EES (502 [33.7%]). The mean (SD) age was 62.7 (10.8) years, and 363 (24.3%) were female. At 5 years, the main composite outcome events occurred in 111 patients (11.2%) in the TiNO group vs 60 patients (12%) in the EES group (hazard ratio [HR], 0.94; 95% CI, 0.69-1.28; P = .69). The rate of cardiac death was 0.9% (9 of 989) vs 3.0% (15 of 502) (HR, 0.30; 95% CI, 0.13-0.69; P = .005), the rate of MI was 4.6% (45 of 989) vs 7.0% (35 of 502) (HR, 0.64; 95% CI, 0.41-0.99; P = .049), the rate of stent thrombosis was 1.2% (12 of 989) vs 2.8% (14 of 502) (HR, 0.43; 95% CI, 0.20-0.93; P = .034), and the rate of target lesion revascularization was 7.4% (73 of 989) vs 6.4% (32 of 502) (HR, 1.16; 95% CI, 0.77-1.76; P = .47) in the TiNO-coated stent arm and in the EES arm, respectively.<br /><br /><b>Conclusion:</b><br/>and relevance</b><br />In this study, patients with ACS had a main composite outcome that was not different 5 years after TiNO-coated stent or EES.<br /><b>Trial registration</b><br />ClinicalTrials.gov Identifier: NCT02049229.<br /><br /><br /><br /><small>JAMA Cardiol: 19 May 2023; epub ahead of print</small></div>

<div><h4>Vigorous Exercise in Patients With Hypertrophic Cardiomyopathy.</h4><i>Lampert R, Ackerman MJ, Marino BS, Burg M, ... Day SM, LIVE Consortium</i><br /><b>Importance</b><br />Whether vigorous intensity exercise is associated with an increase in risk of ventricular arrhythmias in individuals with hypertrophic cardiomyopathy (HCM) is unknown.<br /><b>Objective</b><br />To determine whether engagement in vigorous exercise is associated with increased risk for ventricular arrhythmias and/or mortality in individuals with HCM. The a priori hypothesis was that participants engaging in vigorous activity were not more likely to have an arrhythmic event or die than those who reported nonvigorous activity.<br /><b>Design, setting, and participants</b><br />This was an investigator-initiated, prospective cohort study. Participants were enrolled from May 18, 2015, to April 25, 2019, with completion in February 28, 2022. Participants were categorized according to self-reported levels of physical activity: sedentary, moderate, or vigorous-intensity exercise. This was a multicenter, observational registry with recruitment at 42 high-volume HCM centers in the US and internationally; patients could also self-enroll through the central site. Individuals aged 8 to 60 years diagnosed with HCM or genotype positive without left ventricular hypertrophy (phenotype negative) without conditions precluding exercise were enrolled.<br /><b>Exposures</b><br />Amount and intensity of physical activity.<br /><b>Main outcomes and measures</b><br />The primary prespecified composite end point included death, resuscitated sudden cardiac arrest, arrhythmic syncope, and appropriate shock from an implantable cardioverter defibrillator. All outcome events were adjudicated by an events committee blinded to the patient\'s exercise category.<br /><b>Results</b><br />Among the 1660 total participants (mean [SD] age, 39 [15] years; 996 male [60%]), 252 (15%) were classified as sedentary, and 709 (43%) participated in moderate exercise. Among the 699 individuals (42%) who participated in vigorous-intensity exercise, 259 (37%) participated competitively. A total of 77 individuals (4.6%) reached the composite end point. These individuals included 44 (4.6%) of those classified as nonvigorous and 33 (4.7%) of those classified as vigorous, with corresponding rates of 15.3 and 15.9 per 1000 person-years, respectively. In multivariate Cox regression analysis of the primary composite end point, individuals engaging in vigorous exercise did not experience a higher rate of events compared with the nonvigorous group with an adjusted hazard ratio of 1.01. The upper 95% 1-sided confidence level was 1.48, which was below the prespecified boundary of 1.5 for noninferiority.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />Results of this cohort study suggest that among individuals with HCM or those who are genotype positive/phenotype negative and are treated in experienced centers, those exercising vigorously did not experience a higher rate of death or life-threatening arrhythmias than those exercising moderately or those who were sedentary. These data may inform discussion between the patient and their expert clinician around exercise participation.<br /><br /><br /><br /><small>JAMA Cardiol: 17 May 2023; epub ahead of print</small></div>

<div><h4>Skeletal Muscle Mitochondrial Respiration and Exercise Intolerance in Patients With Heart Failure With Preserved Ejection Fraction.</h4><i>Scandalis L, Kitzman DW, Nicklas BJ, Lyles M, ... Gnaiger E, Molina AJA</i><br /><b>Importance</b><br />The pathophysiology of exercise intolerance in patients with heart failure with preserved ejection fraction (HFpEF) remains incompletely understood. Multiple lines of evidence suggest that abnormal skeletal muscle metabolism is a key contributor, but the mechanisms underlying metabolic dysfunction remain unresolved.<br /><b>Objective</b><br />To evaluate the associations of skeletal muscle mitochondrial function using respirometric analysis of biopsied muscle fiber bundles from patients with HFpEF with exercise performance.<br /><b>Design, setting, and participants</b><br />In this cross-sectional study, muscle fiber bundles prepared from fresh vastus lateralis biopsies were analyzed by high-resolution respirometry to provide detailed analyses of mitochondrial oxidative phosphorylation, including maximal capacity and the individual contributions of complex I-linked and complex II-linked respiration. These bioenergetic data were compared between patients with stable chronic HFpEF older than 60 years and age-matched healthy control (HC) participants and analyzed for intergroup differences and associations with exercise performance. All participants were treated at a university referral center, were clinically stable, and were not undergoing regular exercise or diet programs. Data were collected from March 2016 to December 2017, and data were analyzed from November 2020 to May 2021.<br /><b>Main outcomes and measures</b><br />Skeletal muscle mitochondrial function, including maximal capacity and respiration linked to complex I and complex II. Exercise performance was assessed by peak exercise oxygen consumption, 6-minute walk distance, and the Short Physical Performance Battery.<br /><b>Results</b><br />Of 72 included patients, 50 (69%) were women, and the mean (SD) age was 69.6 (6.1) years. Skeletal muscle mitochondrial function measures were all markedly lower in skeletal muscle fibers obtained from patients with HFpEF compared with HCs, even when adjusting for age, sex, and body mass index. Maximal capacity was strongly and significantly correlated with peak exercise oxygen consumption (R = 0.69; P < .001), 6-minute walk distance (R = 0.70; P < .001), and Short Physical Performance Battery score (R = 0.46; P < .001).<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />In this study, patients with HFpEF had marked abnormalities in skeletal muscle mitochondrial function. Severely reduced maximal capacity and complex I-linked and complex II-linked respiration were associated with exercise intolerance and represent promising therapeutic targets.<br /><br /><br /><br /><small>JAMA Cardiol: 10 May 2023; epub ahead of print</small></div>

<div><h4>Automated Assessment of Cardiac Systolic Function From Coronary Angiograms With Video-Based Artificial Intelligence Algorithms.</h4><i>Avram R, Barrios JP, Abreau S, Goh CY, ... Olgin JE, Tison GH</i><br /><b>Importance</b><br />Understanding left ventricular ejection fraction (LVEF) during coronary angiography can assist in disease management.<br /><b>Objective</b><br />To develop an automated approach to predict LVEF from left coronary angiograms.<br /><b>Design, setting, and participants</b><br />This was a cross-sectional study with external validation using patient data from December 12, 2012, to December 31, 2019, from the University of California, San Francisco (UCSF). Data were randomly split into training, development, and test data sets. External validation data were obtained from the University of Ottawa Heart Institute. Included in the analysis were all patients 18 years or older who received a coronary angiogram and transthoracic echocardiogram (TTE) within 3 months before or 1 month after the angiogram.<br /><b>Exposure</b><br />A video-based deep neural network (DNN) called CathEF was used to discriminate (binary) reduced LVEF (≤40%) and to predict (continuous) LVEF percentage from standard angiogram videos of the left coronary artery. Guided class-discriminative gradient class activation mapping (GradCAM) was applied to visualize pixels in angiograms that contributed most to DNN LVEF prediction.<br /><b>Results</b><br />A total of 4042 adult angiograms with corresponding TTE LVEF from 3679 UCSF patients were included in the analysis. Mean (SD) patient age was 64.3 (13.3) years, and 2212 patients were male (65%). In the UCSF test data set (n = 813), the video-based DNN discriminated (binary) reduced LVEF (≤40%) with an area under the receiver operating characteristic curve (AUROC) of 0.911 (95% CI, 0.887-0.934); diagnostic odds ratio for reduced LVEF was 22.7 (95% CI, 14.0-37.0). DNN-predicted continuous LVEF had a mean absolute error (MAE) of 8.5% (95% CI, 8.1%-9.0%) compared with TTE LVEF. Although DNN-predicted continuous LVEF differed 5% or less compared with TTE LVEF in 38.0% (309 of 813) of test data set studies, differences greater than 15% were observed in 15.2% (124 of 813). In external validation (n = 776), video-based DNN discriminated (binary) reduced LVEF (≤40%) with an AUROC of 0.906 (95% CI, 0.881-0.931), and DNN-predicted continuous LVEF had an MAE of 7.0% (95% CI, 6.6%-7.4%). Video-based DNN tended to overestimate low LVEFs and underestimate high LVEFs. Video-based DNN performance was consistent across sex, body mass index, low estimated glomerular filtration rate (≤45), presence of acute coronary syndromes, obstructive coronary artery disease, and left ventricular hypertrophy.<br /><br /><b>Conclusion:</b><br/>and relevance</b><br />This cross-sectional study represents an early demonstration of estimating LVEF from standard angiogram videos of the left coronary artery using video-based DNNs. Further research can improve accuracy and reduce the variability of DNNs to maximize their clinical utility.<br /><br /><br /><br /><small>JAMA Cardiol: 10 May 2023; epub ahead of print</small></div>

<div><h4>Cardiovascular Disease Risk Assessment Using Traditional Risk Factors and Polygenic Risk Scores in the Million Veteran Program.</h4><i>Vassy JL, Posner DC, Ho YL, Gagnon DR, ... Cho K, Wilson PWF</i><br /><b>Importance</b><br />Primary prevention of atherosclerotic cardiovascular disease (ASCVD) relies on risk stratification. Genome-wide polygenic risk scores (PRSs) are proposed to improve ASCVD risk estimation.<br /><b>Objective</b><br />To determine whether genome-wide PRSs for coronary artery disease (CAD) and acute ischemic stroke improve ASCVD risk estimation with traditional clinical risk factors in an ancestrally diverse midlife population.<br /><b>Design, setting, and participants</b><br />This was a prognostic analysis of incident events in a retrospectively defined longitudinal cohort conducted from January 1, 2011, to December 31, 2018. Included in the study were adults free of ASCVD and statin naive at baseline from the Million Veteran Program (MVP), a mega biobank with genetic, survey, and electronic health record data from a large US health care system. Data were analyzed from March 15, 2021, to January 5, 2023.<br /><b>Exposures</b><br />PRSs for CAD and ischemic stroke derived from cohorts of largely European descent and risk factors, including age, sex, systolic blood pressure, total cholesterol, high-density lipoprotein (HDL) cholesterol, smoking, and diabetes status.<br /><b>Main outcomes and measures</b><br />Incident nonfatal myocardial infarction (MI), ischemic stroke, ASCVD death, and composite ASCVD events.<br /><b>Results</b><br />A total of 79 151 participants (mean [SD] age, 57.8 [13.7] years; 68 503 male [86.5%]) were included in the study. The cohort included participants from the following harmonized genetic ancestry and race and ethnicity categories: 18 505 non-Hispanic Black (23.4%), 6785 Hispanic (8.6%), and 53 861 non-Hispanic White (68.0%) with a median (5th-95th percentile) follow-up of 4.3 (0.7-6.9) years. From 2011 to 2018, 3186 MIs (4.0%), 1933 ischemic strokes (2.4%), 867 ASCVD deaths (1.1%), and 5485 composite ASCVD events (6.9%) were observed. CAD PRS was associated with incident MI in non-Hispanic Black (hazard ratio [HR], 1.10; 95% CI, 1.02-1.19), Hispanic (HR, 1.26; 95% CI, 1.09-1.46), and non-Hispanic White (HR, 1.23; 95% CI, 1.18-1.29) participants. Stroke PRS was associated with incident stroke in non-Hispanic White participants (HR, 1.15; 95% CI, 1.08-1.21). A combined CAD plus stroke PRS was associated with ASCVD deaths among non-Hispanic Black (HR, 1.19; 95% CI, 1.03-1.17) and non-Hispanic (HR, 1.11; 95% CI, 1.03-1.21) participants. The combined PRS was also associated with composite ASCVD across all ancestry groups but greater among non-Hispanic White (HR, 1.20; 95% CI, 1.16-1.24) than non-Hispanic Black (HR, 1.11; 95% CI, 1.05-1.17) and Hispanic (HR, 1.12; 95% CI, 1.00-1.25) participants. Net reclassification improvement from adding PRS to a traditional risk model was modest for the intermediate risk group for composite CVD among men (5-year risk >3.75%, 0.38%; 95% CI, 0.07%-0.68%), among women, (6.79%; 95% CI, 3.01%-10.58%), for age older than 55 years (0.25%; 95% CI, 0.03%-0.47%), and for ages 40 to 55 years (1.61%; 95% CI, -0.07% to 3.30%).<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />Study results suggest that PRSs derived predominantly in European samples were statistically significantly associated with ASCVD in the multiancestry midlife and older-age MVP cohort. Overall, modest improvement in discrimination metrics were observed with addition of PRSs to traditional risk factors with greater magnitude in women and younger age groups.<br /><br /><br /><br /><small>JAMA Cardiol: 03 May 2023; epub ahead of print</small></div>

<div><h4>Association Between Intensive vs Standard Blood Pressure Control and Incident Left Ventricular Conduction Disease: A Post Hoc Analysis of the SPRINT Randomized Clinical Trial.</h4><i>Frimodt-Møller EK, Vittinghoff E, Kaur G, Biering-Sørensen T, Soliman EZ, Marcus GM</i><br /><b>Importance</b><br />Left ventricular conduction disease predicts heart failure and death, and the only strategies to mitigate its effects involve implantation of a permanent pacemaker. There are currently no proven preventive strategies for this common condition.<br /><b>Objective</b><br />To determine the association between targeting intensive blood pressure (BP) control and the risk of developing left ventricular conduction disease.<br /><b>Design, setting, and participants</b><br />This was a post hoc analysis of the 2-arm multicenter Systolic Blood Pressure Intervention Trial (SPRINT), which recruited participants from 102 sites in the US and Puerto Rico and was conducted from November 2010 until August 2015. Adults 50 years and older with hypertension and at least 1 other cardiovascular risk factor were included. Participants with baseline left ventricular conduction disease, ventricular pacing, or ventricular pre-excitation were excluded for the current analysis. Data were analyzed from November 2021 to November 2022.<br /><b>Intervention</b><br />Participants were randomly assigned to a systolic BP target of less than 140 mm Hg (standard treatment group) or less than 120 mm Hg (intensive treatment group).<br /><b>Main outcome</b><br />The primary outcome was incident left ventricular conduction disease, including any fascicular or left bundle-branch block, assessed by serial electrocardiography. Incident right bundle-branch block was examined as a negative control.<br /><b>Results</b><br />Among 3918 participants randomized to standard treatment and 3956 to intensive treatment (mean [SD] age, 67.6 [9.2] years; 2815 [36%] female) monitored for a median [IQR] 3.5 (0.02-5.2) years, 203 developed left ventricular conduction disease. Older age (hazard ratio per 10-year increase [HR], 1.42; 95% CI, 1.21-1.67; P < .001), male sex (HR, 2.31; 95% CI, 1.63-3.32; P < .001), and cardiovascular disease (HR, 1.46; 95% CI, 1.06-2.00; P = .02) were associated with a higher risk of left ventricular conduction disease. Assignment to intensive treatment was associated with a 26% lower risk of left ventricular conduction disease (HR, 0.74; 95% CI, 0.56-0.98; P = .04). These results persisted when incident ventricular pacing was included in the outcome and when considering all-cause death as a competing risk. In contrast, no association between randomization assignment and right bundle-branch block was observed (HR, 0.95; 95% CI, 0.71-1.27; P = .75).<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />In this study, targeting intensive BP control was associated with lower risk of left ventricular conduction disease in a randomized clinical trial, suggesting that clinically relevant conduction disease may be preventable.<br /><b>Trial registration</b><br />ClinicalTrials.gov Identifier: NCT01206062.<br /><br /><br /><br /><small>JAMA Cardiol: 03 May 2023; epub ahead of print</small></div>

<div><h4>Effect of Dapagliflozin on Total Heart Failure Events in Patients With Heart Failure With Mildly Reduced or Preserved Ejection Fraction: A Prespecified Analysis of the DELIVER Trial.</h4><i>Jhund PS, Claggett BL, Talebi A, Butt JH, ... Solomon SD, McMurray JJV</i><br /><b>Importance</b><br />In the Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure (DELIVER) trial, dapagliflozin reduced the risk of time to first worsening heart failure (HF) event or cardiovascular death in patients with HF with mildly reduced or preserved ejection fraction (EF).<br /><b>Objective</b><br />To evaluate the effect of dapagliflozin on total (ie, first and recurrent) HF events and cardiovascular death in this population.<br /><b>Design, setting, and participants</b><br />In this prespecified analysis of the DELIVER trial, the proportional rates approach of Lin, Wei, Yang, and Ying (LWYY) and a joint frailty model were used to examine the effect of dapagliflozin on total HF events and cardiovascular death. Several subgroups were examined to test for heterogeneity in the effect of dapagliflozin, including left ventricular EF. Participants were enrolled from August 2018 to December 2020, and data were analyzed from August to October 2022.<br /><b>Interventions</b><br />Dapagliflozin, 10 mg, once daily or matching placebo.<br /><b>Main outcomes and measures</b><br />The outcome was total episodes of worsening HF (hospitalization for HF or urgent HF visit requiring intravenous HF therapies) and cardiovascular death.<br /><b>Results</b><br />Of 6263 included patients, 2747 (43.9%) were women, and the mean (SD) age was 71.7 (9.6) years. There were 1057 HF events and cardiovascular deaths in the placebo group compared with 815 in the dapagliflozin group. Patients with more HF events had features of more severe HF, such as higher N-terminal pro-B-type natriuretic peptide level, worse kidney function, more prior HF hospitalizations, and longer duration of HF, although EF was similar to those with no HF events. In the LWYY model, the rate ratio for total HF events and cardiovascular death for dapagliflozin compared with placebo was 0.77 (95% CI, 0.67-0.89; P < .001) compared with a hazard ratio of 0.82 (95% CI, 0.73-0.92; P < .001) in a traditional time to first event analysis. In the joint frailty model, the rate ratio was 0.72 (95% CI, 0.65-0.81; P < .001) for total HF events and 0.87 (95% CI, 0.72-1.05; P = .14) for cardiovascular death. The results were similar for total HF hospitalizations (without urgent HF visits) and cardiovascular death and in all subgroups, including those defined by EF.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />In the DELIVER trial, dapagliflozin reduced the rate of total HF events (first and subsequent HF hospitalizations and urgent HF visits) and cardiovascular death regardless of patient characteristics, including EF.<br /><b>Trial registration</b><br />ClinicalTrials.gov Identifier: NCT03619213.<br /><br /><br /><br /><small>JAMA Cardiol: 26 Apr 2023; epub ahead of print</small></div>

<div><h4>Efficacy and Safety of Low-Dose Triple and Quadruple Combination Pills vs Monotherapy, Usual Care, or Placebo for the Initial Management of Hypertension: A Systematic Review and Meta-analysis.</h4><i>Wang N, Rueter P, Atkins E, Webster R, ... Patel A, Rodgers A</i><br /><b>Importance</b><br />Low-dose combination (LDC) antihypertensives consisting of 3 or 4 blood pressure (BP)-lowering drugs have emerged as a potentially important therapy for the initial management of hypertension.<br /><b>Objective</b><br />To assess the efficacy and safety of LDC therapies for the management of hypertension.<br /><b>Data sources</b><br />PubMed and Medline were searched from date of inception until September 2022.<br /><b>Study selection</b><br />Randomized clinical trials comparing LDC consisting of 3 or 4 BP-lowering drugs compared to either monotherapy, usual care, or placebo.<br /><b>Data extraction and synthesis</b><br />Data were extracted by 2 independent authors and synthesized using both random and fixed-effects models using risk ratios (RR) for binary outcomes and mean differences for continuous outcomes.<br /><b>Main outcomes and measures</b><br />The primary outcome was mean reduction in systolic BP (SBP) between LDC and monotherapy, usual care, or placebo. Other outcomes of interest included the proportion of patients achieving BP less than 140/90 mm Hg, rates of adverse effects, and treatment withdrawal.<br /><b>Results</b><br />Seven trials with a total of 1918 patients (mean [mean range] age, 59 [50-70] years; 739 [38%] female) were included. Four trials involved triple-component LDC and 3 involved quadruple-component LDC. At 4 to 12 weeks follow-up, LDC was associated with a greater mean reduction in SBP than initial monotherapy or usual care (mean reduction, 7.4 mm Hg; 95% CI, 4.3-10.5) and placebo (mean reduction, 18.0 mm Hg; 95% CI, 15.1-20.8). LDC was associated with a higher proportion of participants achieving BP less than 140/90 mm Hg at 4 to 12 weeks compared to both monotherapy or usual care (66% vs 46%; RR, 1.40; 95% CI, 1.27-1.52) and placebo (54% vs 18%; RR, 3.03; 95% CI, 1.93-4.77). There was no significant heterogeneity between trials enrolling patients with and without baseline BP-lowering therapy. Results from 2 trials indicated LDC remained superior to monotherapy or usual care at 6 to 12 months. LDC was associated with more dizziness (14% vs 11%; RR 1.28, 95% CI 1.00-1.63) but no other adverse effects nor treatment withdrawal.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />The findings in the study showed that LDCs with 3 or 4 antihypertensives were an effective and well-tolerated BP-lowering treatment option for the initial or early management of hypertension.<br /><br /><br /><br /><small>JAMA Cardiol: 26 Apr 2023; epub ahead of print</small></div>

<div><h4>Quality of Care and Clinical Outcomes for Patients With Heart Failure at Hospitals Caring for a High Proportion of Black Adults: Get With The Guidelines-Heart Failure Registry.</h4><i>Diamond J, Ayodele I, Fonarow GC, Joynt-Maddox KE, ... Yancy C, Wadhera RK</i><br /><b>Importance</b><br />Black adults with heart failure (HF) disproportionately experience higher population-level mortality than White adults with HF. Whether quality of care for HF differs at hospitals with high proportions of Black patients compared with other hospitals is unknown.<br /><b>Objective</b><br />To compare quality and outcomes for patients with HF at hospitals with high proportions of Black patients vs other hospitals.<br /><b>Design, setting, and participants</b><br />Patients hospitalized for HF at Get With The Guidelines (GWTG) HF sites from January 1, 2016, through December 1, 2019. These data were analyzed from May 2022 through November 2022.<br /><b>Exposures</b><br />Hospitals caring for high proportions of Black patients.<br /><b>Main outcomes and measures</b><br />Quality of HF care based on 14 evidence-based measures, overall defect-free HF care, and 30-day readmissions and mortality in Medicare patients.<br /><b>Results</b><br />This study included 422 483 patients (224 270 male [53.1%] and 284 618 White [67.4%]) with a mean age of 73.0 years. Among 480 hospitals participating in GWTG-HF, 96 were classified as hospitals with high proportions of Black patients. Quality of care was similar between hospitals with high proportions of Black patients compared with other hospitals for 11 of 14 GWTG-HF measures, including use of angiotensin-converting enzyme inhibitors/angiotensin receptor blocker/angiotensin receptor neprilysin inhibitors for left ventricle systolic dysfunction (high-proportion Black hospitals: 92.7% vs other hospitals: 92.4%; adjusted odds ratio [OR], 0.91; 95% CI, 0.65-1.27), evidence-based β-blockers (94.7% vs 93.7%; OR, 1.02; 95% CI, 0.82-1.28), angiotensin receptor neprilysin inhibitors at discharge (14.3% vs 16.8%; OR, 0.74; 95% CI, 0.54-1.02), anticoagulation for atrial fibrillation/flutter (88.8% vs 87.5%; OR, 1.05; 95% CI, 0.76-1.45), and implantable cardioverter-defibrillator counseling/placement/prescription at discharge (70.9% vs 71.0%; OR, 0.75; 95% CI, 0.50-1.13). Patients at high-proportion Black hospitals were less likely to be discharged with a follow-up visit made within 7 days or less (70.4% vs 80.1%; OR, 0.68; 95% CI, 0.53-0.86), receive cardiac resynchronization device placement/prescription (50.6% vs 53.8%; OR, 0.63; 95% CI, 0.42-0.95), or an aldosterone antagonist (50.4% vs 53.5%; OR, 0.69; 95% CI, 0.50-0.97). Overall defect-free HF care was similar between both groups of hospitals (82.6% vs 83.4%; OR, 0.89; 95% CI, 0.67-1.19) and there were no significant within-hospital differences in quality for Black patients vs White patients. Among Medicare beneficiaries, the risk-adjusted hazard ratio (HR) for 30-day readmissions was higher at high-proportion Black vs other hospitals (HR, 1.14; 95% CI, 1.02-1.26), but similar for 30-day mortality (HR 0.92; 95% CI,0.84-1.02).<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />Quality of care for HF was similar across 11 of 14 measures at hospitals caring for high proportions of Black patients compared with other hospitals, as was overall defect-free HF care. There were no significant within-hospital differences in quality for Black patients vs White patients.<br /><br /><br /><br /><small>JAMA Cardiol: 19 Apr 2023; epub ahead of print</small></div>

<div><h4>Comprehensive Cardiovascular Magnetic Resonance Tissue Characterization and Cardiotoxicity in Women With Breast Cancer.</h4><i>Thavendiranathan P, Shalmon T, Fan CS, Houbois C, ... Hanneman K, Wintersperger BJ</i><br /><b>Importance</b><br />There is a growing interest in understanding whether cardiovascular magnetic resonance (CMR) myocardial tissue characterization helps identify risk of cancer therapy-related cardiac dysfunction (CTRCD).<br /><b>Objective</b><br />To describe changes in CMR tissue biomarkers during breast cancer therapy and their association with CTRCD.<br /><b>Design, setting, and participants</b><br />This was a prospective, multicenter, cohort study of women with ERBB2 (formerly HER2)-positive breast cancer (stages I-III) who were scheduled to receive anthracycline and trastuzumab therapy with/without adjuvant radiotherapy and surgery. From November 7, 2013, to January 16, 2019, participants were recruited from 3 University of Toronto-affiliated hospitals. Data were analyzed from July 2021 to June 2022.<br /><b>Exposures</b><br />Sequential therapy with anthracyclines, trastuzumab, and radiation.<br /><b>Main outcomes and measures</b><br />CMR, high-sensitivity cardiac troponin I (hs-cTnI), and B-type natriuretic peptide (BNP) measurements were performed before anthracycline treatment, after anthracycline and before trastuzumab treatment, and at 3-month intervals during trastuzumab therapy. CMR included left ventricular (LV) volumes, LV ejection fraction (EF), myocardial strain, early gadolinium enhancement imaging to assess hyperemia (inflammation marker), native/postcontrast T1 mapping (with extracellular volume fraction [ECV]) to assess edema and/or fibrosis, T2 mapping to assess edema, and late gadolinium enhancement (LGE) to assess replacement fibrosis. CTRCD was defined using the Cardiac Review and Evaluation Committee criteria. Fixed-effects models or generalized estimating equations were used in analyses.<br /><b>Results</b><br />Of 136 women (mean [SD] age, 51.1 [9.2] years) recruited from 2013 to 2019, 37 (27%) developed CTRCD. Compared with baseline, tissue biomarkers of myocardial hyperemia and edema peaked after anthracycline therapy or 3 months after trastuzumab initiation as demonstrated by an increase in mean (SD) relative myocardial enhancement (baseline, 46.3% [16.8%] to peak, 56.2% [18.6%]), native T1 (1012 [26] milliseconds to 1035 [28] milliseconds), T2 (51.4 [2.2] milliseconds to 52.6 [2.2] milliseconds), and ECV (25.2% [2.4%] to 26.8% [2.7%]), with P <.001 for the entire follow-up. The observed values were mostly within the normal range, and the changes were small and recovered during follow-up. No new replacement fibrosis developed. Increase in T1, T2, and/or ECV was associated with increased ventricular volumes and BNP but not hs-cTnI level. None of the CMR tissue biomarkers were associated with changes in LVEF or myocardial strain. Change in ECV was associated with concurrent and subsequent CTRCD, but there was significant overlap between patients with and without CTRCD.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />In women with ERBB2-positive breast cancer receiving sequential anthracycline and trastuzumab therapy, CMR tissue biomarkers suggest inflammation and edema peaking early during therapy and were associated with ventricular remodeling and BNP elevation. However, the increases in CMR biomarkers were transient, were not associated with LVEF or myocardial strain, and were not useful in identifying traditional CTRCD risk.<br /><br /><br /><br /><small>JAMA Cardiol: 12 Apr 2023; epub ahead of print</small></div>

<div><h4>Aspirin vs Clopidogrel for Long-term Maintenance After Coronary Stenting in Patients With Diabetes: A Post Hoc Analysis of the HOST-EXAM Trial.</h4><i>Rhee TM, Bae JW, Park KW, Rha SW, ... Kim HS, HOST-EXAM Investigators</i><br /><b>Importance</b><br />Selecting the optimal antiplatelet agent in patients who have received percutaneous coronary intervention is especially important in those with diabetes due to the heightened risk of ischemic events in this population. Studies on the efficacy and safety of clopidogrel vs aspirin for long-term maintenance after percutaneous coronary intervention in patients with diabetes are lacking.<br /><b>Objective</b><br />To investigate cardiovascular outcomes with clopidogrel vs aspirin in patients with and without diabetes.<br /><b>Design, setting, and participants</b><br />This was a post hoc analysis of the HOST-EXAM randomized clinical trial, an investigator-initiated, prospective, randomized, open-label, multicenter trial performed at 37 centers in Korea. Patients who received dual antiplatelet therapy without clinical events for 6 to 18 months after percutaneous coronary intervention with drug-eluting stents were enrolled from March 2014 to May 2018 with follow-up at 6, 12, 18, and 24 months. All 5438 patients in the original trial were included in this analysis, which was conducted from June to October 2021.<br /><b>Interventions and exposures</b><br />Enrolled patients were randomized 1:1 to clopidogrel or aspirin monotherapy. Subgroup analyses were performed by the presence of diabetes.<br /><b>Main outcomes and measures</b><br />The main outcome was primary composite end point of all-cause death, nonfatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and major bleeding (Bleeding Academic Research Consortium type 3 or 5) at 24-month follow-up.<br /><b>Results</b><br />Of 5438 patients (mean [SD] age, 63.5 [10.7] years; 1384 [25.5%] female), 1860 (34.2%) had diabetes (925 in the clopidogrel arm and 935 in the aspirin arm), and 5338 (98.2%) completed follow-up. The rate of the primary composite end point was significantly lower in the clopidogrel group compared to the aspirin group in patients with diabetes (6.3% vs 9.2%; hazard ratio [HR], 0.69; 95% CI, 0.49-0.96; P = .03; absolute risk difference [ARD], 2.7%; number needed to treat [NNT], 37) and without diabetes (5.3% vs 7.0%; HR, 0.76; 95% CI, 0.58-1.00; P = .046; ARD, 1.6%, NNT, 63; P for interaction = .65). The presence of diabetes was not associated with a difference in benefit observed with clopidogrel monotherapy over aspirin for the thrombotic composite end point (HR, 0.68; 95% CI, 0.45-1.04 for patients with diabetes vs HR, 0.68; 95% CI, 0.49-0.93 for those without; P for interaction = .99) and any bleeding with Bleeding Academic Research Consortium 2, 3, or 5 (HR, 0.65; 95% CI, 0.39-1.09 for patients with diabetes vs HR, 0.74; 95% CI, 0.48-1.13 for those without; P for interaction = .71).<br /><br /><b>Conclusion:</b><br/>and relevance</b><br />In this study, clopidogrel monotherapy was associated with a lower rate of the primary composite end point compared to aspirin monotherapy as long-term maintenance therapy after dual antiplatelet therapy for coronary stenting in both patients with and without diabetes. Clopidogrel might thus be considered rather than aspirin in patients who have undergone coronary stenting and successfully completed dual antiplatelet therapy, regardless of diabetes status.<br /><b>Trial registration</b><br />ClinicalTrials.gov Identifier: NCT02044250.<br /><br /><br /><br /><small>JAMA Cardiol: 12 Apr 2023; epub ahead of print</small></div>

<div><h4>Modeling the Association of Volume vs Composite Outcome Thresholds With Outcomes and Access to Transcatheter Aortic Valve Implantation in the US.</h4><i>Nelson AJ, Wegermann ZK, Gallup D, O\'Brien S, ... Cohen DJ, Vemulapalli S</i><br /><b>Importance</b><br />Professional societies and the Centers for Medicare & Medicaid Services suggest volume thresholds to ensure quality in transcatheter aortic valve implantation (TAVI).<br /><b>Objective</b><br />To model the association of volume thresholds vs spoke-and-hub implementation of outcome thresholds with TAVI outcomes and geographic access.<br /><b>Design, setting, and participants</b><br />This cohort study included patients who enrolled in the US Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy registry. Site volume and outcomes were determined from a baseline cohort of adults undergoing TAVI between July 1, 2017, and June 30, 2020.<br /><b>Exposures</b><br />Within each hospital referral region, TAVI sites were categorized by volume (<50 or ≥50 TAVIs per year) and separately by risk-adjusted outcome on the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy 30-day TAVI composite during the baseline period (July 2017 to June 2020). Outcomes of patients undergoing TAVIs from July 1, 2020, to March 31, 2022, were then modeled as though the patients had been treated at (1) the nearest higher volume (≥50 TAVIs per year) or (2) the best outcome site within the hospital referral region.<br /><b>Main outcomes and measures</b><br />The primary outcome was the absolute difference in events between the adjusted observed and modeled 30-day composite of death, stroke, major bleeding, stage III acute kidney injury, and paravalvular leak. Data are presented as the number of events reduced under the above scenarios with 95% bayesian credible intervals (CrIs) and median (IQR) driving distance.<br /><b>Results</b><br />The overall cohort included 166 248 patients with a mean (SD) age of 79.5 (8.6) years; 74 699 (47.3%) were female and 6657 (4.2%) were Black; 158 025 (95%) were treated in higher-volume sites (≥50 TAVIs) and 75 088 (45%) were treated in best-outcome sites. Modeling a volume threshold, there was no significant reduction in estimated adverse events (-34; 95% CrI, -75 to 8), while the median (IQR) driving time from the existing site to the alternate site was 22 (15-66) minutes. Transitioning care to the best outcome site in a hospital referral region resulted in an estimated 1261 fewer adverse outcomes (95% CrI, 1013-1500), while the median (IQR) driving time from the original site to the best site was 23 (15-41) minutes. Directionally similar findings were observed for Black individuals, Hispanic individuals, and individuals from rural areas.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />In this study, compared with the current system of care, a modeled outcome-based spoke-and-hub paradigm of TAVI care improved national outcomes to a greater extent than a simulated volume threshold, at the cost of increased driving time. To improve quality while maintaining geographic access, efforts should focus on reducing site variation in outcomes.<br /><br /><br /><br /><small>JAMA Cardiol: 05 Apr 2023; epub ahead of print</small></div>

<div><h4>Association of the Timing and Extent of Cardiac Implantable Electronic Device Infections With Mortality.</h4><i>Han HC, Wang J, Birnie DH, Alings M, ... Longtin Y, Krahn AD</i><br /><b>Importance</b><br />Cardiac implantable electronic device (CIED) infection is a potentially devastating complication with an estimated 12-month mortality of 15% to 30%. The association of the extent (localized or systemic) and timing of infection with all-cause mortality has not been established.<br /><b>Objective</b><br />To evaluate the association of the extent and timing of CIED infection with all-cause mortality.<br /><b>Design, setting, and participants</b><br />This prospective observational cohort study was conducted between December 1, 2012, and September 30, 2016, in 28 centers across Canada and the Netherlands. The study included 19 559 patients undergoing CIED procedures, 177 of whom developed an infection. Data were analyzed from April 5, 2021, to January 14, 2023.<br /><b>Exposures</b><br />Prospectively identified CIED infections.<br /><b>Main outcomes and measures</b><br />Time-dependent analysis of the timing (early [≤3 months] or delayed [3-12 months]) and extent (localized or systemic) of infection was performed to determine the risk of all-cause mortality associated with CIED infections.<br /><b>Results</b><br />Of 19 559 patients undergoing CIED procedures, 177 developed a CIED infection. The mean (SD) age was 68.7 (12.7) years, and 132 patients were male (74.6%). The cumulative incidence of infection was 0.6%, 0.7%, and 0.9% within 3, 6, and 12 months, respectively. Infection rates were highest in the first 3 months (0.21% per month), reducing significantly thereafter. Compared with patients who did not develop CIED infection, those with early localized infections were not at higher risk for all-cause mortality (no deaths at 30 days [0 of 74 patients]: adjusted hazard ratio [aHR], 0.64 [95% CI, 0.20-1.98]; P = .43). However, patients with early systemic and delayed localized infections had an approximately 3-fold increase in mortality (8.9% 30-day mortality [4 of 45 patients]: aHR, 2.88 [95% CI, 1.48-5.61]; P = .002; 8.8% 30-day mortality [3 of 34 patients]: aHR, 3.57 [95% CI, 1.33-9.57]; P = .01), increasing to a 9.3-fold risk of death for those with delayed systemic infections (21.7% 30-day mortality [5 of 23 patients]: aHR, 9.30 [95% CI, 3.82-22.65]; P < .001).<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />Findings suggest that CIED infections are most common within 3 months after the procedure. Early systemic infections and delayed localized infections are associated with increased mortality, with the highest risk for patients with delayed systemic infections. Early detection and treatment of CIED infections may be important in reducing mortality associated with this complication.<br /><br /><br /><br /><small>JAMA Cardiol: 05 Apr 2023; epub ahead of print</small></div>

<div><h4>Association of Preexisting Heart Failure With Outcomes in Older Patients With Diffuse Large B-Cell Lymphoma.</h4><i>Upshaw JN, Nelson J, Rodday AM, Kumar AJ, ... Kent DM, Parsons SK</i><br /><b>Importance</b><br />Anthracycline-containing regimens are highly effective for diffuse large B-cell lymphoma (DLBCL); however, patients with preexisting heart failure (HF) may be less likely to receive anthracyclines and may be at higher risk of lymphoma mortality.<br /><b>Objective</b><br />To assess the prevalence of preexisting HF in older patients with DLBCL and its association with treatment patterns and outcomes.<br /><b>Design, setting, and participants</b><br />This longitudinal cohort study used data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare registry from 1999 to 2016. The SEER registry is a system of population-based cancer registries, capturing more than 25% of the US population. Linkage to Medicare offers additional information from billing claims. This study included individuals 65 years and older with newly diagnosed DLBCL from 2000 to 2015 with Medicare Part A or B continuously in the year prior to lymphoma diagnosis. Data were analyzed from September 2020 to December 2022.<br /><b>Exposures</b><br />Preexisting HF in the year prior to DLBCL diagnosis ascertained from billing codes required one of the following: (1) 1 primary inpatient discharge diagnosis, (2) 2 outpatient diagnoses, (3) 3 secondary inpatient discharge diagnoses, (4) 3 emergency department diagnoses, or (5) 2 secondary inpatient discharge diagnoses plus 1 outpatient diagnosis.<br /><b>Main outcomes and measures</b><br />The primary outcome was anthracycline-based treatment. The secondary outcomes were (1) cardioprotective medications and (2) cause-specific mortality. The associations between preexisting HF and cancer treatment were estimated using multivariable logistic regression. The associations between preexisting HF and cause-specific mortality were evaluated using cause-specific Cox proportional hazards models with adjustment for comorbidities and cancer treatment.<br /><b>Results</b><br />Of 30 728 included patients with DLBCL, 15 474 (50.4%) were female, and the mean (SD) age was 77.8 (7.2) years. Preexisting HF at lymphoma diagnosis was present in 4266 patients (13.9%). Patients with preexisting HF were less likely to be treated with an anthracycline (odds ratio, 0.55; 95% CI, 0.49-0.61). Among patients with preexisting HF who received an anthracycline, dexrazoxane or liposomal doxorubicin were used in 78 of 1119 patients (7.0%). One-year lymphoma mortality was 41.8% (95% CI, 40.5-43.2) with preexisting HF and 29.6% (95% CI, 29.0%-30.1%) without preexisting HF. Preexisting HF was associated with higher lymphoma mortality in models adjusting for baseline and time-varying treatment factors (hazard ratio, 1.24; 95% CI, 1.18-1.31).<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />In this study, preexisting HF in patients with newly diagnosed DLBCL was common and was associated with lower use of anthracyclines and lower use of any chemotherapy. Trials are needed for this high-risk population.<br /><br /><br /><br /><small>JAMA Cardiol: 29 Mar 2023; epub ahead of print</small></div>

<div><h4>Standard vs Augmented Ablation of Paroxysmal Atrial Fibrillation for Reduction of Atrial Fibrillation Recurrence: The AWARE Randomized Clinical Trial.</h4><i>Nair GM, Birnie DH, Nery PB, Redpath CJ, ... Wells GA, Essebag V</i><br /><b>Importance</b><br />Recurrent atrial fibrillation (AF) commonly occurs after catheter ablation and is associated with patient morbidity and health care costs.<br /><b>Objective</b><br />To evaluate the superiority of an augmented double wide-area circumferential ablation (WACA) compared with a standard single WACA in preventing recurrent atrial arrhythmias (AA) (atrial tachycardia, atrial flutter, or atrial fibrillation [AF]) in patients with paroxysmal AF.<br /><b>Design, setting, and participants</b><br />This was a pragmatic, multicenter, prospective, randomized, open, blinded end point superiority clinical trial conducted at 10 university-affiliated centers in Canada. The trial enrolled patients 18 years and older with symptomatic paroxysmal AF from March 2015 to May 2017. Analysis took place between January and April 2022. Analyses were intention to treat.<br /><b>Interventions</b><br />Patients were randomized (1:1) to receive radiofrequency catheter ablation for pulmonary vein isolation with either a standard single WACA or an augmented double WACA.<br /><b>Main outcomes and measures</b><br />The primary outcome was AA recurrence between 91 and 365 days postablation. Patients underwent 42 days of ambulatory electrocardiography monitoring after ablation. Secondary outcomes included need for repeated catheter ablation and procedural and safety variables.<br /><b>Results</b><br />Of 398 patients, 195 were randomized to the single WACA (control) arm (mean [SD] age, 60.6 [9.3] years; 65 [33.3%] female) and 203 to the double WACA (experimental) arm (mean [SD] age, 61.5 [9.3] years; 66 [32.5%] female). Overall, 52 patients (26.7%) in the single WACA arm and 50 patients (24.6%) in the double WACA arm had recurrent AA at 1 year (relative risk, 0.92; 95% CI, 0.66-1.29; P = .64). Twenty patients (10.3%) in the single WACA arm and 15 patients (7.4%) in the double WACA arm underwent repeated catheter ablation (relative risk, 0.72; 95% CI, 0.38-1.36). Adjudicated serious adverse events occurred in 13 patients (6.7%) in the single WACA arm and 14 patients (6.9%) in the double WACA arm.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />In this randomized clinical trial of patients with paroxysmal AF, additional ablation by performing a double ablation lesion set did not result in improved freedom from recurrent AA compared with a standard single ablation set.<br /><b>Trial registration</b><br />ClinicalTrials.gov Identifier: NCT02150902.<br /><br /><br /><br /><small>JAMA Cardiol: 22 Mar 2023; epub ahead of print</small></div>

<div><h4>Prevalence of Statin Use for Primary Prevention of Atherosclerotic Cardiovascular Disease by Race, Ethnicity, and 10-Year Disease Risk in the US: National Health and Nutrition Examination Surveys, 2013 to March 2020.</h4><i>Jacobs JA, Addo DK, Zheutlin AR, Derington CG, ... Bress AP, Pandey A</i><br /><b>Importance</b><br />The burden of atherosclerotic cardiovascular disease (ASCVD) in the US is higher among Black and Hispanic vs White adults. Inclusion of race in guidance for statin indication may lead to decreased disparities in statin use.<br /><b>Objective</b><br />To evaluate prevalence of primary prevention statin use by race and ethnicity according to 10-year ASCVD risk.<br /><b>Design, setting, and participants</b><br />This serial, cross-sectional analysis performed in May 2022 used data from the National Health and Nutrition Examination Survey, a nationally representative sample of health status in the US, from 2013 to March 2020 (limited cycle due to the COVID-19 pandemic), to evaluate statin use for primary prevention of ASCVD and to estimate 10-year ASCVD risk. Participants aged 40 to 75 years without ASCVD, diabetes, low-density lipoprotein cholesterol levels 190 mg/dL or greater, and with data on medication use were included.<br /><b>Exposures</b><br />Self-identified race and ethnicity (Asian, Black, Hispanic, and White) and 10-year ASCVD risk category (5%-<7.5%, 7.5%-<20%, ≥20%).<br /><b>Main outcomes and measures</b><br />Prevalence of statin use, defined as identification of statin use on pill bottle review.<br /><b>Results</b><br />A total of 3417 participants representing 39.4 million US adults after applying sampling weights (mean [SD] age, 61.8 [8.0] years; 1289 women [weighted percentage, 37.8%] and 2128 men [weighted percentage, 62.2%]; 329 Asian [weighted percentage, 4.2%], 1032 Black [weighted percentage, 12.7%], 786 Hispanic [weighted percentage, 10.1%], and 1270 White [weighted percentage, 73.0%]) were included. Compared with White participants, statin use was lower in Black and Hispanic participants and comparable among Asian participants in the overall cohort (Asian, 25.5%; Black, 20.0%; Hispanic, 15.4%; White, 27.9%) and within ASCVD risk strata. Within each race and ethnicity group, a graded increase in statin use was observed across increasing ASCVD risk strata. Statin use was low in the highest risk stratum overall with significantly lower rates of use among Black (23.8%; prevalence ratio [PR], 0.90; 95% CI, 0.82-0.98 vs White) and Hispanic participants (23.9%; PR, 0.90; 95% CI, 0.81-0.99 vs White). Among other factors, routine health care access and health insurance were significantly associated with higher statin use in Black, Hispanic, and White adults. Prevalence of statin use did not meaningfully change over time by race and ethnicity or by ASCVD risk stratum.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />In this study, statin use for primary prevention of ASCVD was low among all race and ethnicity groups regardless of ASCVD risk, with the lowest use occurring among Black and Hispanic adults. Improvements in access to care may promote equitable use of primary prevention statins in Black and Hispanic adults.<br /><br /><br /><br /><small>JAMA Cardiol: 22 Mar 2023; epub ahead of print</small></div>

<div><h4>State-Level Cardiovascular Mortality Rates Among Hispanic, Non-Hispanic Black, and Non-Hispanic White Populations, 1990 to 2019.</h4><i>Johnson CO, DeCleene NK, Blacker BF, Cunningham MW, ... Zheng P, Roth GA</i><br /><b>Importance</b><br />Cardiovascular disease (CVD) is the leading cause of death in the US, with considerable variation by both state and race and ethnicity group. Consistent, comparable measures of mortality by specific CVD cause at the state level and by race and ethnicity have not previously been available and are necessary for supporting policy decisions aimed at reducing health inequities.<br /><b>Objective</b><br />To quantify and describe levels and trends of mortality due to overall CVD and its component causes for 3 mutually exclusive race and ethnicity groups and by state.<br /><b>Design, setting, and participants</b><br />This cross-sectional study used Census data, population surveys, and US vital registration records to estimate cause-specific cardiovascular mortality by state and by the following race and ethnicity groups, defined by the US Office of Management and Budget: Hispanic of any race, non-Hispanic Black (hereafter, Black), and non-Hispanic White (hereafter, White). Data were analyzed from January 2020 to September 2022.<br /><b>Exposures</b><br />State of residence at time of death; Hispanic ethnicity and Black or White race.<br /><b>Main outcomes and measures</b><br />CVD death counts and mortality rates.<br /><b>Results</b><br />An estimated 25 397 029 persons died of cardiovascular diseases from 1990 to 2019. The mean (SD) age of individuals was 78.20 (14.01); 13 087 290 individuals (51.53%) were female and 12 309 739 (48.47%) were male; 2 921 650 (11.50%) were Black, 1 159 498 (4.57%) were Hispanic, and 21 315 880 (83.93%) were White. Age-standardized CVD mortality per 100 000 persons in 2019 was 194.4 (95% uncertainty interval [UI], 172.7 to 207.4), 107.7 (95% UI, 92.9 to 121.4), and 153.8 (95% UI, 133.8 to 163.8) among Black, Hispanic, and White populations, respectively. The median (IQR) percentage change across states was smaller for 2010 to 2019 compared with 1990 to 2000 for both White female and White male populations (-6.8 [-10.1 to -4.3] vs -10.2 [-12.9 to -5.9] and -4.6 [-8.6 to -2.5] vs -16.5 [-19.3 to -15.4]). For the Black and Hispanic groups, the percentage change (IQR) was larger for the female populations for the latter time period (-15.1 [-18.9 to -11.7] vs -12.6 [-19.6 to -7.8] and -23.5 [-29.2 to -18.5] vs -8.2 [-17.8 to 5.96]). The converse was observed among male individuals in both groups, with smaller percentage change (IQR) values in 2010 to 2019 compared with 1990 to 2000 (-13.1 [-18.7 to -8.6] vs -18.6 [-25.5 to -14.7] among the Black male population and -20.4 [-25.6 to -15.6] vs -21.5 [-31.1 to -5.7] among the Hispanic male population). There was substantial variability at the state level for death due to total CVD and component causes in 2019 and changes in CVD mortality from 1990 through 2019.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />The findings of this study indicate that CVD mortality varied widely by state and race and ethnicity group. Changes over the time period were not consistent for all groups and varied by cardiovascular subcause. These results highlight ongoing health disparities in cardiovascular mortality.<br /><br /><br /><br /><small>JAMA Cardiol: 15 Mar 2023; epub ahead of print</small></div>

<div><h4>Associations Between Kidney Histopathologic Lesions and Incident Cardiovascular Disease in Adults With Chronic Kidney Disease.</h4><i>Buckley LF, Schmidt IM, Verma A, Palsson R, ... Srivastava A, Waikar SS</i><br /><b>Importance</b><br />Histologic lesions in the kidney may reflect or contribute to systemic processes that may lead to adverse cardiovascular events.<br /><b>Objective</b><br />To assess the association between kidney histopathologic lesion severity and the risk of incident major adverse cardiovascular events (MACE).<br /><b>Design, setting, and participants</b><br />This prospective observational cohort study included participants without a history of myocardial infarction, stroke, or heart failure from the Boston Kidney Biopsy Cohort recruited from 2 academic medical centers in Boston, Massachusetts. Data were collected from September 2006 and November 2018, and data were analyzed from March to November 2021.<br /><b>Exposures</b><br />Semiquantitative severity scores for kidney histopathologic lesions adjudicated by 2 kidney pathologists, a modified kidney pathology chronicity score, and primary clinicopathologic diagnostic categories.<br /><b>Main outcomes and measures</b><br />The main outcome was the composite of death or incident MACE, which included myocardial infarction, stroke, and heart failure hospitalization. All cardiovascular events were independently adjudicated by 2 investigators. Cox proportional hazards models estimated associations of histopathologic lesions and scores with cardiovascular events adjusted for demographic characteristics, clinical risk factors, estimated glomerular filtration rate (eGFR), and proteinuria.<br /><b>Results</b><br />Of 597 included participants, 308 (51.6%) were women, and the mean (SD) age was 51 (17) years. The mean (SD) eGFR was 59 (37) mL/min per 1.73 m2, and the median (IQR) urine protein to creatinine ratio was 1.54 (0.39-3.95). The most common primary clinicopathologic diagnoses were lupus nephritis, IgA nephropathy, and diabetic nephropathy. Over a median (IQR) of 5.5 (3.3-8.7) years of follow-up, the composite of death or incident MACE occurred in 126 participants (37 per 1000 person-years). Compared with the reference group of individuals with proliferative glomerulonephritis, the risk of death or incident MACE was highest in individuals with nonproliferative glomerulopathy (hazard ratio [HR], 2.61; 95% CI, 1.30-5.22; P = .002), diabetic nephropathy (HR, 3.56; 95% CI, 1.62-7.83; P = .002), and kidney vascular diseases (HR, 2.86; 95% CI, 1.51-5.41; P = .001) in fully adjusted models. The presence of mesangial expansion (HR, 2.98; 95% CI, 1.08-8.30; P = .04) and arteriolar sclerosis (HR, 1.68; 95% CI, 1.03-2.72; P = .04) were associated with an increased risk of death or MACE. Compared with minimal chronicity, greater chronicity was significantly associated with an increased risk of death or MACE (severe: HR, 2.50; 95% CI, 1.06-5.87; P = .04; moderate: HR, 1.66; 95% CI, 0.74-3.75; P = .22; mild: HR, 2.22; 95% CI, 1.01-4.89; P = .047) in fully adjusted models.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />In this study, specific kidney histopathological findings were associated with increased risks of CVD events. These results provide potential insight into mechanisms of the heart-kidney relationship beyond those provided by eGFR and proteinuria.<br /><br /><br /><br /><small>JAMA Cardiol: 08 Mar 2023; epub ahead of print</small></div>

<div><h4>Effect of Sacubitril/Valsartan vs Valsartan on Left Atrial Volume in Patients With Pre-Heart Failure With Preserved Ejection Fraction: The PARABLE Randomized Clinical Trial.</h4><i>Ledwidge M, Dodd JD, Ryan F, Sweeney C, ... Murphy DJ, McDonald K</i><br /><b>Importance</b><br />Pre-heart failure with preserved ejection fraction (pre-HFpEF) is common and has no specific therapy aside from cardiovascular risk factor management.<br /><b>Objective</b><br />To investigate the hypothesis that sacubitril/valsartan vs valsartan would reduce left atrial volume index using volumetric cardiac magnetic resonance imaging in patients with pre-HFpEF.<br /><b>Design, setting, and participants</b><br />The Personalized Prospective Comparison of ARNI [angiotensin receptor/neprilysin inhibitor] With ARB [angiotensin-receptor blocker] in Patients With Natriuretic Peptide Elevation (PARABLE) trial was a prospective, double-blind, double-dummy, randomized clinical trial carried out over 18 months between April 2015 and June 2021. The study was conducted at a single outpatient cardiology center in Dublin, Ireland. Of 1460 patients in the STOP-HF program or outpatient cardiology clinics, 461 met initial criteria and were approached for inclusion. Of these, 323 were screened and 250 asymptomatic patients 40 years and older with hypertension or diabetes, elevated B-type natriuretic peptide (BNP) greater than 20 pg/mL or N-terminal pro-b type natriuretic peptide greater than 100 pg/mL, left atrial volume index greater than 28 mL/m2, and preserved ejection fraction greater than 50% were included.<br /><b>Interventions</b><br />Patients were randomized to angiotensin receptor neprilysin inhibitor sacubitril/valsartan titrated to 200 mg twice daily or matching angiotensin receptor blocker valsartan titrated to 160 mg twice daily.<br /><b>Main outcomes and measures</b><br />Maximal left atrial volume index and left ventricular end diastolic volume index, ambulatory pulse pressure, N-terminal pro-BNP, and adverse cardiovascular events.<br /><b>Results</b><br />Among the 250 participants in this study, the median (IQR) age was 72.0 (68.0-77.0) years; 154 participants (61.6%) were men and 96 (38.4%) were women. Most (n = 245 [98.0%]) had hypertension and 60 (24.0%) had type 2 diabetes. Maximal left atrial volume index was increased in patients assigned to receive sacubitril/valsartan (6.9 mL/m2; 95% CI, 0.0 to 13.7) vs valsartan (0.7 mL/m2; 95% CI, -6.3 to 7.7; P < .001) despite reduced markers of filling pressure in both groups. Changes in pulse pressure and N-terminal pro-BNP were lower in the sacubitril/valsartan group (-4.2 mm Hg; 95% CI, -7.2 to -1.21 and -17.7%; 95% CI, -36.9 to 7.4, respectively; P < .001) than the valsartan group (-1.2 mm Hg; 95% CI, -4.1 to 1.7 and 9.4%; 95% CI, -15.6 to 4.9, respectively; P < .001). Major adverse cardiovascular events occurred in 6 patients (4.9%) assigned to sacubitril/valsartan and 17 (13.3%) assigned to receive valsartan (adjusted hazard ratio, 0.38; 95% CI, 0.17 to 0.89; adjusted P = .04).<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />In this trial of patients with pre-HFpEF, sacubitril/valsartan treatment was associated with a greater increase in left atrial volume index and improved markers of cardiovascular risk compared to valsartan. More work is needed to understand the observed increased cardiac volumes and long-term effects of sacubitril/valsartan in patients with pre-HFpEF.<br /><b>Trial registration</b><br />ClinicalTrials.gov Identifier: NCT04687111.<br /><br /><br /><br /><small>JAMA Cardiol: 08 Mar 2023; epub ahead of print</small></div>

<div><h4>Cost-effectiveness of Sodium-Glucose Cotransporter-2 Inhibitors for the Treatment of Heart Failure With Preserved Ejection Fraction.</h4><i>Cohen LP, Isaza N, Hernandez I, Lewis GD, ... Kazi DS, Bellows BK</i><br /><b>Importance</b><br />Adding a sodium-glucose cotransporter-2 inhibitor (SGLT2-I) to standard-of-care treatment in patients with heart failure with preserved ejection fraction (HFpEF) reduces the risk of a composite outcome of worsening heart failure or cardiovascular mortality, but the cost-effectiveness in US patients with HFpEF is uncertain.<br /><b>Objective</b><br />To evaluate the lifetime cost-effectiveness of standard therapy plus an SGLT2-I compared with standard therapy in individuals with HFpEF.<br /><b>Design, setting, and participants</b><br />In this economic evaluation conducted from September 8, 2021, to December 12, 2022, a state-transition Markov model simulated monthly health outcomes and direct medical costs. Input parameters including hospitalization rates, mortality rates, costs, and utilities were extracted from HFpEF trials, published literature, and publicly available data sets. The base-case annual cost of SGLT2-I was $4506. A simulated cohort with similar characteristics as participants of the Empagliflozin in Heart Failure With a Preserved Ejection Fraction (EMPEROR-Preserved) and Dapagliflozin in Heart Failure With Mildly Reduced or Preserved Ejection Fraction (DELIVER) trials was used.<br /><b>Exposures</b><br />Standard of care plus SGLT2-I vs standard of care.<br /><b>Main outcomes and measures</b><br />The model simulated hospitalizations, urgent care visits, and cardiovascular and noncardiovascular death. Future medical costs and benefits were discounted by 3% per year. Main outcomes were quality-adjusted life-years (QALYs), direct medical costs (2022 US dollars), and incremental cost-effectiveness ratio (ICER) of SGLT2-I therapy from a US health care sector perspective. The ICER of SGLT2-I therapy was evaluated according to the American College of Cardiology/American Heart Association value framework (high value: <$50 000; intermediate value: $50 000 to <$150 000; and low value: ≥$150 000).<br /><b>Results</b><br />The simulated cohort had a mean (SD) age of 71.7 (9.5) years and 6828 of 12 251 participants (55.7%) were male. Standard of care plus SGLT2-I increased quality-adjusted survival by 0.19 QALYs at an increased cost of $26 300 compared with standard of care. The resulting ICER was $141 200 per QALY gained, with 59.1% of 1000 probabilistic iterations indicating intermediate value and 40.9% indicating low value. The ICER was most sensitive to SGLT2-I costs and effect of SGLT2-I therapy on cardiovascular death (eg, increasing to $373 400 per QALY gained if SGLT2-I therapy was assumed to have no effect on mortality).<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />Results of this economic evaluation suggest that at 2022 drug prices, adding an SGLT2-I to standard of care was of intermediate or low economic value compared with standard of care in US adults with HFpEF. Efforts to expand access to SGLT2-I for individuals with HFpEF should be coupled with efforts to lower the cost of SGLT2-I therapy.<br /><br /><br /><br /><small>JAMA Cardiol: 04 Mar 2023; epub ahead of print</small></div>