<div><h4>Exercise Stress Echocardiography of the Right Ventricle and Pulmonary Circulation.</h4><i>Gargani L, Pugliese NR, De Biase N, Mazzola M, ... Bossone E, RIGHT Heart International NETwork (RIGHT-NET) Investigators</i><br /><b>Background</b><br />Exercise echocardiography is used for assessment of pulmonary circulation and right ventricular function, but limits of normal and disease-specific changes remain insufficiently established.<br /><b>Objectives</b><br />The objective of this study was to explore the physiological vs pathologic response of the right ventricle and pulmonary circulation to exercise.<br /><b>Methods</b><br />A total of 2,228 subjects were enrolled: 375 healthy controls, 40 athletes, 516 patients with cardiovascular risk factors, 17 with pulmonary arterial hypertension, 872 with connective tissue diseases without overt pulmonary hypertension, 113 with left-sided heart disease, 30 with lung disease, and 265 with chronic exposure to high altitude. All subjects underwent resting and exercise echocardiography on a semirecumbent cycle ergometer. All-cause mortality was recorded at follow-up.<br /><b>Results</b><br />The 5th and 95th percentile of the mean pulmonary artery pressure-cardiac output relationships were 0.2 to 3.5 mm Hg.min/L in healthy subjects without cardiovascular risk factors, and were increased in all patient categories and in high altitude residents. The 5th and 95th percentile of the tricuspid annular plane systolic excursion to systolic pulmonary artery pressure ratio at rest were 0.7 to 2.0 mm/mm Hg at rest and 0.5 to 1.5 mm/mm Hg at peak exercise, and were decreased at rest and exercise in all disease categories and in high-altitude residents. An increased all-cause mortality was predicted by a resting tricuspid annular plane systolic excursion to systolic pulmonary artery pressure <0.7 mm/mm Hg and mean pulmonary artery pressure-cardiac output >5 mm Hg.min/L.<br /><b>Conclusions</b><br />Exercise echocardiography of the pulmonary circulation and the right ventricle discloses prognostically relevant differences between healthy subjects, athletes, high-altitude residents, and patients with various cardio-respiratory conditions. (Right Heart International NETwork During Exercise in Different Clinical Conditions; NCT03041337).<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 20 Nov 2023; 82:1973-1985</small></div>

<div><h4>Sleep-Related Hypoxia, Right Ventricular Dysfunction, and Survival in Patients With Group 1 Pulmonary Arterial Hypertension.</h4><i>Lowery MM, Hill NS, Wang L, Rosenzweig EB, ... Mehra R, Pulmonary Vascular Disease Phenomics (PVDOMICS) Study Group</i><br /><b>Background</b><br />Group 1 pulmonary arterial hypertension (PAH) is a progressive fatal condition characterized by right ventricular (RV) failure with worse outcomes in connective tissue disease (CTD). Obstructive sleep apnea and sleep-related hypoxia may contribute to RV dysfunction, though the relationship remains unclear.<br /><b>Objectives</b><br />The aim of this study was to prospectively evaluate the association of the apnea-hypopnea index (AHI) and sleep-related hypoxia with RV function and survival.<br /><b>Methods</b><br />Pulmonary Vascular Disease Phenomics (National Heart, Lung, and Blood Institute) cohort participants (patients with group 1 PAH, comparators, and healthy control participants) with sleep studies were included. Multimodal RV functional measures were examined in association with AHI and percentage of recording time with oxygen saturation <90% (T90) per 10-unit increment. Linear models, adjusted for demographics, oxygen, diffusing capacity of the lungs for carbon monoxide, pulmonary hypertension medications, assessed AHI and T90, and RV measures. Log-rank test/Cox proportional hazards models adjusted for demographics, oxygen, and positive airway pressure were constructed for transplantation-free survival analyses.<br /><b>Results</b><br />Analysis included 186 participants with group 1 PAH with a mean age of 52.6 ± 14.1 years; 71.5% were women, 80.8% were Caucasian, and there were 43 events (transplantation or death). AHI and T90 were associated with decreased RV ejection fraction (on magnetic resonance imaging), by 2.18% (-2.18; 95% CI: -4.00 to -0.36; P = 0.019) and 0.93% (-0.93; 95% CI: -1.47 to -0.40; P < 0.001), respectively. T90 was associated with increased RV systolic pressure (on echocardiography), by 2.52 mm Hg (2.52; 95% CI: 1.61 to 3.43; P < 0.001); increased mean pulmonary artery pressure (on right heart catheterization), by 0.27 mm Hg (0.27; 95% CI: 0.05 to 0.49; P = 0.019); and RV hypertrophy (on electrocardiography), 1.24 mm (1.24; 95% CI: 1.10 to 1.40; P < 0.001). T90, but not AHI, was associated with a 17% increased 5-year risk for transplantation or death (HR: 1.17; 95% CI: 1.07 to 1.28). In non-CTD-associated PAH, T90 was associated with a 21% increased risk for transplantation or death (HR: 1.21; 95% CI: 1.08 to 1.34). In CTD-associated PAH, T90 was associated with RV dysfunction, but not death or transplantation.<br /><b>Conclusions</b><br />Sleep-related hypoxia was more strongly associated than AHI with measures of RV dysfunction, death, or transplantation overall and in group 1 non-CTD-associated PAH but only with RV dysfunction in CTD-associated PAH. (Pulmonary Vascular Disease Phenomics Program [PVDOMICS]; NCT02980887).<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 20 Nov 2023; 82:1989-2005</small></div>

<div><h4>Long-Term Outcomes of Invasive vs Conservative Strategies for Older Patients With Non-ST-Segment Elevation Acute Coronary Syndromes.</h4><i>Berg ES, Tegn NK, Abdelnoor M, Røysland K, ... Bendz B, After Eighty Study Investigators</i><br /><b>Background</b><br />Non-ST-segment elevation acute coronary syndrome (NSTE-ACS) is a frequent cause of hospital admission in older people, but clinical trials targeting this population are scarce.<br /><b>Objectives</b><br />The After Eighty Study assessed the effect of an invasive vs a conservative treatment strategy in a very old population with NSTE-ACS.<br /><b>Methods</b><br />Between 2010 and 2014, the investigators randomized 457 patients with NSTE-ACS aged ≥80 years (mean age 85 years) to an invasive strategy involving early coronary angiography with immediate evaluation for revascularization and optimal medical therapy or to a conservative strategy (ie, optimal medical therapy). The primary endpoint was a composite of myocardial infarction, need for urgent revascularization, stroke, and death. The long-term outcomes are presented.<br /><b>Results</b><br />After a median follow up of 5.3 years, the invasive strategy was superior to the conservative strategy in the reduction of the primary endpoint (incidence rate ratio: 0.76; 95% CI: 0.63-0.93; P = 0.0057). The invasive strategy demonstrated a significant gain in event-free survival of 276 days (95% CI: 151-400 days; P = 0.0001) at 5 years and 337 days (95% CI: 123-550 days; P = 0.0001) at 10 years. These results were consistent across subgroups of patients with respect to major cardiovascular prognostic factors.<br /><b>Conclusions</b><br />In patients aged ≥80 years with NSTE-ACS, the invasive strategy was superior to the conservative strategy in the reduction of composite events and demonstrated a significant gain in event-free survival. (The After Eighty Study: a randomized controlled trial; NCT01255540).<br /><br />Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 20 Nov 2023; 82:2021-2030</small></div>

<div><h4>Challenges and Controversies in Peer Review: JACC Review Topic of the Week.</h4><i>Kusumoto FM, Bittl JA, Creager MA, Dauerman HL, ... Fuster V, Peer Review Task Force of the Scientific Publications Committee</i><br /><AbstractText>The process of peer review has been the gold standard for evaluating medical science, but significant pressures from the recent COVID-19 pandemic, new methods of communication, larger amounts of research, and an evolving publication landscape have placed significant pressures on this system. A task force convened by the American College of Cardiology identified the 5 most significant controversies associated with the current peer-review process: the effect of preprints, reviewer blinding, reviewer selection, reviewer incentivization, and publication of peer reviewer comments. Although specific solutions to these issues will vary, regardless of how scientific communication evolves, peer review must remain an essential process for ensuring scientific integrity, timely dissemination of information, and better patient care. In medicine, the peer-review process is crucial because harm can occur if poor-quality data or incorrect conclusions are published. With the dramatic increase in scientific publications and new methods of communication, high-quality peer review is more important now than ever.</AbstractText><br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 20 Nov 2023; 82:2054-2062</small></div>

<div><h4>Plasma Proteomics to Identify Drug Targets for Ischemic Heart Disease.</h4><i>Mazidi M, Wright N, Yao P, Kartsonaki C, ... Chen Z, China Kadoorie Biobank Collaborative Group</i><br /><b>Background</b><br />Integrated analyses of plasma proteomic and genetic markers in prospective studies can clarify the causal relevance of proteins and discover novel targets for ischemic heart disease (IHD) and other diseases.<br /><b>Objectives</b><br />The purpose of this study was to examine associations of proteomics and genetics data with IHD in population studies to discover novel preventive treatments.<br /><b>Methods</b><br />We conducted a nested case-cohort study in the China Kadoorie Biobank (CKB) involving 1,971 incident IHD cases and 2,001 subcohort participants who were genotyped and free of prior cardiovascular disease. We measured 1,463 proteins in the stored baseline samples using the OLINK EXPLORE panel. Cox regression yielded adjusted HRs for IHD associated with individual proteins after accounting for multiple testing. Moreover, cis-protein quantitative loci (pQTLs) identified for proteins in genome-wide association studies of CKB and of UK Biobank were used as instrumental variables in separate 2-sample Mendelian randomization (MR) studies involving global CARDIOGRAM+C4D consortium (210,842 IHD cases and 1,378,170 controls).<br /><b>Results</b><br />Overall 361 proteins were significantly associated at false discovery rate <0.05 with risk of IHD (349 positively, 12 inversely) in CKB, including N-terminal prohormone of brain natriuretic peptide and proprotein convertase subtilisin/kexin type 9. Of these 361 proteins, 212 had cis-pQTLs in CKB, and MR analyses of 198 variants in CARDIOGRAM+C4D identified 13 proteins that showed potentially causal associations with IHD. Independent MR analyses of 307 cis-pQTLs identified in Europeans replicated associations for 4 proteins (FURIN, proteinase-activated receptor-1, Asialoglycoprotein receptor-1, and matrix metalloproteinase-3). Further downstream analyses showed that FURIN, which is highly expressed in endothelial cells, is a potential novel target and matrix metalloproteinase-3 a potential repurposing target for IHD.<br /><b>Conclusions</b><br />Integrated analyses of proteomic and genetic data in Chinese and European adults provided causal support for FURIN and multiple other proteins as potential novel drug targets for treatment of IHD.<br /><br />Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 13 Nov 2023; 82:1906-1920</small></div>

<div><h4>Multiomics Analysis Provides Novel Pathways Related to Progression of Heart Failure.</h4><i>Ouwerkerk W, Belo Pereira JP, Maasland T, Emmens JE, ... Levin E, Voors AA</i><br /><b>Background</b><br />Despite major advances in pharmacological treatment for patients with heart failure, residual mortality remains high. This suggests that important pathways are not yet targeted by current heart failure therapies.<br /><b>Objectives</b><br />We sought integration of genetic, transcriptomic, and proteomic data in a large cohort of patients with heart failure to detect major pathways related to progression of heart failure leading to death.<br /><b>Methods</b><br />We used machine learning methodology based on stacked generalization framework and gradient boosting algorithms, using 54 clinical phenotypes, 403 circulating plasma proteins, 36,046 transcript expression levels in whole blood, and 6 million genomic markers to model all-cause mortality in 2,516 patients with heart failure from the BIOSTAT-CHF (Systems BIOlogy Study to TAilored Treatment in Chronic Heart Failure) study. Results were validated in an independent cohort of 1,738 patients.<br /><b>Results</b><br />The mean age of the patients was 70 years (Q1-Q3: 61-78 years), 27% were female, median N-terminal pro-B-type natriuretic peptide was 4,275 ng/L (Q1-Q3: 2,360-8,486 ng/L), and 7% had heart failure with preserved ejection fraction. During a median follow-up of 21 months, 657 (26%) of patients died. The 4 major pathways with a significant association to all-cause mortality were: 1) the PI3K/Akt pathway; 2) the MAPK pathway; 3) the Ras signaling pathway; and 4) epidermal growth factor receptor tyrosine kinase inhibitor resistance. Results were validated in an independent cohort of 1,738 patients.<br /><b>Conclusions</b><br />A systems biology approach integrating genomic, transcriptomic, and proteomic data identified 4 major pathways related to mortality. These pathways are related to decreased activation of the cardioprotective ERBB2 receptor, which can be modified by neuregulin.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 13 Nov 2023; 82:1921-1931</small></div>

<div><h4>Deep Learning-Enabled Assessment of Left Heart Structure and Function Predicts Cardiovascular Outcomes.</h4><i>Lau ES, Di Achille P, Kopparapu K, Andrews CT, ... Lubitz SA, Ho JE</i><br /><b>Background</b><br />Deep learning interpretation of echocardiographic images may facilitate automated assessment of cardiac structure and function.<br /><b>Objectives</b><br />We developed a deep learning model to interpret echocardiograms and examined the association of deep learning-derived echocardiographic measures with incident outcomes.<br /><b>Methods</b><br />We trained and validated a 3-dimensional convolutional neural network model for echocardiographic view classification and quantification of left atrial dimension, left ventricular wall thickness, chamber diameter, and ejection fraction. The training sample comprised 64,028 echocardiograms (n = 27,135) from a retrospective multi-institutional ambulatory cardiology electronic health record sample. Validation was performed in a separate longitudinal primary care sample and an external health care system data set. Cox models evaluated the association of model-derived left heart measures with incident outcomes.<br /><b>Results</b><br />Deep learning discriminated echocardiographic views (area under the receiver operating curve >0.97 for parasternal long axis, apical 4-chamber, and apical 2-chamber views vs human expert annotation) and quantified standard left heart measures (R<sup>2</sup> range = 0.53 to 0.91 vs study report values). Model performance was similar in 2 external validation samples. Model-derived left heart measures predicted incident heart failure, atrial fibrillation, myocardial infarction, and death. A 1-SD lower model-left ventricular ejection fraction was associated with 43% greater risk of heart failure (HR: 1.43; 95% CI: 1.23-1.66) and 17% greater risk of death (HR: 1.17; 95% CI: 1.06-1.30). Similar results were observed for other model-derived left heart measures.<br /><b>Conclusions</b><br />Deep learning echocardiographic interpretation accurately quantified standard measures of left heart structure and function, which in turn were associated with future clinical outcomes. Deep learning may enable automated echocardiogram interpretation and disease prediction at scale.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 13 Nov 2023; 82:1936-1948</small></div>

<div><h4>Imaging Methods for Evaluation of Chronic Aortic Regurgitation in Adults: JACC State-of-the-Art Review.</h4><i>Ranard LS, Bonow RO, Nishimura R, Mack MJ, ... Rigolin VH, Heart Valve Collaboratory</i><br /><AbstractText>A global multidisciplinary workshop was convened to discuss the multimodality diagnostic evaluation of aortic regurgitation (AR). Specifically, the focus was on assessment tools for AR severity and analyzing evolving data on the optimal timing of aortic valve intervention. The key concepts from this expert panel are summarized as: 1) echocardiography is the primary imaging modality for assessment of AR severity; however, when data is incongruent or incomplete, cardiac magnetic resonance may be helpful; 2) assessment of left ventricular size and function is crucial in determining the timing of intervention; 3) recent evidence suggests current cutpoints for intervention in asymptomatic severe AR patients requires further scrutiny; 4) left ventricular end-systolic volume index has emerged as an additional parameter that has promise in guiding timing of intervention; and 5) the role of additional factors (including global longitudinal strain, regurgitant fraction, and myocardial extracellular volume) is worthy of future investigation.</AbstractText><br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 13 Nov 2023; 82:1953-1966</small></div>

<div><h4>Outcomes According to Coronary Revascularization Modality in the ISCHEMIA Trial.</h4><i>Redfors B, Stone GW, Alexander JH, Bates ER, ... Sandner S, Gaudino MF</i><br /><b>Background</b><br />In the ISCHEMIA trial, the risk of ischemic events was similar in patients with stable coronary artery disease treated with an invasive (INV) strategy of angiography and percutaneous (PCI) or surgical (CABG) coronary revascularization and a conservative (CON) strategy of initial medical therapy.<br /><b>Objective</b><br />To analyze separately the outcomes of INV patients treated with PCI or CABG.<br /><b>Methods</b><br />Patients without preceding primary outcome events were categorized as INV-PCI or INV-CABG from the time of revascularization. The ISCHEMIA primary outcome (composite of cardiovascular death, protocol-defined myocardial infarction (MI) or hospitalization for unstable angina, heart failure or resuscitated cardiac arrest) was used.<br /><b>Results</b><br />Among INV-CABG patients, primary outcome events occurred in 84/512 (16.4%) at median follow-up of 2.85 years; 48 events (57.1%) occurred within 30 days after CABG, including 40 procedural MIs; among INV-PCI patients, primary outcome events occurred in 147/1500 (9.8%) at median follow-up of 2.94 years; 31 of which (21.1%) within 30 days after PCI, including 23 procedural MIs. In comparison, 352/2591 (13.6%) CON patients had primary outcome events at median follow-up 3.2 years, 22 of which (6.3%) within 30 days of randomization. The adjusted primary outcome risks (HR [95%CI]) were higher after both CABG and PCI within 30 days (16.25 (11.44-23.07) and 2.99 (1.97-4.53)) and lower thereafter (0.63 (0.44-0.89) and 0.66(0.53-0.82)).<br /><b>Conclusions</b><br />In ISCHEMIA, early revascularization by PCI and CABG was associated with higher early risks and lower long-term risks of cardiovascular events compared with CON. The early risk was greatest after CABG, due to protocol-defined procedural MIs.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Am Coll Cardiol: 07 Nov 2023; epub ahead of print</small></div>

<div><h4>Safety and Efficacy of Renal Denervation in Patients Taking Antihypertensive Medications.</h4><i>Kandzari DE, Townsend RR, Kario K, Mahfoud F, ... Böhm M, SPYRAL HTN-ON MED Investigators</i><br /><b>Background</b><br />Renal denervation (RDN) reduces blood pressure (BP) in patients with uncontrolled hypertension in the absence of antihypertensive medications.<br /><b>Objectives</b><br />This trial assessed the safety and efficacy of RDN in the presence of antihypertensive medications.<br /><b>Methods</b><br />SPYRAL HTN-ON MED is a prospective, randomized, sham-controlled, patient- and assessor-blinded trial enrolling patients from 56 clinical centers worldwide. Patients were prescribed 1 to 3 antihypertensive medications. Patients were randomized to radiofrequency RDN or sham control procedure. The primary efficacy endpoint was the baseline-adjusted change in mean 24-hour ambulatory systolic BP at 6 months between groups using a Bayesian trial design and analysis.<br /><b>Results</b><br />The treatment difference in the mean 24-hour ambulatory systolic BP from baseline to 6 months between the RDN group (n = 206; -6.5 ± 10.7 mm Hg) and sham control group (n = 131; -4.5 ± 10.3 mm Hg) was -1.9 mm Hg (95% CI: -4.4 to 0.5 mm Hg; P = 0.12). There was no significant difference between groups in the primary efficacy analysis with a posterior probability of superiority of 0.51 (Bayesian treatment difference: -0.03 mm Hg [95% CI: -2.82 to 2.77 mm Hg]). However, there were changes and increases in medication intensity among sham control patients. RDN was associated with a reduction in office systolic BP compared with sham control at 6 months (adjusted treatment difference: -4.9 mm Hg; P = 0.0015). Night-time BP reductions and win ratio analysis also favored RDN. There was 1 adverse safety event among 253 assessed patients.<br /><b>Conclusions</b><br />There was no significant difference between groups in the primary analysis. However, multiple secondary endpoint analyses favored RDN over sham control. (SPYRAL HTN-ON MED Study [Global Clinical Study of Renal Denervation With the Symplicity Spyral Multi-electrode Renal Denervation System in Patients With Uncontrolled Hypertension in the Absence of Antihypertensive Medications]; NCT02439775).<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 07 Nov 2023; 82:1809-1823</small></div>

<div><h4>Stress Perfusion Cardiac Magnetic Resonance vs SPECT Imaging for Detection of Coronary Artery Disease.</h4><i>Arai AE, Schulz-Menger J, Shah DJ, Han Y, ... Berman DS, Pennell DJ</i><br /><b>Background</b><br />GadaCAD2 was 1 of 2 international, multicenter, prospective, Phase 3 clinical trials that led to U.S. Food and Drug Administration approval of gadobutrol to assess myocardial perfusion and late gadolinium enhancement (LGE) in adults with known or suspected coronary artery disease (CAD).<br /><b>Objectives</b><br />A prespecified secondary objective was to determine if stress perfusion cardiovascular magnetic resonance (CMR) was noninferior to single-photon emission computed tomography (SPECT) for detecting significant CAD and for excluding significant CAD.<br /><b>Methods</b><br />Participants with known or suspected CAD underwent a research rest and stress perfusion CMR that was compared with a gated SPECT performed using standard clinical protocols. For CMR, adenosine or regadenoson served as vasodilators. The total dose of gadobutrol was 0.1 mmol/kg body weight. The standard of reference was a 70% stenosis defined by quantitative coronary angiography (QCA). A negative coronary computed tomography angiography could exclude CAD. Analysis was per patient. CMR, SPECT, and QCA were evaluated by independent central core lab readers blinded to clinical information.<br /><b>Results</b><br />Participants were predominantly male (61.4% male; mean age 58.9 ± 10.2 years) and were recruited from the United States (75.0%), Australia (14.7%), Singapore (5.7%), and Canada (4.6%). The prevalence of significant CAD was 24.5% (n = 72 of 294). Stress perfusion CMR was statistically superior to gated SPECT for specificity (P = 0.002), area under the receiver operating characteristic curve (P < 0.001), accuracy (P = 0.003), positive predictive value (P < 0.001), and negative predictive value (P = 0.041). The sensitivity of CMR for a 70% QCA stenosis was noninferior and nonsuperior to gated SPECT.<br /><b>Conclusions</b><br />Vasodilator stress perfusion CMR, as performed with gadobutrol 0.1 mmol/kg body weight, had superior diagnostic accuracy for diagnosis and exclusion of significant CAD vs gated SPECT.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Am Coll Cardiol: 07 Nov 2023; 82:1828-1838</small></div>

<div><h4>Efficacy of Sotagliflozin in Adults With Type 2 Diabetes in Relation to Baseline Hemoglobin A1c.</h4><i>Aggarwal R, Bhatt DL, Szarek M, Cannon CP, ... Pitt B, Steg PG</i><br /><b>Background</b><br />The SCORED (Effect of Sotagliflozin on Cardiovascular and Renal Events in Patients with Type 2 Diabetes and Moderate Renal Impairment Who Are at Cardiovascular Risk) and SOLOIST-WHF (Effect of Sotagliflozin on Cardiovascular Events in Patients with Type 2 Diabetes Post Worsening Heart Failure) trials demonstrated that sotagliflozin, an SGLT1 and SGLT2 inhibitor, improves outcomes in individuals with type 2 diabetes who have heart failure (HF) or kidney disease.<br /><b>Objectives</b><br />We assessed the efficacy of sotagliflozin on HF clinical outcomes in individuals with differing baseline glycosylated hemoglobin (HbA1c) levels.<br /><b>Methods</b><br />We included all adults from SCORED and SOLOIST-WHF. The primary outcome was a composite of cardiovascular death, hospitalizations for HF, and urgent visits for HF. The efficacy of sotagliflozin compared with placebo was evaluated by baseline HbA1c using competing-risk marginal proportional hazards models.<br /><b>Results</b><br />We identified 11,744 adults. Individuals with HbA1c ≤7.5% experienced the primary outcome at a lower rate in the sotagliflozin group (11.2 per 100 person-years) than the placebo group (15.5 per 100 person-years) (HR: 0.73; 95% CI: 0.57-0.93). Similarly, individuals with HbA1c of 7.6% to 9.0% experienced the primary outcome at a lower rate in the sotagliflozin group (7.3 per 100 person-years) than the placebo group (9.4 per 100 person-years) (HR: 0.77; 95% CI: 0.63-0.96). These findings were also consistent among individuals with HbA1c >9.0%, with a primary outcome rate in the sotagliflozin group (7.8 per 100 person-years) that was lower than the placebo group (11.6 per 100 person-years) (HR: 0.65; 95% CI: 0.50-0.84). The efficacy of sotagliflozin was consistent by baseline HbA1c level (P for interaction = 0.58).<br /><b>Conclusions</b><br />In individuals with type 2 diabetes and either HF or kidney disease, sotagliflozin reduced HF outcomes irrespective of baseline HbA1c.<br /><br />Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 07 Nov 2023; 82:1842-1851</small></div>

<div><h4>Patients With Hypertrophic Cardiomyopathy and Normal Genetic Investigations Have Few Affected Relatives.</h4><i>Nielsen SK, Hansen FG, Rasmussen TB, Fischer T, ... Jensen MSK, Mogensen J</i><br /><b>Background</b><br />Current guidelines recommend that relatives of index patients with hypertrophic cardiomyopathy (HCM) are offered clinical investigations to identify individuals at risk of adverse disease complications and sudden cardiac death. However, the value of family screening in relatives of index patients with a normal genetic investigation of recognized HCM genes is largely unknown.<br /><b>Objectives</b><br />The purpose of this study was to perform family screening among relatives of HCM index patients with a normal genetic investigation to establish the frequency of familial disease and the clinical characteristics of affected individuals.<br /><b>Methods</b><br />Clinical and genetic investigations were performed in consecutive and unrelated HCM index patients. Relatives of index patients who did not carry pathogenic/likely pathogenic variants in recognized HCM genes were invited for clinical investigations.<br /><b>Results</b><br />In total, 60% (270 of 453) of HCM index patients had a normal genetic investigation. A total of 80% of their relatives (751 of 938, median age 44 years) participated in the study. Of these, 5% (34 of 751) were diagnosed with HCM at baseline, whereas 0.3% (2 of 717 [751-34]) developed the condition during 5 years of follow-up. Their median age at diagnosis was 57 years (IQR: 51-70 years). Two-thirds (22 of 36) were diagnosed following family screening, whereas one-third (14 of 36) had been diagnosed previously because of cardiac symptoms, a murmur, or an abnormal electrocardiogram. None of the affected relatives experienced adverse disease complications. The risk of SCD was low.<br /><b>Conclusions</b><br />Systematic family screening of index patients with HCM and normal genetic investigations was associated with a low frequency of affected relatives who appeared to have a favorable prognosis.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 31 Oct 2023; 82:1751-1761</small></div>

<div><h4>Public Out-of-Hospital Cardiac Arrest in Residential Neighborhoods.</h4><i>Juul Grabmayr A, Folke F, Tofte Gregers MC, Kollander L, ... Kjær Ersbøll A, Malta Hansen C</i><br /><b>Background</b><br />Although one-half of all public out-of-hospital cardiac arrests (OHCAs) occur outside private homes in residential neighborhoods, their characteristics and outcomes remain unexplored.<br /><b>Objectives</b><br />The authors assessed interventions before ambulance arrival and survival for public OHCA patients in residential neighborhoods.<br /><b>Methods</b><br />Public OHCAs from Vienna (2018-2021) and Copenhagen (2016-2020) were designated residential neighborhoods or nonresidential areas. Interventions (cardiopulmonary resuscitation [CPR], automated external defibrillator [AED] attached, and defibrillation) and 30-day survival were compared using a generalized estimation equation model adjusted for age and time of day and presented as ORs.<br /><b>Results</b><br />We included 1,052 and 654 public OHCAs from Vienna and Copenhagen, respectively, and 68% and 55% occurred in residential neighborhoods, respectively. The likelihood of CPR, defibrillation, and survival in residential neighborhoods vs nonresidential areas (reference) were as follows: CPR Vienna, 73% vs 78%, OR: 0.78 (95% CI: 0.57-1.06), CPR Copenhagen, 83% vs 90%, OR: 0.54 (95% CI: 0.34-0.88), and CPR combined, 76% vs 84%, OR: 0.70 (95% CI: 0.53-0.90); AED attached Vienna, 36% vs 44%, OR: 0.69 (95% CI: 0.53-0.90), AED attached Copenhagen, 21% vs 43%, OR: 0.33 (95% CI: 0.24-0.48), and AED attached combined, 31% vs 44%, OR: 0.53 (95% CI: 0.42-0.65); defibrillation Vienna, 14% vs 20%, OR: 0.61 (95% CI: 0.43-0.87), defibrillation Copenhagen, 16% vs 36%, OR: 0.35 (95% CI: 0.24-0.51), and defibrillation combined, 15% vs 27%, OR: 0.46 (95% CI: 0.36-0.61); and 30-day survival rate Vienna, 21% vs 26%, OR: 0.84 (95% CI: 0.58-1.20), 30-day survival rate Copenhagen, 33% vs 44%, OR: 0.65 (95% CI: 0.47-0.90), and 30-day survival rate combined, 25% vs 36%, OR: 0.73 (95% CI: 0.58-0.93).<br /><b>Conclusions</b><br />Two-thirds of public OHCAs occurred in residential neighborhoods with fewer resuscitative efforts before ambulance arrival and lower survival than in nonresidential areas. Targeted efforts to improve early CPR and defibrillation for public OHCA patients in residential neighborhoods are needed.<br /><br />Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 31 Oct 2023; 82:1777-1788</small></div>

<div><h4>Cardiovascular Fellowship Training in Cardio-Obstetrics: JACC Review Topic of the Week.</h4><i>Davis MB, Bello NA, Berlacher K, Harrington CM, ... DeFaria Yeh D, Damp JB</i><br /><AbstractText>The United States has the highest maternal mortality in the developed world with cardiovascular disease as the leading cause of pregnancy-related deaths. In response to this, the emerging subspecialty of cardio-obstetrics has been growing over the past decade. Cardiologists with training and expertise in caring for patients with cardiovascular disease in pregnancy are essential to provide effective, comprehensive, multidisciplinary, and high-quality care for this vulnerable population. This document provides a blueprint on incorporation of cardio-obstetrics training into cardiovascular disease fellowship programs to improve knowledge, skill, and expertise among cardiologists caring for these patients, with the goal of improving maternal and fetal outcomes.</AbstractText><br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 31 Oct 2023; 82:1792-1803</small></div>

<div><h4>Growth of the Neo-Aortic Root and Prognosis of Transposition of the Great Arteries.</h4><i>Sengupta A, Carreon CK, Gauvreau K, Lee JM, ... Mayer JE, Nathan M</i><br /><b>Background</b><br />Neo-aortic root dilatation can lead to significant late morbidity after the arterial switch operation (ASO) for dextro-transposition of the great arteries (d-TGA).<br /><b>Objectives</b><br />We sought to examine the growth of the neo-aortic root in d-TGA.<br /><b>Methods</b><br />A single-center, retrospective cohort study of patients that underwent the ASO from 07/1981-09/2022 was performed. Morphology was categorized as d-TGA with intact ventricular septum (d-TGA-IVS), d-TGA with ventricular septal defect (d-TGA-VSD), and double-outlet right ventricle-TGA type (DORV-TGA). Echocardiographically-determined diameters and derived z-scores were measured at the annulus, sinus of Valsalva (SoV), and sinotubular junction (STJ) immediately before the ASO and throughout follow-up. Trends in root dimensions over time were assessed using linear mixed-effects models. The association between intrinsic morphology and the composite of moderate-severe aortic regurgitation (AR) and neo-aortic valve or root reintervention was evaluated with uni- and multivariable Cox proportional hazards models.<br /><b>Results</b><br />Of 1359 patients that underwent the ASO, 593 (44%), 666 (49%), and 100 (7%) patients had d-TGA-IVS, d-TGA-VSD, and DORV-TGA, respectively. Each patient underwent a median of 5 (IQR 3-10) echocardiograms over a median follow-up of 8.6 years (range 0.1-39.3 years). At 30 years, DORV-TGA patients demonstrated greater annular (p<0.001), SoV (p=0.039), and STJ (p=0.041) dilatation relative to d-TGA-IVS patients. On multivariable analysis, intrinsic anatomy, older age at ASO, at least mild AR at baseline, and high-risk root dilatation were associated with moderate-severe AR and neo-aortic valve or root reintervention at late follow-up (all p<0.05).<br /><b>Conclusions</b><br />Longitudinal surveillance of the neo-aortic root is warranted long after the ASO.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Am Coll Cardiol: 30 Oct 2023; epub ahead of print</small></div>

<div><h4>Psychosocial Factors of Women Presenting With Myocardial Infarction With or Without Obstructive Coronary Arteries.</h4><i>Hausvater A, Spruill TM, Xia Y, Smilowitz NR, ... Hochman JS, Reynolds HR</i><br /><b>Background</b><br />Women with myocardial infarction (MI) are more likely to have elevated stress levels and depression than men with MI.<br /><b>Objectives</b><br />We investigated psychosocial factors in women with myocardial infarction with nonobstructive coronary arteries (MINOCA) and those with MI and obstructive coronary artery disease (CAD).<br /><b>Methods</b><br />Women with MI enrolled in a multicenter study and completed measures of perceived stress (Perceived Stress Scale-4) and depressive symptoms (Patient Health Questionnaire-2) at the time of MI (baseline) and 2 months later. Stress, depression, and changes over time were compared between MI subtypes.<br /><b>Results</b><br />We included 172 MINOCA and 314 MI-CAD patients. Women with MINOCA were younger (age 59.4 years vs 64.2 years; P < 0.001) and more diverse than those with MI-CAD. Women with MINOCA were less likely to have high stress (Perceived Stress Scale-4 ≥6) at the time of MI (51.0% vs 63.0%; P = 0.021) and at 2 months post-MI (32.5% vs 46.3%; P = 0.019) than women with MI-CAD. There was no difference in elevated depressive symptoms (Patient Health Questionnaire-2 ≥2) at the time of MI (36% vs 43%; P = 0.229) or at 2 months post-MI (39% vs 40%; P = 0.999). No differences in the rate of 2-month decline in stress and depression scores were observed between groups.<br /><b>Conclusions</b><br />Stress and depression are common among women at the time of and 2 months after MI. MINOCA patients were less likely to report high stress compared with MI-CAD patients, but the frequency of elevated depressive symptoms did not differ between the 2 groups. Stress and depressive symptoms decreased in both MI-CAD and MINOCA patients over time.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 24 Oct 2023; 82:1649-1658</small></div>

<div><h4>Impact of Positron Emission Tomographic Myocardial Perfusion Imaging on Patient Selection for Revascularization.</h4><i>Patel KK, McGhie AI, Kennedy KF, Thompson RC, ... Shaw LJ, Bateman TM</i><br /><b>Background</b><br />Positron emission tomography (PET) myocardial perfusion imaging (MPI) quantifies left ventricular ejection fraction (LVEF) at peak stress. PET LVEF reserve (LVEF-R = stress LVEF - rest LVEF) offers diagnostic and prognostic value.<br /><b>Objectives</b><br />The purpose of this study was to determine if PET LVEF-R identifies patients with survival benefit postrevascularization.<br /><b>Methods</b><br />We followed 14,649 unique consecutive patients undergoing <sup>82</sup>Rb rest/stress PET MPI from January 2010 to January 2016 (excluding known cardiomyopathy). Adjusted Cox models were built to predict all-cause death, and the 3-way interaction of known coronary artery disease (CAD) (prior myocardial infarction/revascularization), LVEF-R, and 90-day revascularization was tested.<br /><b>Results</b><br />Known CAD was present in 4,982 (34.0%). Ischemia was detected in 5,396 (36.8%; ≥10% in 1,909 [13%]). Mean LVEF-R was 4.2% ± 5.7%, and was ≤0, 1 to 5, and >5 in 3,349 (22.9%), 5,266 (35.9%), and 6,034 (41.2%). Over median follow-up of 3.4 years (IQR: 1.9-5.2 years), 1,324 (8.1%) had 90-day revascularization, and there were 2,192 (15.0%) deaths. In multivariable modeling, there was a significant 3-way interaction among known CAD, LVEF-R, and 90-day revascularization (P = 0.025), such that LVEF-R ≤0 identified patients with survival benefit with 90-day revascularization in those without prior CAD (interaction P = 0.005), independently beyond percent ischemia and myocardial flow reserve. Among patients with known CAD, LVEF-R was not prognostic of death (HR: 0.99; 95% CI: 0.98-1.02; P = 0.98).<br /><b>Conclusions</b><br />A lack of augmentation or drop in LVEF with vasodilator stress on PET MPI independently identifies patients who have better survival with revascularization within 90 days post-MPI compared with medical therapy, in absence of prior myocardial infarction or revascularization. Multiparametric assessment of ischemia with PET can optimize post-test management.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 24 Oct 2023; 82:1662-1672</small></div>

<div><h4>Systematic Assessment of Shock Severity in Postoperative Cardiac Surgery Patients.</h4><i>Roeschl T, Hinrichs N, Hommel M, Pfahringer B, ... Schoenrath F, Meyer A</i><br /><b>Background</b><br />The Society for Cardiovascular Angiography and Interventions (SCAI) shock classification has been shown to provide robust mortality risk stratification in a variety of cardiovascular patients.<br /><b>Objectives</b><br />This study sought to evaluate the SCAI shock classification in postoperative cardiac surgery intensive care unit (CSICU) patients.<br /><b>Methods</b><br />This study retrospectively analyzed 26,792 postoperative CSICU admissions at a heart center between 2012 and 2022. Patients were classified into SCAI shock stages A to E using electronic health record data. Moreover, the impact of late deterioration (LD) as an additional risk modifier was investigated.<br /><b>Results</b><br />The proportions of patients in SCAI shock stages A to E were 24.4%, 18.8%, 8.4%, 35.5%, and 12.9%, and crude hospital mortality rates were 0.4%, 0.6%, 3.3%, 4.9%, and 30.2%, respectively. Similarly, the prevalence of postoperative complications and organ dysfunction increased across SCAI shock stages. After multivariable adjustment, each higher SCAI shock stage was associated with increased hospital mortality (adjusted OR: 1.26-16.59) compared with SCAI shock stage A, as was LD (adjusted OR: 8.2). The SCAI shock classification demonstrated a strong diagnostic performance for hospital mortality (area under the receiver operating characteristic: 0.84), which noticeably increased when LD was incorporated into the model (area under the receiver operating characteristic: 0.90).<br /><b>Conclusions</b><br />The SCAI shock classification effectively risk-stratifies postoperative CSICU patients for mortality, postoperative complications, and organ dysfunction. Its application could, therefore, be extended to the field of cardiac surgery as a triage tool in postoperative care and as a selection criterion in research.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 24 Oct 2023; 82:1691-1706</small></div>

<div><h4>The Mortality Burden of Untreated Aortic Stenosis.</h4><i>Généreux P, Sharma RP, Cubeddu RJ, Aaron L, ... Leon MB, Gillam LD</i><br /><b>Background</b><br />The American College of Cardiology/American Heart Association guidelines recommend the assessment and grading of severity of aortic stenosis (AS) as mild, moderate, or severe, per echocardiogram, and recommend aortic valve replacement (AVR) when the AS is severe.<br /><b>Objectives</b><br />The authors sought to describe mortality rates across the entire spectrum of untreated AS from a contemporary, large, real-world database.<br /><b>Methods</b><br />We analyzed a deidentified real-world data set including 1,669,536 echocardiographic reports (1,085,850 patients) from 24 U.S. hospitals (egnite Database, egnite). Patients >18 years of age were classified by diagnosed AS severity. Untreated mortality and treatment rates were examined with Kaplan-Meier (KM) estimates, with results compared using the log-rank test. Multivariate hazards analysis was performed to assess associations with all-cause mortality.<br /><b>Results</b><br />Among 595,120 patients with available AS severity assessment, the KM-estimated 4-year unadjusted, untreated, all-cause mortality associated with AS diagnosis of none, mild, mild-to-moderate, moderate, moderate-to-severe, or severe was 13.5% (95% CI: 13.3%-13.7%), 25.0% (95% CI: 23.8%-26.1%), 29.7% (95% CI: 26.8%-32.5%), 33.5% (95% CI: 31.0%-35.8%), 45.7% (95% CI: 37.4%-52.8%), and 44.9% (95% CI: 39.9%-49.6%), respectively. Results were similar when adjusted for informative censoring caused by treatment. KM-estimated 4-year observed treatment rates were 0.2% (95% CI: 0.2%-0.2%), 1.0% (95% CI: 0.7%-1.3%), 4.2% (95% CI: 2.0%-6.3%), 11.4% (95% CI: 9.5%-13.3%), 36.7% (95% CI: 31.8%-41.2%), and 60.7% (95% CI: 58.0%-63.3%), respectively. After adjustment, all degrees of AS severity were associated with increased mortality.<br /><b>Conclusions</b><br />Patients with AS have high mortality risk across all levels of untreated AS severity. Aortic valve replacement rates remain low for patients with severe AS, suggesting that more research is needed to understand barriers to diagnosis and appropriate approach and timing for aortic valve replacement.<br /><br />Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 20 Oct 2023; epub ahead of print</small></div>

<div><h4>Risk of Type B Dissection in Marfan Syndrome: The Cornell Aortic Aneurysm Registry.</h4><i>Narula N, Devereux RB, Arbustini E, Ma X, ... Malonga GP, Roman MJ</i><br /><b>Background</b><br />With preventive aortic grafting decreasing the incidence of type A dissections in Marfan syndrome (MFS), most dissections are now type B, for which risk factors remain largely uncertain.<br /><b>Objectives</b><br />We explored the determinants of type B dissection risk in a large, single-center MFS registry.<br /><b>Methods</b><br />Demographic and anthropometric features, cardiovascular disease, and surgical history were compared in patients with MFS with and without type B dissection.<br /><b>Results</b><br />Of 336 patients with MFS, 47 (14%) experienced a type B dissection (vs type A in 9%). Patients with type B dissection were more likely to have undergone elective aortic root replacement (ARR) (79 vs 46%; P < 0.001). Of the patients, 55% had type B dissection a mean of 13.3 years after ARR, whereas 45% experienced type B dissection before or in the absence of ARR; 41 patients (87%) were aware of their MFS diagnosis before type B dissection. Among those with predissection imaging, the descending aorta was normal or minimally dilated (<4.0 cm) in 88%. In multivariable analyses, patients with type B dissection were more likely to have undergone ARR and independent mitral valve surgery, to have had a type II dissection, and to have lived longer.<br /><b>Conclusions</b><br />In our contemporary cohort, type B dissections are more common than type A dissections and occur at traditional nonsurgical thresholds. The associations of type B dissection with ARR, independent mitral valve surgery, and type II dissection suggest a more severe phenotype in the setting of prolonged life expectancy.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 18 Oct 2023; epub ahead of print</small></div>

<div><h4>Clopidogrel versus Aspirin Monotherapy Beyond 1 Year After PCI: STOPDAPT-2 5-Year Results.</h4><i>Watanabe H, Morimoto T, Natsuaki M, Yamamoto K, ... Kimura T, STOPDAPT-2 investigators</i><br /><b>Background</b><br />It remains unclear whether clopidogrel is better suited than aspirin as the long-term antiplatelet monotherapy following dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI).<br /><b>Objectives</b><br />We compared clopidogrel monotherapy following 1-month DAPT (clopidogrel group) with aspirin monotherapy following 12-month DAPT (aspirin group) after PCI for 5 years.<br /><b>Methods</b><br />STOPDAPT-2 is a multicenter, open-label, adjudicator-blinded, randomized clinical trial conducted in Japan. Patients who underwent PCI with cobalt-chromium everolimus-eluting stents were randomized in a 1-to-1 fashion either to clopidogrel or aspirin groups. The primary endpoint was a composite of cardiovascular outcomes (cardiovascular death, myocardial infarction, stroke, or definite stent thrombosis) or major bleeding (TIMI major or minor bleeding).<br /><b>Results</b><br />Among 3005 study patients (Age: 68.6±10.7 years; Women: 22.3%; Acute coronary syndrome: 38.3%), 2934 patients (97.6%) completed 5-year follow-up (adherence to the study drugs at 395 days: 84.7% and 75.9%). Clopidogrel group compared with aspirin group was noninferior, but not superior for the primary endpoint (11.75% and 13.57%; HR 0.85 [95%CI: 0.70-1.05], P<sub>noninferiority</sub><0.001, P<sub>superiority</sub>=0.13), while it was superior for the cardiovascular outcomes (8.61% and 11.05%, HR 0.77 [95%CI: 0.61-0.97], P=0.03), and not superior for major bleeding (4.44% and 4.92%; HR 0.89 [95%CI: 0.64-1.25], P=0.51). By the 1-year landmark analysis, clopidogrel was numerically, but not significantly, superior to aspirin for cardiovascular events (6.79% and 8.68%; HR 0.77 [95%CI: 0.59-1.01], P=0.06) without difference in major bleeding (3.99% and 3.32%; HR 1.23 [95%CI: 0.84-1.81], P=0.31).<br /><b>Conclusions</b><br />Clopidogrel might be an attractive alternative to aspirin with a borderline ischemic benefit beyond 1-year after PCI.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Am Coll Cardiol: 18 Oct 2023; epub ahead of print</small></div>

<div><h4>Guiding Intervention for Complex Coronary Lesions by Optical Coherence Tomography or Intravascular Ultrasound.</h4><i>Kang DY, Ahn JM, Yun SC, Hur SH, ... Park DW, OCTIVUS Investigators*</i><br /><b>Background</b><br />Optical coherence tomography (OCT) and intravascular ultrasound (IVUS) have shown comparable outcomes in guiding percutaneous coronary intervention (PCI). However, their comparative effectiveness in complex coronary-artery lesions remains unclear.<br /><b>Objectives</b><br />This study compared the effectiveness and safety of OCT-guided vs. IVUS-guided PCI for complex coronary-artery lesions.<br /><b>Methods</b><br />This was a pre-specified, main subgroup analysis of complex coronary-artery lesions in the OCTIVUS trial, which included unprotected left main disease, bifurcation disease, an aorto-ostial lesion, a chronic total occlusion, a severely calcified lesion, an in-stent restenotic lesion, a diffuse long lesion, or multivessel PCI. The primary end-point was a composite of death from cardiac causes, target-vessel-related myocardial infarction, or ischemia-driven target-vessel revascularization.<br /><b>Results</b><br />In 2008 randomized patients, 1475 (73.5%) underwent imaging-guided PCI for complex coronary-artery lesions; 719 (48.7%) received OCT-guided and 756 (51.3%) received IVUS-guided PCI. At a median follow-up of 2.0 years, primary end-point event had occurred in 47 (6.5%) patients in the OCT-guided group and in 56 (7.4%) patients in the IVUS-guided group (hazard ratio [HR] 0.87; 95% confidence interval [CI] 0.59-1.29; P=0.50). These findings were consistent in adjusted analyses. The incidence of contrast-induced nephropathy was similar between two groups (1.9% vs. 1.5%; P=0.46). The incidence of major procedural complications was lower in the OCT-guided group than the IVUS-guided group (1.7% vs. 3.4%; P=0.03).<br /><b>Conclusions</b><br />Among patients with complex coronary-artery lesions, OCT-guided PCI showed a similar risk of primary-composite event of death from cardiac causes, target-vessel-related myocardial infarction, or target-vessel revascularization as compared with IVUS-guided PCI.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Am Coll Cardiol: 17 Oct 2023; epub ahead of print</small></div>

<div><h4>Comparison of Antiplatelet Monotherapies After Percutaneous Coronary Intervention According to Clinical, Ischemic, and Bleeding Risks.</h4><i>Yang S, Kang J, Park KW, Hur SH, ... Koo BK, Kim HS</i><br /><b>Background</b><br />Clopidogrel was superior to aspirin monotherapy in secondary prevention after percutaneous coronary intervention (PCI).<br /><b>Objectives</b><br />The purpose of this study was to evaluate the benefits of clopidogrel across high-risk subgroups <br /><b>Methods:</b><br/>This was a post hoc analysis of the HOST-EXAM (Harmonizing Optimal Strategy for Treatment of coronary artery diseases-EXtended Antiplatelet Monotherapy) trial that randomly assigned patients who were event free for 6 to 18 months post-PCI on dual antiplatelet therapy (DAPT) to clopidogrel or aspirin monotherapy. Two clinical risk scores were used for risk stratification: the DAPT score and the Thrombolysis In Myocardial Infarction Risk Score for Secondary Prevention (TRS 2°P) (the sum of age ≥75 years, diabetes, hypertension, current smoking, peripheral artery disease, stroke, coronary artery bypass grafting, heart failure, and renal dysfunction). The primary composite endpoint was a composite of all-cause death, nonfatal myocardial infarction, stroke, readmission because of acute coronary syndrome, and major bleeding (Bleeding Academic Research Consortium type ≥3) at 2 years after randomization.<br /><b>Results</b><br />Among 5,403 patients, clopidogrel monotherapy showed a lower rate of the primary composite endpoint than aspirin monotherapy (HR: 0.73; 95% CI: 0.59-0.90). The benefit of clopidogrel over aspirin was consistent regardless of TRS 2°P (high TRS 2°P [≥3] group: HR: 0.65 [95% CI: 0.44-0.96]; and low TRS 2°P [<3] group: HR: 0.77 [95% CI: 0.60-0.99]) (P for interaction = 0.454) and regardless of DAPT score (high DAPT score [≥2] group: HR: 0.68 [95% CI: 0.46-1.00]; and low DAPT score [<2] group: HR: 0.75 [95% CI: 0.59-0.96]) (P for interaction = 0.662). The association was similar for the individual outcomes.<br /><b>Conclusions</b><br />The beneficial effect of clopidogrel over aspirin monotherapy was consistent regardless of clinical risk or relative ischemic and bleeding risks compared with aspirin monotherapy. (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis- EXtended Antiplatelet Monotherapy [HOST-EXAM]; NCT02044250).<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 17 Oct 2023; 82:1565-1578</small></div>

<div><h4>10-Year Cardiovascular Risk in Patients With Newly Diagnosed Type 2 Diabetes Mellitus.</h4><i>Gyldenkerne C, Mortensen MB, Kahlert J, Thrane PG, ... Thomsen RW, Maeng M</i><br /><b>Background</b><br />Contemporary data on cardiovascular disease (CVD) risk in patients with newly diagnosed type 2 diabetes mellitus (T2DM) is needed to guide appropriate preventive management.<br /><b>Objectives</b><br />The authors sought to investigate sex- and age-specific 10-year CVD risk in patients with newly diagnosed T2DM compared with the general population.<br /><b>Methods</b><br />A cohort study was conducted of all Danish patients with T2DM diagnosed between 2006 and 2013 (n = 142,587) and sex- and age-matched individuals from the general population (n = 388,410), all without prior atherosclerotic CVD. Ten-year CVD risk (myocardial infarction, stroke, and fatal CVD) was estimated.<br /><b>Results</b><br />A total of 52,471 CVD events were recorded. Compared with the general population, the 10-year CVD risks were higher in patients with T2DM in both sexes and across all age groups, especially among younger individuals. For example, patients aged 40 to 49 years had the largest 10-year CVD risk difference (T2DM 6.1% vs general population 3.3%; risk difference: 2.8%, subdistribution HR: 1.91; 95% CI: 1.76-2.07). The age when a given CVD risk was reached differed substantially between the cohorts. Thus, a 10-year CVD risk of 5% was reached at age 43 in men with T2DM compared with 12 years later, at age 55, in men without T2DM. A 10-year CVD risk of 5% was reached at age 51 in women with T2DM and 10 years later, at age 61, in women without T2DM.<br /><b>Conclusions</b><br />Newly diagnosed T2DM increased 10-year CVD risk across both sexes and all age groups, especially among younger patients, with CVD occurring ≤12 years earlier than in general population individuals.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 17 Oct 2023; 82:1583-1594</small></div>

<div><h4>Flurpiridaz F-18 PET Myocardial Perfusion Imaging in Patients With Suspected Coronary Artery Disease.</h4><i>Maddahi J, Agostini D, Bateman TM, Bax JJ, ... Tranquart F, Udelson JE</i><br /><b>Background</b><br />Flurpiridaz F-18 (flurpiridaz) is a novel positron emission tomography (PET) myocardial perfusion imaging tracer.<br /><b>Objectives</b><br />The purpose of this study was to further assess the diagnostic efficacy and safety of flurpiridaz for the detection and evaluation of coronary artery disease (CAD) defined as ≥50% stenosis by quantitative invasive coronary angiography (ICA).<br /><b>Methods</b><br />In this second phase 3 prospective multicenter clinical study, 730 patients with suspected CAD from 48 clinical sites in the United States, Canada, and Europe were enrolled. Patients underwent 1-day rest/stress flurpiridaz PET and 1- or 2-day rest-stress Tc-99m-labeled single photon emission computed tomography (SPECT) before ICA. PET and SPECT images were read by 3 experts blinded to clinical and ICA data.<br /><b>Results</b><br />A total of 578 patients (age 63.7 ± 9.5 years) were evaluable; 32.5% were women, 52.3% had body mass index ≥30 kg/m<sup>2</sup>, and 33.6% had diabetes. Flurpiridaz PET met the efficacy endpoints of the study; its sensitivity and specificity were significantly higher than the prespecified threshold value by 2 of the 3 readers. The sensitivity of flurpiridaz PET was higher than SPECT (80.3% vs 68.7%; P = 0.0003) and its specificity was noninferior to SPECT (63.8% vs 61.7%; P = 0.0004). PET area under the receiver-operating characteristic curves were higher than SPECT in the overall population (0.80 vs 0.68; P < 0.001), women, and obese patients (P < 0.001 for both). Flurpiridaz PET was superior to SPECT (P < 0.001) for perfusion defect size/severity evaluation, image quality, diagnostic certainty, and radiation exposure. Flurpiridaz PET was safe and well tolerated.<br /><b>Conclusions</b><br />This second flurpiridaz PET myocardial perfusion imaging trial shows that flurpiridaz has utility as a new tracer for CAD detection, specifically in women and obese patients. (An International Study to Evaluate Diagnostic Efficacy of Flurpiridaz [18F] Injection PET MPI in the Detection of Coronary Artery Disease [CAD]; NCT03354273).<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 17 Oct 2023; 82:1598-1610</small></div>

<div><h4>Magnetic Resonance Spectroscopy of Brain Metabolism in Fetuses With Congenital Heart Disease.</h4><i>Andescavage NN, Pradhan S, Gimovsky AC, Kapse K, ... du Plessis AJ, Limperopoulos C</i><br /><b>Background</b><br />Congenital heart disease (CHD) remains a significant risk factor for neurologic injury because altered fetal hemodynamics may be unable to support typical brain development during critical periods of growth and maturation.<br /><b>Objectives</b><br />The primary objective was to assess differences in the cerebral biochemical profile between healthy fetuses and fetuses with complex CHD and to relate these with infant outcomes.<br /><b>Methods</b><br />Pregnant participants underwent fetal magnetic resonance imaging with cerebral proton magnetic resonance spectroscopy acquisitions as part of a prospective observational study. Cerebral metabolites of N-acetyl aspartate, creatine, choline, myo-inositol, scyllo-inositol, lactate, and relevant ratios were quantified using LCModel.<br /><b>Results</b><br />We acquired 503 proton magnetic resonance spectroscopy images (controls = 333; CHD = 170) from 333 participants (controls = 221; CHD = 112). Mean choline levels were higher in CHD compared with controls (CHD 2.47 IU [Institutional Units] ± 0.44 and Controls 2.35 IU ± 0.45; P = 0.02), whereas N-acetyl aspartate:choline ratios were lower among CHD fetuses compared with controls (CHD 1.34 ± 0.40 IU vs controls 1.44 ± 0.48 IU; P = 0.001). Cerebral lactate was detected in all cohorts but increased in fetuses with transposition of the great arteries and single-ventricle CHD (median: 1.63 [IQR: 0.56-3.27] in transposition of the great arteries and median: 1.28 [IQR: 0-2.42] in single-ventricle CHD) compared with 2-ventricle CHD (median: 0.79 [IQR: 0-1.45]). Cerebral lactate also was associated with increased odds of death before discharge (OR: 1.75; P = 0.04).<br /><b>Conclusions</b><br />CHD is associated with altered cerebral metabolites in utero, particularly in the third trimester period of pregnancy, which is characterized by exponential brain growth and maturation, and is associated with survival to hospital discharge. The long-term neurodevelopmental consequences of these findings warrant further study.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Am Coll Cardiol: 17 Oct 2023; 82:1614-1623</small></div>

<div><h4>International Consensus on Differential Diagnosis and Management of Patients With Danon Disease: JACC State-of-the-Art Review.</h4><i>Hong KN, Eshraghian EA, Arad M, Argirò A, ... Garcia-Pavia P, Adler ED</i><br /><AbstractText>Danon disease is a rare X-linked autophagic vacuolar cardioskeletal myopathy associated with severe heart failure that can be accompanied with extracardiac neurologic, skeletal, and ophthalmologic manifestations. It is caused by loss of function variants in the LAMP2 gene and is among the most severe and penetrant of the genetic cardiomyopathies. Most patients with Danon disease will experience symptomatic heart failure. Male individuals generally present earlier than women and die of either heart failure or arrhythmia or receive a heart transplant by the third decade of life. Herein, the authors review the differential diagnosis of Danon disease, diagnostic criteria, natural history, management recommendations, and recent advances in treatment of this increasingly recognized and extremely morbid cardiomyopathy.</AbstractText><br /><br />Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 17 Oct 2023; 82:1628-1647</small></div>

<div><h4>Management of Adults With Anomalous Aortic Origin of the Coronary Arteries: State-of-the-Art Review.</h4><i>Gaudino M, Di Franco A, Arbustini E, Bacha E, ... Zimpfer D, Mery CM</i><br /><AbstractText>As a result of increasing adoption of imaging screening, the number of adult patients with a diagnosis of anomalous aortic origin of the coronary arteries (AAOCA) has grown in recent years. Existing guidelines provide a framework for management and treatment, but patients with AAOCA present with a wide range of anomalies and symptoms that make general recommendations of limited applicability. In particular, a large spectrum of interventions can be used for treatment, and there is no consensus on the optimal approach to be used. In this paper, a multidisciplinary group of clinical and interventional cardiologists and cardiac surgeons performed a systematic review and critical evaluation of the available evidence on the interventional treatment of AAOCA in adult patients. Using a structured Delphi process, the group agreed on expert recommendations that are intended to complement existing clinical practice guidelines.</AbstractText><br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 16 Oct 2023; epub ahead of print</small></div>

<div><h4>Health Status after Transcatheter Tricuspid-Valve Repair in Patients with Severe Tricuspid Regurgitation: Results from the TRILUMINATE Pivotal Trial.</h4><i>Arnold SV, Goates S, Sorajja P, Adams DH, ... Cohen DJ, TRILUMINATE Pivotal Trial Investigators</i><br /><b>Background</b><br />In the TRILUMINATE Pivotal trial, tricuspid transcatheter edge-to-edge repair (T-TEER) reduced TR and improved health status compared with medical therapy alone with no benefit on heart failure hospitalizations or survival.<br /><b>Objective</b><br />To better understand the health status benefits of T-TEER within the TRILUMINATE Pivotal trial.<br /><b>Methods</b><br />TRILUMINATE randomized patients with severe TR to T-TEER (n=175) or medical therapy (n=175). Health status was assessed at baseline and at 1, 6, and 12 months with the KCCQ (range 0-100; higher=better), which was compared between treatment groups using mixed effects linear regression. Alive and well was defined as KCCQ-OS >=60 and no decline from baseline of >10 points at 1 year.<br /><b>Results</b><br />Compared with medical therapy, T-TEER significantly improved health status at 1 month (mean between-group difference in KCCQ-OS 9.4 points, 95% CI 5.3-13.4), with a small additional improvement at 1 year (mean between-group difference 10.4 points, 95% CI 6.3-14.6). T-TEER patients were more likely to be alive and well at 1 year (T-TEER vs. medical therapy: 74.8% vs. 45.9%, p<0.001), with a number needed-to-treat of 3.5. Interaction analyses demonstrated that the benefit of T-TEER diminished as baseline KCCQ-OS increased (p<sub>int</sub><0.001). Exploratory analyses suggested that much of the health status benefit of T-TEER could be explained by TR reduction and that improvement in health status after T-TEER was strongly correlated with reduced 1-year mortality and heart failure hospitalization.<br /><b>Conclusion</b><br />T-TEER with the TriClip system resulted in substantial and sustained health status improvement in patients with severe TR compared with medical therapy alone.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Am Coll Cardiol: 16 Oct 2023; epub ahead of print</small></div>

<div><h4>Cardiac Re-operation or Transcatheter Mitral Valve Replacement for Patients with Failed Mitral Prostheses.</h4><i>Ueyama HA, Miyamoto Y, Watanabe A, Gotanda H, ... Kuno T, Tsugawa Y</i><br /><b>Background</b><br />Evidence is limited regarding patient outcomes comparing redo surgical mitral valve replacement (redo SMVR) versus transcatheter mitral valve replacement (TMVR) for failed prostheses.<br /><b>Objectives</b><br />To compare the outcomes of redo SMVR versus TMVR in patients with failed prostheses, as well as evaluate the association between case volume and outcomes.<br /><b>Methods</b><br />Medicare beneficiaries aged ≥65 years who underwent redo SMVR or TMVR for failed mitral prostheses between 2016 and 2020 were included. Primary endpoint was mid-term (up to 3 years) major adverse cardiovascular events (MACE), including all-cause death, heart failure rehospitalization, stroke, or reintervention. Propensity score-matched analysis was used.<br /><b>Results</b><br />A total of 4,293 patients were included (redo SMVR:64%;TMVR:36%). TMVR recipients were older with higher comorbidity burden. In matched cohort (n=1,317 in each group), mid-term risk of MACE was similar (adjusted HR, 0.92; 95%CI, 0.80-1.04; p=0.2). However, landmark analysis revealed a lower risk of MACE with TMVR in the first 6 months (adjusted HR, 0.75; 95%CI, 0.63-0.88; p<0.001) albeit a higher risk beyond 6 months (adjusted HR, 1.28; 95%CI, 1.04-1.58; p=0.02). Increasing procedural volume was associated with decreased risk of mid-term MACE after redo SMVR (p=0.001), but not after TMVR (p=0.3).<br /><b>Conclusions</b><br />In this large cohort of Medicare beneficiaries with failed mitral prostheses, outcomes were similar between redo SMVR and TMVR at 3 years, with TMVR showing lower initial risk but a higher risk of MACE after 6 months. These findings highlight the importance of striking a balance between surgical risk, anticipated longevity, and hospital expertise when selecting interventions.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Am Coll Cardiol: 16 Oct 2023; epub ahead of print</small></div>

<div><h4>Association of Age and Sex With Use of Transcatheter Aortic Valve Replacement in France.</h4><i>Prosperi-Porta G, Nguyen V, Willner N, Dreyfus J, ... Chevreul K, Messika-Zeitoun D</i><br /><b>Background</b><br />Current guidelines recommend selecting surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR) based on age, comorbidities, and surgical risk. Nevertheless, reports from the United States suggest a rapid expansion of TAVR in young patients.<br /><b>Objectives</b><br />The authors sought to evaluate the trends in TAVR uptake at a nationwide level in France according to age and sex.<br /><b>Methods</b><br />Using a nationwide administrative database, we evaluated age- and sex-related trends in TAVR uptake, patient demographics, and in-hospital outcomes between 2015 and 2020.<br /><b>Results</b><br />A total of 107,397 patients (44.0% female) underwent an isolated aortic valve replacement (AVR) (59.1% TAVR, 40.9% SAVR). In patients <65 years of age, the proportion of TAVR increased by 63.2% (P < 0.001) from 2015 to 2020 but remained uncommon at 11.1% of all AVR by 2020 (12.4% in females, 10.6% in males) while TAVR was the dominant modality in patients ≥65 years of age. In patients undergoing TAVR, the Charlson comorbidity index (CCI) (P = 0.119 for trend) and in-hospital mortality (P = 0.740 for trend) remained unchanged in patients <65 years of age but declined in those ≥65 years of age irrespective of sex (all P < 0.001 for trends). Females were older (P < 0.001), had lower CCI (P < 0.001), were more likely to undergo TAVR (P < 0.001), and experienced higher in-hospital mortality (TAVR, P = 0.015; SAVR, P < 0.001) that persisted despite adjustment for age and CCI.<br /><b>Conclusions</b><br />In France, the use of TAVR remained uncommon in young patients, predominantly restricted to those at high risk. Important sex differences were observed in patent demographics, selection of AVR modality, and patient outcomes. Additional research evaluating the long-term impact of TAVR use in young patients and prospective data evaluating sex differences in AVR modality selection and outcomes are needed.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 11 Oct 2023; epub ahead of print</small></div>

<div><h4>Performance of the ACC/AHA Pooled Cohort Cardiovascular Risk Equations in Clinical Practice.</h4><i>Medina-Inojosa JR, Somers VK, Garcia M, Thomas RJ, ... Mulvagh SL, Lopez-Jimenez F</i><br /><b>Background</b><br />The performance of the American College of Cardiology/American Heart Association pooled cohort equation (PCE) for atherosclerotic cardiovascular disease (ASCVD) in real-world clinical practice has not been evaluated extensively.<br /><b>Objectives</b><br />The goal of this study was to test the performance of PCE to predict ASCVD risk in the community, and determine if including individuals with values outside the PCE range (ie, age, blood pressure, cholesterol) or statin therapy initiation over follow-up would significantly affect PCE predictive capabilities.<br /><b>Methods</b><br />The PCE was validated in a community-based cohort of consecutive patients who sought primary care in Olmsted County, Minnesota, between 1997 and 2000, followed-up through 2016. Inclusion criteria were similar to those of PCE derivation. Patient information was ascertained by using the record linkage system of the Rochester Epidemiology Project. ASCVD events (nonfatal and fatal myocardial infarction and ischemic stroke) were validated in duplicate. Calculated and observed ASCVD risk and c-statistics were compared across predefined groups.<br /><b>Results</b><br />This study included 30,042 adults, with a mean age of 48.5 ± 12.2 years; 46% were male. Median follow-up was 16.5 years, truncated at 10 years for this analysis. Mean ASCVD risk was 5.6% ± 8.73%. There were 1,555 ASCVD events (5.2%). The PCE revealed good performance overall (c-statistic 0.78) and in sex and race subgroups; it was highest among non-White female subjects (c-statistic 0.81) and lowest in White male subjects (c-statistic 0.77). Out-of-range values and initiation of statin medication did not affect model performance.<br /><b>Conclusions</b><br />The PCE performed well in a community cohort representing real-world clinical practice. Values outside PCE ranges and initiation of statin medication did not affect performance. These results have implications for the applicability of current strategies for the prevention of ASCVD.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 10 Oct 2023; 82:1499-1508</small></div>

<div><h4>Outcomes of Heart Transplant Donation After Circulatory Death.</h4><i>Siddiqi HK, Trahanas J, Xu M, Wells Q, ... Shah A, Schlendorf K</i><br /><b>Background</b><br />Heart transplantation using donation after circulatory death (DCD) allografts is increasingly common, expanding the donor pool and reducing transplant wait times. However, data remain limited on clinical outcomes.<br /><b>Objectives</b><br />We sought to compare 6-month and 1-year clinical outcomes between recipients of DCD hearts, most of them recovered with the use of normothermic regional perfusion (NRP), and recipients of donation after brain death (DBD) hearts.<br /><b>Methods</b><br />We conducted a single-center retrospective observational study of all adult heart-only transplants from January 2020 to January 2023. Recipient and donor data were abstracted from medical records and the United Network for Organ Sharing registry, respectively. Survival analysis and Cox regression were used to compare the groups.<br /><b>Results</b><br />During the study period, 385 adults (median age 57.4 years [IQR: 48.0-63.7 years]) underwent heart-only transplantation, including 122 (32%) from DCD donors, 83% of which were recovered with the use of NRP. DCD donors were younger and had fewer comorbidities than DBD donors. DCD recipients were less often hospitalized before transplantation and less likely to require pretransplantation temporary mechanical circulatory support compared with DBD recipients. There were no significant differences between groups in 1-year survival, incidence of severe primary graft dysfunction, treated rejection during the first year, or likelihood of cardiac allograft vasculopathy at 1 year after transplantation.<br /><b>Conclusions</b><br />In the largest single-center comparison of DCD and DBD heart transplantations to date, outcomes among DCD recipients are noninferior to those of DBD recipients. This study adds to the published data supporting DCD donors as a safe means to expand the heart donor pool.<br /><br />Copyright © 2023 American College of Cardiology Foundation. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 10 Oct 2023; 82:1512-1520</small></div>

<div><h4>Prognostic Implications of the Extent of Cardiac Damage in Patients With Fabry Disease.</h4><i>Meucci MC, Lillo R, Del Franco A, Monda E, ... Olivotto I, Graziani F</i><br /><b>Background</b><br />There is limited evidence on the risk stratification of cardiovascular outcomes in patients with Fabry disease (FD).<br /><b>Objectives</b><br />This study sought to classify FD patients into disease stages, based on the extent of the cardiac damage evaluated by echocardiography, and to assess their prognostic impact in a multicenter cohort.<br /><b>Methods</b><br />Patients with FD from 5 Italian referral centers were categorized into 4 stages: stage 0, no cardiac involvement; stage 1, left ventricular (LV) hypertrophy (LV maximal wall thickness >12 mm); stage 2, left atrium (LA) enlargement (LA volume index >34 mL/m<sup>2</sup>); stage 3, ventricular impairment (LV ejection fraction <50% or E/e\' ≥15 or TAPSE <17 mm). The study endpoint was the composite of all-cause death, hospitalization for heart failure, new-onset atrial fibrillation, major bradyarrhythmias or tachyarrhythmias, and ischemic stroke.<br /><b>Results</b><br />A total of 314 patients were included. Among them, 174 (56%) were classified as stage 0, 41 (13%) as stage 1, 57 (18%) as stage 2 and 42 (13%) as stage 3. A progressive increase in the composite event rate at 8 years was observed with worsening stages of cardiac damage (log-rank P < 0.001). On multivariable Cox regression analysis, the staging was independently associated with the risk of cardiovascular events (HR: 2.086 per 1-stage increase; 95% CI: 1.487-2.927; P < 0.001). Notably, cardiac staging demonstrated a stronger and additive prognostic value, as compared with the degree of LV hypertrophy.<br /><b>Conclusions</b><br />In FD patients, a novel staging classification of cardiac damage, evaluated by echocardiography, is strongly associated with cardiovascular outcomes and may be helpful to refine risk stratification.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 10 Oct 2023; 82:1524-1534</small></div>

<div><h4>Antithrombotic Therapy for Primary and Secondary Prevention of Ischemic Stroke: JACC State-of-the-Art Review.</h4><i>Greco A, Occhipinti G, Giacoppo D, Agnello F, ... Raffo C, Capodanno D</i><br /><AbstractText>Stroke is a devastating condition with significant morbidity and mortality worldwide. Antithrombotic therapy plays a crucial role in both primary and secondary prevention of stroke events. Single or dual antiplatelet therapy is generally preferred in cases of large-artery atherosclerosis and small-vessel disease, whereas anticoagulation is recommended in conditions of blood stasis or hypercoagulable states that mostly result in red thrombi. However, the benefit of antithrombotic therapies must be weighed against the increased risk of bleeding, which can pose significant challenges in the pharmacological management of this condition. This review provides a comprehensive summary of the currently available evidence on antithrombotic therapy for ischemic stroke and outlines an updated therapeutic algorithm to support physicians in tailoring the strategy to the individual patient and the underlying mechanism of stroke.</AbstractText><br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 10 Oct 2023; 82:1538-1557</small></div>

<div><h4>Childhood Screening for Familial Hypercholesterolemia: JACC Review Topic of the Week.</h4><i>Gidding SS</i><br /><AbstractText>Screening for familial hypercholesterolemia (FH) in childhood remains controversial. Existing guidelines offer practitioners conflicting advice despite generally agreeing on the evidence and areas in which evidence is lacking, including a lack of long-term clinical trials demonstrating coronary event reduction as a result of screening and long-term data on statin side effects. A limitation of existing evidence-based frameworks is reliance on 1 evidence grading system to determine recommendations. However, rigorous evidence evaluation alternatives relevant to FH exist. FH is considered a tier 1 genetic condition, meaning that identification and treatment will improve health outcomes among those affected. Elevated low-density lipoprotein cholesterol, the primary consequence of FH, can be considered causal for atherosclerosis and coronary heart disease. Incorporating these concepts into existing evidence pathways allows the inclusion of surrogate clinical trial outcomes (low-density lipoprotein cholesterol reduction and atherosclerosis regression) and observational data on medication safety, strengthening the evidence for pediatric screening for FH.</AbstractText><br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 10 Oct 2023; 82:1558-1563</small></div>

<div><h4>LDL-C Reduction With Lipid-Lowering Therapy for Primary Prevention of Major Vascular Events Among Older Individuals.</h4><i>Andersson NW, Corn G, Dohlmann TL, Melbye M, Wohlfahrt J, Lund M</i><br /><b>Background</b><br />Reducing low-density lipoprotein (LDL) cholesterol with lipid-lowering therapy has consistently been shown to lower the risk of cardiovascular disease in primary prevention trials where the majority of individuals are aged <70 years. For older individuals, however, evidence is less clear.<br /><b>Objectives</b><br />In this study, the authors sought to compare the clinical effectiveness of lowering LDL cholesterol by means of lipid-lowering therapy for primary prevention of cardiovascular disease among older and younger individuals in a Danish nationwide cohort.<br /><b>Methods</b><br />We included individuals aged ≥50 years who had initiated lipid-lowering therapy from January 1, 2008, to October 31, 2017, had no history of atherosclerotic cardiovascular disease, and had a baseline and a within-1-year LDL cholesterol measurement. We assessed the associated risk of major vascular events among older individuals (≥70 years) by HRs per 1 mmol/L reduction in LDL cholesterol compared with younger individuals (<70 years).<br /><b>Results</b><br />For both the 16,035 older and the 49,155 younger individuals, the median LDL cholesterol reduction was 1.7 mmol/L. Each 1 mmol/L reduction in LDL cholesterol in older individuals was significantly associated with a 23% lower risk of major vascular events (HR: 0.77; 95% CI: 0.71-0.83), which was equal to that of younger individuals (HR: 0.76; 95% CI: 0.71-0.80; P value for difference = 0.79). Similar results were observed across all secondary analyses.<br /><b>Conclusions</b><br />Our study supports a relative clinical benefit of lowering LDL cholesterol for primary prevention of major vascular events in individuals aged ≥70 years similarly as in individuals aged <70 years.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 03 Oct 2023; 82:1381-1391</small></div>

<div><h4>Validation of Risk Stratification for Cardiac Events in Pregnant Women With Valvular Heart Disease.</h4><i>Pande SN, Yavana Suriya J, Ganapathy S, Pillai AA, ... D\'Souza R, Keepanasseril A</i><br /><b>Background</b><br />Most risk stratification tools for pregnant patients with heart disease were developed in high-income countries and in populations with predominantly congenital heart disease, and therefore, may not be generalizable to those with valvular heart disease (VHD).<br /><b>Objectives</b><br />The purpose of this study was to validate and establish the clinical utility of 2 risk stratification tools-DEVI (VHD-specific tool) and CARPREG-II-for predicting adverse cardiac events in pregnant patients with VHD.<br /><b>Methods</b><br />We conducted a cohort study involving consecutive pregnancies complicated with VHD admitted to a tertiary center in a middle-income setting from January 2019 to April 2022. Individual risk for adverse composite cardiac events was calculated using DEVI and CARPREG-II models. Performance was assessed through discrimination and calibration characteristics. Clinical utility was evaluated with Decision Curve Analysis.<br /><b>Results</b><br />Of 577 eligible pregnancies, 69 (12.1%) experienced a component of the composite outcome. A majority (94.7%) had rheumatic etiology, with mitral regurgitation as the predominant lesion (48.2%). The area under the receiver-operating characteristic curve was 0.884 (95% CI: 0.844-0.923) for the DEVI and 0.808 (95% CI: 0.753-0.863) for the CARPREG-II models. Calibration plots suggested that DEVI score overestimates risk at higher probabilities, whereas CARPREG-II score overestimates risk at both extremes and underestimates risk at middle probabilities. Decision curve analysis demonstrated that both models were useful across predicted probability thresholds between 10% and 50%.<br /><b>Conclusions</b><br />In pregnant patients with VHD, DEVI and CARPREG-II scores showed good discriminative ability and clinical utility across a range of probabilities. The DEVI score showed better agreement between predicted probabilities and observed events.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 03 Oct 2023; 82:1395-1406</small></div>

<div><h4>Genetic Insights on the Relation of Vascular Risk Factors and Cervical Artery Dissection.</h4><i>Le Grand Q, Ecker Ferreira L, Metso TM, Schilling S, ... Debette S, CADISP Consortium</i><br /><b>Background</b><br />The association between vascular risk factors and cervical artery dissections (CeADs), a leading cause of ischemic stroke (IS) in the young, remains controversial.<br /><b>Objectives</b><br />This study aimed to explore the causal relation of vascular risk factors with CeAD risk and recurrence and compare it to their relation with non-CeAD IS.<br /><b>Methods</b><br />This study used 2-sample Mendelian randomization analyses to explore the association of blood pressure (BP), lipid levels, type 2 diabetes, waist-to-hip ratio, smoking, and body mass index with CeAD and non-CeAD IS. To simulate effects of the most frequently used BP-lowering drugs, this study constructed genetic proxies and tested their association with CeAD and non-CeAD IS. In analyses among patients with CeAD, the investigators studied the association between weighted genetic risk scores of vascular risk factors and the risk of multiple or early recurrent dissections.<br /><b>Results</b><br />Genetically determined higher systolic BP (OR: 1.51; 95% CI: 1.32-1.72) and diastolic BP (OR: 2.40; 95% CI: 1.92-3.00) increased the risk of CeAD (P < 0.0001). Genetically determined higher body mass index was inconsistently associated with a lower risk of CeAD. Genetic proxies for β-blocker effects were associated with a lower risk of CeAD (OR: 0.65; 95% CI: 0.50-0.85), whereas calcium-channel blockers were associated with a lower risk of non-CeAD IS (OR: 0.75; 95% CI: 0.63-0.90). Weighted genetic risk scores for systolic BP and diastolic BP were associated with an increased risk of multiple or early recurrent CeAD.<br /><b>Conclusions</b><br />These results are supportive of a causal association between higher BP and increased CeAD risk and recurrence and provide genetic evidence for lower CeAD risk under β-blockers. This may inform secondary prevention strategies and trial design for CeAD.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 03 Oct 2023; 82:1411-1423</small></div>

<div><h4>Outcomes After Hybrid Palliation for Infants With Critical Left Heart Obstruction.</h4><i>Argo MB, Barron DJ, Eghtesady P, Yerebakan C, ... McCrindle BW, Congenital Heart Surgeons Society Critical Left Heart Obstruction Work Group</i><br /><b>Background</b><br />Hybrid palliation (bilateral pulmonary artery banding with or without ductal stenting) is an initial management strategy for infants with critical left heart obstruction and serves as palliation until subsequent operations are pursued.<br /><b>Objectives</b><br />This study sought to determine patient characteristics and factors associated with subsequent outcomes for infants who underwent hybrid palliation.<br /><b>Methods</b><br />From 2005 to 2019, 214 of 1,236 prospectively enrolled infants within the Congenital Heart Surgeons\' Society\'s critical left heart obstruction cohort underwent hybrid palliation across 24 institutions. Multivariable hazard modeling with competing risk methodology was performed to determine risk and factors associated with outcomes of biventricular repair, Fontan procedure, transplantation, or death.<br /><b>Results</b><br />Preoperative comorbidities (eg, prematurity, low birth weight, genetic syndrome) were identified in 70% of infants (150 of 214). Median follow-up was 7 years, ranging up to 17 years. Overall 12-year survival was 55%. At 5 years after hybrid palliation, 9% had biventricular repair, 36% had Fontan procedure, 12% had transplantation, 35% died without surgical endpoints, and 8% were alive without an endpoint. Factors associated with transplantation were absence of ductal stent, older age, absent interatrial communication, smaller aortic root size, larger tricuspid valve area z-score, and larger left ventricular volume. Factors associated with death were low birth weight, concomitant genetic syndrome, cardiopulmonary bypass use during hybrid palliation, moderate to severe tricuspid valve regurgitation, and smaller ascending aortic size.<br /><b>Conclusions</b><br />Mortality remains high after hybrid palliation for infants with critical left heart obstruction. Nonetheless, hybrid palliation may facilitate biventricular repair for some infants and for others may serve as stabilization for intended functional univentricular palliation or primary transplantation.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 03 Oct 2023; 82:1427-1441</small></div>

<div><h4>Recurrent Events in Cardiovascular Trials: JACC State-of-the-Art Review.</h4><i>Gregson J, Stone GW, Bhatt DL, Packer M, ... Redfors B, Pocock SJ</i><br /><AbstractText>Many randomized trials in cardiovascular disease have repeat nonfatal events (such as hospitalizations) occurring during patient follow-up; yet, it remains common practice to have time-to-first event as the primary outcome. We explore the value of analyses that include repeat events. Do they help us understand the effect of treatment and total disease burden? Do they enhance statistical power? Should they become a trial\'s primary analysis? It may also be difficult to choose which of the various statistical methods for analyzing repeat events to use, and we provide a nontechnical guide to what each method is doing. We compare several methods for repeat events: Lin Wei Yang Ying, negative binomial, joint frailty, win ratio, and area under the curve. We illustrate their performance in 5 large cardiovascular trials and compare them with time-to-first-event analyses. We review their use in recently published heart failure trials and make recommendations for their use in future trials.</AbstractText><br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 03 Oct 2023; 82:1445-1463</small></div>

<div><h4>Durable Mechanical Circulatory Support: JACC Scientific Statement.</h4><i>Tedford RJ, Leacche M, Lorts A, Drakos SG, Pagani FD, Cowger J</i><br /><AbstractText>Despite advances in medical therapy for patients with stage C heart failure (HF), survival for patients with advanced HF is <20% at 5 years. Durable left ventricular assist device (dLVAD) support is an important treatment option for patients with advanced HF. Innovations in dLVAD technology have reduced the risk of several adverse events, including pump thrombosis, stroke, and bleeding. Average patient survival is now similar to that of heart transplantation at 2 years, with 5-year dLVAD survival now approaching 60%. Unfortunately, greater adoption of dLVAD therapy has not been realized due to delayed referral of patients to advanced HF centers, insufficient clinician knowledge of contemporary dLVAD outcomes (including gains in quality of life), and deprioritization of patients with dLVAD support waiting for heart transplantation. Despite these challenges, novel devices are on the horizon of clinical investigation, offering smaller size, permitting less invasive surgical implantation, and eliminating the percutaneous lead for power supply.</AbstractText><br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 03 Oct 2023; 82:1464-1481</small></div>

<div><h4>Tricuspid Valve Academic Research Consortium Definitions for Tricuspid Regurgitation and Trial Endpoints.</h4><i>Hahn RT, Lawlor MK, Davidson CJ, Badhwar V, ... Hausleiter J, TVARC Steering Committee</i><br /><AbstractText>Interest in the pathophysiology, etiology, management, and outcomes of patients with tricuspid regurgitation (TR) has grown in the wake of multiple natural history studies showing progressively worse outcomes associated with increasing TR severity, even after adjusting for multiple comorbidities. Historically, isolated tricuspid valve surgery has been associated with high in-hospital mortality rates, leading to the development of transcatheter treatment options. The aim of this first Tricuspid Valve Academic Research Consortium document is to standardize definitions of disease etiology and severity, as well as endpoints for trials that aim to address the gaps in our knowledge related to identification and management of patients with TR. Standardizing endpoints for trials should provide consistency and enable meaningful comparisons between clinical trials. A second Tricuspid Valve Academic Research Consortium document will focus on further defining trial endpoints and will discuss trial design options.</AbstractText><br /><br />Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 28 Sep 2023; epub ahead of print</small></div>

<div><h4>Transcatheter Edge-to-Edge Repair in 5,000 Patients With Secondary Mitral Regurgitation: COAPT Post-Approval Study.</h4><i>Goel K, Lindenfeld J, Makkar R, Naik H, ... Lindman BR, Barker CM</i><br /><b>Background</b><br />Real-world applicability of the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) randomized controlled trial (RCT) has been debated because of careful patient selection and the contrasting results of the MITRA-FR (Multicentre Study of Percutaneous Mitral Valve Repair MitraClip Device in Patients with Severe Secondary Mitral Regurgitation) RCT.<br /><b>Objectives</b><br />The COAPT-PAS (COAPT Post-Approval Study) was initiated to assess the safety and effectiveness of the MitraClip in patients with secondary mitral regurgitation (SMR).<br /><b>Methods</b><br />COAPT-PAS is a prospective, single-arm, observational study of 5,000 consecutive patients with SMR treated with the MitraClip at 406 U.S. centers participating in the TVT (Transcatheter Valve Therapy) registry from 2019 to 2020. The 1-year outcomes from the COAPT-PAS full cohort and the COAPT-like and MITRA-FR-like subgroups who met RCT inclusion/exclusion criteria are reported.<br /><b>Results</b><br />Patients in the COAPT-PAS had more comorbidities, more severe HF and functional limitations, and less guideline-directed medical therapy than those in the COAPT or MITRA-FR RCTs. Patients in the COAPT-PAS full cohort and the COAPT-like (n = 991) and MITRA-FR-like (n = 917) subgroups achieved a 97.7% MitraClip implant rate, a similar and durable reduction of mitral regurgitation to ≤2+ at 1 year (90.7%, 89.7%, and 86.6%, respectively), a large improvement in quality of life at 1 year (Kansas City Cardiomyopathy Questionnaire +29 COAPT-PAS, +27 COAPT-like, and +33 MITRA-FR-like), faster procedure times, similar or lower clinical event rates compared with the RCTs\' MitraClip arms, and lower clinical event rates than the RCTs\' guideline-directed medical therapy only arms. One-year heart failure hospitalizations was 18.9% in COAPT-PAS, 19.7% in COAPT-like compared with 24.9% in COAPT-RCT, and 28.7% in COAPT-PAS-MITRA-FR-like compared with 47.4% in MITRA-FR-RCT.<br /><b>Conclusions</b><br />This large, contemporary, real-world study reinforces the safety and effectiveness of the MitraClip System in patients with SMR, including those who met the COAPT or MITRA-FR RCT inclusion/exclusion criteria and patients excluded from the RCTs.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 26 Sep 2023; 82:1281-1297</small></div>

<div><h4>Association of High-Sensitivity Cardiac Troponin T With 30-Day and 5-Year Mortality After Cardiac Surgery.</h4><i>Pölzl L, Engler C, Sterzinger P, Lohmann R, ... Holfeld J, Gollmann-Tepeköylü C</i><br /><b>Background</b><br />The relevance of perioperative myocardial injury (PMI) after cardiac surgery for 30-day mortality and long-term survival remains to be determined.<br /><b>Objectives</b><br />This study assessed the association of PMI after cardiac surgery, reflected by postoperative troponin release, with 30-day mortality and long-term survival after: 1) coronary artery bypass grafting (CABG); 2) isolated aortic valve replacement (AVR) surgery; and 3) all other cardiac surgeries.<br /><b>Methods</b><br />A consecutive cohort of 8,292 patients undergoing cardiac surgery with serial perioperative high-sensitivity cardiac troponin T (hs-cTnT) measurements was retrospectively analyzed. The relationship between postoperative hs-cTnT release and 30-day mortality or 5-year mortality was analyzed after adjustment with EuroSCORE II using a Cox proportional hazards model. hs-cTnT thresholds for 30-day and 5-year mortality were determined for isolated CABG (32.3%), AVR (14%), and other cardiac surgery (53.8%).<br /><b>Results</b><br />High postoperative hs-cTnT levels were associated with higher 30-day mortality but not 5-year mortality. In CABG, median peak concentration of postoperative hs-cTnT was 1,044 ng/L, in AVR it was 502 ng/L, and in other cardiac surgery it was 1,110 ng/L. hs-cTnT thresholds defining mortality-associated PMI were as follows: for CABG, 2,385 ng/L (170× the upper reference limit of normal in a seemingly healthy population [URL]); for AVR, 568 ng/L (41× URL); and for other cardiac procedures, 1,873 ng/L (134× URL). hs-cTnT levels above the cutoffs resulted in an HR for 30-day mortality for CABG of 12.56 (P < 0.001), for AVR of 4.44 (P = 0.004), and for other cardiac surgery of 3.97 (P < 0.001).<br /><b>Conclusions</b><br />PMI reflected by perioperative hs-cTnT release is associated with the expected 30-day mortality but not 5-year mortality. Postoperative hs-cTnT cutoffs to identify survival-relevant PMI are higher than suggested in current definitions.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 26 Sep 2023; 82:1301-1312</small></div>

<div><h4>Impaired Renal Function and Major Cardiovascular Events in Young Adults.</h4><i>Hussain J, Imsirovic H, Canney M, Clark EG, ... Knoll GA, Sood MM</i><br /><b>Background</b><br />Cardiovascular (CV) disease in young adults (aged 18-39 years) is on the rise. Whether subclinical reductions in kidney function (ie, estimated glomerular filtration rate [eGFR] above the current threshold for chronic kidney disease but below age-expected values) are associated with elevated CV risk is unknown.<br /><b>Objectives</b><br />The goal of this study was to examine age-specific associations of subclinical eGFR reductions in young adults with major adverse cardiovascular events (MACEs) and MACE plus heart failure (MACE+).<br /><b>Methods</b><br />A retrospective cohort study of 8.7 million individuals (3.6 million aged 18-39 years) was constructed using linked provincial health care data sets from Ontario, Canada (January 2008-March 2021). Cox models were used to examine the association of categorized eGFR (50-120 mL/min/1.73 m<sup>2</sup>) with MACE (first of CV mortality, acute coronary syndrome, and ischemic stroke) and MACE+, stratified according to age (18-39, 40-49, and 50-65 years).<br /><b>Results</b><br />In the study cohort (mean age 41.3 years; mean eGFR 104.2 mL/min/1.73 m<sup>2</sup>; median follow-up 9.2 years), a stepwise increase in the relative risk of MACE and MACE+ was observed as early as eGFR <80 mL/min/1.73 m<sup>2</sup> in young adults (eg, for MACE, at eGFR 70-79 mL/min/1.73 m<sup>2</sup>, ages 18-30 years: 2.37 events per 1,000 person years [HR: 1.31; 95% CI: 1.27-1.40]; ages 40-49 years: 6.26 events per 1,000 person years [HR: 1.09; 95% CI: 1.06-1.12]; ages 50-65 years: 14.9 events per 1,000 person years [HR: 1.07; 95% CI: 1.05-1.08]). Results persisted for each MACE component and in additional analyses (stratifying according to past CV disease, accounting for albuminuria at index, and using repeated eGFR measures).<br /><b>Conclusions</b><br />In young adults, eGFR below age-expected values were associated with an elevated risk for MACE and MACE+, warranting age-appropriate risk stratification, proactive monitoring, and timely intervention.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 26 Sep 2023; 82:1316-1327</small></div>

<div><h4>Chronic Medication Burden After Cardiac Surgery for Pediatric Medicaid Beneficiaries.</h4><i>Woo JL, Nash KA, Dragan K, Crook S, ... Anderson BR, New York State Congenital Heart Surgery Collaborative for Longitudinal Outcomes and Utilization of Resources (CHS-COLOUR)</i><br /><b>Background</b><br />Congenital heart defects are the most common and resource-intensive birth defects. As children with congenital heart defects increasingly survive beyond early childhood, it is imperative to understand longitudinal disease burden.<br /><b>Objectives</b><br />The purpose of this study was to examine chronic outpatient prescription medication use and expenditures for New York State pediatric Medicaid enrollees, comparing children who undergo cardiac surgery (cardiac enrollees) and the general pediatric population.<br /><b>Methods</b><br />This was a retrospective cohort study of all Medicaid enrollees age <18 years using the New York State Congenital Heart Surgery Collaborative for Longitudinal Outcomes and Utilization of Resources database (2006-2019). Primary outcomes were total chronic medications per person-year, enrollees per 100 person-years using ≥1 and ≥3 medications, and medication expenditures per person-year. We described and compared outcomes between cardiac enrollees and the general pediatric population. Among cardiac enrollees, multivariable regression examined associations between outcomes and clinical characteristics.<br /><b>Results</b><br />We included 5,459 unique children (32,131 person-years) who underwent cardiac surgery and 4.5 million children (22 million person-years) who did not. More than 4 in 10 children who underwent cardiac surgery used ≥1 chronic medication compared with approximately 1 in 10 children who did not have cardiac surgery. Medication expenditures were 10 times higher per person-year for cardiac compared with noncardiac enrollees. Among cardiac enrollees, disease severity was associated with chronic medication use; use was highest among infants; however, nearly one-half of adolescents used ≥1 chronic medication.<br /><b>Conclusions</b><br />Children who undergo cardiac surgery experience high medication burden that persists throughout childhood. Understanding chronic medication use can inform clinicians (both pediatricians and subspecialists) and policymakers, and ultimately the value of care for this medically complex population.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 26 Sep 2023; 82:1331-1340</small></div>

<div><h4>Clinical Pathway for Coronary Atherosclerosis in Patients Without Conventional Modifiable Risk Factors: JACC State-of-the-Art Review.</h4><i>Figtree GA, Vernon ST, Harmer JA, Gray MP, ... Nicholls SJ, CRE for CAD Collaborators</i><br /><AbstractText>Reducing the incidence and prevalence of standard modifiable cardiovascular risk factors (SMuRFs) is critical to tackling the global burden of coronary artery disease (CAD). However, a substantial number of individuals develop coronary atherosclerosis despite no SMuRFs. SMuRFless patients presenting with myocardial infarction have been observed to have an unexpected higher early mortality compared to their counterparts with at least 1 SMuRF. Evidence for optimal management of these patients is lacking. We assembled an international, multidisciplinary team to develop an evidence-based clinical pathway for SMuRFless CAD patients. A modified Delphi method was applied. The resulting pathway confirms underlying atherosclerosis and true SMuRFless status, ensures evidence-based secondary prevention, and considers additional tests and interventions for less typical contributors. This dedicated pathway for a previously overlooked CAD population, with an accompanying registry, aims to improve outcomes through enhanced adherence to evidence-based secondary prevention and additional diagnosis of modifiable risk factors observed.</AbstractText><br /><br />Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 26 Sep 2023; 82:1343-1359</small></div>

<div><h4>Generalized Pairwise Comparisons to Assess Treatment Effects: JACC Review Topic of the Week.</h4><i>Verbeeck J, De Backer M, Verwerft J, Salvaggio S, ... Buyse M, Brunner E</i><br /><AbstractText>A time-to-first-event composite endpoint analysis has well-known shortcomings in evaluating a treatment effect in cardiovascular clinical trials. It does not fully describe the clinical benefit of therapy because the severity of the events, events repeated over time, and clinically relevant nonsurvival outcomes cannot be considered. The generalized pairwise comparisons (GPC) method adds flexibility in defining the primary endpoint by including any number and type of outcomes that best capture the clinical benefit of a therapy as compared with standard of care. Clinically important outcomes, including bleeding severity, number of interventions, and quality of life, can easily be integrated in a single analysis. The treatment effect in GPC can be expressed by the net treatment benefit, the success odds, or the win ratio. This review provides guidance on the use of GPC and the choice of treatment effect measures for the analysis and reporting of cardiovascular trials.</AbstractText><br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 26 Sep 2023; 82:1360-1372</small></div>

<div><h4>Implementation of Global Hearts Hypertension Control Programs in 32 Low- and Middle-Income Countries: JACC International.</h4><i>Moran AE, Gupta R, Global Hearts Initiative Collaborators</i><br /><AbstractText>In 2017, the World Health Organization (WHO) and Resolve to Save Lives partnered with country governments and other stakeholders to design, test, and scale up the WHO HEARTS hypertension services package in 32 low- and middle-income countries. Facility-based HEARTS performance indicators included number of patients enrolled, number treated and with blood pressure controlled, number who missed a scheduled follow-up visit, and number lost to follow-up. By 2022, HEARTS hypertension control programs treated 12.2 million patients in 165,000 primary care facilities. Hypertension control was 38% (median 48%; range 5%-86%). In 4 HEARTS countries using the same digital health information system, facility-based control improved from 18% at baseline to 46% in 48 months. At the population level, median estimated population-based hypertension control was 11.0% of all hypertension patients (range 2.0%-34.7%). The Global Hearts experience of implementing WHO HEARTS demonstrates the feasibility of controlling hypertension in low- and middle-income country primary care settings.</AbstractText><br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Am Coll Cardiol: 19 Sep 2023; epub ahead of print</small></div>

<div><h4>Association of Coronary Artery Calcium Detected by Routine Ungated CT Imaging With Cardiovascular Outcomes.</h4><i>Peng AW, Dudum R, Jain SS, Maron DJ, ... Sandhu AT, Rodriguez F</i><br /><b>Background</b><br />Coronary artery calcium (CAC) is a strong predictor of cardiovascular events across all racial and ethnic groups. CAC can be quantified on nonelectrocardiography (ECG)-gated computed tomography (CT) performed for other reasons, allowing for opportunistic screening for subclinical atherosclerosis.<br /><b>Objectives</b><br />The authors investigated whether incidental CAC quantified on routine non-ECG-gated CTs using a deep-learning (DL) algorithm provided cardiovascular risk stratification beyond traditional risk prediction methods.<br /><b>Methods</b><br />Incidental CAC was quantified using a DL algorithm (DL-CAC) on non-ECG-gated chest CTs performed for routine care in all settings at a large academic medical center from 2014 to 2019. We measured the association between DL-CAC (0, 1-99, or ≥100) with all-cause death (primary outcome), and the secondary composite outcomes of death/myocardial infarction (MI)/stroke and death/MI/stroke/revascularization using Cox regression. We adjusted for age, sex, race, ethnicity, comorbidities, systolic blood pressure, lipid levels, smoking status, and antihypertensive use. Ten-year atherosclerotic cardiovascular disease risk was calculated using the pooled cohort equations.<br /><b>Results</b><br />Of 5,678 adults without ASCVD (51% women, 18% Asian, 13% Hispanic/Latinx), 52% had DL-CAC >0. Those with DL-CAC ≥100 had an average 10-year ASCVD risk of 24%; yet, only 26% were on statins. After adjustment, patients with DL-CAC ≥100 had increased risk of death (HR: 1.51; 95% CI: 1.28-1.79), death/MI/stroke (HR: 1.57; 95% CI: 1.33-1.84), and death/MI/stroke/revascularization (HR: 1.69; 95% CI: 1.45-1.98) compared with DL-CAC = 0.<br /><b>Conclusions</b><br />Incidental CAC ≥100 was associated with an increased risk of all-cause death and adverse cardiovascular outcomes, beyond traditional risk factors. DL-CAC from routine non-ECG-gated CTs identifies patients at increased cardiovascular risk and holds promise as a tool for opportunistic screening to facilitate earlier intervention.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 19 Sep 2023; 82:1192-1202</small></div>

<div><h4>20-Year Experience With Repair of Pulmonary Atresia or Stenosis and Major Aortopulmonary Collateral Arteries.</h4><i>McElhinney DB, Asija R, Zhang Y, Jaggi A, ... Martin E, Hanley FL</i><br /><b>Background</b><br />We have followed a consistent, albeit evolving, strategy for the management of patients with pulmonary atresia or severe stenosis and major aortopulmonary collateral arteries (MAPCAs) that aims to achieve complete repair with low right ventricular pressure by completely incorporating blood supply and relieving stenoses to all lung segments.<br /><b>Objectives</b><br />The purpose of this study was to characterize our 20-year institutional experience managing patients with MAPCAs.<br /><b>Methods</b><br />We reviewed all patients who underwent surgery for MAPCAs and biventricular heart disease from November 2001 through December 2021.<br /><b>Results</b><br />During the study period, 780 unique patients underwent surgery. The number of new patients undergoing surgery annually was relatively steady during the first 15 years, then increased substantially thereafter. Surgery before referral had been performed in almost 40% of patients, more often in our recent experience than earlier. Complete repair was achieved in 704 patients (90%), 521 (67%) during the first surgery at our center, with a median right ventricular to aortic pressure ratio of 0.34 (25th, 75th percentiles: 0.28, 0.40). The cumulative incidence of mortality was 15% (95% CI: 12%-19%) at 10 years, with no difference according to era of surgery (P = 0.53). On multivariable Cox regression, Alagille syndrome (HR: 2.8; 95% CI: 1.4-5.7; P = 0.004), preoperative respiratory support (HR: 2.0; 95% CI: 1.2-3.3; P = 0.008), and palliative first surgery at our center (HR: 3.5; 95% CI: 2.3-5.4; P < 0.001) were associated with higher risk of death.<br /><b>Conclusions</b><br />In a growing pulmonary artery reconstruction program, with increasing volumes and an expanding population of patients who underwent prior surgery, outcomes of patients with pulmonary atresia or stenosis and MAPCAs have continued to improve.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 19 Sep 2023; 82:1206-1222</small></div>

<div><h4>Survival After Cardiac Transplantation in Adults With Single-Ventricle Congenital Heart Disease.</h4><i>Bakhtiyar SS, Sakowitz S, Ali K, Chervu NL, ... D\'Alessandro D, Benharash P</i><br /><b>Background</b><br />Without large-scale analyses of adults with single-ventricle congenital heart disease (CHD) undergoing heart transplantation, little evidence exists to guide listing practices and patient counseling.<br /><b>Objectives</b><br />This study aims to evaluate survival after heart transplantation in adults with single and biventricular CHD and compare it to that of non-CHD transplant recipients.<br /><b>Methods</b><br />In this 15-year (2005-2020) retrospective analysis, outcome-blinded investigators used probability-linkage to merge the National (Nationwide) Inpatient Sample and Organ Procurement and Transplantation Network data sets.<br /><b>Results</b><br />Of 382 adult (≥18 years of age) heart transplant recipients with CHD, 185 (48%) had single-ventricle physiology. Compared to biventricular CHD, single-ventricle patients showed significantly reduced survival at 1 (80% vs 91%; HR: 2.50; 95% CI: 1.40-4.49; P = 0.002) and 10 years (54% vs 71%; HR: 2.10; 95% CI: 1.38-3.18; P < 0.001). Among patients who survived the first post-transplantation year, biventricular CHD patients exhibited similar 10-year survival as single-ventricle patients, except for those with hypoplastic left heart syndrome (79% vs 71%; HR: 1.58; 95% CI: 0.85-2.92; P = 0.15). Additionally, biventricular CHD transplant recipients showed significantly better 10-year conditional survival compared to their non-CHD counterparts (79% vs 68%; HR: 0.73; 95% CI: 0.59-0.90; P = 0.003).<br /><b>Conclusions</b><br />Among adult CHD transplant recipients, single-ventricle physiology correlated with higher short-term mortality. However, 10-year conditional survival was similar for biventricular and most single-ventricle CHD patients, and notably better for biventricular CHD patients compared to non-CHD heart transplant recipients. These findings have significant implications towards patient selection and listing strategies, easing concerns related to heart transplantation in adults with CHD and destigmatizing most subtypes of single-ventricle CHD.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 19 Sep 2023; 82:1226-1241</small></div>

<div><h4>Comprehensive Management of ANOCA, Part 1-Definition, Patient Population, and Diagnosis: JACC State-of-the-Art Review.</h4><i>Samuels BA, Shah SM, Widmer RJ, Kobayashi Y, ... Tremmel JA, Microvascular Network (MVN)</i><br /><AbstractText>Angina with nonobstructive coronary arteries (ANOCA) is increasingly recognized and may affect nearly one-half of patients undergoing invasive coronary angiography for suspected ischemic heart disease. This working diagnosis encompasses coronary microvascular dysfunction, microvascular and epicardial spasm, myocardial bridging, and other occult coronary abnormalities. Patients with ANOCA often face a high burden of symptoms and may experience repeated presentations to multiple medical providers before receiving a diagnosis. Given the challenges of establishing a diagnosis, patients with ANOCA frequently experience invalidation and recidivism, possibly leading to anxiety and depression. Advances in scientific knowledge and diagnostic testing now allow for routine evaluation of ANOCA noninvasively and in the cardiac catheterization laboratory with coronary function testing (CFT). CFT includes diagnostic coronary angiography, assessment of coronary flow reserve and microcirculatory resistance, provocative testing for endothelial dysfunction and coronary vasospasm, and intravascular imaging for identification of myocardial bridging, with hemodynamic assessment as needed.</AbstractText><br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Am Coll Cardiol: 19 Sep 2023; 82:1245-1263</small></div>

<div><h4>Comprehensive Management of ANOCA, Part 2-Program Development, Treatment, and Research Initiatives: JACC State-of-the-Art Review.</h4><i>Smilowitz NR, Prasad M, Widmer RJ, Toleva O, ... Tremmel JA, Microvascular Network (MVN)</i><br /><AbstractText>Centers specializing in coronary function testing are critical to ensure a systematic approach to the diagnosis and treatment of angina with nonobstructive coronary arteries (ANOCA). Management leveraging lifestyle, pharmacology, and device-based therapeutic options for ANOCA can improve angina burden and quality of life in affected patients. Multidisciplinary care teams that can tailor and titrate therapies based on individual patient needs are critical to the success of comprehensive programs. As coronary function testing for ANOCA is more widely adopted, collaborative research initiatives will be fundamental to improve ANOCA care. These efforts will require standardized symptom assessments and data collection, which will propel future large-scale clinical trials.</AbstractText><br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Am Coll Cardiol: 19 Sep 2023; 82:1264-1279</small></div>

<div><h4>Coronary Computed Tomographic Angiography With Fractional Flow Reserve in Patients With Type 2 Myocardial Infarction.</h4><i>McCarthy CP, Murphy SP, Amponsah DK, Rambarat PK, ... Hedgire S, Januzzi JL</i><br /><b>Background</b><br />Type 2 myocardial infarction (T2MI) related to a supply/demand imbalance of coronary blood flow is common and associated with poor prognosis. Coronary artery disease (CAD) may predispose some individuals to T2MI and contribute to its high rate of recurrent cardiovascular events. Little is known about the presence and extent of CAD in this population.<br /><b>Objectives</b><br />The goal of this study was to evaluate the presence and characteristics of CAD among patients with T2MI.<br /><b>Methods</b><br />In this prospective study, consecutive eligible individuals with Fourth Universal Definition of Myocardial Infarction criteria for T2MI were enrolled. Participants underwent coronary computed tomography angiography (CTA), fractional flow reserve derived with coronary CTA (FFR<sub>CT</sub>), and plaque volume analyses.<br /><b>Results</b><br />Among 50 participants, 25 (50%) were female, and the mean age was 68.0 ± 11.4 years. Atherosclerotic risk factors were common. Coronary CTA revealed coronary plaque in 46 participants (92%). A moderate or greater stenosis (≥50%) was identified in 42% of participants, and obstructive disease (≥50% left main stenosis or ≥70% stenosis in any other epicardial coronary artery) was present in 26%. Prevalence of obstructive CAD did not differ according to T2MI cause (P = 0.54). A hemodynamically significant focal stenosis identified by FFR<sub>CT</sub> was present in 13 participants (26%). Among participants with a stenosis ≥50% (n = 21), FFR<sub>CT</sub> excluded lesion-specific hemodynamically significant stenosis in 8 cases (38%).<br /><b>Conclusions</b><br />Among individuals with adjudicated T2MI, CAD was prevalent, but the majority of patients had nonobstructive CAD. Mediators of ischemia are likely multifactorial in this population. (Defining the Prevalence and Characteristics of Coronary Artery Disease Among Patients with Type 2 Myocardial Infarction using CT-FFR [DEFINE TYPE 2 MI]; NCT04864119).<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 18 Sep 2023; epub ahead of print</small></div>

<div><h4>Long-Term Outcome and Prognosis of Noninfectious Thoracic Aortitis.</h4><i>Espitia O, Bruneval P, Assaraf M, Pouchot J, ... Saadoun D, French Study Group for Large Vessel Vasculitides (GEFA)</i><br /><b>Background</b><br />Aortitis is a group of disorders characterized by the inflammation of the aorta. The large-vessel vasculitides are the most common causes of aortitis. Aortitis long-term outcomes are not well known.<br /><b>Objectives</b><br />The purpose of this study was to assess the long-term outcome and prognosis of noninfectious surgical thoracic aortitis.<br /><b>Methods</b><br />This was a retrospective multicenter study of 5,666 patients with thoracic aorta surgery including 217 (3.8%) with noninfectious thoracic aortitis (118 clinically isolated aortitis, 57 giant cells arteritis, 21 Takayasu arteritis, and 21 with various systemic autoimmune disorders). Factors associated with vascular complications and a second vascular procedure were assessed by multivariable analysis.<br /><b>Results</b><br />Indications for aortic surgery were asymptomatic aneurysm with a critical size (n = 152 [70%]), aortic dissection (n = 28 [13%]), and symptomatic aortic aneurysm (n = 30 [14%]). The 10-year cumulative incidence of vascular complication and second vascular procedure was 82.1% (95% CI: 67.6%-90.6%), and 42.6% (95% CI: 28.4%-56.1%), respectively. Aortic arch aortitis (HR: 2.08; 95% CI: 1.26-3.44; P = 0.005) was independently associated with vascular complications. Descending thoracic aortitis (HR: 2.35; 95% CI: 1.11-4.96; P = 0.031) and aortic dissection (HR: 3.08; 95% CI: 1.61-5.90; P = 0.002) were independently associated with a second vascular procedure, while treatment with statins after aortitis diagnosis (HR: 0.47; 95% CI: 0.24-0.90; P = 0.028) decreased it. After a median follow-up of 3.9 years, 19 (16.1%) clinically isolated aortitis patients developed features of a systemic inflammatory disease and 35 (16%) patients had died.<br /><b>Conclusions</b><br />This multicenter study shows that 82% of noninfectious surgical thoracic aortitis patients will experience a vascular complication within 10 years. We pointed out specific characteristics that identified those at highest risk for subsequent vascular complications and second vascular procedures.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 12 Sep 2023; 82:1053-1064</small></div>

<div><h4>Cardiovascular Events After Aortic Root Repair in Patients With Marfan Syndrome.</h4><i>David TE, Park J, Tatangelo M, Steve Fan CP, Ouzounian M</i><br /><b>Background</b><br />The usefulness of aortic valve sparing operations to treat aortic root aneurysm in patients with Marfan syndrome (MS) remains controversial.<br /><b>Objectives</b><br />The purpose of this study was to evaluate the occurrence of cardiovascular events in patients with MS who have undergone valve-preserving aortic root replacement.<br /><b>Methods</b><br />Patients with MS who had aortic valve sparing operations (reimplantation of the aortic valve or remodeling of the aortic root) from 1988 through 2019 were followed prospectively for a median of 14 years. Pertinent data from clinical, echocardiographic, computed tomography, and magnetic resonance images of the aorta were collected and analyzed.<br /><b>Results</b><br />There were 189 patients whose mean age was 36 years, and 67% were men. Ten patients presented with acute type A dissection and 29 had mitral regurgitation. There were 52 patients at risk at 20 years. Mortality rate at 20 years was 21.5% (95% CI: 14.7%-30.8%); advancing age and preoperative aortic dissections were associated with increased risk of death by multivariable analysis. At 20 years, the cumulative incidence of moderate or severe aortic insufficiency was 14.5% (95% CI: 9.5%-22.0%), reoperation on the aortic valve was 7.5% (95% CI: 3.9%-14.7%), and new distal aortic dissections was 19.9% (95% CI: 13.9%-28.5%). Remodeling of aortic root was associated with greater risk of developing aortic insufficiency and aortic valve reoperation than reimplantation of the aortic valve.<br /><b>Conclusions</b><br />Aortic valve sparing operations provide stable aortic valve function and low rates of valve-related complications during the first 2 decades of follow-up but aortic dissections remain problematic in patients with MS.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 12 Sep 2023; 82:1068-1076</small></div>

<div><h4>Vasovagal Responses to Human Monomorphic Ventricular Tachycardia: Hemodynamic Implications From Sinus Rate Analysis.</h4><i>Pujol-Lopez M, Du Fay de Lavallaz J, Rangan P, Beaser A, ... Su W, Tung R</i><br /><b>Background</b><br />Factors determining hemodynamic stability during human ventricular tachycardia (VT) are incompletely understood.<br /><b>Objectives</b><br />The purposes of this study were to characterize sinus rate (SR) responses during monomorphic VT in association with hemodynamic stability and to prospectively assess the effects of vagolytic therapy on VT tolerance.<br /><b>Methods</b><br />This is a retrospective analysis of patients undergoing scar-related VT ablation. Vasovagal responses were evaluated by analyzing sinus cycle length before VT induction and during VT. SR responses were classified into 3 groups: increasing (≥5 beats/min, sympathetic), decreasing (≥5 beats/min, vagal), and unchanged, with the latter 2 categorized as inappropriate SR. In a prospective cohort (n = 30) that exhibited a failure to increase SR, atropine was administered to improve hemodynamic tolerance to VT.<br /><b>Results</b><br />In 150 patients, 261 VT episodes were analyzed (29% untolerated, 71% tolerated) with median VT duration 1.6 minutes. A total of 52% of VT episodes were associated with a sympathetic response, 31% had unchanged SR, and 17% of VTs exhibited a vagal response. A significantly higher prevalence of inappropriate SR responses was observed during untolerated VT (sustained VT requiring cardioversion within 150 seconds) compared with tolerated VT (84% vs 34%; P < 0.001). Untolerated VT was significantly different between groups: 9% (sympathetic), 82% (vagal), and 32% (unchanged) (P < 0.001). Atropine administration improved hemodynamic tolerance to VT in 70%.<br /><b>Conclusions</b><br />Nearly one-half of VT episodes are associated with failure to augment SR, indicative of an under-recognized pathophysiological vasovagal response to VT. Inappropriate SR responses were more predictive of hemodynamic instability than VT rate and ejection fraction. Vagolytic therapy may be a novel method to augment blood pressure during VT.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 12 Sep 2023; 82:1096-1105</small></div>

<div><h4>Ventricular Arrhythmias in Adults With Congenital Heart Disease, Part I: JACC State-of-the-Art Review.</h4><i>Bessière F, Waldmann V, Combes N, Metton O, ... Triedman J, Khairy P</i><br /><AbstractText>Patients with congenital heart disease associated with a higher risk for ventricular arrhythmias (VA) and sudden cardiac death (SCD) can be divided conceptually into those with discrete mechanisms for reentrant monomorphic ventricular tachycardia (VT) (Group A) and those with more diffuse substrates (Group B). Part I of this review addresses Group A lesions, which predominantly consist of tetralogy of Fallot and related variants. Well-defined anatomic isthmuses for reentrant monomorphic VT are interposed between surgical scars and the pulmonary or tricuspid annulus. The most commonly implicated critical isthmus for VT is the conal septum that divides subpulmonary from subaortic outlets. Programmed ventricular stimulation can be helpful in risk stratification. Although catheter ablation is not generally considered an alternative to the implantable cardioverter-defibrillator (ICD) for prevention of SCD, emerging data suggest that there is a subset of carefully selected patients who may not require ICDs after successful monomorphic VT ablation.</AbstractText><br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 12 Sep 2023; 82:1108-1120</small></div>

<div><h4>Ventricular Arrhythmias in Adults With Congenital Heart Disease, Part II: JACC State-of-the-Art Review.</h4><i>Bessière F, Waldmann V, Combes N, Metton O, ... Triedman J, Khairy P</i><br /><AbstractText>There are marked variations in the incidence of sudden cardiac death (SCD) and in the substrates for ventricular arrhythmias (VAs) across the gamut of congenital heart defects. In this 2-part review, patients with higher-risk forms of congenital heart disease (CHD) were conceptually categorized into those with discrete anatomic isthmuses for macro-reentrant ventricular tachycardia (VT) (Group A) and those with more diffuse or less well-defined substrates (Group B) that include patchy or extensive myocardial fibrosis. The latter category encompasses CHD lesions such as Ebstein anomaly, transposition of the great arteries with a systemic right ventricle (RV), and congenital aortic stenosis. For Group B patients, polymorphic VT and ventricular fibrillation account for a higher proportion of VA. The prognostic value of programmed ventricular stimulation is less well established, and catheter ablation plays a less prominent role. As cardiomyopathies evolve over time, pathophysiological mechanisms for VA among Groups A and B become increasingly blurred.</AbstractText><br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 12 Sep 2023; 82:1121-1130</small></div>

<div><h4>Impact of Sex on Cardiovascular Adaptations to Exercise: JACC Review Topic of the Week.</h4><i>Petek BJ, Chung EH, Kim JH, Lampert R, ... Stewart KM, Wasfy MM</i><br /><AbstractText>Routine exercise leads to cardiovascular adaptations that differ based on sex. Use of cardiac testing to screen athletes has driven research to define how these sex-based adaptations manifest on the electrocardiogram and cardiac imaging. Importantly, sex-based differences in cardiovascular structure and outcomes in athletes often parallel findings in the general population, underscoring the importance of understanding their mechanisms. Substantial gaps exist in the understanding of why cardiovascular adaptations and outcomes related to exercise differ by sex because of underrepresentation of female participants in research. As female sports participation rates have increased dramatically over several decades, it also remains unknown if differences observed in older athletes reflect biological mechanisms vs less lifetime access to sports in females. In this review, we will assess the effect of sex on cardiovascular adaptations and outcomes related to exercise, identify the impact of sex hormones on exercise performance, and highlight key areas for future research.</AbstractText><br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 05 Sep 2023; 82:1030-1038</small></div>

<div><h4>Ablation to Reduce Atrial Fibrillation Burden and Improve Outcomes: JACC Review Topic of the Week.</h4><i>Schwennesen HT, Andrade JG, Wood KA, Piccini JP</i><br /><AbstractText>Atrial fibrillation is the most common atrial arrhythmia and accounts for a significant burden of cardiovascular disease globally. With advances in implanted and wearable cardiac monitoring technology, it is now possible to readily and accurately quantify an individual\'s time spent in atrial fibrillation. This review summarizes the relationship between atrial fibrillation burden and adverse cardiovascular and cerebrovascular outcomes and discusses the role of catheter ablation to mitigate the morbidity and mortality associated with greater burden of atrial fibrillation.</AbstractText><br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 05 Sep 2023; 82:1039-1050</small></div>

<div><h4>Temporal Trends in Noncardiovascular Morbidity and Mortality Following Acute Myocardial Infarction.</h4><i>Christensen DM, Strange JE, El-Chouli M, Falkentoft AC, ... Torp-Pedersen C, Sehested TSG</i><br /><b>Background</b><br />Due to improved management, diagnosis, and care of myocardial infarction (MI), patients may now survive long enough to increasingly develop serious noncardiovascular conditions.<br /><b>Objectives</b><br />This study aimed to test this hypothesis by investigating the temporal trends in noncardiovascular morbidity and mortality following MI.<br /><b>Methods</b><br />We conducted a registry-based nationwide cohort study of all Danish patients with MI during 2000 to 2017. Outcomes were cardiovascular and noncardiovascular mortality, incident cancer, incident renal disease, and severe infectious disease.<br /><b>Results</b><br />From 2000 to 2017, 136,293 consecutive patients were identified (63.2% men, median age 69 years). The 1-year risk of cardiovascular mortality between 2000 to 2002 and 2015 to 2017 decreased from 18.4% to 7.6%, whereas noncardiovascular mortality decreased from 5.8% to 5.0%. This corresponded to an increase in the proportion of total 1-year mortality attributed to noncardiovascular causes from 24.1% to 39.5%. Furthermore, increases in 1-year risk of incident cancer (1.9%-2.4%), incident renal disease (1.0%-1.6%), and infectious disease (5.5%-9.1%) were observed (all P trend <0.01). In analyses standardized for changes in patient characteristics, the increased risk of cancer in 2015 to 2017 compared with 2000 to 2002 was no longer significant (standardized risk ratios for cancer: 0.99 [95% CI: 0.91-1.07]; renal disease: 1.28 [95% CI: 1.15-1.41]; infectious disease: 1.28 [95% CI: 1.23-1.34]).<br /><b>Conclusions</b><br />Although cardiovascular mortality following MI improved substantially during 2000 to 2017, the risk of noncardiovascular morbidity increased. Moreover, noncardiovascular causes constitute an increasing proportion of post-MI mortality. These findings suggest that further attention on noncardiovascular outcomes is warranted in guidelines and clinical practice and should be considered in the design of future clinical trials.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 05 Sep 2023; 82:971-981</small></div>

<div><h4>Long-Term Outcomes of Cardiogenic Shock Complicating Myocardial Infarction.</h4><i>Sterling LH, Fernando SM, Talarico R, Qureshi D, ... Tanuseputro P, Hibbert B</i><br /><b>Background</b><br />Cardiogenic shock secondary to acute myocardial infarction (AMI-CS) is associated with substantial short-term mortality; however, there are limited data on long-term outcomes and trends.<br /><b>Objectives</b><br />This study sought to examine long-term outcomes of AMI-CS patients.<br /><b>Methods</b><br />This was a population-based, retrospective cohort study in Ontario, Canada of critically ill adult patients with AMI-CS who were admitted to hospitals between April 1, 2009 and March 31, 2019. Outcome data were captured using linked health administrative databases.<br /><b>Results</b><br />A total of 9,789 consecutive patients with AMI-CS from 135 centers were included. The mean age was 70.5 ± 12.3 years, and 67.7% were male. The incidence of AMI-CS was 8.2 per 100,000 person-years, and it increased over the study period. Critical care interventions were common, with 5,422 (55.4%) undergoing invasive mechanical ventilation, 1,425 (14.6%) undergoing renal replacement therapy, and 1,484 (15.2%) receiving mechanical circulatory support. A total of 2,961 patients (30.2%) died in the hospital, and 4,004 (40.9%) died by 1 year. Mortality at 5 years was 58.9%. Small improvements in short- and long-term mortality were seen over the study period. Among survivors to discharge, 2,870 (42.0%) required increased support in care from their preadmission baseline, 3,244 (47.5%) were readmitted to the hospital within 1 year, and 1,047 (15.3%) died within 1 year. The mean number of days at home in the year following discharge was 307.9 ± 109.6.<br /><b>Conclusions</b><br />Short- and long-term mortality among patients with AMI-CS is high, with minimal improvement over time. AMI-CS survivors experience significant morbidity, with high risks of readmission and death. Future studies should evaluate interventions to minimize postdischarge morbidity and mortality among AMI-CS survivors.<br /><br />Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 05 Sep 2023; 82:985-995</small></div>

<div><h4>Mortality Trends After Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction.</h4><i>Thrane PG, Olesen KKW, Thim T, Gyldenkerne C, ... Kristensen SD, Maeng M</i><br /><b>Background</b><br />Observational studies have reported that mortality rates after ST-segment elevation myocardial infarction (STEMI) have been stable since 2006 to 2010.<br /><b>Objectives</b><br />The aim of this study was to evaluate the temporal trends in 1-year, 30-day, and 31- to 365-day mortality after STEMI in Western Denmark where primary percutaneous coronary intervention (PCI) has been the national reperfusion strategy since 2003.<br /><b>Methods</b><br />Using the Western Denmark Heart Registry, the study identified first-time PCI-treated patients undergoing primary PCI (pPCI) for STEMI from 2003 to 2018. Based on the year of pPCI, patients were divided into 4 time-interval groups and followed up for 1 year using the Danish national health registries.<br /><b>Results</b><br />A total of 19,613 patients were included. Median age was 64 years, and 74% were male. One-year mortality decreased gradually from 10.8% in 2003-2006, 10.4% in 2007-2010, 9.1% in 2011-2014, to 7.7% in 2015-2018 (2015-2018 vs 2003-2006: adjusted HR [aHR]: 0.71; 95% CI: 0.62-0.82). The largest absolute mortality decline occurred in the 0- to 30-day period with a 2.3% reduction (aHR: 0.69; 95% CI: 0.59-0.82), and to a lesser extent in the 31- to 365-day period (risk reduction: 1.0%; aHR: 0.71; 95% CI: 0.56-0.90).<br /><b>Conclusions</b><br />In a high-income European country with a fully implemented pPCI strategy, 1-year mortality in pPCI-treated patients with STEMI decreased substantially between 2003 and 2018. Approximately three-quarters of the absolute mortality reduction occurred within the first 30 days after pPCI. These results indicate that optimization of early management of pPCI-treated patients with STEMI offers great opportunities for improving overall survival in contemporary clinical practice.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 05 Sep 2023; 82:999-1010</small></div>

<div><h4>Prevalence, Characteristics, and Prognostic Relevance of Donor-Transmitted Coronary Artery Disease in Heart Transplant Recipients.</h4><i>Couto-Mallón D, Almenar-Bonet L, Barge-Caballero E, Hernández-Pérez FJ, ... Muñiz J, Crespo-Leiro MG</i><br /><b>Background</b><br />The reported prevalence of donor-transmitted coronary artery disease (TCAD) in heart transplantation (HT) is variable, and its prognostic impact remains unclear.<br /><b>Objectives</b><br />The goal of this study was to characterize TCAD in a contemporary multicentric cohort and to study its prognostic relevance.<br /><b>Methods</b><br />This was a retrospective study of consecutive patients >18 years old who underwent HT in 11 Spanish centers from 2008 to 2018. Only patients with a coronary angiography (c-angio) within the first 3 months after HT were studied. Significant TCAD (s-TCAD) was defined as any stenosis ≥50% in epicardial coronary arteries, and nonsignificant TCAD (ns-TCAD) as stenosis <50%. Clinical outcomes were assessed by means of Cox regression and competing risks regression. Patients were followed-up for a median period of 6.3 years after c-angio.<br /><b>Results</b><br />From a cohort of 1,918 patients, 937 underwent c-angio. TCAD was found in 172 patients (18.3%): s-TCAD in 65 (6.9%) and ns-TCAD in 107 (11.4%). Multivariable Cox regression analysis did not show a statistically significant association between s-TCAD and all-cause mortality (adjusted HR: 1.44; 95% CI: 0.89-2.35; P = 0.141); however, it was an independent predictor of cardiovascular mortality (adjusted HR: 2.25; 95% CI: 1.20-4.19; P = 0.011) and the combined event cardiovascular death or nonfatal MACE (adjusted HR: 2.42; 95% CI: 1.52-3.85; P < 0.001). No statistically significant impact of ns-TCAD on clinical outcomes was detected. The results were similar when reassessed by means of competing risks regression.<br /><b>Conclusions</b><br />TCAD was not associated with reduced survival in patients alive and well enough to undergo post-HT angiography within the first 3 months; however, s-TCAD patients showed increased risk of cardiovascular death and MACE.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 29 Aug 2023; 82:753-767</small></div>

<div><h4>Predictors of 5-Year Mortality in Patients Managed With a Magnetically Levitated Left Ventricular Assist Device.</h4><i>Nayak A, Hall SA, Uriel N, Goldstein DJ, ... Wang A, Mehra MR</i><br /><b>Background</b><br />In advanced heart failure patients implanted with a fully magnetically levitated HeartMate 3 (HM3, Abbott) left ventricular assist device (LVAD), it is unknown how preimplant factors and postimplant index hospitalization events influence 5-year mortality in those able to be discharged.<br /><b>Objectives</b><br />The goal was to identify risk predictors of mortality through 5 years among HM3 LVAD recipients conditional on discharge from index hospitalization in the MOMENTUM 3 pivotal trial.<br /><b>Methods</b><br />This analysis evaluated 485 of 515 (94%) patients discharged after implantation of the HM3 LVAD. Preimplant (baseline), implant surgery, and index hospitalization characteristics were analyzed individually, and as multivariable predictors for mortality risk through 5 years.<br /><b>Results</b><br />Cumulative 5-year mortality in the cohort (median age: 62 years, 80% male, 65% White, 61% destination therapy due to transplant ineligibility) was 38%. Two preimplant characteristics (elevated blood urea nitrogen and prior coronary artery bypass graft or valve procedure) and 3 postimplant characteristics (hemocompatibility-related adverse events, ventricular arrhythmias, and estimated glomerular filtration rate <60 mL/min/1.73 m<sup>2</sup> at discharge) were predictors of 5-year mortality. In 171 of 485 patients (35.3%) without any risk predictors, 5-year mortality was reduced to 22.6% (95% CI: 15.4%-32.7%). Even among those with 1 or more predictors, mortality was <50% at 5 years (45.7% [95% CI: 39.0%-52.8%]).<br /><b>Conclusions</b><br />Long-term survival in successfully discharged HM3 LVAD recipients is largely influenced by clinical events experienced during the index surgical hospitalization in tandem with baseline factors, with mortality of <50% at 5 years. In patients without identified predictors of risk, long-term 5-year mortality is low and rivals that achieved with heart transplantation, even though most were implanted with destination therapy intent. (MOMENTUM 3 IDE Clinical Study Protocol, NCT02224755; MOMENTUM 3 Pivotal Cohort Extended Follow-up PAS, NCT03982979).<br /><br />Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 29 Aug 2023; 82:771-781</small></div>

<div><h4>Monitoring of Myocardial Involvement in Early Arrhythmogenic Right Ventricular Cardiomyopathy Across the Age Spectrum.</h4><i>Kirkels FP, van Osta N, Rootwelt-Norberg C, Chivulescu M, ... Haugaa KH, Lumens J</i><br /><b>Background</b><br />Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by fibrofatty replacement of primarily the right ventricular myocardium, a substrate for life-threatening ventricular arrhythmias (VAs). Repeated cardiac imaging of at-risk relatives is important for early disease detection. However, it is not known whether screening should be age-tailored.<br /><b>Objectives</b><br />The goal of this study was to assess the need for age-tailoring of follow-up protocols in early ARVC by evaluating myocardial disease progression in different age groups.<br /><b>Methods</b><br />We divided patients with early-stage ARVC and genotype-positive relatives without overt structural disease and VA at first evaluation into 3 groups: age <30 years, 30 to 50 years, and ≥50 years. Longitudinal biventricular deformation characteristics were used to monitor disease progression. To link deformation abnormalities to underlying myocardial disease substrates, Digital Twins were created using an imaging-based computational modeling framework.<br /><b>Results</b><br />We included 313 echocardiographic assessments from 82 subjects (57% female, age 39 ± 17 years, 10% probands) during 6.7 ± 3.3 years of follow-up. Left ventricular global longitudinal strain slightly deteriorated similarly in all age groups (0.1%-point per year [95% CI: 0.05-0.15]). Disease progression in all age groups was more pronounced in the right ventricular lateral wall, expressed by worsening in longitudinal strain (0.6%-point per year [95% CI: 0.46-0.70]) and local differences in myocardial contractility, compliance, and activation delay in the Digital Twin. Six patients experienced VA during follow-up.<br /><b>Conclusions</b><br />Disease progression was similar in all age groups, and sustained VA also occurred in patients aged >50 years without overt ARVC phenotype at first evaluation. Unlike recommended by current guidelines, our study suggests that follow-up of ARVC patients and relatives should not stop at older age.<br /><br />Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 29 Aug 2023; 82:785-797</small></div>

<div><h4>Neighborhood Childhood Opportunity, Race/Ethnicity, and Surgical Outcomes in Children With Congenital Heart Disease.</h4><i>Duong SQ, Elfituri MO, Zaniletti I, Ressler RW, ... Seiden HS, Anderson BR</i><br /><b>Background</b><br />Racial and ethnic disparities in outcomes for children with congenital heart disease (CHD) coexist with disparities in educational, environmental, and economic opportunity.<br /><b>Objectives</b><br />We sought to determine the associations between childhood opportunity, race/ethnicity, and pediatric CHD surgery outcomes.<br /><b>Methods</b><br />Pediatric Health Information System encounters aged <18 years from 2016 to 2022 with International Classification of Diseases-10th edition codes for CHD and cardiac surgery were linked to ZIP code-level Childhood Opportunity Index (COI), a score of neighborhood educational, environmental, and socioeconomic conditions. The associations of race/ethnicity and COI with in-hospital surgical death were modeled with generalized estimating equations and formal mediation analysis. Neonatal survival after discharge was modeled by Cox proportional hazards.<br /><b>Results</b><br />Of 54,666 encounters at 47 centers, non-Hispanic Black (Black) (OR: 1.20; P = 0.01), Asian (OR: 1.75; P < 0.001), and Other (OR: 1.50; P < 0.001) groups had increased adjusted mortality vs non-Hispanic Whites. The lowest COI quintile had increased in-hospital mortality in unadjusted and partially adjusted models (OR: 1.29; P = 0.004), but not fully adjusted models (OR: 1.14; P = 0.13). COI partially mediated the effect of race/ethnicity on in-hospital mortality between 2.6% (P = 0.64) and 16.8% (P = 0.029), depending on model specification. In neonatal multivariable survival analysis (n = 13,987; median follow-up: 0.70 years), the lowest COI quintile had poorer survival (HR: 1.21; P = 0.04).<br /><b>Conclusions</b><br />Children in the lowest COI quintile are at risk for poor outcomes after CHD surgery. Disproportionally increased mortality in Black, Asian, and Other populations may be partially mediated by COI. Targeted investment in low COI neighborhoods may improve outcomes after hospital discharge. Identification of unmeasured factors to explain persistent risk attributed to race/ethnicity is an important area of future exploration.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 29 Aug 2023; 82:801-813</small></div>

<div><h4>Sex Differences in Thoracic Aortic Disease and Dissection: JACC Review Topic of the Week.</h4><i>Crousillat D, Briller J, Aggarwal N, Cho L, ... Scott N, Narula N</i><br /><AbstractText>Despite its higher prevalence among men, women with thoracic aortic aneurysm and dissection (TAAD) have lower rates of treatment and surgical intervention and often have worse outcomes. A growing number of women with TAAD also desire pregnancy, which can be associated with an increased risk of aortic complications. Understanding sex-specific differences in TAAD has the potential to improve care delivery, reduce disparities in treatment, and optimize outcomes for women with TAAD.</AbstractText><br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 29 Aug 2023; 82:817-827</small></div>