<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>