<div><h4>Pathophysiology, Echocardiographic Diagnosis, and Treatment of Atrial Functional Mitral Regurgitation: JACC State-of-the-Art Review.</h4><i>Farhan S, Silbiger JJ, Halperin JL, Zhang L, ... Sharma S, Lerakis S</i><br /><AbstractText>The conventional view holds that functional mitral regurgitation (MR) is caused by restriction of leaflet motion resulting from displacement of the papillary muscle-bearing segments of the left ventricle. In the past decade, evidence has accrued suggesting functional MR can also be caused by left atrial enlargement. This underrecognized cause of secondary MR-atrial functional MR (AF-MR)-is mechanistically linked to annular enlargement, perturbations of annular contraction, and atriogenic leaflet tethering. AF-MR has been described in patients with atrial fibrillation and heart failure with preserved ejection fraction. Preliminary data suggest rhythm control may decrease MR severity in patients with atrial fibrillation. Additionally, several studies have reported reductions in MR and symptomatic improvement with restrictive annuloplasty and transcatheter edge-to-edge repair. This review discusses the pathophysiology, echocardiographic diagnosis, and treatment of AF-MR. AF-tricuspid regurgitation is also discussed.</AbstractText><br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 13 Dec 2022; 80:2314-2330</small></div>

<div><h4>Hospitalizations and Mortality in Patients With Secondary Mitral Regurgitation and Heart Failure: The COAPT Trial.</h4><i>Giustino G, Camaj A, Kapadia SR, Kar S, ... Mack MJ, Stone GW</i><br /><b>Background</b><br />The impact of transcatheter edge-to-edge repair (TEER) on the rate and prognostic impact of hospitalizations in patients with heart failure (HF) and severe secondary mitral regurgitation is unknown.<br /><b>Objectives</b><br />This study sought to evaluate the effect of the MitraClip percutaneous edge-to edge repair system on fatal and nonfatal hospitalizations and their relationship with mortality in the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial.<br /><b>Methods</b><br />Patients with HF (n = 614) with severe secondary mitral regurgitation were randomized to TEER plus guideline-directed medical therapy (GDMT) versus GDMT alone. Hospitalizations were classified as fatal if death occurred during that hospitalization or nonfatal if the patient was discharged alive.<br /><b>Results</b><br />At 2 years, TEER treatment, compared with GDMT alone, resulted in lower time-to-first-event rates of any heart failure hospitalization (HFH) (34.8% vs 56.4%; HR: 0.51; 95% CI: 0.39-0.66) and fatal HFH (6.5% vs 12.6%; HR: 0.47; 95% CI: 0.26-0.85). TEER also resulted in lower rates of all-cause nonfatal and fatal hospitalizations. During the 2-year follow-up period, patients who underwent TEER spent an average of 2 more months alive and out of the hospital than did patients treated with GDMT alone (581 ± 27 days vs 519 ± 26 days; P = 0.002). All HFHs (adjusted HR: 6.37; 95% CI: 4.63-8.78) and nonfatal HFHs (adjusted HR: 1.78; 95% CI: 1.27-2.49) were consistently independently associated with increased 2-year mortality in both the TEER and GDMT groups (P<sub>interaction</sub> = 0.34 and 0.39, respectively).<br /><b>Conclusions</b><br />In the COAPT trial, compared with GDMT alone, patients with HF and severe secondary mitral regurgitation undergoing TEER with the percutaneous edge-to edge repair system had lower 2-year rates of fatal and nonfatal all-cause hospitalizations and HFH and spent more time alive and out of the hospital. HFHs were strongly associated with mortality, irrespective of treatment. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [The COAPT Trial] and COAPT CAS [COAPT]; NCT01626079).<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 15 Nov 2022; 80:1857-1868</small></div>

<div><h4>Neurometabolism and Ventricular Dyssynchrony in Patients With Heart Failure and Reduced Ejection Fraction.</h4><i>Bai Y, Yun M, Nie B, Shan L, ... Zhang X, Li X</i><br /><b>Background</b><br />The brain coordinates the heart through the autonomic nervous system (ANS). Numerous mediator signals along the brain-heart axis interact with the neuronal-metabolic system in heart failure (HF). Disturbances in cardio-neural interactions influence the disease progression in patients with HF.<br /><b>Objectives</b><br />The purpose of this study was to investigate the interactome between ANS-associated neurometabolism and ventricular dyssynchrony in patients with heart failure with reduced ejection fraction (HFrEF). Further, we studied the association of neurometabolism with major arrhythmic events (MAEs).<br /><b>Methods</b><br />A total of 197 patients with HFrEF who underwent gated single-photon emission computed tomography myocardial perfusion imaging and the brain <sup>18</sup>F-fluorodeoxyglucose positron emission tomography/computed tomography were prospectively enrolled. Relationships between the brain metabolism and MAEs were assessed using Cox models and mediation analyses. Finally, metabolic central autonomic networks were constructed and statistically compared between patients with and without MAEs.<br /><b>Results</b><br />In total, 35 (17.8%) patients experienced MAEs during a median follow-up of 3.1 years. In patients with HFrEF (age 58 years [IQR: 50-64 years], left ventricular ejection fraction: 20.0% [IQR: 15.0%-25.0%]), glucose hypometabolism in the insula, hippocampus, amygdala, cingulate gyrus, and caudate nucleus were independent predictors for MAEs (all P < 0.05). Cerebral hypometabolism was related to ventricular dyssynchrony, which was the predominant risk factor of MAEs. Additionally, patients who experienced MAEs presented hypoconnectivity in the metabolic central autonomic network compared with those without MAEs (P < 0.05).<br /><b>Conclusions</b><br />We found an interaction of the neuronal metabolic-ventricular dyssynchronization axis in HF, which might be related to MAEs. This new brain-heart axis could expand our understanding of the distinct pathomechanisms of HFrEF.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 15 Nov 2022; 80:1884-1896</small></div>

<div><h4>Relationship of Circulating Vegetable Omega-3 to Prognosis in Patients With Heart Failure.</h4><i>Lázaro I, Lupón J, Cediel G, Codina P, ... Sala-Vila A, Bayés-Genís A</i><br /><b>Background</b><br />There is an urgent need for cost-effective strategies to promote quality of life in patients with heart failure (HF). Several studies reported benefits in HF prognosis for marine omega-3 fatty acids and plant-based dietary patterns.<br /><b>Objectives</b><br />The aim of this study was to explore whether dietary alpha-linolenic acid (ALA), the main plant omega-3, relates to a better HF prognosis.<br /><b>Methods</b><br />ALA was determined in serum phospholipids (which reflect long-term dietary ALA intake and metabolism) by gas chromatography in 905 ambulatory patients with HF caused by different etiologies.<br /><b>Results</b><br />After a median follow-up of 2.4 years (range: 0.02-3 years), 140 all-cause deaths, 85 cardiovascular (CV) deaths, and 141 first HF hospitalizations (composite of all-cause death and first HF hospitalization, n = 238) were documented. Using Cox regression analyses, we observed that, compared with patients at the lowest quartile of ALA in serum phospholipids (Q1), those at the 3 upper quartiles (Q2-Q4) exhibited a reduction in the risk of composite of all-cause death and first HF hospitalization (HR: 0.61; 95% CI: 0.46-0.81). Statistically significant reductions were observed for all-cause death (HR: 0.58; 95% CI: 0.41-0.82), CV death (HR: 0.51; 95% CI: 0.32-0.80), first HF hospitalization (HR: 0.58; 95% CI: 0.40-0.84), and the composite of CV death and HF hospitalization (HR: 0.58; 95% CI: 0.42-0.79).<br /><b>Conclusions</b><br />HF patients with bottom 25% ALA levels in serum phospholipids had a worse prognosis during a mid-term follow-up compared with those with the highest levels. This might be a target population in whom to test dietary ALA-rich interventions to promote quality of life.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 01 Nov 2022; 80:1751-1758</small></div>

<div><h4>Acute Coronary Occlusion in Patients With Non-ST-Segment Elevation Out-of-Hospital Cardiac Arrest.</h4><i>Spirito A, Vaisnora L, Papadis A, Iacovelli F, ... Windecker S, Räber L</i><br /><b>Background</b><br />According to current guidelines, hemodynamic status should guide the decision between immediate and delayed coronary angiography (CAG) in out-of-hospital cardiac arrest (OHCA) patients without ST-segment elevation. A delayed strategy is advised in hemodynamically stable patients, and an immediate approach is recommended in unstable patients.<br /><b>Objectives</b><br />This study sought to assess the frequency, predictors, and clinical impact of acute coronary occlusion in hemodynamically stable and unstable OHCA patients without ST-segment elevation.<br /><b>Methods</b><br />Consecutive unconscious OHCA patients without ST-segment elevation who were undergoing CAG at Bern University Hospital (Bern, Switzerland) between 2011 and 2019 were included. Frequency and predictors of acute coronary artery occlusions and their impact on all-cause and cardiovascular mortality at 1 year were assessed.<br /><b>Results</b><br />Among the 386 patients, 169 (43.8%) were hemodynamically stable. Acute coronary occlusions were found in 19.5% of stable and 24.0% of unstable OHCA patients (P = 0.407), and the presence of these occlusions was predicted by initial chest pain and shockable rhythm, but not by hemodynamic status. Acute coronary occlusion was associated with an increased risk of cardiovascular death (adjusted HR: 2.74; 95% CI: 1.22-6.15) but not of all-cause death (adjusted HR: 0.72; 95% CI: 0.44-1.18). Hemodynamic instability was not predictive of fatal outcomes.<br /><b>Conclusions</b><br />Acute coronary artery occlusions were found in 1 in 5 OHCA patients without ST-segment elevation. The frequency of these occlusions did not differ between stable and unstable patients, and the occlusions were associated with a higher risk of cardiovascular death. In OHCA patients without ST-segment elevation, chest pain or shockable rhythm rather than hemodynamic status identifies patients with acute coronary occlusion.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 07 Feb 2023; 81:446-456</small></div>

<div><h4>Infective Endocarditis After Transcatheter Aortic Valve Replacement: JACC State-of-the-Art Review.</h4><i>Del Val D, Panagides V, Mestres CA, Miró JM, Rodés-Cabau J</i><br /><AbstractText>Infective endocarditis (IE) is a rare but serious complication following transcatheter aortic valve replacement (TAVR). Despite substantial improvements in the TAVR procedure (less invasive) and its expansion to younger and healthier patients, the incidence of IE after TAVR remains stable, with incidence rates similar to those reported after surgical aortic valve replacement. Although IE after TAVR is recognized as a subtype of prosthetic valve endocarditis, this condition represents a particularly challenging scenario given its unique clinical and microbiological profile, the high incidence of IE-related complications, the uncertain role of cardiac surgery, and the dismal prognosis in most patients with TAVR-IE. The number of TAVR procedures is expected to grow exponentially in the coming years, increasing the number of patients at risk of developing this life-threatening complication. Therefore, a detailed understanding of this disease and its complications will be essential to improve clinical 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 Jan 2023; 81:394-412</small></div>

<div><h4>Left Ventricular Filling Pressure in Chronic Thromboembolic Pulmonary Hypertension.</h4><i>Gerges C, Pistritto AM, Gerges M, Friewald R, ... Klepetko W, Lang IM</i><br /><b>Background</b><br />Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by obstruction of major pulmonary arteries with organized thrombi. Clinical risk factors for pulmonary hypertension due to left heart disease including metabolic syndrome, left-sided valvular heart disease, and ischemic heart disease are common in CTEPH patients.<br /><b>Objectives</b><br />The authors sought to investigate prevalence and prognostic implications of elevated left ventricular filling pressures (LVFP) in CTEPH.<br /><b>Methods</b><br />A total of 593 consecutive CTEPH patients undergoing a first diagnostic right and left heart catheterization were included in this study. Mean pulmonary arterial wedge pressure (mPAWP) and left ventricular end-diastolic pressure (LVEDP) were utilized for assessment of LVFP. Two cutoffs were applied to identify patients with elevated LVFP: 1) for the primary analysis mPAWP and/or LVEDP >15 mm Hg, as recommended by the current pulmonary hypertension guidelines; and 2) for the secondary analysis mPAWP and/or LVEDP >11 mm Hg, representing the upper limit of normal. Clinical and echocardiographic features, and long-term mortality were assessed.<br /><b>Results</b><br />LVFP was >15 mm Hg in 63 (10.6%) and >11 mm Hg in 222 patients (37.4%). Univariable logistic regression analysis identified age, systemic hypertension, diabetes, atrial fibrillation, calcific aortic valve stenosis, mitral regurgitation, and left atrial volume as significant predictors of elevated LVFP. Atrial fibrillation, calcific aortic valve stenosis, mitral regurgitation, and left atrial volume remained independent determinants of LVFP in adjusted analysis. At follow-up, higher LVFPs were measured in patients who had meanwhile undergone pulmonary endarterectomy (P = 0.002). LVFP >15 mm Hg (P = 0.021) and >11 mm Hg (P = 0.006) were both associated with worse long-term survival.<br /><b>Conclusions</b><br />Elevated LVFP is common, appears to be due to comorbid left heart disease, and predicts prognosis in CTEPH.<br /><br />Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 21 Feb 2023; 81:653-664</small></div>

<div><h4>Association of Cardiac Remodeling with Aortic Regurgitation Outcomes: The AR Consortium of the SCMR Registry.</h4><i>Malahfji M, Crudo V, Kaolawanich Y, Nguyen DT, ... Kim R, Shah DJ</i><br /><b>Background</b><br />Quantitative cardiac magnetic resonance (CMR) outcome studies in aortic regurgitation (AR) are few. It is unclear if volume measurements are beneficial over diameters.<br /><b>Objectives</b><br />To evaluate the association of CMR quantitative thresholds and outcomes in AR patients.<br /><b>Methods</b><br />in a multicenter study, asymptomatic patients with moderate or severe AR on CMR with preserved LV ejection fraction (LVEF) were evaluated. Primary outcome was development of symptoms or decrease in LVEF to <50%, guideline indications for surgery based on LV dimensions, or death under medical management. Secondary outcome was the same excluding surgery for remodeling indications. We excluded patients who underwent surgery within 30 days of CMR. ROC analyses for the association with outcome were performed.<br /><b>Results</b><br />We studied 458 patients, median age 60 (IQR 46-70) years. During a median follow-up of 2.4 years (IQR 0.9, 5.3), 133 events occurred. Optimal thresholds were regurgitant volume of 47 ml and regurgitant fraction of 43%, indexed LV end-systolic (iLVES) volume of 43 ml/m<sup>2,</sup> iLVED volume of 109 ml/m<sup>2</sup>, and iLVES diameter of 2 cm/m<sup>2</sup>. In multivariable regression analysis, iLVES volume ≥43 ml/m<sup>2</sup> (HR 2.53 (1.75, 3.66), P<0.001) and and iLVED volume ≥ 109 ml/m<sup>2</sup> were independently associated with the outcomes and provided additional discrimination improvement over iLVES diameter, whereas iLVES diameter was independently associated with the primary outcome but not the secondary outcome.<br /><b>Conclusion</b><br />In asymptomatic AR patients with preserved LVEF, CMR findings can be used to guide management. CMR based LV end-systolic volume assessment performed favorably compared to LV diameters.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Am Coll Cardiol: 03 Mar 2023; epub ahead of print</small></div>

<div><h4>Nonthrombogenic Roles of the Left Atrial Appendage: JACC Review Topic of the Week.</h4><i>Alkhouli M, Di Biase L, Natale A, Rihal CS, ... Lakkireddy D, Friedman PA</i><br /><AbstractText>The atrial appendage (LAA) is a well-established source of cardioembolism in patients with atrial fibrillation. Therefore, research involving the LAA has largely focused on its thrombogenic attribute and the utility of its exclusion in stroke prevention. However, recent studies have highlighted several novel functions of the LAA that may have important therapeutic implications. In this paper, we provide a concise overview of the LAA anatomy and summarize the emerging data on its nonthrombogenic roles.</AbstractText><br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 21 Mar 2023; 81:1063-1075</small></div>

<div><h4>Medicare Coverage and Out-of-Pocket Costs of Quadruple Drug Therapy for Heart Failure.</h4><i>Faridi KF, Dayoub EJ, Ross JS, Dhruva SS, Ahmad T, Desai NR</i><br /><b>Background</b><br />Beta-blockers, angiotensin receptor-neprilysin inhibitor (ARNI), mineralocorticoid receptor antagonists, and sodium-glucose cotransporter-2 inhibitors (SGLT2i), known as quadruple therapy, are recommended for patients with heart failure with reduced ejection fraction (HFrEF).<br /><b>Objectives</b><br />This study sought to determine Medicare coverage and out-of-pocket (OOP) costs of quadruple therapy and regimens excluding ARNI or SGLT2i.<br /><b>Methods</b><br />This study assessed cost sharing, prior authorization, and step therapy in all 4,068 Medicare prescription drug plans in 2020. OOP costs were determined during the standard coverage period and annually based on the Medicare Part D standard benefit, inclusive of deductible, standard coverage, coverage gap, and catastrophic coverage.<br /><b>Results</b><br />Tier ≥3 cost sharing was required by 99.1% of plans for ARNI and 98.5% for at least 1 SGLT2i. Only ARNI required prior authorization (24.3% of plans), and step therapy was required only for SGLT2is (5.4%) and eplerenone (0.8%). The median 30-day standard coverage OOP cost of quadruple therapy was $94 (IQR: $84-$100), including $47 (IQR: $40-$47) for ARNI and $45 (IQR: $40-$47) for SGLT2i. The median annual OOP cost of quadruple therapy was $2,217 (IQR: $1,956-$2,579) compared with $1,319 (IQR: $1,067-$1,675) when excluding SGLT2i and $1,322 (IQR: $1,025-$1,588) when including SGLT2i and substituting an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker for ARNI. The median 30-day OOP cost of generic regimens was $3 (IQR: $0-$9).<br /><b>Conclusions</b><br />Medicare drug plans restrict coverage of quadruple therapy through cost sharing, with OOP costs that are substantially higher than generic regimens. Quadruple therapy may be unaffordable for many Medicare patients with HFrEF unless medication prices and cost sharing are reduced.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 28 Jun 2022; 79:2516-2525</small></div>

<div><h4>Intravascular Imaging During Percutaneous Coronary Intervention: JACC State-of-the-Art Review.</h4><i>Truesdell AG, Alasnag MA, Kaul P, Rab ST, ... Kirtane AJ, ACC Interventional Council</i><br /><AbstractText>Coronary angiography has historically served as the gold standard for diagnosis of coronary artery disease and guidance of percutaneous coronary intervention (PCI). Adjunctive use of contemporary intravascular imaging (IVI) technologies has emerged as a complement to conventional angiography-to further characterize plaque morphology and optimize the performance of PCI. IVI has utility for preintervention lesion and vessel assessment, periprocedural guidance of lesion preparation and stent deployment, and postintervention assessment of optimal endpoints and exclusion of complications. The role of IVI in reducing major adverse cardiac events in complex lesion subsets is emerging, and further studies evaluating broader use are underway or in development. This paper provides an overview of currently available IVI technologies, reviews data supporting their utilization for PCI guidance and optimization across a variety of lesion subsets, proposes best practices, and advocates for broader use of these technologies as a part of contemporary practice.</AbstractText><br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Am Coll Cardiol: 14 Feb 2023; 81:590-605</small></div>

<div><h4>Preoperative Atrial Fibrillation and Cardiovascular Outcomes After Noncardiac Surgery.</h4><i>Prasada S, Desai MY, Saad M, Smilowitz NR, ... Nakhla S, Mentias A</i><br /><b>Background</b><br />The impact of pre-existing atrial fibrillation (AF) on outcomes after noncardiac surgery is not clear.<br /><b>Objectives</b><br />We aimed to study the impact of AF on the risk of adverse outcomes after noncardiac surgery in a nationwide cohort.<br /><b>Methods</b><br />We identified Medicare beneficiaries admitted for noncardiac surgery from 2015 to 2019 and divided the study cohort into 2 groups: with and without AF. Noncardiac surgery was classified into vascular, thoracic, general, genitourinary, gynecological, orthopedics and neurosurgery, breast, head and neck, and transplant. We used propensity score matching on exact age, sex, race, urgency and type of surgery, revised cardiac risk index (RCRI) and CHA<sub>2</sub>DS<sub>2</sub>-VASc score, and tight caliper on other comorbidities. The study outcomes were 30-day mortality, stroke, myocardial infarction, and heart failure. We examined the incremental utility of AF in addition to RCRI to predict adverse events after noncardiac surgery.<br /><b>Results</b><br />The study cohort included 8,635,758 patients who underwent noncardiac surgery (16.4% with AF). Patients with AF were older, more likely to be men, and had higher prevalence of comorbidities. After propensity score matching, AF was associated with higher risk of mortality (OR: 1.31; 95% CI: 1.30-1.32), heart failure (OR: 1.31; 95% CI: 1.30-1.33), and stroke (OR: 1.40; 95% CI: 1.37-1.43) and lower risk of myocardial infarction (OR: 0.81; 95% CI: 0.79-0.82). Results were consistent in subgroup analysis by sex, race, type of surgery, and all strata of RCRI and CHA<sub>2</sub>DS<sub>2</sub>-VASc score. AF improved the discriminative ability of RCRI (C-statistic 0.73 to 0.76).<br /><b>Conclusion</b><br />Pre-existing AF is independently associated with postoperative adverse outcomes after NCS.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 28 Jun 2022; 79:2471-2485</small></div>

<div><h4>Cigarette Smoking, Cessation, and Risk of Heart Failure With Preserved and Reduced Ejection Fraction.</h4><i>Ding N, Shah AM, Blaha MJ, Chang PP, Rosamond WD, Matsushita K</i><br /><b>Background</b><br />Smoking is well-recognized as a risk factor for heart failure (HF). However, few studies have evaluated the prospective association of cigarette smoking and smoking cessation with heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) as distinct phenotypes.<br /><b>Objectives</b><br />The aim of this study was to quantify the association of cigarette smoking and smoking cessation with the incidence of HFpEF and HFrEF.<br /><b>Methods</b><br />In 9,345 ARIC (Atherosclerosis Risk In Communities) study White and Black participants without history of HF at baseline in 2005 (age range 61-81 years), we quantified the associations of several established cigarette smoking parameters (smoking status, pack-years, intensity, duration, and years since cessation) with physician-adjudicated incident acute decompensated HF using multivariable Cox models.<br /><b>Results</b><br />Over a median follow-up of 13.0 years, there were 1,215 incident HF cases. Compared with never smokers, current cigarette smoking was similarly associated with HFpEF and HFrEF, with adjusted HRs ∼2. There was a dose-response relationship for pack-years of smoking and HF. A more extended period of smoking cessation was associated with a lower risk of HF, but significantly elevated risk persisted up to a few decades for HFpEF and HFrEF.<br /><b>Conclusions</b><br />All cigarette smoking parameters consistently showed significant and similar associations with HFpEF and HFrEF. Smoking cessation significantly reduced the risk of HF, but excess HF risk persisted for a few decades. Our results strengthened the evidence that smoking is an important modifiable risk factor for HF and highlighted the importance of smoking prevention and cessation for the prevention of HF, including HFpEF.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 14 Jun 2022; 79:2298-2305</small></div>

<div><h4>Transcatheter Closure of Atrial and Ventricular Septal Defects: JACC Focus Seminar.</h4><i>Turner ME, Bouhout I, Petit CJ, Kalfa D</i><br /><AbstractText>The field of congenital interventional cardiology has experienced tremendous growth in recent years. Beginning with the development of early devices for transcatheter closure of septal defects in the 1970s and 1980s, such technologies have evolved to become a mainstay of treatment for many atrial septal defects (ASDs) and ventricular septal defects (VSDs). Percutaneous device closure is now the preferred approach for the majority of secundum ASDs. It is also a viable treatment option for selected VSDs, though limitations still exist. In this review, the authors describe the current state of transcatheter closure of ASDs and VSDs in children and adults, including patient selection, procedural approach, and outcomes. Potential areas for future evolution and innovation are also discussed.</AbstractText><br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 07 Jun 2022; 79:2247-2258</small></div>

<div><h4>Inflammasome Signaling in Atrial Fibrillation: JACC State-of-the-Art Review.</h4><i>Ajoolabady A, Nattel S, Lip GYH, Ren J</i><br /><AbstractText>As the most prevalent form of arrhythmia, atrial fibrillation (AF) increases the risk of heart failure, thromboembolism, and stroke, contributing to the raising mortality and morbidity in patients with cardiovascular diseases. Despite the multifaceted nature of AF pathogenesis and complexity of AF pathophysiology, a growing body of evidence indicates that the NLRP3 inflammasome activation contributes to onset and progression of AF. Herein, the authors aim at reviewing the current literature on the role of inflammasome signaling in AF pathogenesis, and novel therapeutic options in the management of AF.</AbstractText><br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 14 Jun 2022; 79:2349-2366</small></div>

<div><h4>Care Models for Acute Chest Pain That Improve Outcomes and Efficiency: JACC State-of-the-Art Review.</h4><i>Dawson LP, Smith K, Cullen L, Nehme Z, ... Taylor AJ, Stub D</i><br /><AbstractText>Existing assessment pathways for acute chest pain are often resource-intensive, prolonged, and expensive. In this review, the authors describe existing chest pain pathways and current issues at the patient and system level, and provide an overview of recent advances in chest pain research that could inform improved outcomes for both patients and health systems. There are multiple avenues to improve existing models of chest pain care, including novel risk stratification pathways incorporating highly sensitive point-of-care troponin assays; new devices available before first medical contact that could allow clinicians to access vital signs and electrocardiogram data; artificial intelligence and precision medicine tools that may guide indications for further testing; and strategies to improve hospital benchmarking and performance monitoring to standardize care. Improving the speed and accuracy of chest pain diagnosis and management should be a priority for researchers and is likely to translate to substantive benefits for patients and health systems.</AbstractText><br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 14 Jun 2022; 79:2333-2348</small></div>

<div><h4>Early Coronary Atherosclerosis in Women With Previous Preeclampsia.</h4><i>Hauge MG, Damm P, Kofoed KF, Ersbøll AS, ... Gustafsson F, Linde JJ</i><br /><b>Background</b><br />Women with previous preeclampsia have an increased risk of coronary artery disease later in life.<br /><b>Objectives</b><br />This study aimed to determine the prevalence of coronary atherosclerosis in younger women with previous preeclampsia in comparison with women from the general population.<br /><b>Methods</b><br />Women aged 40-55 years with previous preeclampsia were matched 1:1 on age and parity with women from the general population. Participants completed an extensive questionnaire, a clinical examination, and a coronary computed tomography angiography (CTA). The main study outcome was the prevalence of any coronary atherosclerosis on coronary CTA or a calcium score >0 in case of a nondiagnostic coronary CTA.<br /><b>Results</b><br />A total of 1,417 women, with a mean age of 47 years, were included (708 women with previous preeclampsia and 709 control subjects from the general population). Women with previous preeclampsia were more likely to have hypertension (284 [40.1%] vs 162 [22.8%]; P < 0.001), dyslipidemia (338 [47.7%] vs 296 [41.7%]; P = 0.023), diabetes mellitus (24 [3.4%] vs 8 [1.1%]; P = 0.004), and high body mass index (27.3 ± 5.7 kg/m<sup>2</sup> vs 25.0 ± 4.2 kg/m<sup>2</sup>; P < 0.001). Cardiac computed tomography was performed in all women. The prevalence of any coronary atherosclerosis was higher in the preeclampsia group (193 [27.4%] vs 141 [20.0%]; P = 0.001) with an OR: 1.41 (95% CI: 1.08-1.85; P = 0.012) after adjustment for age, dyslipidemia, diabetes mellitus, smoking, body mass index, menopause, and parity.<br /><b>Conclusions</b><br />Younger women with previous preeclampsia had a slightly higher prevalence of coronary atherosclerosis compared with age- and parity-matched women from the general population. Preeclampsia remained an independent risk factor after adjustment for traditional cardiovascular risk factors. (The CoPenHagen PREeClampsia and cardIOvascUlar diSease study [CPH-PRECIOUS]; NCT03949829).<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 14 Jun 2022; 79:2310-2321</small></div>

<div><h4>Safety of Provocative Testing With Intracoronary Acetylcholine and Implications for Standard Protocols.</h4><i>Takahashi T, Samuels BA, Li W, Parikh MA, ... Kobayashi Y, Microvascular Network</i><br /><b>Background</b><br />Heterogeneity in diagnostic criteria and provocation protocols has posed challenges in understanding the safety of coronary provocation testing with intracoronary acetylcholine (ACh) for the contemporary diagnosis of epicardial and microvascular spasm.<br /><b>Objectives</b><br />We examined the safety of testing and subgroup differences in procedural risks based on ethnicity, diagnostic criteria, and provocation protocols.<br /><b>Methods</b><br />PubMed and Embase were searched in November 2021 to identify original articles reporting procedural complications associated with intracoronary ACh administration. The primary outcome was the pooled estimate of the incidence of major complications including death, myocardial infarction, ventricular tachycardia/fibrillation, and shock.<br /><b>Results</b><br />A total of 16 studies with 12,585 patients were included in the meta-analysis. The overall pooled estimate of the incidence of major complications was 0.5% (95% CI: 0.0%-1.3%) without any reports of death. Exploratory subgroup analyses revealed that the pooled incidence of major complications was significantly higher in the studies that followed the contemporary diagnosis criteria for epicardial spasm defined as ≥90% diameter reduction (1.0%; 95% CI: 0.3%-2.0%) but significantly lower in Western populations (0.0%; 95% CI: 0.0%-0.45%). The rate of positive epicardial spasm and the incidence of major complications were similar between provocation protocols using the maximum ACh doses of 100 μg and 200 μg.<br /><b>Conclusions</b><br />Intracoronary ACh administration for the contemporary diagnosis of epicardial and microvascular spasm is a safe procedure. Moreover, excellent safety records are observed in Western populations primarily presenting with myocardial ischemia and/or infarction with nonobstructive coronary arteries. This study will help standardize ACh testing to improve clinical diagnosis and ensure procedural safety.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 21 Jun 2022; 79:2367-2378</small></div>

<div><h4>Elevated Remnant Cholesterol Reclassifies Risk of Ischemic Heart Disease and Myocardial Infarction.</h4><i>Doi T, Langsted A, Nordestgaard BG</i><br /><b>Background</b><br />Elevated remnant cholesterol causes ischemic heart disease.<br /><b>Objectives</b><br />We tested the hypothesis that the inclusion of elevated remnant cholesterol will lead to appropriate reclassification of individuals who later experience myocardial infarction and ischemic heart disease.<br /><b>Methods</b><br />For >10 years we followed up 41,928 white Danish individuals from the Copenhagen General Population Study without a history of ischemic cardiovascular disease, diabetes, and statin use. Using predefined cut points for elevated remnant cholesterol, we calculated net reclassification index (NRI) from below to above 5%, 7.5%, and/or 10% 10-year occurrence of myocardial infarction and ischemic heart disease defined as a composite of death from ischemic heart disease, myocardial infarction, and coronary revascularization.<br /><b>Results</b><br />For individuals with remnant cholesterol levels ≥95th percentile (≥1.6 mmol/L, 61 mg/dL), 23% (P < 0.001) of myocardial infarction and 21% (P < 0.001) of ischemic heart disease were reclassified correctly from below to above 5% for 10-year occurrence when remnant cholesterol levels were added to models based on conventional risk factors, whereas no events were reclassified incorrectly. Consequently, the addition of remnant cholesterol levels yielded NRI of 10% (95% CI: 1%-20%) for myocardial infarction and 5% (95% CI: -3% to 13%) for ischemic heart disease. Correspondingly, when reclassifications were combined from below to above 5%, 7.5%, and 10% risk of events, 42% (P < 0.001) of individuals with myocardial infarction and 41% (P < 0.001) with ischemic heart disease were reclassified appropriately, leading to NRI of respectively 20% (95% CI: 9%-31%) and 11% (95% CI: 2%-21%).<br /><b>Conclusions</b><br />Elevated remnant cholesterol levels considerably improve myocardial infarction and ischemic heart disease risk prediction.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 21 Jun 2022; 79:2383-2397</small></div>

<div><h4>Transcatheter Cardiac Interventions in the Newborn: JACC Focus Seminar.</h4><i>Barry OM, Bouhout I, Turner ME, Petit CJ, Kalfa DM</i><br /><AbstractText>For neonates with critical congenital heart disease requiring intervention, transcatheter approaches for many conditions have been established over the past decades. These interventions may serve to stabilize or palliate to surgical next steps or effectively primarily treat the condition. Many transcatheter interventions have evidence-based records of effectiveness and safety, which have led to widespread acceptance as first-line therapies. Other techniques continue to innovatively push the envelope and challenge the optimal strategies for high-risk neonates with right ventricular outflow tract obstruction or ductal-dependent pulmonary blood flow. In this review, the most commonly performed neonatal transcatheter interventions will be described to illustrate the current state of the field and highlight areas of future opportunity.</AbstractText><br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 07 Jun 2022; 79:2270-2283</small></div>

<div><h4>Cardiovascular Risks of Hydroxychloroquine vs Methotrexate in Patients With Rheumatoid Arthritis.</h4><i>D\'Andrea E, Desai RJ, He M, Glynn RJ, ... Weinblatt ME, Kim SC</i><br /><b>Background</b><br />Hydroxychloroquine is often used as a first-line treatment of rheumatoid arthritis despite limited evidence on its cardiovascular risk.<br /><b>Objectives</b><br />We conducted a cardiovascular safety evaluation comparing hydroxychloroquine to methotrexate among patients with rheumatoid arthritis.<br /><b>Methods</b><br />Using Medicare data (2008-2016), we identified 54,462 propensity score-matched patients with rheumatoid arthritis, aged ≥65 years, who initiated hydroxychloroquine or methotrexate. Primary outcomes were sudden cardiac arrest or ventricular arrythmia (SCA/VA) and major adverse cardiovascular event (MACE). Secondary outcomes were cardiovascular mortality, all-cause mortality, myocardial infarction, stroke, and hospitalized heart failure (HF). We also examined treatment effect modification by history of HF.<br /><b>Results</b><br />Hydroxychloroquine was not associated with risk of SCA/VA (HR: 1.03; 95% CI: 0.79-1.35) or MACE (HR: 1.07; 95% CI: 0.97-1.18) compared with methotrexate. In patients with history of HF, hydroxychloroquine initiators had a higher risk of MACE (HR: 1.30; 95% CI: 1.08-1.56), cardiovascular mortality (HR: 1.34; 95% CI: 1.06-1.70), all-cause mortality (HR: 1.22; 95% CI: 1.04-1.43), myocardial infarction (HR: 1.74; 95% CI: 1.25-2.42), and hospitalized HF (HR: 1.29; 95% CI: 1.07-1.54) compared to methotrexate initiators. Cardiovascular risks were not different in patients without history of HF except for an increased hospitalized HF risk (HR: 1.57; 95% CI: 1.30-1.90) among hydroxychloroquine initiators.<br /><b>Conclusions</b><br />In older patients with rheumatoid arthritis, hydroxychloroquine and methotrexate showed similar SCA/VA and MACE risks; however, hydroxychloroquine initiators with history of HF had higher risks of MACE, cardiovascular mortality, all-cause mortality, and myocardial infarction. An increased hospitalized HF risk was observed among hydroxychloroquine initiators regardless of an HF history.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 05 Jul 2022; 80:36-46</small></div>

<div><h4>Pericardial Effusion Provoking Atrial Fibrillation After Cardiac Surgery: JACC Review Topic of the Week.</h4><i>Gaudino M, Di Franco A, Rong LQ, Cao D, ... DiMaio JM, Girardi LN</i><br /><AbstractText>Postoperative atrial fibrillation (POAF) is the most common complication after cardiac surgery. Patients who develop POAF are more likely to experience adverse outcomes, including increased rates of death, stroke, heart failure, and hospitalizations, and higher hospital costs. Understanding the mechanisms underlying POAF is important to improve patients\' outcome and optimize health systems\' efficiency. Beyond classic pathogenic hypotheses, emerging evidence suggests that postoperative pericardial effusion and localized pericardial inflammation may trigger POAF. This hypothesis is supported by data from nonhuman animal models and a growing body of evidence showing that reducing postoperative pericardial effusion might reduce POAF incidence. In this review, we summarize the classic pathophysiology theories of POAF following cardiac surgery and discuss new etiologic mechanisms with a specific focus on the role of pericardial effusion and inflammation.</AbstractText><br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 28 Jun 2022; 79:2529-2539</small></div>

<div><h4>Interventions for Congenital Atrioventricular Valve Dysfunction: JACC Focus Seminar.</h4><i>Barry OM, Bouhout I, Kodali SK, George I, ... Petit CJ, Kalfa D</i><br /><AbstractText>Innovation and creativity have led to tremendous advancements in the care and management of patients with congenital heart disease (CHD) that have resulted in considerably increased survival. Catheter-based interventions have contributed significantly to these advancements. However, catheter-based interventions for congenital lesions of the atrioventricular (AV) valves have been limited in scope and effectiveness mainly because of patient size and anatomical challenges. Thus, surgical repair and replacement for congenital AV valve lesions have remained the preferred therapy. However, the ongoing transcatheter heart valve revolution has led to techniques and technologies that are changing the landscape, particularly for adult CHD patients. Many devices for AV valve repair and replacement are being studied in adult patients without CHD, and translation of select practices to CHD patients has begun, with many more to come. Transcatheter AV valve interventions represent exciting opportunities for the growing numbers of adult CHD patients.</AbstractText><br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 07 Jun 2022; 79:2259-2269</small></div>

<div><h4>Cardiovascular Disease Risk Among Cancer Survivors: The Atherosclerosis Risk In Communities (ARIC) Study.</h4><i>Florido R, Daya NR, Ndumele CE, Koton S, ... Platz EA, Selvin E</i><br /><b>Background</b><br />More than 80% of adult patients diagnosed with cancer survive long term. Long-term complications of cancer and its therapies may increase the risk of cardiovascular disease (CVD), but prospective studies using adjudicated cancer and CVD events are lacking.<br /><b>Objectives</b><br />The aim of this study was to assess the risk of CVD in cancer survivors in a prospective community-based study.<br /><b>Methods</b><br />We included 12,414 ARIC (Atherosclerosis Risk In Communities) study participants. Cancer diagnoses were ascertained via linkage with state registries supplemented with medical records. Incident CVD outcomes were coronary heart disease (CHD), heart failure (HF), stroke, and a composite of these. We used multivariable Poisson and Cox regressions to estimate the association of cancer with incident CVD.<br /><b>Results</b><br />Mean age was 54 years, 55% were female, and 25% were Black. A total of 3,250 participants (25%) had incident cancer over a median 13.6 years of follow-up. Age-adjusted incidence rates of CVD (per 1,000 person-years) were 23.1 (95% CI: 24.7-29.1) for cancer survivors and 12.0 (95% CI: 11.5-12.4) for subjects without cancer. After adjustment for cardiovascular risk factors, cancer survivors had significantly higher risks of CVD (HR: 1.37; 95% CI: 1.26-1.50), HF (HR: 1.52; 95% CI: 1.38-1.68), and stroke (HR: 1.22; 95% CI: 1.03-1.44), but not CHD (HR: 1.11; 95% CI: 0.97-1.28). Breast, lung, colorectal, and hematologic/lymphatic cancers, but not prostate cancer, were significantly associated with CVD risk.<br /><b>Conclusions</b><br />Compared with persons without cancer, adult cancer survivors have significantly higher risk of CVD, especially HF, independent of traditional cardiovascular risk factors. There is an unmet need to define strategies for CVD prevention in this high-risk population.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 05 Jul 2022; 80:22-32</small></div>

<div><h4>Precision Phenotyping of Dilated Cardiomyopathy Using Multidimensional Data.</h4><i>Tayal U, Verdonschot JAJ, Hazebroek MR, Howard J, ... Heymans SRB, Prasad SK</i><br /><b>Background</b><br />Dilated cardiomyopathy (DCM) is a final common manifestation of heterogenous etiologies. Adverse outcomes highlight the need for disease stratification beyond ejection fraction.<br /><b>Objectives</b><br />The purpose of this study was to identify novel, reproducible subphenotypes of DCM using multiparametric data for improved patient stratification.<br /><b>Methods</b><br />Longitudinal, observational UK-derivation (n = 426; median age 54 years; 67% men) and Dutch-validation (n = 239; median age 56 years; 64% men) cohorts of DCM patients (enrolled 2009-2016) with clinical, genetic, cardiovascular magnetic resonance, and proteomic assessments. Machine learning with profile regression identified novel disease subtypes. Penalized multinomial logistic regression was used for validation. Nested Cox models compared novel groupings to conventional risk measures. Primary composite outcome was cardiovascular death, heart failure, or arrhythmia events (median follow-up 4 years).<br /><b>Results</b><br />In total, 3 novel DCM subtypes were identified: profibrotic metabolic, mild nonfibrotic, and biventricular impairment. Prognosis differed between subtypes in both the derivation (P < 0.0001) and validation cohorts. The novel profibrotic metabolic subtype had more diabetes, universal myocardial fibrosis, preserved right ventricular function, and elevated creatinine. For clinical application, 5 variables were sufficient for classification (left and right ventricular end-systolic volumes, left atrial volume, myocardial fibrosis, and creatinine). Adding the novel DCM subtype improved the C-statistic from 0.60 to 0.76. Interleukin-4 receptor-alpha was identified as a novel prognostic biomarker in derivation (HR: 3.6; 95% CI: 1.9-6.5; P = 0.00002) and validation cohorts (HR: 1.94; 95% CI: 1.3-2.8; P = 0.00005).<br /><b>Conclusions</b><br />Three reproducible, mechanistically distinct DCM subtypes were identified using widely available clinical and biological data, adding prognostic value to traditional risk models. They may improve patient selection for novel interventions, thereby enabling precision medicine.<br /><br />Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 07 Jun 2022; 79:2219-2232</small></div>

<div><h4>Long-Term Outcomes of Patients Requiring Unplanned Repeated Interventions After Surgery for Congenital Heart Disease.</h4><i>Sengupta A, Gauvreau K, Kohlsaat K, Colan SD, ... Del Nido PJ, Nathan M</i><br /><b>Background</b><br />Unplanned catheter-based or surgical reinterventions after congenital heart operations are independently associated with operative mortality and increased postoperative length of stay.<br /><b>Objectives</b><br />This study assessed the long-term outcomes of transplant-free survivors of hospital discharge requiring predischarge reinterventions after congenital cardiac surgery.<br /><b>Methods</b><br />Data from patients who required predischarge reinterventions in the anatomic area of repair after congenital cardiac surgery and survived to hospital discharge at a quaternary referral center from January 2011 to December 2019 were retrospectively reviewed. Previously published echocardiographic criteria were used to assess the severity of persistent residual lesions at discharge (Grade 1, no residua; Grade 2, minor residua; and Grade 3, major residua). Outcomes included postdischarge (late) mortality or transplant and unplanned reintervention. Associations between predischarge residual lesion severity and outcomes were assessed by using Cox or competing risk models, adjusting for baseline patient characteristics, case complexity, and preoperative risk factors.<br /><b>Results</b><br />Among the 408 patients who met entry criteria, there were 58 (14.2%) postdischarge deaths or transplants and 208 (51.0%) late reinterventions at a median follow-up of 3.0 years (IQR: 1.1-6.8 years). Greater predischarge residual lesion severity was associated with worse transplant-free survival and freedom from reintervention (both, P < 0.05). On multivariable analyses, Grade 3 patients had an increased risk of postdischarge mortality or transplant (HR: 4.8; 95% CI: 2.0-11; P < 0.001) and late reintervention (subdistribution HR: 2.1; 95% CI: 1.4-3.1; P < 0.001) vs Grade 1 patients.<br /><b>Conclusions</b><br />Among transplant-free survivors requiring predischarge reinterventions after congenital cardiac surgery, those with persistent major residua have significantly worse long-term outcomes. These high-risk patients warrant closer surveillance.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 28 Jun 2022; 79:2489-2499</small></div>

<div><h4>Socioeconomic Status and Risk of Bleeding After Mechanical Aortic Valve Replacement.</h4><i>Dalén M, Persson M, Glaser N, Sartipy U</i><br /><b>Background</b><br />Whether low socioeconomic status (SES) is associated with increased risk of anticoagulation-related adverse events in patients with mechanical heart valves is unknown.<br /><b>Objectives</b><br />This study sought to investigate the impact of patients\' SES on the risk of bleeding after mechanical aortic valve replacement (AVR).<br /><b>Methods</b><br />This nationwide population-based cohort study included all patients aged 18-70 years who underwent mechanical AVR in Sweden from 1997 to 2018. Data were obtained from the SWEDEHEART register and other national health data registers. The exposure was quartiles of household disposable income. The primary outcome was hospitalization for a bleeding event.<br /><b>Results</b><br />Among 5974 patients, the absolute risk for bleeding after 20 years of follow-up was 20% (95% CI: 17%-24%) in the lowest income quartile (Q1) and 16% (95% CI: 13%-20%) in the highest quartile (Q4). The risk of bleeding decreased with increasing income level and was significantly lower in patients in income level Q3 (HR: 0.77; 95% CI: 0.60-0.99) and Q4 (HR: 0.68; 95% CI: 0.50-0.92) than Q1. The risk of death from intracranial hemorrhage was five times higher in the lowest income quartile than the age- and sex-matched general Swedish population (standardized mortality ratio: 5.0; 95% CI: 3.3-7.4).<br /><b>Conclusions</b><br />We observed a strong association between SES and risk of bleeding among patients who underwent mechanical AVR. These findings suggest suboptimal anticoagulation treatment in patients with lower SES and the need for strategies to optimize anticoagulation treatment in patients with a mechanical heart valve. (Health-Data Register Studies of Risk and Outcomes in Cardiac Surgery [HARTROCS]; NCT02276950).<br /><br />Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 28 Jun 2022; 79:2502-2513</small></div>

<div><h4>Empagliflozin Improves Outcomes in Patients With Heart Failure and Preserved Ejection Fraction Irrespective of Age.</h4><i>Böhm M, Butler J, Filippatos G, Ferreira JP, ... Anker SD, EMPEROR-Preserved Trial Committees and Investigators</i><br /><b>Background</b><br />Empagliflozin reduces cardiovascular death (CVD) or heart failure (HF) hospitalization (HFH) in patients with HF and preserved ejection fraction. Treatment effects and safety in relation to age have not been studied.<br /><b>Objectives</b><br />The purpose of this study was to evaluate the interplay of age and empagliflozin effects in EMPEROR-Preserved (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction).<br /><b>Methods</b><br />We grouped patients (n = 5,988) according to their baseline age (<65 years [n = 1,199], 65-74 years [n = 2,214], 75-79 years [n = 1,276], ≥80 years [n = 1,299]). We explored the influence of age on empagliflozin effects on CVD or HFH (primary outcome), total HFH, rate of decline in estimated glomerular filtration rate, health-related quality of life with the Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score, and frequency of adverse events.<br /><b>Results</b><br />Considering only patients on placebo, the incidence of primary outcomes (P trend = 0.02) and CVD (P trend = 0.003) increased with age. Empagliflozin reduced primary outcomes (P trend = 0.33), first HFH (P trend = 0.22), and first and recurrent HFH (P trend = 0.11) across all age groups with an effect being similar at ≥75 years (P interaction = 0.22) or >80 years (P interaction = 0.51). Empagliflozin improved Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score at week 52 and attenuated the decline of estimated glomerular filtration rate without age interaction (P = 0.48 and P = 0.32, respectively). There were no clinically relevant differences in adverse events between empagliflozin and placebo across the age groups.<br /><b>Conclusions</b><br />Empagliflozin reduced primary outcomes and first and recurrent HFH and improved symptoms across a broad age spectrum. High age was not associated with reduced efficacy or meaningful intolerability. (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction [EMPEROR-Preserved]; NCT0305951).<br /><br />Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 05 Jul 2022; 80:1-18</small></div>

<div><h4>Prospective Evaluation of Cardiovascular Risk 10 Years After a Hypertensive Disorder of Pregnancy.</h4><i>Levine LD, Ky B, Chirinos JA, Koshinksi J, ... Koelper N, Lewey J</i><br /><b>Background</b><br />Hypertensive disorders of pregnancy (HDP) are associated with increased risk of cardiovascular disease (CVD) 20-30 years later; however, cardiovascular (CV) risk in the decade after HDP is less studied.<br /><b>Objectives</b><br />The purpose of this study was to evaluate differences in CV risk factors as well as subclinical CVD among a well-characterized group of racially diverse patients with and without a history of HDP 10 years earlier.<br /><b>Methods</b><br />This is a prospective study of patients with and without a diagnosis of HDP ≥10 years earlier (2005-2007) who underwent in-person visits with echocardiography, arterial tonometry, and flow-mediated dilation of the brachial artery.<br /><b>Results</b><br />A total of 135 patients completed assessments (84 with and 51 without a history of HDP); 85% self-identified as Black. Patients with a history of HDP had a 2.4-fold increased risk of new hypertension compared with those without HDP (56.0% vs. 23.5%; adjusted relative risk: 2.4; 95% CI: 1.39-4.14) with no differences in measures of left ventricular structure, global longitudinal strain, diastolic function, arterial stiffness, or endothelial function. Patients who developed hypertension, regardless of HDP history, had greater left ventricular remodeling, including greater relative wall thickness; worse diastolic function, including lower septal and lateral e\' and E/A ratio; more abnormal longitudinal strain; and higher effective arterial elastance than patients without hypertension.<br /><b>Conclusions</b><br />We found a 2.4-fold increased risk of hypertension 10 years after HDP. Differences in noninvasive measures of CV risk were driven mostly by the hypertension diagnosis, regardless of HDP history, suggesting that the known long-term risk of CVD after HDP may primarily be a consequence of hypertension development.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 21 Jun 2022; 79:2401-2411</small></div>

<div><h4>False Lumen Flow Assessment by Magnetic Resonance Imaging and Long-Term Outcomes in Uncomplicated Aortic Dissection.</h4><i>Evangelista A, Pineda V, Guala A, Bijnens B, ... Ferreira I, Rodríguez-Palomares J</i><br /><b>Background</b><br />Despite the absence of clinical complications after an acute aortic dissection (AD) with persistent patent false lumen (FL), a high risk for clinical events may persist.<br /><b>Objectives</b><br />The aim of this study was to assess the natural evolution of noncomplicated AD and ascertain whether different FL flow patterns by magnetic resonance imaging (MRI) have independent prognostic value for AD-related events beyond established morphologic parameters.<br /><b>Methods</b><br />One hundred thirty-one consecutive patients, 78 with surgically treated type A dissections and 53 with medically treated type B dissections, were followed up prospectively after acute AD with persistent patent FL in the descending aorta. Maximum aortic diameter, true lumen compression, entry tear, and partial FL thrombosis by computed tomography were assessed. Systolic antegrade true lumen and FL flow volumes and diastolic antegrade and retrograde flows were analyzed by MRI during the first year after AD.<br /><b>Results</b><br />After a median follow-up period of 8.0 years (IQR: 4.6-10.9 years), 43 patients presented aorta-related events (25 died and 18 required endovascular treatment). FL systolic antegrade flow ≥30% with respect to total systolic antegrade flow and retrograde diastolic flow ≥80% with respect to total diastolic FL flow were predictors of aortic events. In multivariate analysis, aortic diameter >45 mm (HR: 2.91), type B dissection (HR: 2.44), and MRI flow pattern (HR: 16.87) were independent predictors of AD-related events.<br /><b>Conclusions</b><br />High systolic antegrade flow volume in the FL with significant diastolic retrograde flow assessed by MRI and aortic diameter >45 mm identify patients with higher risk for complications in whom more aggressive management would be indicated.<br /><br />Copyright © 2022. Published by Elsevier Inc.<br /><br /><small>J Am Coll Cardiol: 21 Jun 2022; 79:2415-2427</small></div>

<div><h4>LMNA Variants and Risk of Adult-Onset Cardiac Disease.</h4><i>Lazarte J, Jurgens SJ, Choi SH, Khurshid S, ... Lunetta KL, Lubitz SA</i><br /><b>Background</b><br />Genetic variants in LMNA may cause cardiac disease, but population-level contributions of variants to cardiac disease burden are not well-characterized.<br /><b>Objectives</b><br />We sought to determine the frequency and contribution of rare LMNA variants to cardiomyopathy and arrhythmia risk among ambulatory adults.<br /><b>Methods</b><br />We included 185,990 UK Biobank participants with whole-exome sequencing. We annotated rare loss-of-function and missense LMNA variants for functional effect using 30 in silico prediction tools. We assigned a predicted functional effect weight to each variant and calculated a score for each carrier. We tested associations between the LMNA score and arrhythmia (atrial fibrillation, bradyarrhythmia, ventricular arrhythmia) or cardiomyopathy outcomes (dilated cardiomyopathy and heart failure). We also examined associations for variants located upstream vs downstream of the nuclear localization signal.<br /><b>Results</b><br />Overall, 1,167 (0.63%) participants carried an LMNA variant and 15,079 (8.11%) had an arrhythmia or cardiomyopathy event during a median follow-up of 10.9 years. The LMNA score was associated with arrhythmia or cardiomyopathy (OR: 2.21; P < 0.001) and the association was more significant when restricted to variants upstream of the nuclear localization signal (OR: 5.05; P < 0.001). The incidence rate of arrhythmia or cardiomyopathy was 8.43 per 1,000 person-years (95% CI: 6.73-10.12 per 1,000 person-years) among LMNA variant carriers and 6.38 per 1,000 person-years (95% CI: 6.27-6.50 per 1,000 person-years) among noncarriers. Only 3 (1.2%) of the variants were reported as pathogenic in ClinVar.<br /><b>Conclusions</b><br />Middle-aged adult carriers of rare missense or loss-of-function LMNA variants are at increased risk for arrhythmia and cardiomyopathy.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 05 Jul 2022; 80:50-59</small></div>

<div><h4>Diabetes and Progression of Heart Failure: The Atherosclerosis Risk In Communities (ARIC) Study.</h4><i>Echouffo-Tcheugui JB, Ndumele CE, Zhang S, Florido R, ... Shah AM, Selvin E</i><br /><b>Background</b><br />The influence of diabetes on progression from preclinical heart failure (HF) stages to overt HF is poorly understood.<br /><b>Objectives</b><br />The purpose of this study was to characterize the influence of diabetes on the progression from preclinical HF stages (A or B based on the 2021 Universal Definition) to overt HF.<br /><b>Methods</b><br />We included 4,774 adults with preclinical HF (stage A [n = 1,551] or B [n = 3,223]) who attended the ARIC (Atherosclerosis Risk In Communities) study Visit 5 (2011-2013). Within each stage (A or B), we assessed the associations of diabetes and glycemic control (hemoglobin A<sub>1C</sub> [HbA<sub>1C</sub>] <7% vs ≥7%) with progression to HF, and of cross-categories of HF stages (A vs B), diabetes, and glycemic control with incident HF.<br /><b>Results</b><br />Among the participants (mean age 75.4 years, 58% women, 20% Black), there were 470 HF events during 8.6 years of follow-up. Stage B participants with HbA<sub>1C</sub> ≥7% experienced clinical HF at a younger age than those with controlled diabetes or without diabetes (mean age 80 years vs 83 years vs 82 years; P < 0.001). HbA<sub>1C</sub> ≥7% was more strongly associated with HF in stage B (HR: 1.83; 95% CI: 1.33-2.51) compared with stage A (HR: 1.52; 95% CI: 0.53-4.38). In cross-categories of preclinical HF stage and HbA<sub>1C</sub>, participants with stage B and HbA<sub>1C</sub> ≥7% had increased risk of HF progression compared with stage A without diabetes (HR: 7.56; 95% CI: 4.68-12.20).<br /><b>Conclusions</b><br />Among older adults with preclinical HF stages, uncontrolled diabetes was associated with substantial risk of HF progression. Our results suggest that targeting diabetes early in the HF process is critical.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 14 Jun 2022; 79:2285-2293</small></div>

<div><h4>Causes, Angiographic Characteristics, and Management of Premature Myocardial Infarction: JACC State-of-the-Art Review.</h4><i>Rallidis LS, Xenogiannis I, Brilakis ES, Bhatt DL</i><br /><AbstractText>Among patients presenting with acute myocardial infarction (AMI), the proportion of young individuals has increased in recent years. Although coronary atherosclerosis is less extensive in young patients with AMI, with higher prevalence of single-vessel disease and rare left main involvement, the long-term prognosis is not benign. Young patients with AMI with obstructive coronary artery disease have similar risk factors as older patients except for higher prevalence of smoking, lipid disorders, and family history of premature coronary artery disease, and lower prevalence of diabetes mellitus and hypertension. Smoking cessation is by far the most effective secondary preventive measure. Myocardial infarction with nonobstructive coronary arteries is a relatively common clinical entity (10%-20%) among young patients with AMI, with intravascular and cardiac magnetic resonance imaging being key for diagnosis and potentially treatment. Spontaneous coronary artery dissection is a frequent pathogenetic mechanism of AMI among young women, requiring a high degree of suspicion, especially in the peripartum period.</AbstractText><br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 21 Jun 2022; 79:2431-2449</small></div>

<div><h4>Trends and Disparities in Cardiometabolic Health Among U.S. Adults, 1999-2018.</h4><i>O\'Hearn M, Lauren BN, Wong JB, Kim DD, Mozaffarian D</i><br /><b>Background</b><br />Few studies have assessed U.S. cardiometabolic health trends-optimal levels of multiple risk factors and absence of clinical cardiovascular disease (CVD)-or its impact on health disparities.<br /><b>Objectives</b><br />The purpose of this study was to investigate U.S. trends in optimal cardiometabolic health from 1999 to 2018.<br /><b>Methods</b><br />We assessed proportions of adults with optimal cardiometabolic health, based on adiposity, blood glucose, blood lipids, blood pressure, and clinical CVD; and optimal, intermediate, and poor levels of each component among 55,081 U.S. adults in the National Health and Nutrition Examination Survey.<br /><b>Results</b><br />In 2017-2018, only 6.8% (95% CI: 5.4%-8.1%) of U.S. adults had optimal cardiometabolic health, declining from 1999-2000 (P trend = 0.02). Among components of cardiometabolic health, the largest declines were for adiposity (optimal levels: 33.8%-24.0%; poor levels: 47.7%-61.9%) and glucose (optimal levels: 59.4%-36.9%; poor levels: 8.6%-13.7%) (P trend <0.001 for each). Optimal levels of blood lipids increased from 29.9%-37.0%, whereas poor decreased from 28.3%-14.7% (P trend <0.001). Trends over time for blood pressure and CVD were smaller. Disparities by age, sex, education, and race/ethnicity were evident in all years, and generally worsened over time. By 2017-2018, prevalence of optimal cardiometabolic health was lower among Americans with lower (5.0% [95% CI: 2.8%-7.2%]) vs higher education (10.3% [95% CI: 7.6%-13.0%]); and among Mexican American (3.2% [95% CI: 1.4%-4.9%]) vs non-Hispanic White (8.4% [95% CI: 6.3%-10.4%]) adults.<br /><b>Conclusions</b><br />Between 1999 and 2000 and 2017 and 2018, U.S. cardiometabolic health has been poor and worsening, with only 6.8% of adults having optimal cardiometabolic health, and disparities by age, sex, education, and race/ethnicity. These novel findings inform the need for nationwide clinical and public health interventions to improve cardiometabolic health and health equity.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 12 Jul 2022; 80:138-151</small></div>

<div><h4>Analysis of Worsening Heart Failure Events in an Integrated Health Care System.</h4><i>Ambrosy AP, Parikh RV, Sung SH, Tan TC, ... Cristino J, Go AS</i><br /><b>Background</b><br />There is growing interest to disentangle worsening heart failure (WHF) from location of care and move away from hospitalization as a surrogate for acuity.<br /><b>Objectives</b><br />The purpose of this study was to describe the incidence of WHF events across the care continuum from ambulatory encounters to hospitalizations.<br /><b>Methods</b><br />We studied calendar year cohorts of adults with diagnosed heart failure (HF) from 2010-2019 within a large, integrated health care delivery system. Electronic health record (EHR) data were accessed for outpatient encounters, emergency department (ED) visits/observation stays, and hospitalizations. WHF was defined as ≥1 symptom, ≥2 objective findings including ≥1 sign, and ≥1 change in HF-related therapy. Symptoms and signs were ascertained using natural language processing.<br /><b>Results</b><br />We identified 103,138 eligible individuals with mean age 73.6 ± 13.7 years, 47.5% women, and mean left ventricular ejection fraction of 51.4% ± 13.7%. There were 1,136,750 unique encounters including 743,039 (65.4%) outpatient encounters, 224,670 (19.8%) ED visits/observation stays, and 169,041 (14.9%) hospitalizations. A total of 126,008 WHF episodes were identified, including 34,758 (27.6%) outpatient encounters, 28,301 (22.5%) ED visits/observation stays, and 62,949 (50.0%) hospitalizations. The annual incidence (events per 100 person-years) of WHF increased from 25 to 33 during the study period primarily caused by outpatient encounters (7 to 10) and ED visits/observation stays (4 to 7). The 30-day rate of hospitalizations for WHF ranged from 8.2% for outpatient encounters to 12.4% for hospitalizations.<br /><b>Conclusions</b><br />ED visits/observation stays and outpatient encounters account for approximately one-half of WHF events, are driving the underlying growth in HF morbidity, and portend a poor short-term prognosis.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 12 Jul 2022; 80:111-122</small></div>

<div><h4>Inappropriate Sinus Tachycardia: Etiology, Pathophysiology, and Management: JACC Review Topic of the Week.</h4><i>Ahmed A, Pothineni NVK, Charate R, Garg J, ... Gopinathannair R, Lakkireddy D</i><br /><AbstractText>Inappropriate sinus tachycardia (IST) is a clinical syndrome that generally affects young patients and is associated with distressing symptoms. Although the most common symptom is palpitations, it can be accompanied by a myriad of symptoms, including anxiety, dizziness, presyncope, and syncope. The pathogenesis of IST is not well understood and considered multifactorial, with autonomic dysfunction being the central abnormality. IST is a diagnosis of exclusion. Management presents a clinical challenge. The overall efficacy of lifestyle modifications and medical therapy may be limited. Recent advances in catheter and surgical sinus node sparing ablation techniques have led to improvement in outcomes. In addition, increased focus has led to development of multimodality team-based interventions to improve outcomes in this group of patients. In this review, we discuss the mechanistic basis of IST, review current approaches to diagnosis, and outline contemporary therapeutic approaches.</AbstractText><br /><br />Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 21 Jun 2022; 79:2450-2462</small></div>

<div><h4>Carotid Artery Stenting: JACC State-of-the-Art Review.</h4><i>White CJ, Brott TG, Gray WA, Heck D, ... Sachar R, Siddiqui A</i><br /><AbstractText>Significant advances in the field of carotid artery stenting (CAS) have occurred, including new randomized trial data, recent professional societal statements for competency, new techniques and new devices that have been developed, and perhaps most importantly, our understanding of how to better select candidates for CAS to avoid periprocedural complications. The current Centers for Medicare and Medicaid Services coverage decision regarding CAS is outdated, and our review supports our recommendation to approve CAS in selected candidates who are symptomatic with a carotid stenosis ≥50% and ≤99% and for asymptomatic patients with carotid stenosis ≥70% and ≤99% for stroke prevention. Optimized CAS strategies have allowed experienced operators to better assess procedure risk before CAS and have led to continued improvement in CAS outcomes. New technologies including enhanced embolic protection devices and dual-layered stents should result in further improvement.</AbstractText><br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 12 Jul 2022; 80:155-170</small></div>

<div><h4>Secular Trends in Risk Profiles Among Adults With Cardiovascular Disease in the United States.</h4><i>Gao Y, Isakadze N, Duffy E, Sheng Q, ... Matsushita K, Martin SS</i><br /><b>Background</b><br />Documenting trends in risk factors among individuals with cardiovascular disease (CVD) may inform policy and secondary prevention initiatives.<br /><b>Objectives</b><br />This study aimed to examine 20-year trends in risk profiles among U.S. adults with CVD and any racial/ethnic disparities.<br /><b>Methods</b><br />In this serial cross-sectional analysis of 6,335 adults with self-reported CVD participating in the National Health and Nutrition Examination Survey from 1999 through 2018, we calculated age- and sex-adjusted proportions with ideal risk factor attainment.<br /><b>Results</b><br />The proportions with ideal hemoglobin A1c (<7% if diabetes or <5.7% if not) and body mass index (<25 kg/m<sup>2</sup>) worsened from 58.7% (95% CI: 55.2%-62.1%) to 52.4% (95% CI: 48.2%-56.6%) and 23.9% (95% CI: 21.5%-26.4%) to 18.2% (95% CI: 15.6%-21.2%) from 1999-2002 to 2015-2018, respectively. After initial improvement, the proportion with blood pressure <130/80 mm Hg declined from 52.1% (95% CI: 48.9%-55.4%) in 2007-2010 to 48.6% (95% CI: 44.2%-52.7%) in 2015-2018. The proportion with non-high-density lipoprotein cholesterol levels <100 mg/dL increased from 7.3% (95% CI: 5.6%-9.5%) in 1999-2002 to 30.3% (95% CI: 25.7%-35.5%) in 2015-2018. The proportions with ideal smoking, physical activity, and diet profiles were unchanged over time, and in 2015-2018 were 77.8% (95% CI: 73.6%-81.4%), 22.4% (95% CI: 19.3%-25.9%), and 1.3% (95% CI: 0.7%-2.6%). Worsening trends were observed in Hispanic adults for cholesterol, and in Black adults for smoking (both P < 0.05 for nonlinear and linear trends). Persistently lower ideal risk factor attainment was observed for blood pressure in Black adults and for hemoglobin A1c levels in Asian adults compared with White adults (all P < 0.05 for differences).<br /><b>Conclusions</b><br />Trends in cardiovascular risk factor profiles in U.S. adults with CVD were suboptimal from 1999 through 2018, with persistent racial/ethnic disparities.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 12 Jul 2022; 80:126-137</small></div>

<div><h4>Myosin Inhibition in Patients With Obstructive Hypertrophic Cardiomyopathy Referred for Septal Reduction Therapy.</h4><i>Desai MY, Owens A, Geske JB, Wolski K, ... Sehnert AJ, Nissen SE</i><br /><b>Background</b><br />Septal reduction therapy (SRT), surgical myectomy or alcohol ablation, is recommended for obstructive hypertrophic cardiomyopathy (oHCM) patients with intractable symptoms despite maximal medical therapy, but is associated with morbidity and mortality.<br /><b>Objectives</b><br />This study sought to determine whether the oral myosin inhibitor mavacamten enables patients to improve sufficiently to no longer meet guideline criteria or choose to not undergo SRT.<br /><b>Methods</b><br />Patients with left ventricular (LV) outflow tract (LVOT) gradient ≥50 mm Hg at rest/provocation who met guideline criteria for SRT were randomized, double blind, to mavacamten, 5 mg daily, or placebo, titrated up to 15 mg based on LVOT gradient and LV ejection fraction. The primary endpoint was the composite of the proportion of patients proceeding with SRT or who remained guideline-eligible after 16 weeks\' treatment.<br /><b>Results</b><br />One hundred and twelve oHCM patients were enrolled, mean age 60 ± 12 years, 51% men, 93% New York Heart Association (NYHA) functional class III/IV, with a mean post-exercise LVOT gradient of 84 ± 35.8 mm Hg. After 16 weeks, 43 of 56 placebo patients (76.8%) and 10 of 56 mavacamten patients (17.9%) met guideline criteria or underwent SRT, difference (58.9%; 95% CI: 44.0%-73.9%; P < 0.001). Hierarchical testing of secondary outcomes showed significant differences (P < 0.001) favoring mavacamten, mean differences in post-exercise peak LVOT gradient -37.2 mm Hg; ≥1 NYHA functional class improvement 41.1%; improvement in patient-reported outcome 9.4 points; and NT-proBNP and cardiac troponin I between-groups geometric mean ratio 0.33 and 0.53.<br /><b>Conclusions</b><br />In oHCM patients with intractable symptoms, mavacamten significantly reduced the fraction of patients meeting guideline criteria for SRT after 16 weeks. Long-term freedom from SRT remains to be determined. (A Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive HCM Who Are Eligible for Septal Reduction Therapy [VALOR-HCM]; NCT04349072).<br /><br />Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 12 Jul 2022; 80:95-108</small></div>

<div><h4>Randomized Trial of Targeted Transendocardial Mesenchymal Precursor Cell Therapy in Patients With Heart Failure.</h4><i>Perin EC, Borow KM, Henry TD, Mendelsohn FO, ... Itescu S, Greenberg B</i><br /><b>Background</b><br />Mesenchymal precursor cells (MPCs) are allogeneic, immunoselected cells with anti-inflammatory properties that could improve outcomes in heart failure with reduced ejection fraction (HFrEF).<br /><b>Objectives</b><br />This study assessed the efficacy and safety of MPCs in patients with high-risk HFrEF.<br /><b>Methods</b><br />This randomized, double-blind, multicenter study evaluated a single transendocardial administration procedure of MPCs or sham-control in 565 intention-to-treat patients with HFrEF on guideline-directed therapies. The primary endpoint was time-to-recurrent events caused by decompensated HFrEF or successfully resuscitated symptomatic ventricular arrhythmias. Hierarchical secondary endpoints included components of the primary endpoint, time-to-first terminal cardiac events, and all-cause death. Separate and composite major adverse cardiovascular events analyses were performed for myocardial infarction or stroke or cardiovascular death. Baseline and 12-month echocardiography was performed. Baseline plasma high-sensitivity C-reactive protein levels were evaluated for disease severity.<br /><b>Results</b><br />The primary endpoint was similar between treatment groups (HR: 1.17; 95% CI: 0.81-1.69; P = 0.41) as were terminal cardiac events and secondary endpoints. Compared with control subjects, MPCs increased left ventricular ejection fraction from baseline to 12 months, especially in patients with inflammation. MPCs decreased the risk of myocardial infarction or stroke by 58% (HR: 0.42; 95% CI: 0.23-0.76) and the risk of 3-point major adverse cardiovascular events by 28% (HR: 0.72; 95% CI: 0.51-1.03) in the analysis population (n = 537), and by 75% (HR: 0.25; 95% CI: 0.09-0.66) and 38% (HR: 0.62; 95% CI: 0.39-1.00), respectively, in patients with inflammation (baseline high-sensitivity C-reactive protein ≥2 mg/L).<br /><b>Conclusions</b><br />The primary and secondary endpoints of the trial were negative. Positive signals in prespecified, and post hoc exploratory analyses suggest MPCs may improve outcomes, especially in patients with inflammation.<br /><br />Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 07 Mar 2023; 81:849-863</small></div>

<div><h4>Enhanced Mitochondrial Calcium Uptake Suppresses Atrial Fibrillation Associated With Metabolic Syndrome.</h4><i>Fossier L, Panel M, Butruille L, Colombani S, ... Montaigne D, Fauconnier J</i><br /><b>Background</b><br />Patients with metabolic syndrome (MetS) have an increased risk of atrial fibrillation (AF). Impaired Ca<sup>2+</sup> homeostasis and mitochondrial dysfunction have emerged as an arrhythmogenic substrate in both patients and animal models of MetS. Whether impaired mitochondrial Ca<sup>2+</sup> handling underlies AF associated with MetS remains poorly explored.<br /><b>Objectives</b><br />The aim of this study was to determine the initial mechanisms related to AF susceptibility and mitochondrial dysfunction encountered in metabolic cardiomyopathy.<br /><b>Methods</b><br />A total of 161 mice and 34 patients were studied. Mitochondrial Ca<sup>2+</sup> and mitochondrial Ca<sup>2+</sup> uniporter complex (MCUC) were investigated in right atrial tissue of patients with (n = 18) or without (n = 16) MetS and of C57Bl/6J mice fed with a high-fat sucrose diet (HFS) for 2 (n = 42) or 12 (n = 39) weeks. Susceptibility to AF was evaluated in isolated sinoatrial tissue and in vivo in mice.<br /><b>Results</b><br />Increased expression of the MICUs subunits of the MCUC (1.00 ± 0.33 AU vs 1.29 ± 0.23 AU; P = 0.034) was associated with impaired mitochondrial Ca<sup>2+</sup> uptake in patients (168.7 ± 31.3 nmol/min/mg vs 127.3 ± 18.4 nmol/min/mg; P = 0.026) and HFS mice (0.10 ± 0.04 ΔF/F0 × ms<sup>-1</sup> vs 0.06 ± 0.03 ΔF/F0 × ms<sup>-1</sup>; P = 0.0086, and 0.15 ± 0.07 ΔF/F0 × ms<sup>-1</sup> vs 0.046 ± 0.03 ΔF/F0 × ms<sup>-1</sup>; P = 0.0076 in 2- and 12-week HFS mice, respectively). HFS mice elicited a 70% increased susceptibility to AF. The MCUC agonist kaempferol restored MCUC activity in vitro and abolished the occurrence of AF in HFS mice.<br /><b>Conclusions</b><br />Impaired MCUC activity and mitochondrial Ca<sup>2+</sup> homeostasis from the early stage of metabolic cardiomyopathy in mice lead to AF. Given that similar defects in cardiac mitochondrial Ca<sup>2+</sup> handling are present in MetS patients, the modulation of the MCUC activity represents an attractive antiarrhythmic strategy.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 06 Dec 2022; 80:2205-2219</small></div>

<div><h4>Benefit of Early Revascularization Based on Inducible Ischemia and Left Ventricular Ejection Fraction.</h4><i>Rozanski A, Miller RJH, Gransar H, Han D, ... Thomson L, Berman DS</i><br /><b>Background</b><br />The utility of performing early myocardial revascularization among patients presenting with inducible myocardial ischemia and low left ventricular ejection fraction (LVEF) is currently unknown.<br /><b>Objectives</b><br />In this study, we sought to assess the relationship between stress-induced myocardial ischemia, revascularization, and all-cause mortality (ACM) among patients with normal vs low LVEF.<br /><b>Methods</b><br />We evaluated 43,443 patients undergoing stress-rest single-photon emission computed tomography myocardial perfusion imaging from 1998 to 2017. Median follow-up was 11.4 years. Myocardial ischemia was assessed for its interaction between early revascularization and mortality. A propensity score was used to adjust for nonrandomization to revascularization, followed by multivariable Cox modeling adjusted for the propensity score and clinical variables to predict ACM.<br /><b>Results</b><br />The frequency of myocardial ischemia varied markedly according to LVEF and angina, ranging from 6.7% among patients with LVEF ≥55% and no typical angina to 64.0% among patients with LVEF <45% and typical angina (P < 0.001). Among 39,883 patients with LVEF ≥45%, early revascularization was associated with increased mortality risk among patients without ischemia and lower mortality risk among patients with severe (≥15%) ischemia (HR: 0.70; 95% CI: 0.52-0.95). Among 3,560 patients with LVEF <45%, revascularization was not associated with mortality benefit among patients with no or mild ischemia, and was associated with decreased mortality among patients with moderate (10%-14%) (HR: 0.67; 95% CI: 0.49-0.91) and severe (≥15%) (HR: 0.55; 95% CI: 0.38-0.80) ischemia.<br /><b>Conclusions</b><br />Within this cohort, early myocardial revascularization was associated with a significant reduction in mortality among both patients with normal LVEF and severe inducible myocardial ischemia and patients with low LVEF and moderate or severe inducible myocardial ischemia.<br /><br />Copyright © 2022. Published by Elsevier Inc.<br /><br /><small>J Am Coll Cardiol: 19 Jul 2022; 80:202-215</small></div>

<div><h4>Standardized Definitions for Bioprosthetic Valve Dysfunction Following Aortic or Mitral Valve Replacement: JACC State-of-the-Art Review.</h4><i>Pibarot P, Herrmann HC, Wu C, Hahn RT, ... Leon MB, Heart Valve Collaboratory</i><br /><AbstractText>Bioprosthetic valve dysfunction (BVD) and bioprosthetic valve failure (BVF) may be caused by structural or nonstructural valve dysfunction. Both surgical and transcatheter bioprosthetic valves have limited durability because of structural valve deterioration. The main objective of this summary of experts participating in a virtual workshop was to propose standardized definitions for nonstructural and structural BVD and BVF following aortic or mitral biological valve replacement with the goal of facilitating research reporting and implementation of these terms in clinical practice. Definitions of structural BVF, based on valve reintervention or death, underestimate the true incidence of BVF. However, definitions solely based on the presence of high transprosthetic gradient at a given echocardiogram during follow-up overestimate the incidence of structural BVD and BVF. Definitions of aortic or mitral structural BVD must therefore include the confirmation by imaging of permanent structural changes to the leaflets alongside evidence of deterioration in valve hemodynamic function at echocardiography follow-up.</AbstractText><br /><br />Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 02 Aug 2022; 80:545-561</small></div>

<div><h4>Criteria for Defining Stages of Cardiogenic Shock Severity.</h4><i>Kapur NK, Kanwar M, Sinha SS, Thayer KL, ... Blumer V, Burkhoff D</i><br /><b>Background</b><br />Risk-stratifying patients with cardiogenic shock (CS) is a major unmet need. The recently proposed Society for Cardiovascular Angiography and Interventions (SCAI) staging system for CS severity lacks uniform criteria defining each stage.<br /><b>Objectives</b><br />The purpose of this study was to test parameters that define SCAI stages and explore their utility as predictors of in-hospital mortality in CS.<br /><b>Methods</b><br />The CS Working Group registry includes patients from 17 hospitals enrolled between 2016 and 2021 and was used to define clinical profiles for CS. We selected parameters of hypotension and hypoperfusion and treatment intensity, confirmed their association with mortality, then defined formal criteria for each stage and tested the association between both baseline and maximum Stage and mortality.<br /><b>Results</b><br />Of 3,455 patients, CS was caused by heart failure (52%) or myocardial infarction (32%). Mortality was 35% for the total cohort and higher among patients with myocardial infarction, out-of-hospital cardiac arrest, and treatment with increasing numbers of drugs and devices. Systolic blood pressure, lactate level, alanine transaminase level, and systemic pH were significantly associated with mortality and used to define each stage. Using these criteria, baseline and maximum stages were significantly associated with mortality (n = 1,890). Lower baseline stage was associated with a higher incidence of stage escalation and a shorter duration of time to reach maximum stage.<br /><b>Conclusions</b><br />We report a novel approach to define SCAI stages and identify a significant association between baseline and maximum stage and mortality. This approach may improve clinical application of the staging system and provides new insight into the trajectory of hospitalized CS patients. (Cardiogenic Shock Working Group Registry [CSWG]; NCT04682483).<br /><br />Copyright © 2022. Published by Elsevier Inc.<br /><br /><small>J Am Coll Cardiol: 19 Jul 2022; 80:185-198</small></div>

<div><h4>Contributions of the Women\'s Health Initiative to Cardiovascular Research: JACC State-of-the-Art Review.</h4><i>LaMonte MJ, Manson JE, Anderson GL, Baker LD, ... Rossouw JE, WHI Investigators</i><br /><AbstractText>The WHI (Women\'s Health Initiative) enrolled 161,808 racially and ethnically diverse postmenopausal women, ages 50-79 years, from 1993 to 1998 at 40 clinical centers across the United States. In its clinical trial component, WHI evaluated 3 randomized interventions (menopausal hormone therapy; diet modification; and calcium/vitamin D supplementation) for the primary prevention of major chronic diseases, including cardiovascular disease, in older women. In the WHI observational study, numerous clinical, behavioral, and social factors have been evaluated as predictors of incident chronic disease and mortality. Although the original interventions have been completed, the WHI data and biomarker resources continue to be leveraged and expanded through ancillary studies to yield novel insights regarding cardiovascular disease prevention and healthy aging in women.</AbstractText><br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 19 Jul 2022; 80:256-275</small></div>

<div><h4>Subclinical Atherosclerosis in Young, Socioeconomically Vulnerable Hispanic and Non-Hispanic Black Adults.</h4><i>Iglesies-Grau J, Fernandez-Jimenez R, Diaz-Munoz R, Jaslow R, ... Fayad ZA, Fuster V</i><br /><b>Background</b><br />Non-Hispanic Black persons are at greater risk of cardiovascular (CV) events than other racial/ethnic groups; however, their differential vulnerability to early subclinical atherosclerosis is poorly understood.<br /><b>Objectives</b><br />This work aims to study the impact of race/ethnicity on early subclinical atherosclerosis in young socioeconomically disadvantaged adults.<br /><b>Methods</b><br />Bilateral carotid and femoral 3-dimensional vascular ultrasound examinations were performed on 436 adults (parents/caregivers and staff) with a mean age of 38.0 ± 11.1 years, 82.3% female, 66% self-reported as Hispanic, 34% self-reported as non-Hispanic Black, and no history of CV disease recruited in the FAMILIA (Family-Based Approach in a Minority Community Integrating Systems-Biology for Promotion of Health) trial from 15 Head Start preschools in Harlem (neighborhood in New York, New York, USA). The 10-year Framingham CV risk score was calculated, and the relationship between race/ethnicity and the presence and extent of subclinical atherosclerosis was analyzed with multivariable logistic and linear regression models.<br /><b>Results</b><br />The mean 10-year Framingham CV risk was 4.0%, with no differences by racial/ethnic category. The overall prevalence of subclinical atherosclerosis was significantly higher in the non-Hispanic Black (12.9%) than in the Hispanic subpopulation (6.6%). After adjusting for 10-year Framingham CV risk score, body mass index, fruit and vegetable consumption, physical activity, and employment status, non-Hispanic Black individuals were more likely than Hispanic individuals to have subclinical atherosclerosis (OR: 3.45; 95% CI: 1.44-8.29; P = 0.006) and multiterritorial disease (P = 0.026).<br /><b>Conclusions</b><br />After adjustment for classic CV risk, lifestyle, and socioeconomic factors, non-Hispanic Black younger adults seem more vulnerable to early subclinical atherosclerosis than their Hispanic peers, suggesting that the existence of emerging or undiscovered CV factors underlying the residual excess risk (Family-Based Approach in a Minority Community Integrating Systems-Biology for Promotion of Health [FAMILIA (Project 2)]; NCT02481401).<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 19 Jul 2022; 80:219-229</small></div>

<div><h4>Cardiorespiratory Fitness and Mortality Risk Across the Spectra of Age, Race, and Sex.</h4><i>Kokkinos P, Faselis C, Samuel IBH, Pittaras A, ... Zhang J, Myers J</i><br /><b>Background</b><br />Cardiorespiratory fitness (CRF) is inversely associated with all-cause mortality. However, the association of CRF and mortality risk for different races, women, and elderly individuals has not been fully assessed.<br /><b>Objectives</b><br />The aim of this study was to evaluate the association of CRF and mortality risk across the spectra of age, race, and sex.<br /><b>Methods</b><br />A total of 750,302 U.S. veterans aged 30 to 95 years (mean age 61.3 ± 9.8 years) were studied, including septuagenarians (n = 110,637), octogenarians (n = 26,989), African Americans (n = 142,798), Hispanics (n = 35,197), Native Americans (n = 16,050), and women (n = 45,232). Age- and sex-specific CRF categories (quintiles and 98th percentile) were established objectively on the basis of peak METs achieved during a standardized exercise treadmill test. Multivariable Cox models were used to estimate HRs and 95% CIs for mortality across the CRF categories.<br /><b>Results</b><br />During follow-up (median 10.2 years, 7,803,861 person-years of observation), 174,807 subjects died, averaging 22.4 events per 1,000 person-years. The adjusted association of CRF and mortality risk was inverse and graded across the age spectrum, sex, and race. The lowest mortality risk was observed at approximately 14.0 METs for men (HR: 0.24; 95% CI: 0.23-0.25) and women (HR: 0.23; 95% CI: 0.17-0.29), with no evidence of an increase in risk with extremely high CRF. The risk for least fit individuals (20th percentile) was 4-fold higher (HR: 4.09; 95% CI: 3.90-4.20) compared with extremely fit individuals.<br /><b>Conclusions</b><br />The association of CRF and mortality risk across the age spectrum (including septuagenarians and octogenarians), men, women, and all races was inverse, independent, and graded. No increased risk was observed with extreme fitness. Being unfit carried a greater risk than any of the cardiac risk factors examined.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 09 Aug 2022; 80:598-609</small></div>

<div><h4>Association of Blood Viscosity With Mortality Among Patients Hospitalized With COVID-19.</h4><i>Choi D, Waksman O, Shaik A, Mar P, ... Goonewardena SN, Rosenson RS</i><br /><b>Background</b><br />Coronavirus disease-2019 (COVID-19) is characterized by a dysfunctional immune response and abnormal blood rheology that contribute to endothelial dysfunction and thrombotic complications. Whole blood viscosity (WBV) is a clinically validated measure of blood rheology and an established predictor of cardiovascular risk. We hypothesize that increased WBV is associated with mortality among patients hospitalized with COVID-19.<br /><b>Objectives</b><br />This study sought to determine the association between estimated BV (eBV) and mortality among hospitalized COVID-19 patients.<br /><b>Methods</b><br />The study population included 5,621 hospitalized COVID-19 patients at the Mount Sinai Health System from February 27, 2020, to November 27, 2021. eBV was calculated using the Walburn-Schneck model. Multivariate Cox proportional hazards models were used to evaluate the association between eBV and mortality. Considered covariates included age, sex, race, cardiovascular and metabolic comorbidities, in-house pharmacotherapy, and baseline inflammatory biomarkers.<br /><b>Results</b><br />Estimated high-shear BV (eHSBV) and estimated low-shear BV were associated with increased in-hospital mortality. One-centipoise increases in eHSBV and estimated low-shear BV were associated with a 36.0% and 7.0% increase in death, respectively (P < 0.001). Compared with participants in the lowest quartile of eHSBV, those in the highest quartile of eHSBV had higher mortality (adjusted HR: 1.53; 95% CI: 1.27-1.84). The association was consistent among multiple subgroups, notably among patients without any comorbidities (adjusted HR: 1.69; 95% CI: 1.28-2.22).<br /><b>Conclusions</b><br />Among hospitalized COVID-19 patients, increased eBV is significantly associated with higher mortality. This suggests that eBV can prognosticate patient outcomes in earlier stages of COVID-19, and that future therapeutics aimed at reducing WBV should be evaluated.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 26 Jul 2022; 80:316-328</small></div>

<div><h4>Impact of Age and Sex on Left Ventricular Remodeling in Patients With Aortic Regurgitation.</h4><i>Akintoye E, Saijo Y, Braghieri L, Badwan O, ... Griffin BP, Popović ZB</i><br /><b>Background</b><br />Current guidelines for aortic regurgitation (AR) recommend the same linear left ventricular (LV) dimension for intervention regardless of age and sex.<br /><b>Objectives</b><br />The purpose of this study was to evaluate the impact of age and sex on the degree of LV remodeling and outcomes.<br /><b>Methods</b><br />We included consecutive patients with severe AR who were serially monitored by echocardiogram between 2010 and 2016. The 2 main endpoints were as follows: 1) LV end-systolic volume indexed to body surface area (LVESVi) and LV end-diastolic volume indexed to body surface area; and 2) adverse events (AE). We evaluated the longitudinal rate of LV remodeling and determined the association between LV volume and AE by age and sex.<br /><b>Results</b><br />A total of 525 adult patients (26% women) with a median echocardiogram follow-up of 2.0 years (IQR: 1.0-3.6 years) were included. At baseline, older patients (age ≥60 years) had smaller LV volumes compared with younger patients (age <60 years), eg, the mean LVESVi was 27.3 mL/m<sup>2</sup> vs 32.3 mL/m<sup>2</sup>, respectively. Similarly, women had smaller LV volumes compared with men (mean LVESVi was 23.3 mL/m<sup>2</sup> vs 32.4 mL/m<sup>2</sup>). On serial evaluation, older patients and women maintained smaller LV volumes compared with younger patients and men, respectively. There were 210 (40%) AE during follow-up. The optimal discriminatory threshold for AE varies by age and sex, eg, the LVESVi threshold was highest for young men (50 mL/m<sup>2</sup>), intermediate for older men (35 mL/m<sup>2</sup>), and lowest for women (27 mL/m<sup>2</sup>).<br /><b>Conclusions</b><br />On serial evaluation, older patients and women with chronic AR maintained smaller LV volumes than younger patients and men, respectively, and develop AE at lower LV volumes.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 18 Apr 2023; 81:1474-1487</small></div>

<div><h4>Combined Minimally Invasive Surgical and Percutaneous Catheter Ablation of Atrial Fibrillation: JACC Review Topic of the Week.</h4><i>Bisleri G, Pandey AK, Verma S, Ali Hassan SM, ... Bhatt DL, Ha ACT</i><br /><AbstractText>Hybrid ablation is a novel therapy in the invasive management of patients with atrial fibrillation (AF) which combines minimally invasive surgical and percutaneous catheter-based techniques. The evidence is mainly based on observational studies from experienced centers, with success rates of approximately 70% and risks that are 2.0-fold to 3.6-fold higher than catheter-based ablation. Hybrid ablation is offered typically to patients with persistent or longstanding persistent AF which, by design, requires 2 procedures (epicardial surgical and endocardial catheter-based ablation). One randomized trial demonstrated that hybrid ablation was more effective than catheter-based ablation, but with higher complication rates. The incidence of the most serious complications has decreased in contemporary studies of hybrid ablation. At present, hybrid ablation should be performed by experienced centers on selected patients with persistent or longstanding persistent AF. Additional randomized trials are needed to define the risks, benefits, and cost effectiveness of hybrid ablation to identify its most appropriate application in clinical practice.</AbstractText><br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Am Coll Cardiol: 14 Feb 2023; 81:606-619</small></div>

<div><h4>Bioprosthetic Aortic Valve Hemodynamics: Definitions, Outcomes, and Evidence Gaps: JACC State-of-the-Art Review.</h4><i>Herrmann HC, Pibarot P, Wu C, Hahn RT, ... Leon MB, Heart Valve Collaboratory</i><br /><AbstractText>A virtual workshop was organized by the Heart Valve Collaboratory to identify areas of expert consensus, areas of disagreement, and evidence gaps related to bioprosthetic aortic valve hemodynamics. Impaired functional performance of bioprosthetic aortic valve replacement is associated with adverse patient outcomes; however, this assessment is complicated by the lack of standardization for labelling, definitions, and measurement techniques, both after surgical and transcatheter valve replacement. Echocardiography remains the standard assessment methodology because of its ease of performance, widespread availability, ability to do serial measurements over time, and correlation with outcomes. Management of a high gradient after replacement requires integration of the patient\'s clinical status, physical examination, and multimodality imaging in addition to shared patient decisions regarding treatment options. Future priorities that are underway include efforts to standardize prosthesis sizing and labelling for both surgical and transcatheter valves as well as trials to characterize the consequences of adverse hemodynamics.</AbstractText><br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 02 Aug 2022; 80:527-544</small></div>

<div><h4>Impact of Peridevice Leak on 5-Year Outcomes After Left Atrial Appendage Closure.</h4><i>Dukkipati SR, Holmes DR, Doshi SK, Kar S, ... Allocco DJ, Reddy VY</i><br /><b>Background</b><br />In the U.S. Food and Drug Administration (FDA) clinical trials of left atrial appendage (LAA) closure, a postimplantation peridevice leak (PDL) of ≤5 mm (PDL≤5) was accepted as sufficient LAA \"closure.\" However, the clinical consequences of these PDLs on subsequent thromboembolism are poorly characterized.<br /><b>Objectives</b><br />We sought to assess the impact of PDL≤5 on clinical outcomes after implantation of the Watchman device.<br /><b>Methods</b><br />Using combined data from the FDA studies PROTECT-AF (Watchman Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation), PREVAIL (Evaluation of the Watchman Left Atrial Appendage Closure Device in Patients With Atrial Fibrillation vs Long Term Warfarin Therapy), and CAP2 (Continued Access to PREVAIL), we assessed patients with successful device implantation for PDL by means of protocol-mandated transesophageal echocardiograms (TEEs) at 45 days and 1 year. Five-year outcomes were assessed as a function of the absence or presence of PDL≤5.<br /><b>Results</b><br />The cohort included 1,054 patients: mean age 74 ± 8.3 years, 65% male, and CHA<sub>2</sub>DS<sub>2</sub>-VASc 4.1 ± 1.4. TEE imaging at 45 days revealed 634 patients (60.2%) without and 404 (38.3%) with PDL≤5, and 1-year TEE revealed 704 patients (71.6%) without and 272 (27.7%) with PDL≤5. The presence of PDL≤5 at 1 year, but not at 45 days, was associated with an increased 5-year risk of ischemic stroke or systemic embolism (adjusted HR: 1.94; 95% CI: 1.15-3.29; P = 0.014), largely driven by an increase in nondisabling stroke (HR: 1.97; 95% CI: 1.03-3.78; P = 0.04), while disabling or fatal stroke rates were similar (HR: 0.69; 95% CI: 0.19-2.46; P = 0.56). PDL≤5 was not associated with an increased risk of cardiovascular or unexplained death (HR: 1.20; P = 0.45) or all-cause death (HR: 0.87; P = 0.42).<br /><b>Conclusions</b><br />PDL≤5 at 1 year after percutaneous LAA closure with the Watchman device are associated with increased thromboembolism, driven by increased nondisabling stroke, but similar mortality. (Watchman Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation [PROTECT-AF; NCT00129545]; Evaluation of the Watchman Left Atrial Appendage Closure Device in Patients With Atrial Fibrillation vs Long Term Warfarin Therapy [PREVAIL; NCT01182441]; Continued Access to PREVAIL [CAP2; NCT01760291]).<br /><br />Copyright © 2022. Published by Elsevier Inc.<br /><br /><small>J Am Coll Cardiol: 02 Aug 2022; 80:469-483</small></div>

<div><h4>Criteria for Referral of Patients With Advanced Heart Failure for Specialized Palliative Care.</h4><i>Chang YK, Allen LA, McClung JA, Denvir MA, ... Collins A, Hui D</i><br /><b>Background</b><br />Patients with advanced heart failure have substantial supportive care needs. Specialist palliative care can be beneficial, but it is unclear who is most appropriate for referral and when patients should be referred.<br /><b>Objectives</b><br />We conducted a Delphi study of international experts to identify consensus referral criteria for specialist palliative care for patients with advanced heart failure.<br /><b>Methods</b><br />Clinicians from 5 continents with expertise in the integration of cardiology and palliative care were asked to rate 34 disease-based, 24 needs-based, and 9 time-based criteria over 3 rounds. Consensus was defined a priori as ≥70% agreement. A criterion was coded as major if the experts endorsed that meeting that criterion alone was adequate to justify a referral.<br /><b>Results</b><br />The response rate was 44 of 46 (96%), 41 of 46 (89%), and 43 of 46 (93%) in the first, second, and third rounds, respectively. Panelists reached consensus on 25 major criteria for specialist palliative care referral. The 25 major criteria were categorized under 6 topics, including \"advanced/refractory heart failure, comorbidities, and complications\" (eg, cardiac cachexia, cardiorenal syndrome) (n = 8), \"advanced heart failure therapies\" (eg, chronic inotropes, precardiac transplant) (n = 4), \"hospital utilization\" (eg, emergency room visits, hospitalization) (n = 2), \"prognostic estimate\" (n = 1), \"symptom burden/distress\" (eg, severe physical/emotional/spiritual distress) (n = 6), and \"decision making/social support\" (eg, goals-of-care discussions) (n = 4). The majority (68%) of major criteria had ≥90% agreement.<br /><b>Conclusions</b><br />International experts reached consensus on a large number of criteria for referral to specialist palliative care. With further validation, these criteria may be useful for standardizing palliative care access in the inpatient and/or outpatient settings.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 26 Jul 2022; 80:332-344</small></div>

<div><h4>Spatially Distinct Genetic Determinants of Aortic Dimensions Influence Risks of Aneurysm and Stenosis.</h4><i>Nekoui M, Pirruccello JP, Di Achille P, Choi SH, ... Lindsay ME, Ellinor PT</i><br /><b>Background</b><br />The left ventricular outflow tract (LVOT) and ascending aorta are spatially complex, with distinct pathologies and embryologic origins. Prior work examined the genetics of thoracic aortic diameter in a single plane.<br /><b>Objectives</b><br />We sought to elucidate the genetic basis for the diameter of the LVOT, aortic root, and ascending aorta.<br /><b>Methods</b><br />Using deep learning, we analyzed 2.3 million cardiac magnetic resonance images from 43,317 UK Biobank participants. We computed the diameters of the LVOT, the aortic root, and at 6 locations of ascending aorta. For each diameter, we conducted a genome-wide association study and generated a polygenic score. Finally, we investigated associations between these scores and disease incidence.<br /><b>Results</b><br />A total of 79 loci were significantly associated with at least 1 diameter. Of these, 35 were novel, and most were associated with 1 or 2 diameters. A polygenic score of aortic diameter approximately 13 mm from the sinotubular junction most strongly predicted thoracic aortic aneurysm (n = 427,016; mean HR: 1.42 per SD; 95% CI: 1.34-1.50; P = 6.67 × 10<sup>-21</sup>). A polygenic score predicting a smaller aortic root was predictive of aortic stenosis (n = 426,502; mean HR: 1.08 per SD; 95% CI: 1.03-1.12; P = 5 × 10<sup>-6</sup>).<br /><b>Conclusions</b><br />We detected distinct genetic loci underpinning the diameters of the LVOT, aortic root, and at several segments of ascending aorta. We spatially defined a region of aorta whose genetics may be most relevant to predicting thoracic aortic aneurysm. We further described a genetic signature that may predispose to aortic stenosis. Understanding genetic contributions to proximal aortic diameter may enable identification of individuals at risk for aortic disease and facilitate prioritization of therapeutic targets.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 02 Aug 2022; 80:486-497</small></div>

<div><h4>Presenting Pattern of Atrial Fibrillation and Outcomes of Early Rhythm Control Therapy.</h4><i>Goette A, Borof K, Breithardt G, Camm AJ, ... Kirchhof P, EAST-AFNET 4 Investigators</i><br /><b>Background</b><br />Whether atrial fibrillation (AF) pattern or timing of AF therapy modifies the effectiveness of early rhythm control (ERC) is not known.<br /><b>Objectives</b><br />This study sought to compare clinical characteristics and outcomes in patients presenting with different AF patterns on ERC vs usual care.<br /><b>Methods</b><br />The effects of ERC were compared in first-diagnosed AF (FDAF), paroxysmal AF (paroxAF), and persistent AF (persAF) in this prespecified analysis of the EAST-AFNET 4 (Early treatment of atrial fibrillation for stroke prevention) trial. Associations between AF pattern and primary outcomes (first primary outcome: cardiovascular death, stroke, and hospitalization for heart failure and acute coronary syndrome; second primary outcome: nights spent in hospital per year) were compared over a mean follow-up of 5.1 years. Changes in health-related quality of life were assessed by the EQ-5D.<br /><b>Results</b><br />FDAF patients (n = 1,048, enrolled 7 days after diagnosing AF) were slightly older (71 years of age, 48.0% female) than patients with paroxAF (n = 994, 70 years of age, 50.0% female) and persAF (n = 743, 70 years of age, 38.0% female). ERC reduced the primary outcome in all 3 AF patterns. Hospitalizations for acute coronary syndrome were highest in FDAF (incidence rate ratio [IRR]: 1.50; 95% CI: 0.83-2.69; P for interaction = 0.032) compared with paroxAF (IRR: 0.64; 95% CI: 0.32-1.25) and persAF (IRR: 0.50; 95% CI: 0.25-1.00). FDAF patients spent more nights in hospital (IRR: 1.38; 95% CI: 1.12-1.70; P for interaction = 0.004) than paroxAF (IRR: 0.84; 95% CI: 0.67-1.03), and persAF (IRR: 1.02; 95% CI: 0.80-1.30) patients. ERC improved health-related quality of life (EQ-5D score) in patients with paroxAF and persAF but not in patients with FDAF (P = 0.019).<br /><b>Conclusions</b><br />ERC reduces the first primary composite outcome in all AF patterns. Patients with FDAF are at high risk for hospitalization and acute coronary syndrome, particularly on ERC. (Early treatment of atrial fibrillation for stroke prevention trial; ISRCTN04708680; Early Treatment of Atrial Fibrillation for Stroke Prevention Trial [EAST]; NCT01288352; Early treatment of Atrial fibrillation for Stroke prevention Trial [EAST]; EudraCT2010-021258-20).<br /><br />Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 26 Jul 2022; 80:283-295</small></div>

<div><h4>Effects of Cyproheptadine on Mitral Valve Remodeling and Regurgitation After Myocardial Infarction.</h4><i>Marsit O, Clavel MA, Paquin A, Deschênes V, ... Pibarot P, Beaudoin J</i><br /><b>Background</b><br />Ischemic mitral regurgitation (MR) is primarily caused by left ventricle deformation, but leaflet thickening with fibrotic changes are also observed in the valve. Increased levels of 5-hydroxytryptamine (5-HT; ie, serotonin) are described after myocardial infarction (MI); 5-HT can induce valve fibrosis through the 5-HT type 2B receptor (5-HT2BR).<br /><b>Objectives</b><br />This study aims to test the hypothesis that post-MI treatment with cyproheptadine (5-HT2BR antagonist) can prevent ischemic MR by reducing the effect of serotonin on mitral biology.<br /><b>Methods</b><br />Thirty-six sheep were divided into 2 groups: inferior MI and inferior MI treated with cyproheptadine (0.5 mg/kg/d). Animals were followed for 90 days. Blood 5-HT, infarct size, left ventricular volume and function, MR fraction and mitral leaflet size were assessed. In a complementary in vitro study, valvular interstitial cells were exposed to pre-MI and post-MI serum collected from the experimental animals.<br /><b>Results</b><br />Increased 5-HT levels were observed after MI in nontreated animals, but not in the group treated with cyproheptadine. Infarct size was similar in both groups (11 ± 3 g vs 9 ± 5 g; P = 0.414). At 90 days, MR fraction was 16% ± 7% in the MI group vs 2% ± 6% in the cyproheptadine group (P = 0.0001). The increase in leaflet size following MI was larger in the cyproheptadine group (+40% ± 9% vs +22% ± 12%; P = 0.001). Mitral interstitial cells overexpressed extracellular matrix genes when treated with post-MI serum, but not when exposed to post-MI serum collected from treated animals.<br /><b>Conclusions</b><br />Cyproheptadine given after inferior MI reduces post-MI 5-HT levels, prevents valvular fibrotic remodeling, is associated with larger increase in mitral valve size and less MR.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 02 Aug 2022; 80:500-510</small></div>

<div><h4>Phenotypic Heterogeneity of Fulminant COVID-19--Related Myocarditis in Adults.</h4><i>Barhoum P, Pineton de Chambrun M, Dorgham K, Kerneis M, ... Gorochov G, Hékimian G</i><br /><b>Background</b><br />Adults who have been infected with SARS-CoV-2 can develop a multisystem inflammatory syndrome (MIS-A), including fulminant myocarditis. Yet, several patients fail to meet MIS-A criteria, suggesting the existence of distinct phenotypes in fulminant COVID-19-related myocarditis.<br /><b>Objectives</b><br />This study sought to compare the characteristics and clinical outcome between patients with fulminant COVID-19-related myocarditis fulfilling MIS-A criteria (MIS-A<sup>+</sup>) or not (MIS-A<sup>-</sup>).<br /><b>Methods</b><br />A monocentric retrospective analysis of consecutive fulminant COVID-19-related myocarditis in a 26-bed intensive care unit (ICU).<br /><b>Results</b><br />Between March 2020 and June 2021, 38 patients required ICU admission (male 66%; mean age 32 ± 15 years) for suspected fulminant COVID-19-related myocarditis. In-ICU treatment for organ failure included dobutamine 79%, norepinephrine 60%, mechanical ventilation 50%, venoarterial extracorporeal membrane oxygenation 42%, and renal replacement therapy 29%. In-hospital mortality was 13%. Twenty-five patients (66%) met the MIS-A criteria. MIS-A<sup>-</sup> patients compared with MIS-A<sup>+</sup> patients were characterized by a shorter delay between COVID-19 symptoms onset and myocarditis, a lower left ventricular ejection fraction, and a higher rate of in-ICU organ failure, and were more likely to require mechanical circulatory support with venoarterial extracorporeal membrane oxygenation (92% vs 16%; P < 0.0001). In-hospital mortality was higher in MIS-A<sup>-</sup> patients (31% vs 4%). MIS-A<sup>+</sup> had higher circulating levels of interleukin (IL)-22, IL-17, and tumor necrosis factor-α (TNF-α), whereas MIS-A<sup>-</sup> had higher interferon-α2 (IFN-α2) and IL-8 levels. RNA polymerase III autoantibodies were present in 7 of 13 MIS-A<sup>-</sup> patients (54%) but in none of the MIS-A<sup>+</sup> patients.<br /><b>Conclusion</b><br />MIS-A<sup>+</sup> and MIS-A<sup>-</sup> fulminant COVID-19-related myocarditis patients have 2 distinct phenotypes with different clinical presentations, prognosis, and immunological profiles. Differentiating these 2 phenotypes is relevant for patients\' management and further understanding of their pathophysiology.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 26 Jul 2022; 80:299-312</small></div>

<div><h4>New Cardiovascular Risk Assessment Techniques for Primary Prevention: JACC Review Topic of the Week.</h4><i>Verma KP, Inouye M, Meikle PJ, Nicholls SJ, Carrington MJ, Marwick TH</i><br /><AbstractText>Risk factor-based models fail to accurately estimate risk in select populations, in particular younger individuals. A sizable number of people are also classified as being at intermediate risk, for whom the optimal preventive strategy could be more precise. Several personalized risk prediction tools, including coronary artery calcium scoring, polygenic risk scores, and metabolic risk scores may be able to improve risk assessment, pending supportive outcome data from clinical trials. Other tools may well emerge in the near future. A multidimensional approach to risk prediction holds the promise of precise risk prediction. This could allow for targeted prevention minimizing unnecessary costs and risks while maximizing benefits. High-risk individuals could also be identified early in life, creating opportunities to arrest the development of nascent coronary atherosclerosis and prevent future clinical events.</AbstractText><br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 26 Jul 2022; 80:373-387</small></div>

<div><h4>Impact of the COVID-19 Pandemic on Cardiovascular Health in 2020: JACC State-of-the-Art Review.</h4><i>Roth GA, Vaduganathan M, Mensah GA</i><br /><AbstractText>The impact of COVID-19 on the burden of cardiovascular diseases (CVD) during the early pandemic remains unclear. COVID-19 has become one of the leading causes of global mortality, with a disproportionate impact on persons with CVD. Studies of health facility admissions for CVD found significant decreases during the pandemic. Studies of hospital mortality for CVD were more variable. Studies of population-level CVD mortality differed across countries, with most showing decreases, although some revealed increases in deaths. In some countries where large increases in CVD deaths were reported in vital registration systems, misclassification of COVID-19 as CVD may have occurred. Taken together, studies suggest heterogeneous effects of the COVID-19 pandemic on CVD without large increases in CVD mortality in 2020 for a number of countries. Clinical and population science research is needed to examine the ways in which the pandemic has affected CVD burden.</AbstractText><br /><br />Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 09 Aug 2022; 80:631-640</small></div>

<div><h4>Nurse-Provided Lung and Inferior Vena Cava Assessment in Patients With Heart Failure.</h4><i>Zisis G, Yang Y, Huynh Q, Whitmore K, ... Carrington MJ, Marwick TH</i><br /><b>Background</b><br />Residual congestion detected using handheld ultrasound may be associated with increased risk of readmission and death after hospitalization for acute decompensated heart failure (ADHF). However, effective application necessitates routine use by nonexperts delivering clinical care.<br /><b>Objectives</b><br />The objective of this study was to determine the ability of heart failure (HF) nurses to deliver a predischarge lung and inferior vena cava (IVC) assessment (LUICA) to predict 90-day outcomes.<br /><b>Methods</b><br />In this multisite, prospective, observational study, HF nurses scanned 240 patients with ADHF (median age: 77 years; 56% men) using a 9-zone LUICA protocol. Obtained images were reviewed by independent nurses who were blinded to clinical characteristics and outcomes. Based on a B-line cut-off of 10, patients were dichotomized as congested (n = 115) or not congested (n = 125).<br /><b>Results</b><br />Congested patients were more likely to have previous cardiac operations, long-standing HF (>6 months), and renal impairment. At 90 days, HF readmission or mortality occurred in 42 congested patients (37%) compared with 18 noncongested patients (14%). Pulmonary congestion increased at 30-day (OR: 3.86; 95% CI: 1.65-8.99; P < 0.01) and 90-day (OR: 3.42; 95% CI: 1.82-6.4; P < 0.01) HF readmission or mortality risk and 90-day mortality (OR: 5.18; 95% CI: 1.44-18.69; P < 0.01). Pulmonary congestion increased the 90-day odds of HF readmission and/or death by 3.3- to 4.2-fold (P < 0.01), independent of demographics, HF characteristics, comorbidities, and event risk score. Over 90 days, days alive out of hospital were fewer (78.3 ± 21.4 days vs 85.5 ± 12.4 days; P < 0.01) in congested patients.<br /><b>Conclusions</b><br />LUICA can be a powerful tool for detection of predischarge residual congestion. HF nurses can obtain images and provide diagnostic reports that are predictive of ADHF outcomes.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 02 Aug 2022; 80:513-523</small></div>

<div><h4>Coronary In-Stent Restenosis: JACC State-of-the-Art Review.</h4><i>Giustino G, Colombo A, Camaj A, Yasumura K, ... Kini A, Sharma SK</i><br /><AbstractText>The introduction and subsequent iterations of drug-eluting stent technologies have substantially improved the efficacy and safety of percutaneous coronary interventions. However, the incidence of in-stent restenosis (ISR) and the resultant need for repeated revascularization still occur at a rate of 1%-2% per year. Given that millions of drug-eluting stents are implanted each year around the globe, ISR can be considered as a pathologic entity of public health significance. The mechanisms of ISR are multifactorial. Since the first description of the angiographic patterns of ISR, the advent of intracoronary imaging has further elucidated the mechanisms and patterns of ISR. The armamentarium and treatment strategies of ISR have also evolved over time. Currently, an individualized approach using intracoronary imaging to characterize the underlying substrate of ISR is recommended. In this paper, we comprehensively reviewed the incidence, mechanisms, and imaging characterization of ISR and propose a contemporary treatment algorithm.</AbstractText><br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 26 Jul 2022; 80:348-372</small></div>

<div><h4>Sustained-Release Ivabradine Hemisulfate in Patients With Systolic Heart Failure.</h4><i>Ye F, Wang X, Wu S, Ma S, ... Wang J, FIRST Investigators</i><br /><b>Background</b><br />Ivabradine has potent actions in reducing heart rate and improving clinical outcomes of chronic heart failure with reduced ejection fraction (HFrEF). At present, only the short-acting formulation of ivabradine is available that needs to be administered twice daily.<br /><b>Objectives</b><br />This study sought to evaluate the role of ivabradine hemisulfate sustained release (SR), a novel long-acting formulation of ivabradine dosed once daily, in stable patients with HFrEF.<br /><b>Methods</b><br />Patients with stabilized HFrEF in New York Heart Association functional class II-IV were enrolled and randomized to receive placebo or ivabradine SR in addition to standard medications. The primary endpoint was the change of left ventricular (LV) end-systolic volume index from baseline to week 32.<br /><b>Results</b><br />We randomly assigned 181 patients to placebo and 179 patients to ivabradine SR. After 32 weeks, a significant improvement of LV end-systolic volume index from baseline was observed in both arms with a greater effect in the ivabradine SR arm. Ivabradine SR therapy also exhibited superiority in improving LV end-diastolic volume index, LV ejection fraction, resting heart rate, the Kansas City Cardiomyopathy Questionnaire score, and hospital admission for heart failure worsening and cardiovascular disease in comparison to placebo. Overall adverse events showed no difference between the treatment arms. There were fewer occurrences of worsening heart failure in the ivabradine SR arm.<br /><b>Conclusions</b><br />The present study demonstrates that ivabradine SR once daily in addition to optimum standard therapy improved heart function in patients with HFrEF. (Clinical Trial of Systolic Heart Failure Treatment of IvabRadine Hemisulfate Sustained-release Tablets [FIRST]; NCT02188082).<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 09 Aug 2022; 80:584-594</small></div>

<div><h4>Cardiovascular Disease Projections in the United States Based on the 2020 Census Estimates.</h4><i>Mohebi R, Chen C, Ibrahim NE, McCarthy CP, ... Wasfy JH, Januzzi JL</i><br /><b>Background</b><br />Understanding trends in cardiovascular (CV) risk factors and CV disease according to age, sex, race, and ethnicity is important for policy planning and public health interventions.<br /><b>Objectives</b><br />The goal of this study was to project the number of people with CV risk factors and disease and further explore sex, race, and ethnical disparities.<br /><b>Methods</b><br />The prevalence of CV risk factors (diabetes mellitus, hypertension, dyslipidemia, and obesity) and CV disease (ischemic heart disease, heart failure, myocardial infarction, and stroke) according to age, sex, race, and ethnicity was estimated by using logistic regression models based on 2013-2018 National Health and Nutrition Examination Survey data and further combining them with 2020 U.S. Census projection counts for years 2025-2060.<br /><b>Results</b><br />By the year 2060, compared with the year 2025, the number of people with diabetes mellitus will increase by 39.3% (39.2 million [M] to 54.6M), hypertension by 27.2% (127.8M to 162.5M), dyslipidemia by 27.5% (98.6M to 125.7M), and obesity by 18.3% (106.3M to 125.7M). Concurrently, projected prevalence will similarly increase compared with 2025 for ischemic heart disease by 31.1% (21.9M to 28.7M), heart failure by 33.0% (9.7M to 12.9M), myocardial infarction by 30.1% (12.3M to 16.0M), and stroke by 34.3% (10.8M to 14.5M). Among White individuals, the prevalence of CV risk factors and disease is projected to decrease, whereas significant increases are projected in racial and ethnic minorities.<br /><b>Conclusions</b><br />Large future increases in CV risk factors and CV disease prevalence are projected, disproportionately affecting racial and ethnic minorities. Future health policies and public health efforts should take these results into account to provide quality, affordable, and accessible health care.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 09 Aug 2022; 80:565-578</small></div>

<div><h4>Deep Learning Electrocardiographic Analysis for Detection of Left-Sided Valvular Heart Disease.</h4><i>Elias P, Poterucha TJ, Rajaram V, Moller LM, ... Leon MB, Perotte AJ</i><br /><b>Background</b><br />Valvular heart disease is an important contributor to cardiovascular morbidity and mortality and remains underdiagnosed. Deep learning analysis of electrocardiography (ECG) may be useful in detecting aortic stenosis (AS), aortic regurgitation (AR), and mitral regurgitation (MR).<br /><b>Objectives</b><br />This study aimed to develop ECG deep learning algorithms to identify moderate or severe AS, AR, and MR alone and in combination.<br /><b>Methods</b><br />A total of 77,163 patients undergoing ECG within 1 year before echocardiography from 2005-2021 were identified and split into train (n = 43,165), validation (n = 12,950), and test sets (n = 21,048; 7.8% with any of AS, AR, or MR). Model performance was assessed using area under the receiver-operating characteristic (AU-ROC) and precision-recall curves. Outside validation was conducted on an independent data set. Test accuracy was modeled using different disease prevalence levels to simulate screening efficacy using the deep learning model.<br /><b>Results</b><br />The deep learning algorithm model accuracy was as follows: AS (AU-ROC: 0.88), AR (AU-ROC: 0.77), MR (AU-ROC: 0.83), and any of AS, AR, or MR (AU-ROC: 0.84; sensitivity 78%, specificity 73%) with similar accuracy in external validation. In screening program modeling, test characteristics were dependent on underlying prevalence and selected sensitivity levels. At a prevalence of 7.8%, the positive and negative predictive values were 20% and 97.6%, respectively.<br /><b>Conclusions</b><br />Deep learning analysis of the ECG can accurately detect AS, AR, and MR in this multicenter cohort and may serve as the basis for the development of a valvular heart disease screening program.<br /><br />Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 09 Aug 2022; 80:613-626</small></div>

<div><h4>Hematopoietic Somatic Mosaicism Is Associated With an Increased Risk of Postoperative Atrial Fibrillation.</h4><i>Ninni S, Dombrowicz D, Kuznetsova T, Vicario R, ... Staels B, Montaigne D</i><br /><b>Background</b><br />On-pump cardiac surgery triggers sterile inflammation and postoperative complications such as postoperative atrial fibrillation (POAF). Hematopoietic somatic mosaicism (HSM) is a recently identified risk factor for cardiovascular diseases and results in a shift toward a chronic proinflammatory monocyte transcriptome and phenotype.<br /><b>Objectives</b><br />The aim of this study was to assess the prevalence, characteristics, and impact of HSM on preoperative blood and myocardial myeloid cells as well as on outcomes after cardiac surgery.<br /><b>Methods</b><br />Blood DNA from 104 patients referred for surgical aortic valve replacement (AVR) was genotyped using the HemePACT panel (576 genes). Four screening methods were applied to assess HSM, and postoperative outcomes were explored. In-depth blood and myocardial leukocyte phenotyping was performed in selected patients using mass cytometry and preoperative and postoperative RNA sequencing analysis of classical monocytes.<br /><b>Results</b><br />The prevalence of HSM in the patient cohort ranged from 29%, when considering the conventional HSM panel (97 genes) with variant allelic frequencies ≥2%, to 60% when considering the full HemePACT panel and variant allelic frequencies ≥1%. Three of 4 explored HSM definitions were significantly associated with higher risk for POAF. On the basis of the most inclusive definition, HSM carriers exhibited a 3.5-fold higher risk for POAF (age-adjusted OR: 3.5; 95% CI: 1.52-8.03; P = 0.003) and an exaggerated inflammatory response following AVR. HSM carriers presented higher levels of activated CD64<sup>+</sup>CD14<sup>+</sup>CD16<sup>-</sup> circulating monocytes and inflammatory monocyte-derived macrophages in presurgery myocardium.<br /><b>Conclusions</b><br />HSM is frequent in candidates for AVR, is associated with an enrichment of proinflammatory cardiac monocyte-derived macrophages, and predisposes to a higher incidence of POAF. HSM assessment may be useful in the personalized management of patients in the perioperative period. (Post-Operative Myocardial Incident & Atrial Fibrillation [POMI-AF]; NCT03376165).<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 04 May 2023; 81:1263-1278</small></div>

<div><h4>Virtual Care Team-Guided Therapeutic Optimization During Hospitalization in Patients with Heart Failure: The IMPLEMENT-HF Study.</h4><i>Bhatt AS, Varshney AS, Moscone A, Claggett BL, ... Adler DS, Vaduganathan M</i><br /><b>Background</b><br />Scalable and safe approaches for heart failure GDMT optimization are needed.<br /><b>Objective</b><br />We assessed the safety and effectiveness of a virtual care team-guided strategy on GDMT use in hospitalized patients with HFrEF.<br /><b>Methods</b><br />In a multicenter implementation trial, we allocated 252 hospital encounters in patients with LVEF≤40% to a virtual care team-guided strategy(107 encounters among 83 patients) or usual care(145 encounters among 115 patients) across 3 centers in an integrated health system. In the virtual care team group, clinicians received up to 1 daily GDMT optimization suggestion from a physician-pharmacist team. Primary effectiveness outcome was in-hospital change in GDMT optimization score (+2 initiations, +1 dose uptitrations, -1 dose downtitrations, -2 discontinuations summed across classes). In-hospital safety outcomes were adjudicated by an independent clinical events committee.<br /><b>Results</b><br />Among 252 encounters, mean age was 69±14 years, 85(34%) were women, 35(14%) were Black, and 43(17%) were Hispanic. The virtual care team strategy significantly improved GDMT scores vs. usual care (adjusted difference +1.2;95% CI:0.7-1.8;P<0.001). New initiations (44% vs.23%;P=0.001) and intensifications of ≥1 GDMT (50% vs.28%;P=0.001) were higher in the virtual care team group, translating to a number-needed-to-intervene of 5 encounters. Overall, 23(21%) in virtual care team group and 40(28%) in usual care experienced 1 or more safety events(P=0.30). AKI, bradycardia, hypotension, and hyperkalemia were similar between groups.<br /><b>Conclusion</b><br />Among patients hospitalized with HFrEF, a virtual care team-guided strategy for GDMT optimization was safe and improved GDMT across multiple hospitals in an integrated health system. Virtual teams represent a centralized, scalable approach to optimize GDMT.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Am Coll Cardiol: 21 Feb 2023; epub ahead of print</small></div>

<div><h4>2-Year Outcomes of Angiographic Quantitative Flow Ratio-Guided Coronary Interventions.</h4><i>Song L, Xu B, Tu S, Guan C, ... Stone GW, FAVOR III China Study Group</i><br /><b>Background</b><br />In the multicenter, randomized, sham-controlled FAVOR (Comparison of Quantitative Flow Ratio Guided and Angiography Guided Percutaneous Intervention in Patients with Coronary Artery Disease) III China trial, quantitative flow ratio (QFR)-based lesion selection improved 1-year clinical outcomes compared with conventional angiographic guidance for percutaneous coronary intervention (PCI).<br /><b>Objectives</b><br />The purpose of this study was to determine whether the benefits of QFR guidance persist at 2 years, particularly for patients in whom QFR changed the revascularization strategy.<br /><b>Methods</b><br />Eligible patients were randomized to a QFR-guided strategy (PCI performed only if QFR ≤0.80) or a standard angiography-guided strategy. Major adverse cardiac events (MACE), a composite of all-cause death, myocardial infarction (MI), or ischemia-driven revascularization occurring within 2 years were analyzed in the intention-to-treat population.<br /><b>Results</b><br />Among 3,825 randomized participants, 2-year MACE occurred in 161 of 1,913 (8.5%) patients in the QFR-guided group and in 237 of 1,912 (12.5%) patients in the angiography-guided group (HR: 0.66; 95% CI: 0.54-0.81; P < 0.0001), driven by fewer MIs (4.0% vs 6.8%; HR: 0.58; 95% CI: 0.44-0.77; P = 0.0002) and ischemia-driven revascularizations (4.2% vs 5.8%; HR: 0.71; 95% CI: 0.53-0.95; P = 0.02) in the QFR-guided group. Landmark analysis showed consistent results within the first year and between 1-2 years (P<sub>int</sub> = 0.99). Although the 2-year MACE rate was lower in the QFR-guided group in both patients with and without revascularization strategy changes, the extent of outcome improvement was greater (P<sub>int</sub> = 0.009) among those patients in whom the preplanned PCI strategy was modified by QFR.<br /><b>Conclusions</b><br />QFR-guided lesion selection improved 2-year clinical outcomes compared with standard angiography guidance. The benefits were most pronounced among patients in whom QFR assessment altered the planned revascularization strategy. (FAVOR III China Study [The Comparison of Quantitative Flow Ratio Guided and Angiography Guided Percutaneous Intervention in Patients with Coronary Artery Disease] NCT03656848).<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 29 Nov 2022; 80:2089-2101</small></div>

<div><h4>Variation in Renal Function Following Transition to Sacubitril/Valsartan in Patients with Heart Failure.</h4><i>Chatur S, Claggett BL, McCausland FR, Rouleau J, ... Solomon SD, Vaduganathan M</i><br /><b>Background</b><br />Some patients with heart failure may experience transient changes in kidney function upon transition to sacubitril/valsartan. Whether such changes portend adverse outcomes or influence long-term treatment benefits with sacubitril/valsartan continuation is unknown.<br /><b>Objectives</b><br />To evaluate the association between the occurrence of moderate eGFR decline(>15%) after initial exposure to sacubitril/valsartan and subsequent cardiovascular outcomes and its treatment benefits in PARADIGM-HF and PARAGON-HF.<br /><b>Methods</b><br />In sequential run-in phases, patients were titrated to enalapril 10mg twice daily and then sacubitril/valsartan 97/103mg twice daily (in PARADIGM-HF) or valsartan 80mg twice daily and then sacubitril/valsartan 49/51mg twice daily (in PARAGON-HF).<br /><b>Results</b><br />Among randomized participants, 11% in PARADIGM-HF and 10% in PARAGON-HF experienced eGFR decline (>15%) during sacubitril/valsartan run-in. eGFR partially recovered(from nadir to post-randomization week 16) regardless of sacubitril/valsartan continuation or switch to RASi, post-randomization. Initial eGFR decline was not consistently associated with clinical outcomes in either trial. Treatment benefits of sacubitril/valsartan vs. RASi on primary outcomes were similar irrespective of run-in eGFR decline in PARADIGM-HF (eGFR decline: HR 0.69; 95%CI: 0.53-0.90 and no eGFR decline: HR 0.80; 95%CI: 0.73-0.88, P<sub>interaction</sub>=0.32) and PARAGON-HF (eGFR decline: RR 0.84; 95%CI 0.52-1.36 and no eGFR decline: RR 0.87; 95%CI: 0.75-1.02, P<sub>interaction</sub>=0.92). The treatment effect of sacubitril/valsartan remained consistent across a range of eGFR declines.<br /><b>Conclusion</b><br />Moderate eGFR decline when transitioning from RASi to sacubitril/valsartan is not consistently associated with adverse outcomes, and its long-term benefits are retained in heart failure across a broad range of eGFR declines. Early eGFR changes should not deter sacubitril/valsartan continuation or stall up-titration.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Am Coll Cardiol: 09 Feb 2023; epub ahead of print</small></div>

<div><h4>Intensive Blood Pressure Lowering in Patients With Malignant Left Ventricular Hypertrophy.</h4><i>Ascher SB, de Lemos JA, Lee M, Wu E, ... Shlipak MG, Berry JD</i><br /><b>Background</b><br />Left ventricular hypertrophy (LVH) combined with elevations in cardiac biomarkers reflecting myocardial injury and neurohormonal stress (malignant LVH) is associated with a high risk for heart failure and death.<br /><b>Objectives</b><br />The aim of this study was to determine the impact of intensive systolic blood pressure (SBP) control on the prevention of malignant LVH and its consequences.<br /><b>Methods</b><br />A total of 8,820 participants in SPRINT (Systolic Blood Pressure Intervention Trial) were classified into groups based on the presence or absence of LVH assessed by 12-lead ECG, and elevations in biomarker levels (high-sensitivity cardiac troponin T ≥14 ng/L or N-terminal pro-B-type natriuretic peptide ≥125 pg/mL) at baseline. The effects of intensive vs standard SBP lowering on rates of acute decompensated heart failure (ADHF) events and death and on the incidence and regression of malignant LVH were determined.<br /><b>Results</b><br />Randomization to intensive SBP lowering led to similar relative reductions in ADHF events and death across the combined LVH/biomarker groups (P for interaction = 0.68). The absolute risk reduction over 4 years in ADHF events and death was 4.4% (95% CI: -5.2% to 13.9%) among participants with baseline malignant LVH (n = 449) and 1.2% (95% CI: 0.0%-2.5%) for those without LVH and nonelevated biomarkers (n = 4,361). Intensive SBP lowering also reduced the incidence of malignant LVH over 2 years (2.5% vs 1.1%; OR: 0.44; 95% CI: 0.30-0.63).<br /><b>Conclusions</b><br />Intensive SBP lowering prevented malignant LVH and may provide substantial absolute risk reduction in the composite of ADHF events and death among SPRINT participants with baseline malignant LVH.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 18 Oct 2022; 80:1516-1525</small></div>

<div><h4>Effect of Prosthesis-Patient Mismatch on Long-Term Clinical Outcomes After Bioprosthetic Aortic Valve Replacement.</h4><i>Dismorr M, Glaser N, Franco-Cereceda A, Sartipy U</i><br /><b>Background</b><br />Prosthesis-patient mismatch (PPM) is common following surgical aortic valve replacement (SAVR).<br /><b>Objectives</b><br />The purpose of this study was to quantify the impact of PPM on all-cause mortality, heart failure hospitalization, and reintervention following bioprosthetic SAVR.<br /><b>Methods</b><br />This observational nationwide cohort study from SWEDEHEART (Swedish Web system for Enhancement and Development of Evidence based care in Heart disease Evaluated According to Recommended Therapies) and other national registers included all patients who underwent primary bioprosthetic SAVR in Sweden from 2003 to 2018. PPM was defined according to the Valve Academic Research Consortium 3 criteria. Outcomes were all-cause mortality, heart failure hospitalization, and aortic valve reintervention. Regression standardization was used to account for intergroup differences and to estimate cumulative incidence differences.<br /><b>Results</b><br />We included 16,423 patients (no PPM: 7,377 [45%]; moderate PPM: 8,502 [52%]; and severe PPM: 544 [3%]). After regression standardization, the cumulative incidence of all-cause mortality at 10 years was 43% (95% CI: 24%-44%) in the no PPM group compared with 45% (95% CI: 43%-46%) and 48% (95% CI: 44%-51%) in the moderate and severe PPM groups, respectively. The survival difference at 10 years was 4.6% (95% CI: 0.7%-8.5%) and 1.7% (95% CI: 0.1%-3.3%) in no vs severe PPM and no vs moderate PPM, respectively. The difference in heart failure hospitalization at 10 years was 6.0% (95% CI: 2.2%-9.7%) in severe vs no PPM. There was no difference in aortic valve reintervention in patients with or without PPM.<br /><b>Conclusions</b><br />Increasing grades of PPM were associated with long-term mortality, and severe PPM was associated with increased heart failure. Moderate PPM was common, but the clinical significance may be negligible because the absolute risk differences in clinical outcomes were small.<br /><br />Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 14 Mar 2023; 81:964-975</small></div>

<div><h4>P2Y Inhibitor Monotherapy or Dual Antiplatelet Therapy After Complex Percutaneous Coronary Interventions.</h4><i>Gragnano F, Mehran R, Branca M, Franzone A, ... Valgimigli M, Single Versus Dual Antiplatelet Therapy (Sidney-2) Collaboration</i><br /><b>Background</b><br />It remains unclear whether P2Y<sub>12</sub> inhibitor monotherapy preserves ischemic protection while limiting bleeding risk compared with dual antiplatelet therapy (DAPT) after complex percutaneous coronary intervention (PCI).<br /><b>Objectives</b><br />We sought to assess the effects of P2Y<sub>12</sub> inhibitor monotherapy after 1-month to 3-month DAPT vs standard DAPT in relation to PCI complexity.<br /><b>Methods</b><br />We pooled patient-level data from randomized controlled trials comparing P2Y<sub>12</sub> inhibitor monotherapy and standard DAPT on centrally adjudicated outcomes after coronary revascularization. Complex PCI was defined as any of 6 criteria: 3 vessels treated, ≥3 stents implanted, ≥3 lesions treated, bifurcation with 2 stents implanted, total stent length >60 mm, or chronic total occlusion. The primary efficacy endpoint was all-cause mortality, myocardial infarction, and stroke. The key safety endpoint was Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding.<br /><b>Results</b><br />Of 22,941 patients undergoing PCI from 5 trials, 4,685 (20.4%) with complex PCI had higher rates of ischemic events. The primary efficacy endpoint was similar between P2Y<sub>12</sub> inhibitor monotherapy and DAPT among patients with complex PCI (HR: 0.87; 95% CI: 0.64-1.19) and noncomplex PCI (HR: 0.91; 95% CI: 0.76-1.09; P<sub>interaction</sub> = 0.770). The treatment effect was consistent across all the components of the complex PCI definition. Compared with DAPT, P2Y<sub>12</sub> inhibitor monotherapy consistently reduced BARC 3 or 5 bleeding in complex PCI (HR: 0.51; 95% CI: 0.31-0.84) and noncomplex PCI patients (HR: 0.49; 95% CI: 0.37-0.64; P<sub>interaction</sub> = 0.920).<br /><b>Conclusions</b><br />P2Y<sub>12</sub> inhibitor monotherapy after 1-month to 3-month DAPT was associated with similar rates of fatal and ischemic events and lower risk of major bleeding compared with standard DAPT, irrespective of PCI complexity. (PROSPERO [P2Y12 Inhibitor Monotherapy Versus Standard Dual Antiplatelet Therapy After Coronary Revascularization: Individual Patient Data Meta-Analysis of Randomized Trials]; CRD42020176853).<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 14 Feb 2023; 81:537-552</small></div>

<div><h4>Impact of Moderate Aortic Stenosis in Patients With Heart Failure With Reduced Ejection Fraction.</h4><i>Khan KR, Khan OA, Chen C, Liu Y, ... Langer NB, Elmariah S</i><br /><b>Background</b><br />Afterload from moderate aortic stenosis (AS) may contribute to adverse outcomes in patients with heart failure with reduced ejection fraction (HFrEF).<br /><b>Objectives</b><br />The authors evaluated clinical outcomes in patients with HFrEF and moderate AS relative to those without AS and with severe AS.<br /><b>Methods</b><br />Patients with HFrEF, defined by left ventricular ejection fraction (LVEF) <50% and no, moderate, or severe AS were retrospectively identified. The primary endpoint, defined as a composite of all-cause mortality and heart failure (HF) hospitalization, was compared across groups and within a propensity score-matched cohort.<br /><b>Results</b><br />We included 9,133 patients with HFrEF, of whom 374 and 362 had moderate and severe AS, respectively. Over a median follow-up time of 3.1 years, the primary outcome occurred in 62.7% of patients with moderate AS vs 45.9% with no AS (P < 0.0001); rates were similar with severe and moderate AS (62.0% vs 62.7%; P = 0.68). Patients with severe AS had a lower incidence of HF hospitalization (36.2% vs 43.6%; P < 0.05) and were more likely to undergo AVR within the follow-up period. Within a propensity score-matched cohort, moderate AS was associated with an increased risk of HF hospitalization and mortality (HR: 1.24; 95% CI: 1.04-1.49; P = 0.01) and fewer days alive outside of the hospital (P < 0.0001). Aortic valve replacement (AVR) was associated with improved survival (HR: 0.60; CI: 0.36-0.99; P < 0.05).<br /><b>Conclusions</b><br />In patients with HFrEF, moderate AS is associated with increased rates of HF hospitalization and mortality. Further investigation is warranted to determine whether AVR in this population improves clinical outcomes.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 04 May 2023; 81:1235-1244</small></div>

<div><h4>Dose-Response to Sacubitril/Valsartan in Patients With Heart Failure and Reduced Ejection Fraction.</h4><i>Mohebi R, Liu Y, Piña IL, Prescott MF, ... Solomon SD, Januzzi JL</i><br /><b>Background</b><br />Doses of sacubitril/valsartan (Sac/Val) achieved in clinical trials of heart failure with reduced ejection fraction (HFrEF) are often not reached in clinical practice.<br /><b>Objectives</b><br />The purpose of this study was to investigate associations among Sac/Val doses and changes in prognostic biomarkers, health status, and cardiac remodeling among individuals with HFrEF through 12 months of treatment with Sac/Val administered per usual care.<br /><b>Methods</b><br />A total of 794 persons with HFrEF (ejection fraction [EF] ≤40%) were categorized according to average daily doses of Sac/Val divided into tertiles. Change from baseline to 12 months in biomarkers (N-terminal pro-B-type natriuretic peptide, high-sensitivity cardiac troponin T, soluble ST2, atrial natriuretic peptide, urinary cyclic guanosine monophosphate), Kansas City Cardiomyopathy Questionnaire-23 scores, and parameters of cardiac reverse remodeling (left ventricular EF, indexed left atrial and ventricular volumes, and E/e\') were assessed.<br /><b>Results</b><br />The average daily dose was 112 mg in Tertile 1 (low dose), 342 mg in Tertile 2 (moderate dose), and 379 mg in Tertile 3 (high dose). Similar changes in prognostic biomarkers were observed in all dose tertiles. Gains in Kansas City Cardiomyopathy Questionnaire-23 scores were comparable regardless of dose category. Consistent reverse cardiac remodeling in all dose categories occurred; the median absolute left ventricular EF improvement across HF dose groups was 9.3%, 8.7%, and 10.2%, for low, moderate, and high doses, respectively; similar improvements in left atrial and ventricular volumes and E/e\' were also observed across dose categories.<br /><b>Conclusions</b><br />Among patients with HFrEF, similar improvement in prognostic biomarkers, health status, and cardiac remodeling were observed across various Sac/Val doses. (Effects of Sacubitril/Valsartan Therapy on Biomarkers, Myocardial Remodeling and Outcomes [PROVE-HF]; NCT02887183.<br /><br />Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 18 Oct 2022; 80:1529-1541</small></div>

<div><h4>Incidence and Burden of Tricuspid Regurgitation in Patients With Atrial Fibrillation.</h4><i>Patlolla SH, Schaff HV, Nishimura RA, Stulak JM, ... Pislaru SV, Nkomo VT</i><br /><b>Background</b><br />Atrial fibrillation (AF) is considered a risk factor for isolated tricuspid valve regurgitation (TR) in the absence of other known etiologies.<br /><b>Objectives</b><br />This study sought to identify the incidence of clinically significant isolated TR and its impact in patients with AF.<br /><b>Methods</b><br />A population-based record linkage system was used to identify adult patients with new-onset AF. Patients with evidence of moderate or greater tricuspid valve disease, left-sided valve disease, pulmonary hypertension, prior cardiac surgery, impaired left ventricular systolic/diastolic function at baseline were excluded. The remaining patients (n = 691) were followed over time to identify development of moderate or greater TR and assess its impact on subsequent survival.<br /><b>Results</b><br />A total of 232 patients (33.6%) developed moderate or greater TR. Among these, 73 patients (10.6%) had isolated TR without significant underlying structural heart disease. Incidence rate of any moderate or greater TR was 3.9 cases and that of isolated TR was 1.3 cases per 100 person-years. Permanent/persistent AF and female sex were associated with increased risk of developing TR, whereas rhythm control was associated with lower risk of TR. Over a median clinical follow-up of 13.3 years (IQR: 10.0-15.9 years), development of any moderate or greater TR (HR: 2.92; 95% CI: 2.29-3.73; P < 0.001) and isolated significant TR (HR: 1.51; 95% CI: 1.03-2.22; P = 0.03) were associated with an adjusted increased risk of subsequent mortality.<br /><b>Conclusions</b><br />In this population-based cohort of patients with AF, nearly one-third developed moderate or greater TR over time. Incident significant TR and incident isolated significant TR portend a worse survival in patients with AF.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 13 Dec 2022; 80:2289-2298</small></div>

<div><h4>The Genetic Determinants of Aortic Distention.</h4><i>Pirruccello JP, Rämö JT, Choi SH, Chaffin MD, ... Lindsay ME, Ellinor PT</i><br /><b>Background</b><br />As the largest conduit vessel, the aorta is responsible for the conversion of phasic systolic inflow from ventricular ejection into more continuous peripheral blood delivery. Systolic distention and diastolic recoil conserve energy and are enabled by the specialized composition of the aortic extracellular matrix. Aortic distensibility decreases with age and vascular disease.<br /><b>Objectives</b><br />In this study, we sought to discover epidemiologic correlates and genetic determinants of aortic distensibility and strain.<br /><b>Methods</b><br />We trained a deep learning model to quantify thoracic aortic area throughout the cardiac cycle from cardiac magnetic resonance images and calculated aortic distensibility and strain in 42,342 UK Biobank participants.<br /><b>Results</b><br />Descending aortic distensibility was inversely associated with future incidence of cardiovascular diseases, such as stroke (HR: 0.59 per SD; P = 0.00031). The heritabilities of aortic distensibility and strain were 22% to 25% and 30% to 33%, respectively. Common variant analyses identified 12 and 26 loci for ascending and 11 and 21 loci for descending aortic distensibility and strain, respectively. Of the newly identified loci, 22 were not significantly associated with thoracic aortic diameter. Nearby genes were involved in elastogenesis and atherosclerosis. Aortic strain and distensibility polygenic scores had modest effect sizes for predicting cardiovascular outcomes (delaying or accelerating disease onset by 2%-18% per SD change in scores) and remained statistically significant predictors after accounting for aortic diameter polygenic scores.<br /><b>Conclusions</b><br />Genetic determinants of aortic function influence risk for stroke and coronary artery disease and may lead to novel targets for medical intervention.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 11 Apr 2023; 81:1320-1335</small></div>

<div><h4>Vein Graft Use and Long-Term Survival Following Coronary Bypass Grafting.</h4><i>Shih E, Squiers JJ, Banwait JK, Mack MJ, ... DiMaio JM, Schaffer JM</i><br /><b>Background</b><br />Although placement of at least 1 arterial graft during coronary artery bypass grafting (CABG) has a proven survival benefit, it is unknown what degree of revascularization with saphenous vein grafting (SVG) is associated with improved survival.<br /><b>Objectives</b><br />The authors sought to determine whether undergoing surgery performed by a surgeon who is liberal with vein graft utilization is associated with improved survival in patients undergoing single arterial graft CABG (SAG-CABG).<br /><b>Methods</b><br />This was a retrospective, observational study of SAG-CABG performed in Medicare beneficiaries from 2001 to 2015. Surgeons were stratified by number of SVG utilized per SAG-CABG into conservative (≥1 SD below mean), average (within 1 SD of mean), and liberal (≥1 SD above mean). Long-term survival was estimated using Kaplan-Meier analysis and compared among surgeon groups before and after augmented inverse-probability weighting.<br /><b>Results</b><br />There were 1,028,264 Medicare beneficiaries undergoing SAG-CABG from 2001 to 2015 (mean age 72.0 ± 7.9 years, 68.3% male). Over time, 1-vein and 2-vein SAG-CABG utilization increased, whereas 3-vein and ≥4-vein SAG-CABG utilization decreased (P < 0.001). Surgeons who were conservative vein graft users performed a mean 1.7 ± 0.2 vein grafts per SAG-CABG, whereas those who were liberal vein graft users performed a mean 2.9 ± 0.2 vein grafts per SAG-CABG. Weighted analysis demonstrated no difference in median survival among patients undergoing SAG-CABG by liberal vs conservative vein graft users (adjusted median survival difference 27 days).<br /><b>Conclusions</b><br />Among Medicare beneficiaries undergoing SAG-CABG, there is no association between surgeon proclivity for vein graft utilization and long-term survival, suggesting that a conservative approach to vein graft utilization is reasonable.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 28 Feb 2023; 81:713-725</small></div>

<div><h4>Short-Term Risk Stratification of Non-Flow-Limiting Coronary Stenosis by Angiographically Derived Radial Wall Strain.</h4><i>Tu S, Xu B, Chen L, Hong H, ... Wijns W, FAVOR III China Study Group</i><br /><b>Background</b><br />Deferred revascularization of mildly stenotic coronary vessels based exclusively on physiological evaluation is associated with up to 5% residual incidence of future adverse events at 1 year.<br /><b>Objectives</b><br />We aimed to evaluate the incremental value of angiography-derived radial wall strain (RWS) in risk stratification of non-flow-limiting mild coronary narrowings.<br /><b>Methods</b><br />This is a post hoc analysis of 824 non-flow-limiting vessels in 751 patients from the FAVOR III China (Comparison of Quantitative Flow Ratio Guided and Angiography Guided Percutaneous Intervention in Patients With Coronary Artery Disease) trial. Each individual vessel had ≥1 mildly stenotic lesion. The primary outcome was vessel-oriented composite endpoint (VOCE), defined as the composite of vessel-related cardiac death, vessel-related myocardial infarction (nonprocedural), and ischemia-driven target vessel revascularization at 1-year follow-up.<br /><b>Results</b><br />During 1-year follow-up, VOCE occurred in 46 of 824 vessels, with a cumulative incidence of 5.6%. Maximum RWS (RWS<sub>max</sub>) was predictive of 1-year VOCE with an area under the curve of 0.68 (95% CI: 0.58-0.77; P < 0.001). The incidence of VOCE was 14.3% in vessels with RWS<sub>max</sub> >12% vs 2.9% in those with RWS<sub>max</sub> ≤12%. In the multivariable Cox regression model, RWS<sub>max</sub> >12% was a strong independent predictor of 1-year VOCE in deferred non-flow-limiting vessels (adjusted HR: 4.44; 95% CI: 2.43-8.14; P < 0.001). The risk of deferred revascularization based on combined normal RWS<sub>max</sub> and Murray-law-based quantitative flow ratio (μQFR) was significantly reduced compared with μQFR alone (adjusted HR: 0.52; 95% CI: 0.30-0.90; P = 0.019).<br /><b>Conclusions</b><br />Among vessels with preserved coronary flow, angiography-derived RWS analysis has the potential to further discriminate vessels at risk of 1-year VOCE. (Comparison of Quantitative Flow Ratio Guided and Angiography Guided Percutaneous Intervention in Patients With Coronary Artery Disease [FAVOR III China Study]; NCT03656848).<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 28 Feb 2023; 81:756-767</small></div>

<div><h4>Bleeding Events After Transcatheter Aortic Valve Replacement: JACC State-of-the-Art Review.</h4><i>Avvedimento M, Nuche J, Farjat-Pasos JI, Rodés-Cabau J</i><br /><AbstractText>Transcatheter aortic valve replacement (TAVR) has gained over time a major reduction in procedural complications. Despite this, clinically relevant bleeding still occurs in a non-negligible proportion of patients and adversely affects prognosis. Patients with severe aortic stenosis are at heightened risk for spontaneous bleeding due to advanced age and a high comorbidity burden. Also, procedural factors and antithrombotic management contribute to define individual bleeding susceptibility. Bleeding prevention represents an emerging area for improving patient care. Because of the tight hemorrhagic/ischemic balance, a tailored approach based on individual bleeding-risk profile, such as a less invasive antithrombotic regimen or appropriate diagnostic preprocedural evaluation, should be pursued to avoid bleeding events. This review aims to provide an in-depth overview of bleeding events in the TAVR field, including definitions, timing and the extent of risk, and clinical impact, as well as updates on antithrombotic management and its potential influence on bleeding complications.</AbstractText><br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 21 Feb 2023; 81:684-702</small></div>

<div><h4>Clinical Characteristics and Transplant-Free Survival Across the Spectrum of Pulmonary Vascular Disease.</h4><i>Hemnes AR, Leopold JA, Radeva MK, Beck GJ, ... Horn EM, PVDOMICS Study Group</i><br /><b>Background</b><br />PVDOMICS (Pulmonary Vascular Disease Phenomics) is a precision medicine initiative to characterize pulmonary vascular disease (PVD) using deep phenotyping. PVDOMICS tests the hypothesis that integration of clinical metrics with omic measures will enhance understanding of PVD and facilitate an updated PVD classification.<br /><b>Objectives</b><br />The purpose of this study was to describe clinical characteristics and transplant-free survival in the PVDOMICS cohort.<br /><b>Methods</b><br />Subjects with World Symposium Pulmonary Hypertension (WSPH) group 1-5 PH, disease comparators with similar underlying diseases and mild or no PH and healthy control subjects enrolled in a cross-sectional study. PH groups, comparators were compared using standard statistical tests including log-rank tests for comparing time to transplant or death.<br /><b>Results</b><br />A total of 1,193 subjects were included. Multiple WSPH groups were identified in 38.9% of PH subjects. Nocturnal desaturation was more frequently observed in groups 1, 3, and 4 PH vs comparators. A total of 50.2% of group 1 PH subjects had ground glass opacities on chest computed tomography. Diffusing capacity for carbon monoxide was significantly lower in groups 1-3 PH than their respective comparators. Right atrial volume index was higher in WSPH groups 1-4 than comparators. A total of 110 participants had a mean pulmonary artery pressure of 21-24 mm Hg. Transplant-free survival was poorest in group 3 PH.<br /><b>Conclusions</b><br />PVDOMICS enrolled subjects across the spectrum of PVD, including mild and mixed etiology PH. Novel findings include low diffusing capacity for carbon monoxide and enlarged right atrial volume index as shared features of groups 1-3 and 1-4 PH, respectively; unexpected, frequent presence of ground glass opacities on computed tomography; and sleep alterations in group 1 PH, and poorest survival in group 3 PH. PVDOMICS will facilitate a new understanding of PVD and refine the current PVD classification. (Pulmonary Vascular Disease Phenomics Program PVDOMICS [PVDOMICS]; NCT02980887).<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 16 Aug 2022; 80:697-718</small></div>

<div><h4>Influence of Culprit Lesion Intervention on Outcomes in Infarct-Related Cardiogenic Shock With Cardiac Arrest.</h4><i>Zeymer U, Alushi B, Noc M, Mamas MA, ... Lauten A, Thiele H</i><br /><b>Background</b><br />Cardiac arrest (CA) is common in patients with infarct-related cardiogenic shock (CS).<br /><b>Objectives</b><br />The goal of this study was to identify the characteristics and outcomes of culprit lesion percutaneous coronary intervention (PCI) of patients with infarct-related CS stratified according to CA in the CULPRIT-SHOCK (Culprit Lesion Only PCI Versus Multivessel PCI in Cardiogenic Shock) randomized trial and registry.<br /><b>Methods</b><br />Patients with CS with and without CA from the CULPRIT-SHOCK study were analyzed. All-cause death or severe renal failure leading to renal replacement therapy within 30 days and 1-year death were assessed.<br /><b>Results</b><br />Among 1,015 patients, 550 (54.2%) had CA. Patients with CA were younger, more frequently male, had lower rates of peripheral artery disease, a glomerular filtration rate <30 mL/min, and left main disease, and they presented more often with clinical signs of impaired organ perfusion. The composite of all-cause death or severe renal failure within 30 days occurred in 51.2% of patients with CA vs 48.5% in non-CA patients (P = 0.39) and 1-year death in 53.8% vs 50.4% (P = 0.29), respectively. In a multivariate analysis, CA was an independent predictor of 1-year mortality (HR: 1.27; 95% CI: 1.01-1.59). In the randomized trial, culprit lesion-only PCI was superior to immediate multivessel PCI in patients both with and without CA (P for interaction = 0.6).<br /><b>Conclusions</b><br />More than 50% of patients with infarct-related CS had CA. These patients with CA were younger and had fewer comorbidities, but CA was an independent predictor of 1-year mortality. Culprit lesion-only PCI is the preferred strategy, both in patients with and without CA. (Culprit Lesion Only PCI Versus Multivessel PCI in Cardiogenic Shock [CULPRIT-SHOCK]; NCT01927549).<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 28 Mar 2023; 81:1165-1176</small></div>

<div><h4>Impact of Left Ventricular Ejection Fraction on Clinical Outcomes in Bicuspid Aortic Valve Disease.</h4><i>Hecht S, Butcher SC, Pio SM, Kong WKF, ... Bax JJ, Pibarot P</i><br /><b>Background</b><br />The prognostic impact of left ventricular ejection fraction (LVEF) in patients with bicuspid aortic valve (BAV) disease has not been previously studied.<br /><b>Objectives</b><br />The purpose of this study was to determine the prognostic impact of LVEF in BAV patients according to the type of aortic valve dysfunction.<br /><b>Methods</b><br />We retrospectively analyzed the data collected in 2,672 patients included in an international registry of patients with BAV. Patients were classified according to the type of aortic valve dysfunction: isolated aortic stenosis (AS) (n = 749), isolated aortic regurgitation (AR) (n = 554), mixed aortic valve disease (MAVD) (n = 190), or no significant aortic valve dysfunction (n = 1,179; excluded from this analysis). The study population was divided according to LVEF strata to investigate its impact on clinical outcomes.<br /><b>Results</b><br />The risk of all-cause mortality and the composite endpoint of aortic valve replacement or repair (AVR) and all-cause mortality increased when LVEF was <60% in the whole cohort as well as in the AS and AR groups, and when LVEF was <55% in MAVD group. In multivariable analysis, LVEF strata were significantly associated with increased rate of mortality (LVEF 50%-59%: HR: 1.83 [95% CI: 1.09-3.07]; P = 0.022; LVEF 30%-49%: HR: 1.97 [95% CI: 1.13-3.41]; P = 0.016; LVEF <30%: HR: 4.20 [95% CI: 2.01-8.75]; P < 0.001; vs LVEF 60%-70%, reference group).<br /><b>Conclusions</b><br />In BAV patients, the risk of adverse clinical outcomes increases significantly when the LVEF is <60%. These findings suggest that LVEF cutoff values proposed in the guidelines to indicate intervention should be raised from 50% to 60% in AS or AR and 55% in MAVD.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 13 Sep 2022; 80:1071-1084</small></div>

<div><h4>Sex Differences in Epidemiology, Care, and Outcomes in Patients With Acute Chest Pain.</h4><i>Dawson LP, Nehme E, Nehme Z, Davis E, ... Smith K, Stub D</i><br /><b>Background</b><br />Discrepancies in cardiovascular care for women are well described, but few data assess the entire patient journey for chest pain care.<br /><b>Objectives</b><br />This study aimed to assess sex differences in epidemiology and care pathways from emergency medical services (EMS) contact through to clinical outcomes following discharge.<br /><b>Methods</b><br />This is a state-wide population-based cohort study including consecutive adult patients attended by EMS for acute undifferentiated chest pain in Victoria, Australia (January 1, 2015, to June 30, 2019). EMS clinical data were individually linked to emergency and hospital administrative datasets, and mortality data and differences in care quality and outcomes were assessed using multivariable analyses.<br /><b>Results</b><br />In 256,901 EMS attendances for chest pain, 129,096 attendances (50.3%) were women, and mean age was 61.6 years. Age-standardized incidence rates were marginally higher for women compared with men (1,191 vs 1,135 per 100,000 person-years). In multivariable models, women were less likely to receive guideline-directed care across most care measures including transport to hospital, prehospital aspirin or analgesia administration, 12-lead electrocardiogram, intravenous cannula insertion, and off-load from EMS or review by emergency department clinicians within target times. Similarly, women with acute coronary syndrome were less likely to undergo angiography or be admitted to a cardiac or intensive care unit. Thirty-day and long-term mortality was higher for women diagnosed with ST-segment elevation myocardial infarction, but lower overall.<br /><b>Conclusions</b><br />Substantial differences in care are present across the spectrum of acute chest pain management from first contact through to hospital discharge. Women have higher mortality for STEMI, but better outcomes for other etiologies of chest pain compared with men.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 14 Mar 2023; 81:933-945</small></div>

<div><h4>Outcomes of Repair of Congenital Aortic Valve Lesions Using Autologous Pericardium vs Porcine Intestinal Submucosa.</h4><i>Sengupta A, Beroukhim R, Baird CW, Del Nido PJ, ... Sanders SP, Nathan M</i><br /><b>Background</b><br />Outcomes following congenital aortic valve (AoV) repair are plagued by progressive dysfunction of currently available leaflet substitute materials.<br /><b>Objectives</b><br />We compared the long-term outcomes of congenital AoV repair using porcine intestinal submucosa vs autologous pericardium (AP).<br /><b>Methods</b><br />This was a single-center retrospective review of all patients who underwent congenital AoV repair with either porcine intestinal submucosa or AP from October 2009 to March 2013. The primary outcome was postdischarge (late) unplanned AoV reintervention. Secondary outcomes included number of late AoV reinterventions and a composite of at least moderate aortic regurgitation or stenosis at latest follow-up or before the first reintervention. Associations between leaflet repair material and outcomes were assessed using multivariable regression models, adjusting for prespecified patient-related and operative variables.<br /><b>Results</b><br />Of 26 porcine intestinal submucosa and 49 AP patients who met entry criteria, the median age was 11.0 years (IQR: 4.7-16.6 years). At a median follow-up of 8.5 years (IQR: 4.4-9.6 years), 17 (65.4%) porcine intestinal submucosa and 22 (44.9%) AP patients underwent at least 1 AoV reintervention. On multivariable analysis, porcine intestinal submucosa use was significantly associated with unplanned AoV reintervention (HR: 4.6; 95% CI: 2.2-9.8; P < 0.001), number of postdischarge AoV reinterventions (incidence rate ratio: 1.7; 95% CI: 1.0-2.9; P = 0.037), and at least moderate aortic regurgitation or stenosis at latest follow-up or before the first reintervention (OR: 5.0; 95% CI: 1.2-21.0; P = 0.027).<br /><b>Conclusions</b><br />Aortic valvuloplasty with porcine intestinal submucosa is associated with earlier time to reintervention compared with autologous pericardium. The search for the ideal AoV leaflet repair material continues.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 13 Sep 2022; 80:1060-1068</small></div>

<div><h4>Biomarker Prediction of Complex Coronary Revascularization Procedures in the FOURIER Trial.</h4><i>Fagundes A, Morrow DA, Oyama K, Furtado RHM, ... Sabatine MS, Bergmark BA</i><br /><b>Background</b><br />Biomarkers are known to predict major adverse cardiovascular events. However, the association of biomarkers with complex coronary revascularization procedures or high-risk coronary anatomy at the time of revascularization is not understood.<br /><b>Objectives</b><br />We examined the associations between baseline biomarkers and major coronary events (MCE) and complex revascularization procedures.<br /><b>Methods</b><br />FOURIER was a randomized trial of the proprotein convertase subtilisin-kexin type 9 inhibitor evolocumab vs placebo in 27,564 patients with stable atherosclerosis. We analyzed adjusted associations among the biomarkers, MCE (coronary death, myocardial infarction, or revascularization), and complex revascularization (coronary artery bypass graft or complex percutaneous coronary intervention) using a multimarker score with 1 point assigned for each elevated biomarker (high-sensitivity C-reactive protein ≥2 mg/L; N-terminal pro-B-type natriuretic peptide ≥450 pg/mL; high-sensitivity troponin I ≥6 ng/L; growth-differentiation factor-15 ≥1,800 pg/mL).<br /><b>Results</b><br />When patients were grouped by the number of elevated biomarkers (0 biomarkers, n = 6,444; 1-2 biomarkers, n = 12,439; ≥3 biomarkers, n = 2,761), there was a significant graded association between biomarker score and the risk of MCE (intermediate score: HR<sub>adj</sub>: 1.57 [95% CI: 1.38-1.78]; high score: HR<sub>adj</sub>: 2.90 [95% CI: 2.47-3.40]), and for complex revascularization (intermediate: HR<sub>adj</sub>: 1.33 [95% CI: 1.06-1.67]; high score: HR<sub>adj</sub>: 2.07 [95% CI: 1.52-2.83]) and its components (P<sub>trend</sub> <0.05 for each). The number of elevated biomarkers also correlated with the presence of left main disease, multivessel disease, or chronic total occlusion at the time of revascularization (P < 0.05 for each).<br /><b>Conclusions</b><br />A biomarker-based strategy identifies stable patients at risk for coronary events, including coronary artery bypass graft surgery and complex percutaneous coronary intervention, and predicts high-risk coronary anatomy at the time of revascularization. These findings provide insight into the relationships between cardiovascular biomarkers, coronary anatomical complexity, and incident clinical events. (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk [FOURIER]; NCT01764633).<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 30 Aug 2022; 80:887-897</small></div>

<div><h4>Randomized Trials of Percutaneous Microaxial Flow Pump Devices: JACC State-of-the-Art Review.</h4><i>Pahuja M, Johnson A, Kabir R, Bhogal S, ... Sheikh FH, Waksman R</i><br /><AbstractText>The use of mechanical circulatory support devices in cardiovascular practice has risen exponentially over the past decade. These devices are currently used for hemodynamic support in patients with cardiogenic shock, high-risk percutaneous coronary intervention, left ventricular unloading, protection of kidneys, and right ventricular failure. The Impella (Abiomed) percutaneous microaxial flow pump devices are rapidly gaining popularity. However, despite their increasing use, there are limited randomized clinical trials (RCTs) to support the benefits of the therapy and growing concern regarding complication rates. Vascular problems, including bleeding and acute limb ischemia, are associated with the devices, but published reports also highlight risks for cardiac perforations, mitral chordae rupture, and stroke. In this review, we summarize the history, mechanism of action, previously published RCT data, and upcoming RCTs on these devices.</AbstractText><br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 22 Nov 2022; 80:2028-2049</small></div>

<div><h4>Abbreviated Antiplatelet Therapy After Coronary Stenting in Patients With Myocardial Infarction at High Bleeding Risk.</h4><i>Smits PC, Frigoli E, Vranckx P, Ozaki Y, ... Valgimigli M, MASTER DAPT Investigators</i><br /><b>Background</b><br />The optimal duration of antiplatelet therapy (APT) after coronary stenting in patients at high bleeding risk (HBR) presenting with an acute coronary syndrome remains unclear.<br /><b>Objectives</b><br />The objective of this study was to investigate the safety and efficacy of an abbreviated APT regimen after coronary stenting in an HBR population presenting with acute or recent myocardial infarction.<br /><b>Methods</b><br />In the MASTER DAPT trial, 4,579 patients at HBR were randomized after 1 month of dual APT (DAPT) to abbreviated (DAPT stopped and 11 months single APT or 5 months in patients with oral anticoagulants) or nonabbreviated APT (DAPT for minimum 3 months) strategies. Randomization was stratified by acute or recent myocardial infarction at index procedure. Coprimary outcomes at 335 days after randomization were net adverse clinical outcomes events (NACE); major adverse cardiac and cerebral events (MACCE); and type 2, 3, or 5 Bleeding Academic Research Consortium bleeding.<br /><b>Results</b><br />NACE and MACCE did not differ with abbreviated vs nonabbreviated APT regimens in patients with an acute or recent myocardial infarction (n = 1,780; HR: 0.83; 95% CI: 0.61-1.12 and HR: 0.86; 95% CI: 0.62-1.19, respectively) or without an acute or recent myocardial infarction (n = 2,799; HR: 1.03; 95% CI: 0.77-1.38 and HR: 1.13; 95% CI: 0.80-1.59; P<sub>interaction</sub> = 0.31 and 0.25, respectively). Bleeding Academic Research Consortium 2, 3, or 5 bleeding was significantly reduced in patients with or without an acute or recent myocardial infarction (HR: 0.65; 95% CI: 0.46-0.91 and HR: 0.71; 95% CI: 0.54-0.92; P<sub>interaction</sub> = 0.72) with abbreviated APT.<br /><b>Conclusions</b><br />A 1-month DAPT strategy in patients with HBR presenting with an acute or recent myocardial infarction results in similar NACE and MACCE rates and reduces bleedings compared with a nonabbreviated DAPT strategy. (Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With an Abbreviated Versus Prolonged DAPT Regimen [MASTER DAPT]; NCT03023020).<br /><br />Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 27 Sep 2022; 80:1220-1237</small></div>

<div><h4>Heart Failure Following Anti-Inflammatory Medications in Patients With Type 2 Diabetes Mellitus.</h4><i>Holt A, Strange JE, Nouhravesh N, Nielsen SK, ... Schou M, Lamberts M</i><br /><b>Background</b><br />Fluid retention and endothelial dysfunction have been related to use of nonsteroidal anti-inflammatory drugs (NSAIDs), and type 2 diabetes mellitus (T2DM) has been linked to both a decline in kidney function and subclinical cardiomyopathy.<br /><b>Objectives</b><br />The authors hypothesized that short-term use of NSAIDs could lead to subsequent development of incident heart failure (HF) in patients with T2DM.<br /><b>Methods</b><br />Using nationwide Danish registers, we identified patients diagnosed with T2DM during 1998 to 2021 and included patients without previous HF, rheumatic disease, or use of NSAIDs 120 days before diagnosis. Associations between NSAIDs and first-time HF hospitalization were investigated using a case-crossover design with 28-day exposure windows, and ORs with 95% CIs were reported.<br /><b>Results</b><br />Included were 331,189 patients with T2DM: 44.2% female, median age of 62 years (IQR: 52-71 years); 23,308 patients were hospitalized with HF during follow-up, and 16% of patients claimed at least 1 NSAID prescription within 1 year. Short-term use of NSAIDs was associated with increased risk of HF hospitalization (OR: 1.43; 95% CI: 1.27-1.63), most notably in subgroups with age ≥80 years (OR: 1.78; 95% CI: 1.39-2.28), elevated hemoglobin (Hb) A1c levels treated with 0 to 1 antidiabetic drug (OR: 1.68; 95% CI: 1.00-2.88), and without previous use of NSAIDs (OR: 2.71; 95% CI: 1.78-4.23).<br /><b>Conclusions</b><br />NSAIDs were widely used and were associated with an increased risk of first-time HF hospitalization in patients with T2DM. Patients with advanced age, elevated HbA1c levels, and new users of NSAID seemed more susceptible. These findings could guide physicians prescribing NSAIDs.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 18 Apr 2023; 81:1459-1470</small></div>

<div><h4>The Association of Socioeconomic Status With Hypertension in 76 Low- and Middle-Income Countries.</h4><i>Kirschbaum TK, Sudharsanan N, Manne-Goehler J, De Neve JW, ... Jaacks LM, Geldsetzer P</i><br /><b>Background</b><br />Effective equity-focused health policy for hypertension in low- and middle-income countries (LMICs) requires an understanding of the condition\'s current socioeconomic gradients and how these are likely to change in the future as countries develop economically.<br /><b>Objectives</b><br />This cross-sectional study aimed to determine how hypertension prevalence in LMICs varies by individuals\' education and household wealth, and how these socioeconomic gradients in hypertension prevalence are associated with a country\'s gross domestic product (GDP) per capita.<br /><b>Methods</b><br />We pooled nationally representative household survey data from 76 LMICs. We disaggregated hypertension prevalence by education and household wealth quintile, and used regression analyses to adjust for age and sex.<br /><b>Results</b><br />We included 1,211,386 participants in the analysis. Pooling across all countries, hypertension prevalence tended to be similar between education groups and household wealth quintiles. The only world region with a clear positive association of hypertension with education or household wealth quintile was Southeast Asia. Countries with a lower GDP per capita had, on average, a more positive association of hypertension with education and household wealth quintile than countries with a higher GDP per capita, especially in rural areas and among men.<br /><b>Conclusions</b><br />Differences in hypertension prevalence between socioeconomic groups were generally small, with even the least educated and least wealthy groups having a substantial hypertension prevalence. Our cross-sectional interaction analyses of GDP per capita with the socioeconomic gradients of hypertension suggest that hypertension may increasingly affect adults in the lowest socioeconomic groups as LMICs develop economically.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 23 Aug 2022; 80:804-817</small></div>

<div><h4>Thoracoabdominal Aortic Disease and Repair: JACC Focus Seminar, Part 3.</h4><i>Ouzounian M, Tadros RO, Svensson LG, Lyden SP, Oderich GS, Coselli JS</i><br /><AbstractText>Thoracoabdominal aortic disease is a rare but life-threatening condition that requires expert multidisciplinary collaborative management. Intervention is indicated in patients with symptomatic aneurysms or when an aneurysm reaches a certain threshold of diameter or rate of expansion. The strategies for spinal cord and end-organ protection have evolved over several decades, resulting in improved outcomes after repair. Open repair, although invasive, provides definitive and durable repair. Endovascular approaches are rapidly evolving, and the results with fenestrated and branched endografts are promising. Both open repair and endovascular repair require highly specialized expertise, and outcomes are best when repair is undertaken in an elective setting by a dedicated team. Patients with degenerative thoracoabdominal aortic aneurysms and chronic dissections should be followed up closely and referred for elective repair when indicated.</AbstractText><br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 23 Aug 2022; 80:845-856</small></div>

<div><h4>Comparative Risks of Initial Aortic Events Associated With Genetic Thoracic Aortic Disease.</h4><i>Regalado ES, Morris SA, Braverman AC, Hostetler EM, ... Jondeau G, Milewicz DM</i><br /><b>Background</b><br />Pathogenic variants in 11 genes predispose individuals to heritable thoracic aortic disease (HTAD), but limited data are available to stratify the risk for aortic events associated with these genes.<br /><b>Objectives</b><br />This study sought to compare the risk of first aortic event, specifically thoracic aortic aneurysm surgery or an aortic dissection, among 7 HTAD genes and variant types within each gene.<br /><b>Methods</b><br />A retrospective cohort of probands and relatives with rare variants in 7 genes for HTAD (n = 1,028) was assessed for the risk of first aortic events based on the gene altered, pathogenic variant type, sex, proband status, and location of recruitment.<br /><b>Results</b><br />Significant differences in aortic event risk were identified among the smooth muscle contraction genes (ACTA2, MYLK, and PRKG1; P = 0.002) and among the genes for Loeys-Dietz syndrome, which encode proteins in the transforming growth factor (TGF)-β pathway (SMAD3, TGFB2, TGFBR1, and TGFBR2;P < 0.0001). Cumulative incidence of type A aortic dissection was higher than elective aneurysm surgery in patients with variants in ACTA2, MYLK, PRKG1, and SMAD3; in contrast, patients with TGFBR2 variants had lower cumulative incidence of type A aortic dissection than elective aneurysm surgery. Cumulative incidence of type B aortic dissection was higher for ACTA2, PRKG1, and TGFBR2 than other genes. After adjusting for proband status, sex, and recruitment location, specific variants in ACTA2 and TGFBR2 were associated with substantially higher risk of aortic event with childhood onset.<br /><b>Conclusions</b><br />Gene- and variant-specific data on aortic events in individuals with HTAD support personalized aortic surveillance and clinical management.<br /><br />Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 30 Aug 2022; 80:857-869</small></div>