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A global multidisciplinary workshop was convened to discuss the multimodality diagnostic evaluation of aortic regurgitation (AR). Specifically, the focus was on assessment tools for AR severity and analyzing evolving data on the optimal timing of aortic valve intervention. The key concepts from this expert panel are summarized as: 1) echocardiography is the primary imaging modality for assessment of AR severity; however, when data is incongruent or incomplete, cardiac magnetic resonance may be helpful; 2) assessment of left ventricular size and function is crucial in determining the timing of intervention; 3) recent evidence suggests current cutpoints for intervention in asymptomatic severe AR patients requires further scrutiny; 4) left ventricular end-systolic volume index has emerged as an additional parameter that has promise in guiding timing of intervention; and 5) the role of additional factors (including global longitudinal strain, regurgitant fraction, and myocardial extracellular volume) is worthy of future investigation., Competing Interests: Funding Support and Author Disclosures Dr Ranard has received institutional funding to Columbia University from Boston Scientific. Dr Bax has received speaker bureau fees from Abbott and Edwards Lifesciences. Dr Delgado has received speaker fees from Abbott Vascular, Edwards Lifesciences, GE Healthcare, Medtronic, Novartis, and Philips; and has received consulting fees from Edwards Lifesciences and Novo Nordisk. Dr Leipsic has received institutional CT core lab contracts with Edwards Lifesciences, Abbott, Boston Scientific, Medtronic, and PI Cardia. Dr Lang is on the Speakers Bureau and has received grants from Philips Medical Systems. Dr Vahl has received institutional funding to Columbia University Irving Medical Center from Boston Scientific, Edwards Lifesciences, JenaValve, Medtronic, and Siemens Healthineers; and has personally received consulting fees from 4C Medical, Abbott Vascular, and Boston Scientific. Dr Leon has received institutional clinical research grants from Abbott, Boston Scientific, Edwards Lifesciences, Medtronic, and JenaValve. Dr Rigolin has stock ownership in Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Quantitative cardiac magnetic resonance (CMR) outcome studies in aortic regurgitation (AR) are few. It is unclear if volume measurements are beneficial over diameters., Objectives: This study sought to evaluate the association of CMR quantitative thresholds and outcomes in AR patients., Methods: In a multicenter study, asymptomatic patients with moderate or severe AR on CMR with preserved left ventricular ejection fraction (LVEF) were evaluated. Primary outcome was development of symptoms or decrease in LVEF to <50%, development of guideline indications for surgery based on LV dimensions, or death under medical management. Secondary outcome was the same as the primary outcome, excluding surgery for remodeling indications. We excluded patients who underwent surgery within 30 days of CMR. Receiver-operating characteristic analyses for the association with outcomes were performed., Results: We studied 458 patients (median age: 60 years; IQR: 46-70 years). During a median follow-up of 2.4 years (IQR: 0.9-5.3 years), 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 2 , indexed LV end-diastolic volume of 109 mL/m 2 , and iLVES diameter of 2 cm/m 2 . In multivariable regression analysis, iLVES volume of ≥43 mL/m 2 (HR: 2.53; 95% CI: 1.75-3.66; P < 0.001) and indexed LV end-diastolic volume of ≥109 mL/m 2 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., Conclusions: In asymptomatic AR patients with preserved LVEF, CMR findings can be used to guide management. CMR-based LVES volume assessment performed favorably compared to LV diameters., Competing Interests: Funding Support and Author Disclosures This research was conducted using the SCMR Registry Resource. Dr Malahfji has received research support from the Houston Methodist Research Institute and Guerbet LLC. Dr Reardon is a consultant to Medtronic, Boston Scientific, Abbott Medical, and Gore Medical. Dr Shah has received support from the National Science Foundation (CNS-1931884) and the Beverly B. and Daniel C. Arnold Distinguished Centennial Chair Endowment. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The treatment of left main (LM) coronary artery disease (CAD) requires complex decision-making. Recent clinical practice guidelines provide clinicians with guidance; however, decisions regarding treatment for individual patients can still be difficult. The American College of Cardiology's Cardiac Surgery Team and Interventional Council joined together to develop a practical approach to the treatment of LM CAD, taking into account randomized clinical trial, meta-analyses, and clinical practice guidelines. The various presentations of LM CAD based on anatomy and physiology are presented. Recognizing the complexity of LM CAD, which rarely presents isolated and is often in combination with multivessel disease, a treatment algorithm with medical therapy alone or in conjunction with percutaneous coronary intervention or coronary artery bypass grafting is proposed. A heart team approach is recommended that accounts for clinical, procedural, operator, and institutional factors, and features shared decision-making that meets the needs and preferences of each patient and their specific clinical situation., Competing Interests: Funding Support and Author Disclosures Dr Davidson is a co-investigator for Edwards Lifesciences and Abbott clinical trials. Dr Cleveland has received research grants from Medtronic and Abbott; has served on research committees for Abbott; has been a consultant for and received honoraria from ConneX Biomedical and Medtronic; and has received honoraria from Edwards Lifesciences. Dr Welt has been a consultant for and received honoraria from Medtronic; and holds stock in Xenter, Inc. Dr Anwaruddin has been a consultant and proctor for Edwards Lifesciences and Medtronic; has served on a steering committee for Boston Scientific; and holds equity in East End Medical. Dr Grubb has been a speaker for Edwards Lifesciences, Boston Scientific, and Medtronic; has been a proctor for Edwards Lifesciences and Medtronic; has served on advisory boards for Medtronic and Abbott; has been a principal investigator for trials sponsored by Edwards Lifesciences and Medtronic; and has been a consultant for Gore. Dr Kirtane has been a consultant for IMDS; has received travel expenses/meals from Medtronic, Boston Scientific, Abbott Vascular, CSI, Siemens, Philips, ReCor Medical, Chiesi, OpSens, Zoll, and Regeneron; and has received research grants from, been a consultant for, an/or received speaker fees from Medtronic, Boston Scientific, Abbott Vascular, Amgen, CSI, Philips, ReCor Medical, Neurotronic, Biotronik, Chiesi, Bolt Medical, Magenta Medical, Canon, and SoniVie, paid to his institution. Dr Truesdell has received consultant and speaker fees, paid to his institution, from Abiomed Inc. Dr Windecker has received research and educational grants paid to employer from Abbott, Abiomed, Amgen, AstraZeneca, Bayer, Biotronik, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardinal Health, CardioValve, Corflow Therapeutics, CSL Behring, Daiichi-Sankyo, Edwards Lifesciences, Guerbet, InfraRedx, Janssen-Cilag, Johnson & Johnson, Medicure, Medtronic, Merck Sharp & Dohm, Miracor Medical, Novartis, Novo Nordisk, Organon, OrPha Suisse, Pfizer, Polares, Regeneron, Sanofi, Servier, Sinomed, Terumo, Vifor, V-Wave; has served as advisory board member and/or member of the steering/executive group of trials funded by Abbott, Abiomed, Amgen, AstraZeneca, Bayer, Boston Scientific, Biotronik, Bristol Myers Squibb, Edwards Lifesciences, Janssen, MedAlliance, Medtronic, Novartis, Polares, Recardio, Sinomed, Terumo, V-Wave, and Xeltis with payments to employer but no personal payments; and has been a member of the steering/executive committee group of several investigator-initiated trials that receive funding by industry without impact on his personal remuneration. Dr Malaisrie has been a consultant for and received research funding from Edwards Lifesciences, Medtronic, Terumo Aortic, and Artivion. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022. Published by Elsevier Inc.)

Ischemic cardiomyopathy results from the combination of scar with fibrosis replacement and areas of dysfunctional but viable myocardium that may improve contractile function with revascularization. Observational studies reported that only patients with substantial amounts of myocardial viability had better outcomes following surgical revascularization. Accordingly, dedicated noninvasive techniques have evolved to quantify viable myocardium with the objective of selecting patients for this form of therapeutic intervention. However, prospective trials have not confirmed the interaction between myocardial viability and the treatment effect of revascularization. Furthermore, recent observations indicate that recovery of left ventricular function is not the principal mechanism by which surgical revascularization improves prognosis. In this paper, the authors describe a more contemporary application of viability testing that is founded on the alternative concept that the main goal of surgical revascularization is to prevent further damage by protecting the residual viable myocardium from subsequent acute coronary events., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Coronary artery disease (CAD) is treated with medical therapy with or without percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). The latter 2 options are commonly referred to as "myocardial revascularization" procedures. We reason that this term is inappropriate because it is suggestive of a single treatment effect of PCI and CABG (ie, the reestablishment of blood flow to ischemic myocardium) and obscures key mechanisms, such as the improvement in coronary flow capability in the absence of ongoing ischemia, the reperfusion in the presence of ischemia, and the prevention of myocardial infarction from CAD progression. We review the current evidence on the topic and suggest the use of a purely descriptive terminology ("invasive treatment by PCI or CABG") which has the potential to improve clinical decision making and guide future trial design., Competing Interests: Funding Support and Author Disclosures Dr. Bhatt has served on the Advisory Board for Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, Level Ex, Medscape Cardiology, MyoKardia, PhaseBio, PLx Pharma, and Regado Biosciences; has served on the Board of Directors for Boston VA Research Institute, Society of Cardiovascular Patient Care, TobeSoft; has served as Chair for the American Heart Association Quality Oversight Committee; has served on the Data Monitoring Committees for the Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Contego Medical (Chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi- Sankyo), Population Health Research Institute; has received honoraria from the American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Vice-Chair, ACC Accreditation Committee), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor-in-Chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor-in-Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), K2P (Co-Chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), WebMD (CME steering committees); Other: Clinical Cardiology (Deputy Editor), NCDR-ACTION Registry Steering Committee (Chair), VA CART Research and Publications Committee (Chair); Research Funding: Abbott, Afimmune, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardax, Chiesi, CSL Behring, Eisai, Ethicon, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Lexicon, Lilly, Medtronic, MyoKardia, Owkin, Pfizer, PhaseBio, PLx Pharma, Regeneron, Roche, Sanofi, Synaptic, The Medicines Company; has received royalties from Elsevier (Editor, Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease); has been a site co-investigator for Biotronik, Boston Scientific, CSI, St Jude Medical (now Abbott), and Svelte; has been a trustee for theAmerican College of Cardiology; has performed unfunded researchfor FlowCo, Merck, Novo Nordisk, andTakeda. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aim: This executive summary of the valvular heart disease guideline provides recommendations for clinicians to diagnose and manage valvular heart disease as well as supporting documentation to encourage their use., Methods: A comprehensive literature search was conducted from January 1, 2010, to March 1, 2020, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, Cochrane, Agency for Healthcare Research and Quality Reports, and other selected database relevant to this guideline., Structure: Many recommendations from the earlier valvular heart disease guidelines have been updated with new evidence and provides newer options for diagnosis and treatment of valvular heart disease. This summary includes only the recommendations from the full guideline which focus on diagnostic work-up, the timing and choice of surgical and catheter interventions, and recommendations for medical therapy. The reader is referred to the full guideline for graphical flow charts, text, and tables with additional details about the rationale for and implementation of each recommendation, and the evidence tables detailing the data considered in developing these guidelines., (Copyright © 2021 American College of Cardiology Foundation and the American Heart Association, Inc. Published by Elsevier Inc. All rights reserved.)

Mitral regurgitation (MR) is a complex valve lesion that can pose significant management challenges. This expert consensus decision pathway emphasizes that recognition of MR should prompt an assessment of its etiology, mechanism, and severity, as well as consideration of the indications for treatment. The document is a focused update of the 2017 ACC Expert Consensus Decision Pathway on the Management of Mitral Regurgitation, with some sections updated and others added in light of the publication of new trial data related to secondary MR, among other developments. A structured approach to evaluation based on clinical findings, accurate echocardiographic imaging, and, when necessary, adjunctive testing can help clarify decision making. Treatment goals include timely intervention by an experienced multidisciplinary heart team to prevent left ventricular dysfunction, heart failure, reduced quality of life, and premature death., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) are considered revascularization procedures, but only CABG can prolong life in stable coronary artery disease. Thus, PCI and CABG mechanisms may differ. Viability and/or ischemia detection to guide revascularization have been unable to accurately predict treatment effects of CABG or PCI, questioning a revascularization mechanism for improving survival. By contrast, preventing myocardial infarction may save lives. However, the majority of infarcts are generated by non-flow-limiting stenoses, but PCI is solely focused on treating flow-limiting lesions. Thus, PCI cannot be expected to significantly limit new infarcts, but CABG may do so through providing flow distal to vessel occlusions. All comparisons of CABG to PCI or medical therapy that demonstrate survival effects with CABG also demonstrate infarct reduction. Thus, CABG may differ from PCI by providing "surgical collateralization," prolonging life by preventing myocardial infarctions. The evidence is reviewed here., (Copyright © 2019 American College of Cardiology Foundation. All rights reserved.)

The ideal aortic valve substitute for young and middle-aged adults remains elusive. The Ross procedure (pulmonary autograft replacement) is the only operation that allows replacement of the diseased aortic valve with a living substitute. However, use of this procedure has declined significantly due to concerns over increased surgical risk and potential long-term failure of the operation. Several recent publications from expert centers have shown that in the current era, the Ross procedure can be performed safely and reproducibly in appropriately selected patients. Furthermore, an increasing body of evidence suggests that the Ross procedure is associated with better long-term outcomes compared with conventional aortic valve replacement in young and middle-aged adults. In this paper, the authors review the indications and technical considerations of the Ross procedure, describe its advantages and drawbacks, and discuss patient selection criteria. Finally, the authors provide a comprehensive synthesis of the current Ross published reports to enable cardiologists and surgeons to make appropriate decisions for their patients with aortic valve disease., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Recent studies reported left ventricular (LV) fibrosis in patients with primary mitral regurgitation (MR) thought to be principally due to mitral valve prolapse (MVP)., Objectives: This study sought to evaluate the prevalence, characteristics, and prognostic implications of LV fibrosis in a large cohort of primary MR patients with and without MVP using cardiovascular magnetic resonance (CMR)., Methods: Patients referred for contrast CMR assessment of chronic primary MR were enrolled and underwent comprehensive assessment of cardiac remodeling, severity of MR, and LV replacement fibrosis. Primary MR patients were stratified into: an MVP group if there was >2 mm mitral leaflet displacement on cine-CMR, or a non-MVP group. Patients were followed for arrhythmic events (sudden cardiac death, aborted sudden cardiac arrest, and sustained or inducible ventricular arrhythmia)., Results: A total of 356 primary MR patients (177 MVP and 179 non-MVP) were enrolled. LV fibrosis was more prevalent in the MVP group than the non-MVP group (36.7% vs. 6.7%; p < 0.001). The presence of MVP had the strongest association (odds ratio: 6.82; p < 0.001) with LV fibrosis even after adjustment for clinical variables, measures of cardiac remodeling, and MR severity. During follow-up (median 1,354 days), MVP patients with LV fibrosis had the highest event rate for arrhythmic events., Conclusions: In primary MR patients, LV fibrosis is more prevalent in MVP than non-MVP, suggesting a unique pathophysiology beyond volume overload in MVP. LV fibrosis in primary MR may represent a risk marker of arrhythmic events., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Aortic stenosis (AS) is one of the most common valvular diseases encountered in clinical practice. Current guidelines recommend aortic valve replacement (AVR) when the aortic valve is severely stenotic and the patient is symptomatic; however, a substantial proportion of patients with severe AS are asymptomatic at the time of first diagnosis. Although specific morphological valve features, exercise testing, stress imaging, and biomarkers can help to identify patients with asymptomatic severe AS who may benefit from early AVR, the optimal management of these patients remains uncertain and controversial. The current report presents a comprehensive review of the natural history and the diagnostic evaluation of asymptomatic patients with severe AS, and is followed by a meta-analysis from reported studies comparing an early AVR strategy to active surveillance, with an emphasis on the level of evidence substantiating the current guideline recommendations. Finally, perspectives on directions for future investigation are discussed., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Treatment of acute myocardial infarction (AMI) has improved significantly in recent years, but many patients have adverse left ventricular (LV) remodeling, a maladaptive change associated with progressive heart failure. Although this change is usually associated with large infarcts, some patients with relatively small infarcts have adverse remodeling, whereas other patients with larger infarcts (who survive the first several days after AMI) do not. This paper reviews the relevant data supporting the hypothesis that individual differences in the intensity of the post-AMI inflammatory response, involving 1 or more inflammatory-modulating pathways, may contribute to adverse LV remodeling. It concludes by outlining how individual variations in the inflammatory response could provide important novel therapeutic targets and strategies., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Two guidelines from the American College of Cardiology (ACC), the American Heart Association (AHA), and collaborating societies address the risk of aortic dissection in patients with bicuspid aortic valves and severe aortic enlargement: the "2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM Guidelines for the Diagnosis and Management of Patients With Thoracic Aortic Disease" (J Am Coll Cardiol 2010;55:e27-130) and the "2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease" (J Am Coll Cardiol 2014;63:e57-185). However, the 2 guidelines differ with regard to the recommended threshold of aortic root or ascending aortic dilatation that would justify surgical intervention in patients with bicuspid aortic valves. The ACC and AHA therefore convened a subcommittee representing members of the 2 guideline writing committees to review the evidence, reach consensus, and draft a statement of clarification for both guidelines. This statement of clarification uses the ACC/AHA revised structure for delineating the Class of Recommendation and Level of Evidence to provide recommendations that replace those contained in Section 9.2.2.1 of the thoracic aortic disease guideline and Section 5.1.3 of the valvular heart disease guideline., (Copyright © 2016 American College of Cardiology Foundation and American Heart Association, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Patients with left ventricular (LV) systolic dysfunction, coronary artery disease (CAD), and angina are often thought to have a worse prognosis and a greater prognostic benefit from coronary artery bypass graft (CABG) surgery than those without angina., Objectives: This study investigated: 1) whether angina was associated with a worse prognosis; 2) whether angina identified patients who had a greater survival benefit from CABG; and 3) whether CABG improved angina in patients with LV systolic dysfunction and CAD., Methods: We performed an analysis of the STICH (Surgical Treatment for Ischemic Heart Failure) trial, in which 1,212 patients with an ejection fraction ≤35% and CAD were randomized to CABG or medical therapy. Multivariable Cox and logistic models were used to assess long-term clinical outcomes., Results: At baseline, 770 patients (64%) reported angina. Among patients assigned to medical therapy, all-cause mortality was similar in patients with and without angina (hazard ratio [HR]: 1.05; 95% confidence interval [CI]: 0.79 to 1.38). The effect of CABG was similar whether the patient had angina (HR: 0.89; 95% CI: 0.71 to 1.13) or not (HR: 0.68; 95% CI: 0.50 to 0.94; p interaction = 0.14). Patients assigned to CABG were more likely to report improvement in angina than those assigned to medical therapy alone (odds ratio: 0.70; 95% CI: 0.55 to 0.90; p < 0.01)., Conclusions: Angina does not predict all-cause mortality in medically treated patients with LV systolic dysfunction and CAD, nor does it identify patients who have a greater survival benefit from CABG. However, CABG does improve angina to a greater extent than medical therapy alone. (Comparison of Surgical and Medical Treatment for Congestive Heart Failure and Coronary Artery Disease [STICH]; NCT00023595)., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Over the past 1.5 decades, numerous stem cell trials have been performed in patients with cardiovascular disease. Although encouraging outcome signals have been reported, these have been small, leading to uncertainty as to whether they will translate into significantly improved outcomes. A reassessment of the rationale for the use of stem cells in cardiovascular disease is therefore timely. Such a rationale should include analyses of why previous trials have not produced significant benefit and address whether mechanisms contributing to disease progression might benefit from known activities of stem cells. The present paper provides such a reassessment, focusing on patients with left ventricular systolic dysfunction, either nonischemic or ischemic. We conclude that many mechanisms contributing to progressive left ventricular dysfunction are matched by stem cell activities that could attenuate the myocardial effect of such mechanisms. This suggests that stem cell strategies may improve patient outcomes and justifies further testing., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Beta-blocker therapy after acute myocardial infarction (MI) improves survival. Beta-blocker doses used in clinical practice are often substantially lower than those used in the randomized trials establishing their efficacy., Objectives: This study evaluated the association of beta-blocker dose with survival after acute MI, hypothesizing that higher dose beta-blocker therapy will be associated with increased survival., Methods: A multicenter registry enrolled 7,057 consecutive patients with acute MI. Discharge beta-blocker dose was indexed to the target beta-blocker doses used in randomized clinical trials, grouped as >0% to 12.5%, >12.5% to 25%, >25% to 50%, and >50% of target dose. Follow-up vital status was assessed, with the primary endpoint of time-to-death right-censored at 2 years. Multivariable and propensity score analyses were used to account for group differences., Results: Of 6,682 patients with follow-up (median 2.1 years), 91.5% were discharged on a beta-blocker (mean dose 38.1% of the target dose). Lower mortality was observed with all beta-blocker doses (p < 0.0002) versus no beta-blocker therapy. After multivariable adjustment, hazard ratios for 2-year mortality compared with the >50% dose were 0.862 (95% confidence interval [CI]: 0.677 to 1.098), 0.799 (95% CI: 0.635 to 1.005), and 0.963 (95% CI: 0.765 to 1.213) for the >0% to 12.5%, >12.5% to 25%, and >25% to 50% of target dose groups, respectively. Multivariable analysis with an extended set of covariates and propensity score analysis also demonstrated that higher doses were not associated with better outcome., Conclusions: These data do not demonstrate increased survival in patients treated with beta-blocker doses approximating those used in previous randomized clinical trials compared with lower doses. These findings provide the rationale to re-engage in research to establish appropriate beta-blocker dosing after MI to derive optimal benefit from this therapy. (The PACE-MI Registry Study-Outcomes of Beta-blocker Therapy After Myocardial Infarction [OBTAIN]: NCT00430612)., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Suspected genetic causes for extracellular matrix (ECM) dysregulation in the ascending aorta in patients with bicuspid aortic valves (BAV) have influenced strategies and thresholds for surgical resection of BAV aortopathy. Using 4-dimensional (4D) flow cardiac magnetic resonance imaging (CMR), we have documented increased regional wall shear stress (WSS) in the ascending aorta of BAV patients., Objectives: This study assessed the relationship between WSS and regional aortic tissue remodeling in BAV patients to determine the influence of regional WSS on the expression of ECM dysregulation., Methods: BAV patients (n = 20) undergoing ascending aortic resection underwent pre-operative 4D flow CMR to regionally map WSS. Paired aortic wall samples (i.e., within-patient samples obtained from regions of elevated and normal WSS) were collected and compared for medial elastin degeneration by histology and ECM regulation by protein expression., Results: Regions of increased WSS showed greater medial elastin degradation compared to adjacent areas with normal WSS: decreased total elastin (p = 0.01) with thinner fibers (p = 0.00007) that were farther apart (p = 0.001). Multiplex protein analyses of ECM regulatory molecules revealed an increase in transforming growth factor β-1 (p = 0.04), matrix metalloproteinase (MMP)-1 (p = 0.03), MMP-2 (p = 0.06), MMP-3 (p = 0.02), and tissue inhibitor of metalloproteinase-1 (p = 0.04) in elevated WSS regions, indicating ECM dysregulation in regions of high WSS., Conclusions: Regions of increased WSS correspond with ECM dysregulation and elastic fiber degeneration in the ascending aorta of BAV patients, implicating valve-related hemodynamics as a contributing factor in the development of aortopathy. Further study to validate the use of 4D flow CMR as a noninvasive biomarker of disease progression and its ability to individualize resection strategies is warranted., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The highest-risk patients with heart failure with reduced ejection fraction are those with ischemic cardiomyopathy and severe left ventricular systolic dysfunction (ejection fraction≤35%). The cornerstone of treatment is guideline-driven medical therapy for all patients and implantable device therapy for appropriately selected patients. Surgical revascularization offers the potential for improved survival and quality of life, particularly in patients with more extensive multivessel disease and the greatest degree of left ventricular systolic dysfunction and remodeling. These are also the patients at greatest short-term risk of mortality with coronary artery bypass graft surgery. The short-term risks of surgery need to be balanced against the potential for long-term benefit. This review discusses the evolving data on the role of surgical revascularization, surgical ventricular reconstruction, and mitral valve surgery in this high-risk patient population., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Most cardiomyopathies are familial diseases. Cascade family screening identifies asymptomatic patients and family members with early traits of disease. The inheritance is autosomal dominant in a majority of cases, and recessive, X-linked, or matrilinear in the remaining. For the last 50 years, cardiomyopathy classifications have been based on the morphofunctional phenotypes, allowing cardiologists to conveniently group them in broad descriptive categories. However, the phenotype may not always conform to the genetic characteristics, may not allow risk stratification, and may not provide pre-clinical diagnoses in the family members. Because genetic testing is now increasingly becoming a part of clinical work-up, and based on the genetic heterogeneity, numerous new names are being coined for the description of cardiomyopathies associated with mutations in different genes; a comprehensive nosology is needed that could inform the clinical phenotype and involvement of organs other than the heart, as well as the genotype and the mode of inheritance. The recently proposed MOGE(S) nosology system embodies all of these characteristics, and describes the morphofunctional phenotype (M), organ(s) involvement (O), genetic inheritance pattern (G), etiological annotation (E) including genetic defect or underlying disease/substrate, and the functional status (S) of the disease using both the American College of Cardiology/American Heart Association stage and New York Heart Association functional class. The proposed nomenclature is supported by a web-assisted application and assists in the description of cardiomyopathy in symptomatic or asymptomatic patients and family members in the context of genetic testing. It is expected that such a nomenclature would help group cardiomyopathies on their etiological basis, describe complex genetics, and create collaborative registries., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

New therapeutic targets, agents, and strategies are needed to prevent and treat heart failure (HF) after a decade of failed research efforts to improve long-term patient outcomes, especially in patients after hospitalization for HF. Conceptually, an accurate assessment of left ventricular structure is an essential step in the development of novel therapies because heterogeneous pathophysiologies underlie chronic HF and hospitalization for HF. Improved left ventricular characterization permits the identification and targeting of the intrinsic fundamental disease-modifying pathways that culminate in HF. Interstitial heart disease is one such pathway, characterized by extracellular matrix (ECM) expansion that is associated with mechanical, electrical, and vasomotor dysfunction and adverse outcomes. Previous landmark trials that appear to treat interstitial heart disease were effective in improving outcomes. Advances in cardiovascular magnetic resonance now enable clinicians and researchers to assess the interstitium and quantify ECM expansion using extracellular volume fraction measures and other derangements in cardiovascular structure. These capabilities may provide a mechanistic platform to advance understanding of the role of the ECM, foster the development of novel therapeutics, and target specific disease-modifying pathways intrinsic to the ventricle. Refocusing on the interstitium may potentially improve care through the identification and targeted treatment of key patient subgroups., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to report full 1-year results, detailed magnetic resonance imaging analysis, and determinants of efficacy in the prospective, randomized, controlled CADUCEUS (CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction) trial., Background: Cardiosphere-derived cells (CDCs) exerted regenerative effects at 6 months in the CADUCEUS trial. Complete results at the final 1-year endpoint are unknown., Methods: Autologous CDCs (12.5 to 25 × 10(6)) grown from endomyocardial biopsy specimens were infused via the intracoronary route in 17 patients with left ventricular dysfunction 1.5 to 3 months after myocardial infarction (MI) (plus 1 infused off-protocol 14 months post-MI). Eight patients were followed as routine-care control patients., Results: In 13.4 months of follow-up, safety endpoints were equivalent between groups. At 1 year, magnetic resonance imaging revealed that CDC-treated patients had smaller scar size compared with control patients. Scar mass decreased and viable mass increased in CDC-treated patients but not in control patients. The single patient infused 14 months post-MI responded similarly. CDC therapy led to improved regional function of infarcted segments compared with control patients. Scar shrinkage correlated with an increase in viability and with improvement in regional function. Scar reduction correlated with baseline scar size but not with a history of temporally remote MI or time from MI to infusion. The changes in left ventricular ejection fraction in CDC-treated subjects were consistent with the natural relationship between scar size and ejection fraction post-MI., Conclusions: Intracoronary administration of autologous CDCs did not raise significant safety concerns. Preliminary indications of bioactivity include decreased scar size, increased viable myocardium, and improved regional function of infarcted myocardium at 1 year post-treatment. These results, which are consistent with therapeutic regeneration, merit further investigation in future trials. (CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction [CADUCEUS]; NCT00893360)., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The study objectives were to test the hypotheses that ischemia during stress testing has prognostic value and identifies those patients with coronary artery disease (CAD) with left ventricular (LV) dysfunction who derive the greatest benefit from coronary artery bypass grafting (CABG) compared with medical therapy., Background: The clinical significance of stress-induced ischemia in patients with CAD and moderately to severely reduced LV ejection fraction (EF) is largely unknown., Methods: The STICH (Surgical Treatment for IsChemic Heart Failure) trial randomized patients with CAD and EF ≤35% to CABG or medical therapy. In the current study, we assessed the outcomes of those STICH patients who underwent a radionuclide (RN) stress test or a dobutamine stress echocardiogram (DSE). A test was considered positive for ischemia by RN testing if the summed difference score (difference in tracer activity between stress and rest) was ≥4 or if ≥2 of 16 segments were ischemic during DSE. Clinical endpoints were assessed by intention to treat during a median follow-up of 56 months., Results: Of the 399 study patients (51 women, mean EF 26 ± 8%), 197 were randomized to CABG and 202 were randomized to medical therapy. Myocardial ischemia was induced during stress testing in 256 patients (64% of the study population). Patients with and without ischemia were similar in age, multivessel CAD, previous myocardial infarction, LV EF, LV volumes, and treatment allocation (all p = NS). There was no difference between patients with and without ischemia in all-cause mortality (hazard ratio: 1.08; 95% confidence interval: 0.77 to 1.50; p = 0.66), cardiovascular mortality, or all-cause mortality plus cardiovascular hospitalization. There was no interaction between ischemia and treatment for any clinical endpoint., Conclusions: In CAD with severe LV dysfunction, inducible myocardial ischemia does not identify patients with worse prognosis or those with greater benefit from CABG over optimal medical therapy. (Comparison of Surgical and Medical Treatment for Congestive Heart Failure and Coronary Artery Disease [STICH]; NCT00023595)., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The timing of surgery in patients with mitral regurgitation (MR) and aortic regurgitation (AR) continues to elicit uncertainty and considerable controversy. Some patients will incur myocardial structural changes, pulmonary hypertension, or arrhythmias before they manifest symptoms, with the risk that these adverse endpoints will not be reversible after valve repair or replacement. Imaging to assess valve morphology, severity of regurgitation, and left ventricular (LV) volume and function is firmly established, and the guidelines of the American College of Cardiology/American Heart Association and the European Society of Cardiology support this approach. However, with improvement in surgical technique and outcomes, there is momentum toward earlier intervention before patients reach class I indications of symptoms or LV systolic dysfunction, particularly in patients with degenerative MR who are candidates for mitral repair. In expert centers, mitral valve repair is achieved at low risk and with excellent long-term durability of repair, returning patients to a lifespan equivalent to that of the normal population. In AR, decision making is more complex because patients almost invariably require valve replacement. Prospective clinical trials are needed to provide the evidence base for more objective decisions regarding timing of surgery. Biomarkers and new methods to assess interstitial fibrosis and regional myocardial function have also evolved for clinical investigation and hold the promise of enhanced determination of those in whom early surgical intervention is warranted., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

With a prevalence of 5.8 million in the United States alone, heart failure (HF) is associated with high morbidity, mortality, and healthcare expenditures. Close to 1 million hospitalizations for heart failure (HHF) occur annually, accounting for over 6.5 million hospital days and a substantial portion of the estimated $37.2 billion that is spent each year on HF in the United States. Although some progress has been made in reducing mortality in patients hospitalized with HF, rates of rehospitalization continue to rise, and approach 30% within 60 to 90 days of discharge. Approximately half of HHF patients have preserved or relatively preserved ejection fraction (EF). Their post-discharge event rate is similar to those with reduced EF. HF readmission is increasingly being used as a quality metric, a basis for hospital reimbursement, and an outcome measure in HF clinical trials. In order to effectively prevent HF readmissions and improve overall outcomes, it is important to have a complete and longitudinal characterization of HHF patients. This paper highlights management strategies that when properly implemented may help reduce HF rehospitalizations and include adopting a mechanistic approach to cardiac abnormalities, treating noncardiac comorbidities, increasing utilization of evidence-based therapies, and improving care transitions, monitoring, and disease management., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Approximately 800,000 times a year, an emergency physician admits a patient with symptomatic heart failure (HF). Yet only a minority of emergency department patients with HF are severely ill as a result of pulmonary edema, myocardial ischemia, or cardiogenic shock. The majority of patients are not in need of an acute intervention beyond decongestion, and few patients during hospitalization undergo invasive diagnostic testing or therapeutic procedures that require intense monitoring. Although hospitalization is clearly an inflection point, marking a threshold that independently predicts a worse outcome, the exact impact of hospitalization on post-discharge events has not been well elucidated. Thus, large subsets of patients with HF are hospitalized without a clear need for time-sensitive therapies or procedures. The authors estimate that up to 50% of emergency department patients with HF could be safely discharged after a brief period of observation, thus avoiding unnecessary admissions and minimizing readmissions. Observation unit management may be beneficial for low-risk and intermediate-risk patients with HF as continued treatment, and more precise risk stratification may ensue, avoiding inpatient admission. Whether observation unit management is comparable with or superior to the current approach must be determined in a randomized clinical trial. Critical end points include time to symptom resolution and discharge, post-discharge event rates, and a cost-effective analysis of each management strategy. It is the authors' strong assertion that now is the time for such a trial and that the results will be critically important if we are to effectively influence hospitalizations for HF in the near future., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

In the current pathophysiological model of chronic ischemic heart disease (IHD), myocardial ischemia and exertional angina are caused by obstructive atherosclerotic plaque, and the clinical management of IHD is centered on the identification and removal of the stenosis. Although this approach has been in place for years, several lines of evidence, including poor prognostic impact, suggest that this direct relationship may present an oversimplified view of IHD. Indeed, a large number of studies have found that IHD can occur in the presence or absence of obstructive coronary artery disease and that atherosclerosis is just 1 element in a complex multifactorial pathophysiological process that includes inflammation, microvascular coronary dysfunction, endothelial dysfunction, thrombosis, and angiogenesis. Furthermore, the high recurrence rates underscore the fact that removing stenosis in patients with stable IHD does not address the underlying pathological mechanisms that lead to the progression of nonculprit lesions. The model proposed herein shifts the focus away from obstructive epicardial coronary atherosclerosis and centers it on the microvasculature and myocardial cell where the ischemia is taking place. If the myocardial cell is placed at the center of the model, all the potential pathological inputs can be considered, and strategies that protect the cardiomyocytes from ischemic damage, regardless of the causative mechanism, can be developed., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The American College of Cardiology Foundation, in collaboration with the Society for Cardiovascular Angiography and Interventions and key specialty and subspecialty societies, conducted a review of common clinical scenarios where diagnostic catheterization is frequently considered. The indications (clinical scenarios) were derived from common applications or anticipated uses, as well as from current clinical practice guidelines and results of studies examining the implementation of noninvasive imaging appropriate use criteria. The 166 indications in this document were developed by a diverse writing group and scored by a separate independent technical panel on a scale of 1 to 9, to designate appropriate use (median 7 to 9), uncertain use (median 4 to 6), and inappropriate use (median 1 to 3). Diagnostic catheterization may include several different procedure components. The indications developed focused primarily on 2 aspects of diagnostic catheterization. Many indications focused on the performance of coronary angiography for the detection of coronary artery disease with other procedure components (e.g., hemodynamic measurements, ventriculography) at the discretion of the operator. The majority of the remaining indications focused on hemodynamic measurements to evaluate valvular heart disease, pulmonary hypertension, cardiomyopathy, and other conditions, with the use of coronary angiography at the discretion of the operator. Seventy-five indications were rated as appropriate, 49 were rated as uncertain, and 42 were rated as inappropriate. The appropriate use criteria for diagnostic catheterization have the potential to impact physician decision making, healthcare delivery, and reimbursement policy. Furthermore, recognition of uncertain clinical scenarios facilitates identification of areas that would benefit from future research.