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Contrast enhanced ultrasound (CEUS) offers a safe, reliable imaging option to establish a clinical diagnosis across a variety of multidisciplinary settings. This Expert Consensus Statement serves to outline expert opinion on what constitutes appropriate supervision and the essential components of safe CEUS practice. The purpose of this document is to empower institutions to allow sonographers, along with other trained medical professionals, to administer UCAs at the point of care, consistent with the updated scope of practice documentation and within the broad parameters of an individual's training and licensure, while subject to appropriate supervision and meeting or exceeding minimum safety standards. This guidance was developed by the International Contrast Ultrasound Society and endorsed by the following organizations that represent ultrasound professionals: the British Society of Echocardiography, the Canadian Society of Echocardiography, the Society of Diagnostic Medical Sonography, the Society for Pediatric Radiology, the World Federation of Ultrasound in Medicine and Biology, the Brazilian College of Radiology, the Joint Review Committee for Diagnostic Medical Sonography, the Chinese Ultrasound Doctors Association, and the American Society of Neuroimaging. Additionally, this guidance document was affirmed or supported by the American Society of Echocardiography, the Association for Medical Ultrasound, and the Society for Vascular Ultrasound., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Competing Interests: Conflicts of Interest None.

Purpose of Review: To provide a contemporary update on the American Society of Echocardiography's ImageGuideEcho Registry and present a case study of an individual institution's experience with enrollment., Recent Findings: Technical innovation in clinical echocardiography has expanded the impact of echocardiography in cardiovascular care and provides new opportunities to leverage clinical data to inform quality improvement initiatives and research. The ImageGuideEcho Registry is the first echocardiography-specific imaging registry in the United States and provides a data infrastructure for quality improvement and multicenter research. The ImageGuideEcho Registry continues to grow, offering a window into echocardiography care across the United States in a variety of practice settings. This early experience highlights its value, opportunities, and ongoing challenges. Continued innovation, such as the addition of primary images, will further add to the substantial value of the registry., Competing Interests: Declarations. Human and Animal Rights and Informed Consent: This article does not contain any studies with human or animal subjects performed by any of the authors. Competing Interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Abbreviation use in clinical and academic cardiology is widespread, yet there are few guidelines regulating the creation and utilization of abbreviations. Inconsistent abbreviations can introduce ambiguity and pose challenges to practice and research., Objectives: The authors aimed to analyze how abbreviations are created and utilized in general cardiology and cardiac imaging society guidelines in order to assess whether ambiguities and discrepancies exist between societies., Methods: Abbreviation data were collected from 7 national and international societies of general cardiology and cardiac imaging over a 6-year span (2018-2023). Data were linguistically coded for abbreviation type, unique occurrence, meaning or sense count, and frequency of discrepancy between societies., Results: Among a total of 5,394 abbreviation tokens, there were 1,782 unique entries. Among the unique entries, 227 (12.7%) had 2 or more associated meanings (senses), and thus were potentially ambiguous. Cardiac societies differed from each other, and also internally, in their use of abbreviations, with the European Society of Cardiology representing the highest frequency of discrepant abbreviation usage (14.5%)., Conclusions: More than 12.7% of abbreviations in cardiology society guidelines had 2 or more corresponding meanings, potentially increasing the risks of miscommunication and misrepresentation. We call on cardiology and cardiac imaging societies to define and publish best practices regarding abbreviation creation and utilization., Competing Interests: This research did not receive any specific grant funding from any public or private sources. Dr Hill is a consultant for Philips Healthcare. Dr Mitchell reports author textbook chapters with Elsevier and contracted research grants from W. L. Gore & Associates to University of Wisconsin-Madison, consulting Acoustic Range Estimates. Dr Rigolin owns stock ownership in Amgen, Edwards, Intuitive Surgical, Organon, Rednivia, Regeneron, AstraZeneca, Bristol Myers Squibb, Merck/Schering-Plough, Pfizer, and Viatris. Dr Strom received research grants from the National Heart, Lung, and Blood Institute (1R01HL169517) and National Institute of Aging (1R01AG063937), Anumana, Philips Healthcare, EVERSANA Lifesciences, and Bracco Diagnostics; reports consulting for Bracco Diagnostics, Edwards Lifesciences, Philips Healthcare, General Electric Healthcare, and EVERSANA, and is a scientific advisory board member for Ultromics, HeartSciences, Bristol Myers Squibb, and EchoIQ. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. The content of this manuscript is solely the responsibility of the authors and does not necessarily reflect the official views of the NHLBI, NIH, or the United States Department of Health and Human Services., (© 2025 The Authors.)

Background: Risk-benefit tradeoffs between restrictive versus liberal red blood cell transfusion strategies may vary across individuals. This exploratory analysis aimed to derive and evaluate individualized treatment effects of defined transfusion strategies in patients with acute MI and anemia with the goal of minimizing adverse cardiovascular outcomes., Methods: This study analyzed 3,447 (98.4%) patients randomized in the MINT (Myocardial Ischemia and Transfusion) trial between April 2017 to April 2023. Outcomes for this analysis included 30-day death or recurrent MI, death, and major adverse cardiovascular events (MACE, a composite of death, MI, stroke, and ischemia-driven unscheduled revascularization). Machine learning methods were used to identify baseline patient characteristics that informed the individualized treatment effect of a restrictive versus liberal transfusion strategy for each patient. The expected population risk of an outcome under a scenario in which patients received their optimal treatment, as indicated by the individualized treatment effect, was contrasted with expected risks for universally applying a restrictive strategy or a liberal strategy to all patients., Results: Baseline characteristics did not inform individualized treatment effects on 30-day death and death or MI, suggesting minimal heterogeneity in treatment effect on these outcomes. An algorithm for estimating the individualized treatment effect on 30-day MACE included 12 baseline factors. If all patients received the optimal treatment as indicated by their estimated individualized treatment effect, the predicted risk of 30-day MACE in the sample population was 15.2% (95% CI 14.2%-16.2%). This corresponded to 4.0 (difference: -4.0%, 95% CI -5.8, -2.1) and 2.3 (difference: -2.3%, 95% CI -3.7, -0.9) percentage point risk reductions compared to applying a restrictive or liberal strategy to everyone respectively., Conclusions: The MINT trial average treatment effect, favoring a liberal strategy, may be optimal to minimize risk of 30-day death and death or MI for acute MI patients with anemia represented in the MINT sample as no individualized treatment effects were estimated on these outcomes. However, individualized transfusion strategy decisions have potential to reduce risk of 30-day MACE. External validation of the MACE algorithm is required before clinical use., Trial Registration: ClinicalTrials.gov, NCT02981407, https://clinicaltrials.gov/study/NCT02981407., Competing Interests: Declaration of competing interest GTP: None. GD: Speaker and/or consulting fees: Abbott, Amarin, Amgen, Astra Zeneca, Bayer, Boston scientific, BMS, Novo Nordisk, Sanofi. CEC, DSMB, Steering committee: Amgen, Novo Nordisk, Janssen. Proctoring: Boston scientific. Travel fees: Sanofi Ownership interest: Bioquantis. MB: None. JHA: Research grants through Duke University from Artivion/CryoLife, Bayer, Bristol-Myers Squibb, CSL Behring, Ferring, the U.S. FDA, Humacyte, and the U.S. NIH and has received advisory board or consulting payments from AbbVie, Artivion/CryoLife, AtriCure, Bayer, Bristol-Myers Squibb, Curis, Eli Lilly, Ferring, GlaxoSmithKline, Janssen, Novostia, Pfizer, Portola, Theravance, and Veralox. SGG: Research grant support (e.g., steering committee or data and safety monitoring committee) and/or speaker/consulting honoraria (e.g., advisory boards) from: Alnylam, Amgen, Anthos Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CSL Behring, CYTE Ltd., Daiichi-Sankyo/American Regent, Eli Lilly, Esperion, Ferring Pharmaceuticals, HLS Therapeutics, Idorsia, JAMP Pharma, Merck, Novartis, Novo Nordisk A/C, Pendopharm/Pharmascience, Pfizer, Regeneron, Roche, Sanofi, Servier, Tolmar Pharmaceuticals, Valeo Pharma; and salary support/honoraria from the Canadian Heart Failure Society, Canadian Heart Research Centre and MD Primer, Canadian VIGOUR Centre, Cleveland Clinic Coordinating Centre for Clinical Research, Duke Clinical Research Institute, Jewish General Hospital\ CIUSSS Centre-Ouest-de-l'Ile-de-Montreal, New York University Clinical Coordinating Centre, PERFUSE Research Institute, Peter Munk Cardiac Centre Clinical Trials and Translation Unit, Ted Rogers Centre for Heart Research, TIMI Study Group (Brigham Health). SG: None. JBS: Dr. Strom reports research grants from the National Heart, Lung, and Blood Institute (1R01HL169517, 1K23HL144907) and National Institute of Aging (1R01AG063937), Anumana, Ultromics, Philips Healthcare, and Bracco Diagnostics; consulting for Bracco Diagnostics, Edwards Lifesciences, Philips Healthcare, General Electric Healthcare, and EVERSANA, and is a member of the scientific advisory boards for Ultromics, HeartSciences, and EchoIQ, and the data safety monitoring board for Pfizer. He additionally serves on the Board of Directors for the Joint Review Committee on Diagnostic Medical Sonography, and the American College of Cardiology commissioner to the Commission on Accreditation of Allied Health Education Programs. SAS: None. GL: None. SVR: None. MT: None. TP: None. MG: Dr. Goldfarb is supported by a Clinical Research Award by the Fonds de Recherche du Québec – Santé. JHT: None. LU: None. BMH: None. JS: Dr Silvain declares the following relation with the industry during the last 2 years, all outside the submitted work. Consulting Fees or Lecture Fees: BIOTRONIK FRANCE SAS; SANOFI AVENTIS FRANCE, CSL BEHRING S.A. Travel Support, Hospitality: ABBOTT MEDICAL FRANCE SAS, BIOTRONIK FRANCE SAS; MEDTRONIC INTERNATIONAL TRADING SARL, NOVO NORDISK. Stockholder: 4P-PHARMA. JLC: DSMB member for Cerus Corporation project. MMB: DSMB member for Cerus Corporation., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Degenerative mitral valve disease is common. Up to a quarter of patients with degenerative mitral valve disease may be asymptomatic despite having severe valve regurgitation. Current guideline indications for intervention in asymptomatic patient are centred on left ventricular dimensions and ejection fraction and may include consideration in atrial fibrillation, pulmonary hypertension and those with left atrial dilatation. However, despite intervention according to these recommendations, patients remain at risk of post-operative heart failure and mortality. Newer risk markers have been developed including left ventricular and atrial strain, myocardial fibrosis demonstrated using late gadolinium enhancement, mitral annular disjunction and ventricular arrhythmia burden. Translating newer markers into clinical practice will require integrating and identifying high-risk phenotypes that benefit from early intervention using machine learning techniques and artificial intelligence. Valve repair is the recommended intervention. However, repair rate and durability are dependent on both operator and centre volumes as well as valve characteristics. Recent advancements, including robotic surgery, may enhance repair rates; however, larger datasets are necessary to confirm these improvements. Efforts should focus on establishing high-volume regional centres of excellence for mitral valve repair., Competing Interests: Competing interests: JBS reports research grants from the National Heart, Lung, and Blood Institute (1R01HL169517) and National Institute of Aging (1R01AG063937), Anumana, Philips Healthcare and Bracco Diagnostics; consulting for Bracco Diagnostics, Edwards Lifesciences, Philips Healthcare, General Electric Healthcare and EVERSANA and is a member of the scientific advisory boards for Ultromics, HeartSciences, Bristol Myers Squibb, and EchoIQ. All remaining authors declared no conflicts of interest., (© Author(s) (or their employer(s)) 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Background: The optimal hemoglobin threshold to guide red blood cell (RBC) transfusion for patients with acute myocardial infarction (MI) and anemia is uncertain., Objective: To estimate the efficacy of 4 individual hemoglobin thresholds (<10 g/dL [<100 g/L], <9 g/dL [<90 g/L], <8 g/dL [<80 g/L], and <7 g/dL [<70 g/L]) to guide transfusion in patients with acute MI and anemia., Design: Prespecified secondary analysis of the MINT (Myocardial Ischemia and Transfusion) trial using target trial emulation methods. (ClinicalTrials.gov: NCT02981407)., Setting: 144 clinical sites in 6 countries., Participants: 3492 MINT trial participants with acute MI and a hemoglobin level below 10 g/dL., Intervention: Four transfusion strategies to maintain patients' hemoglobin concentrations at or above thresholds of 10, 9, 8, or 7 g/dL. Protocol exceptions were permitted for specified adverse clinical events., Measurements: Data from the MINT trial were leveraged to emulate 4 transfusion strategies and estimate per protocol effects on the composite outcome of 30-day death or recurrent MI (death/MI) and 30-day death using inverse probability weighting., Results: The 30-day risk for death/MI was 14.8% (95% CI, 11.8% to 18.4%) for a <10-g/dL strategy, 15.1% (CI, 11.7% to 18.2%) for a <9-g/dL strategy, 15.9% (CI, 12.4% to 19.0%) for a <8-g/dL strategy, and 18.3% (CI, 14.6% to 22.0%) for a <7-g/dL strategy. Absolute risk differences and risk ratios relative to the <10-g/dL strategy for 30-day death/MI increased as thresholds decreased, although 95% CIs were wide. Findings were similar and imprecise for 30-day death., Limitation: Unmeasured confounding may have persisted despite adjustment., Conclusion: The 30-day risks for death/MI and death among patients with acute MI and anemia seem to increase progressively with lower hemoglobin concentration thresholds for transfusion. However, the imprecision around estimates from this target trial analysis precludes definitive conclusions about individual hemoglobin thresholds., Primary Funding Source: National Heart, Lung, and Blood Institute., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M24-0571.

Background: Frailty is associated with adverse cardiovascular outcomes independent of age and comorbidities, yet the independent influence of frailty progression on cardiovascular outcomes remains uncertain., Methods: To determine whether frailty progression is associated with adverse cardiovascular outcomes, independent of baseline frailty and age, we evaluated all Medicare Fee-for-Service beneficiaries ≥65 years at cohort inception with continuous enrollment from 2003 to 2015. Linear mixed effects models, adjusted for baseline frailty and age, were used to estimate change in a validated claims-based frailty index (CFI) over a 5-year period. Survival analysis was used to examine frailty progression and risk of adverse health outcomes., Results: There were 8.9 million unique patients identified, mean age 77.3 ± 7.2 years, 58.7% female, 10.9% non-White race. In total, 60% had frailty progression and 40% frailty regression over median follow-up of 2.4 years. Compared to those with frailty regression, when adjusting for age and baseline CFI, those with frailty progression had a significantly greater risk of incident major adverse cardiovascular and cerebrovascular events (MACCE) (hazard ratio [HR] 1.31, 95% confidence interval [CI] 1.31-1.31), all-cause mortality (HR 1.34, 95% CI 1.34-1.34), acute myocardial infarction (HR 1.08, 95% CI 1.07-1.09), heart failure exacerbation (HR 1.30, 95% CI 1.29-1.30), ischemic stroke (HR 1.14, 95% CI 1.14-1.15). There was also a graded increase in risk of each outcome with more rapid progression, as well as significantly fewer days alive at home (DAH) with more rapid progression compared to the slowest progression group (270.4 ± 112.3 vs. 308.6 ± 93.0 days, rate ratio 0.88, 95% CI 0.87-0.88, p < 0.001)., Conclusions: In this large, nationwide sample of older Medicare beneficiaries, frailty progression, independent of age and baseline frailty, was associated with fewer DAH and a graded risk of MACCE, all-cause mortality, myocardial infarction, heart failure, and ischemic stroke compared to those with frailty regression., (© 2024 The American Geriatrics Society.)

Background: Identifying individuals with severe aortic stenosis (AS) at high risk of mortality remains challenging using current clinical imaging methods., Objectives: The purpose of this study was to evaluate an artificial intelligence decision support algorithm (AI-DSA) to augment the detection of severe AS within a well-resourced health care setting., Methods: Agnostic to clinical information, an AI-DSA trained to identify echocardiographic phenotype associated with an aortic valve area (AVA)<1 cm 2 using minimal input data (excluding left ventricular outflow tract measures) was applied to routine transthoracic echocardiograms (TTE) reports from 31,141 U.S. Medicare beneficiaries at an academic medical center (2003-2017)., Results: Performance of AI-DSA to detect the phenotype associated with an AVA<1 cm 2 was excellent (sensitivity 82.2%, specificity 98.1%, negative predictive value 9.2%, c-statistic = 0.986). In addition to identifying clinical severe AS cases, AI-DSA identified an additional 1,034 (3.3%) individuals with guideline-defined moderate AS but with a similar clinical and TTE phenotype to those with severe AS with low rates of aortic valve replacement (6.6%). Five-year mortality was 75.9% in those with known severe AS, 73.5% in those with a similar phenotype to severe AS, and 44.6% in those without severe AS. The AI-DSA continued to perform well to identify severe AS among those with a depressed left ventricular ejection fraction. Overall rates of aortic valve replacement remained low, even in those with an AVA<1 cm 2 (21.9%)., Conclusions: Without relying on left ventricular outflow tract measurements, an AI-DSA used echocardiographic reports to reliably identify the phenotype of severe AS. These results suggest possible utility for this AI-DSA to enhance detection of severe AS individuals at risk for adverse outcomes., Competing Interests: This work was supported by Echo IQ Pty Ltd. Dr Stewart is supported by the 10.13039/501100000925National Health and Medical Research Council of Australia (GNT1135894). Dr Strom is supported by the 10.13039/100000002National Institutes of Health (1K23HL144907, R01AG063937), 10.13039/100006520Edwards Lifesciences, Ultromics, HeartSciences, Anumana, and EchoIQ. Unrelated to this work, Dr Strom has served on the Scientific Advisory Board for Edwards Lifesciences and EchoIQ and has received consulting fees from Bracco Diagnostics, General Electric Healthcare, and Lantheus Medical Imaging. Prof Strange has received consulting fees from Edwards, Medtronic, and Echo IQ and has received speaker fees from Edwards, Medtronic, Abbott, and Echo IQ. Prof Playford has received consulting fees from Edwards, Medtronic, and Echo IQ. Prof Stewart has received consulting fees from Echo IQ., (© 2024 The Authors.)

Background: Female sex is frequently cited as a risk factor for anthracycline cardiotoxicity based on pediatric data, but the role of sex in the development of cardiotoxicity has not been clearly established in adults., Objectives: To assess the effect of female sex on the development of incident heart failure (HF) in adult patients treated with anthracyclines., Methods: This was a retrospective cohort study of 1525 adult patients with no prior history of HF or cardiomyopathy who were treated with anthracyclines between 1992 and 2019. The primary outcome was new HF within 5 years of the first dose of anthracyclines. The effect of sex was assessed using Cox proportional hazards and competing risk models., Results: Over a median (IQR) follow-up of 1.02 (0.30-3.01) years, 4.78% of patients developed HF (44 men and 29 women). Female sex was not associated with the primary outcome in a multivariable Cox proportional hazards model (HR 0.87; 95% CI 0.53-1.43; P = 0.58). Similar results were observed in a multivariable model accounting for the competing risk of death (HR 0.94; 95% CI 0.39-2.25; P = 0.88). Age, coronary artery disease and hematopoietic stem cell transplant were associated with the primary outcome in a multivariable Cox proportional hazards model. Age and body mass index were associated with the primary outcome in a multivariable competing risk model., Conclusions: In this large, single-center, retrospective cohort study, female sex was not associated with incident HF in adult patients treated with anthracyclines., Condensed Abstract: Female sex is frequently cited as a risk factor for anthracycline cardiotoxicity based on pediatric data, but the role of sex in the development of cardiotoxicity has not been clearly established in adults. In this retrospective cohort study, we assessed the effect of female sex on the development of incident heart failure in adult patients treated with anthracyclines. Using Cox proportional hazards and competing risk regression models, we found that there was no association between female sex and heart failure after treatment with anthracyclines., Competing Interests: DISCLOSURES AA has consulted for Sanofi, AstraZeneca, Cytokinetics, and OncLive and serves as the principal investigator for a sponsored research agreement with Genentech, all unrelated to the submitted work. JS reports grant funding from Edwards Lifesciences, Anumana, Ultromics, and HeartSciences, consulting for Bracco Diagnostics, and speaker fees from Northwest Imaging Forums, unrelated to the submitted work. The remaining authors have nothing to disclose., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Right ventricular (RV) to pulmonary arterial (PA) coupling describes the ability of the RV to augment contractility in response to increased afterload. Several echocardiographic indexes of RV-PA coupling have been defined; however, the optimal numerator in the coupling ratio is unclear. We sought to establish which of these ratios is best for assessing RV-PA coupling based on their relations with 6-minute walk distance (6MWD), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and the Kansas City Cardiomyopathy Questionnaire (KCCQ) in aging adults. In this study of 1,611 Multi-Ethnic Study of Atherosclerosis participants who underwent echocardiography at Exam 6, we evaluated the association between different numerators, including tricuspid annular planar systolic excursion (TAPSE), fractional area change (FAC), RV free wall strain, and tissue Doppler imaging S' velocity to pulmonary artery systolic pressure (PASP) with 6MWD, NT-proBNP, and KCCQ score, adjusted for socioeconomic and cardiovascular disease risk factors. Our cohort had a mean age of 73 ± 8 years, 54% female, 17% Chinese American, 22% African American, 22% Hispanic, and 39% White participants. The mean ( ± SD) TAPSE/PASP, FAC/PASP, tissue Doppler imaging S' velocity/PASP, and RV free wall strain:PASP ratios were 0.7 ± 0.2, 1.3 ± 0.3, 0.5 ± 0.1, and 0.8 ± 0.2, respectively. All RV-PA coupling indices decreased with age (p <0.0001 for all). TAPSE:PASP ratio was lower in older (³85 years) female (0.59 ± 0.14) versus male (0.65 ± 0.17) participants (p = 0.01), whereas FAC/PASP ratio was higher in the same female versus male participants (p <0.01). TAPSE/PASP and FAC/PASP ratios were significantly and strongly associated with all NT-proBNP, 6MWD, and KCCQ scores in fully adjusted and receiver operating characteristic analysis. In older community-dwelling adults free of heart failure and pulmonary hypertension, both FAC/PASP and TAPSE:PASP ratios are optimal for assessment of RV-PA coupling based on its association with 6MWD, NT-proBNP, and KCCQ score. FAC/PASP ratio has the additional benefit of reflecting age and gender-related geometric and functional changes., Competing Interests: Declaration of competing interest Unrelated to this work, Dr. Shah receives consulting fees from Abbott, Actelion, AstraZeneca, Amgen, Axon Therapeutics, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardiora, CVRx, Cytokinetics, Eisai, Glaxo-SmithKline, Ionis, Ironwood, Lilly, Merck, MyoKardia, Novartis, Novo Nordisk, Pfizer (New York, NY, United States), Regeneron, Sanofi, Shifamed, Tenax, and United Therapeutics. Unrelated to this work, Dr. Strom serves on the Scientific Advisory Board for Edwards Lifesciences and EchoIQ and receives consulting fees from Bracco Diagnostics, General Electric Healthcare, and Lantheus Medical Imaging. Unrelated to this work, Dr. Michos has received consulting fees from Amarin, Amgen, Boehringer Ingelheim (Ingelheim, Germany), Edwards Lifesciences, Esperion, Medtronic, Novo Nordisk, and Pfizer. Unrelated to this work, Dr. Mukherjee serves on the DSMB for Advarra, Inc. None of the other authors report any conflicts of interest. The remaining authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This document on cardiovascular infection, including infective endocarditis, is the first in the American Society of Nuclear Cardiology Imaging Indications (ASNC I 2 ) series to assess the role of radionuclide imaging in the multimodality context for the evaluation of complex systemic diseases with multisocietal involvement including pertinent disciplines. A rigorous modified Delphi approach was used to determine consensus clinical indications, diagnostic criteria, and an algorithmic approach to diagnosis of cardiovascular infection including infective endocarditis. Cardiovascular infection incidence is increasing and is associated with high morbidity and mortality. Current strategies based on clinical criteria and an initial echocardiographic imaging approach are effective but often insufficient in complicated cardiovascular infection. Radionuclide imaging with fluorine-18 fluorodeoxyglucose ( 18 F-FDG) positron emission tomography/computed tomography (CT) and single photon emission computed tomography/CT leukocyte scintigraphy can enhance the evaluation of suspected cardiovascular infection by increasing diagnostic accuracy, identifying extracardiac involvement, and assessing cardiac implanted device pockets, leads, and all portions of ventricular assist devices. This advanced imaging can aid in key medical and surgical considerations. Consensus diagnostic features include focal/multifocal or diffuse heterogenous intense 18 F-FDG uptake on valvular and prosthetic material, perivalvular areas, device pockets and leads, and ventricular assist device hardware persisting on non-attenuation corrected images. There are numerous clinical indications with a larger role in prosthetic valves, and cardiac devices particularly with possible infective endocarditis or in the setting of prior equivocal or non-diagnostic imaging. Illustrative cases incorporating these consensus recommendations provide additional clarification. Future research is necessary to refine application of these advanced imaging tools for surgical planning, to identify treatment response, and more., (Copyright © 2024 by the American Society of Nuclear Cardiology, the American College of Cardiology, Heart Rhythm Society, and the Infectious Diseases Society of America. Published by Elsevier on behalf of the American Society of Nuclear Cardiology, the American College of Cardiology, Heart Rhythm Society, and by Oxford University Press on behalf of the Infectious Diseases Society of America. Published by Elsevier Inc. All rights reserved.)

Background: The mortality risk attributable to moderate aortic stenosis (AS) remains incompletely characterized and has historically been underestimated. We aim to evaluate the association between moderate AS and all-cause death, comparing it with no/mild AS (in a general referral population and in patients with heart failure with reduced ejection fraction)., Methods and Results: A systematic review and pooled meta-analysis of Kaplan-Meier-derived reconstructed time-to-event data of studies published by June 2023 was conducted to evaluate survival outcomes among patients with moderate AS in comparison with individuals with no/mild AS. Ten studies were included, encompassing a total of 409 680 patients (11 527 with moderate AS and 398 153 with no/mild AS). In the overall population, the 15-year overall survival rate was 23.3% (95% CI, 19.1%-28.3%) in patients with moderate AS and 58.9% (95% CI, 58.1%-59.7%) in patients with no/mild aortic stenosis (hazard ratio [HR], 2.55 [95% CI, 2.46-2.64]; P <0.001). In patients with heart failure with reduced ejection fraction, the 10-year overall survival rate was 15.5% (95% CI, 10.0%-24.0%) in patients with moderate AS and 37.3% (95% CI, 36.2%-38.5%) in patients with no/mild AS (HR, 1.83 [95% CI, 1.69-2.0]; P <0.001). In both populations (overall and heart failure with reduced ejection fraction), these differences correspond to significant lifetime loss associated with moderate AS during follow-up (4.4 years, P <0.001; and 1.9 years, P <0.001, respectively). A consistent pattern of elevated mortality rate associated with moderate AS in sensitivity analyses of matched studies was observed., Conclusions: Moderate AS was associated with higher risk of death and lifetime loss compared with patients with no/mild AS.

Background: Echocardiographic (2-dimensional echocardiography) thresholds indicating disease or impaired functional status compared with normal physiological aging in individuals aged ≥65 years are not clearly defined. In the present study, we sought to establish standard values for 2-dimensional echocardiography parameters related to chamber size and function in older adults without cardiopulmonary or cardiometabolic conditions., Methods: In this cross-sectional study of 3032 individuals who underwent 2-dimensional echocardiography at exam 6 in the MESA (Multi-Ethnic Study of Atherosclerosis), 608 participants fulfilled our inclusion criteria of healthy aging, with normative values defined as the mean ± 1.96 standard deviation and compared across sex and race and ethnicity. Functional status measures included NT-proBNP (N-terminal pro-B-type natriuretic peptide), 6-minute walk distance, and Kansas City Cardiomyopathy Questionnaire. Prognostic performance using MESA cutoffs was compared with established guideline cutoffs using time-to-event analysis., Results: The normative aging cohort (69.5±7.0 years, 46.2% male, 47.5% White) had lower NT-proBNP, higher 6-minute walk distance, and higher (better) Kansas City Cardiomyopathy Questionnaire summary values. Women had significantly smaller chamber sizes and better biventricular systolic function. White participants had the largest chamber dimensions, whereas Chinese participants had the smallest, even after adjustment for body size. Current guidelines identified 81.6% of healthy older adults in MESA as having cardiac abnormalities., Conclusions: Among a large, diverse group of healthy older adults, we found significant differences in cardiac structure and function by sex and race/ethnicity, which may signal sex-specific cardiac remodeling with advancing age. It is crucial for existing guidelines to consider the observed and clinically significant differences in cardiac structure and function associated with healthy aging. Our study highlights that existing guidelines, which grade abnormalities in echocardiographic cardiac chamber size and function based on younger individuals, may not adequately address the anticipated changes associated with normal aging., Competing Interests: Disclosures Dr Michos served on a Medical Advisory Board for Pfizer, Novo Nordisk, Bayer, Boehringer Ingelheim, Esperion, Amarin, Amgen, and AstraZeneca. Dr Shah receives consulting fees from Abbott, Actelion, AstraZeneca, Amgen, Axon Therapeutics, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardiora, CVRx, Cytokinetics, Eisai, Glaxo Smith Kline, Ionis, Ironwood, Lilly, Merck, MyoKardia, Novartis, Novo Nordisk, Pfizer, Regeneron, Sanofi, Shifamed, Tenax, and United Therapeutics (unrelated to this work). Dr Strom serves on the Scientific Advisory Board for Edwards Lifesciences and EchoIQ and receives consulting fees from Bracco Diagnostics, General Electric Healthcare, and Lantheus Medical Imaging (unrelated to this work). Dr Mukherjee serves on the data, safety, and managing board for Advarra, Inc (unrelated to this work). The other authors report no conflicts.

This document on cardiovascular infection, including infective endocarditis, is the first in the American Society of Nuclear Cardiology Imaging Indications (ASNC I 2 ) series to assess the role of radionuclide imaging in the multimodality context for the evaluation of complex systemic diseases with multi-societal involvement including pertinent disciplines. A rigorous modified Delphi approach was used to determine consensus clinical indications, diagnostic criteria, and an algorithmic approach to diagnosis of cardiovascular infection including infective endocarditis. Cardiovascular infection incidence is increasing and is associated with high morbidity and mortality. Current strategies based on clinical criteria and an initial echocardiographic imaging approach are effective but often insufficient in complicated cardiovascular infection. Radionuclide imaging with 18 F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (CT) and single photon emission computed tomography/CT leukocyte scintigraphy can enhance the evaluation of suspected cardiovascular infection by increasing diagnostic accuracy, identifying extracardiac involvement, and assessing cardiac implanted device pockets, leads, and all portions of ventricular assist devices. This advanced imaging can aid in key medical and surgical considerations. Consensus diagnostic features include focal/multi-focal or diffuse heterogenous intense 18 F-FDG uptake on valvular and prosthetic material, perivalvular areas, device pockets and leads, and ventricular assist device hardware persisting on non-attenuation corrected images. There are numerous clinical indications with a larger role in prosthetic valves, and cardiac devices particularly with possible infective endocarditis or in the setting of prior equivocal or non-diagnostic imaging. Illustrative cases incorporating these consensus recommendations provide additional clarification. Future research is necessary to refine application of these advanced imaging tools for surgical planning, to identify treatment response, and more., (Copyright © 2024 2024 The American Society of Nuclear Cardiology, the American College of Cardiology, Heart Rhythm Society, and the Infectious Diseases Society of America. Published by Elsevier on behalf of the American Society of Nuclear Cardiology, the American College of Cardiology, Heart Rhythm Society, and by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. Published by Elsevier Inc. All rights reserved.)

Background: Normalization of echocardiographic chamber measurements for body surface area may result in misclassification of individuals with obesity or sarcopenia. Normalization for alternative measures of body size may be preferable, but there remains a dearth of information on their normative values and association with cardiovascular function metrics., Methods and Results: A total of 3032 individuals underwent comprehensive 2-dimensional echocardiography at Exam 6 in MESA (Multi-Ethnic Study of Atherosclerosis). In the subgroup of 608 individuals free of cardiopulmonary disease (69.5±7.0 years, 46% male, 48% White, 17% Chinese, 15% Black, 21% Hispanic), normative values were derived for left and right cardiac chamber measurements across a variety of ratiometric (body surface area, body mass index, height) and allometric (height 1.6 , height 2.7 ) scaling parameters. Normative upper and lower reference values were provided for each scaling parameter stratified across age groups, sex, and race or ethnicity. Among scaling parameters, body surface area and height were associated with the least variability across race and ethnicity categories and height 2.7 was associated with the least variability across sex categories., Conclusions: In this diverse cohort of community-dwelling older adults, we provide normative values for common echocardiographic parameters across a variety of indexation methods.

This document on cardiovascular infection, including infective endocarditis, is the first in the American Society of Nuclear Cardiology Imaging Indications (ASNC I 2 ) series to assess the role of radionuclide imaging in the multimodality context for the evaluation of complex systemic diseases with multi-societal involvement including pertinent disciplines. A rigorous modified Delphi approach was used to determine consensus clinical indications, diagnostic criteria, and an algorithmic approach to diagnosis of cardiovascular infection including infective endocarditis. Cardiovascular infection incidence is increasing and is associated with high morbidity and mortality. Current strategies based on clinical criteria and an initial echocardiographic imaging approach are effective but often insufficient in complicated cardiovascular infection. Radionuclide imaging with 18 F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (CT) and single photon emission computed tomography/CT leukocyte scintigraphy can enhance the evaluation of suspected cardiovascular infection by increasing diagnostic accuracy, identifying extracardiac involvement, and assessing cardiac implanted device pockets, leads, and all portions of ventricular assist devices. This advanced imaging can aid in key medical and surgical considerations. Consensus diagnostic features include focal/multi-focal or diffuse heterogenous intense 18 F-FDG uptake on valvular and prosthetic material, perivalvular areas, device pockets and leads, and ventricular assist device hardware persisting on non-attenuation corrected images. There are numerous clinical indications with a larger role in prosthetic valves, and cardiac devices particularly with possible infective endocarditis or in the setting of prior equivocal or non-diagnostic imaging. Illustrative cases incorporating these consensus recommendations provide additional clarification. Future research is necessary to refine application of these advanced imaging tools for surgical planning, to identify treatment response, and more., (Copyright © 2024 The American Society of Nuclear Cardiology, the American College of Cardiology, Heart Rhythm Society, the Infectious Diseases Society of America. Published by Elsevier Inc. All rights reserved.)

This document on cardiovascular infection, including infective endocarditis, is the first in the American Society of Nuclear Cardiology Imaging Indications (ASNC I2) series to assess the role of radionuclide imaging in the multimodality context for the evaluation of complex systemic diseases with multi-societal involvement including pertinent disciplines. A rigorous modified Delphi approach was used to determine consensus clinical indications, diagnostic criteria, and an algorithmic approach to diagnosis of cardiovascular infection including infective endocarditis. Cardiovascular infection incidence is increasing and is associated with high morbidity and mortality. Current strategies based on clinical criteria and an initial echocardiographic imaging approach are effective but often insufficient in complicated cardiovascular infection. Radionuclide imaging with 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and single photon emission computed tomography/CT leukocyte scintigraphy can enhance the evaluation of suspected cardiovascular infection by increasing diagnostic accuracy, identifying extracardiac involvement, and assessing cardiac implanted device pockets, leads, and all portions of ventricular assist devices. This advanced imaging can aid in key medical and surgical considerations. Consensus diagnostic features include focal/multi-focal or diffuse heterogenous intense 18F-FDG uptake on valvular and prosthetic material, perivalvular areas, device pockets and leads, and ventricular assist device hardware persisting on non-attenuation corrected images. There are numerous clinical indications with a larger role in prosthetic valves, and cardiac devices particularly with possible infective endocarditis or in the setting of prior equivocal or non-diagnostic imaging. Illustrative cases incorporating these consensus recommendations provide additional clarification. Future research is necessary to refine application of these advanced imaging tools for surgical planning, to identify treatment response, and more., (© 2024 The American Society of Nuclear Cardiology, The American College of Cardiology, Heart Rhythm Society, and the Infectious Disease Society of America. Published by Elsevier on behalf of the American Society of Nuclear Cardiology, the American College of Cardiology, Heart Rhythm Society, and by Oxford University Press on behalf of the Infectious Disease Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Competing Interests: Dr Strom additionally reports research grants from Anumana, HeartSciences, Ultromics, and Philips Healthcare; consulting for Edwards Lifesciences, Bracco Diagnostics, Philips Healthcare, General Electric Healthcare, and EVERSANA Lifesciences and is a member of the scientific advisory boards for Ultromics, EchoIQ, and HeartSciences, and serves on a data safety monitoring board for Pfizer. Dr Osborn reports research grants from the National Heart, Lung, and Blood Institute (R43HL167290), Philips Healthcare, and Zoll Circulation; consulting for Gentuity,NuPulse CV, and OpSens, and is a member of the scientific advisory board for Dyad Medical and holds equity in this company. Ms. Stout reports consulting for Bracco Diagnostics. All other authors report no conflicts.

Background: Frailty is associated with adverse cardiovascular outcomes independent of age and comorbidities, yet the independent influence of frailty progression remains uncertain., Methods: Medicare Fee-for-service beneficiaries ≥ 65 years at cohort inception with continuous enrollment from 2003-2015 were included. Frailty trajectory was measured by annualized change in a validated claims-based frailty index (CFI) over a 5-year period. Linear mixed effects models, adjusting for baseline frailty, were used to estimate CFI change over a 5-year period. Survival analysis was used to evaluate associations of frailty progression and future health outcomes (major adverse cardiovascular and cerebrovascular events [MACCE], all-cause death, heart failure, myocardial infarction, ischemic stroke, and days alive at home [DAH] within the following calendar year)., Results: 26.4 million unique beneficiaries were included (mean age 75.4 ± 7.0 years, 57% female, 13% non-White). In total, 20% had frailty progression, 66% had no change in frailty, and 14% frailty regression over median follow-up of 2.4 years. Compared to those without a change in CFI, when adjusting for baseline frailty, those with frailty progression had significantly greater risk of incident MACCE (hazard ratio [HR] 2.30, 95% confidence interval [CI] 2.30-2.31), all-cause mortality (HR 1.59, 95% CI 1.58-1.59), acute myocardial infarction (HR 1.78, 95% CI 1.77-1.79), heart failure (HR 2.78, 95% CI 2.77-2.79), and stroke (HR 1.78, 95% CI 1.77-1.79). There was also a graded increase in risk of each outcome with more rapid progression and significantly fewer DAH with the most rapid vs. the slowest progression group (270.4 ± 112.3 vs. 308.6 ± 93.0 days, rate ratio 0.88, 95% CI 0.87-0.88, p < 0.001)., Conclusions: In this large, nationwide sample of Medicare beneficiaries, frailty progression, independent of baseline frailty, was associated with fewer DAH and a graded risk of MACCE, all-cause mortality, myocardial infarction, heart failure, and stroke compared to those without progression., Competing Interests: DISCLOSURES Dr. Strom reports research grants from the National Heart, Lung, and Blood Institute (1R01HL169517, 1K23HL144907), Anumana, HeartSciences, Ultromics, Philips Healthcare, Lantheus Medical Imaging, and EchoIQ; consulting for Bracco Diagnostics, Philips Healthcare, and General Electric Healthcare, and is a member of the scientific advisory boards for Edwards Lifesciences, Ultromics, and EchoIQ, and the data safety monitoring board for Pfizer.

Background: Ultrasound enhancing agents (UEAs) are an invaluable adjunct to stress and transthoracic echocardiography (STE) to improve left ventricular visualization. Despite multiple single center studies evaluating UEA use, investigation into the rates, sources of variation, and outcomes of UEA use on a national level in the United States (US) has been limited by lack of validation of UEA codes for claims analyses., Methods: We conducted a retrospective cross-sectional study, 2019-2022, using linked multicenter electronic medical record (EMR) data from > 30 health systems linked to all-payor claims data representing > 90% of the US population. Individuals receiving STE in both EMR and claims data on the same day during the study window were included. UEA receipt as identified by presence of a Current Procedural Terminology (CPT) or National Drug Code (NDC) for UEA use within 1-day of the index STE event. We evaluated the performance of claims to identify UEA use, using EMR data as the gold standard, stratified by inpatient and outpatient status., Results: Amongst 54,525 individuals receiving STE in both EMR and claims data, 12,853 (23.6%) had a UEA claim in EMR, 10,461 (19.2%) had a UEA claim in claims, and 9140 (16.8%) had a UEA claim in both within the 1-day window. The sensitivity, specificity, accuracy, positive, and negative predictive values for UEA claims were 71.1%, 96.8%, 90.8%, 87.4%. and 91.6% respectively. However, amongst inpatients, the sensitivity of UEA claims was substantially lower (6.8%) compared to outpatients (79.7%)., Conclusions: While the overall accuracy of claims to identify UEA use was high, there was substantial under-capture of UEA use by claims amongst inpatients. These results call into question published rates of UEA use amongst inpatients in studies using administrative claims, and highlight ongoing need to improve inpatient coding for UEA use., (© 2024. The Author(s).)

Background: A strategy of administering a transfusion only when the hemoglobin level falls below 7 or 8 g per deciliter has been widely adopted. However, patients with acute myocardial infarction may benefit from a higher hemoglobin level., Methods: In this phase 3, interventional trial, we randomly assigned patients with myocardial infarction and a hemoglobin level of less than 10 g per deciliter to a restrictive transfusion strategy (hemoglobin cutoff for transfusion, 7 or 8 g per deciliter) or a liberal transfusion strategy (hemoglobin cutoff, <10 g per deciliter). The primary outcome was a composite of myocardial infarction or death at 30 days., Results: A total of 3504 patients were included in the primary analysis. The mean (±SD) number of red-cell units that were transfused was 0.7±1.6 in the restrictive-strategy group and 2.5±2.3 in the liberal-strategy group. The mean hemoglobin level was 1.3 to 1.6 g per deciliter lower in the restrictive-strategy group than in the liberal-strategy group on days 1 to 3 after randomization. A primary-outcome event occurred in 295 of 1749 patients (16.9%) in the restrictive-strategy group and in 255 of 1755 patients (14.5%) in the liberal-strategy group (risk ratio modeled with multiple imputation for incomplete follow-up, 1.15; 95% confidence interval [CI], 0.99 to 1.34; P = 0.07). Death occurred in 9.9% of the patients with the restrictive strategy and in 8.3% of the patients with the liberal strategy (risk ratio, 1.19; 95% CI, 0.96 to 1.47); myocardial infarction occurred in 8.5% and 7.2% of the patients, respectively (risk ratio, 1.19; 95% CI, 0.94 to 1.49)., Conclusions: In patients with acute myocardial infarction and anemia, a liberal transfusion strategy did not significantly reduce the risk of recurrent myocardial infarction or death at 30 days. However, potential harms of a restrictive transfusion strategy cannot be excluded. (Funded by the National Heart, Lung, and Blood Institute and others; MINT ClinicalTrials.gov number, NCT02981407.)., (Copyright © 2023 Massachusetts Medical Society.)

Background: Echocardiographic (2DE) thresholds indicating disease or impaired functional status compared to normal physiologic aging in individuals ≥ 65 years are not clearly defined. In the present study, we sought to establish standard values for 2DE parameters related to chamber size and function in older adults without cardiopulmonary or cardiometabolic conditions., Methods: In this cross-sectional study of 3032 individuals who underwent 2DE at Exam 6 in the Multi-Ethnic Study of Atherosclerosis (MESA), 608 participants fulfilled our inclusion criteria, with normative values defined as the mean value ± 1.96 standard deviations and compared across sex and race/ethnicity. Functional status measures included NT-proBNP, 6-minute walk distance [6MWD], and Kansas City Cardiomyopathy Questionnaire [KCCQ]. Prognostic performance using MESA cutoffs was compared to established guideline cutoffs using time-to-event analysis., Results: Participants meeting our inclusion criteria (69.5 ± 7.0 years, 46.2% male, 47.5% White) had lower NT-proBNP, higher 6MWD, and higher (better) KCCQ summary values. Women had significantly smaller chamber sizes and better biventricular systolic function. White participants had the largest chamber dimensions, while Chinese participants had the smallest, even after adjustment for body size. Current guidelines identified 81.6% of healthy older adults in MESA as having cardiac abnormalities., Conclusions: Among a large, diverse group of healthy older adults, we found significant differences in cardiac structure and function across sexes and races/ethnicities, which may signal sex-specific cardiac remodeling with advancing age. It is crucial for existing guidelines to consider the observed and clinically significant differences in cardiac structure and function associated with healthy aging. Our study highlights that existing guidelines, which grade abnormalities in echocardiographic cardiac chamber size and function based on younger individuals, may not adequately address the anticipated changes associated with normal aging.

Background: Right heart thrombus is a rare but serious form of venous thromboembolic disease that may be associated with pulmonary embolism. The prognosis of patients with right heart thrombus presenting without a concomitant pulmonary embolism remains ill-defined., Methods: We conducted a multi-center observational cohort study to compare patients presenting with right heart thrombus with and without a concurrent pulmonary embolism. The primary endpoint was 90-day all-cause mortality. Multivariable regression was utilized to assess primary and secondary outcomes., Results: Of 231 patients with right heart thrombus, 104 (45.0%) had a pulmonary embolism at admission. The median age of the cohort was 59.4 years (interquartile range 44.9-71.3). Pulmonary embolism in the setting of a right heart thrombus was associated with an increased adjusted hazard of 90-day mortality (hazard ratio 3.68; 95% confidence interval [CI], 1.51-8.97). Additionally, these patients had a higher adjusted risk of in-hospital mortality (odds ratio [OR] 2.55; 95% CI, 1.15-5.94) and admission to the intensive care unit (OR 2.45; 95% CI, 1.23-4.94). Thrombus mobility (OR 2.99; 95% CI, 1.35-6.78) and larger thrombus sizes (OR 1.04; 95% CI, 1.00-1.07) were associated with development of concurrent pulmonary embolism., Conclusions: Patients with right heart thrombus and pulmonary embolism had a more severe clinical presentation, required more advanced therapies, and had reduced survival compared with those without a concomitant pulmonary embolism. Important variables associated with development of concomitant pulmonary embolism include thrombus mobility and size. Right heart thrombus in the setting of acute pulmonary embolism represents a unique clinical entity that is associated with worse prognosis compared with right heart thrombus only., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Frailty is increasingly recognized as a useful measure of vulnerability in older adults. Multiple claims-based frailty indices (CFIs) can readily identify individuals with frailty, but whether 1 CFI improves prediction over another is unknown. We sought to assess the ability of 5 distinct CFIs to predict long-term institutionalization (LTI) and mortality in older Veterans., Methods: Retrospective study conducted in U.S. Veterans ≥65 years without prior LTI or hospice use in 2014. Five CFIs were compared: Kim, Orkaby (Veteran Affairs Frailty Index [VAFI]), Segal, Figueroa, and the JEN-FI, grounded in different theories of frailty: Rockwood cumulative deficit (Kim and VAFI), Fried physical phenotype (Segal), or expert opinion (Figueroa and JFI). The prevalence of frailty according to each CFI was compared. CFI performance for the coprimary outcomes of any LTI or mortality from 2015 to 2017 was examined. Because Segal and Kim include age, sex, or prior utilization, these variables were added to regression models to compare all 5 CFIs. Logistic regression was used to calculate model discrimination and calibration for both outcomes., Results: A total of 3 million Veterans were included (mean age 75, 98% male participants, 80% White, and 9% Black). Frailty was identified for between 6.8% and 25.7% of the cohort with 2.6% identified as frail by all 5 CFIs. There was no meaningful difference between CFIs in the area under the receiver operating characteristic curve for LTI (0.78-0.80) or mortality (0.77-0.79)., Conclusions: Based on different frailty constructs, and identifying different subsets of the population, all 5 CFIs similarly predicted LTI or death, suggesting each could be used for prediction or analytics., (Published by Oxford University Press on behalf of The Gerontological Society of America 2023.)

Background: The recommendation for transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR) in patients 65 to 80 years of age is equivocal, leaving patients with a difficult decision. We evaluated whether TAVR compared to SAVR is associated with reduced odds for loss of independent living in patients ≤65, 66 to 79, and ≥80 years of age. Further, we explored mechanisms of the association of TAVR and adverse discharge., Methods: Adult patients undergoing TAVR or SAVR within a large academic medical system who lived independently before the procedure were included. A multivariable logistic regression model, adjusting for a priori defined confounders including patient demographics, preoperative comorbidities, and a risk score for adverse discharge after cardiac surgery, was used to assess the primary association. We tested the interaction of patient age with the association between aortic valve replacement (AVR) procedure and loss of independent living. We further assessed whether the primary association was mediated (ie, percentage of the association that can be attributed to the mediator) by the procedural duration as prespecified mediator., Results: A total of 1751 patients (age median [quartiles; min-max], 76 [67, 84; 23-100]; sex, 56% female) were included. A total of 27% (222/812) of these patients undergoing SAVR and 20% (188/939) undergoing TAVR lost the ability to live independently. In our cohort, TAVR was associated with reduced odds for loss of independent living compared to SAVR (adjusted odds ratio [OR adj ] 0.19 [95% confidence interval {CI}, 0.14-0.26]; P < .001). This association was attenuated in patients ≤65 years of age (OR adj 0.63 [0.26-1.56]; P = .32) and between 66 and 79 years of age (OR adj 0.23 [0.15-0.35]; P < .001), and magnified in patients ≥80 years of age (OR adj 0.16 [0.10-0.25]; P < .001; P -for-interaction = .004). Among those >65 years of age, a shorter procedural duration mediated 50% (95% CI, 28-76; P < .001) of the beneficial association of TAVR and independent living., Conclusions: Patients >65 years of age undergoing TAVR compared to SAVR had reduced odds for loss of independent living. This association was partly mediated by shorter procedural duration. No association between AVR approach and the primary end point was found in patients ≤65 years of age., Competing Interests: Conflicts of Interest: See Disclosures at the end of this article., (Copyright © 2023 International Anesthesia Research Society.)

Background: Peak tricuspid regurgitant velocity (TRV) on transthoracic echocardiography (TTE) is a commonly obtained parameter and robust predictor of subsequent adverse clinical outcomes., Objectives: The purpose of this study was to determine the predictors and clinical significance of TRV progression., Methods: We retrospectively linked consecutive outpatient TTE reports from our institution to 2005 to 2017 Medicare claims. Individuals with prior tricuspid surgery, endocarditis, tricuspid stenosis, missing TRV values, TTEs performed during inpatient hospitalization, or <2 TTEs were excluded., Results: A total of 4,572 patients (mean age 67.8 ± 11.9 years, 50.4% female) received 13,273 TTEs over a median follow-up of 7.4 (IQR: 4.5-6.9) years. TRV increased by a mean of 0.23 (95% CI: 0.22 to 0.23 m/s/y, P < 0.001) (range, 0.01-0.80 m/s/y). Older age, depressed left ventricular ejection fraction, diabetes, hypertension, hyperlipidemia, atrial fibrillation, heart failure, and chronic kidney disease were associated with faster progression (all P < 0.05). Accounting for 23 demographic, clinical, and TTE variables, faster TRV progression was associated with a stepwise increased risk of all-cause mortality (TRV progression quartile 4 vs 1; adjusted HR: 2.17; 95% CI: 1.74-2.71; P < 0.001). Those with regression of TRV (n = 384 [8.4%]) had a lower mortality risk (adjusted HR: 0.40; 95% CI: 0.28-0.57; P < 0.001)., Conclusions: In this large, multidecade study of Medicare beneficiaries with serial TTEs performed in the outpatient setting, the mean rate of TRV progression was 0.23 m/s/y. Older age, left heart disease, and adverse metabolic features were associated with faster progression. Faster progression was associated with a graded risk for all-cause mortality.

Background Frailty is rarely assessed in clinical trials of patients who receive dual antiplatelet therapy (DAPT) after percutaneous coronary intervention. This study investigated whether frailty defined using claims data is associated with outcomes following percutaneous coronary intervention, and if there is a differential association in patients receiving standard versus extended duration DAPT. Methods and Results Patients ≥65 years of age in the DAPT (Dual Antiplatelet Therapy) Study, a randomized trial comparing 30 versus 12 months of DAPT following percutaneous coronary intervention, had data linked to Medicare claims (n=1326), and a previously validated claims-based index was used to define frailty. Net adverse clinical events, a composite of all-cause mortality, myocardial infarction, stroke, and major bleeding, were compared between frail and nonfrail patients. Patients defined as frail using claims data (12.0% of the cohort) had higher incidence of net adverse clinical events (23.1%) compared with nonfrail patients (10.7%; P <0.001) at 18-month follow-up and increased risk after multivariable adjustment (adjusted hazard ratio [HR], 2.24 [95% CI, 1.38-3.63]). There were no differences in effects of extended duration DAPT on net adverse clinical events for frail (HR, 1.42 [95% CI, 0.73-2.75]) and nonfrail patients (HR, 1.18 [95% CI, 0.83-1.68]; interaction P =0.61), although analyses were underpowered. Bleeding was highest among frail patients who received extended duration DAPT. Conclusions Among older patients in the DAPT Study, claims-defined frailty was associated with higher net adverse clinical events. Effects of extended duration DAPT were not different for frail patients, although comparisons were underpowered. Further investigation of how frailty influences ischemic and bleeding risks with DAPT are warranted. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00977938.

Aims: Frailty is associated with increased morbidity and mortality in patients undergoing left atrial appendage closure (LAAC). This study aimed to compare the performance of two claims-based frailty measures in predicting adverse outcomes following LAAC., Methods: We identified patients 66 years and older who underwent LAAC between October 1, 2016, and December 31, 2019, in Medicare fee-for-service claims. Frailty was assessed using the previously validated Hospital Frailty Risk Score (HFRS) and Kim Claims-based Frailty Index (CFI). Patients were identified as frail based on HFRS ≥5 and CFI ≥0.25., Results: Of the 21,787 patients who underwent LAAC, frailty was identified in 45.6% by HFRS and 15.4% by CFI. There was modest agreement between the two frailty measures (kappa 0.25, Pearson's correlation 0.62). After adjusting for age, sex, and comorbidities, frailty was associated with higher risk of 30-day mortality, 1-year mortality, 30-day readmission, long hospital stay, and reduced days at home (p < .01 for all) regardless of the frailty measure used. The addition of frailty to standard comorbidities significantly improved model performance to predict 1-year mortality, long hospital stay, and reduced days at home (Delong p-value < .001)., Conclusion: Despite significant variation in frailty detection and modest agreement between the two frailty measures, frailty status remained highly predictive of mortality, readmissions, long hospital stay, and reduced days at home among patients undergoing LAAC. Measuring frailty in clinical practice, regardless of the method used, may provide prognostic information useful for patients being considered for LAAC, and may inform shared decision-making in this population., (© 2022 Wiley Periodicals LLC.)

We report a case of a 70-year-old woman who presented for a cavotricuspid isthmus atrial flutter ablation that was aborted prematurely. On subsequent imaging, she was discovered to have a right atrial diverticulum, which was present on prior imaging but not reported, likely due to unfamiliarity with the entity. ( Level of Difficulty: Intermediate. )., Competing Interests: Dr Waks has received grant support from Anumana. Dr Strom has received funding from the National Institutes of Health/National Heart, Lung, and Blood Institute (1K23HL144907); has received grant support from Edwards Lifesciences, Ultromics, HeartSciences, and Anumana; has received consulting fees from Bracco Diagnostics and General Electric Healthcare; and has served on the advisory boards for Edwards Lifesciences, Ultromics, and EchoIQ. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2023 The Authors.)

Background: Aortic stenosis (AS) is the most common valvular heart disease in high-income countries. Adjusted for clinical confounders, the risk associated with increasing AS severity across the spectrum of AS severity remains uncertain., Methods: The authors conducted an international, multicenter, parallel-cohort study of 217,599 Australian (mean age, 76.0 ± 7.3 years; 49.3% women) and 30,865 US (mean age, 77.4 ± 7.3 years; 52.2% women) patients aged ≥65 years who underwent echocardiography. Patients with previous aortic valve replacement were excluded. The risk of increasing AS severity, quantified by peak aortic velocity (Vmax), was assessed through linkage to 97,576 and 14,481 all-cause deaths in Australia and the United States, respectively., Results: The distribution of AS severity (mean Vmax, 1.7 ± 0.7 m/sec) was similar in both cohorts. Compared with those with Vmax of 1.0 to 1.49 m/sec, those with Vmax of 2.50 to 2.99 m/sec (US cohort) or Vmax of 3.0 to 3.49 m/sec (Australian cohort) had a 1.5-fold increase in mortality risk within 10 years, adjusting for age, sex, presence of left heart disease, and left ventricular ejection fraction. Overall, the adjusted risk for mortality plateaued (1.75- to 2.25-fold increased risk) above a Vmax of 3.5 m/sec. This pattern of mortality persisted despite adjustment for a comprehensive list of comorbidities and treatments within the US cohort., Conclusions: Within large, parallel patient cohorts managed in different health systems, similar patterns of mortality linked to increasingly severe AS were observed. These findings support ongoing clinical trials of aortic valve replacement in patients with nonsevere AS and suggest the need to develop and apply more proactive surveillance strategies in this high-risk population., (Copyright © 2022 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background: In response to COVID-19 pandemic state restrictions, our institution deferred elective procedures from 3/15/2020 to 6/13/2020, and removed cardiology fellows from the echocardiography rotation to staff clinical services. We assessed the impact of the COVID-19 pandemic on fellow education and echocardiography volumes., Methods: Our institutional database was used to examine volumes of transthoracic (TTE), stress (SE), and transesophageal echocardiograms (TEE) from 7/1/2018 to 10/10/2020. Study volumes were compared in three intervals: pre-pandemic (7/1/2018- 3/14/2020), pandemic (3/15/2020-6/13/2020), and pandemic recovery (6/14/2020-10/10/2020). We examined weekly number of TTEs performed or interpreted by cardiology fellows during the study period, and compared these to the two previous academic years., Results: Weekly TTE volume declined by 54% during the pandemic, and increased by 99% during pandemic recovery, (p < 0.05). SE and TEE revealed similar trends. A strong correlation between weekly TTE volume and inpatient admissions was observed during the study period (r s =0.67, p < 0.05). Weekly fellow TTE scans declined by 78% during the pandemic, with a 380% increase during pandemic recovery (p < 0.05). Weekly fellow TTE interpretations declined by 56% during the pandemic, with a 76% increase during pandemic recovery (p < 0.05)., Conclusion: COVID restrictions between 3/15/2020- 6/14/2020 coincided with a marked decline in TTE, SE, and TEE volumes, with an increase similar to near pre-pandemic volumes during the pandemic recovery period. A similar decline with the onset of COVID restrictions, and increase to pre-restriction volumes thereafter was observed with fellow scans and interpretations, but total academic year fellow training volumes remained depressed. With the ongoing COVID-19 pandemic and rise of multiple variants, training programs may need to adjust fellows' clinical responsibilities so as to support achievement of echocardiography training certification., (© 2022. The Author(s).)

Aims: Prediction of mitral (MR) and tricuspid (TR) regurgitation progression on transthoracic echocardiography (TTE) is needed to personalize valvular surveillance intervals and prognostication., Methods and Results: Structured TTE report data at Beth Israel Deaconess Medical Center, 26 January 2000-31 December 2017, were used to determine time to progression (≥1+ increase in severity). TTE predictors of progression were used to create a progression score, externally validated at Massachusetts General Hospital, 1 January 2002-31 December 2019. In the derivation sample (MR, N = 34 933; TR, N = 27 526), only 5379 (15.4%) individuals with MR and 3630 (13.2%) with TR had progression during a median interquartile range) 9.0 (4.1-13.4) years of follow-up. Despite wide inter-individual variability in progression rates, a score based solely on demographics and TTE variables identified individuals with a five- to six-fold higher rate of MR/TR progression over 10 years (high- vs. low-score tertile, rate of progression; MR 20.1% vs. 3.3%; TR 21.2% vs. 4.4%). Compared to those in the lowest score tertile, those in the highest tertile of progression had a four-fold increased risk of mortality. On external validation, the score demonstrated similar performance to other algorithms commonly in use., Conclusion: Four-fifths of individuals had no progression of MR or TR over two decades. Despite wide interindividual variability in progression rates, a score, based solely on TTE parameters, identified individuals with a five- to six-fold higher rate of MR/TR progression. Compared to the lowest tertile, individuals in the highest score tertile had a four-fold increased risk of mortality. Prediction of long-term MR/TR progression is not only feasible but prognostically important., Competing Interests: Conflict of interest: Dr Strom additionally reports grant funding from Edwards Lifesciences, Anumana, Heartsciences, and Ultromics, consulting for Bracco Diagnostics, and speaker fees from Northwest Imaging Forums, unrelated to the submitted work. Dr Yeh reports additional grant support from Abbott Vascular, Astra Zeneca, BD Bard, Boston Scientific Cook, Philips Medical and Medtronic, and consulting fees from Abbott, AstraZeneca, Boston Scientific, Edwards Life Sciences, Medtronic, Shockwave Medical and Zoll outside the submitted work. Dr Wasfy reports grant support from the American Heart Association, National Institutes of Health, consulting fees from Pfizer and Biotronik, and honoraria from the New England Comparative Effectiveness Public Affairs Council. The remaining authors have nothing to disclose., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

The association of mitral regurgitation (MR) severity and mortality in heart failure with preserved ejection fraction (HFpEF) is uncertain. We sought to evaluate the relation between MR severity on transthoracic echocardiography (TTE) and subsequent all-cause mortality in Medicare beneficiaries with HFpEF. We linked 57,608 patients referred for TTE at Beth Israel Deaconess Medical Center to Medicare inpatient claims from 2003 to 2017. In those with a history of HF and a physician-reported left ventricular ejection fraction ≥50%, we evaluated the relation of MR severity and time to the primary end point of all-cause mortality using Kaplan-Meier methods. A total of 7,778 individuals (14.5%) met inclusion criteria (mean age 75.5 years ± 11.9, 55.9% female). Over a median follow-up of 8.1 years, 2,016 (25.9%) died at a median (interquartile range) of 1.7 (0.3 to 4.1) years. At 1 year, 15.8% with 3 to 4+ MR had died versus 10.5% with 0 to 2+ MR (hazard ratio 1.54, 95% confidence interval 1.22 to 1.95, p <0.001). After multivariable adjustment, 3 to 4+ MR continued to be associated with increased all-cause mortality (hazard ratio 1.48, 95% confidence interval 1.14 to 1.94, p = 0.004) except in the subset with atrial fibrillation (interaction p = 0.03) or recent (<3 months) HF hospitalization (p = 0.54). In conclusion, in this large, single-institution retrospective study of Medicare beneficiaries with HFpEF who underwent TTE, moderate-to-severe and severe MR were significantly associated with an increased risk of all-cause mortality after multivariable adjustment, except in those with atrial fibrillation or recent HF. Prospective studies are needed to assess the role of MR reduction in mitigating this risk., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Administrative claims for aortic stenosis (AS) regurgitation may be useful, but their accuracy and ability to identify individuals at risk for valve-related outcomes have not been well characterized., Methods: Using echocardiographic (transthoracic echocardiogram [TTE]) reports linked to US Medicare claims, 2017 to 2018, the performance of candidate International Classification of Diseases, Tenth Revision claims to ascertain AS/aortic regurgitation was evaluated. The optimal performing algorithm was tested against outcomes at 1-year after TTE in a separate 100% sample of US Medicare claims, 2017 to 2019., Results: Of those included in the derivation (N=5497, mean age 74.4±11.0 years, 49.7% female), any AS or aortic regurgitation was present in 24% and 38.8%, respectively. The sensitivity and specificity of International Classification of Diseases, Tenth Revision code I35.0 for identification of any AS was 53.1% and 94.8%, respectively. Among those with an I35.0 code, 40.3% had severe AS. Claims were unable to distinguish disease severity (ie, severe versus nonsevere) or subtype (eg, bicuspid or rheumatic AS), and were insensitive and nonspecific for aortic regurgitation of any severity. Among all beneficiaries who received a TTE (N=4 033 844), adjusting for age, sex, and 27 comorbidities, those with an I35.0 code had a higher adjusted risk of all-cause mortality (adjusted hazard ratio, 1.33 [95% CI, 1.31-1.34]), heart failure hospitalization (adjusted hazard ratio, 1.37 [95% CI, 1.34-1.41]), and aortic valve replacement (adjusted hazard ratio, 34.96 [95% CI, 33.74-36.22])., Conclusions: Among US Medicare beneficiaries receiving a TTE, International Classification of Diseases, Tenth Revision claims, though identifying a population at significant greater risk of valve-related outcomes, failed to identify nearly half of individuals with AS and were unable to distinguish disease severity or subtype. These results argue against the widespread use of International Classification of Diseases, Tenth Revision claims to screen for patients with AS and suggests the need for improved coding algorithms and alternative systems to extract TTE data for quality improvement and hospital benchmarking.

Purpose of Review: Ultrasound enhancing agents (UEAs), microbubbles which are composed of lipid or albumin shells containing high molecular weight gases with nonlinear acoustic properties in the ultrasound field, are important components of the diagnostic armamentarium in echocardiography. This review highlights the substantial value of UEAs in delineating endocardial border definition and influencing downstream decision-making in cardiovascular ultrasound., Recent Findings: In this article, we review recent updates to the clinical applications of UEAs, special circumstances regarding use, the impact of use on downstream testing and cost-effectiveness, and recommended approaches for optimizing workflow in the echocardiography laboratory with UEAs., Summary: In multiple studies, UEAs have been identified as a useful tool in echocardiography, improving study accuracy and reader confidence, while reducing downstream testing and procedures and resulting in significant changes in clinical management. Despite their proven efficacy and cost-effectiveness, recent studies have suggested utilization remains low, in part due to perceived concerns and workflow issues that impair uptake. With an increasingly broader list of indications for echocardiography, UEAs will continue to play an important role in the diagnosis and management of patients with cardiovascular and noncardiovascular diseases., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Aortic stenosis is the most common cardiac valve disorder requiring clinical management. However, there is little evidence on the societal cost of progressive aortic stenosis. We sought to quantify the societal burden of premature mortality associated with progressively worse aortic stenosis., Methods: In this observational clinical cohort study, we examined echocardiograms on native aortic valves of 98 565 men and 99 357 women aged 65 years or older across 23 sites in Australia, from Jan 1, 2003, to Dec 31, 2017. Individuals were grouped according to their peak aortic valve velocity in 0·50 m/s increments up to 4·00 m/s or more (severe aortic stenosis), using 1·00-1·99 m/s (no aortic stenosis) as the reference group. Sex-specific premature mortality and years of life lost during a 5-year follow-up were calculated, along with willingness-to-pay to regain quality-adjusted life years (QALYs)., Findings: Overall, 20 701 (21·0%) men and 18 576 (18·7%) women had evidence of mild-to-severe aortic stenosis. The actual 5-year mortality in men with normal aortic valves was 32·1% and in women was 26·1%, increasing to 40·9% (mild aortic stenosis) and 52·2% (severe aortic stenosis) in men and to 35·9% (mild aortic stenosis) and 55·3% (severe aortic stenosis) in women. Overall, the estimated societal cost of premature mortality associated with aortic stenosis was AU$629 million in men and $735 million in women. Per 1000 men and women investigated, aortic stenosis was associated with eight more premature deaths in men resulting in 32·5 more QALYs lost (societal cost of $1·40 million) and 12 more premature deaths in women resulting in 57·5 more QALYs lost (societal cost of $2·48 million) when compared with those without aortic stenosis., Interpretation: Any degree of aortic stenosis in older individuals is associated with premature mortality and QALYs. In this context, there is a crucial need for cost-effective strategies to promptly detect and optimally manage this common condition within our ageing populations., Funding: Edwards LifeSciences, National Health and Medical Research Council of Australia, and the National Heart, Lung, and Blood Institute., Competing Interests: Declaration of interests GAS and DP are the co-principal investigators and directors of the National Echo Database of Australia (NEDA; a not-for-profit research entity). NEDA has received investigator-initiated funding support from Novartis Pharmaceuticals, Pfizer Pharmaceuticals, ECHO IQ, and Edward Lifesciences in the past 3 years. SS has received consultancy fees from NEDA. SS, DP, and GAS have previously received consultancy or speaking fees from Edwards Lifesciences. DP and GAS have previously received consultancy or speaking fees from Medtronic. JBS reports grant support from Ultromics, HeartSciences, and Anumana; consulting fees from Bracco Diagnostics; and speaker fees from Northwest Imaging Forums. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

The present CEUS Cardiac Exam Protocols represent the first effort to promulgate a standard set of protocols for optimal administration of ultrasound enhancing agents (UEAs) in echocardiography, based on more than two decades of experience in the use of UEAs for cardiac imaging. The protocols reflect current clinical CEUS practice in many modern echocardiography laboratories throughout the world. Specific attention is given to preparation and dosing of three UEAs that have been approved by the United States Food and Drug Administration (FDA) and additional regulatory bodies in Europe, the Americas and Asia-Pacific. Consistent with professional society guidelines (J Am Soc Echocardiogr 31:241-274, 2018; J Am Soc Echocardiogr 27:797-810, 2014; Eur Heart J Cardiovasc Imaging 18:1205, 2017), these protocols cover unapproved "off-label" uses of UEAs-including stress echocardiography and myocardial perfusion imaging-in addition to approved uses. Accordingly, these protocols may differ from information provided in product labels, which are generally based on studies performed prior to product approval and may not always reflect state of the art clinical practice or guidelines., (© 2022. The Author(s).)

Background: Despite improvements in the safety of transcatheter aortic valve implantation (TAVI), ~4% of patients experience a procedure-related stroke. Understanding long-term health and healthcare implications of these events may motivate the development and adoption of preventative strategies.  Aims: We aimed to assess the association of TAVI-related ischaemic stroke with subsequent clinical outcomes and healthcare utilisation., Methods: We used Medicare fee-for-service claims to identify patients who underwent their first TAVI between January 2012 and December 2017. Previously used ICD-9-CM and ICD-10-CM codes were used to identify TAVI-related ischaemic stroke. Among those with and without TAVI-related ischaemic stroke, we compared the risk of a composite endpoint that included all-cause mortality, acute myocardial infarction, and subsequent stroke using inverse probability treatment weighted Cox regression. We also performed a difference-in-difference analysis to compare 1-year Medicare expenditures and days spent at home during the first year after TAVI., Results:  Among 129,628 primary TAVI patients, 5,549 (4.3%) had a procedure-related stroke. These patients were more likely to be female and have had prior stroke, peripheral vascular disease, ischaemic heart disease, or renal failure. After adjustment, TAVI-related ischaemic stroke was associated with a higher risk of the 1-year composite outcome (HR 1.67, 95% CI: 1.56-1.78), higher 1-year Medicare expenditures (difference $9,245 [standard error 790], p<0.001), and fewer days at home during the first year (difference 16 days [standard error 1], p<0.001)., Conclusions: Among Medicare beneficiaries undergoing TAVI, procedure-related ischaemic stroke was associated with worse outcomes, increased Medicare expenditures, and less time spent at home. Procedure-related ischaemic stroke during TAVI remains a critically important and potentially preventable source of patient mortality, morbidity and healthcare utilisation.

Background: As automated echocardiographic analysis is increasingly utilized, continued evaluation within hospital settings is important to further understand its potential value. The importance of cardiac involvement in patients hospitalized with COVID-19 provides an opportunity to evaluate the feasibility and clinical relevance of automated analysis applied to limited echocardiograms., Methods: In this multisite US cohort, the feasibility of automated AI analysis was evaluated on 558 limited echocardiograms in patients hospitalized with COVID-19. Reliability of automated assessment of left ventricular (LV) volumes, ejection fraction (EF), and LV longitudinal strain (LS) was assessed against clinically obtained measures and echocardiographic findings. Automated measures were evaluated against patient outcomes using ROC analysis, survival modeling, and logistic regression for the outcomes of 30-day mortality and in-hospital sequelae., Results: Feasibility of automated analysis for both LVEF and LS was 87.5% (488/558 patients). AI analysis was performed with biplane method in 300 (61.5%) and single plane apical 4- or 2-chamber analysis in 136 (27.9%) and 52 (10.7%) studies, respectively. Clinical LVEF was assessed using visual estimation in 192 (39.3%), biplane in 163 (33.4%), and single plane or linear methods in 104 (21.2%) of the 488 studies; 29 (5.9%) studies did not have clinically reported LVEF. LV LS was clinically reported in 80 (16.4%). Consistency between automated and clinical values demonstrated Pearson's R, root mean square error (RMSE) and intraclass correlation coefficient (ICC) of 0.61, 11.3% and 0.72, respectively, for LVEF; 0.73, 3.9% and 0.74, respectively for LS; 0.76, 24.4ml and 0.87, respectively, for end-diastolic volume; and 0.82, 12.8 ml, and 0.91, respectively, for end-systolic volume. Abnormal automated measures of LVEF and LS were associated with LV wall motion abnormalities, left atrial enlargement, and right ventricular dysfunction. Automated analysis was associated with outcomes, including survival., Conclusion: Automated analysis was highly feasible on limited echocardiograms using abbreviated protocols, consistent with equivalent clinically obtained metrics, and associated with echocardiographic abnormalities and patient outcomes., (Copyright © 2022 Pellikka, Strom, Pajares-Hurtado, Keane, Khazan, Qamruddin, Tutor, Gul, Peterson, Thamman, Watson, Mandale, Scott, Naqvi, Woodward and Hawkes.)

Background: While large scientific and medical evidence has demonstrated the increased risk of death and cardiovascular mortality in patients with severe AS, the independent contribution of moderate AS to an increased risk of death remains uncertain., Methods and Findings: We conducted a multicenter study including a cohort of 30,865 US patients and another cohort of 217,599 Australian patients with equivalent echocardiographic and aortic valve profiling over the same period (2003-2017). During a median 5.2 years (US) and 4.4 years (Australian) follow-up, the risk of death (hazard ratio) of patients with moderate AS as compared to those without AS was 1.66 (95%CI 1.52-1.80) and 1.37 (95%CI 1.34-1.41) in the US and Australian cohorts, even after adjusting this analysis for age and sex. This increased risk of death and cardiovascular mortality (odds ratio) in patients with moderate AS was consistent also across subgroups of left ventricular ejection fraction (LVEF) (subgroups of LVEF < 40%, 40-49%, 50-59%, and ≥ 60%: OR of moderate AS for CV mortality 2.0 [95%CI 1.4-2.7], 1.7 [95%CI 1.2-2.4], 1.5 [95%CI 1.1-1.9], and 1.4 [95%CI 1.2-1.6], respectively)., Conclusions: The findings of this study suggest that patients with moderate AS have a potential increased risk of death and cardiovascular mortality, regardless of age, sex, and LVEF. Hence, these data suggest the need to develop specific strategies to detect and treat individuals with moderate AS., Competing Interests: Dr. Strom additionally reports grant funding from the NIH/NHLBI, Ultromics, HeartSciences, and Anumana, consulting for Bracco Diagnostics, and speaker honoraria from Northwest Imaging Forums. Dr. Strange reports consulting for Edwards Lifesciences. Changyu Shen is currently an employee of Biogen. All other authors report no relevant disclosures.