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Background: Candidates for transcatheter aortic valve replacement (TAVR) occasionally have a "borderline-size" aortic annulus between 2 transcatheter heart valve sizes, based on the manufacturer's sizing chart. Data on TAVR outcomes in such patients are limited., Methods: We retrospectively reviewed 1816 patients who underwent transfemoral-TAVR with balloon-expandable valve (BEV) at our institution between 2016 and 2020. We divided patients into borderline and non-borderline groups based on computed tomography-derived annular measurements and compared outcomes. Furthermore, we analyzed procedural characteristics and compared outcomes between the smaller- and larger-valve strategies in patients with borderline-size annulus., Results: During a median follow-up of 23.3 months, there was no significant difference between the borderline (n = 310, 17.0 %) and non-borderline (n = 1506) groups in mortality (17.3 % vs. 19.5 %; hazard ratio [HR] = 0.86 [95% CI = 0.62-1.20], p = 0.39), major adverse cardiac/cerebrovascular events (MACCE: death/myocardial infarction/stroke, 21.2 % vs. 21.5 %; HR = 0.97 [0.71-1.32], p = 0.85), paravalvular leak (PVL: mild 21.8 % vs. 20.6 %, p = 0.81; moderate 0 % vs. 1.2 %; p = 0.37), or mean gradient (12.9 ± 5.8 vs. 12.6 ± 5.2 mmHg, p = 0.69) at 1 year. There was no significant difference between the larger-(n = 113) and smaller-valve(n = 197) subgroups in mortality (23.7 % vs. 15.2 %; HR = 1.57 [0.89-2.77], p = 0.12), MACCE (28.1 % vs. 18.4 %; HR = 1.52 [0.91-2.54], p = 0.11), mild PVL (13.3 % vs. 25.9 %; p = 0.12), or mean gradient (12.3 ± 4.5 vs. 13.6 ± 5.3 mmHg, p = 0.16); however, the rate of permanent pacemaker implantation (PPI) was higher in the larger-valve subgroup (15.9 % vs. 2.6 %, p < 0.001)., Conclusion: Borderline-size annulus is not associated with higher risk of adverse outcomes after BEV-TAVR. However, the larger-valve strategy for borderline-size annulus is associated with higher PPI risk, suggesting a greater risk of injury to the conduction system., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Echocardiography, in all its forms (transthoracic echocardiography [TTE], transesophageal echocardiography [TEE], and intracardiac echocardiography [ICE]), is pivotal for the evaluation, guidance, and follow-up of transcatheter tricuspid edge-to-edge repair (TV-TEER) therapies. Although two-dimensional (2D) echocardiography remains essential, three-dimensional (3D) echo with multiplanar reconstruction (MPR) has revolutionized the field of structural imaging. In addition, the advent of 3D ICE has added an important modality to the imaging toolbox, particularly helpful when intraprocedural TEE images are challenging. In this review, we provide a detailed, step-by-step approach for advanced echocardiographic guidance of TV-TEER using 3D MPR., Competing Interests: Disclosure None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The CLASP IID randomized trial (Edwards PASCAL TrAnScatheter Valve RePair System Pivotal Clinical Trial) demonstrated the safety and effectiveness of the PASCAL system for mitral transcatheter edge-to-edge repair (M-TEER) in patients at prohibitive surgical risk with significant symptomatic degenerative mitral regurgitation (DMR)., Objectives: This study describes the echocardiographic methods and outcomes from the CLASP IID trial and analyzes baseline variables associated with residual mitral regurgitation (MR) ≤1+., Methods: An independent echocardiographic core laboratory assessed echocardiographic parameters based on American Society of Echocardiography guidelines focusing on MR mechanism, severity, and feasibility of M-TEER. Factors associated with residual MR ≤1+ were identified using logistic regression., Results: In 180 randomized patients, baseline echocardiographic parameters were well matched between the PASCAL (n = 117) and MitraClip (n = 63) groups, with flail leaflets present in 79.2% of patients. Baseline MR was 4+ in 76.4% and 3+ in 23.6% of patients. All patients achieved MR ≤2+ at discharge. The proportion of patients with MR ≤1+ was similar in both groups at discharge but diverged at 6 months, favoring PASCAL (83.7% vs 71.2%). Overall, patients with a smaller flail gap were significantly more likely to achieve MR ≤1+ at discharge (adjusted OR: 0.70; 95% CI: 0.50-0.99). Patients treated with PASCAL and those with a smaller flail gap were significantly more likely to sustain MR ≤1+ to 6 months (adjusted OR: 2.72 and 0.76; 95% CI: 1.08-6.89 and 0.60-0.98, respectively)., Conclusions: The study used DMR-specific echocardiographic methodology for M-TEER reflecting current guidelines and advances in 3-dimensional echocardiography. Treatment with PASCAL and a smaller flail gap were significant factors in sustaining MR ≤1+ to 6 months. Results demonstrate that MR ≤1+ is an achievable benchmark for successful M-TEER. (Edwards PASCAL TrAnScatheter Valve RePair System Pivotal Clinical Trial [CLASP IID]; NCT03706833)., Competing Interests: Funding Support and Author Disclosures The CLASP IID trial is funded by Edwards Lifesciences. Dr Marcoff has served as a member of the echocardiography core laboratory for Edwards Lifesciences, Abbott, and Medtronic, with no direct compensation. Dr Koulogiannis has served as a consultant and advisory board member for Edwards Lifesciences; has served as a speaker for Abbott; has served as a member of the echocardiography core laboratory for Edwards Lifesciences, Abbott, and Medtronic, with no direct compensation. Dr Lilian Aldaia has served as a member of the echocardiography core laboratory for Edwards Lifesciences, Abbott, and Medtronic, with no direct compensation. Dr Mediratta has served as a member of the echocardiography core laboratory for Edwards Lifesciences, Abbott, and Medtronic, with no direct compensation. Dr Chadderdon has served as a consultant for Edwards Lifesciences and Medtronic; and has received research grants from GE Healthcare. Dr Makar has served as a consultant for Boston Scientific and Abbott Vascular. Dr Ruf has received speaker, consulting, and proctoring fees from Abbott Laboratories and Edwards Lifesciences. Dr Nabauer has received speaker, consulting, and proctoring fees from Edwards Lifesciences. Dr Grayburn has received research grants from Abbott Vascular, Boston Scientific, Cardiovalve, Edwards Lifesciences, Medtronic, Neochord, W. L. Gore and Associates, and 4C Medical; and has also served as a consultant and advisory board member for Abbott Vascular, Cardiovalve, Edwards Lifesciences, Medtronic, W. L. Gore and Associates, and 4C Medical. Dr Vannan has received research grants and speaker honoraria from Piedmont Heart Institute for Abbott, Medtronic, Edwards Lifesciences, Philips, Siemens Healthineers, and GE Healthcare. Dr Ender has received institutional honoraria from Edwards Lifesciences, Abbott, and Medela, with no direct compensation. Dr Puthumana has served on the Speakers Bureau and as a training consultant for Abbott Structural and Edwards Lifesciences. Dr Mansoor has served as a consultant for Atricure. Dr Hahn has received speaker fees from Abbott Structural, Baylis Medical, Edwards Lifesciences, and Philips Healthcare; has stock options with Navigate; has held institutional consulting contracts with Abbott Structural, Boston Scientific, Edwards Lifesciences, Medtronic, and Novartis; and has served as a Chief Scientific Officer for the echocardiography core laboratory at the Cardiovascular Research Foundation for multiple industry-sponsored trials, with no direct industry compensation for either. Dr Mahmood has served as a consultant for education materials for Abbott Medical and GE Ultrasound. Dr Haeffele has served as a consultant to Edwards Lifesciences. Dr Ong has received speaker fees from Abbott. Dr Schneider has served as a speaker, proctor, and advisor for Edwards Lifesciences and Abbott; and has served as an advisor for Boehringer and Lilly. Dr D. Wang has served as a consultant to Edwards Lifesciences, Abbott Vascular, Materialise, and Boston Scientific. Dr Koss has served as an educational speaker for Abbott and Edwards Lifesciences. Dr Harb has served as a consultant for Abbott, Boston Scientific, and Mitria. Dr Miyasaka has served as a consultant for Abbott. Dr Ivannikova has received speaker fees from Edwards Lifesciences. Dr Mitchel has served on the Abbott Speakers Bureau. Dr Raissi has served as a consultant for Abbott. Dr Kalbacher has received proctor fees from Edwards Lifesciences and PiCardia Ltd; and has received lecture fees from Edwards Lifesciences and Abbott Medical. Dr Ho has served as an advisor for Neochord, Half Moon Medical, and Valgen; and has held institutional consulting contracts with GE Healthcare and Edwards Lifesciences. Dr Smith has served in clinical trial leadership and has received institutional grant and travel support for device evaluation from Edwards Lifesciences; has received institutional grants from Artivion; and has received speaker honoraria from Artivion and Medtronic. Dr Hausleiter has served as a consultant and has received speaker honoraria and institutional research support from Edwards Lifesciences. Dr Lim has served as a consultant for Ancora, LagunaTech, Nyra, Opus, Philips, Venus, and Valgen; and has received research grants from Abbott, Boston Scientific, Edwards Lifesciences, and Medtronic. Dr Gillam has served as a consultant for Philips, Bracco, Edwards Lifesciences, and Medtronic; and has institutional echocardiography core laboratory contracts from Abbott, Edwards Lifesciences, and Medtronic, with no direct compensation. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Structural heart disease interventions rely heavily on preprocedural planning and simulation to improve procedural outcomes and predict and prevent potential procedural complications. Modeling technologies, namely 3-dimensional (3D) printing and computational modeling, are nowadays increasingly used to predict the interaction between cardiac anatomy and implantable devices. Such models play a role in patient education, operator training, procedural simulation, and appropriate device selection. However, current modeling is often limited by the replication of a single static configuration within a dynamic cardiac cycle. Recognizing that health systems may face technical and economic limitations to the creation of "in-house" 3D-printed models, structural heart teams are pivoting to the use of computational software for modeling purposes., Competing Interests: Funding Support and Author Disclosures Dr Harb has received consulting fees from Abbott, Boston Scientific, and Mitria Medical LLC. Dr Wang is a consultant for Edwards Lifesciences, Abbott, Boston Scientific, and Materialise; and has received research grant support from Boston Scientific assigned to employer Henry Ford Health. Dr Little has received support from the John S. Dunn Chair in Clinical Cardiovascular Research and Education. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: There are limited data on the sex differences in the hemodynamic progression and outcomes of early-stage aortic stenosis (AS)., Objectives: The authors sought to determine sex differences in hemodynamic progression and outcomes of mild to moderate native AS., Methods: This was a retrospective observational cohort study including patients with mild to moderate native tricuspid AS from the Cleveland Clinic echocardiographic database between 2008 and 2016 and followed until 2018. All-cause mortality, aortic valve replacement (AVR), and disease progression assessed by annualized changes in echocardiographic parameters were analyzed based on sex., Results: The authors included 2,549 patients (mean age, 74 ± 7 years and 42.5% women) followed over a median duration of 5.7 years. There was no difference in all-cause mortality between sexes irrespective of age, baseline disease severity, progression to severe AS, and receipt of AVR. Relative to men, women had similar all-cause mortality but lower risk of AVR (adjusted HR: 0.81 [95% CI: 0.67-0.91]; P = 0.009) at 10 years. On 1:1 propensity-matched analysis, men had a significantly faster disease progression represented by greater increases in the median of annualized change in mean gradient (2.10 vs 1.15 mm Hg/y, respectively, P < 0.001), maximum transvalvular velocity (0.42 vs 0.28 m/s/y), left ventricular end-diastolic diameters (0.15 vs 0.048 mm/m 2.7 /y) (P = 0.014). Women have significantly higher left ventricular ejection fraction, filling pressures, and left ventricular septum thickness over time on follow-up echocardiograms compared with men., Conclusions: Women with mild to moderate AS had slower hemodynamic progression of AS, were more likely to have preserved left ventricular ejection fraction and concentric left ventricular hypertrophy in addition to lower incidence of AVR compared with men despite similar mortality. These findings provide further evidence that there are distinct sex-specific longitudinal echocardiographic and clinical profiles in patients with AS., Competing Interests: Funding Support and Author Disclosures This work was supported by unrestricted philanthropic support to the Cleveland Clinic Heart, Vascular, and Thoracic Institute. The funders had no role in the design or conduct of the study; the collection, management, analyses, or interpretation of the data; the preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The Ozaki procedure using autologous pericardium is an interesting but complex alternative for aortic valve replacement. We present a standardized approach to minimize the learning curve and confirm reproducibility., Methods: After careful preparation, from May 2015 to February 2021, an Ozaki procedure was performed on 46 patients age 51 ± 14 years. Seven had unicuspid (15%), 29 bicuspid (63%), and 10 tricuspid (22%) aortic valves, and 2 patients had endocarditis. Endpoints were operative learning curves, perioperative outcomes, intermediate-term valve hemodynamics, reintervention, health-related quality of life (MacNew Heart Disease Health-Related Quality of Life questionnaire), and mortality., Results: Cardiopulmonary bypass and aortic clamp times decreased from 145 to 125 ​minutes and 120 to 100 ​minutes, respectively, over the first 20 cases, reflecting the learning curve. There was no major perioperative morbidity or mortality. Median postoperative stay was 6.9 days. Aortic regurgitation was mild or less in all but 2 patients who developed moderate aortic regurgitation. Mean aortic valve gradient was 7.9 mmHg postoperatively, 9.2 mmHg by 6 months, and constant thereafter. Left ventricular ejection fraction was 58% preoperatively, 60% at 6 months, and remained stable thereafter. One patient developed infective endocarditis 7 months postoperatively, failed medical management, and underwent valve replacement at 14 months. Two-year survival was 96%, with 1 noncardiac death at 16 months. Health-related quality of life in mental, physical, and emotional domains was better than matched norms, global 6.2 vs. 5.0 ( p < 0.0001)., Conclusions: Using a well-prepared standardized approach, the Ozaki procedure is reproducible with a short learning curve, excellent hemodynamic performance, and good quality of life., Competing Interests: Dr Blackstone had statistical consultation related to valve trials with Edwards Lifesciences and Abiomed. The other authors had no conflicts to declare., (© 2023 The Author(s).)

Background: Computed tomography angiography (CTA) and invasive coronary angiography (ICA) are routinely performed before transcatheter aortic valve replacement (TAVR) to assess aortic root anatomy and screen for coronary artery disease (CAD), respectively., Objectives: This study explored the efficacy of CTA as a screening tool for significant proximal CAD before TAVR., Methods: With proper ethical oversight, patients undergoing TAVR at Cleveland Clinic with a preprocedural CTA and invasive coronary angiography (ICA), and no prior percutaneous intervention, were identified from 2015 to 2021. Blinded to ICA results, the authors reviewed the left main, proximal left anterior descending coronary artery, proximal left circumflex coronary artery, and proximal right coronary artery by CTA coronary reconstruction to assess for nonsignificant stenosis (0% to 49%), moderate stenosis (50% to 69%), and severe stenosis (≥70%). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and Cohen Kappa statistic were analyzed., Results: 2,217 patients (53.4% male, age 79.2 ± 8.5 years) met inclusion criteria. CTA evaluation revealed a sensitivity of 90%, specificity of 92%, PPV of 74%, and NPV of 97% for detecting ≥50% stenosis. Using a ≥70% stenosis cutoff, evaluation revealed a sensitivity of 91%, specificity of 97%, PPV of 83%, and NPV of 99%. Assessment of bypass graft patency revealed a sensitivity of 86%, specificity of 97%, PPV of 84%, and NPV of 98%. Cohen Kappa analysis indicated substantial to near perfect agreement between pre-TAVR CTA and ICA., Conclusions: Pre-TAVR CTA has a high NPV for high-grade proximal stenosis of each coronary artery. As a result, CTA can be used as a screening tool to rule out significant proximal CAD in patients undergoing TAVR., Competing Interests: Funding Support and Author Disclosures This study was supported by the Department of Cardiovascular Medicine and the Heart, Vascular, and Thoracic Institute at Cleveland Clinic. The 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.)

Competing Interests: The authors report no conflict of interest.

Background: Invasive coronary angiography (ICA) is the traditional screening modality for cardiac allograft vasculopathy (CAV). Positron emission tomography/computed tomography (PET/CT) scan with myocardial blood flow (MBF) quantification has emerged as a potential noninvasive alternative., Objectives: The aim of the study was to validate the diagnostic and prognostic value of a previously published algorithm for diagnosing CAV via PET/CT scans with MBF in a larger population. The study also sought to assess the downstream use of ICA when using PET/CT scanning as a screening modality., Methods: Patients with heart transplantation without prior revascularization who underwent PET/CT scans with MBF were identified retrospectively. The accuracy of the algorithm was assessed in patients who underwent PET/CT scanning within 1 year of ICA. The prognostic value was assessed via a composite outcome of heart failure hospitalization, myocardial infarction, retransplantation, and all-cause mortality., Results: A total of 88 patients for the diagnostic portion and 401 patients for the prognostic portion were included. PET CAV 0 had high negative predictive value for moderate to severe CAV (97%) and PET CAV 2/3 had a high positive predictive value for moderate to severe CAV (68%) by ICA. The cohort was followed for a median of 1.2 (IQR: 1.0-1.8) years with 46 patients having an adverse event. The annualized event rates were 6.9%, 9.3%, and 30.8% for PET CAV 0, 1, and 2/3, respectively (P < 0.001)., Conclusions: An algorithm using PET/CT scanning with MBF demonstrates high a negative predictive value for CAV. PET CAV 2/3 is associated with a higher risk of adverse events and need for revascularization. PET/CT scanning with MBF is a reasonable alternative to ICA for screening for CAV., 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 © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Transcatheter mitral valve repair (TMVr) has shown to reduce heart failure (HF) rehospitalization and all cause mortality. However, the 30-day all-cause readmission remains high (∼15%) after TMVr. Therefore, we sought to develop and validate a 30-day readmission risk calculator for TMVr. Nationwide Readmission Database from January 2014 to December 2017 was utilized. A linear calculator was developed to determine the probability for 30-day readmission. Internal calibration with bootstrapped calculations was conducted to assess model accuracy. The root mean square error and mean absolute error were calculated to determine model performance. Of 8339 patients who underwent TMVr, 1246 (14.2%) were readmitted within 30 days. The final 30-day readmission risk prediction tool included the following variables: Heart failure, Atrial Fibrillation, Anemia, length of stay ≥4 days, Acute kidney injury (AKI), and Non-Home discharge, Non-Elective admission and Bleeding/Transfusion. The c-statistic of the prediction model was 0.63. The validation c-statistic for readmission risk tool was 0.628. On internal calibration, our tool was extremely accurate in predicting readmissions up to 20%. A simple and easy to use risk prediction tool identifies TMVr patients at increased risk of 30-day readmissions. The tool can guide in optimal discharge planning and reduce resource utilization., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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.

Study Objective: Data is scarce regarding which dialysis modality portends more severe cardiac valvular calcification (CVC). Our aim was to compare the degree of CVC in hemodialysis (HD) and peritoneal dialysis (PD) patient cohorts prior to open heart surgery (OHS) using a CT calcium score., Design Setting and Participants: Dialysis patients who underwent OHS at our institution from 2009 to 2019 and who had pre-surgical cardiac CT were included in our study. We obtained duration of dialysis modality prior to their surgical date. There were two study cohorts to evaluate outcomes of interest: mitral and aortic calcification. CVC was assessed using the Agatston score. Logistic regression was performed to test for the association of PD and HD cumulative dialysis duration with presence of CVC., Results: A total of 214 and 166 patients met inclusion for the mitral and aortic strata, respectively. Age, female sex, and BMI were associated with higher odds of presence of mitral calcification. Age and BMI were associated with higher odds of presence of aortic calcification, while female sex was associated with lower odds in the aortic strata. Cumulative years on PD and cumulative years on HD were not significantly associated with presence of CVC in either cohort., Conclusion: Presence of mitral and aortic calcification for patients undergoing OHS was not significantly associated with cumulative length of PD or HD after adjusting for age, gender, and BMI suggesting that there may be more factors at play in the progression of CVC in end stage renal disease patients than what was previously established., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this manuscript., (© 2022 The Authors.)

Degenerative calcific aortic stenosis (AS) is the most common valvular heart disease and often co-exists with left ventricular (LV) systolic dysfunction at the time of diagnosis. Impaired LV systolic function has been associated with worse outcomes in the setting of AS, even after successful aortic valve replacement (AVR). Myocyte apoptosis and myocardial fibrosis are the 2 key mechanisms responsible for the transition from the initial adaptation phase of LV hypertrophy to the phase of heart failure with reduced ejection fraction. Novel advanced imaging methods, based on echocardiography and cardiac magnetic resonance imaging, can detect LV dysfunction and remodeling at an early and reversible stage, with important implications for the optimal timing of AVR especially in patients with asymptomatic severe AS. Furthermore, the advent of transcatheter AVR as a first-line treatment for AS with excellent procedural outcomes, and evidence that even moderate AS portends worse prognosis in heart failure with reduced ejection fraction patients, has raised the question of early valve intervention in this patient population. With this review, we describe the pathophysiology and outcomes of LV systolic dysfunction in the setting of AS, present imaging predictors of LV recovery after AVR, and discuss future directions in the treatment of AS extending beyond the traditional indications defined in the current guidelines., Competing Interests: Dr Trejeeve Martyn receives research support from Ionis Therapeutics and is an advisor to Recora Health. The other authors have no conflicts to declare., (© 2022 The Author(s).)

Background: Recently, the hemodynamic gain index (HGI) has shown to be a strong independent predictor of all-cause mortality and associated with metabolic equivalents (METs) in a cohort of male patients. However, the prognostic implications of the HGI have never been externally validated with subgroup analyses based on gender, body mass index (BMI) of 35 kg/m 2 , history of heart failure (HF), coronary artery disease (CAD) and beta-blocker use., Methods: We identified 126,356 consecutive patients undergoing treadmill exercise testing between January 1st, 1991 and February 27th, 2015. HGI was calculated using the formula: [(SBP peak × HR peak ) - (SBP rest × HR rest )] / (SBP rest × HR rest ). Cox regression models were used to determine the associations between HGI quartiles and all-cause mortality with adjustment for cardiovascular risk factors and exercise testing parameters., Results: Mean age was 53.5 ± 12.6 years. There were 74,724 (59.1 %) male, 5940 (4.7 %) HF, 21,123 (16.7 %) CAD, and 30,568 (24.2 %) beta-blocker-using patients. During the median follow up of 7.1 years, 9929 (7.9 %) died. Median HGI was 1.93 (interquartile range [IQR] 1.40-2.54) bpm/mmHg. After adjustment for the covariates, lower HGI was independently associated with all-cause mortality in the entire cohort (quartile 1 vs 4, adjusted hazard ratio [95 % confidence interval] 1.33 [IQR 1.21-1.45], p < 0.001), and subgroups of men, women, patients with body mass index <35 kg/m 2 , with and without HF, CAD, and beta-blocker use. The HGI also correlates well with METs in every subgroup., Conclusions: The HGI is a strong predictor of long-term mortality independently of traditional cardiovascular risk factors, and exercise performance across patient subgroups., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Tang is a consultant for Sequana Medical A.V., Cardiol Therapeutics Inc., Genomics plc, Zehna Therapeutics Inc., and has received honorarium from Springer Nature for authorship/editorship and American Board of Internal Medicine for exam writing committee participation - all unrelated to the subject and contents of this paper. Dr. Grodin is a consultant for Pfizer, Eidos, Alnylam, and Sarepta - all unrelated to the subject and contents of this paper.

Background: MitraClip (MC) implantation is the recommended treatment for severe symptomatic mitral regurgitation in patients not responding to medical therapy and at prohibitive surgical risk. It is important to quantify immediate mortality during postdischarge-to-30-day period so as to improve the procedural outcomes. Hence, we aim to identify the incidence of postdischarge-to-30-day mortality and its associated predictors using the technique of meta-analysis., Methods: We searched Medline, Embase, and Cochrane CENTRAL databases from inception until July 3, 2019 for studies reporting mortality prior to discharge, at 30 days and 1 year after MC implantation. The primary outcome was postdischarge-to-30-day all-cause mortality., Results: Of 2394 references, 15 studies enrolling 7498 patients were included. Random effects analysis showed that all-cause cumulative inpatient, 30-day, and 1-year mortality was 2.40% (2.08, 2.77; I 2 = 0%), 4.31% (3.64, 5.09, I 2 = 41.9%), and 20.71% (18.32; 23.33, I 2 = 81.5%), respectively. The postdischarge-to-30-day mortality was 1.70% (95% confidence interval: 1.0, 2.70; I 2 = 84%). A total of 71.50% of deaths (95% confidence interval: 36.80-91.50, I 2 = 63%) in the postdischarge-to-30-day period were due to cardiac etiology. On meta-regression, pre-MC left ventricular ejection fraction ( p = 0.003), Log.Euroscore ( p = 0.047), Society of Thoracic Surgeons Predicted Risk of Mortality ( p < 0.001), and prolonged ventilation >48 ​hours ( p < 0.001) were found to be its significant predictors., Conclusions: Our meta-analysis reports an additional mortality of ∼2% immediately after MC implantation during the postdischarge-to-30-day period. Majority of deaths occurred due to cardiac causes. Pre-MC left ventricular ejection fraction, Log.Euroscore, Society of Thoracic Surgeons Predicted Risk of Mortality score, and prolonged ventilation were found to be its significant predictors. Further studies are needed to better understand the causes of this early mortality to maximize benefits of this important therapy., Competing Interests: The authors report no conflict of interest., (© 2022 The Authors.)

Background: Cardiorespiratory fitness (CRF) varies with sex and is an independent predictor of mortality. We sought to investigate sex differences in the exercise protocol selected, CRF levels, and their relationships with long term all-cause mortality., Methods: In a 25-year stress testing registry spanning from 1991 to 2014, consecutive all-comer patients who underwent exercise stress testing at Cleveland Clinic were categorized by sex, stress protocol and imaging modality. All tests were conducted by one or more of stress test technicians, sonographers and nuclear medicine technologists, and interpreted by cardiologists. The primary outcome all-cause mortality was analyzed in using multivariable Cox regression., Results: In 120,705 patients, the mean age was 53.3 ± 12.5 years, and 41% were female. Females were more commonly referred for non-Bruce exercise protocols (modified Bruce, Cornell 0, 5 and 10, Naughton and modified Naughton) with odds ratio of 2.62; 95% confidence interval (95%CI) (2.54-2.70) after adjusting for age and comorbidities. When also adjusting for the protocol chosen, females achieved lower CRF with beta -1.40, 95% CI (-1.43, -1.37). There were 8426 (6.9%) deaths during a mean follow-up of 8.7 years. Both female sex and CRF were independently associated with lower all-cause mortality with hazards ratio (95%CI) of 0.44 (0.41-0.46) and 0.41 (0.39-0.42) respectively, after adjusting for age, co-morbidities and protocol chosen., Conclusions: Women were more likely referred for less demanding exercise protocols, more imaging protocols and achieved lower CRF than men. Despite this, female sex was associated with significantly lower long term mortality for equivalent CRF level in adjusted analyses., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Mitral annular disjunction (MAD) is an increasingly recognized entity associated with mitral valve prolapse (MVP), ventricular arrhythmias and death. Few studies have investigated the utility of myocardial deformation analysis in MAD. We compared chamber quantification including strain by transthoracic echocardiography (TTE) and cardiac magnetic resonance imaging (CMR) between MVP patients with and without MAD., Methods: Forty-two patients with MVP (21 with MAD, 21 without MAD) and 21 controls were studied. Global, basal and basal inferolateral (BIL) segmental strains were measured and compared using velocity-vector imaging TTE and feature-tracking CMR., Results: Mean age was 54 ± 17 years, 19 (46%) were female, and 19 (46%) underwent surgical mitral valve repair with no deaths during follow-up in the 2 groups with MVP. Patients with MAD and MVP had lower basal longitudinal strain by TTE than those with MVP without MAD. Those with MAD and MVP had lower magnitude in BIL and basal segments by circumferential and radial strain by CMR compared to those with MVP without MAD and controls. Amongst global strain parameters, CMR-derived global circumferential strain was independently associated with MAD diagnosis odds ratio 1.49 (per 1%), 95% confidence interval 1.09-2.05, P = 0.014, with optimal threshold of -18.0% having 76% sensitivity and specificity for MAD., Conclusion: Abnormal circumferential and radial strain patterns in the basal segments by CMR may be useful for identifying regional LV dysfunction associated with MAD., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objectives: This study was designed to compare the clinical and echocardiographic characteristics, management, and outcomes of severe atrial functional mitral regurgitation (AFMR) to primary mitral regurgitation (PMR)., Background: AFMR remains poorly defined clinically., Methods: Consecutive patients who underwent transesophageal echocardiography at our institution between 2011 and 2018 for severe mitral regurgitation with preserved left ventricular function were screened. We excluded patients with endocarditis, any form of cardiomyopathy, or prior mitral intervention. The absence of leaflet pathology defined AFMR. Outcomes included death and heart failure hospitalizations., Results: A total of 283 patients were included (AFMR = 14%, PMR = 86%). Compared to PMR, patients with AFMR had more comorbidities, including hypertension (94.9% vs. 76.2%; p = 0.015), diabetes mellitus (46.2% vs. 18.4%; p < 0.001), long-standing atrial fibrillation (28.2% vs. 13.1%; p = 0.015), prior nonmitral cardiac surgery (25.6% vs. 9.8%; p = 0.004), and pacemaker placement (33.3% vs. 13.5%; p = 0.002). They also had higher average E/e' (median [interquartile range]:16.04 [13.1 to 22.46] vs. 14.1 [10.89 to 19]; p = 0.036) and worse longitudinal left atrial strain peak positive value (16.86 ± 12.15% vs. 23.67 ± 14.09%; p = 0.002) compared to PMR. During follow-up (median: 22 months), patients with AFMR had worse survival (log-rank p = 0.009) and more heart failure hospitalizations (log-rank p = 0.002). They were also less likely to undergo mitral valve intervention (59.0% vs. 83.6%; p = 0.001), although surgery was associated with improved survival (log-rank p = 0.021). On multivariable regression analysis, AFMR was independently associated with mortality [adjusted odds ratio: 2.61, 95% confidence interval: 1.17 to 5.83; p = 0.02]., Conclusions: AFMR constitutes an under-recognized high-risk group, with significant comorbidities, limited therapeutic options, and poor outcomes., 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.)

Transcatheter aortic valve replacement (TAVR) is a safe and feasible alternative to surgery in patients with symptomatic severe aortic stenosis regardless of the surgical risk. Conduction abnormalities requiring permanent pacemaker (PPM) implantation remain a common finding after TAVR due to the close proximity of the atrioventricular conduction system to the aortic root. High-grade atrioventricular block and new onset left bundle branch block (LBBB) are the most commonly reported conduction abnormalities after TAVR. The overall rate of PPM implantation after TAVR varies and is related to pre-procedural and intraprocedural factors. The available literature regarding the impact of conduction abnormalities and PPM requirement on morbidity and mortality is still conflicting. Pre-procedural conduction abnormalities such as right bundle branch block and LBBB have been linked with increased PPM implantation and mortality after TAVR. When screening patients for TAVR, heart teams should be aware of various anatomical and pathophysiological conditions that make patients more susceptible to increased risk of conduction abnormalities and PPM requirement after the procedure. This is particularly important as TAVR has been recently approved for patients with low surgical risk. The purpose of this review is to discuss the incidence, predictors, impact, and management of the various conduction abnormalities requiring PPM implantation in patients undergoing TAVR., Competing Interests: 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.)

Objectives: The aim of this study was to assess the impact of atrial fibrillation (AF) on mortality and efficacy in patients with functional mitral regurgitation (FMR) undergoing MitraClip implantation., Background: AF is a common arrhythmia in patients with severe FMR undergoing transcatheter mitral valve repair with the MitraClip device. Although AF has been consistently shown to be associated with poor outcomes after mitral valve surgery, the impact of AF on outcomes of MitraClip placement in patients with FMR has not been well studied., Methods: Prospective, retrospective registries, observational studies, and randomized controlled trials on MitraClip reporting AF and FMR as one of the variables from inception until January 2019 were included., Results: Of the initial 1,694 studies, 15 studies met the inclusion criteria. From a total of 5,184 patients, 2,105 patients were identified to have FMR and AF. All-cause 30-day mortality in patients with FMR was 3.7% (95% confidence interval: 2.87 to 4.66) and 1-year mortality was 17.9% (95% confidence interval: 16.01 to 19.71). The meta-regression analysis studying the impact of AF among patients with FMR treated with the MitraClip demonstrated no difference in mortality at 30 days but demonstrated significantly increased mortality at 1 year (95% confidence interval: 0.0006 to 0.0027) (p = 0.004). AF did not influence procedural success., Conclusions: This meta-regression identifies AF as an independent negative predictor of long-term mortality after MitraClip implantation in patients with FMR. The mechanism of worse outcomes in patients with AF requires further study., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Cardiorespiratory fitness (CRF) has been shown to correlate with incident atrial fibrillation (AF) and AF burden. In recent years there has been increasing recognition of the pivotal role of modifying risk factors before AF ablation., Objective: The purpose of this study was to investigate whether higher baseline CRF measured using exercise stress testing (EST) was associated with improved outcomes after AF ablation., Methods: We studied 591 patients who underwent EST within 12 months before AF ablation. Patients were categorized into low (<85% predicted), adequate (85%-100% predicted), and high (>100% predicted) CRF groups. Outcomes of interest included arrhythmia recurrence, cessation of antiarrhythmic therapy, repeat hospitalization for arrhythmia, repeat rhythm control procedures, and all-cause mortality., Results: During mean follow-up of 32 months after ablation, arrhythmia recurrence was observed in 79% of patients in the low CRF group compared to 54% in the adequate CRF group and 27.5% in the high CRF group (P <.0001). Similarly, rates of repeat arrhythmia-related hospitalization, repeat rhythm control procedures, and need for ongoing antiarrhythmic therapy were significantly lower in the high CRF group (P <.0001). Death occurred in 2.5% of patients in the high CRF group compared to 4% in the adequate CRF group and 11% in the low CRF group (P <.0001). In Cox proportional hazards analyses, high CRF was significantly associated with lower arrhythmia recurrence., Conclusion: Higher CRF is associated with reduced arrhythmia recurrence rates and death among patients undergoing AF ablation. Efforts should be made to enhance CRF before AF ablation., (Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to compare outcomes after transcatheter aortic valve replacement (TAVR) in patients with pure aortic stenosis (AS) (i.e., no or trivial associated aortic regurgitation [AR]) with those in patients with AS and mild or more severe AR (i.e., mixed aortic valve disease [MAVD])., Background: TAVR is indicated in treating patients with severe AS. Limited data exist regarding the outcomes of TAVR in patients with MAVD., Methods: A total of 1,133 patients who underwent TAVR between January 2014 and December 2017 were included. The primary outcome was all-cause mortality. The comparison was adjusted to account for post-TAVR AR development in both groups. The secondary outcomes included composite endpoints of early safety and clinical efficacy as specified in the Valve Academic Research Consortium-2 criteria. Variables were compared using Mann-Whitney, chi-square, and Fisher exact tests, while Kaplan-Meier analyses were used to compare survival., Results: A total of 688 patients (61%) had MAVD (median age 83 years , 43% women). Among these, 17% developed mild, 2% moderate, and <1% severe post-TAVR AR. Overall, patients with MAVD had better survival compared with patients with pure AS (p = 0.03). Among patients who developed post-TAVR AR, those in the MAVD group had better survival (p = 0.04). In contrast, in patients who did not develop post-TAVR AR, pre-TAVR AR did not improve survival (p = 0.11)., Conclusions: Patients with MAVD who underwent TAVR had better survival compared with patients with pure AS. This is explained by the better survival of patients with MAVD who developed post-TAVR AR, likely due to left ventricular adaptation to AR., (Copyright © 2019. Published by Elsevier Inc.)

With the expanding use of cardiac implantable electronic device (CIEDs) in an ever-aging population, the looming problem of CIED-associated interference with the tricuspid valve is significant. The first pacemaker was implanted in 1958 for severe symptomatic bradycardia. The concept of a device to avert sudden cardiac death (i.e., the defibrillator) was first published in 1970 by Mirowski and Mower. The first reports of CIED-mediated tricuspid valve apparatus interference surfaced in the late 1900s, but it was not until recently that concentrated efforts have been made to better define the scope of CIED-mediated interference with the tricuspid valve apparatus. Because stopping implantation of these devices is not an option, better understanding of their mechanical complications could potentially lead to improvements in device design or epicardial device implantation, as an alternative, in select patients. This review covers existing evidence for CIED-mediated tricuspid regurgitation, discusses potential mechanisms of CIED-mediated interference of the tricuspid valve apparatus, provides an overview of how to diagnose CIED-mediated interference on echocardiography, and discusses management strategies for patients who have CIED-mediated severe tricuspid regurgitation., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Introduction: Percutaneous left atrial appendage (LAA) occlusion is an emerging treatment option for patients with non-valvular atrial fibrillation who cannot tolerate oral anticoagulation. The Watchman device (Boston Scientific Corporation, Natick, MA, USA) is deployed at the ostium of the LAA, and an appropriately sized device is critical for successful occlusion. However, standardized imaging protocols for device sizing have not been established., Objectives: We investigated the clinical utility of a standardized imaging protocol, with pre-procedural multi-detector cardiac computed tomography (MDCT), and intra-procedural transesophageal echocardiography (TEE), for Watchman device sizing., Methods: Patients who underwent Watchman device implantation between 2010 and 2016 at our center, and who had pre-procedural MDCT and intra-procedural TEE were included. MDCT measurements (CTmax, CTmin, CTmean), and TEE measurement (TEEmax) of the LAA ostium were determined for each case, and correlated with the final size of the Watchman device implanted. Demographic data and clinical outcomes were collected., Results: The study included 80 patients (mean age: 75 ± 9.6 years; male: 68%; mean CHA2DS2-VASc score: 4.5 ± 1.4). CTmax of the LAA ostium correlated strongly with the final deployed Watchman device size (Spearman's rho: 0.81, p < 0.001), while TEEmax of the LAA ostium showed only moderate correlation with the final deployed Watchman device size (Spearman's rho: 0.61, p < 0.001). Implantation success rate was 100%. At a mean duration of follow-up of 197 days, there were no device-related complications (device embolization, cardiac perforation and pericardial tamponade). At follow-up, the vast majority of patients (76 patients; 95%) had either no or trivial (≤3 mm) residual peri-device leak on TEE., Conclusions: A standardized imaging protocol for assessment of Watchman device implantation incorporating pre-procedural MDCT and intra-procedural TEE, was associated with excellent procedural outcomes at a mean duration of follow-up of 197 days., (Copyright © 2018 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)