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Competing Interests: Funding Support and Author Disclosures The VALOR-HCM study was funded by Bristol Myers Squibb. Dr Desai has served as a consultant for Bristol Myers Squibb, Cytokinetics, Tenaya, Edgewise and Viz.AI; and has received research support (to Cleveland Clinic) from Bristol Myers Squibb, Cytokinetics, and Tenaya. Dr Owens has served as a consultant for Bristol Myers Squibb, Cytokinetics, Pfizer, Biomarin, Tenaya, Lexicon, Stealth, Edgewise, and Renovacor; and has received grant support for research from Bristol Myers Squibb. Ms Wolski works for C5 Research and is an employee of Cleveland Clinic, which received payments for current research from Bristol Myers Squibb. Dr Geske has served as a consultant for Bristol Myers Squibb. Dr Saberi has served as a consultant for Bristol Myers Squibb and Cytokinetics. Dr Wang has received research grants (to institution) from Bristol Myers Squibb, Cytokinetics, and Abbott Vascular; has served on a consulting/advisory board for Bristol Myers Squibb; has served on steering committees for Bristol Myers Squibb and Cytokinetics; and has received speaker fees from Bristol Myers Squibb. Dr Sherrid has served as a consultant for Bristol Myers Squibb and Cytokinetics. Dr. Cremer works for C5 Research; and is an employee of Cleveland Clinic, which received payments for current research from Bristol Myers Squibb. Dr Lakdawala has received consulting fees from Bristol Myers Squibb, Pfizer, Tenaya, Cytokinetics, and Akros; and has received research support from Bristol Myers Squibb and Pfizer. Dr Tower-Rader has served as a consultant for Bristol Myers Squibb and Cytokinetics. Dr Fermin has received consulting/speaker fees from Bristol Myers Squibb and BridgeBio; and has served as a consultant for Pfizer. Dr Naidu has served as a consultant for Bristol Myers Squibb and Cytokinetics. Dr Smedira has served as a consultant for Bristol Myers Squibb. Ms McErlean and Sewell work for C5 Research; and are employees of Cleveland Clinic, which received payments for current research from Bristol Myers Squibb. Dr Zhong is an employee of and has stock ownership in Bristol Myers Squibb. Dr Wyrwich was employed by and had stock ownership in Bristol Myers Squibb at the time of the study. Drs Lampl and Sehnert are employed by and have stock ownership in Bristol Myers Squibb. Dr Nissen works for C5 Research; and is an employee of Cleveland Clinic, which received payments for current research from Bristol Myers Squibb. Dr Spertus has consulted for Bristol Myers Squibb and Cytokinetics; and holds the copyright to the KCCQ. Dr Schaff has reported that he has no relationships relevant to contents of this paper to disclose.

Background: Current guidelines for aortic regurgitation (AR) recommend the same linear left ventricular (LV) dimension for intervention regardless of age and sex., Objectives: The purpose of this study was to evaluate the impact of age and sex on the degree of LV remodeling and outcomes., Methods: We included consecutive patients with severe AR who were serially monitored by echocardiogram between 2010 and 2016. The 2 main endpoints were as follows: 1) LV end-systolic volume indexed to body surface area (LVESVi) and LV end-diastolic volume indexed to body surface area; and 2) adverse events (AE). We evaluated the longitudinal rate of LV remodeling and determined the association between LV volume and AE by age and sex., Results: A total of 525 adult patients (26% women) with a median echocardiogram follow-up of 2.0 years (IQR: 1.0-3.6 years) were included. At baseline, older patients (age ≥60 years) had smaller LV volumes compared with younger patients (age <60 years), eg, the mean LVESVi was 27.3 mL/m 2 vs 32.3 mL/m 2 , respectively. Similarly, women had smaller LV volumes compared with men (mean LVESVi was 23.3 mL/m 2 vs 32.4 mL/m 2 ). On serial evaluation, older patients and women maintained smaller LV volumes compared with younger patients and men, respectively. There were 210 (40%) AE during follow-up. The optimal discriminatory threshold for AE varies by age and sex, eg, the LVESVi threshold was highest for young men (50 mL/m 2 ), intermediate for older men (35 mL/m 2 ), and lowest for women (27 mL/m 2 )., Conclusions: On serial evaluation, older patients and women with chronic AR maintained smaller LV volumes than younger patients and men, respectively, and develop AE at lower LV volumes., 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.)

Background: Obstructive hypertrophic cardiomyopathy (oHCM) is increasingly being diagnosed in elderly patients., Objectives: The authors sought to study long-term outcomes of septal reduction therapies (SRT) in Medicare patients with oHCM, and hospital volume-outcome relation., Methods: Medicare beneficiaries aged >65 years who underwent SRT, septal myectomy (SM) or alcohol septal ablation (ASA), from 2013 through 2019 were identified. Primary outcome was all-cause mortality, and secondary outcomes included heart failure (HF) readmission and need for redo SRT in follow-up. Overlap propensity score weighting was used to adjust for differences between both groups. Relation between hospital SRT volume and short-term and long-term mortality was studied., Results: The study included 5,679 oHCM patients (SM = 3,680 and ASA = 1,999, mean age 72.9 vs 74.8 years, women 67.2% vs 71.1%; P < 0.01). SM patients had fewer comorbidities, but after adjustment, both groups were well balanced. At 4 years (IQR: 2-6 years), although there was no difference in long-term mortality between SM and ASA (HR: 0.87; 95% CI: 0.74-1.03; P = 0.1), on landmark analysis, SM was associated with lower mortality after 2 years of follow-up (HR: 0.72; 95% CI: 0.60-0.87; P < 0.001) and had lower need for redo SRT. Both reduced HF readmissions in follow-up vs 1 year pre-SRT. Higher-volume centers had better outcomes vs lower-volume centers, but 70% of SRT were performed in low-volume centers., Conclusions: SRT reduced HF readmission in Medicare patients with oHCM. SM is associated with lower redo and better long-term survival compared with ASA. Despite better outcomes in high-volume centers, 70% of SRT are performed in low-volume U.S. centers., Competing Interests: Funding Support and Author Disclosures The current research was funded by philanthropic gifts by the Haslam Family, Bailey Family, and Khouri family to the Cleveland Clinic for Dr. Milind Desai's research. Dr Smedira has received personal fees from Bristol Myers Squibb. Dr Desai is a consultant for Medtronic and Bristol Myers Squibb; and is on the executive steering committee of trials sponsored by Bristol Myers Squibb. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Septal reduction therapy (SRT), surgical myectomy or alcohol ablation, is recommended for obstructive hypertrophic cardiomyopathy (oHCM) patients with intractable symptoms despite maximal medical therapy, but is associated with morbidity and mortality., Objectives: This study sought to determine whether the oral myosin inhibitor mavacamten enables patients to improve sufficiently to no longer meet guideline criteria or choose to not undergo SRT., Methods: Patients with left ventricular (LV) outflow tract (LVOT) gradient ≥50 mm Hg at rest/provocation who met guideline criteria for SRT were randomized, double blind, to mavacamten, 5 mg daily, or placebo, titrated up to 15 mg based on LVOT gradient and LV ejection fraction. The primary endpoint was the composite of the proportion of patients proceeding with SRT or who remained guideline-eligible after 16 weeks' treatment., Results: One hundred and twelve oHCM patients were enrolled, mean age 60 ± 12 years, 51% men, 93% New York Heart Association (NYHA) functional class III/IV, with a mean post-exercise LVOT gradient of 84 ± 35.8 mm Hg. After 16 weeks, 43 of 56 placebo patients (76.8%) and 10 of 56 mavacamten patients (17.9%) met guideline criteria or underwent SRT, difference (58.9%; 95% CI: 44.0%-73.9%; P < 0.001). Hierarchical testing of secondary outcomes showed significant differences (P < 0.001) favoring mavacamten, mean differences in post-exercise peak LVOT gradient -37.2 mm Hg; ≥1 NYHA functional class improvement 41.1%; improvement in patient-reported outcome 9.4 points; and NT-proBNP and cardiac troponin I between-groups geometric mean ratio 0.33 and 0.53., Conclusions: In oHCM patients with intractable symptoms, mavacamten significantly reduced the fraction of patients meeting guideline criteria for SRT after 16 weeks. Long-term freedom from SRT remains to be determined. (A Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive HCM Who Are Eligible for Septal Reduction Therapy [VALOR-HCM]; NCT04349072)., Competing Interests: Funding Support and Author Disclosures The VALOR-HCM study was funded by MyoKardia, Inc, a wholly owned subsidiary of Bristol Myers Squibb. Funding support for open access was provided by MyoKardia Inc, a wholly owned subsidiary of Bristol Myers Squibb. The Cleveland Clinic Center for Clinical (C5) Research received funding for the trial, but none of the C5 Research personnel received any honoraria from the sponsor. Dr Desai serves as a consultant for Myokardia (now MyoKardia Inc, a wholly owned subsidiary of Bristol Myers Squibb) and Medtronic. Drs Owens and Naidu serve as consultants for MyoKardia Inc, a wholly owned subsidiary of Bristol Myers Squibb and Cytokinetics. Drs Li, Sterling, Lampl, and Sehnert are employees of MyoKardia Inc, a wholly owned subsidiary of Bristol Myers Squibb. Dr Edelberg is a former employee of MyoKardia Inc, a wholly owned subsidiary of Bristol Myers Squibb. The sponsor had no role in the decision to submit the manuscript. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The impact of pre-existing atrial fibrillation (AF) on outcomes after noncardiac surgery is not clear., Objectives: We aimed to study the impact of AF on the risk of adverse outcomes after noncardiac surgery in a nationwide cohort., Methods: We identified Medicare beneficiaries admitted for noncardiac surgery from 2015 to 2019 and divided the study cohort into 2 groups: with and without AF. Noncardiac surgery was classified into vascular, thoracic, general, genitourinary, gynecological, orthopedics and neurosurgery, breast, head and neck, and transplant. We used propensity score matching on exact age, sex, race, urgency and type of surgery, revised cardiac risk index (RCRI) and CHA 2 DS 2 -VASc score, and tight caliper on other comorbidities. The study outcomes were 30-day mortality, stroke, myocardial infarction, and heart failure. We examined the incremental utility of AF in addition to RCRI to predict adverse events after noncardiac surgery., Results: The study cohort included 8,635,758 patients who underwent noncardiac surgery (16.4% with AF). Patients with AF were older, more likely to be men, and had higher prevalence of comorbidities. After propensity score matching, AF was associated with higher risk of mortality (OR: 1.31; 95% CI: 1.30-1.32), heart failure (OR: 1.31; 95% CI: 1.30-1.33), and stroke (OR: 1.40; 95% CI: 1.37-1.43) and lower risk of myocardial infarction (OR: 0.81; 95% CI: 0.79-0.82). Results were consistent in subgroup analysis by sex, race, type of surgery, and all strata of RCRI and CHA 2 DS 2 -VASc score. AF improved the discriminative ability of RCRI (C-statistic 0.73 to 0.76)., Conclusion: Pre-existing AF is independently associated with postoperative adverse outcomes after NCS., Competing Interests: Funding Support and Author Disclosures The current research was partly funded by philanthropic gifts by the Haslam Family, Bailey Family, and Khouri family to the Cleveland Clinic for Dr Milind Desai's research. Dr Desai is a consultant for Medtronic and Bristol Myers Squibb; and is on the executive steering committee of a trial sponsored by Bristol Myers Squibb. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The long-term effect of bariatric surgery on cardiovascular outcomes in the elderly population is not well studied., Objectives: The aim of this study was to evaluate the association between bariatric surgery and long-term cardiovascular outcomes in the Medicare population., Methods: Medicare beneficiaries who underwent bariatric surgery from 2013 to 2019 were matched to a control group of patients with obesity with a 1:1 exact matching based on age, sex, body mass index, and propensity score matching on 87 clinical variables. The study outcomes included all-cause mortality, new-onset heart failure (HF), myocardial infarction (MI), and ischemic stroke. An instrumental variable analysis was performed as a sensitivity analysis., Results: The study cohort included 189,770 patients (94,885 matched patients in each group). By study design, the 2 groups had similar age (mean: 62.33 ± 10.62 years), sex (70% female), and degree of obesity (mean body mass index: 44.7 ± 7.3 kg/m 2 ) and were well balanced on all clinical variables. After a median follow-up of 4.0 years (IQR: 2.4-5.7 years), bariatric surgery was associated with a lower risk of mortality (9.2 vs 14.7 per 1,000 person-years; HR: 0.63; 95% CI: 0.60-0.66), new-onset HF (HR: 0.46; 95% CI: 0.44-0.49), MI (HR: 0.63; 95% CI: 0.59-0.68), and stroke (HR: 0.71; 95%: CI: 0.65-0.79) (P < 0.001). The benefit of bariatric surgery was evident in patients who were 65 years and older. Using instrumental variable analysis, bariatric surgery was associated with a lower risk of mortality, HF, and MI., Conclusions: Among Medicare beneficiaries with obesity, bariatric surgery is associated with lower risk of mortality, new-onset HF, and MI., Competing Interests: Funding Support and Author Disclosures The current research was partly funded by philanthropic gifts by the Haslam family, Bailey family, and Khouri family to the Cleveland Clinic for Dr Desai’s research. Dr Desai is a consultant for Medtronic and Bristol Myers Squibb; and is on the executive steering committee of a trial sponsored by Bristol Myers Squibb. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Hypertrophic cardiomyopathy (HCM), a relatively common, globally distributed, and often inherited primary cardiac disease, has now transformed into a contemporary highly treatable condition with effective options that alter natural history along specific personalized adverse pathways at all ages. HCM patients with disease-related complications benefit from: matured risk stratification in which major markers reliably select patients for prophylactic defibrillators and prevention of arrhythmic sudden death; low risk to high benefit surgical myectomy (with percutaneous alcohol ablation a selective alternative) that reverses progressive heart failure caused by outflow obstruction; anticoagulation prophylaxis that prevents atrial fibrillation-related embolic stroke and ablation techniques that decrease the frequency of paroxysmal episodes; and occasionally, heart transplant for end-stage nonobstructive patients. Those innovations have substantially improved outcomes by significantly reducing morbidity and HCM-related mortality to 0.5%/y. Palliative pharmacological strategies with currently available negative inotropic drugs can control symptoms over the short-term in some patients, but generally do not alter long-term clinical course. Notably, a substantial proportion of HCM patients (largely those identified without outflow obstruction) experience a stable/benign course without major interventions. The expert panel has critically appraised all available data and presented management insights and recommendations with concise principles for clinical decision-making., Competing Interests: Funding Support and Author Disclosures Dr Desai has served as a consultant for Bristol Myers Squibb, Medtronic, and Caristo Diagnostics. Dr Rowin has received a research grant from Pfizer. Dr Martin Maron has served as a steering committee member for Cytokinetics and Imbria Pharmaceuticals; and has served as a consultant and has a research grant from Takeda Pharmaceuticals. Dr Sherrid has served as a consultant for Celltrion. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Hypertrophic cardiomyopathy (HCM) is a relatively common often inherited global heart disease, with complex phenotypic and genetic expression and natural history, affecting both genders and many races and cultures. Prevalence is 1:200-1:500, largely based on the disease phenotype with imaging, inferring that 750,000 Americans may be affected by HCM. However, cross-sectional data show that only a fraction are clinically diagnosed, suggesting under-recognition, with most clinicians exposed to small segments of the broad disease spectrum. Highly effective HCM management strategies have emerged, altering clinical course and substantially lowering mortality and morbidity rates. These advances underscore the importance of reliable HCM diagnosis with echocardiography and cardiac magnetic resonance. Family screening with noninvasive imaging will identify relatives with the HCM phenotype, while genetic analysis recognizes preclinical sarcomere gene carriers without left ventricular hypertrophy, but with the potential to transmit disease. Comprehensive initial patient evaluations are important for reliable diagnosis, accurate portrayal of HCM and family history, risk stratification, and distinguishing obstructive versus nonobstructive forms., Competing Interests: Funding Support and Author Disclosures Dr Desai has served as a consultant for Bristol Myers Squibb, Medtronic, and Caristo Diagnostics. Dr Martin Maron has served as a steering committee member for Cytokinetics, Imbria Pharmaceuticals, and Takeda Pharmaceuticals; and has received research grant support from Takeda Pharmaceuticals. Dr Sherrid has served as a consultant for Celltrion, Inc. Dr Rowin has received research grant support from Pfizer. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Patient-centric measures of hospital performance for transcatheter aortic valve replacement (TAVR) are needed., Objectives: This study evaluated 30-day, risk-adjusted home time as a hospital performance metric for patients who underwent TAVR., Methods: This study identified 160,792 Medicare beneficiaries who underwent elective TAVR from 2015 to 2019. Home time was calculated for each patient as the number of days alive and spent outside the hospital, skilled nursing facility (SNF), and long-term acute care facility for 30 days after the TAVR procedure date. Correlations between risk-adjusted, 30-day home time and other metrics (30-day, risk-adjusted readmission rate [RSRR], 30-day, risk-adjusted mortality rate [RSMR], and annual TAVR volume) were estimated using Pearson's correlation. Meaningful upward or downward reclassification (≥2 quartile ranks) in hospital performance based on quartiles of risk-adjusted, 30-day home time compared with quartiles of other measures were assessed., Results: Median risk-adjusted, 30-day home time was 27.4 days (interquartile range [IQR]: 26.3-28.5 days). The largest proportion of days lost from 30-day home time was hospital stay after TAVR and SNF stay. An inverse correlation was observed between hospital-level, risk-adjusted, 30-day home time and 30-day RSRR (r = -0.465; P < 0.001) and 30-day RSMR (r = -0.3996; P < 0.001). The use of the 30-day, risk-adjusted home time was associated with reclassification in hospital performance rank hospitals compared with other metrics (9.1% up-classified, 11.2% down-classified vs RSRR; 9.1% up-classified, 10.3% down-classified vs RSMR; and 20.1% up-classified, 19.3% down-classified vs annual TAVR volume)., Conclusions: Risk-adjusted, 30-day home time represents a novel patient-centered performance metric for TAVR hospitals that may provide a complimentary assessment to currently used metrics., Competing Interests: Funding Support and Author Disclosures Dr Mack has received consulting fees from Gore; has served as a trial co-primary investigator for Edwards Lifesciences and Abbott; and has served as a study chair for Medtronic. Dr Desai has been a consultant for Medtronic, Myokardia, and Bristol Myers Squibb; and has been on the executive steering committee of a trial sponsored by Bristol Myers Squibb. Dr Pandey has served on the advisory board of Roche Diagnostics; has received nonfinancial support from Pfizer and Merck; and has received research support from the Texas Health Resources Clinical Scholarship, the Gilead Sciences Research Scholar Program, the National Institute on Aging GEMSSTAR Grant (1R03AG067960-01), and Applied Therapeutics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Patients with rheumatic aortic stenosis (AS) were excluded from transcatheter aortic valve replacement (TAVR) trials., Objectives: The authors sought to examine outcomes with TAVR versus surgical aortic valve replacement (SAVR) in patients with rheumatic AS, and versus TAVR in nonrheumatic AS., Methods: The authors identified Medicare beneficiaries who underwent TAVR or SAVR from October 2015 to December 2017, and then identified patients with rheumatic AS using prior validated International Classification of Diseases, Version 10 codes. Overlap propensity score weighting analysis was used to adjust for measured confounders. The primary study outcome was all-cause mortality. Multiple secondary outcomes were also examined., Results: The final study cohort included 1,159 patients with rheumatic AS who underwent aortic valve replacement (SAVR, n = 554; TAVR, n = 605), and 88,554 patients with nonrheumatic AS who underwent TAVR. Patients in the SAVR group were younger and with lower prevalence of most comorbidities and frailty scores. After median follow-up of 19 months (interquartile range: 13 to 26 months), there was no difference in all-cause mortality with TAVR versus SAVR (11.2 vs. 7.0 per 100 person-year; adjusted hazard ratio: 1.53; 95% confidence interval: 0.84 to 2.79; p = 0.2). Compared with TAVR in nonrheumatic AS, TAVR for rheumatic AS was associated with similar mortality (15.2 vs. 17.7 deaths per 100 person-years (adjusted hazard ratio: 0.87; 95% confidence interval: 0.68 to 1.09; p = 0.2) after median follow-up of 17 months (interquartile range: 11 to 24 months). None of the rheumatic TAVR patients, <11 SAVR patients, and 242 nonrheumatic TAVR patients underwent repeat aortic valve replacement (124 redo-TAVR and 118 SAVR) at follow-up., Conclusions: Compared with SAVR, TAVR could represent a viable and possibly durable option for patients with rheumatic AS., Competing Interests: Funding Support and Author Disclosures Dr. Mentias received support from National Institute of Health NRSA institutional grant (T32 HL007121) to the Abboud Cardiovascular Research Center. Dr. Sarrazin is supported by funding from the National Institute on Aging (NIA R01AG055663-01), and by the Health Services Research and Development Service (HSR&D) of the Department of Veterans Affairs. Dr. Horwitz has received grant support from Edwards Lifesciences and Boston Scientific. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The HCMR (Hypertrophic Cardiomyopathy Registry) is a National Heart, Lung, and Blood Institute-funded, prospective registry of 2,755 patients with hypertrophic cardiomyopathy (HCM) recruited from 44 sites in 6 countries., Objectives: The authors sought to improve risk prediction in HCM by incorporating cardiac magnetic resonance (CMR), genetic, and biomarker data., Methods: Demographic and echocardiographic data were collected. Patients underwent CMR including cine imaging, late gadolinium enhancement imaging (LGE) (replacement fibrosis), and T1 mapping for measurement of extracellular volume as a measure of interstitial fibrosis. Blood was drawn for the biomarkers N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (cTnT), and genetic analysis., Results: A total of 2,755 patients were studied. Mean age was 49 ± 11 years, 71% were male, and 17% non-white. Mean ESC (European Society of Cardiology) risk score was 2.48 ± 0.56. Eighteen percent had a resting left ventricular outflow tract (LVOT) gradient ≥30 mm Hg. Thirty-six percent had a sarcomere mutation identified, and 50% had any LGE. Sarcomere mutation-positive patients were more likely to have reverse septal curvature morphology, LGE, and no significant resting LVOT obstruction. Those that were sarcomere mutation negative were more likely to have isolated basal septal hypertrophy, less LGE, and more LVOT obstruction. Interstitial fibrosis was present in segments both with and without LGE. Serum NT-proBNP and cTnT levels correlated with increasing LGE and extracellular volume in a graded fashion., Conclusions: The HCMR population has characteristics of low-risk HCM. Ninety-three percent had no or only mild functional limitation. Baseline data separated patients broadly into 2 categories. One group was sarcomere mutation positive and more likely had reverse septal curvature morphology, more fibrosis, but less resting obstruction, whereas the other was sarcomere mutation negative and more likely had isolated basal septal hypertrophy with obstruction, but less fibrosis. Further follow-up will allow better understanding of these subgroups and development of an improved risk prediction model incorporating all these markers., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Radiation-associated cardiac disease, a heterogeneous and complex disease, manifests years or even decades following radiation exposure to the chest. It is associated with a significantly higher morbidity and mortality. Often, the presentation is vague and overlaps with many diseases, presenting unique diagnostic and management issues. As a result, a high index of suspicion followed by multimodality imaging is crucial, along with comprehensive screening to enable early detection. Timing of intervention should be carefully considered in these patients, because surgery is often complex with an emerging role of percutaneous interventions., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: A high proportion of patients with hypertrophic cardiomyopathy (HCM) have evidence of late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR)., Objectives: This study sought to assess the incremental prognostic utility of LGE in patients with HCM., Methods: We studied 1,423 consecutive low-/intermediate-risk patients with HCM (age ≥18 years) with preserved left ventricular (LV) ejection fraction (mean age 66 ± 14 years, 60% men) who underwent transthoracic echocardiography (TTE) (including dimensions and LV outflow tract gradients) and CMR (including LGE as a % of LV mass) at our center between January 2008 and December 2015. The primary composite endpoint was sudden cardiac death (SCD) and appropriate implantable cardioverter-defibrillator discharge. The percent 5-year SCD risk score was calculated., Results: The mean 5-year SCD risk score was 2.3 ± 2.0. Mean maximal LV outflow tract gradient (TTE) was 70 ± 55 mm Hg (median 74 mm Hg [interquartile range (IQR): 10 to 67 mm Hg]); indexed LV mass and LGE (both on CMR) were 91 ± 10 g/m 2 and 8.4 ± 12% (IQR: 0% to 19%); 50% had LGE on CMR. Of these, 458 were nonobstructive and 965 were obstructive (of which 686 were underwent myectomy). At 4.7 ± 2.0 years of follow-up, 60 (4%) met the composite endpoint. On quadratic spline analysis, LGE ≥15% was associated with increased risk of composite events. In the obstructive subgroup, on competing risk regression analysis, ≥15% LGE (subhazard ratio: 3.04 [95% confidence interval: 1.48 to 6.10]) was associated with a higher rate and myectomy (subhazard ratio: 0.44 [95% confidence interval: 0.20 to 0.76]) was associated with a lower rate of composite endpoints (both p < 0.01). Similarly, sequential addition of LGE ≥15% and myectomy to % 5-year SCD risk score improved the log likelihood ratios from -227.85 to -219.14 (chi-square 17) and to -215.14 (chi-square 8; both p < 0.01). Association of %LGE with composite events was similar even in myectomy and nonobstructive subgroups., Conclusions: In low-/intermediate-risk adult patients with HCM (obstructive, myectomy, and nonobstructive subgroups) with preserved systolic function, %LGE was significantly associated with a higher rate of composite endpoint, providing incremental prognostic utility., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Chronic severe aortic regurgitation (AR) imposes significant volume and pressure overload on the left ventricle (LV), but such patients typically remain in an asymptomatic state for a very long time., Objectives: This study sought to examine long-term outcomes in a contemporary group of patients with grade III+ chronic AR and preserved left ventricular ejection fraction (LVEF) and the value of aortic valve (AV) surgery on long-term survival. We also wanted to reassess the threshold of LV dimension, beyond which mortality significantly increases., Methods: The authors studied 1,417 such patients (mean 54 ± 16 years of age, 75% men) seen between 2002 and 2010. Clinical data were obtained and Society of Thoracic Surgeons (STS) score was calculated. The primary endpoint was mortality., Results: Mean STS score was 5.5% ± 8%, and mean LVEF was 57 ± 4%, whereas 1,228 patients (87%) were asymptomatic, and 93 patients (7%) had indexed LV end-systolic dimension (iLVESD) ≥2.5 cm/m 2 . At 6.6 ± 3 years, 933 patients (66%) underwent AV surgery (36% isolated AV surgery, 16% concomitant coronary bypass, and 58% aortic replacement), and 262 patients (19%) died. In-hospital postoperative mortality was 2% (0.6% in isolated AV surgery). On multivariate Cox survival analysis, compared to the group of iLVESD <2.5 cm/m 2 and no AV surgery, the 2 groups of iLVESD <2.5 cm/m 2 with AV surgery and iLVESD ≥2.5 cm/m 2 with AV surgery were associated with improved survival (hazard ratios: 0.62 and 0.42, respectively; both p < 0.01). Survival of patients who underwent AV surgery was similar to that of an age- and sex-matched U.S. population with 96% of deaths occurring in those with iLVESD <2.5 cm/m 2 ., Conclusions: At a high-volume experienced center, patients with grade III or greater AR and preserved LVEF demonstrated significantly improved long-term survival following AV surgery. The risk of death significantly increased at a lower LV dimension threshold than previously described., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The potential additive utility of baseline resting left ventricular global longitudinal strain (LV-GLS) and exercise stress testing in risk stratification of patients with significant mitral regurgitation (MR) has not been studied., Objectives: The goal of this study was to determine whether resting LV-GLS and exercise testing provide incremental prognostic utility in asymptomatic patients with ≥3+ primary MR and preserved left ventricular ejection fraction., Methods: Between 2000 and 2011, resting and exercise echocardiography data, Society of Thoracic Surgeons (STS) scores, and death were recorded in 737 patients (mean age 58 ± 13 years; 68% men)., Results: Coronary artery disease and flail leaflet were seen in 10% and 28% of patients, respectively. STS score, resting left ventricular ejection fraction, mitral effective regurgitant orifice, resting right ventricular systolic pressure (RVSP), exercise metabolic equivalents (METs), and percentage of age-/sex-predicted METs were 1.5 ± 1%, 62 ± 2%, 0.45 ± 0.2 cm 2 , 31 ± 12 mm Hg, 9.8 ± 3, and 115 ± 27, respectively. Median LV-GLS was -21.7%. Within 3 months (interquartile range: 1 to 15 months), 65% underwent mitral valve surgery. At 8.3 ± 3 years, 64 (9%) patients died (0% 30-day post-operative deaths). On multivariable Cox survival analysis, higher STS score (hazard ratio [HR]: 1.14), more abnormal resting LV-GLS (HR: 1.60), higher baseline RVSP (HR: 1.35), and lower percentage of age-/sex-predicted METs (HR: 1.13) were associated with higher mortality, whereas mitral valve surgery (HR: 0.82) was associated with improved survival (all p < 0.01). Addition of predicted METs and resting LV-GLS to STS, resting RVSP, left ventricular end-systolic dimension, and mitral effective regurgitant orifice increased the C-statistic for longer-term mortality from 0.61 to 0.69 and 0.78, respectively (all p < 0.01). On quadratic spline analysis, the risk of death progressively increased as resting LV-GLS worsened below -21%., Conclusions: Reduced exercise capacity and worsening resting LV-GLS were associated with mortality, providing additive prognostic utility., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Primary mitral regurgitation (MR) is a growing health problem due to the aging population., Objectives: The purpose of this study was to assess the impact of baseline pulmonary hypertension on long-term outcomes in patients with significant primary MR and preserved left ventricular ejection fraction (LVEF)., Methods: We studied 1,318 patients with ≥3+ primary MR and LVEF ≥60% using echocardiography at rest; they were evaluated at our center from 2005 to 2008. Baseline clinical and echocardiography data were recorded, and the Society of Thoracic Surgeons (STS) score was calculated. The primary outcome was death., Results: Mean STS score was 3.98 ± 1%; 54% of patients were in New York Heart Association (NYHA) functional class I and 31% were in NYHA functional class II; and 18% had atrial fibrillation (AF). Mean LVEF, mitral effective regurgitant orifice, indexed LV end-systolic diameter (LVESD), and right ventricular systolic pressure (RVSP) were 62 ± 2%, 0.56 ± 0.30 cm(2), 1.6 ± 0.3 cm/m(2), and 37 ± 14 mm Hg, respectively. At 7.1 ± 2.0 years, 86% had mitral valve (MV) surgery. Death occurred in 130 (10%) patients. On Cox multivariable analysis, baseline RVSP, together with age, baseline NYHA functional class, pre-operative AF, coronary artery disease, and indexed LVESD were associated with a higher rate of longer term mortality (all p < 0.01), whereas MV surgery (as a time-dependent covariate) was associated with improved survival (p < 0.001). Addition of RVSP to the STS score significantly reclassified the risk for longer term mortality (integrated discrimination index: 0.07; p < 0.001); 77% patients who died had RVSP ≥35 mm Hg., Conclusions: In patients with significant primary MR and preserved LVEF, baseline RVSP is independently associated with long-term survival. Impact of RVSP is progressive and not confined to those with the highest baseline values., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This meta-analysis was designed to update data on clinical outcomes with aspiration thrombectomy or mechanical thrombectomy before primary percutaneous coronary intervention (PCI) compared with conventional primary PCI alone., Background: The clinical efficacy of thrombectomy in acute myocardial infarction (AMI) remains uncertain., Methods: Clinical trials that randomized AMI patients to aspiration (18 trials, n = 3,936) or mechanical thrombectomy (7 trials, n = 1,598) before PCI compared with conventional PCI alone were included., Results: The weighted mean duration of clinical follow-up was 6 months. Aspiration thrombectomy vs. conventional primary PCI (18 trials, n=3,936): Major adverse cardiac events (MACE) (risk ratio [RR]: 0.76; 95% confidence interval [CI]: 0.63 to 0.92; p = 0.006) and all-cause mortality (RR: 0.71; 95% CI: 0.51 to 0.99; p = 0.049) were significantly reduced with aspiration thrombectomy. Beneficial trends were noted for recurrent MI (p = 0.11) and target vessel revascularization (p = 0.06). Final infarct size (p = 0.64) and ejection fraction (p = 0.32) at 1 month were similar. ST-segment resolution (STR) at 60 min (RR: 1.31; 95% CI: 1.16 to 1.48; p < 0.0001) and Thrombolysis In Myocardial Infarction blush grade (TBG) 3 post-procedure (RR: 1.37; 95% CI: 1.19 to 1.59; p < 0.0001) were both improved with aspiration thrombectomy. Mechanical thrombectomy vs. conventional primary PCI (7 trials, n = 1,598): there was no difference between the mechanical thrombectomy and conventional primary PCI arms in the incidence of MACE (RR: 1.10; 95% CI: 0.59 to 2.05; p = 0.77), mortality (p = 0.57), recurrent MI (p = 0.32), target vessel revascularization (p = 0.19), or final infarct size (p = 0.47). A benefit in STR at 60 min (RR: 1.25; 95% CI: 1.06 to 1.47; p = 0.007), but not TBG 3 (RR: 1.09; 95% CI: 0.86 to 1.38; p = 0.48) was noted., Conclusions: Thrombectomy during AMI by manual catheter aspiration, but not mechanically, is beneficial in reducing MACE, including mortality, at 6 to 12 months compared with conventional primary PCI alone., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The American College of Cardiology Foundation (ACCF), along with key specialty and subspecialty societies, conducted an appropriate use review of common clinical scenarios where cardiac computed tomography (CCT) is frequently considered. The present document is an update to the original CCT/cardiac magnetic resonance (CMR) appropriateness criteria published in 2006, written to reflect changes in test utilization, to incorporate new clinical data, and to clarify CCT use where omissions or lack of clarity existed in the original criteria (1). The indications for this review were drawn from common applications or anticipated uses, as well as from current clinical practice guidelines. Ninety-three clinical scenarios were developed by a writing group and scored by a separate technical panel on a scale of 1 to 9 to designate appropriate use, inappropriate use, or uncertain use. In general, use of CCT angiography for diagnosis and risk assessment in patients with low or intermediate risk or pretest probability for coronary artery disease (CAD) was viewed favorably, whereas testing in high-risk patients, routine repeat testing, and general screening in certain clinical scenarios were viewed less favorably. Use of noncontrast computed tomography (CT) for calcium scoring was rated as appropriate within intermediate- and selected low-risk patients. Appropriate applications of CCT are also within the category of cardiac structural and functional evaluation. It is anticipated that these results will have an impact on physician decision making, performance, and reimbursement policy, and that they will help guide future research.

Objectives: The purpose of this study was to perform a systematic review and meta-analysis of comparative studies to compare outcomes of septal ablation (SA) with septal myectomy (SM) for treatment of hypertrophic obstructive cardiomyopathy (HOCM)., Background: SM is considered the gold standard for treatment of HOCM. However, SA has emerged as an attractive therapeutic alternative., Methods: A Medline search using standard terms was conducted to determine eligible studies. Due to a lack of randomized control trials, we included observational studies for review., Results: Twelve studies were found eligible for review. No significant differences between short-term (risk difference [RD]: 0.01; 95% confidence interval [CI]: -0.01 to 0.03) and long-term mortality (RD: 0.02; 95% CI: -0.05 to 0.09) were found between the SA and SM groups. In addition, no significant differences could be found in terms of post-intervention functional status as well as improvement in New York Heart Association functional class, ventricular arrhythmia occurrence, re-interventions performed, and post-procedure mitral regurgitation. However, SA was found to increase the risk of right bundle branch block (RBBB) (pooled odds ratio [OR]: 56.3; 95% CI: 11.6 to 273.9) along with need for permanent pacemaker implantation post-procedure (pooled OR: 2.6; 95% CI: 1.7 to 3.9). Although the efficacy of both SA and SM in left ventricular outflow tract gradient (LVOTG) reduction seems comparable, there is a small yet significantly higher residual LVOTG amongst the SA group patients as compared with the SM group patients., Conclusion: SA does seem to show promise in treatment of HOCM owing to similar mortality rates as well as functional status compared with SM; however, the caveat is increased conduction abnormalities and a higher post-intervention LVOTG. The choice of treatment strategy should be made after a thorough discussion of the procedures with the individual patient., (Copyright (c) 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: In hypertrophic cardiomyopathy (HCM) patients undergoing surgical myectomy, we sought to determine the association between pre-operative cardiac magnetic resonance (CMR) findings, small intramural coronary arteriole dysplasia (SICAD) on histopathology, and ventricular tachycardia (VT)., Background: Myocardial scarring (fibrosis) and SICAD are frequently observed on histopathology in HCM patients. CMR measures wall thickness and detects scar., Methods: Sixty symptomatic HCM patients (62% men; mean age 51 +/- 14 years), with preserved ejection fraction (mean 64 +/- 5%) and no angiographic coronary disease underwent CMR (cine and delayed post-contrast) using a Siemens 1.5 T scanner, followed by septal myectomy. Maximal basal septal thickness was recorded on cine CMR. Scar was determined (percentage of total myocardium) on delayed post-contrast CMR images and quantified as none, mild (0% to 25%), moderate (26% to 50%), or severe (>50%). VT was assessed using Holter monitoring. Degree of SICAD was determined (normal, mild, moderate, and severe) on histopathology of surgical specimen., Results: SICAD and scar were seen in 45 (75%) and 38 (63%) patients, respectively. In 15 patients without SICAD, 12 (80%) had no scar; 23 (70%) patients with mild SICAD had mild scar on CMR. On multivariate analysis, degree of SICAD was independently associated with scar on CMR (Wald chi-square statistic: 6.8, p < 0.01). Patients with basal septal scar on CMR had higher VT frequency compared with those without (27% vs. 5%, p = 0.03)., Conclusions: A strong association exists between degree of SICAD and myocardial scarring seen on CMR.

Objectives: The aim of the study was to determine if patients with hypertrophic cardiomyopathy (HCM), both with and without myocardial fibrosis, have altered aortic stiffness as assessed by magnetic resonance imaging (MRI) pulse wave velocity (PWV) measurements., Background: Abnormal aortic stiffness implies an unfavorable prognosis and has been established in a variety of aortic diseases and ischemic cardiomyopathy. However, the relationship between aortic stiffness and HCM has not been studied previously., Methods: The study was institutional review board approved and Health Insurance Portability and Accountability Act of 1996 compliant. Velocity-encoded MRI was performed in 100 HCM and 35 normal control subjects. PWV was determined between the mid-ascending and -descending thoracic aorta. Delayed-enhancement MRI was acquired for identification of myocardial fibrosis., Results: Mean age was 52.4 years in HCM and 45.3 years in control subjects. The prevalence of myocardial fibrosis in HCM was 70%. PWV was significantly higher in HCM patients compared with control subjects (8.72 +/- 5.83 m/s vs. 3.74 +/- 0.86 m/s, p < 0.0001). PWV was higher (i.e., increased aortic stiffness) in HCM patients with myocardial fibrosis than in those without (9.66 +/- 6.43 m/s vs. 6.51 +/- 3.25 m/s, p = 0.005)., Conclusions: Increased aortic stiffness, as indicated by increased PWV, is evident in HCM patients, and is more pronounced in those with myocardial fibrosis. Further, aortic stiffening may adversely affect left ventricular performance. In addition, increased aortic stiffness correlates with myocardial fibrosis, and may represent another potentially important parameter for risk stratification in HCM, warranting further study.

Objectives: This study sought to determine whether multidetector computed tomography (MDCT) may be able to detect occlusive coronary disease in transplanted hearts., Background: In heart transplant recipients, asymptomatic coronary disease requiring frequent surveillance commonly develops. Recent advancements in MDCT allow for noninvasive assessment of the coronary vessels., Methods: Electrocardiogram-gated contrast-enhanced MDCT scans (16 x 0.75-mm detectors, 420 ms rotation, 100 ml contrast) with multisegment reconstruction were performed on 54 transplant recipients within 6 +/- 11 days of quantitative coronary angiography (QCA). Heart rate at the time of the scan was 90 +/- 11 beats/min. Coronary arterial segments >1.5 mm in diameter were analyzed by independent investigators., Results: There was a good correlation between MDCT and QCA percent stenosis (r = 0.75, p < 0.01, SEE = 15%). Of the 791 segments identified by QCA, 754 (95%) were analyzable by MDCT. The sensitivity, specificity, and positive and negative predictive values of MDCT compared with QCA for the detection of segments with significant (>50%) stenosis were 86%, 99%, 81%, and 99%, respectively. The MDCT correctly identified 15 of the 16 (94%) transplant patients classified by QCA as having occlusive coronary artery disease and 29 of the 37 patients without significant stenosis (78%). In 1 patient who received intravenous beta-blockers, transient bradycardia requiring temporary pacing developed, but there were no other complications., Conclusions: Detection of occlusive coronary disease in heart transplant recipients with elevated resting heart rate by MDCT is feasible using multicycle reconstruction. The need for surveillance invasive coronary angiography in transplant recipients might be mitigated by use of MDCT.

Objectives: The aim of this study was to determine the effect of transient myocardial ischemia on circulating natriuretic peptide levels., Background: Natriuretic peptides are released by the heart in response to wall stress. We hypothesized that transient myocardial ischemia would cause acute changes in circulating natriuretic peptide levels., Methods: B-type natriuretic peptide (BNP), N-terminal fragment of BNP pro-hormone (NT-pro-BNP), and N-terminal fragment of atrial natriuretic peptide pro-hormone (NT-pro-ANP) levels were measured in 112 patients before, immediately after, and 4 h after exercise testing with nuclear perfusion imaging., Results: Baseline levels of BNP were associated with the subsequent severity of provoked ischemia, with median levels of 43, 62, and 101 pg/ml in patients with none, mild-to-moderate, and severe inducible ischemia, respectively (p = 0.03). Immediately after exercise, the median increase in BNP was 14.2 pg/ml in patients with mild-to-moderate ischemia (p = 0.0005) and 23.7 pg/ml in those with severe ischemia (p = 0.017). In contrast, BNP levels only rose by 2.3 pg/ml in those who did not develop ischemia (p = 0.31). A similar relationship was seen between baseline NT-pro-BNP levels and inducible ischemia, but the changes in response to ischemia were less pronounced. NT-pro-ANP levels rose with exercise in both ischemic and non-ischemic patients. When added to traditional clinical predictors of ischemia, a post-stress test BNP >or=80 pg/ml remained a strong and independent predictor of inducible myocardial ischemia (odds ratio 3.0, p = 0.025)., Conclusions: Transient myocardial ischemia was associated with an immediate rise in circulating BNP levels, and the magnitude of rise was proportional to the severity of ischemia. These findings demonstrate an important link between the severity of an acute ischemic insult and the circulating levels of BNP.

Magnetic resonance (MR) imaging is gaining importance in cardiology as the newest, most complex, and rapidly emerging noninvasive test of choice for patients with a multitude of cardiovascular problems. It has long been recognized to provide an accurate and reliable means of assessing the function and anatomy of the heart and great vessels, but its emerging role as one of the dominant imaging modalities in other aspects of cardiology such as perfusion imaging, atherosclerosis imaging, and coronary artery imaging cannot be understated. As MR technology evolves, newer therapeutic applications are also being developed, including specific MR-compatible catheters for electrophysiology studies/ablation as well as interventional cardiology related procedures, which may alter the way we practice cardiology in the future. Also, MR is entering an important phase in its evolution, with an anticipated exponential growth in its current applications and through the development of newer molecular imaging applications. It is anticipated that such developments will be coupled to the utilization of molecular markers to index biologic processes to allow for their in vivo visualization. This combination of biochemical markers and imaging methodology will also usher in an era of molecular imaging during which much progress in the diagnosis and treatment of cardiovascular disease is anticipated.