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Background: Heart failure patients who are candidates for CRT frequently display longitudinal rotation (LR) - a swinging motion of the heart when imaged in a horizontal long-axis plane. Objectives: To identify the magnitude and predictors of LR in patients with ischaemic (ICM) and idiopathic dilated (DCM) cardiomyopathy, and to assess predictive value of LR in patients undergoing cardiac resynchronisation therapy (CRT). Design and Setting: A retrospective study in a tertiary heart care setting. Methods: Echocardiography was performed in 45 ICM and 41 DCM patients who were CRT candidates and 16 control subjects. Global LR, segmental strains and segmental LR were assessed from echocardiograms using speckle tracking. Repeat echocardiography >40 days after the beginning of CRT was performed in 64 patients. Results: While DCM patients with QRS duration of both <130 ms and > or =130 ms displayed significant clockwise LR (p<0.001 for both vs 0), ICM patients and control subjects had LR that did not differ from 0. The most significant LR predictor was end-diastolic volume (p<0.001) followed by the absence of ischaemia (p<0.001) and QRS duration (p = 0.05). DCM patients with prominent clockwise LR had lower septal but higher lateral strains than DCM patients with minimal LR, or ICM patients with counterclockwise LR. LR correlated with decrease of end-systolic volume in DCM (r = 0.49, p = 0.004), while no relationship was observed in ICM. Conclusion: Clockwise LR is linked to presence of DCM, with the small impact of QRS duration. LR is a moderately strong predictor of end-systolic volume decrease during CRT in DCM. [ABSTRACT FROM AUTHOR]

Background: In severely symptomatic patients with obstructive hypertrophic cardiomyopathy (HCM), the VALOR-HCM (A Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy Who Are Eligible for Septal Reduction Therapy) trial showed that mavacamten reduced the eligibility for septal reduction therapy with sustained improvement in left ventricular outflow tract gradients. Mavacamten also resulted in favorable cardiac remodeling, including improvement in biomarkers (eg, N-terminal pro-B-type natriuretic peptide and troponin T). However, the impact of mavacamten on left atrial (LA) function is unknown., Objectives: The aim of this study was to assess serial changes in LA strain measures in patients enrolled in the VALOR-HCM trial., Methods: VALOR-HCM included 112 symptomatic patients with obstructive HCM (mean age 60 years; 51% male). Patients assigned to receive mavacamten at baseline (n = 56) continued therapy for 56 weeks and those assigned to placebo transitioned to mavacamten (n = 52) from week 16 to week 56. Echocardiographic LA strain (reservoir, conduit, and contraction) was measured by using a vendor-neutral postprocessing software., Results: At baseline, the mean LA volume index (LAVI) and LA strain values (conduit, contraction, and reservoir) were 41.3 ± 16.5 mL/m 2 , -11.8% ± 6.5%, -8.7% ± 5.0%, and 20.5% ± 8.7%, respectively (all worse than reported normal). LAVI significantly improved by -5.6 ± 9.7 mL/m 2 from baseline to week 56 (P < 0.001). There was a significant (P < 0.05) improvement in absolute LA strain values from baseline to week 56 (conduit [-1.7% ± 6%], contraction [-1.2% ± 4.5%], and reservoir [2.8% ± 7.7%]). Patients originally receiving placebo had no differences in LA measurements up to week 16. There was no significant improvement in LA strain values (conduit [-0.9% ± 3.8%], contraction [-0.4% ± 3.4%], and reservoir [1.4% ± 6.1%]; all; P = NS) from baseline to week 56 in patients with history of atrial fibrillation., Conclusions: In VALOR-HCM, mavacamten resulted in an improvement in LAVI and LA strain at week 56, suggesting sustained favorable LA remodeling and improved function, except in the atrial fibrillation subgroup. Whether the advantageous LA remodeling associated with long-term treatment with mavacamten results in a favorable impact on the observed high burden of atrial tachyarrhythmias in HCM remains to be proven. (A Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy Who Are Eligible for Septal Reduction Therapy [VALOR-HCM]; NCT04349072)., Competing Interests: Funding Support and Disclosures Bristol Myers Squibb policy on data sharing is provided at https://www.bms.com/researchers-and-partners/independent-research/data-sharing-request-process.html. The VALOR-HCM study was funded by Bristol Myers Squibb. Dr Desai has received consulting fees from Bristol Myers Squibb, Cytokinetics, Tenaya, Edgewise, and Viz.AI; and has done research support to Cleveland Clinic from Bristol Myers Squibb, Cytokinetics, and Tenaya. Drs Wolski and Nissen work for the Cleveland Clinic Coordinating Center for Clinical Research and are employees of the Cleveland Clinic, which received payments for the current research from Bristol Myers Squibb. Dr Geske has received consulting fees from Bristol Myers Squibb. Dr Owens has received consulting fees from Bristol Myers Squibb, Cytokinetics, Pfizer, BioMarin, Tenaya, Lexicon, Stealth, Edgewise, Renovacor; and has received grant support for research from Bristol Myers Squibb. Dr Saberi has received consulting fees from Bristol Myers Squibb and Cytokinetics. Dr Wang has received research grants (to institution) from Bristol Myers Squibb, Cytokinetics, and Abbott Vascular; has been on the consulting/advisory board from Bristol Myers Squibb; has held steering committee roles for Bristol Myers Squibb and Cytokinetics; and has received speaker fees 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. Drs Sherrid, Tower-Rader, and Naidu have received consulting fees from Bristol Myers Squibb and Cytokinetics. Dr Fermin has received consulting and speaker fees from Bristol Myers-Squibb and BridgeBio; and has received consulting fees from Pfizer. Drs Lampl and Sehnert are employed and have stock ownership at Bristol Myers Squibb. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: In severely symptomatic patients with obstructive hypertrophic cardiomyopathy, VALOR-HCM (A Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy Who Are Eligible for Septal Reduction Therapy) demonstrated that mavacamten reduces the need for septal reduction therapy with sustained improvement in left ventricular (LV) outflow tract gradients and symptoms. Global longitudinal strain (GLS), a measure of regional myocardial function, is a more sensitive marker of systolic function. In VALOR-HCM, we assessed serial changes in LV and right ventricular (RV) strain., Methods: VALOR-HCM included 112 patients with symptomatic obstructive hypertrophic cardiomyopathy (mean, 60 years; 51% male; LV ejection fraction, 68%). Patients assigned to mavacamten at baseline continued the drug for 56 weeks (n=56) and those assigned to placebo (n=52) transitioned to mavacamten from weeks 16 to 56 (40-week exposure). LV-GLS and RV-GLS assessment was performed using a vendor-neutral software. Non-foreshortened apical (4-, 3-, and 2-chamber) views were used to obtain peak LV-GLS. RV focused 4-chamber view was used to calculate RV 4-chamber and free wall strain. A more negative strain value is favorable., Results: At baseline, the mean LV-GLS, RV 4-chamber, and free wall strain values were -14.7%, -22.2%, and -16.8%, respectively (all worse than reported normal means). In the total study sample, LV-GLS significantly improved from baseline to week 56 ( P =0.02). Twelve patients had transient reduction in LV ejection fraction (<50%) requiring temporary drug interruption (including 3 permanent discontinuations). The LV-GLS in this subgroup was worse at baseline versus total study population (-11.4%), with no significant worsening from baseline through week 56 ( P =0.64). Both free wall and 4-chamber RV-GLS remained unchanged from baseline to week 56 ( P =0.62 and P =0.56, respectively)., Conclusions: In VALOR-HCM, treatment with mavacamten improved LV-GLS from baseline through week 56 (with no significant worsening of LV-GLS in patients with a reduction in LV ejection fraction ≤50%), suggesting a favorable long-term impact on regional LV systolic function. Additionally, there was no detrimental impact on RV systolic function., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04349072., Competing Interests: Dr Desai reports consulting for Bristol Myers Squibb, Cytokinetics, Tenaya, Edgewise, and viz.AI and research support to Cleveland Clinic from Bristol Myers Squibb, Cytokinetics, and Tenaya. Dr Owens reports consulting for Bristol Myers Squibb, Cytokinetics, Pfizer, Biomarin, Tenaya, Lexicon, Stealth, Edgewise, and Renovacor and grant support for research from BMS. Dr Saberi reports consulting for Bristol Myers Squibb and Cytokinetics. Dr Lakdawala has received consulting incomes from Bristol Myers Squibb, Pfizer, Tenaya, Cytokinetics, and Akros and research support from Bristol Myers Squibb and Pfizer. Dr Wang reports research grants (to institution) from Bristol Myers Squibb, Cytokinetics, and Abbott Vascular; being on the consulting/advisory board from Bristol Myers Squibb; being on the steering committee for Bristol Myers Squibb and Cytokinetics; and speaker fees from Bristol Myers Squibb. Drs Naidu, Sherrid, and Tower-Rader report consulting for Bristol Myers Squibb and Cytokinetics. Dr Geske reports consultation with Bristol Myers Squibb. Dr Fermin reports conflicts from Bristol Myers Squibb (consulting, speaking), Pfizer (consulting), and BridgeBio (consulting, speaking). Drs Gaballa, Cremer, Popovic, and Yokushi report no conflicts of interest. Dr Nissen and Wang work for C5 Research and are employees of Cleveland Clinic, which received payments for current research from Bristol Myers Squibb. Drs Lampl and Sehnert are employed by and have stock ownership at Bristol Myers Squibb.

Hypertrophic cardiomyopathy (HCM) affects as many as 1 in 200 people in the adult population globally. Patients may present with exertional dyspnea, presyncope or syncope, atrial and ventricular arrhythmias, heart failure, and even sudden cardiac death. Current guideline-based therapy involves medical therapy for treatment of symptoms in milder forms of the disease and surgical or catheter-based septal reduction therapies in obstructive HCM. Until recently, there has existed a gap between these two approaches that is now being filled by a new class of drugs, cardiac myosin inhibitors, which directly target the underlying disease process in HCM. Current investigations examine the effects of two cardiac myosin inhibitors on reported symptoms, echocardiographic evidence of disease, and the associated need for septal reduction. This paper reviews the contemporary evidence for the use of cardiac myosin inhibitors in HCM in adults and highlights future directions for this exciting field of cardiovascular medicine., (© 2024. The Author(s).)

Competing Interests: Funding Support and Author Disclosures The current study was funded by unrestricted philanthropic gifts by the Ratner family, Stinson family, and Anderson family for Dr Desai’s research. Dr Desai is a consultant and has research agreements with Bristol Myers Squibb, Cytokinetics, Tenaya, Viz-AI and Edgewise; and is the Haslam Family Endowed Chair in Cardiovascular Medicine. Mrs Rutkowski and Mrs Ospina have received salary support from unrestricted philanthropic gifts by the Haslam family, Ratner family, Stinson family, and Anderson family. Dr Smedira is a consultant for Bristol Myers Squibb. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Background: There are significant sex and age differences in left ventricular (LV) remodeling that may lead to disparity in outcomes when used to inform the timing of aortic regurgitation (AR) intervention., Objectives: The aim of this study was to examine whether left atrial (LA) parameters might represent better criteria than LV parameters to inform the timing of AR intervention., Methods: Using data on patients with moderate to severe or severe AR with serial echocardiography (2010-2016), the longitudinal trends in left atrial volume index (LAVI) and left atrial reservoir strain (LAr) were evaluated by sex and age. The incremental utility of these parameters in predicting adverse events over LV parameters was also determined., Results: In 525 patients (25.7% women) with 1,687 echocardiograms over a median follow-up period of 2.0 years (Q1-Q3: 1.0-3.6 years), there was significant increase in LAVI (1.0 mL/m 2 per year [95% CI: 0.76-1.2 mL/m 2 per year]) and decrease in LAr (-1.3% per year [95% CI: -1.6% to -0.92%]), without a significant interaction by sex or age category (P for interaction ≥ 0.17). In addition, both LAVI and LAr were significant predictors of adverse events independent of LV parameters. The optimal discriminatory thresholds were 37 mL/m 2 for LAVI and 35% for LAr. These thresholds were similar across categories of sex and age. Within the relatively short-term follow-up, surgery was associated with survival benefit among patients with LAVI ≥37 mL/m 2 (HR: 0.33 [95% CI: 0.15-0.72]; P = 0.006) but was not statistically significant among patients with LAVI <37 mL/m 2 (HR: 0.46 [95% CI: 0.18-1.17]; P = 0.09). Similarly, surgery was associated with survival for the subgroup with LAr ≤35% but not among those with LAr >35%., Conclusions: Unlike LV remodeling, LA remodeling demonstrates a similar rate of progression between categories of sex and age among patients with AR. In addition, LA parameters provide incremental prognostic value over LV parameters., 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 © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: In symptomatic obstructive hypertrophic cardiomyopathy (oHCM) patients, mavacamten is commercially approved to help improve left ventricular (LV) outflow tract (LVOT) gradients, symptoms, and reduce eligibility for septal reduction therapy (SRT) under the risk evaluation and mitigation strategy (REMS) program. We sought to prospectively report the initial real-world clinical experience with the use of commercially available mavacamten in a multi-hospital tertiary healthcare system., Methods: We studied the first 150 consecutive oHCM patients (mean age 65 years, 53% women, 83% on betablockers and 61% in New York Heart Association [NYHA] class III) who were initiated on 5 mg of mavacamten with dose titrations using symptom assessment and echocardiographic measurements of LVOT gradient and LV ejection fraction (LVEF) measurements. We measured changes in NYHA class, LVEF, LVOT gradients (resting and Valsalva) at baseline, 4, 8 and 12 weeks., Results: At 261 ± 143 days (range of 31-571 days), 69 (46%) patients had ≥1 NYHA class, and 27 (18%) additional patients had ≥2 NYHA class improvement. The mean Valsalva LVOT gradient decreased from 72 ± 43 mmHg at baseline to 29 ± 31 mmHg at 4 weeks, 29 ± 28 mmHg at 8 weeks and 30 ± 29 mmHg at 12 weeks (p < 0.001). At baseline, 100% patients had Valsalva LVOT gradients ≥30 mmHg, which reduced to 29% at 4 weeks, 28% at 8 weeks and 30% at 12 weeks. In 40 patients who reported no symptomatic improvement, the mean Valsalva LVOT gradient decreased from 73 ± 39 mmHg at baseline to 34 ± 27 mmHg at 4 weeks, 35 ± 28 mmHg at 8 weeks and 30 ± 24 mmHg at 12 weeks (P < 0.001). The mean LVEF at baseline was 66 ± 6% and changed to 64 ± 5% at 4 weeks, 63 ± 5% at 8 weeks and 62 ± 7% at 12 weeks (p < 0.0001). No patient underwent SRT, developed LVEF ≤30% or developed heart failure requiring admission. Three (2%) patients needed temporary interruption of mavacamten due to LVEF<50%., Conclusions: In a real-world study in symptomatic oHCM patients at a multi-hospital tertiary care referral center, we demonstrate the efficacy and safety, along with the logistic feasibility of prescribing mavacamten under the REMS program., Competing Interests: Declaration of competing interest Dr. Desai is a consultant and has research agreements with Bristol Myers Squibb, Cytokinetics, Tenaya, Viz-AI and Edgewise. No industry support was utilized in the conduct of this study. Dr. Emery is a consultant for Bristol Myers Squibb. Others have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Transthoracic echocardiography (TTE) is the first-line tool to evaluate isolated tricuspid regurgitation (TR) but it has limitations and its TR quantification compared with magnetic resonance imaging (MRI) has been studied infrequently. We compared isolated severe TR quantification by TTE against MRI and developed a novel TTE-based algorithm. Isolated TR patients graded severe by TTE and who underwent MRI January 2007 to June 2019 were studied. The TTE and MRI measurements were analyzed by correlation, area under receiver-operative characteristics curve (AUC), and classification and regression tree algorithm of TTE parameters to best identify MRI-derived severe TR (regurgitant volume ≥45 ml and/or fraction ≥50%). A total of 108 of 262 (41%) that were graded as severe TR by TTE also had severe TR by MRI. There were moderate correlations between TTE and MRI in the quantification of TR severity and right atrial size (Pearson r = 0.428 to 0.645) but none to modest correlations between them in right ventricle quantification. The key TTE parameters to identify MRI-derived severe TR in the decision tree regression algorithm were right atrial volume indexed ≥47 ml/m 2 and effective regurgitant orifice area ≥0.45 cm 2 and especially if there is right ventricle free wall strain ≥ -9.5%. This novel algorithm has an AUC of 0.76% and 79% agreement to detect severe TR by MRI, which higher than the American Society of Echocardiography criteria with AUC 0.68% and 66% agreement (p = 0.006 and p <0.001, respectively). In conclusion, TTE-derived TR and right atrial quantification had moderate correlation and discrimination of severe TR by MRI, from which a novel TTE algorithm was derived, which had incrementally a higher accuracy than contemporary guidelines' criteria alone., Competing Interests: Declaration of Competing Interest Dr. Desai has research and consultant agreements with Myokardia Inc, Medtronic, and Silence therapeutics. Dr. Gillinov is a consultant for AtriCure, Medtronic, Edwards, CryoLife, Abbott, Johnson and Johnson, and ClearFlow and has right to equity in ClearFlow. The remining authors have no competing interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Patient reported outcomes (PRO) can assess quality of life (QOL) in obstructive hypertrophic cardiomyopathy (oHCM). In symptomatic oHCM patients, we sought to study the correlation between various PROs, their association with physician reported New York Heart Association (NYHA) class and changes after surgical myectomy., Methods: We prospectively studied 173 symptomatic oHCM patients undergoing myectomy (age 51 years, 62% men) between 3/17-6/20. PROs, including a) Kansas City Cardiomyopathy Questionnaire (KCCQ) summary score b) Patient-Reported Outcomes Measurement Information System [PROMIS] c) Duke Activity Status Index [DASI] & d) European QOL score [EQ-5D], along with NYHA class, 6-min walk test (6MWT) distance and peak left ventricular outflow tract gradient (PLVOTG) were recorded at baseline and 12 month follow-up., Results: The median baseline PRO scores (KCCQ summary, PROMIS physical, PROMIS mental, DASI, EQ-5D) were 50, 67, 63, 25, 50, 37, 44, 25 and 0.61, respectively; 6MWT distance was 366 m. There were significant correlations between various PROs (r-values between 0.66 and 0.92, p < 0.001), but only modest correlations with 6MWT and provokable LVOTG (r-values between 0.2 and 0.5, p < 0.01). At baseline, 35-49% patients in NYHA class II had PROs worse than median, while 30-39% patients in NYHA Class III/IV had PROs better than median. At follow-up, a 20 point improvement in KCCQ summary score was observed in 80%, 4 point improvement in DASI score in 83%, 4 point improvement in PROMIS physical score 86% and a 0.04 point improvement in EQ-5D in 85%); along with improvements in NYHA class (67% in Class I) and peak LVOTG (median 13 mmHg) and 6MWT (median distance 438 m)., Conclusions: In a prospective study of symptomatic oHCM patients, surgical myectomy significantly improved PROs, LVOT obstruction, and functional capacity, with a high correlation between various PROs. However, there was high rate of discordance between PROs and NYHA class., Study Registration: ClinicalTrials.gov: NCT03092843., Competing Interests: Declaration of Competing Interest Dr. Desai is a consultant for Bristol Myers Squibb, Cytokinetics, Tenaya and Medtronic. Dr. Tower-Rader is a consultant for Bristol Myers Squibb and Cytokinetics. Dr. Smedira is a consultant for Bristol Myers Squibb. Others have no conflicts., (Copyright © 2023 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: Significant tricuspid regurgitation (TR) is associated with poor outcome and high operative mortality resulting from late presentation. Yet, the optimal timing for intervention is unknown., Objectives: The purpose of this study was to evaluate the prognostic value of echocardiographic parameters to inform early intervention in asymptomatic TR., Methods: Using the Cleveland Clinic echocardiography database 2004 to 2018, the authors identified a consecutive cohort of asymptomatic patients with moderate to severe (3+) or severe (4+) TR. Quantitative TR and right heart parameters were retrospectively determined, and their prognostic utility for all-cause mortality was assessed., Results: In 325 asymptomatic patients (mean age: 67.9 years; 79.4% female) with at least 3+ TR, there were 132 deaths (40.6%), with a median survival time of 9.9 years (95% CI: 7.9-12.7 years). By contrast, the median survival time in an age- and sex-matched cohort of symptomatic TR patients was 4.4 years (95% CI: 2.8-5.9 years). Among all the echocardiographic parameters evaluated, right ventricle free wall strain (RVFWS) and tricuspid regurgitant volume (RVol) were the strongest predictors of mortality in asymptomatic TR. The optimal discriminatory thresholds for these parameters were RVFWS <-19% and RVol >45 mL. The 5-year survival rates by number of risk factors (RF) were 93% (95% CI: 86%-96%), 65% (95% CI: 55%-74%), and 38% (95% CI: 26%-49%) for no RF, 1 RF, and both RFs, respectively. Compared with symptomatic TR, mortality was lower for asymptomatic TR with no RF (HR: 0.10; 95% CI: 0.04-0.29) or 1 RF (HR: 0.29; 95% CI: 0.14-0.58), but similar for asymptomatic TR with both RFs (HR: 1.11; 95% CI: 0.56-2.19)., Conclusions: RVFWS and RVol are key prognostic markers that can be serially monitored to inform optimal timing of intervention for severe asymptomatic TR., Competing Interests: Funding Support and Author Disclosures Dr Gillinov has served as a consultant to AtriCure, Medtronic, Edwards Lifesciences, CryoLife, Abbott, and ClearFlow; and has rights to equity in ClearFlow. Dr Desai has been supported by the Haslam Family endowed chair in cardiovascular medicine at the Cleveland Clinic. The current research was supported by a philanthropic gift from the Haslam family, Bailey family, and Khouri family. Dr Desai has research and consulting agreements with Bristol Myers Squibb, Medtronic, and Caristo Diagnostics. 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.)

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: We sought to determine the incremental prognostic value of age-sex adjusted N-terminal prohormone brain natriuretic peptide (NT-pro BNP) ratio in obstructive hypertrophic cardiomyopathy (oHCM) patients., Methods: The study included 2119 consecutive oHCM patients (age 55 ± 13 years, 53% men, maximal LVOT ≥30 mmHg) evaluated between 6/2002-12/2018 with BNP or NT-pro BNP measured at baseline. NT-pro BNP ratio was calculated as: NT-proBNP/ upper limit of normal NT-proBNP derived from age-sex matched controls. Septal reduction therapy (SRT) during follow-up was recorded. Primary endpoint was death, need for cardiac transplantation or appropriate internal cardioverter defibrillator (ICD) discharge., Results: Median NT-proBNP ratio was 5.4 (IQR 2.1-12.3). Using spline analysis, log-transformed NT-pro BNP ratio of 2 (corresponding to NT-pro BNP ratio of 6) was the optimal value where primary endpoint hazards crossed 1; there were 966 patients with high and 1153 patients with low NT-pro BNP ratio. 1665 (79%) patients underwent SRT at 47 days (IQR 7-128 days). At 5.4 years of follow-up (IQR 2.8-9.2 years), the primary outcome occurred in 315 (15%) patients (deaths = 270). High NT-pro BNP ratio was associated with higher risk of primary outcome in unadjusted (30.1 vs. 17.2 events/1000 person-year, hazard ratio or (HR) 1.73, 1.37-2.17, P < 0.001) and adjusted analysis (aHR 1.69, 95% 1.19-2.38, P = 0.003) vs. low NT-pro BNP ratio. Even in asymptomatic patients, NT-pro BNP ratio remained associated with primary outcome (aHR 1.28, 95% CI 1.06-1.54, P = 0.01)., Conclusions: Age-sex adjusted NT-pro BNP ratio is independently associated with long-term outcomes in oHCM patients, including in a subgroup of asymptomatic patients., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The incremental utility of right ventricular (RV) strain on predicting right ventricular failure (RVF) following left ventricular assist device (LVAD) implantation, beyond clinical and haemodynamic indices, is not clear., Methods: Two hundred and forty-six (246) patients undergoing LVAD implantation, who had transthoracic echocardiograms pre and post LVAD, pulmonary artery pulsatility index (PAPI) measurements and Michigan risk score, were included. We analysed RV global longitudinal strain (GLS) using speckle tracking echocardiography. RVF following LVAD implantation was defined as the need for medical support for >14 days, or unplanned RV assist device insertion after LVAD implantation., Results: Mean preoperative RV-GLS was -7.8±2.8%. Among all, 27% developed postoperative RVF. A classification and regression tree analysis identified preoperative Michigan risk score, PAPI and RV-GLS as important parameters in predicting postoperative RVF. Eighty per cent (80%) of patients with PAPI <2.1 developed postoperative RVF, while only 4% of patients with PAPI >6.8 developed RVF. For patients with a PAPI of 2.1-3.2, having baseline Michigan risk score >2 points conferred an 81% probability of subsequent RVF. For patients with a PAPI of 3.3-6.8, having baseline RV-GLS of -4.9% or better conferred an 86% probability of no subsequent RVF. The sensitivity and specificity of this algorithm for predicting postoperative RVF were 67% and 93%, respectively, with an area under the curve of 0.87., Conclusion: RV-GLS has an incremental role in predicting the development of RVF post-LVAD implantation, even after controlling for clinical and haemodynamic parameters., (Copyright © 2022 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Objective: Calcium metabolism has long been implicated in aortic stenosis (AS). Studies assessing the long-term safety of oral calcium and/or vitamin D in AS are scarce yet imperative given the rising use among an elderly population prone to deficiency. We sought to identify the associations between supplemental calcium and vitamin D with mortality and progression of AS., Methods: In this retrospective longitudinal study, patients aged ≥60 years with mild-moderate native AS were selected from the Cleveland Clinic Echocardiography Database from 2008 to 2016 and followed until 2018. Groups were stratified into no supplementation, supplementation with vitamin D alone and supplementation with calcium±vitamin D. The primary outcomes were mortality (all-cause, cardiovascular (CV) and non-CV) and aortic valve replacement (AVR), and the secondary outcome was AS progression by aortic valve area and peak/mean gradients., Results: Of 2657 patients (mean age 74 years, 42% women) followed over a median duration of 69 months, 1292 (49%) did not supplement, 332 (12%) took vitamin D alone and 1033 (39%) supplemented with calcium±vitamin D. Calcium±vitamin D supplementation was associated with a significantly higher risk of all-cause mortality (absolute rate (AR)=43.0/1000 person-years; HR=1.31, 95% CI (1.07 to 1.62); p=0.009), CV mortality (AR=13.7/1000 person-years; HR=2.0, 95% CI (1.31 to 3.07); p=0.001) and AVR (AR=88.2/1000 person-years; HR=1.48, 95% CI (1.24 to 1.78); p<0.001). Any supplementation was not associated with longitudinal change in AS parameters in a linear mixed-effects model., Conclusions: Supplemental calcium with or without vitamin D is associated with lower survival and greater AVR in elderly patients with mild-moderate AS., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: The authors report etiologies and outcomes and devise a risk model in a large contemporary cohort of patients with isolated tricuspid regurgitation (TR)., Background: Isolated TR is a challenging clinical entity with heterogeneous etiology and often poor outcomes, with a paucity of recent research regarding the epidemiology of isolated TR., Methods: Consecutive patients with isolated TR graded at least moderate to severe on echocardiography from January 2004 to December 2018 (n = 9,045, mean age 70.4 ± 15.4 years, 60.3% women) were studied. TR etiologies were individually adjudicated as secondary or primary, with subcategories. All-cause death during follow-up was the primary endpoint, with associations between etiology and outcomes analyzed and a risk model created., Results: Primary and secondary TR etiologies were present in 470 (5.2%) and 8,575 (94.8%) patients, respectively. The main secondary etiologies were left heart disease in 4,664 (54.4%), atrial functional in 2,086 (24.3%), and pulmonary disease in 1,454 (17.0%), and the main primary etiologies were endocarditis in 222 (47.2%), degenerative or prolapse in 86 (18.3%), and prosthetic valve failure in 79 (16.8%). There were 3,987 deaths (44.0%) over a mean follow-up period of 2.6 ± 3.3 years. In unadjusted analyses, patients with secondary TR had worse survival than those with primary TR (HR: 1.56; 95% CI: 1.32-1.85), but this result was not statistically significant in multivariable analysis. The authors devised and internally validated a risk score for predicting 1-year mortality in these patients., Conclusions: Secondary TR constituted 95% of isolated significant TR and conferred worse survival than primary TR in unadjusted but not adjusted analyses. The present novel risk score stratifies the risk for 1-year death and may influence decision making for management in these high-risk patients., Competing Interests: Funding Support and Author Disclosures Dr Wang is supported by the National Heart Foundation of New Zealand Overseas Clinical and Research Fellowship (grant 1775). Dr Desai is supported by the Haslam Family endowed chair in cardiovascular medicine at the Cleveland Clinic, a generous philanthropic gift from the Haslam family, Bailey family, and Khouri family. Dr Desai has research and consulting agreements with Myokardia, Medtronic, and Silence Therapeutics. Dr Gillinov is a consultant to AtriCure, Medtronic, Edwards Lifesciences, CryoLife, Abbott, Johnson & Johnson, and ClearFlow; and has rights to equity in ClearFlow. 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.)

Controversies remain in the management strategy for isolated tricuspid regurgitation (TR) because of adverse prognosis and uncertainties regarding the benefits of tricuspid valve surgery. We compared the characteristics and outcomes of a large cohort of patients with isolated TR, based on downstream tricuspid valve surgery versus medical management. Consecutive patients with isolated TR graded at least moderate-to-severe by echocardiography identified between January 2004 and December 2018 (n = 9,031, age 70 ± 15 years, 60% women) were retrospectively studied. The primary end point was time to all-cause mortality during follow-up. Outcomes were compared by management strategy using unadjusted and adjusted survival and multivariable regression analyses. Tricuspid valve surgery was performed in 632 of 9,031 of the cohort (7%), including 514 valve repairs and 118 valve replacements, with in-hospital mortality in 19 patients (2.9%). Overall, there were 3,985 all-cause deaths (44%) over mean follow-up of 2.6 ± 3.3 years. Tricuspid valve surgery was independently associated with lower mortality rate during follow-up, with hazard ratios (HRs) of 0.53 (95% confidence interval [CI] 0.45 to 0.64), and the association persisted in both primary and secondary TR subgroups. Tricuspid valve surgery also had a significantly higher rate of infective endocarditis and heart failure hospitalizations rates during follow-up, at HRs of 5.55 (95% CI 4.00 to 7.71) and 1.29 (95% CI 1.16 to 1.43), respectively. In conclusion, tricuspid valve surgery is rarely performed in isolated TR, but it is independently associated with greater survival for the overall cohort and both primary and secondary etiology subgroups. Increasing the utilization of this surgery at specialized centers is encouraged to try to improve the clinical outcomes for this challenging clinical entity., Competing Interests: Disclosures Dr. Desai has research and consultant agreements with Myokardia Inc, Medtronic, Silence therapeutics, and Caristo Diagnostics. Dr. Gillinov is consultant to AtriCure, Medtronic, Edwards, CryoLife, Abbott, Johnson and Johnson, and ClearFlow and has right to equity for ClearFlow. The other authors have no conflicts of interest to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background Hypertrophic cardiomyopathy (HCM) and aortic stenosis can cause obstruction to the flow of blood out of the left ventricular outflow tract into the aorta, with obstructive HCM resulting in dynamic left ventricular outflow tract obstruction and moderate or severe aortic stenosis causing fixed obstruction caused by calcific degeneration. We sought to report the characteristics and longer-term outcomes of patients with severe obstructive HCM who also had concomitant moderate or severe aortic stenosis requiring surgical myectomy and aortic valve replacement. Methods and Results We studied 191 consecutive patients (age 67±6 years, 52% men) who underwent myectomy and aortic valve (AV) replacement (90% bioprosthesis) at our center between June 2002 and June 2018. Clinical and echo data including left ventricular outflow tract gradient and indexed AV area were recorded. The primary outcome was death. Prevalence of hypertension (63%) and hyperlipidemia (75%) were high, with a Society of Thoracic Surgeons score of 5±4, and 70% of participants had no HCM-related sudden death risk factors. Basal septal thickness and indexed AV area were 1.9±0.4 cm and 0.72±0.2 cm 2 /m 2 , respectively, while 100% of patients had dynamic left ventricular outflow tract gradient >50 mm Hg. At 6.5±4 years, 52 (27%) patients died (1.5% in-hospital deaths). One-, 2-, and 5-year survival in the current study sample was 94%, 91%, and 83%, respectively, similar to an age-sex-matched general US population. On multivariate Cox survival analysis, age (hazard ratio [HR], 1.65; 95% CI, 1.24-2.18), chronic kidney disease (HR, 1.58; 95% CI, 1.21-2.32), and right ventricular systolic pressure on preoperative echocardiography (HR, 1.28; 95% CI, 1.05-1.57) were associated with longer-term mortality, but traditional HCM risk factors did not. Conclusions In symptomatic patients with severely obstructive HCM and moderate or severe aortic stenosis undergoing a combined surgical myectomy and AV replacement at our center, the observed postoperative mortality was significantly lower than the expected mortality, and the longer-term survival was similar to a normal age-sex-matched US population.

Background: Isolated tricuspid regurgitation (TR) remains a management dilemma with poor outcomes. Echocardiography and cardiac magnetic resonance imaging (CMR) are valuable tools for evaluating TR, but their prognostic utility has rarely been studied together in this setting. We aimed to determine the prognostic value and thresholds for echocardiography and CMR parameters for isolated severe TR., Methods: Consecutive patients with isolated severe TR by echocardiography and undergoing CMR during January 2007 to June 2019 were studied. Echocardiography and CMR-derived quantitative parameters were analyzed for independent associations with and thresholds for predicting the primary end point of all-cause mortality during follow-up., Results: Among 262 patients studied, mean age was 62.8±15.6 years, 156 (59.5%) were females, 207 (79.0%) had secondary TR, and 87 (33.2%) underwent tricuspid valve surgery after CMR. There were 68 (26.0%) deaths during a mean follow-up of 2.5 years. Both CMR-derived tricuspid regurgitant fraction (per 5% increase) and right ventricle free wall longitudinal strain (per 1% decrease in magnitude) were independently associated with worse survival, with hazard ratios (95% CIs) of 1.15 (1.05-1.25) and 1.10 (1.04-1.17), respectively, along with right heart failure symptoms of 2.03 (1.14-3.60), while tricuspid valve surgery was borderline protective with 0.55 (0.31-0.997). Regurgitant fraction ≥30%, regurgitant volume ≥35 mL and right ventricle free wall longitudinal strain ≥-11% (by velocity vector imaging technique, which yields lower magnitude values than other conventional strain techniques) were the optimal thresholds for mortality during follow-up., Conclusions: TR quantification by CMR and right ventricle free wall longitudinal strain by echocardiography were the key imaging parameters independently associated with reduced survival in isolated TR, incremental to conventional clinical factors. Clinically significant thresholds for these parameters were determined and may help guide decision-making for TR management.

Objectives: To describe the use of echocardiography in patients hospitalised with suspected coronavirus infection and to assess its impact on clinical management., Methods: We studied 79 adults from a prospective registry of inpatients with suspected coronavirus infection at a single academic centre. Echocardiographic indications included abnormal biomarkers, shock, cardiac symptoms, arrhythmia, worsening hypoxaemia or clinical deterioration. Study type (limited or complete) was assessed for each patient. The primary outcome measure was echocardiography-related change in clinical management, defined as intensive care transfer, medication changes, altered ventilation parameters or subsequent cardiac procedures within 24 hours of echocardiography. Coronavirus-positive versus coronavirus-negative patient groups were compared. The relationship between echocardiographic findings and coronavirus mortality was assessed., Results: 56 patients were coronavirus-positive and 23 patients were coronavirus-negative with symptoms attributed to other diagnoses. Coronavirus-positive patients more often received limited echocardiograms (70% vs 26%, p=0.001). The echocardiographic indication for coronavirus-infected patients was frequently worsening hypoxaemia (43% vs 4%) versus chest pain, syncope or clinical heart failure (23% vs 44%). Echocardiography changed management less frequently in coronavirus-positive patients (18% vs 48%, p=0.01). Among coronavirus-positive patients, 14 of 56 (25.0%) died during hospitalisation. Those who died more often had echocardiography to evaluate clinical deterioration (71% vs 24%) and had elevated right ventricular systolic pressures (37 mm Hg vs 25 mm Hg), but other parameters were similar to survivors., Conclusions: Echocardiograms performed on hospitalised patients with coronavirus infection were often technically limited, and their findings altered patient management in a minority of patients., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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.)

Objective: Patients with constrictive pericarditis (CP) with active inflammation may show resolution with anti-inflammatory therapy. We aimed to investigate the impact of anti-inflammatory medications on constrictive pathophysiology using echocardiography in patients with CP., Methods: We identified 35 patients with CP who were treated with anti-inflammatory medications (colchicine, prednisone, non-steroidal anti-inflammatory drugs) after diagnosis of CP (mean age 58±13; 80% male). Clinical resolution of CP (transient CP) was defined as improvement in New York Heart Association class during follow-up. We assessed constrictive pathophysiology using regional myocardial mechanics by the ratio of peak early diastolic tissue velocity (e') at the lateral and septal mitral annulus by tissue Doppler imaging (lateral/septal e') or the ratio of the left ventricular lateral and septal wall longitudinal strain (LS lateral /LS septal ) by two-dimensional speckle-tracking echocardiography. Longitudinal data were analysed using a mixed effects model., Results: During a median follow-up of 323 days, 20 patients had transient CP, whereas 15 patients had persistent CP. Transient CP had higher baseline erythrocyte sedimentation rates (ESR) (p=0.003) compared with persistent CP. There were no significant differences in LS lateral /LS septal and lateral/septal e'. During follow-up, only transient CP showed improvement in lateral/septal e' (p<0.001) and LS lateral /LS septal (p=0.003), and recovery of inflammatory markers was similar between the two groups. In the logistic model, higher baseline ESR and greater improvement in lateral/septal e' and LS lateral /LS septal were associated with clinical resolution of CP using anti-inflammatory therapy., Conclusions: Improvement of constrictive physiology detected by lateral/septal e' and LS lateral /LS septal was associated with resolution of clinical symptoms after anti-inflammatory treatment. Serial monitoring of these markers could be used to identify transient CP., Competing Interests: Competing interests: ALK: research grant and scientific advisory board for Kiniksa; scientific advisory board for Sobi and Pfizer. PCC: scientific advisory board for Kiniksa., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Cardiac MRI is central to the evaluation of cardiac amyloidosis (CA). Native T 1 mapping and extracellular volume (ECV) are novel MR techniques with evolving utility in cardiovascular diseases, including CA., Purpose: To perform a meta-analysis of the diagnostic and prognostic data of native T 1 mapping and ECV techniques for assessing CA., Study Type: Systematic review and meta-analysis., Population: In all, 3520 patients including 1539 with CA from 22 studies retrieved following systematic search of Pubmed, Cochrane, and Embase., Field Strength/sequence: 1.5T or 3.0T/modified Look-Locker inversion recovery (MOLLI) or shortened MOLLI (shMOLLI) sequences., Assessment: Meta-analysis was performed for all CA and for light-chain (AL) and transthyretin (ATTR) subtypes. Thresholds were calculated to classify native T 1 and ECV values as not suggestive, indeterminate, or suggestive of CA., Statistical Analysis: Area under the receiver-operating characteristic curves (AUCs) and hazards ratios (HRs) with 95% confidence intervals (95% CI) were pooled using random-effects models and Open-Meta(Analyst) software., Results: Six studies were diagnostic, 16 studies reported T 1 and ECV values to determine reference range, and six were prognostic. Pooled AUCs (95% CI) for diagnosing CA were 0.92 (0.89-0.96) for native T 1 mapping and 0.96 (0.93-1.00) for ECV, with similarly high detection rates for AL- and ATTR-CA. Based on the pooled values of native T 1 and ECV in CA and control subjects, the thresholds that suggested the absence, indeterminate, or presence of CA were identified as <994 msec, 994-1073 msec, and >1073 msec, respectively, for native T 1 at 1.5T. Pooled HRs (95% CI) for predicting all-cause mortality were 1.15 (1.08-1.22) for native T 1 mapping as a continuous parameter, 1.19 (1.01-1.40) for ECV as a continuous parameter, and 4.93 (2.64-9.20) for ECV as a binary threshold., Data Conclusion: Native T 1 mapping and ECV had high diagnostic performance and predicted all-cause mortality in CA., Level of Evidence: 1 TECHNICAL EFFICACY STAGE: 2., (© 2020 International Society for Magnetic Resonance in Medicine.)

Background We report characteristics and outcomes of elderly patients with hypertrophic cardiomyopathy (HCM) with basal septal hypertrophy and dynamic left ventricular outflow tract obstruction. Methods and Results We studied 1110 consecutive elderly patients with HCM (excluding moderate or greater aortic stenosis or subaortic membrane, age 80±5 years [range, 75-92 years], 66% women), evaluated at our center between June 2002 and December 2018. Clinical and echocardiographic data, including maximal left ventricular outflow tract gradient, were recorded. The primary outcome was death and appropriate internal defibrillator discharge. Hypertension was observed in 72%, with a Society of Thoracic Surgeons (STS) score (8.6±6); while 80% had no HCM-related sudden cardiac death risk factors. Left ventricular mass index, basal septal thickness, and maximal left ventricular outflow tract gradient were 127±43 g/m 2 , 1.7±0.4 cm, and 49±31 mm Hg, respectively. A total of 597 (54%) had a left ventricular outflow tract gradient >30 mm Hg, of which 195 (33%) underwent septal reduction therapy (SRT; 79% myectomy and 21% alcohol ablation). At 5.1±4 years, 556 (50%) had composite events (273 [53%] in nonobstructive, 220 [55%] in obstructive without SRT, and 63 [32%] in obstructive subgroup with SRT). One- and 5-year survival, respectively were 93% and 63% in nonobstructive, 90% and 63% in obstructive subgroup without SRT, and 94% and 84% in the obstructive subgroup with SRT. Following SRT, there were 5 (2.5%) in-hospital deaths (versus an expected Society of Thoracic Surgeons mortality of 9.2%). Conclusions Elderly patients with HCM have a high prevalence of traditional cardiovascular rather than HCM risk factors. Longer-term outcomes of the obstructive SRT subgroup were similar to a normal age-sex matched US population.

Surveillance of left ventricular function, part of current US Food and Drug Administration recommendations for anti-human epidermal growth factor receptor 2 (anti-HER2) chemotherapy, is based on historical data involving patients who received concomitant anthracycline therapy, a key enhancer of cardiac risk. More recent anti-HER2 treatment data suggest that cardiotoxicity detected by screening is rare and usually benign for patients who do not have cardiovascular risk factors and are not taking an anthracycline. Because of the burden of repetitive echocardiography required for surveillance and the risk of false-positive results, potentially leading to discontinuing lifesaving treatment, we advocate for a more focused cardiac surveillance strategy., (Copyright © 2021 The Cleveland Clinic Foundation. All Rights Reserved.)

Background In patients with obstructive hypertrophic cardiomyopathy, surgical myectomy (SM) is indicated for severe symptoms. We sought to compare long-term outcomes of patients with obstructive hypertrophic cardiomyopathy where SM was based on guideline-recommended Class I indication (Functional Class or FC ≥3 or angina/exertional syncope despite maximal medical therapy) versus earlier (FC 2 and/or impaired exercise capacity on exercise echocardiography with severe obstruction). Methods and Results We studied 2268 consecutive patients (excluding <18 years, ≥ moderate aortic stenosis and subaortic membrane, 56±14 years, 55% men), who underwent SM at our center between June 2002 and March 2018. Clinical data, including left ventricular outflow tract gradient, were recorded. Death and/or appropriate internal defibrillator discharge were primary composite end points. One thousand three hundred eighteen (58%) patients met Class I indication and 950 (42%) underwent earlier surgery; 222 (10%) had a history of obstructive coronary artery disease. Basal septal thickness, and resting and maximal left ventricular outflow tract gradient were 2.0±0.3 cm, 61±44 mm Hg, and 100±31 mm Hg, respectively. At 6.2±4 years after SM, 248 (11%) had composite events (13 [0.6%] in-hospital deaths). Age (hazard ratio [HR], 1.61; 95% CI, 1.26-1.91), obstructive coronary artery disease (HR, 1.46; 95% CI, 1.06-1.91), and Class I versus earlier SM (HR, 1.61; 95% CI, 1.14-2.12) were associated with higher primary composite events (all P <0.001). Earlier surgery had better longer-term survival (similar to age-sex-matched normal population) versus surgery for Class I indication (76 [8%] versus 193 [15%], P <0.001). Conclusions In patients with obstructive hypertrophic cardiomyopathy, earlier versus surgery for Class I indication had a better long-term survival, similar to the age-sex-matched US population.

To evaluate the temporal relations of cardiovascular disease in oncology patients referred to cardio-oncology and describe the impact of cardiovascular disease and cardiovascular risk factors on outcomes. All adult oncology patients referred to the cardio-oncology service at the Cleveland Clinic from January 2011 to June 2018 were included in the study. Comprehensive clinical information were collected. The impact on survival of temporal trends of cardiovascular disease in oncology patients were assessed with a Cox proportional hazards model and time-varying covariate adjustment for confounders. In total, 6,754 patients were included in the study (median age, 57 years; [interquartile range, 47 to 65 years]; 3,898 women [58%]; oncology history [60% - breast cancer, lymphoma, and leukemia]). Mortality and diagnosis of clinical cardiac disease peaked around the time of chemotherapy. 2,293 patients (34%) were diagnosed with a new cardiovascular risk factor after chemotherapy, over half of which were identified in the first year after cancer diagnosis. Patients with preexisting and post-chemotherapy cardiovascular disease had significantly worse outcomes than patients that did not develop any cardiovascular disease (p < 0.0001). The highest 1-year hazard ratios (HR) of post-chemotherapy cardiovascular disease were significantly associated with male (HR 1.81; 95% confidence interval 1.55 to 2.11; p < 0.001] and diabetes [HR 1.51; 95% confidence interval 1.26 to 1.81; p < 0.001]. In conclusion, patients referred to cardio-oncology, first diagnosis of cardiac events peaked around the time of chemotherapy. Those with preexisting or post-chemotherapy cardiovascular disease had worse survival. In addition to a high rate of cardiovascular risk factors at baseline, risk factor profile worsened over course of follow-up., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Mitral annular calcification (MAC) is prevalent in the aging population, with recent renewed interest regarding its associations with cardiovascular risk factors, outcomes, and influence on valvular heart disease and interventions. This meta-analysis aimed to report the relationships between MAC and cardiovascular mortality and morbidity events., Methods: Relevant studies were searched from PubMed, Cochrane, and Embase databases until November 30, 2019. Associations between MAC as a binary variable with death and cardiovascular events were pooled using random-effects models. The main outcomes of interest were all-cause and cardiovascular mortality, myocardial infarction, stroke, heart failure, atrial fibrillation, and procedural outcomes., Results: Among 799 article abstracts and 122 full-text articles screened, 26 (16 prospective and 10 retrospective) studies totaling 35 070 subjects were analyzed. MAC was associated with higher all-cause death, hazard ratio (95% confidence interval) 1.76 (1.43-2.22), and cardiovascular mortality 1.85 (1.45-23.5). It also positively correlated with myocardial infarction 1.48 (1.22-1.79), stroke 1.51 (1.22-2.05), incidental heart failure 1.55 (1.30-1.84), atrial fibrillation 1.75 (1.43-2.15), and their composite, major adverse cardiovascular events (MACE). Finally, conversion to mitral valve replacement at time of cardiac surgery was more in patients with MAC than without MAC, with odds ratio (95% confidence interval) 2.82 (1.28-6.18)., Conclusion: Mitral annular calcification was overall associated with higher rates of death, and both individual and composite cardiovascular events. The presence of increasingly encountered MAC has significant clinical implications for cardiovascular risk assessment and valvular interventions., (© 2020 Wiley Periodicals LLC.)

Background: Cardiac computed tomography (CT) is emerging as an adjunctive modality to echocardiography in the evaluation of infective endocarditis (IE) and surgical planning. CT studies in IE have, however, focused on its diagnostic rather than prognostic utility, the latter of which is important in high-risk diseases like IE. We evaluated the associations between cardiac CT and transesophageal echocardiography (TEE) findings and adverse outcomes after IE surgery., Methods: Of 833 consecutive patients with surgically proven IE during May 1, 2014 to May 1, 2019, at Cleveland Clinic, 155 underwent both preoperative ECG-gated contrast-enhanced CT and TEE. Multivariable analyses were performed to identify CT and TEE biomarkers that predict adverse outcomes after IE surgery, adjusting for EuroSCORE II (European System for Cardiac operative Risk Evaluation II)., Results: CT and TEE were positive for IE in 123 (75.0%) and 124 (75.6%) of patients, respectively. Thirty-day mortality occurred in 3 (1.9%) patients and composite mortality or morbidities in 72 (46.5%). Pseudoaneurysm or abscess detected on TEE was the only imaging biomarker to show independent association with composite mortality or morbidities in-hospital, with odds ratio (95% CI) of 3.66 (1.76-7.59), P =0.001. There were 17 late deaths, and both pseudoaneurysm or abscess detected on CT and fistula detected on CT were the only independent predictors of total mortality during follow-up, with hazards ratios (95% CI) of 3.82 (1.25-11.7), P <0.001 and 9.84 (1.89-51.0), P =0.007, respectively., Conclusions: We identified cardiac CT and TEE features that predicted separate adverse outcomes after IE surgery. Imaging biomarkers can play important roles incremental to conventional clinical factors for risk stratification in patients undergoing IE surgery.

Background We sought to determine (1) long-term outcomes in patients presenting with documented Takotsubo syndrome (TS), (2) whether left ventricular global longitudinal strain (LV-GLS) provides incremental prognostic value, and (3) prognostic cutoffs of LV ejection fraction (LVEF) and LV-GLS during an acute TS episode. Methods and Results We studied 650 patients with TS (aged 66±14 years, 88% women) who were diagnosed clinically and angiographically between 2006 and 2018. Baseline LVEF and LV-GLS (using velocity vector imaging) were recorded. The primary end point was all-cause mortality. TS triggers were unknown (34%), emotional (16%), physical (41%), and neurologic (10%). Mean LVEF and LV-GLS were 36±10% and -11.6±0.4%; in addition, 94% patients had LVEF <52%, and 80% had apical ballooning. No patient had obstructive coronary artery disease. At a median of 2.2 years (interquartile range, 0.7-4.4), 175 (27%) had died (9% in-hospital deaths). Multivariate Cox survival analysis revealed that higher age (hazard ratio [HR], 1.35), male sex (HR, 1.75), lower baseline LVEF (HR, 1.02), worse LV-GLS (HR, 1.04), neurologic trigger (HR, 2.66), and physical trigger (HR, 2.64) were associated with mortality, whereas aspirin (HR, 0.70) and β-blockers (HR, 0.73) improved survival (all P <0.049). The addition of LVEF and LV-GLS to clinical markers (age, sex, cardiogenic shock at presentation, and peak troponin I) significantly increased log-likelihood ratios: clinical (-521.48), clinical plus LVEF (-511.32, P <0.001), and clinical plus LVEF and LV-GLS (-500.68, P <0.001). On penalized spline analysis, LVEF of 38% and LV-GLS of -10% were cutoffs below which survival was significantly worse. Conclusions Patients with TS with a neurologic or physical trigger had significantly worse survival than those without such a trigger, with baseline LVEF and LV-GLS providing incremental prognostic value.

Objectives: Tricuspid valve disease is increasingly encountered, but surgery is rarely performed in isolation, in part because of a reported higher operative risk than other single-valve operations. Although guidelines recommend valve repair, there is sparse literature for the optimal surgical approach in isolated tricuspid valve disease. We performed a meta-analysis examining outcomes of isolated tricuspid valve repair versus replacement., Methods: We searched Pubmed, Embase, Scopus and Cochrane from January 1980 to June 2019 for studies reporting outcomes of both isolated tricuspid valve repair and replacement, excluding congenital tricuspid aetiologies. Data were extracted and pooled using random-effects models and Review Manager 5.3 software., Results: There were 811 article abstracts screened, from which 52 full-text articles reviewed and 16 studies included, totalling 6808 repairs and 8261 replacements. Mean age ranged from 36 to 68 years and females made up 24%-92% of these studies. Pooled operative mortality rates and odds ratios (95% confidence intervals) for isolated tricuspid repair and replacement surgery were 8.4% vs 9.9%, 0.80 (0.64 to 1.00). Tricuspid repair was also associated with lower in-hospital acute renal failure 12.4% vs 15.6%, 0.82 (0.72 to 0.93) and pacemaker implantation 9.4% vs 21.0%, 0.37 (0.24 to 0.58), but higher stroke rate 1.5% vs 0.9%, 1.63 (1.10 to 2.41). There were no differences in rates of prolonged ventilation, mediastinitis, return to operating room or late mortality., Conclusion: Isolated tricuspid valve repair was associated with significantly reduced in-hospital mortality, renal failure and pacemaker implantation compared with replacement and is therefore recommended where feasible for isolated tricuspid valve disease, although its higher stroke rate warrants further research., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: This study sought to determine whether baseline left ventricular global longitudinal strain (LV-GLS) and changes in left ventricular ejection fraction (LVEF) in a subgroup of subjects at post-operative follow-up added prognostic value in patients undergoing aortic valve (AV) surgery., Background: In patients with chronic severe aortic regurgitation (AR) and preserved LVEF, sensitive markers are needed to decide timing of AV surgery., Methods: This was an observational study in 865 patients (asymptomatic/mildly symptomatic, 52 ± 15 years of age, 79% men) with ≥3+ chronic AR and preserved LVEF of ≥50% who underwent AV surgery between 2003 and 2015. All patients had baseline echocardiography (and LV-GLS imaging), whereas 285 patients underwent post-operative echocardiography (including LV-GLS). Primary outcome was mortality., Results: Only 478 patients (56%) patients had preoperative LV-GLS values better than -19%, despite a mean LVEF of 57 ± 4%. At a median 38 days, 632 patients underwent AV replacement, whereas 233 patients had AV repair. At a median follow-up of 6.95 (interquartile range [IQR]: 5.2 to 9.1) years, 105 patients (12%) died (2% in-hospital deaths). A higher proportion of patients with baseline LV-GLS grades worse than -19% died versus those whose LV-GLS score was better (15% vs. 10%; p < 0.01), and worse LV-GLS value was independently associated with higher longer-term mortality (hazard ratio: 1.62; 95% confidence interval [CI]: 1.40 to 1.86]; p < 0.001). In the 285 patients who underwent echo at 3 to 12 months post-operatively, LVEF normalized in 91% patients; however, only 88 patients (31%) had LV-GLS values better than -19%. Patients whose follow-up LV-GLS value was better than -19% had significantly better longer-term survival than those whose LV-GLS was not (5% vs. 15%, respectively; p < 0.01). An absolute worsening of 5% of LV-GLS from baseline was associated with increased mortality., Conclusions: In patients with ≥3+ chronic AR and preserved LVEF undergoing AV surgery, a baseline LV-GLS value worse than -19% was associated with reduced survival. In a subgroup of patients who returned for 3- and 12-month follow-up examinations, persistently impaired LV-GLS was associated with increased mortality., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The association of left ventricular global longitudinal strain (LV-GLS) with clinical outcomes in patients with hypertrophic cardiomyopathy (HCM) has been examined in multiple studies. The authors conducted a systematic review aimed at summarizing and critically appraising the current evidence., Background: HCM is a common genetic cardiovascular disease with an estimated prevalence of 1 in 500 patients. LV-GLS derived from speckle tracking echocardiography is a sensitive noninvasive method of assessing regional left ventricular function. Several studies have suggested association of abnormal LV-GLS with outcomes in HCM patients., Methods: A computerized literature search of all English language publications in the PubMed and EMBASE databases was made looking at all randomized and nonrandomized studies conducted on patients with HCM where association of LV-GLS with clinical outcomes was studied. We then manually searched the reference lists of included articles. The Preferred Reporting Items for Systematic reviews and Meta-Analyses statement (PRISMA) of reporting systematic reviews was used., Results: Our search yielded a total of 14 observational studies published between 2009 and 2017 with a total of 3,154 patients with HCM. Eleven of the 14 studies included a composite cardiac outcome which included mortality as their primary outcome of interest and 3 of the 14 studies looked at association of LV-GLS with ventricular arrhythmias and/or implantable cardiac defibrillator discharge. We noted wide variability in inclusion, methodology, follow-up, and consequently effect estimates, which was not conducive to performing a meta-analysis. However, despite the variation, all studies revealed a degree of association of abnormal LV-GLS with poor cardiac outcomes., Conclusions: Our systematic review of more than 3000 HCM patients suggests an association of abnormal LV-GLS with adverse composite cardiac outcomes and ventricular arrhythmias., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)