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Background: Septal myectomy and alcohol septal ablation (ASA) are septal reduction therapies for patients with symptomatic obstructive hypertrophic cardiomyopathy. Operator and hospital volume may influence outcomes, but contemporary data on this relationship are limited., Methods and Results: This retrospective cohort study used data from the Vizient Clinical Data Base (2016-2022). Patients with undergoing septal myectomy and ASA were identified using International Classification of Diseases, Tenth Revision, Clinical Modification ( ICD-10-CM ) codes and stratified into low-, medium-, and high-volume groups based on annualized operator and hospital volumes. The outcomes were 30-day in-hospital mortality and 90-day readmission, analyzed using multivariable adjusted logistic and Cox models. Among 5725 patients with hypertrophic cardiomyopathy (3990 septal myectomy; 1735 ASA), most operators and hospitals performed <10 procedures annually. For septal myectomy, low-volume operators were associated with higher odds of 30-day mortality (adjusted odds ratio [aOR], 1.86 [95% CI, 1.11-3.15]) and greater risk for 90-day readmission (aOR, 1.51 [95% CI, 1.22-1.88]), and medium-volume operators had higher odds of 30-day mortality (aOR, 1.93 [95% CI, 1.05-3.55]). Medium-volume hospitals had higher 30-day mortality (aOR, 2.29 [95% CI, 1.32-3.99]), with low-volume hospitals showing greater risk for 90-day readmission (aOR, 1.60 [95% CI, 1.14-2.23]). For ASA, low- and medium-volume operators had increased 30-day mortality (aOR, 2.99 [95% CI, 1.15-7.75] and aOR, 3.86 [95% CI, 1.30-11.46]), but the risk of 90-day readmission was similar. Hospital volumes did not significantly impact outcomes for ASA., Conclusions: Low operator and hospital volumes were associated with worse outcomes for septal reduction therapies, emphasizing the need to refer patients with hypertrophic cardiomyopathy to high-volume centers with experienced operators.

Background: Septal reduction therapy (SRT) provides substantial symptomatic improvement in patients with obstructive hypertrophic cardiomyopathy (HCM). However, long-term disease course after SRT and predictors of adverse outcomes have not been systematically examined., Methods: Data from 13 high clinical volume HCM centers from the international SHARE (Sarcomeric Human Cardiomyopathy Registry) were analyzed. Patients were followed from the time of SRT until last follow-up or occurrence of heart failure (HF) composite outcome (cardiac transplantation, implantation of a left ventricular assist device, left ventricular ejection fraction <35%, development of New York Heart Association class III or IV symptoms), ventricular arrhythmias composite outcome (sudden cardiac death, resuscitated cardiac arrest, or appropriate implantable cardioverter defibrillator therapy), or HCM-related death. Cox proportional hazards models were used to identify predictors of outcome., Results: Of the 10 225 patients in SHARE, 1832 (18%; 968 [53%] male) underwent SRT, including 455 (25%) with alcohol septal ablation and 1377 (75%) with septal myectomy. The periprocedural 30-day mortality rate was 0.4% (8 of 1832) and 1499 of 1565 (92%) had a maximal left ventricular outflow tract gradient <50 mm Hg at 1 year. After 6.8 years (range, 3.4-9.8 years; 12 565 person-years) from SRT, 77 (4%) experienced HCM-related death (0.6% per year), 236 (13%) a composite HF outcome (1.9% per year), and 87 (5%) a composite ventricular arrhythmia outcome (0.7% per year). Among adults, older age at SRT was associated with a higher incidence of HCM death (hazard ratio, 1.22 [95 CI, 1.1-1.3]; P <0.01) and the HF composite (hazard ratio, 1.14 [95 CI, 1.1-1.2] per 5-year increase; P <0.01) in a multivariable model. Female patients also had a higher risk of the HF composite after SRT (hazard ratio, 1.4 [95 CI, 1.1-1.8]; P <0.01). De novo atrial fibrillation occurred after SRT in 387 patients (21%). Among pediatric patients followed for a median of 13 years after SRT, 26 of 343 (16%) developed the HF composite outcome, despite 96% being free of recurrent left ventricular outflow tract obstruction., Conclusions: Successful short- and long-term relief of outflow tract obstruction was observed in experienced multidisciplinary HCM centers. A subset of patients progressed to develop HF, but event-free survival at 10 years was 83% and ventricular arrhythmias were rare. Older age, female sex, and SRT during childhood were associated with a greater risk of developing HF., Competing Interests: Dr Ho is supported by funding from the National Institutes of Health (National Heart, Lung, and Blood Institute grant R01HL155568). Dr Day is supported by funding from the National Institutes of Health (National Heart, Lung, and Blood Institute grants R01 HL167524, R01 HL168841, and R61/R33 HL164376), Lexicon Pharmaceuticals, and the American Heart Association. Dr Ware is supported by the Wellcome Trust (grant 107469/Z/15/Z) and the UK Medical Research Council. Dr Scemsarian is the recipient of a National Health and Medical Research Council investigator grant (grant 2016822) and a New South Wales Health cardiovascular disease clinician scientist grant. Dr Ingles is the recipient of a National Heart Foundation of Australia future leader fellowship grant (grant 106732) and receives research grant support from Bristol Myers Squibb. Dr Reza is supported by funding from the National Institutes of Health (National Heart, Lung, and Blood Institute grant K23HL166961). Dr I. Olivotto has received grants from Bristol Myers Squibb, Cytokinetics, Amicus, Genzyme, Shire, Bayer, Boston Scientific, and Menarini International; fees (honoraria or consulting) from Bristol Myers Squibb, Cytokinetics, Amicus, Genzyme, Shire, and Boston Scientific; and served or is serving as principal investigator for EXPLORER‐HCM (Clinical Study to Evaluate Mavacamten [MYK-461] in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy), MAVA‐LTE (A Long-Term Safety Extension Study of Mavacamten in Adults Who Have Completed EXPLORER-HCM), REDWOOD‐HCM (Randomized Evaluation of Dosing With CK-3773274 in Obstructive Outflow Disease in HCM), REDWOOD‐OLE (REDWOOD‐HCM Open Label Extension), and SEQUOIA‐HCM (Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic oHCM). Dr Maurizi has received fees (honoraria or consulting) from Bristol Myers Squibb. Dr Ho receives research funding from the National Institutes of Health and has received unrestricted research funding or consulting fees from Bristol Myers Squibb, Cytokinetics, Pfizer, Tenaya, Biomarin, viz.AI, and Lexicon Pharmaceuticals. Dr Lakdawala receives research funding from BMS and Pfizer and modest consulting incomes from BMS, Pfizer, Alexion, Tenaya, Akros, Neuvocor, and Cytokinetics. Dr Stendahl serves or has served as site principal investigator for MAVA-LTE, PIONEER-OLE (Phase 2 Open-label Pilot Study Evaluating Mavacamten in Subjects With Symptomatic Hypertrophic Cardiomyopathy and Left Ventricular Outflow Tract Obstruction Open-Label Extension), and VALOR-HCM (A Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy Who Are Eligible for Septal Reduction Therapy), and serves or has served as site subinvestigator for ACACIA-HCM (Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic nHCM), FOREST-HCM (Follow-Up, Open-Label, Research Evaluation of Sustained Treatment with Aficamten in HCM), MAPLE-HCM (Metoprolol vs Aficamten in Patients with LVOT Obstruction on Exercise Capacity in HCM), and SEQUOIA-HCM.

Background: Hypertrophic cardiomyopathy (HCM) is a heterogeneous disorder with varying risks of clinical outcomes, including sudden cardiac death (SCD). We aimed to identify distinct phenotypes among patients with HCM in relation to SCD risk factors, interpret their clinical characteristics, and examine their outcomes., Methods and Results: This retrospective study analyzed 1231 consecutive patients with HCM from 2 tertiary hospitals. We performed latent class analysis to categorize patients into phenotypic groups. Three distinct phenotypic groups were identified using latent class analysis. Group 1 (n=554) consisted of young patients with HCM with minimal SCD risk factors and favorable cardiac remodeling. Group 2 (n=114) comprised young patients with HCM and a high prevalence of SCD risk factors, whereas Group 3 (n=563) included older patients (median age, 68 years). Over a median 6.5-year follow-up, 34 SCD-related events, 131 cardiovascular events, 133 all-cause mortality events, and 70 noncardiovascular mortality events were observed. Group 2 exhibited the highest rate of SCD-related events (5-year SCD rate: Group 1 versus 2 versus 3: 0.8% versus 8.2% versus 4.0%, respectively, P <0.001), and cardiovascular events were more frequent in Groups 2 and 3 compared with Group 1. All-cause and noncardiovascular mortality were the most frequent in Group 3. A simplified decision tree was developed for the straightforward assignment of phenotypic group membership, demonstrating fair concordance., Conclusions: This study identified 3 distinct clinical phenotypes in patients with HCM, each associated with different SCD risks and outcomes. Data-driven phenotyping of patients with HCM offers effective risk stratification and may optimize patient management.

Introduction: The pathophysiology of HCM presents unique challenges for the management of cardiogenic shock and the use of mechanical circulatory support devices (MCSD). However, outcomes investigations for MCSD and HT in HCM patients is limited to case reports. The present study investigated MCSD and HT outcomes in HCM patients in a large retrospective cohort., Methods: The National Inpatient Sample (2016-2019) was used for the retrospective analysis of patients hospitalized for MCSD and HT using ICD-10 codes. Patients with implantation of more than one device category were excluded. These patients were divided into two cohorts, with and without HCM, and compared in terms of in-hospital mortality, trends in mortality rates, hospitalization costs and mean length of stay., Results: Among 267,780 patients hospitalized for MCSD and HT, 1155 patients had underlying HCM. Underlying HCM was associated with increased odds of mortality in patients receiving left ventricular assist devices (LVAD) (OR 3.4, 95% CI 1.03-11.2, p = 0.04) and temporary MCSD (OR 2.5, CI 1.8-3.6, p < 0.001). HCM was not associated with increased mortality in patients hospitalized for HT (OR 0.67, CI 0.15-2.85, p = 0.6). Patients with HCM undergoing MCSD and HT had a longer mean length of stay (22.1 vs 13.2 days, p = 0.004), and higher mean hospitalization charges ($830,103 vs $460,383, p < 0.0001) as compared to non-HCM patients., Conclusion: Underlying HCM is associated with increased in-hospital mortality in patients undergoing LVAD and temporary MCSD placement. Further prospective studies are required to expand our understanding of prognosis among HCM patients undergoing MCSD and establish management guidelines., Competing Interests: Declaration of competing interest Authors have nothing to disclose, (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Right ventricular (RV) involvement has been reported in one out of three patients with hypertrophic cardiomyopathy (HCM), however its prognostic significance remains unknown. We aimed to assess the prognostic value of RV involvement in patients with HCM through a systematic review and meta-analysis., Methods: A literature search was performed on PubMed, ClinicalTrials.gov and Cochrane Library databases from inception through November 15, 2023. Original articles enrolling HCM patients >18 years old and evaluating the association of RV parameters routinely assessed in clinical practice through trans-thoracic echocardiography or cardiac magnetic resonance (i.e., RV hypertrophy, volumes, systolic function, and late gadolinium enhancement) and the risk of a pre-defined composite endpoint including i) all cause death; ii) cardiac death; iii) heart transplantation; iv) heart failure-related hospitalization; v) atrial fibrillation; vi) ventricular tachycardia; and vii) stroke were retrieved. We pooled the effect of RV imaging variables on the combined clinical endpoint in terms of hazard ratio (HR) with 95% confidence interval (CI)., Results: The meta-analysis included 12 articles and 4634 patients. The pooled analysis demonstrated that the presence of RV systolic dysfunction conveyed an increased risk of adverse outcomes (HR 2.46; 95% CI 1.80-3.35; P < 0.001), whereas other RV imaging parameters were not significantly associated with patients' prognosis, except for RV-fractional area change analyzed as a continuous variable (HR 0.96 per % increase; 95% CI 0.93-0.995; P = 0.025)., Conclusions: Our results pinpoint a prognostic role of RV dysfunction, independent of left ventricular involvement, in patients with HCM, and future longitudinal studies, including multi-parametric RV assessment, are encouraged to provide clinically-relevant data to refine risk stratification in patients with HCM., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

Background: Apical hypertrophic cardiomyopathy (ApHCM) is a variant of hypertrophic cardiomyopathy, with distinct clinical characteristics and outcomes. We aimed to clarify the natural history of patients with ApHCM and identify the risk of end-stage heart failure incidence., Methods and Results: This retrospective study was conducted on patients with hypertrophic cardiomyopathy in China between January 2009 and February 2024. Patients were stratified into ApHCM and non-ApHCM groups. The primary outcome was a composite of major adverse cardiovascular events, including all-cause deaths, heart failure hospitalization, sudden cardiac death, and ventricular tachycardia. The secondary outcome was the incidence of end-stage heart failure, defined as left ventricular ejection fraction <50%. Kaplan-Meier and univariable and multivariable Cox proportional analyses were applied. Adjustment variables were included for important baseline characteristics, comorbidities, and medication use. Of 5653 patients enrolled with hypertrophic cardiomyopathy, 584 (10.3%) had ApHCM and 5069 (89.7%) had non-ApHCM. During the median follow-up period of 4.6 years (1.6-8.0 years), major adverse cardiovascular events occurred in 32.2% (n=1808), with a lower incidence in patients with ApHCM than non-ApHCM (20.4% versus 33.3%, P <0.001). Non-ApHCM was an independent predictor of major adverse cardiovascular events (hazard ratio [HR], 1.65 [95% CI, 1.36-1.99]; P <0.001). In the serial cohort, patients with ApHCM exhibited a lower incidence of end-stage heart failure than those with non-ApHCM (12.4% versus 2.7%, P <0.001). Non-ApHCM was associated with a higher risk of end-stage heart failure development (HR, 2.31 [95% CI, 1.28-4.15]; P <0.001). In subgroup and sensitivity analysis, the results were consistent for our main and secondary outcomes., Conclusions: ApHCM is relatively common in hypertrophic cardiomyopathy and shows lower rates of all-cause mortality and heart failure hospitalizations than non-ApHCM.

Background: The cumulative burden of hypertrophic cardiomyopathy (HCM) is significant, with a noteworthy percentage (10%-15%) of patients with HCM per year experiencing major adverse cardiovascular events (MACEs). A current risk stratification scheme for HCM had only limited accuracy in predicting sudden cardiac death (SCD) and failed to account for a broader spectrum of adverse cardiovascular events and cardiac magnetic resonance (CMR) parameters., Objectives: This study sought to develop and evaluate a machine learning (ML) framework that integrates CMR imaging and clinical characteristics to predict MACEs in patients with HCM., Methods: A total of 758 patients with HCM (67% male; age 49 ± 14 years) who were admitted between 2010 and 2017 from 4 medical centers were included. The ML model was built on the internal discovery cohort (533 patients with HCM, admitted to Fuwai Hospital, Beijing, China) by using the light gradient-boosting machine and internally evaluated using cross-validation. The external test cohort consisted of 225 patients with HCM from 3 medical centers. A total of 14 CMR imaging features (strain and late gadolinium enhancement [LGE]) and 23 clinical variables were evaluated and used to inform the ML model. MACEs included a composite of arrhythmic events, SCD, heart failure, and atrial fibrillation-related stroke., Results: MACEs occurred in 191 (25%) patients over a median follow-up period of 109.0 months (Q1-Q3: 73.0-118.8 months). Our ML model achieved areas under the curve (AUCs) of 0.830 and 0.812 (internally and externally, respectively). The model outperformed the classic HCM Risk-SCD model, with significant improvement (P < 0.001) of 22.7% in the AUC. Using the cubic spline analysis, the study showed that the extent of LGE and the impairment of global radial strain (GRS) and global circumferential strain (GCS) were nonlinearly correlated with MACEs: an elevated risk of adverse cardiovascular events was observed when these parameters reached the high enough second tertiles (11.6% for LGE, 25.8% for GRS, -17.3% for GCS)., Conclusions: ML-empowered risk stratification using CMR and clinical features enabled accurate MACE prediction beyond the classic HCM Risk-SCD model. In addition, the nonlinear correlation between CMR features (LGE and left ventricular pressure gradient) and MACEs uncovered in this study provides valuable insights for the clinical assessment and management of HCM., Competing Interests: Funding Support and Author Disclosures This study was co-funded by the National Natural Science Foundation of China (number 81930044), the National Key Research and Development Program of China (numbers 2021YFF0501404, 2021YFF0501400), and the National Natural Science Foundation of China (numbers 81971611, 81830056, 61871373). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024. Published by Elsevier Inc.)

Background: Hypertrophic cardiomyopathy (HCM) is believed to have low overall mortality rate, that could be influenced by gender, particularly among probands. We aimed to evaluate the survival rates and possible gender differences in a homogeneous cohort of HCM proband patients, referred for genetic testing, from the same geographical area, without differences in medical care access nor clinical referral pathways., Methods: we compared the mortality rates of a cohort of consecutive HCM probands referred for genetic testing (2000-2022), from a Spanish region (xxx1) with a centralized genetic testing pathway, with its control reference population by Ederer II method. Gender differences were analyzed., Results: Among the 649 HCM probands included in this study, there were significantly more men than women (61.3% vs 38.7, p < 0.05), with an earlier diagnosis (53.5 vs 61.1 years old, p < 0.05). Clinical evolution or arrhythmogenic HCM profile did no show no significant gender differences. Mean follow up was 9,8 years ±6,6 SD (9,9 ± 7 vs 9,6 ± 6,1, p = 0.59). No statistically significant differences in observed mortality, expected survival and excess mortality were found in the general HCM proband cohort. However, we found a significant excess mortality in female probands with HCM. No additional differences in analysis by genetic status were identified., Conclusion: Expected survival in our HCM probands did not differ from its reference population. However, despite no gender differences in phenotype severity were identified, proband HCM women did present a diagnosis delay and worse mortality outcomes., Competing Interests: Declaration of competing interest There are no conflicts of interest. This research was funded by Instituto de Salud Carlos III (ISCIII) (grant number PI22/00705). All patients signed the informed consent (local Ethical Committee approval CEImPA 2022.254)., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: In this study, we describe the incidence, sites of valve injury, and the influence of aortic valve regurgitation (AR) on outcomes of septal myectomy for obstructive hypertrophic cardiomyopathy., Methods: We analyzed patients who underwent transaortic septal myectomy for obstructive hypertrophic cardiomyopathy from 2001 to 2022. The primary study end point was incidence of procedure-related AR, defined as the need for an unplanned aortic valve (AV) procedure or new-onset moderate AR on early postoperative echocardiography., Results: There were 2807 patients who underwent transaortic septal myectomy for hypertrophic cardiomyopathy and had pre- and postoperative transthoracic echocardiograms. Procedure-related AR was observed in 55 (2%) patients; 27 (1%) required unplanned AV procedures at the time of myectomy, and 29 (1%) additional patients developed moderate AR postoperatively. During follow-up, 9 total patients underwent late AV reoperation, 1 patient who developed new moderate AR postoperatively required late AVR due to severe calcific AS, and none of the patients who had unplanned AV procedures required late reoperation. The overall cumulative incidence of AV reoperation at 10 and 15 years was 1% and 5%. The predicted probability of moderate or severe AR at 5 and 10 years was 1.4% and 1.8%, respectively. There was no difference in survival comparing patients with or without early postoperative mild or worse AR (P = .69)., Conclusions: Procedure-related AR was observed in 2% of patients undergoing transaortic septal myectomy, and unplanned AV procedures were necessary for half of these patients. Intraoperative identification and valve repair mitigate the impact of cusp injury on late reintervention and survival., (Copyright © 2023 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: Hypertrophic cardiomyopathy with left ventricular apical aneurysm is a phenotype associated with a 4-fold increase in the risk for sudden cardiac death. In this study, we describe the surgical outcome of concomitant apical aneurysm repair in patients undergoing transapical myectomy for hypertrophic cardiomyopathy., Methods: We identified 67 patients with left ventricular apical aneurysms who underwent transapical myectomy and apical aneurysm repair between July 2000 and August 2020. Long-term survival was compared with that of 2746 consecutive patients undergoing transaortic septal myectomy for obstructive hypertrophic cardiomyopathy with subaortic obstruction., Results: Transapical myectomy was indicated for midventricular obstruction (n = 44) or left ventricular remodeling for diastolic heart failure (n = 29). Preoperatively, 74.6% (n = 50) of patients were in New York Heart Association class III/IV heart failure, and 34.3% (n = 23) of patients had experienced syncope or presyncope. Atrial fibrillation was documented in 22 patients (32.8%), and episodes of ventricular arrhythmias were recorded in 30 patients (44.8%). Thrombus was present in the apical aneurysm in 6 patients. During a median (interquartile range) follow-up of 4.9 (1.8-7.6) years, the estimated 1- and 5-year survivals were 98.5% and 94.5%, respectively, which were not significantly different from that of patients undergoing transaortic septal myectomy for obstructive hypertrophic cardiomyopathy (P = .52) or an age- and sex-matched US general population (P = .40)., Conclusions: Apical aneurysm repair in conjunction with septal myectomy is a safe procedure, and the good long-term survival of patients suggests that the procedure may reduce cardiac-related death in this high-risk hypertrophic cardiomyopathy population., (Copyright © 2023 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Hypertrophic cardiomyopathy (HCM) is rare in children, and sudden cardiac death (SCD) is difficult to predict. Two prognostic scores - HCM Risk-Kids and Precision Medicine for Cardiomyopathy (PRIMaCY) - were developed to assess the risk of SCD in the next 5 years in children with HCM., Aims: To test the ability of these scores to predict SCD in children with HCM. Also, to identify factors associated with a severe cardiac rhythmic event (SCRE) (ventricular fibrillation, sustained ventricular tachycardia, heart transplant for rhythmic reasons or SCD)., Methods: Retrospective, multicentre, observational study at 10 medical centres in the Nord-Pas-de-Calais region, France., Results: This study included 72 paediatric patients with HCM during 2009-2019 who were followed for a median (interquartile range [IQR]) of 8.5 (5.0-16.2) years. Eleven patients (15.3%) presented with SCRE. HCM Risk-Kids was high, with a median (IQR) score of 6.2% (2.1-12.8%; significant threshold≥6.0%) and the PRIMaCY median (IQR) score was 7.1% (2.6-15.0%; significant threshold≥8.3%). The positive predictive value was only 27.1% (95% confidence interval [CI] 21.5-32.5%) for HCM Risk-Kids (with a threshold of≥6.0%) and 33.2% (95% CI 27.1-38.9%) for the PRIMaCY score (with a threshold of≥8.3%). The negative predictive values were 95.4% (95% CI 92.3-97.7%) and 93.0% (95% CI 89.8-96.2%), respectively. Three of 28 patients with an implantable cardioverter defibrillator (ICD) experienced complications (including inappropriate shocks)., Conclusion: HCM Risk-Kids and the PRIMaCY score have low positive predictive values to predict SCD in paediatric patients. If used alone, they could increase the rate of ICD implantation and thus ICD complications. Therefore, the scores should be used in combination with other data (genetic and magnetic resonance imaging results)., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Backgrounds and Aims: Hypertrophic cardiomyopathy (HCM) causes cardiac death through both sudden cardiac death (SCD) and death due to heart failure (HF). Although adipokines lead to adverse cardiac remodeling in HCM, the prognostic value of plasma adipokines in HCM remains unknown. We aimed to predict cardiac death in patients with HCM using plasma adipokines., Methods and Results: We performed a multicenter prospective cohort study of patients with HCM. The outcome was cardiac death including heart transplant, death due to HF, and SCD. With data from 1 institution (training set), a prediction model was developed using random forest classification algorithm based on 10 plasma adipokines. The performance of the prediction model adjusted for 8 clinical parameters was examined in samples from another institution (test set). Time-to-event analysis was performed in the test set to compare the rate of outcome events between the low-risk and high-risk groups determined by the prediction model. In total, 389 (267 in the training set; 122 in the test set) patients with HCM were included. During the median follow-up of 2.7 years, 21 patients experienced the outcome event. The area under the covariates-adjusted receiver-operating characteristics curve was 0.89 (95 % confidence interval [CI] 0.71-0.99) in the test set. revealed the high-risk group had a significantly higher risk of cardiac death (hazard ratio 17.8, 95 % CI 2.1-148.3, P = 0.008)., Conclusion: The present multicenter prospective study demonstrated that a panel of plasma adipokines predicts cardiac death in patients with HCM., Competing Interests: Declaration of competing interest This work was supported by the National Institutes of Health [R01 HL157216 and R01 HL168382 to Y.J.S., UL1 TR001873 to M.P.R., K24 HL107643 to M.P.R., and K24 AG036778 to M.S.M.], the American Heart Association [2 National Clinical and Population Research Awards and Career Development Award to Y.J.S.], Korea Institute of Oriental Medicine [W22005 to Y.J.S.], Feldstein Medical Foundation to Y.J.S., Columbia University Irving Medical Center Irving Institute for Clinical & Translational Research Precision Medicine Pilot Award to Y.J.S., and Columbia University Irving Medical Center Marjorie and Lewis Katz Cardiovascular Research Prize to Y.J.S. Y.J.S. has also received funding from Bristol-Myers Squibb, and consulting income from Bristol-Myers Squibb and Moderna Japan. M.S.M. has also received consulting income from Akcea, Alnylam, Eidos Therapeutics, Pfizer, Prothena, Novo Nordisk, and Intellia. The funding organizations did not have any role in the study design, collection, analysis, or interpretation of data, in writing of the manuscript, or in the decision to submit the article for publication. The researchers were independent from the funding organizations., (Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: The efficacy of current pharmacological therapies in hypertrophic cardiomyopathy is limited. A cardiac myosin inhibitor, mavacamten, has recently been approved as a first-in-class treatment for symptomatic hypertrophic obstructive cardiomyopathy., Aims: To assess the profile and burden of cardiac myosin inhibitor candidates in the hypertrophic cardiomyopathy prospective Register of hypertrophic cardiomyopathy (REMY) held by the French Society of Cardiology., Methods: Data were collected at baseline and during follow-up from patients with hypertrophic cardiomyopathy enrolled in REMY by the three largest participating centres., Results: Among 1059 adults with hypertrophic cardiomyopathy, 461 (43.5%) had obstruction; 325 (30.7%) of these were also symptomatic, forming the "cardiac myosin inhibitor candidates" group. Baseline features of this group were: age 58±15years; male sex (n=196; 60.3%); diagnosis-to-inclusion delay 5 (1-12)years; maximum wall thickness 20±6mm; left ventricular ejection fraction 69±6%; family history of hypertrophic cardiomyopathy or sudden cardiac death (n=133; 40.9%); presence of a pathogenic sarcomere gene mutation (n=101; 31.1%); beta-blocker or verapamil treatment (n=304; 93.8%), combined with disopyramide (n=28; 8.7%); and eligibility for septal reduction therapy (n=96; 29%). At the end of a median follow-up of 66 (34-106) months, 319 (98.2%) were treated for obstruction (n=43 [13.2%] received disopyramide), 46 (14.2%) underwent septal reduction therapy and the all-cause mortality rate was 1.9/100 person-years (95% confidence interval 1.4-2.6) (46 deaths). Moreover, 41 (8.9%) patients from the initial hypertrophic obstructive cardiomyopathy group became eligible for a cardiac myosin inhibitor., Conclusions: In this cohort of patients with hypertrophic cardiomyopathy selected from the REMY registry, one third were eligible for a cardiac myosin inhibitor., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Hypertrophic cardiomyopathy (HCM) is associated with adverse outcomes, such as heart failure, arrhythmia, and mortality. Sudden cardiac death (SCD) is a common cause of death in HCM patients, and identification of patients at a high risk of SCD is crucial in clinical practice. The China Hypertrophic Cardiomyopathy Project is a hospital-based, multicenter, prospective, registry cohort study of HCM patients, covering a total of 3000 participants and with a 5-year follow-up plan. A large number of demographic characteristics and clinical data will be fully collected to identify prognostic factors in Chinese HCM patients. Furthermore, the main purpose of this study is to integrate demographic and clinical characteristics to establish new 5-year SCD risk predictive equations for Chinese HCM patients by the use of machine learning technologies. The project has crucial clinical significance for risk stratification and determination of HCM patients with high risk of adverse outcomes. CLINICAL TRIALS REGISTRATION: ChiCTR2300070909., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background-Aims: Sudden death in a young adult who showed no prodrome or complaint during his lifetime is a tragedy. The death often remains unexplained by doctors and is often the subject of a judicial investigation following which an autopsy is ordered. Our study joins several studies around the world, where the results have linked sudden death in adults to a cardiac origin., Methods: Through a series of 305 autopsies carried out in the forensic medicine department of the Frantz Fanon hospital in the city of Bejaia in Algeria over a period of two years, 57 cases corresponded to unexplained sudden deaths, i.e. an incidence of 3 cases per 100,000 inhabitants per year., Results: Sudden death was of cardiac origin in 50.8% of cases (N=28). Two epidemiologic profiles emerge in our study: the first is that of a man aged between 50 and 60 years of age, with several deleterious lifestyle habits (in particular smoking) with a cardiovascular history, previously followed by a cardiologist, who died suddenly out-of-hospital, from ischemic heart disease. The second is that of a young adult under 40 years of age, of average build, with no particular medical history, having not previously consulted a cardiologist, who died suddenly of hypertrophic cardiomyopathy., Conclusions: In many instances, we observed major anatomical lesion, which had not motivated any prior medical consultation either with a general practitioner or with a cardiologist., Competing Interests: Déclaration de liens d'intérêts Les auteurs déclarent ne pas avoir de liens d'intérêts., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Background: The impact of hypertrophic cardiomyopathy (HCM) on cardiovascular and obstetrical outcomes in pregnant women remains unclear, particularly in Asian populations. This study aimed to evaluate the maternal cardiovascular and obstetrical outcomes in Korean women with HCM., Methods: Using data from the Korean National Health Insurance Service database, we identified women who gave birth via cesarean section or vaginal delivery after being diagnosed with HCM between 2006 and 2019. Maternal cardiovascular and obstetrical outcomes were assessed based on the trimester of pregnancy., Results: This study included 122 women and 158 pregnancies. No maternal deaths were noted; however, 21 cardiovascular events, such as hospital admission for cardiac problems, including heart failure and atrial fibrillation (AF), new-onset AF or ventricular tachycardia (VT) occurred in 14 pregnancies (8.8%). Cardiac events occurred throughout pregnancy with a higher occurrence in the third trimester. Cesarean sections were performed in 49.3% of the cases, and all cardiovascular outcomes occurring after delivery were observed in patients who had undergone cesarean sections. Seven cases involved preterm delivery, and two of these cases were accompanied by cardiac events, specifically AF. Pre-existing arrhythmia (AF: odds ratio (OR): 7.44, 95% confidence interval (CI): 2.61-21.21, P < 0.001; VT: OR: 31.61, 95% CI: 5.85-172.77, P < 0.001) was identified as a predictor for composite outcomes of cardiovascular events or preterm delivery., Conclusions: Most pregnant women with HCM were well-tolerated. However, cardiovascular complications could occur in some patients. Therefore, planned delivery may be necessary for selected patients, especially the women with pre-existing arrhythmias., (© 2024. The Author(s).)

Background: The genetic basis of hypertrophic cardiomyopathy (HCM) is complex, and the relationship between genotype status and clinical outcome is incompletely resolved., Methods and Results: We assessed a large international HCM cohort to define in contemporary terms natural history and clinical consequences of genotype. Consecutive patients (n=1468) with established HCM diagnosis underwent genetic testing. Patients with pathogenic (or likely pathogenic) variants were considered genotype positive (G+; n=312; 21%); those without definite disease-causing mutations (n=651; 44%) or variants of uncertain significance (n=505; 35%) were considered genotype negative (G-). Patients were followed up for a median of 7.8 years (interquartile range, 3.5-13.4 years); HCM end points were examined by cumulative event incidence. Over follow-up, 135 (9%) patients died, 33 from a variety of HCM-related causes. After adjusting for age, all-cause and HCM-related mortality did not differ between G- versus G+ patients (hazard ratio [HR], 0.78 [95% CI, 0.46-1.31]; P =0.37; HR, 0.93 [95% CI, 0.38-2.30]; P =0.87, respectively). Adverse event rates, including heart failure progression to class III/IV, heart transplant, or heart failure death, did not differ (G- versus G+) when adjusted for age (HR, 1.20 [95% CI, 0.63-2.26]; P =0.58), nor was genotype independently associated with sudden death event risk (HR, 1.39 [95% CI, 0.88-2.21]; P =0.16). In multivariable analysis, age was the only independent predictor of all-cause and HCM-related mortality, heart failure progression, and sudden death events., Conclusions: In this large consecutive cohort of patients with HCM, genotype (G+ or G-) was not a predictor of clinical course, including all-cause and HCM-related mortality and risk for heart failure progression or sudden death. G+ status should not be used to dictate clinical management or predict outcome in HCM.

Background: Ventricular tachycardia (VT) is the primary cause of sudden cardiac death in patients with hypertrophic cardiomyopathy (HCM). However, the strategy for VT treatment in HCM patients remains unclear. This study is aimed to compare the effectiveness of catheter ablation versus antiarrhythmic drug (AAD) therapy for sustained VT in patients with HCM., Methods: A total of 28 HCM patients with sustained VT at 4 different centers between December 2012 and December 2021 were enrolled. Twelve underwent catheter ablation (ablation group) and sixteen received AAD therapy (AAD group). The primary outcome was VT recurrence during follow-up., Results: Baseline characteristics were comparable between two groups. After a mean follow-up of 31.4 ± 17.5 months, the primary outcome occurred in 35.7% of the ablation group and 90.6% of the AAD group (hazard ratio [HR], 0.29 [95%CI, 0.10-0.89]; P = 0.021). No differences in hospital admission due to cardiovascular cause (25.0% vs. 71.0%; P = 0.138) and cardiovascular cause-related mortality/heart transplantation (9.1% vs. 50.6%; P = 0.551) were observed. However, there was a significant reduction in the composite endpoint of VT recurrence, hospital admission due to cardiovascular cause, cardiovascular cause-related mortality, or heart transplantation in ablation group as compared to that of AAD group (42.9% vs. 93.7%; HR, 0.34 [95% CI, 0.12-0.95]; P = 0.029)., Conclusions: In HCM patients with sustained VT, catheter ablation reduced the VT recurrence, and the composite endpoint of VT recurrence, hospital admission due to cardiovascular cause, cardiovascular cause-related mortality, or heart transplantation as compared to AAD., (© 2024. The Author(s).)

Background: Previous studies have shown that women with hypertrophic obstructive cardiomyopathy (HCM) have worse long-term outcomes irrespective of intervention. However, the outcomes of patients undergoing alcohol septal ablation (ASA) based on sex have not been described. Hence, this study aimed to evaluate pressure changes and long-term mortality in patients with HCM undergoing ASA based on sex., Methods and Results: This is a single-center retrospective study evaluating hemodynamic changes and long-term mortality in patients with HCM treated with ASA according to sex. A total of 259 patients were included (aged 68.4±11.9 years, 62.2% women). Women had higher age and baseline pressures at the time of ASA, with a greater percent reduction in mean left atrial pressure (men versus women: 2.2% versus 15.9%, respectively; P =0.02). Women had better survival (median survival rate of men versus women: 8.6 versus 12.5 years, respectively; P =0.011). On Cox multivariable regression, predictors of mortality were age (per group change <60 years, 61-70 years, 71-80 years, and >80 years; hazard ratio [HR], 1.45 [95% CI, 1.10-1.91], P =0.008), female sex (HR, 0.59 [95% CI, 0.35-0.99], P =0.048), chronic kidney disease (HR, 1.88 [95% CI, 1.06-3.33], P =0.031), and left ventricular outflow tract gradient reduction ≤86% (HR, 1.91 [95% CI, 1.14-3.19], P =0.014)., Conclusions: Women with HCM undergoing ASA are older and have higher left-sided baseline pressures compared with men yet have better survival. Further studies exploring the mechanisms of differential outcomes according to sex in patients with HCM undergoing ASA are needed.

Background: The clinical efficacy and safety of alcohol septal ablation (ASA) for obstructive hypertrophic cardiomyopathy (HCM) have been well-established; however, less is known about outcomes in patients undergoing preemptive ASA before transcatheter mitral valve replacement (TMVR)., Aims: The goal of this study is to characterize the procedural characteristics and examine the clinical outcomes of ASA in both HCM and pre-TMVR., Methods: This retrospective study compared procedural characteristics and outcomes in patient who underwent ASA for HCM and TMVR., Results: In total, 137 patients were included, 86 in the HCM group and 51 in the TMVR group. The intraventricular septal thickness (mean 1.8 vs. 1.2 cm; p < 0.0001) and the pre-ASA LVOT gradient (73.6 vs. 33.8 mmHg; p ≤ 0.001) were higher in the HCM group vs the TMVR group. The mean volume of ethanol injected was higher (mean 2.4 vs. 1.7 cc; p < 0.0001). The average neo-left ventricular outflow tract area increased significantly after ASA in the patients undergoing TMVR (99.2 ± 83.37 mm 2 vs. 196.5 ± 114.55 mm 2 ; p = <0.0001). The HCM group had a greater reduction in the LVOT gradient after ASA vs the TMVR group (49.3 vs. 18 mmHg; p = 0.0040). The primary composite endpoint was higher in the TMVR group versus the HCM group (50.9% vs. 25.6%; p = 0.0404) and had a higher incidence of new permanent pacemaker (PPM) (25.5% vs. 18.6%; p = 0.3402). The TMVR group had a higher rate of all-cause mortality (9.8% vs. 1.2%; p = 0.0268)., Conclusions: Preemptive ASA before TMVR was performed in patients with higher degree of clinical comorbidities, and correspondingly is associated with worse short-term clinical outcomes in comparison to ASA for HCM patients. ASA before TMVR enabled percutaneous mitral interventions in a small but significant minority of patients that would have otherwise been excluded. The degree of LVOT and neoLVOT area increase is significant and predictable., (© 2024 Wiley Periodicals LLC.)

Background: Atherosclerotic coronary artery disease (CAD) often occurs concurrently with hypertrophic cardiomyopathy (HCM). However, the influence of concomitant CAD has not been fully assessed in patients with HCM., Methods: Invasive or computed tomography coronary angiography was performed in 461 patients with HCM at our hospital to determine the presence and severity of CAD from March 2010 to April 2022. The primary end points were all-cause, cardiovascular, and sudden cardiac deaths. The survival of HCM patients with severe CAD was compared with that of HCM patients without severe CAD., Results: Of 461 patients with HCM, 235 had concomitant CAD. During the median (interquartile range) follow-up of 49 (31-80) months, 75 patients (16.3%) died. The 5-year survival estimates were 64.3%, 82.5%, and 86.0% for the severe, mild-to-moderate, and no-CAD groups, respectively (log-rank, p = 0.010). Regarding the absence of cardiovascular death, the 5-year survival estimates were 68.5% for patients with severe CAD, 86.4% for patients with mild-to-moderate CAD, and 90.2% for HCM patients with no CAD (log-rank, p = 0.001). In multivariate analyses, severe CAD was associated with all-cause and cardiovascular death after adjusting for age, left ventricular ejection fraction, hypertension, and atrial fibrillation., Conclusions: This study showed a worse prognosis among HCM patients with severe CAD than among HCM patients without severe CAD. Therefore, timely recognition of severe CAD in HCM patients and appropriate treatment are important., (Copyright © 2023 Hellenic Society of Cardiology. Published by Elsevier Inc. All rights reserved.)

Background: Quantitative late gadolinium enhancement (LGE) cardiac magnetic resonance provides important prognostic information for sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM). However, it has not been fully integrated into clinical practice., Objectives: The purpose of this study was to assess the prognostic value of LGE extent in predicting SCD in adults with HCM across different methods of quantification, thresholds, and patients' clinical profile., Methods: The authors searched PubMed, Web of Science, and Cochrane Library for studies investigating the prognostic value of LGE% in predicting SCD in HCM. Pooled ORs were calculated with 95% CIs. The optimal threshold was determined using a multiple cutoffs model., Results: Eleven studies were included in the meta-analysis with a total of 5,550 patients and a median follow-up time of 5.2 years. Two studies quantified LGE manually, 7 studies used the 6 SD technique, 1 study used the 4 SD technique, and 1 study the 2 SD technique. There was no statistically significant difference in predicting SCD between these 4 methods (P = 0.443). Optimal cutoff could be determined only for the 6 SD technique. LGE 10% was the optimal threshold of the 6 SD technique with sensitivity 0.73 and specificity 0.67., Conclusions: The different LGE quantification techniques have comparable accuracy in predicting SCD. When the more extensively studied 6 SD technique is used, LGE 10% is the optimal cutoff and can effectively restratify intermediate-risk patients. LGE extent can improve HCM risk stratification, but it is unlikely to become a standalone tool., 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.)

Aims: Data regarding hypertrophic cardiomyopathy (HCM)-related mortality in United States young adults, defined as those aged between 25 and 44 years, are lacking. We sought to assess the trends in HCM-related mortality among US young adults between 1999 and 2019 and determine differences by sex, race, ethnicity, urbanization and census region., Methods: Mortality data were retrieved by the Centers for Disease Control and Prevention (CDC) Wide-Ranging Online Data for Epidemiologic Research (WONDER) dataset from January 1999 to December 2019. Age-adjusted mortality rates (AAMRs) were assessed using the Joinpoint regression modeling and expressed as estimated average annual percentage change (AAPC) with relative 95% confidence intervals (95% CIs)., Results: Over 20-year period, the AAMR from HCM in US young adults linearly decreased, with no differences between sexes [AAPC: -5.3% (95% CI -6.1 to -4.6), P  < 0.001]. The AAMR decrease was more pronounced in Black patients [AAPC: -6.4% (95% CI -7.6 to -5.1), P  < 0.001], Latinx/Hispanic patients [AAPC: -4.8% (95% CI -7.2 to -2.36), P  < 0.001] and residents of urban areas [AAPC: -5.4% (95% CI -6.2 to -4.6), P  < 0.001]. The higher percentages of HCM-related deaths occurred in the South of the country and at the patient's home., Conclusion: HCM-related mortality in US young adults has decreased over the last two decades in the United States. Subgroup analyses by race, ethnicity, urbanization and census region showed ethnoracial and regional disparities that will require further investigation., (Copyright © 2024 Italian Federation of Cardiology - I.F.C. All rights reserved.)

There are limited data on the mortality trends of HCM in the United States. To study the demographics and trends of mortality in patients with HCM, a retrospective cohort analysis was done with mortality data of patients with HCM listed as an underlying cause of death in the US Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database (CDC-WONDER) from January 1999 to December 2020. The analysis took place in February 2022. First, we measured HCM-related age-adjusted mortality rate (AAMR) per 100,000 US population stratified by sex, race, ethnicity, and geographic area. We then calculated the Annual Percentage Change (APC) for AAMR for each. A total of 24,655 HCM-related deaths occurred between 1999 and 2020. The AAMR for HCM-related deaths declined from 0.5/100,000 patients in 1999 to 0.2 in 2020. The APC changes are as follows: -6.8 (95% CI: -11.8 to -1.5) from 2002 to 2009, -1.23 (95% CI -13.8 to 13.2) from 2009 to 2014, -6.71 (95% CI -46.2 to 61.7) from 2014 to 2017 and remained at 2.07 (95% CI -26.1 to 41.1) from 2017 to 2020. Men had consistently higher AAMR than women. Overall, AAMR in men was 0.4 (95% CI: 0.4-0.5), and in women was 0.3 (95% CI: 0.3-0.3). A similar trend was noticed in men and women over the years, starting from 1999 (AAMR men: 0.7 and women: 0.4) to 2020 (AAMR men: 0.3 and women: 0.2). AAMRs were highest among black or African American patients 0.6 (95% CI: 0.5-0.6), followed by non-Hispanic and Hispanic white 0.3 (95% CI 0.3-0.3) and Asian or Pacific Islander 0.2 (95% CI 0.2-0.2). There was substantial variation in each region in the US. States such as California, Ohio, Michigan, Oregon, and Wyoming had the highest AAMR. Large metropolitan cities had higher AAMR than non-metropolitan cities. During the study period from 1999 to 2020, HCM-related mortality steadily decreased. The highest AAMR was observed among men, black patients, and residents of metropolitan areas. States such as California, Ohio, Michigan, Oregon, and Wyoming had the highest AAMR., (Copyright © 2023 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.)

Aims: Defining the risk of atrial fibrillation (AF) in hypertrophic cardiomyopathy (HCM) patients is an important clinical and prognostic challenge. The aim of this study is to determine HCM phenogroups with different risk of AF occurrence at 5 years., Methods and Results: We applied retrospectively the Bayesian method, which can analyze a large number of variables, to differentiate phenogroups of patients with different risks of AF and prognoses across a French prospective on-going hospital-based registry of adult HCM patients (REMY). Clinical and imaging data were prospectively recorded, and patients were followed for 5 years. A total of 1431 HCM patients were recruited, including 1275 analyzed in the present study after exclusion criteria. The population included 412 women, 369 patients with obstructive HCM, and 252 implanted with an ICD. AF occurred in 167 (11.6%) patients during the 5 year follow-up. Three phenogroups were defined according to their common clinical and echocardiographic characteristics. Patients at the highest risk were oldest, more often female, with more frequent comorbidities, anteroposterior diameter of the left atrium was significantly greater, with diastolic dysfunction, outflow-tract obstruction, and mitral valve abnormality, and presented higher pulmonary artery pressure and/or right-ventricular dysfunction. These also had a higher risk of all-cause hospitalizations and death., Conclusion: Based on a clustering analysis, three phenogroups of HCM according to the risk of AF occurrence can be identified. It can indicate which patients should be more monitored and/or treated, particular to prevent the risk of stroke., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Although numerous studies have suggested that elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) is positively correlated with cardiovascular events, especially the heart failure and heart failure-related death (HFRD), evidence of the association between NT-proBNP and the adverse outcomes of hypertrophic cardiomyopathy (HCM) is still relatively limited. The present study was performed to evaluate the relationship between NT-proBNP and outcomes in patients with HCM., Methods: Observational cohort methodology was used in the present study, and a total of 227 patients were included. And the patients were followed for 44.97 ± 16.37 months. Patients were categorized into three groups according to these NT-proBNP tertiles: first tertile (≤910 pg/ml, n=68), second tertile (913-2141 pg/ml, n=68), and third tertile (≥2151 pg/ml, n=69). The adverse outcomes of the present study were all-cause death (ACD) and cardiac death (CD)., Results: According to the risk category of NT-proBNP, the incidence of ACD (P=0.005) and CD (P=0.032) among the three groups showed significant differences. Multivariate Cox regression analysis suggested that the ACD and CD in the third tertile have 7.022 folds (hazard risk [HR] = 7.022 [95% confidence interval [CI]: 1.397-35.282], P=0.018) and 7.129 folds (HR = 7.129 [95% CI: 1.329-38.237], P=0.022) increased risks as compared with those in the first tertile. Kaplan-Meier survival analyses showed that the cumulative risks of ACD and CD in patients with HCM tended to increase., Conclusion: The present study indicated NT-proBNP was a novel biomarker suitable for predicting adverse prognosis in patients with HCM, which may be used for early recognition and risk stratification., (© 2022 The Author(s).)

Background: We aimed to evaluate early outcomes of septal myectomy in patients with hypertrophic cardiomyopathy., Methods: We retrospectively analyzed data collected over a 9-year period from 583 patients who underwent septal myectomy for hypertrophic cardiomyopathy at our institution., Results: The mean age was 55.7 ± 13.1 years, and 338 (58%) patients were in New York Heart Association class III or IV. There were 11 (1.9%) early deaths, including 3 (0.5%) intraoperative deaths. Early mortality was lowest after isolated septal myectomy (0.8%) and highest after concomitant mitral valve replacement (6.1%). There were 4 (0.7%) and 9 (1.5%) patients with left ventricular wall rupture and ventricular septal defect, respectively, after myectomy. New pacemaker implantation caused by atrioventricular disturbances was required in 29 (5.0%) patients, and was associated with previous alcohol septal ablation (odds ratio 3.34, 95% confidence interval 1.02-11.0, P  = 0.047). Left ventricular wall rupture, intraoperative residual (15.5% moderate, 0.3% severe) mitral regurgitation, and pre-discharge residual outflow tract gradient >30 mm Hg (4.6%) occurrences were surgeon-dependent., Conclusions: The early results are consistent with example targets reported in the 2020 American College of Cardiology/American Heart Association guidelines for septal reduction therapy outcomes. Septal myectomy safety and efficacy are surgeon-dependent. Previous alcohol septal ablation increases the risk of permanent pacemaker implantation due to postoperative complete atrioventricular block. Therefore, continuous education, mentoring, and learning by doing may play an important role in achieving reasonable septal myectomy safety and efficacy.

Background: In patients with hypertrophic obstructive cardiomyopathy, atrial fibrillation is associated with heart failure and increased late mortality. However, the role of surgical ablation in these patients is not well defined. The aim of this study was to evaluate the efficacy of the concomitant Cox-Maze IV procedure in patients undergoing septal myectomy for hypertrophic obstructive cardiomyopathy., Methods: Between 2005 and 2019, 347 patients who underwent septal myectomy at a single institution (Washington University School of Medicine, Barnes-Jewish Hospital, St Louis, MO) were retrospectively reviewed. For patients with hypertrophic obstructive cardiomyopathy and atrial fibrillation who underwent a concomitant Cox-Maze IV procedure, freedom from atrial tachyarrhythmias (ATAs) on or off antiarrhythmic drugs (AADs) was evaluated annually. Predictors of ATA recurrence were identified using Fine-Gray regression, with death as a competing risk., Results: A total of 42 patients underwent concomitant septal myectomy and Cox-Maze IV procedures. The majority of patients, 69% (29 of 42), had paroxysmal atrial fibrillation with a 2.5-year median duration. Operative mortality was 7% (3 of 42). New York Heart Association functional class was reduced after surgery (P < .01). Rates of freedom from recurrent ATAs at 1- and 5-year intervals were 93% (27 of 29) and 100% (14 of 14), respectively. Rates of freedom from ATAs and AADs were 83% (24 of 29) and 100% (14 of 14) at the same time points, respectively. Increased left atrial diameter predicted first ATA recurrence (P < .01). Cerebrovascular accident risk was lower in patients with atrial fibrillation who underwent concomitant Cox-Maze IV and septal myectomy relative to myectomy only (P = .02)., Conclusions: Late freedom from ATAs on or off AADs was excellent after Cox-Maze IV and septal myectomy. Although there was a higher than expected rate of perioperative complications, the study results suggest that concomitant surgical ablation should be considered in selected patients with hypertrophic obstructive cardiomyopathy and atrial fibrillation., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Purpose: The aim of the study was to project the long-term net health benefits of mavacamten for the treatment of symptomatic obstructive hypertrophic cardiomyopathy (HCM) in the United States., Methods: A Markov model with 4 mutually exclusive health states (New York Heart Association [NYHA] functional classes I, II, and III/IV and death) was developed to project the life-years (LYs) and quality-adjusted life-years (QALYs) over a lifetime horizon for patients with symptomatic obstructive HCM receiving mavacamten with or without β-blocker (BB) or calcium channel blocker (CCB) monotherapy or placebo with or without BB or CCB monotherapy. The model simulated a patient cohort with a starting age of 59 years and 41% women. Transition probabilities across NYHA functional classes were estimated using data from the Phase III Clinical Study to Evaluate Mavacamten (MYK-461) in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy (EXPLORER-HCM) and the EXPLORER long-term extension (EXPLORER-LTE) cohort from the Long-term Safety Extension Study of Mavacamten in Adults who Have Completed MAVERICK-HCM or EXPLORER-HCM (MAVA-LTE) trial and were extrapolated after week 30. The mortality risks of NYHA functional class I were assumed to be the age- and sex-specific mortality risks of the US general population. The mortality risks for NYHA class II and III/IV were estimated using those for class I in conjunction with the relative mortality risks derived using patients with obstructive HCM from a large real-world registry. Health state utilities for each treatment were estimated from EXPLORER-HCM. Both LYs and QALYs were aggregated over a lifetime for each treatment arm, discounted at 3% annually, and compared between the 2 arms. Sensitivity analyses were conducted to evaluate the robustness of the model findings., Findings: Over a lifetime, treatment with mavacamten with or without BB or CCB monotherapy was associated with 3.67 incremental LYs compared with placebo with or without BB or CCB monotherapy (13.00 vs 9.33 LYs). Compared with individuals in the placebo group, patients in the mavacamten group were projected to spend 6.17 additional LYs in NYHA functional class I and 0.04 and 2.46 fewer LYs in NYHA functional classes II and III/IV, respectively. With utilities incorporated, mavacamten with or without BB or CCB monotherapy was associated with 4.17 additional QALYs compared with placebo with or without BB or CCB monotherapy (11.74 vs 7.57 QALYs). In the sensitivity analyses, incremental benefits ranged from 1.55 to 6.21 LYs and from 2.48 to 6.19 QALYs across the scenarios., Implications: This model projected substantial net health benefits associated with mavacamten for symptomatic obstructive HCM owing to improved patient survival and quality of life. The projected QALY gain underscored the likely long-term clinical value of mavacamten in symptomatic obstructive HCM., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Our study aimed to determine the prevalence and prognosis of acute coronary syndrome with non-obstructive coronary artery (ACS-NOCA) in patients with hypertrophic cardiomyopathy (HCM)., Methods and Results: We enrolled a total of 200 consecutive patients with HCM over a 139-month period from 2002 to 2013. The study found that 28 patients (14% of overall patients, 51% of patients with ACS) had ACS-NOCA, and 18 patients (9% of overall patients, 86% of patients with acute MI) had MINOCA as initial clinical presentations. The highest prevalence of non-obstructive coronary artery disease (NOCA) in patients with HCM was found in acute ST-elevation myocardial infarction (STEMI) (100%), followed by non-STEMI (82%), and unstable angina (29%). Patients with ACS-NOCA had more frequent ventricular tachycardia and lower resting left ventricular (LV) outflow tract gradients than those with no ACS-NOCA (p < 0.05 for all). The ACS-NOCA group had a lower probability of HCM-related death compared with the no ACS-NOCA group and the significant coronary artery disease (CAD) group (p-log-rank = 0.0018)., Conclusions: MINOCA or ACS-NOCA is not an uncommon initial presentation (prevalence rate 9-14%) in patients with HCM. NOCA was highly prevalent (51-86%) in patients with HCM presenting with ACS and had a favorable prognosis. Our findings highlight as a reminder that in an era of rapid reperfusion therapy, ACS in patients with HCM is not only a result of obstructive epicardial CAD, but also stems from the complex cellular mechanisms of myocardial necrosis., (© 2021. The Author(s).)

Increasing data have indicated that late gadolinium enhancement (LGE) in cardiac magnetic resonance (CMR) images is associated with the clinical prognosis of hypertrophic cardiomyopathy (HCM). Recently, pioneer studies indicated that the location of LGE in CMR images also had potential predictive value for HCM prognosis. The aim of the present study was to investigate the prognostic value of the location of LGE for HCM. This present cohort study included 557 HCM patients who underwent LGE-CMR imaging, and the LGE location was classified as LGE in interventricular septum only (IVS-LGE) and LGE outside the IVS with or without IVS involvement (other than IVS-LGE). All-cause mortality, cardiovascular mortality/cardiac transplantation, and sudden cardiac death (SCD) were evaluated. During a mean follow-up time of 83.0±37.8 months, there was a significantly higher all-cause mortality, cardiovascular mortality/cardiac transplantation, and SCD in patients with other than IVS-LGE than in those with IVS-LGE. Multivariate Cox regression suggested that other than IVS-LGE were one of independent prognostic predictors. Risk reclassification for prognosis showed that there were no differences between the prediction values of the presence of LGE and the location of LGE. The presence and location of LGE in CMR images are equally independent prognostic predictors of HCM, and other than IVS-LGE location is associated with an adverse clinical prognosis. Prognosis Trial Registration: ChiCTR-ONRC-11001902., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Background: Red blood cell distribution width (RDW) has emerged as a useful indicator for adverse outcomes in several cardiovascular diseases. The relation between RDW and the prognosis of hypertrophic cardiomyopathy (HCM) remains to be evaluated. We examined the relation between RDW and all-cause mortality and HCM-related death in a population of adult HCM patients., Methods: We performed clinical evaluation in 414 consecutive adult HCM patients (median age, 57.5 years; male, 54.8%)., Results: During a median follow-up of 3.7 years, all-cause mortality and HCM-related death occurred in 75 (18.1%) and 50 (12.1%) patients, respectively. Based on the tertiles of baseline RDW, mortality increased with higher tertile. With the tertile 1 as reference, adjusted all-cause mortality hazard ratios (HRs) were 3.9 for the tertile 2 (95% confidence interval [CI]: 1.5-10.3) and 3.1 for the tertile 3 (95% CI: 1.1-8.2). Adjusted HCM-related death HRs were higher in the tertile 2 (HR: 5.5; 95% CI: 1.2-24.4) and tertile 3 (HR: 6.6; 95% CI: 1.5-29.0) compared with the tertile 1. Further smooth curve fitting exhibited a saturation effect after adjusting for confounders, and there were a two-stage change and an inflection point. Two-piecewise Cox model suggested mortality significantly increased with RDW level up to the inflection point (about 14.0% for both all-cause mortality and HCM-related death), and RDW was not associated with mortality after the point., Conclusion: In adult HCM patients, we found increased RDW was a significant risk predictor for all-cause mortality and HCM-related death, and a saturation effect was observed., (Copyright © 2021 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Background: The presence of variants in OBSCN was identified to be linked to hypertrophic cardiomyopathy (HCM), but whether OBSCN truncating variants were associated with HCM remained unknown., Methods: Whole-exome sequencing was performed in 986 patients with HCM and 761 non-HCM controls to search for OBSCN truncating variants, and the result was tested in a replication cohort consisting of 529 patients with HCM and 307 controls. The association of the OBSCN truncating variants with baseline characteristics and prognosis of patients with HCM were ascertained., Results: There were 28 qualifying truncating variants in the OBSCN gene detected in 26 (2.6%) patients with HCM and 6 (0.8%) controls. The OBSCN truncating variants were more prevalent in patients with HCM than controls (odds ratio, 3.4, P =0.004). This association was confirmed in the replication cohort (odds ratio, 3.8, P =0.024). The combined effects of the two cohorts estimated the odds ratio to be 3.58 ( P <0.001). Patients with or without OBSCN truncating variants shared similar demographic and echocardiographic variables at baseline. During 3.3±2.4 years (4795 patient-years) follow-up, the patients with OBSCN truncating variants were more likely to experience cardiovascular death (adjusted hazard ratio, 3.1 [95% CI, 1.40-6.70], P =0.005) and all-cause death (adjusted hazard ratio, 2.63 [95% CI, 1.21-5.71], P =0.015)., Conclusions: Our data indicated that OBSCN truncating variants contributed to the disease-onset of HCM, and increased the risk of malignant events in patients with HCM.

Background: On October 18, 2018, the US heart allocation policy was restructured to improve transplant waitlist outcomes. Previously, hypertrophic cardiomyopathy (HCM) patients experienced significant waitlist mortality and functional decline, often requiring status exemptions to be transplanted. This study aims to examine changes in waitlist mortality and transplant rates of HCM patients in the new system., Methods: Retrospective analysis was performed of the United Network for Organ Sharing Transplant Database for all isolated adult single-organ first-time heart transplant patients with HCM listed between October 17, 2013 and September 4, 2020. Patients were divided by listing date into eras based on allocation system. Era 1 spanned October 17, 2013 to October 17th, 2018 and Era 2 spanned October 18th, 2018 to September 4, 2020., Results: During the study period, 436 and 212 HCM patients were listed in Eras 1 and 2, respectively. Across eras, no differences in gender, ethnicity, BMI or functional status were noted (p>0.05). LVAD utilization remained low (Era 1: 3.7% vs Era 2: 3.3%, p = 0.297). Status upgrades decreased from 49.1% to 31.6% across eras (p = 0.001). There was no statistically significant difference in waitlist mortality across eras (p = 0.332). Transplant rates were improved in Era 2 (p = 0.005). Waitlist time among transplanted patients decreased in Era 2 from 97.1 to 63.9 days (p<0.001). There was no difference in one-year survival post-transplant (p = 0.602)., Conclusions: The new allocation system has significantly increased transplant rates, shortened waitlist times, and decreased status upgrade utilization for HCM patients. Moreover, waitlist mortality remained unchanged in the new system., Competing Interests: Disclosure statement The authors have no financial disclosures or conflicts of interest., (Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Objectives: Recommendations on physical activity (PA) for adults with hypertrophic cardiomyopathy (HCM) are not well established. We investigated the association of PA intensity with mortality in the general adult HCM population., Methods: A nationwide population-based cohort of individuals with HCM who underwent health check-ups including questionnaires on PA levels were identified from the years 2009 to 2016 in the National Health Insurance Service database. Subjects who reported no PA at baseline were excluded. To estimate each individual's PA level, the PA score (PAS) was calculated based on the self-reported questionnaires, and the study population was categorised into three groups according to tertiles of PAS. The associations of PAS with all-cause and cardiovascular mortality were analysed., Results: A total of 7666 participants (mean age 59.5 years, 29.9% were women) were followed up for a mean 5.3±2.0 years. All-cause and cardiovascular mortality progressively decreased from the lowest to the highest tertiles of PA intensity: 9.1% (4.7%), 8.9% (3.8%) and 6.4% (2.7%), respectively ( p-for-trend =0.0144 and 0.0023, respectively). Of note, compared with the middle PA group, the highest PA group did not have an increased risk of all-cause and cardiovascular mortality (HR 0.78, (95% CI 0.63 to 0.95) and HR 0.75 (95% CI 0.54 to 1.03), respectively). All subgroup and sensitivity analyses consistently showed that all-cause and cardiovascular mortality did not increase with higher PA levels., Conclusions: Moderate-to-vigorous-intensity PA, in a middle-aged population of patients with HCM, was associated with progressive reduction of all-cause and cardiovascular mortality. The impact of vigorous-intensity PA on a younger age group requires further investigation., Competing Interests: Competing interests: H-KK reports research grants from Actelion, Handok Pharmaceuticals, Dae-Woong Pharmaceuticals, Yuhan, Hanmi, ChongKunDang Pharmaceuticals, and Norvatis., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Purposes: A previous study reported that the ventricular septum is more fragile in geriatric patients, and thus myectomy may expose geriatric patients to a higher risk of serious complications. This single-center study evaluates the impacts of the advanced age on the results following myectomy for symptomatic hypertrophic obstructive cardiomyopathy (HOCM)., Methods: All eligible patients were divided into an elderly group (septuagenarians, n = 35) and a control group (patients under 70 years, n = 197). The patients were followed up for a median of 10 months. Thereafter, the perioperative and follow-up results were compared., Results: Thirteen patients (8.6% for the elderly group and 5.1% for the control group, p = 0.422) underwent immediate repeat surgery. Surgical mortality did not differ between groups (0 vs. 0.5%, p > 0.05). There was no significant difference in the incidence of complete atrioventricular block between groups (5.7 vs. 3.0%, p = 0.346). No follow-up deaths occurred in either group. The maximum gradients at the latest follow-up were significantly lower than the preoperative values in either group. Additionally, grouping (septuagenarians vs. patients under 70 years of age) was not an independent risk factor for surgical complications and results via multivariable logistic regression., Conclusions: Septuagenarians with HOCM may obtain favorable results following septal myectomy, the same as did HOCM patients under 70 years of age., (© 2021. Springer Nature Singapore Pte Ltd.)

Background: Management of young adults with hypertrophic cardiomyopathy (HCM) is challenging., Aims: To evaluate the profile of young adults (16-25 years) with HCM included in the French prospective HCM registry., Methods: Patients were compared according to occurrence of major adverse cardiac events (MACE), comprising sudden cardiac death (SCD) events (implantable cardioverter defibrillator [ICD] discharge, SCD, sustained ventricular tachycardia), atrial fibrillation/embolic stroke, heart failure hospitalisation and unexplained syncope, at a mean follow-up of 4.4±2.2 years., Results: At baseline, among 61 patients (20.5±3.0 years; 16 women, 26.2%), 13 (21.3%) had a prophylactic ICD, 24.6% a family history of SCD, 29.5% obstruction, 86.0% magnetic resonance imaging myocardial fibrosis, 11.8% abnormal exercise blood pressure and 52.8% a European Society of Cardiology (ESC) 5-year SCD score<4% (24.5%≥6%). At follow-up, 15 patients (24.6%; seven women; all with fibrosis) presented 17 MACE, comprising: SCD events (n=7, 41.2%; including three patients with an ICD, five with at least one SCD major classical risk factor and an ESC score≥5% and two with no risk factors and an ESC score<4%); atrial fibrillation/stroke (n=6, 35.3%); heart failure (n=1, 5.9%); syncope (n=3, 17.6%). An ICD was implanted in 11 patients (four for secondary prevention), but in only 61.5% of patients with a score≥6%. Only obstruction significantly increased MACE risk (odds ratio 3.96; P=0.035), with a non-significant trend towards a lower risk in men (OR 0.29; P=0.065)., Conclusions: In young adults with HCM, MACE are common in the short term, especially in obstructive HCM and women, mostly arrhythmic in origin. Prophylactic ICD implantation is frequent and does not strictly follow the guidelines, while the use of European/USA guidelines is helpful but imperfect in identifying SCD risk., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Background The role of late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (c-MRI) for predicting outcomes of patients with hypertrophic cardiomyopathy (HCM) has been debated. Methods We searched PubMed and Embase and various published bibliographies for prospective studies published in English between January 1990 and February 2019. Two investigators screened 2646 abstracts and full-text articles for inclusion and relevant outcomes. We then performed a systematic review and meta-analysis to calculate pooled odds ratios for LGE on c-MRI and a pooled sensitivity and specificity analysis. Results Our systematic review included 8 prospective studies and 3808 patients. LGE positivity was associated with higher odds of the endpoint of sudden cardiac death (SCD;OR 1.69, 95%CI 1.03-2.78), aborted SCD or appropriate implantable cardioverter- defibrillator (ICD) discharge (OR 3.27 [1.75-6.10]), SCD or aborted SCD or appropriate ICD discharge (OR 2.32 [1.56-3.43]), and all-cause mortality (OR 2.10 [CI 1.00-4.41]). The pooled sensitivity and specificity of positive LGE on c-MRI for SCD were 65% and 42%, respectively; for aborted SCD or appropriate ICD discharge, 79% and 39%; for SCD or aborted SCD or appropriate ICD discharge, 74% and 39%; and for all-cause mortality, 78% and 39%. Conclusion In patients with HCM, LGE on c-MRI is a strong predictor of arrhythmic outcomes including SCD, aborted SCD, and appropriate ICD therapy. These data support the routine use of LGE on c-MRI as a marker of SCD risk in this population., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The prognostic value of left atrial (LA) size and function in hypertrophic cardiomyopathy (HCM) is well recognized, but LA function is difficult to routinely analyze. Fast LA long-axis strain (LA-LAS) analysis is a novel technique to assess LA function on cine cardiovascular magnetic resonance (CMR). We aimed to assess the association between fast LA-LAS and adverse clinical outcomes in patients with HCM., Methods: 359 HCM patients and 100 healthy controls underwent routine CMR imaging. Fast LA-LAS was analyzed by automatically tracking the length between the midpoint of posterior LA wall and the left atrioventricular junction based on standard 2- and 4-chamber balanced steady-state free precession cine-CMR. Three strain parameters including reservoir strain (εs), conduit strain (εe), and active strain (εa) were assessed. The endpoint was set as composite adverse events including cardiovascular death, resuscitated cardiac arrest, sudden cardiac death aborted by appropriate implantable cardioverter-defibrillator discharge, and hospital admission related to heart failure., Results: During an average follow-up of 40.9 months, 59 patients (19.7%) reached endpoints. LA strains were correlated with LA diameter, LA volume index (LAVI) and LA empty fraction (LAEF) (all p < 0.05). In the stepwise multivariate Cox regression analysis, εs and εe (hazard ratio, 0.94 and 0.89; p = 0.019 and 0.006, respectively) emerged as independent predictors of the composite adverse events. Fast LA εs and LA εe are stronger prognostic factors than LA size, LAVI and the presence of left ventricular late gadolinium enhancement., Conclusions: Fast LA reservoir and conduit strains are independently associated with adverse outcomes in HCM.

We investigated sex-related differences in the prognosis of patients with hypertrophic cardiomyopathy (HCM) using the Korea National Health Insurance Service database. From 2010 to 2016, 9524 patients diagnosed with HCM and had more than 1-year follow-up period were analyzed. The primary endpoint was the composite of cardiovascular death or new-onset heart failure (HF) admission. Propensity score-matching analysis was performed to adjust for different baseline characteristics. With a 4.4-years' median follow-up interval (range 2.0-6.6 years) and male predominance (77.6%), women with HCM were older (52.6 ± 9.7 vs. 51.4 ± 9.1, p < 0.001), had lower incomes, more comorbidities based on Charlson comorbidity index. Women with HCM had a higher incidence of the primary endpoint than men (incidence rate: 34.15 vs. 22.83 per 1000 person-years, log-rank p < 0.001). Multivariable Cox analysis showed that female sex was a poor prognostic factor for the primary endpoint (HR 1.43, 95% CI 1.24-1.64, p < 0.001). This was mainly driven by a higher incidence of new-onset HF admission (HR 1.55, 95% CI 1.34-1.80). However, there was no difference in the incidence of cardiovascular death between the sexes. This result was concordant in the propensity score-matched cohort. In conclusion, women with HCM have worse prognosis, which was mainly driven by a higher new-onset HF admission.

Major advances in diagnosis and treatment have emerged for hypertrophic cardiomyopathy (HCM), largely in major tertiary referral centers dedicated to this disease. Whether these therapeutic benefits are confined to patients in such highly selected cohorts, or can be implemented effectively in independent regional or community-based populations is not generally appreciated. We assessed management and clinical outcomes in a non-referral HCM center (n = 214 patients) in Eastern Pennsylvania. Over a 6.0 ± 3.2-year follow-up, the HCM-related mortality rate was 0.1% per year attributed to a single disease-related death, in a 49-year-old man with end-stage heart failure, ineligible for heart transplant. Fifteen patients (7%) with prophylactically placed implantable cardioverter-defibrillators (ICDs) experienced appropriate therapy terminating life-threatening ventricular tachyarrhythmias. In 23 other patients (11%; 5%/year), heart failure due to left ventricular outflow obstruction was reversed by surgical septal myectomy (n = 20) or percutaneous alcohol septal ablation (n = 3). This regional HCM cohort was similar to a comparison tertiary center referral population in terms of HCM-mortality: 0.1%/year vs 0.3%/year (p = 0.3) and ICD therapy (31% vs 16% of primary prevention implants), although more frequently with uncomplicated benign clinical course (62% vs 46%; p <0.01). In conclusion, effective contemporary HCM management strategies and outcomes in referral-based HCM centers can be successfully replicated in regional and/or non-referral settings. Therefore, HCM is now a highly treatable disease compatible with normal longevity when assessed in a variety of clinical venues not limited to tertiary centers., (Copyright © 2020. Published by Elsevier Inc.)

Objective: To evaluate the outcomes after septal myectomy in patients with obstructive hypertrophic cardiomyopathy according to atrial fibrillation and surgical ablation of atrial fibrillation., Methods: We reviewed patients with obstructive hypertrophic cardiomyopathy who underwent septal myectomy at the Mayo Clinic from 2001 to 2016. History of atrial fibrillation was obtained from patient histories and electrocardiograms. All-cause mortality was the primary end point., Results: A total of 2023 patients underwent septal myectomy, of whom 394 (19.5%) had at least 1 episode of atrial fibrillation preoperatively. Among patients with atrial fibrillation, 76 (19.3%) had only 1 known episode, 278 (70.6%) had recurrent paroxysmal atrial fibrillation, and 40 (10.2%) had persistent atrial fibrillation. Surgical ablation was performed in 190 patients at the time of septal myectomy, including 148 with pulmonary vein isolation and 42 with the classic maze procedure. Among all patients, operative mortality was 0.4%, and there were no early deaths in patients undergoing surgical ablation. Over a median follow-up of 5.6 years, patients with preoperative atrial fibrillation had increased mortality (hazard ratio, 1.36; 95% confidence interval, 0.97-1.91; P = .070) after multivariable adjustment for comorbidities. When considering the impact of atrial fibrillation with or without surgical treatment, the adjusted hazard ratio for mortality in patients undergoing ablation compared with no ablation was 0.93 (95% confidence interval, 0.52-1.69; P = .824)., Conclusions: Atrial fibrillation is present preoperatively in one-fifth of patients with obstructive hypertrophic cardiomyopathy undergoing myectomy and showed a trend toward higher all-cause mortality. Survival of patients undergoing septal myectomy with preoperative atrial fibrillation was similar between those who did and did not receive concomitant surgical ablation., (Copyright © 2020 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Conventional risk factors for sudden cardiac death (SCD) justify primary prevention through implantable cardioverter-defibrillator (ICD) implantation in hypertrophic cardiomyopathy (HCM) patients. However, the positive predictive values for these conventional SCD risk factors are low. Left ventricular outflow tract obstruction (LVOTO) and midventricular obstruction (MVO) are potential risk modifiers for SCD. The aims of this study were to evaluate whether an elevated intraventricular pressure gradient (IVPG), including LVOTO or MVO, is a potential risk modifier for SCD and ventricular arrhythmias requiring ICD interventions in addition to the conventional risk factors among HCM patients receiving ICDs for primary prevention., Methods: We retrospectively studied 60 HCM patients who received ICDs for primary prevention. An elevated IVPG was defined as a peak instantaneous gradient ≥ 30 mmHg at rest, as detected by continuous-wave Doppler echocardiography. The main outcome was a composite of SCD and appropriate ICD interventions, which were defined as an antitachycardia pacing or shock therapy for ventricular tachycardia or fibrillation. The Cox proportional hazards model was used to assess the relationships between risk factors and the occurrence of SCD and appropriate ICD interventions., Results: Thirty patients met the criteria of elevated IVPG (50%). During the median follow-up period of 66 months, 2 patients experienced SCD, and 10 patients received appropriate ICD interventions. Kaplan-Meier curves showed that the incidence of the main outcome was higher in patients with an IVPG ≥ 30 mmHg than in those without an IVPG ≥ 30 mmHg (log-rank P = 0.03). There were no differences in the main outcome between patients with LVOTO and patients with MVO. The combination of nonsustained ventricular tachycardia (NSVT) and IVPG ≥ 30 mmHg was found to significantly increase the risk of the main outcome (HR 6.31, 95% CI 1.36-29.25, P = 0.02). Five patients experienced ICD implant-related complications., Conclusions: Our findings showed that a baseline IVPG ≥ 30 mmHg was associated with an increased risk of experiencing SCD or appropriate ICD interventions among HCM patients who received ICDs for primary prevention. Combined with NSVT, which is a conventional risk factor, a baseline IVPG ≥ 30 mmHg may be a potential modifier of SCD risk in HCM patients.

The heart muscle diseases hypertrophic (HCM) and dilated (DCM) cardiomyopathies are leading causes of sudden death and heart failure in young, otherwise healthy, individuals. We conducted genome-wide association studies and multi-trait analyses in HCM (1,733 cases), DCM (5,521 cases) and nine left ventricular (LV) traits (19,260 UK Biobank participants with structurally normal hearts). We identified 16 loci associated with HCM, 13 with DCM and 23 with LV traits. We show strong genetic correlations between LV traits and cardiomyopathies, with opposing effects in HCM and DCM. Two-sample Mendelian randomization supports a causal association linking increased LV contractility with HCM risk. A polygenic risk score explains a significant portion of phenotypic variability in carriers of HCM-causing rare variants. Our findings thus provide evidence that polygenic risk score may account for variability in Mendelian diseases. More broadly, we provide insights into how genetic pathways may lead to distinct disorders through opposing genetic effects.

Background The FHOD3 (formin homology 2 domain-containing 3) gene has recently been identified as a causative gene of hypertrophic cardiomyopathy (HCM). However, the pathogenicity of FHOD3 variants remains to be evaluated. This study analyzed the spectrum of FHOD3 variants in a large HCM and control cohort, and explored its correlation with the disease. Methods and Results The genetic analysis of FHOD3 was performed using the whole exome sequencing data from 1000 patients with HCM and 761 controls without HCM. A total of 37 FHOD3 candidate variants were identified, including 25 missense variants and 2 truncating variants. In detail, there were 27 candidate variants detected in 33 (3.3%) patients with HCM, which was significantly higher than in the 12 controls (3.3% versus 1.6%; odds ratio, 2.13; P <0.05). On the basis of familial segregation, we identified one truncating variant (c.1286+2delT) as a causal variant in 4 patients. Furthermore, the FHOD3 candidate variant experienced significantly more risk of cardiovascular death and all-cause death (adjusted hazard ratio [HR], 3.71; 95%, 1.32-8.59; P =0.016; and adjusted HR, 3.02; 95% CI, 1.09-6.85; P= 0.035, respectively). Conclusions Our study suggests that FHOD3 is a causal gene for HCM, and that the presence of FHOD3 candidate variants is an independent risk for cardiovascular death and all-cause death in HCM.

Background: The incremental prognostic value of left atrial (LA) dysfunction, emerging in various clinical contexts, remains poorly explored in hypertrophic cardiomyopathy (HCM)., Objective: To assess LA strain correlation with outcome in HCM., Methods: A cohort of all 307 consecutive patients presenting with HCM between 2007 and 2017 (54±17 years; 34% women), with comprehensive echocardiography at diagnosis and LA peak longitudinal strain (PALS) and LA peak contraction strain (PACS) measurement, was enrolled and occurrence of HCM related cardiac events analysed., Results: Clinically, atrial fibrillation (AF) was present in 13%, New York Heart Association functional class II-III in 54%, and B-type natriuretic peptide (BNP) concentration was 199±278pg/mL. By echocardiography, left ventricular (LV) ejection fraction (EF) was 67±10%, LV thickness 21±5mm and European Society of Cardiology HCM risk score 3±3%, with 109 patients (36%) presenting obstructive HCM (LV outflow gradient 21±32mmHg). LA diameter was 41±8mm [with 109 (36%) presenting LA diameter ≥40mm], LA volume index 50±26mL/m 2 , PALS 24±13%, PACS 11±7% and LA peak systolic strain rate (LASRs) 1.7±0.6 s -1 . In addition to AF, age, BNP, LVEF and LV thickness were all independent determinants of lower PALS, with odd ratios almost unchanged after adjustment (all P ≤0.0004). At a mean follow-up of 21 (range 18-23) months, patients with adverse cardiac events (n=65) presented with more impaired LA function (all P ≤0.0005), with a significant association between impaired PALS and worse outcome, hazard ratio 0.94 [95% confidence interval (CI) 0.92-0.97, P<0.0001]. After comprehensive adjustment, PALS remained strongly associated with worse outcome, adjusted hazard ratio 0.86 (95% CI 0.79-0.94; P=0.0008)., Conclusions: The present study, by gathering a unique HCM cohort, suggests a strong link between LA dysfunction and poor outcome, to be further investigated., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)