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Importance: The ability to predict sudden cardiac death (SCD) in children and adolescents with hypertrophic cardiomyopathy (HCM) is currently inadequate. Late gadolinium enhancement (LGE) by cardiovascular magnetic resonance (CMR) imaging is associated with SCD events in adults with HCM., Objective: To examine the prognostic significance of LGE in patients with HCM who are younger than 21 years., Design, Setting, and Participants: This multicenter, retrospective cohort study was conducted from April 8, 2015, to September 12, 2022, in patients with HCM who were younger than 21 years and had undergone CMR imaging across multiple sites in the US, Europe, and South America. Observers of CMR studies were masked toward outcomes and demographic characteristics., Exposure: Natural history of HCM., Main Outcome and Measures: The primary outcome was SCD and surrogate events, including resuscitated cardiac arrest and appropriate discharges from an implantable defibrillator. Continuous and categorical data are expressed as mean (SD), median (IQR), or number (percentage), respectively. Survivor curves comparing patients with and without LGE were constructed by the Kaplan-Meier method, and likelihood of subsequent clinical events was further evaluated using univariate and multivariable Cox proportional hazards models., Results: Among 700 patients from 37 international centers, median (IQR) age was 14.8 (11.9-17.4) years, and 518 participants (74.0%) were male. During a median (IQR) [range] follow-up period of 1.9 (0.5-4.1) [0.1-14.8] years, 35 patients (5.0%) experienced SCD or equivalent events. LGE was present in 230 patients (32.9%), which constituted an mean (SD) burden of 5.9% (7.3%) of left ventricular myocardium. The LGE amount was higher in older patients and those with greater left ventricular mass and maximal wall thickness; patients with LGE had lower left ventricular ejection fractions and larger left atrial diameters. The presence and burden of LGE was associated with SCD, even after correcting for existing risk stratification tools. Patients with 10% or more LGE, relative to total myocardium, had a higher risk of SCD (unadjusted hazard ratio [HR], 2.19; 95% CI, 1.59-3.02; P < .001). Furthermore, the addition of LGE burden improved the performance of the HCM Risk-Kids score (before LGE addition: 0.66; 95% CI, 0.58-0.75; after LGE addition: 0.73; 95% CI, 0.66-0.81) and Precision Medicine in Cardiomyopathy score (before LGE addition: 0.68; 95% CI, 0.49-0.77; after LGE addition: 0.73; 95% CI, 0.64-0.82) SCD predictive models., Conclusions and Relevance: In this retrospective cohort study, quantitative LGE was a risk factor for SCD in patients younger than 21 years with HCM and improved risk stratification.

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.

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 incidence and prognostic predictors of heart failure (HF) without left ventricular systolic dysfunction (LVSD) in hypertrophic cardiomyopathy (HCM), particularly their differences in terms of developing LVSD (progression to end-stage) or sudden cardiac death (SCD), are not fully elucidated., Methods and Results: This study included 330 consecutive HCM patients with left ventricular ejection fraction (LVEF) ≥50%. HF hospitalization without LVSD and development of LVSD were evaluated as main outcomes. During a median follow-up of 7.3 years, the incidence of HF hospitalization without LVSD was 18.8%, which was higher than the incidence of developing LVSD (10.9%) or SCD (8.8%). Among patients who developed LVSD, only 19.4% experienced HF hospitalization without LVSD before developing LVSD. Multivariable analysis showed that predictors for HF hospitalization without LVSD (higher age, atrial fibrillation, history of HF hospitalization, and higher B-type natriuretic peptide concentrations) were different from those of developing LVSD (male sex, lower LVEF, lower left ventricular outflow tract gradient, and higher tricuspid regurgitation pressure gradient). Known risk factors for SCD did not predict either HF without LVSD or developing LVSD., Conclusions: In HCM with LVEF ≥50%, HF hospitalization without LVSD was more frequently observed than development of LVSD or SCD during mid-term follow-up. The overlap between HF without LVSD and developing LVSD was small (19.4%), and these 2 HF events had different predictors.

Background: In patients with Hypertrophic Cardiomyopathy (HCM) S-ICD is usually the preferred option as pacing is generally not indicated. However, limited data are available on its current practice adoption and long-term follow-up., Methods: Consecutive HCM patients with S-ICD implanted between 2013 and 2021 in 3 international centers were enrolled in this observational study. Baseline, procedural and follow-up data were regularly collected. Efficacy and safety were compared with a cohort of HCM patients implanted with a tv-ICD., Results: Seventy patients (64% males) were implanted with S-ICD at 41 ± 15 years, whereas 168 patients with tv-ICD at 49 ± 16 years. For S-ICD patients, mean ESC SCD risk score was 4,5 ± 1.9%: 25 (40%) at low-risk, 17 (27%) at intermediate and 20 (33%) at high-risk. Patients were followed-up for 5.1 ± 2.3 years. Two patients (0.6 per 100-person-years, vs 0.4 per 100 person-years with tv-ICD, p = 0.45) received an appropriate shock on VF, 17 (24%) were diagnosed with de-novo AF. Inappropriate shocks occurred in 4 patients (1.2 per 100-person-years, vs 0.9 per 100 person-years with tv-ICD, p = 0.74), all before Smart-Pass algorithm implementation. Four patients experienced device-related adverse events (1.2 per 100-person-years, vs 1 per 100 person-years with tv-ICD, p = 0.35%)., Conclusions: S-ICDs were often implanted in patients with an overall low-intermediate ESC SCD risk, reflecting both the inclusion of additional risk markers and a lower decision threshold. S-ICDs in HCM patients followed for over 5 years showed to be effective in conversion of VF and safe. Greater scrutiny may be required to avoid overtreatment in patients with milder risk profiles., Competing Interests: Conflict of interest The authors report no conflict of interest regarding the topic discussed in the present manuscript. The study was supported by an educational grant from Boston Scientific, USA. Disclosures: Dr. I. Olivotto has received grants from Brystol Myers Squibb, Cytokinetics, Amicus, Genzyme, Shire, Bayer, Boston Scientific, Menarini International, and fees (honoraria or consulting) from Bristol Myers Squibb, Cytokinetics, Amicus, Genzyme, Shire, Boston Scientific, and served or currently serving as PI on EXPLORER-HCM, MAVA-LTE, REDWOOD-HCM, REDWOOD-OLE, and SEQUOIA-HCM trial. Dr. F. Cecchi received consultancy fees from Pfizer and Bristol Myers Squibb. Dr. L. Crotti and Dr. N. Maurizi received consultancy fees from Bristol Myers Squibb., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Sudden cardiac death (SCD) represents the most severe complication of hypertrophic cardiomyopathy (HCM). However, the relation between strain, strain rate (SR), and risk factors in SCD risk stratification remains elusive. The study aimed to assess the attenuation of strain and SR in HCM by feature tracking cardiac magnetic resonance. All strain and SRs were obtained automatically by feature tracking, with manual adjustment of endocardial and epicardial borders. Strain indicators included left ventricular global longitudinal, circumferential, global radial strain (GRS), peak diastolic-longitudinal, circumferential, and radial SR. Patients were categorized into high-risk and low-risk groups for SCD based on the 2020 American Heart Association/American College HCM risk-SCD model. The correlation between strain/SR and SCD risk factors was assessed through Spearman correlation analysis. Furthermore, a multivariate logistic regression analysis was conducted to explore the factors that influence SCD risk in HCM patients. A total of 105 HCM patients were analyzed in this study, including 38 patients in the high-risk group, and 67 patients in the low-risk group. Compared with the low-risk group, the high-risk group exhibited significantly worse strain and SR (p <0.001). Furthermore, both circumferential and GRS and SR exhibited meaningful associations with risk factors for SCD. Additionally, GRS emerged as an independent risk factor for predicting heightened SCD risk in HCM patients (p <0.001). In conclusion, left ventricular strain and SR based on feature tracking-cardiac magnetic resonance can be evaluated for SCD risk and are strongly associated with SCD risk factors., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aims: To conduct a contemporary cost-effectiveness analysis examining the use of implantable cardioverter defibrillators (ICDs) for primary prevention in patients with hypertrophic cardiomyopathy (HCM)., Methods: A discrete-time Markov model was used to determine the cost-effectiveness of different ICD decision-making rules for implantation. Several scenarios were investigated, including the reference scenario of implantation rates according to observed real-world practice. A 12-year time horizon with an annual cycle length was used. Transition probabilities used in the model were obtained using Bayesian analysis. The study has been reported according to the Consolidated Health Economic Evaluation Reporting Standards checklist., Results: Using a 5-year SCD risk threshold of 6% was cheaper than current practice and has marginally better total quality adjusted life years (QALYs). This is the most cost-effective of the options considered, with an incremental cost-effectiveness ratio of £834 per QALY. Sensitivity analyses highlighted that this decision is largely driven by what health-related quality of life (HRQL) is attributed to ICD patients and time horizon., Conclusion: We present a timely new perspective on HCM-ICD cost-effectiveness, using methods reflecting real-world practice. While we have shown that a 6% 5-year SCD risk cut-off provides the best cohort stratification to aid ICD decision-making, this will also be influenced by the particular values of costs and HRQL for subgroups or at a local level. The process of explicitly demonstrating the main factors, which drive conclusions from such an analysis will help to inform shared decision-making in this complex area for all stakeholders concerned., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

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.)

Background: Hypertrophic cardiomyopathy is a condition associated with an increased risk of sudden death compared to the general population. Extended septal myectomy surgery has been suggested to impact the reduction of sudden death events according to various publications. The aim of this study was to assess changes in the prevalence of sudden death predictors in a population of patients undergoing extended septal myectomy surgery., Methods: Ninety-four consecutive patients underwent extended septal myectomy surgery due to symptomatic hypertrophic cardiomyopathy. Risk factors for sudden death, as defined by the American Heart Association and the European Society of Cardiology, were evaluated before and three months after surgery., Results: The mean age of the population was 57 ± 13 years. A significant reduction was observed in the maximum septal thickness from 21.3 to 14 mm (p<0.001), along with a decrease in the anteroposterior diameter of the left atrium from 51 to 47 mm (p=0.021). Resting intraventricular gradients decreased from 49.2 to 6.4 mmHg (p<0.001), and Valsalva-induced gradients decreased from 93.9 to 8.7 mmHg (p<0.001). Non-sustained ventricular tachycardia decreased from 6% to 2% (p<0.001), and atrial fibrillation decreased from 30% to 15% (p<0.001). Ischemic behavior during exercise stress echo decreased from 6% to 0%, and the European Society of Cardiology sudden death risk score reduced from 3.32 to 1.44 (p<0.001)., Conclusions: In this cohort of hypertrophic cardiomyopathy patients, extended septal myectomy surgery was associated with a reduction in the number and magnitude of sudden death predictors, potentially explaining the reduced mortality reported in the literature., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective To analyze the research progress and hot topics in hypertrophic cardiomyopathy from 2018 to 2022.Methods The publications in the field of hypertrophic cardiomyopathy from January 1,2018 to December 31,2022 were retrieved from Web of Science core collection database and included for a bibliometric analysis.Results A total of 6355 publications were included,with an average citation frequency of 7 times.The year 2021 witnessed the most publications (1406).The analysis with VOSviewer showed that the research on sudden death related to hypertrophic cardiomyopathy,especially the predictive value of late gadolinium-enhanced cardiac MRI in sudden death,was a hot topic.In addition,gene detection and the new drug mavacamten became hot research topics.The United States was the country with the largest number of publications and the highest citation frequency in this field.Chinese scholars produced the second largest number of publications,which,however,included few high-quality research results.Conclusions Risk stratification and prevention of sudden death is still an important and hot research content in the field of hypertrophic cardiomyopathy.Chinese scholars should carry out multi-center cooperation in the future to improve the research results.

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: Risk assessment tools and effective prevention strategies for sudden cardiac death (SCD) in pediatric patients with hypertrophic cardiomyopathy (HCM) have not been established. This study aimed to evaluate the efficacy of beta-blockers and exercise restriction for SCD prevention in this population., Methods: We retrospectively reviewed the medical records of patients aged <18 years who were diagnosed with HCM at our center between January 1996 and December 2021. SCD and aborted SCD were defined as SCD equivalents. We divided patients based on whether they were prescribed beta-blockers or exercise restriction and compared the outcomes among the groups. The primary outcome was the overall survival (OS), and the secondary outcome was the cumulative SCD equivalent rate. Outcomes were analyzed using Kaplan-Meier curves and Cox proportional hazard analysis. We also compared patients according to the occurrence of SCD equivalents to identify SCD risk predictors., Results: Among the 43 included patients [mean age, 7.7 (1.6-12.1) years; 23 male individuals], SCD equivalents occurred in 13 patients over 11.2 (4.5-15.6) years of follow-up, among whom 12 were resuscitated and 1 died. The OS rate was significantly higher in the beta-blocker and exercise restriction groups than in the non-beta-blocker and non-exercise restriction groups (81.3 % vs. 19.1 %, p < 0.01 and 57.4 % vs. 12.7 %, p < 0.01, respectively). Among the 13 patients with SCD equivalents, 5 had 9 recurrent SCD equivalents. A significant difference was observed between the SCD equivalent and non-SCD equivalent groups in the history of suspected arrhythmogenic syncope (p < 0.01) in the univariable but not in the multivariable analysis., Conclusions: Beta-blockers and exercise restriction may decrease the risk of SCD in pediatric patients with HCM and should be considered for SCD prevention in this population, particularly because predicting SCD in these patients remains challenging., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

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: 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.)

The American approach to predicting sudden cardiac death (SCD) in patients with hypertrophic cardiomyopathy diverges from the European method in that it relies on major risk factors independently justifying the implantation of an implantable cardioverter-defibrillator for primary prevention, whereas the European approach uses a mathematical equation to estimate a 5-year risk percentage. The aim of this review is to outline the differences between the American and European guidelines and to show how they have arisen. Furthermore, it will provide insight into the future of SCD risk prediction in patients with hypertrophic cardiomyopathy. The American SCD risk prediction method has high sensitivity but limited specificity, whereas the European method has the opposite. These differences in sensitivity and specificity likely contribute to the fact that primary prevention implantable cardioverter-defibrillator utilization is twofold higher in the United States. It is highly likely that new insights and new imaging modalities will enhance prediction models in the near future. Genotyping could potentially assume a significant role. Left ventricular global longitudinal strain was recently shown to be an independent predictor of SCD. Furthermore, after late gadolinium enhancement, additional cardiac magnetic resonance techniques such as T1 mapping and diffusion tensor imaging are showing encouraging outcomes in predicting SCD. Ultimately, it is conceivable that integrating diverse morphological and genetic characteristics through deep learning will yield novel insights and enhance SCD prediction methods., (Copyright © 2024 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Up to 20% of children with sarcomeric hypertrophic cardiomyopathy (HCM) have disease-causing variants in genes coding for thin-filament proteins. However, data on genotype-phenotype correlations for thin-filament disease are limited. This study describes the natural history and outcomes of children with thin-filament-associated HCM and compares it to thick-filament-associated disease.Longitudinal data were collected from 40 children under 18 years with a disease-causing variant in a thin-filament protein from a single quaternary referral centre. Twenty-one (female n=6, 35.5%) were diagnosed with HCM at a median age of 13.0 years (IQR 8.3-14.0). Over a median follow-up of 5.0 years (IQR 4.0-8.5), three (14.3%) experienced one or more major adverse cardiac events (MACE) (two patients had an out-of-hospital arrest and eight appropriate implantable cardiac defibrillator (ICD) therapies in three patients). One gene carrier died suddenly at age 9 years. Compared with those with thick-filament disease, children with thin-filament variants more commonly experienced non-sustained ventricular tachycardia [NSVT; n=6 (28.6%) vs n=14 (10.8%), p=0.024] or underwent ICD insertion (thin, n=13 (61.9%) vs thick, n=50 (38.5%), p=0.040). However, there was no difference in the incidence of MACE (thin 2.47/100 pt years (95% CI 0.80 to 7.66) vs thick 3.63/100 pt years (95% CI 2.25 to 5.84)) or an arrhythmic event (thin 1.65/100 pt years (95% CI 0.41 to 6.58) vs thick 2.55/100 pt years (95% CI 1.45 to 4.48), p value 0.43).This study suggests that adverse events in thin-filament disease are predominantly arrhythmic and may occur in the absence of hypertrophy, but overall short-term outcomes do not differ significantly from thick-filament disease., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Hypertrophic cardiomyopathy (HCM) is a relatively common often inherited heart disease encumbered throughout much of its almost 60-year history by the expectation of an unfavorable outcome with shortened longevity. However, it is notable that in 2023, most patients affected with HCM can now achieve normal or extended life expectancy without major disability because of a comprehensive constellation of management strategies that have evolved largely over the last 20 years. Distinct adverse disease pathways dictate high-benefit low-risk personalized treatments, without reliance on genomics and sarcomere mutations, including: primary prevention implantable defibrillators for sudden cardiac death prevention, surgical myectomy and percutaneous alcohol septal ablation to reverse heart failure symptoms, anticoagulation to prevent embolic stroke associated with concomitant atrial fibrillation, external defibrillation and hypothermia for out-of-hospital cardiac arrest, and heart transplant in a small patient subgroup with end-stage disease. Large cohort studies using these contemporary management strategies achieved remarkably low HCM-related mortality (0.5%/year) across all age groups, which is lower than in the other cardiac or noncardiac risks of living, and largely confined to nonobstructive patients with progressive heart failure, including those awaiting heart transplant., Competing Interests: Declaration of competing interest Dr. Martin Maron declares steering committee member SEQUIOA-HCM. Consultant Imbria and Edgewise. The remaining authors have no competing interest to declare., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Hypertrophic cardiomyopathy (HCM) is a complex, heterogeneous disorder that affects approximately 1 in every 500 persons worldwide and about 750,000 Americans. It is characterized by left ventricular hypertrophy that is usually asymmetric, with enlarged myocytes in disarray, unexplained by loading conditions. Obstruction to left ventricular outflow occurs in approximately 60% of patients. The natural history and cardiac morphology of HCM are quite heterogeneous. Although most patients with HCM are asymptomatic or mildly symptomatic, a minority are disabled by dyspnea, angina, or syncope, develop advanced heart failure, or die suddenly., Competing Interests: Declaration of competing interest The author has no competing interests to declare., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

In hypertrophic cardiomyopathy (HCM), late gadolinium enhancement (LGE) extent ≥15% of left ventricular mass is considered a prognostic risk factor. LGE extent increases over time and the clinical role of the progression of LGE over time (LGE rate) was not prospectively evaluated. We sought to evaluate the prognostic role of the LGE rate in HCM. We enrolled 105 patients with HCM who underwent cardiac magnetic resonance (CMR) at baseline (CMR-I) and after ≥2 years of follow-up (CMR-II). LGE rate was defined as the ratio between the increase of LGE extent (grams) and the time interval (months) between examinations. A combined end point of sudden cardiac death, resuscitated cardiac arrest, appropriate Implanted Cardioverter Defibrillator (ICD) intervention, and sustained ventricular tachycardia was used (hard events). The percentage of patients with LGE extent ≥15% increased from 9% to 20% from CMR-I to CMR-II (p = 0.03). During a median follow-up of 52 months, 25 hard events were recorded. The presence of LGE ≥15% at CMR-II allowed a significant reclassification of the risk of patients than at LGE ≥15% at CMR-I (net reclassification improvement 0.21, p = 0.046). On the MaxStat analysis, the optimal prognostic cut point for LGE rate was >0.07 g/month. On the Kaplan-Meier curve, patients with LGE rate >0.07 had worse prognosis than those without (p <0.0001). LGE rate >0.07 allowed a significant reclassification of the risk compared with LGE ≥15% at CMR-I and at CMR-II (net reclassification improvement 0.49, p = 0.003). In the multivariable models, LGE rate >0.07 was the best independent predictor of hard events. In conclusion, CMR should be repeated after 2 years to reclassify the risk for sudden death of those patients. A high LGE rate may be considered a novel prognostic factor in HCM., Competing Interests: Declaration of Competing Interest The authors have no competing interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Hypertrophic cardiomyopathy (HCM) is the commonest genetic cardiomyopathy and may result in sudden cardiac death (SCD). Clinical risk stratification scores are utilised to estimate SCD risk and determine potential utility of a primary prevention implantable cardioverter defibrillator (ICD)., Methods: Patients with a confirmed diagnosis of HCM from a quaternary HCM service were defined according to clinical characteristics, genetic profiles and cardiac imaging results. European Risk-SCD score and American Heart Association / American College of Cardiology (AHA/ACC) Score were calculated. The primary outcome was cardiac arrest., Results: 380 patients with HCM were followed up for a median of 6.4 years. 18 patients (4.7%) experienced cardiac arrest, with predictive factors being younger age (37.2 vs 54.4 years, p = 0.0041), unexplained syncope (33.3% vs 9.4%, p = 0.007), non-sustained ventricular tachycardia (50.0% vs 12.7%, p < 0.0001), increased septal thickness (21.5 vs 17.5 mm, p = 0.0003), and presence of a sarcomeric gene mutation (100.0% vs 65.8%, p = 0.038). The Risk-SCD and AHA/ACC scores had poor agreement (kappa coefficient 0.38). Risk-SCD score had poor sensitivity (44.4%), classifying 55.6% of patients with cardiac arrest as low-risk but was highly specific (93.7%). AHA/ACC risk score did not discriminate between groups significantly. 20 patients (5.3%) died, with most >60-year-olds having a non-cardiac cause of death (p = 0.0223)., Conclusion: This study highlights limited (38%) agreement between the Risk-SCD and AHA/ACC scores. Most cardiac arrests occurred in ostensibly low or medium-risk patients under both scores. Appropriate ICD selection remains challenging. Incorporating newer risk markers such as HCM genotyping and myocardial fibrosis quantification by cardiac MRI may assist future risk refinement., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to disclose., (Crown Copyright © 2023. Published by Elsevier B.V. All rights reserved.)

Aims: Whether pregnancy is a modifier of the long-term course and outcome of women with hypertrophic cardiomyopathy (HCM) is unknown. We assessed the association of pregnancy with long-term outcomes in HCM women., Methods and Results: Retrospective evaluation of women with HCM from 1970 to 2021. Only women with pregnancy-related information (pregnancy present or absent) and a follow-up period lasting ≥1 year were included. The peri-partum period was defined as -1 to 6 months after delivery. The primary endpoint was a composite for major adverse cardiovascular events [MACE: cardiovascular death, sudden cardiac death, appropriate defibrillator shock and heart failure (HF) progression]. Overall, 379 (58%) women were included. There were 432 pregnancies in 242 (63%) patients. In 29 (7.6%) cases, pregnancies (n = 39) occurred after HCM diagnosis. Among these, three carrying likely pathogenic sarcomeric variants suffered MACEs in the peri-partum period. At 10 ± 9 years of follow-up, age at diagnosis [hazard ratio (HR) 1.034, 95% confidence interval (CI) 1.018-1.050, P < 0.001] and New York Heart Association (NYHA) class (II vs. I: HR 1.944, 95% CI 0.896-4.218; III vs. I: HR 5.291, 95% CI 2.392-11.705, P < 0.001) were associated with MACE. Conversely, pregnancy was associated with reduced risk (HR 0.605; 95% CI 0.380-0.963, P = 0.034). Among women with pregnancy, multiple occurrences did not modify risk., Conclusions: Pregnancy is not a modifier of long-term outcome in women with HCM and mostly occurs before a cardiac diagnosis. Most patients tolerate pregnancy well and do not show a survival disadvantage compared to women without. Pregnancy should not be discouraged, except in the presence of severe HF symptoms or high-risk features., Competing Interests: Conflict of interest: The Authors report no conflict of interest for the present work., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Competing Interests: Disclosures Dr Balaji has received an external research grant from Medtronic to study sudden death in children with hypertrophic cardiomyopathy. Dr Balaji is a consultant to Milestone Pharmaceuticals and AltaThera Pharmaceuticals.

Sudden cardiac death (SCD) is associated with nonsustained ventricular tachycardia (NSVT) in patients with hypertrophic cardiomyopathy (HCM). Recently, differences regarding septal morphology have been reported, with an increased probability of sudden death in patients with HCM who had reverse septal curvature (RSC). This study aimed to examine the relation between RSC and NSVT in HCM. A total of 138 patients with HCM were enrolled. Of 138 patients, 47 (34.1%) were diagnosed with RSC and 42 patients (30.4%) had NSVT. Compared with the non-RSC group, those with RSC were much younger and had an increased incidence of NSVT, thicker septal thickness, larger mass, and a higher proportion of HCM or SCD family history. Furthermore, patients with RSC had a higher risk of SCD according to the European Society of Cardiology calculator (2.5 [1.6 to 4.6] vs 1.6 [1.1 to 2.3] [%/5 years], p <0.001). The multivariate analysis showed that RSC was a strong and independent risk factor for NSVT (odds ratio 2.756, 95% confidence interval 1.164 to 6.525, p = 0.021). In conclusion, the presence of RSC in patients with HCM is independently associated with NSVT. Further studies are needed to evaluate the role of RSC as a risk factor for SCD in this population., Competing Interests: Declaration of Competing Interest The authors have no competing interest to declare., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: RASopathies account for nearly 20% of cases of childhood hypertrophic cardiomyopathy (HCM). Sudden cardiac death (SCD) occurs in patients with RASopathy-associated HCM, but the risk factors for SCD have not been systematically evaluated., Aim: To validate the HCM Risk-Kids SCD risk prediction model in children with RASopathy-associated HCM and investigate potential specific SCD predictors in this population., Methods: Validation of HCM Risk-Kids was performed in a retrospective cohort of 169 patients with a RASopathy-associated HCM from 15 international paediatric cardiology centres. Multiple imputation by chained equations was used for missing values related to the HCM Risk-Kids parameters., Results: Eleven patients (6.5%) experienced a SCD or equivalent event at a median age of 12.5 months (IQR 7.7-28.64). The calculated SCD/equivalent event incidence was 0.78 (95% CI 0.43-1.41) per 100 patient years. Six patients (54.54%) with an event were in the low-risk category according to the HCM Risk-Kids model. Harrell's C index was 0.60, with a sensitivity of 9.09%, specificity of 63.92%, positive predictive value of 1.72%, and negative predictive value of 91%; with a poor distinction between the different risk groups. Unexplained syncope (HR 42.17, 95% CI 10.49-169.56, p < 0.001) and non-sustained ventricular tachycardia (HR 5.48, 95% CI 1.58-19.03, p < 0.007) were predictors of SCD on univariate analysis., Conclusion: Unexplained syncope and the presence of NSVT emerge as predictors for SCD in children with RASopathy-associated HCM. The HCM Risk-Kids model may not be appropriate to use in this population, but larger multicentre collaborative studies are required to investigate this further., Competing Interests: Declaration of Competing Interest Wolf CM: consultancy with Day One Biopharmaceuticals, Inc., BioMarin Pharmaceuticals, Adrenomed AG, and Pliant Therapeutics; ownership interest: Preventage Therapeutics. Zenker M: consultancy with Day One Biopharmaceuticals, Inc. and Novo Nordisk., (Copyright © 2023. Published by Elsevier B.V.)

Background: The hypertrophic cardiomyopathy (HCM) risk- sudden cardiac death (SCD) model provides a convenient tool for determining the risk of SCD in patients with HCM even though some patients with low-risk scores still remain at risk of SCD. Hence, the aim of our study was to assess the performance of HCM Risk-SCD in a large series of consecutive patients with HCM who had been followed up in a tertiary center., Methods: The study population consisted of 389 consecutive HCM patients who had been followed up between 2004 and 2021. Demographic and clinical characteristics, estimated 5-year risk using the HCM Risk-SCD model, were compiled, and survival data were collected during follow-up. Patients were divided into 2 groups according to their long-term survival, and HCM risk-SCD scores of these two groups were compared., Results: The long-term mortality was observed in 47 patients out of 389 patients in the during a mean follow-up of 55.5 ± 12.7 months. The mean HCM Risk-SCD score of surviving patients was significantly lower than that of non-survivors (1.8% vs. 3.0%, p < .001). The HCM Risk-SCD score was above 6% in nine (2.6%) survivors and nine (19.1%) non-survivors (p < .001). The ROC curve based on the HCM Risk-SCD score had 61% sensitivity and 61% specificity for risk threshold of for 2.0%, 38% sensitivity and 99% specificity a threshold of ≥4%, 17% sensitivity, and 99% specificity for a threshold of ≥6%., Conclusion: A new risk algorithm with higher sensitivity is needed, although the HCM risk-SCD model is still quite useful in identifying patients at a high risk for SCD., (© 2023 Wiley Periodicals LLC.)

Background: Hypertrophic cardiomyopathy (HCM) is a common cardiac genetic disorder that clinically manifests with sudden death and progressive heart failure. Moreover, thyroid dysfunction is associated with increased cardiovascular morbidity and mortality risks. Therefore, this study aimed to clarify whether thyroid hormones could serve as an independent predictor of adverse events in patients with HCM., Methods: The cohort consisted of 782 patients with HCM who had thyroid hormones baseline data and were admitted to the Affiliated Hospital of Jiaxing University. Patients were divided into two groups according to serum levels of free triiodothyronine (fT3): the normal fT3 and low triiodothyronine (T3) syndrome groups. Low T3 syndrome was defined as fT3 < 2.43 pmol/L with a normal thyroid-stimulating hormone (TSH) level. Patients whose TSH levels were abnormally high or abnormally low were excluded from this study. The primary endpoint was the occurrence of sudden cardiac death (SCD) events, and the secondary endpoint was a composite of worsening heart failure (WHF) events, including heart failure death, cardiac decompensation, hospitalization for heart failure, and HCM-related stroke. The Kaplan-Meier and Cox regression were performed for the survival analysis., Results: After a median follow-up of 52 months, 75 SCD events and 134 WHF events were recorded. The Kaplan-Meier survival curves showed that the cumulative incidence of SCD events and WHF events were significantly higher in patients with low T3 syndrome (log-rank p = .02 and log-rank p = .001, respectively). Furthermore, multivariate Cox regression analysis demonstrated that low T3 syndrome is a strong predictor of SCD events and WHF events (adjusted hazard ratio [HR: 1.53, 95% confidence interval [CI]: 1.13-2.24, p < .01; HR: 3.87, 95% CI: 2.91-4.98, p < .001, respectively)., Conclusions: Low T3 syndrome is highly prevalent among patients with HCM and was independently associated with an increased risk of SCD events and WHF events. The routine assessment of serum fT3 levels may provide risk stratification in this population., (© 2023 The Authors. Clinical Cardiology published by Wiley Periodicals, LLC.)

Aims: The validated HCM Risk-Kids model provides accurate individualized estimates of sudden cardiac death risk in children with hypertrophic cardiomyopathy (HCM). A second validated model, PRIMaCY, also provides individualized estimates of risk, but its performance and clinical impact has not been independently investigated. The aim of this study was to investigate the clinical impact of using the PRIMaCY sudden cardiac death (SCD) risk model in childhood HCM., Methods and Results: The estimated 5-year SCD risk was calculated for children meeting diagnostic criteria for HCM in a large single-centre cohort using PRIMaCY (clinical and genetic) and HCM Risk-Kids model, and model performance was assessed. Three hundred one patients [median age 10 (interquartile range 4-14)] were followed up for an average of 4.9 (±3.8) years, during which 30 (10.0%) reached the SCD or equivalent event endpoint. Harrell's C-statistic for the clinical and genetic models was 0.66 [95% confidence interval (CI) 0.52-0.8] and 0.66 (95% CI 0.54-0.80) with a calibration slope of 0.19 (95% CI 0.04-0.54) and 0.26 (95% CI -0.03-0.62), respectively. The number needed to treat to potentially treat one life-threatening arrhythmia for the PRIMaCY clinical, PRIMaCY genetic, and HCM Risk-Kids models was 13.7, 14.5, and 9.4, respectively., Conclusion: Although PRIMaCY has a similar discriminatory ability to that reported for HCM Risk-Kids, estimated risk estimates did not correlate well with observed risk. A higher proportion of patients met implantable cardioverter-defibrillator thresholds using PRIMaCY model compared with HCM Risk-Kids. This has important clinical implications as these patients will be exposed to a lifetime risk of complications and inappropriate therapies., Competing Interests: Conflict of interest: P.M.E. declares consultancies for Pfizer and Sarepta. J.P.K. declares consultancies for Tenaya, Cytokinetics, and DiNAQOR. The other authors declare no conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Accurate identification of hypertrophic cardiomyopathy (HCM) patients at high risk of sudden cardiac death (SCD) event is challenging. The objective of this study was to validate the three SCD risk stratifications recommended by the 2014 European Society of Cardiology (ESC) guideline, the 2020 American Heart Association /American College of Cardiology (AHA/ACC) guideline, and the 2022 ESC guideline in Chinese patients with HCM. Our study population are made up of a cohort of 856 HCM patients without prior SCD events. The endpoint was defined as SCD or equivalent events (successful resuscitation after cardiac arrest or appropriate ICD shock for ventricular tachycardia or ventricular fibrillation). During a median follow-up of 43 months, SCD endpoints occurred in 44 (5.1%) patients. A total of 34 (77.3%) patients suffering from SCD events were classified correctly into high-risk groups by the 2020 AHA/ACC guideline, 27(61.4%) by the 2022 ESC guideline, and 13 (29.6%) by the 2014 ESC guideline. The C-statistic of the 2020 AHA/ACC guideline was 0.68 (95% CI, 0.60-0.76), which performed better than the 2022 ESC guideline (0.65: 95% CI, 0.56-0.73), and the 2014 ESC guideline (0.58: 95% CI, 0.48-0.67). The 2020 AHA/ACC guideline displayed better discrimination for SCD risk stratification in Chinese HCM patients than the other two guidelines, with a higher sensitivity but lower specificity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Background: Although the 12‑lead electrocardiogram (ECG) is abnormal in most patients with hypertrophic cardiomyopathy (HCM), some present normal ECG. This study aimed to analyse the baseline characteristics, clinical presentation and outcomes of HCM patients with normal ECG and to compare them with those with abnormal ECG., Methods and Results: Baseline characteristics, clinical presentation, data from complementary exams and clinical outcomes of 1070 consecutive patients included in the Portuguese Registry of HCM (Pro-HCM registry) were compared between two groups of patients: normal Vs. abnormal ECG. Among this population, 98 (9.2%) patients had normal ECG at presentation; they were significantly younger and had lower frequency of hypertension, symptoms at presentation, heart failure, angina, cardiac and non-cardiac diseases. ESC and AHA risk scores for Sudden Cardiac Death (SCD) were not significantly different between the two groups. Patients with normal ECG had higher prevalence of family history of SCD and lower degree of left ventricular (LV) hypertrophy, LV systolic dysfunction, LV outflow tract obstruction and myocardial fibrosis. The combined endpoint of cardiac death, SCD, cardiac arrest, appropriate ICD shocks or evolution to systolic dysfunction, during a mean follow-up of 5 years was significantly less frequent in patients with normal ECG (2.1% Vs. 6.5%; p = 0.043)., Conclusions: A normal ECG is not a marker of an overall benign profile in HCM patients. Though a normal ECG at presentation is associated with a less severe phenotype and a lower probability of evolution to heart failure at 5-years, this finding did not show a protective effect in other clinical outcomes., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Current guidelines recommend that relatives of index patients with hypertrophic cardiomyopathy (HCM) are offered clinical investigations to identify individuals at risk of adverse disease complications and sudden cardiac death. However, the value of family screening in relatives of index patients with a normal genetic investigation of recognized HCM genes is largely unknown., Objectives: The purpose of this study was to perform family screening among relatives of HCM index patients with a normal genetic investigation to establish the frequency of familial disease and the clinical characteristics of affected individuals., Methods: Clinical and genetic investigations were performed in consecutive and unrelated HCM index patients. Relatives of index patients who did not carry pathogenic/likely pathogenic variants in recognized HCM genes were invited for clinical investigations., Results: In total, 60% (270 of 453) of HCM index patients had a normal genetic investigation. A total of 80% of their relatives (751 of 938, median age 44 years) participated in the study. Of these, 5% (34 of 751) were diagnosed with HCM at baseline, whereas 0.3% (2 of 717 [751-34]) developed the condition during 5 years of follow-up. Their median age at diagnosis was 57 years (IQR: 51-70 years). Two-thirds (22 of 36) were diagnosed following family screening, whereas one-third (14 of 36) had been diagnosed previously because of cardiac symptoms, a murmur, or an abnormal electrocardiogram. None of the affected relatives experienced adverse disease complications. The risk of SCD was low., Conclusions: Systematic family screening of index patients with HCM and normal genetic investigations was associated with a low frequency of affected relatives who appeared to have a favorable prognosis., Competing Interests: Funding Support and Author Disclosures Dr Nielsen has received funding from the University of Southern Denmark and an unrestricted grant from Sanofi. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Hypertrophic cardiomyopathy (HCM) carries an increased risk of sudden cardiac death. Ventricular fibrillation (VF) is thought to be the common culprit arrhythmia., Objective: The purpose of this study was to describe the incidence and predictors of sustained ventricular arrhythmias (VTAs) in HCM patients., Methods: We retrospectively analyzed all patients with HCM and an implantable cardioverter-defibrillator (ICD) from a prospectively derived registry in 2 tertiary medical centers. Clinical, electrocardiographic, echocardiographic, ICD interrogation, and genetic data were collected and compared, first between patients with and without VTAs and then between patients with only VF and those with ventricular tachycardia (VT) with or without VF., Results: Of the 1328 HCM patients, 207 (145 [70%] male; mean age 33 ± 16 years) were implanted with ICDs. Over a mean follow-up of 10 ± 6 years, 37 patients with ICDs (18%) developed sustained VTAs. These were associated with a family history of sudden cardiac death and a personal history of VTAs (P = .036 and P = .001, respectively). Sustained monomorphic VT was the most common arrhythmia (n = 26, 70%) and was linked to decreased left ventricular (LV) ejection fraction and increased LV end-systolic and end-diastolic diameters. Antitachycardia pacing (ATP) successfully terminated 258 (79%) of the 326 VT events. Mortality rates were comparable between patients with and without VTAs (4 [11%] vs 29 [17%]; P = .42) and between those with and without ICDs (24 [16%] vs 85 [20%]; P = .367)., Conclusion: VT rather than VF is the most common arrhythmia in patients with HCM; it is amenable to ATP and is associated with lower LV ejection fraction and higher LV diameters. Therefore, ATP-capable devices may be considered in HCM patients with these LV features., (Copyright © 2023 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Myocardial bridging (MB) and hypertrophic cardiomyopathy (HCM) are associated with the risk of fatal ventricular arrhythmias (VAs). The goal of the study was to determine the relationship between MB and fatal VAs in HCM patients with implantable cardiac defibrillators (ICD)., Methods: A total of 108 HCM patients (mean age: 46.6 ± 13.6 years; male: 73) were enrolled in this retrospective study. All patients underwent transthoracic echocardiography and coronary computed tomography angiography. Fatal VAs including sustained ventricular tachycardia and ventricular fibrillation were documented in ICD records., Results: There were documented fatal VAs in 29 (26.8%) patients during a mean follow-up time of 71.3 ± 30.9 months. Compared with the other groups, the fatal VA group had a higher incidence of the following: presence of MB (82.8 vs. 38%, p < 0.001), deep MB (62.1 vs. 6.3%, p < 0.001), very deep MB (24.1 vs. 0%, p < 0.001), long MB (65.5 vs. 11.4%, p < 0.001), presence of > 1 MB (17.2 vs. 0%, p = 0.001), and MB of the left anterior descending artery (79.3 vs. 17.7%, p < 0.001) . Sudden cardiac death (SCD) risk score (hazard ratio: 1.194; 95% CI: 1.071-1.330; p = 0.001) and presence of MB (hazard ratio: 3.815; 95% CI: 1.41-10.284; p = 0.008) were found to be independent predictors of fatal VAs in HCM patients., Conclusions: The current data suggest that the SCD risk score and presence of MB were independent risk factors for fatal VAs in patients with HCM. In addition to conventional risk factors, the coronary anatomical course can provide clinicians with valuable information when assessing the risk of fatal VAs in HCM patients., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Individuals with hypertrophic cardiomyopathy (HCM) have historically been advised to limit exercise and sports participation to mild-intensity activities due to concerns for sudden cardiac arrest (SCA). However, more contemporary data have shown SCA is rare in patients with HCM and emerging data is shifting towards support for the safety of exercise in this patient population. Recent guidelines endorse exercise in patients with HCM after a comprehensive evaluation and shared-decision making with an expert provider., Competing Interests: Declaration of Competing Interest Dr. Emery reports personal fees (Advisory Board, Speakers Bureau) from Bristol Meyers Squibb. Dr. Martinez reports compensation for his role with Major League Soccer and from the Bristol Meyers Squibb advisory board. Dr. Bryde has no conflicts to report., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Hypertrophic cardiomyopathy (HCM) is predominantly an autosomal dominant genetic heart disease with an estimated prevalence of 1 in 200 to 1 in 500 in the general population. Clinical manifestations of HCM vary from asymptomatic state to mild functional intolerance to advanced heart failure, angina, and sudden cardiac death (SCD). Current management options for symptomatic HCM include lifestyle modifications, pharmacotherapy for symptom control and arrhythmia management, SCD risk stratification with or without defibrillator implantation, septal reduction therapy and, in some cases, heart transplantation. Until recently, none of the pharmacotherapies for management of HCM had been studied in multicenter randomized controlled trials. Mavacamten, a cardiac myosin inhibitor, is the first drug studied in this fashion and the first-in-class Food and Drug Administration approved medication that specifically targets the pathophysiology of HCM. We will review the currently available medical treatments for HCM and assess future directions., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background There is uncertainty about the appropriate use of primary prevention implantable cardioverter-defibrillators (ICDs) among older patients with hypertrophic cardiomyopathy. Methods and Results Patients with hypertrophic cardiomyopathy who received a primary prevention ICD between 2010 and 2016 were identified using the National Cardiovascular Data Registry ICD Registry. Trends in ICD utilization and patient characteristics were assessed over time. Using linked Centers for Medicare and Medicaid Service claims data, Cox proportional hazard models assessed factors associated with mortality and postdischarge hospitalization for cardiac arrest/ventricular arrhythmia. Of 5571 patients with hypertrophic cardiomyopathy, 1511 (27.1%) were ≥65 years old. ICD utilization increased over time in all age groups. There were no changes in the prevalence of risk factors for sudden cardiac death over time. The variables most strongly associated with postdischarge mortality were older age (adjusted hazard ratio (aHR) 1.80 [95% CI, 1.47-2.21]), New York Heart Association class (III/IV versus I/II aHR 2.17 [95% CI, 1.57-2.98]), and left ventricular ejection fraction (left ventricular ejection fraction ≤35% versus >50% aHR 2.34 [95% CI, 1.58-3.48]; left ventricular ejection fraction 36%-50% versus >50% aHR 2.98 [95% CI, 2.02-4.40]), while history of nonsustained ventricular tachycardia (aHR 2.38 [95% CI, 1.62-3.51]) and New York Heart Association class (III/IV versus I/II aHR 1.84 [95% CI, 1.22-2.78]) were strongly associated with hospitalization for ventricular arrhythmia/cardiac arrest. Conclusions Primary prevention ICD utilization in patients with hypertrophic cardiomyopathy increased over time, including among those ≥65 years old. Among older patients, the strongest risk factors for hospitalization for ventricular arrhythmia/cardiac arrest following ICD implantation were history of nonsustained ventricular tachycardia and New York Heart Association class.

Background: An appropriate indicator of cardiac function in the risk stratification of hypertrophic cardiomyopathy (HCM) patients is urgently needed. Cardiac index that reflects cardiac pumping function may be suitable., Objective: The purpose of this study was to investigate the clinical significance of reduced cardiac index in HCM patients., Methods: A total of 927 HCM patients were enrolled. The primary endpoint was cardiovascular death. The secondary endpoints were sudden cardiac death (SCD) and all-cause death. Combination models were constructed by adding reduced cardiac index and reduced left ventricular ejection fraction (LVEF) to the HCM risk-SCD model. Predictive accuracy was determined by C-statistics., Results: Reduced cardiac index was defined as cardiac index ≤2.42 L/min/m 2 . During median follow-up of 4.3 years, 51 patients reached the endpoint. Reduced cardiac index independently increased the risk of cardiovascular death (adjusted hazard ratio [aHR] 2.976; P = .007), SCD (aHR 6.385; P = .001), and all-cause death (aHR 2.428; P = .010). By adding reduced cardiac index to the HCM risk-SCD model, the model C-statistic increased from 0.691 to 0.762, with an integrated discrimination improvement of 0.021 (P = .018) and a net reclassification improvement of 0.560 (P = .007). The addition of reduced LVEF failed to improve the original model. Better predictive accuracy for all endpoints was also indicated in reduced cardiac index than in reduced LVEF., Conclusion: Reduced cardiac index is an independent predictor of poor prognoses in HCM patients. Combining reduced cardiac index rather than reduced LVEF improved the HCM risk-SCD stratification strategy. The reduced cardiac index showed better predictive accuracy than reduced LVEF for all endpoints., (Copyright © 2023 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Competing interests: None declared.

Objective: To investigate whether low-normal left ventricular ejection fraction (LVEF) is associated with adverse outcomes in hypertrophic cardiomyopathy (HCM) and evaluate the incremental value of predictive power of LVEF in the conventional HCM sudden cardiac death (SCD)-risk model., Methods: This retrospective study included 1858 patients with HCM from two tertiary hospitals between 2008 and 2019. We classified LVEF into three categories: preserved ( ≥ 60%), low normal (50%-60%) and reduced (<50%); there were 1399, 415, and 44 patients with preserved, low-normal, and reduced LVEF, respectively. The primary outcome was a composite of SCD, ventricular tachycardia/fibrillation and appropriate implantable cardioverter-defibrillator shocks. Secondary outcomes were hospitalisation for heart failure (HHF), cardiovascular death and all-cause death., Results: During the median follow-up of 4.09 years, the primary outcomes occurred in 1.9%. HHF, cardiovascular death, and all-cause death occurred in 3.3%, 1.9%, and 5.3%, respectively. Reduced LVEF was an independent predictor of SCD/equivalent events (adjusted HR (aHR) 5.214, 95% CI 1.574 to 17.274, p=0.007), adding predictive value to the HCM risk-SCD model (net reclassification improvement 0.625). Compared with patients with HCM with preserved LVEF, those with low-normal and reduced LVEF had a higher risk of HHF (LVEF 50%-60%, aHR 2.457, 95% CI 1.423 to 4.241, p=0.001; LVEF <50%, aHR 7.937, 95% CI 3.315 to 19.002, p<0.001) and cardiovascular death (LVEF 50%-60%, aHR 2.641, 95% CI 1.314 to 5.309, p=0.006; LVEF <50%, aHR 5.405, 95% CI 1.530 to 19.092, p=0.009), whereas there was no significant association with all-cause death., Conclusions: Low-normal LVEF was an independent predictor of HHF and cardiovascular death in patients with HCM., Competing Interests: Competing interests: G-YC is an International Editorial Advisory Board member for Heart., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Limited data are available on the long-term outcomes in patients with hypertrophic cardiomyopathy (HCM) patients with significant coronary artery disease (CAD) requiring revascularization. We investigated the risk of cardiovascular outcomes in HCM patients who underwent coronary revascularization compared to the control group without HCM. HCM patients aged ≥ 20 years were enrolled from the Korean National Health Insurance Database. Information on the diagnosis and previous medical history was obtained from the claims data. Cardiovascular outcomes were identified during 8-year after coronary revascularization in HCM patients (HCM group) and matched controls without HCM (non-HCM control group). A total of 431 patients in the HCM group and 1968 in the non-HCM control group were analyzed. The risk of all-cause death, cardiovascular death, sudden cardiac death (SCD), ischemic stroke, and hospitalization due to heart failure was significantly higher in the HCM group than in the non-HCM group, with prominent risk increase of cardiovascular death (adjusted hazard ratio [HR] 2.27, 95% confidence interval [CI] 1.63-3.15, P < 0.001) and ischemic stroke (adjusted HR 2.38, 95% CI 1.55-3.64, P < 0.001). Beyond 1-year after revascularization, the HCM group still had a significantly higher risk of cardiovascular death, SCD, and ventricular fibrillation/tachycardia compared to the non-HCM group. Mortality and major cardiovascular outcomes occurred more frequently in HCM patients with significant CAD requiring revascularization, compared to the matched non-HCM control group. Active and regular surveillance for concomitant risk factors and relevant intervention are warranted in HCM patients at increased risk for CAD., (© 2023. The Author(s).)

The most prevalent cause of mortality in children with hypertrophic cardiomyopathy (HCM) is sudden cardiac death (SCD), which happens more frequently than in adult patients. Risk stratification tactics have generally been drawn from adult practice, however emerging data has revealed significant disparities between children and adult cohorts, implying the need for pediatric-specific risk stratification methodologies. We conducted an all-language literature search on Medline, Cochrane, Embase, and Google Scholar until October 2021. The following search strings and Medical Subject Heading (MeSH) terms were used: "HCM," "SCD," "Sudden Cardiac Death," and "Childhood Onset HCM." We explored the literature on the risk of SCD in HCM for its epidemiology, pathophysiology, the role of various genes and their influence, associated complications leading to SCD and preventive and treatment modalities. Childhood-onset HCM is linked to significant life-long morbidity and mortality, including a higher SCD rate in children than in adults. The present focus is on symptom relief and avoiding illness-related consequences, but the prospect of future disease-modifying medicines offers an intriguing opportunity to alter disease expression and outcomes in these young individuals. Current preventive recommendations promote implantable cardioverter defibrillator placement based on cumulative risk factor thresholds, although they have been demonstrated to have weak discriminating capacity. This article addresses questions and discusses the etiology, risk factors, and method to risk stratification for SCD in children with HCM., Competing Interests: Conflicts of Interest & Source of Funding In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Sudden death (SD) has traditionally been the most visible and feared complication of hypertrophic cardiomyopathy (HCM). Substantial progress in reducing the occurrence of these catastrophic events represents a new paradigm in disease management. Prevention of SD in HCM has resulted from introduction of primary prevention ICDs that reliably terminate life-threatening ventricular tachyarrhythmias, as well as a matured risk stratification algorithm capable of reliably identifying those patients at highest risk. This initiative has been a major determinant of reducing HCM-related mortality to a low rate of 0.5%/year. In such a heterogeneous heart disease as HCM, no perfect risk stratification strategy is possible, and available approaches differ in terms of sensitivity and specificity for identifying patients with SD risk. Major cardiovascular societies, American Heart Association/American College of Cardiology in the USA and European Society of Cardiology in Europe have promoted different risk stratification guidelines creating the potential for judging SD risk in a given HCM patient differently based on commitment to a particular societal guideline or country of residence. In this review, we provide a critical but balanced assessment of these two divergent SD prevention strategies with regard to their respective strengths and weaknesses, as a guide to clinicians directly engaged in this important management issue., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Genetic defects in the RAS/mitogen-activated protein kinase pathway are an important cause of hypertrophic cardiomyopathy (RAS-HCM). Unlike primary HCM (P-HCM), the risk of sudden cardiac death (SCD) and long-term survival in RAS-HCM are poorly understood., Objectives: The study's objective was to compare transplant-free survival, incidence of SCD, and implantable cardioverter-defibrillator (ICD) use between RAS-HCM and P-HCM patients., Methods: In an international, 21-center cohort study, we analyzed phenotype-positive pediatric RAS-HCM (n = 188) and P-HCM (n = 567) patients. The between-group differences in cumulative incidence of all outcomes from first evaluation were compared using Gray's tests, and age-related hazard of all-cause mortality was determined., Results: RAS-HCM patients had a lower median age at diagnosis compared to P-HCM (0.9 years [IQR: 0.2-5.0 years] vs 9.8 years [IQR: 2.0-13.9 years], respectively) (P < 0.001). The 10-year cumulative incidence of SCD from first evaluation was not different between RAS-HCM and P-HCM (4.7% vs 4.2%, respectively; P = 0.59). The 10-year cumulative incidence of nonarrhythmic deaths or transplant was higher in RAS-HCM compared with P-HCM (11.0% vs 5.4%, respectively; P = 0.011). The 10-year cumulative incidence of ICD insertions, however, was 5-fold lower in RAS-HCM compared with P-HCM (6.9% vs 36.6%; P < 0.001). Nonarrhythmic deaths occurred primarily in infancy and SCD primarily in adolescence., Conclusions: RAS-HCM was associated with a higher incidence of nonarrhythmic death or transplant but similar incidence of SCD as P-HCM. However, ICDs were used less frequently in RAS-HCM compared to P-HCM. In addition to monitoring for heart failure and timely consideration of advanced heart failure therapies, better risk stratification is needed to guide ICD practices in RAS-HCM., Competing Interests: Funding Support and Author Disclosures The project was supported through funding from the Ted Rogers Centre for Heart Research, the Heart and Stroke Foundation/Robert M Freedom Chair, and the Canadian Institutes of Health Research to Dr Mital. Dr Lynch is supported by a Heart Failure Research Fellowship from Bristol Myers Squibb, Mitacs, and Myant. Dr Mital has served as a consultant for Bristol Myers Squibb and Tenaya Therapeutics; and has received unrestricted education funding from Bristol Myers Squibb. Dr Conway has served as a medical monitor for the PumpKIN trial; and has received unrestricted education funding from Abbott. Dr Rossano has served as a consultant for Merck, Bayer, Myokardia, and Cytokinetics. Dr Kantor has served as a consultant for Novartis and AstraZeneca. Dr Balaji has served as a consultant for Milestone Pharmaceuticals and Janssen Pharmaceuticals; and has received a research support grant from the Medtronic External Research Program. Dr Godown has served as a consultant for Daiichi-Sankyo. Dr Aziz has served on the Medical Advisory Board for Medtronic. Dr Jeewa has served as a medical monitor for the PumpKIN trial; and has served as a consultant for Abbott. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The evolving epidemiology of hypertrophic cardiomyopathy (HCM) has progressively changed our perception of HCM-related mortality. However, recent studies detailing individual causes of death based on age and clinical setting are lacking. Thus, the present study aimed to describe the modes of death in a consecutive cohort of HCM patients based on presenting clinical features and stage of disease., Methods: By retrospective analysis of a large HCM cohort, we identified 161 patients with >1 year follow-up who died between 2000 and 2020 and thoroughly investigated their modes of death. HCM stage at presentation was defined as "classic", "adverse remodeling" or "overt dysfunction"., Results: Of the 161 patients, 103 (64%) died of HCM-related causes, whereas 58 (36%) died of non-HCM-related causes. Patients who died of HCM-related causes were younger than those who died of non-HCM related causes. The most common cause of death was heart failure (HF). Sudden cardiac death (SCD) ranked third, after non cardiovascular death, and mostly occurred in young individuals. The proportion of HF related death and SCD per stage of disease was 14% and 27% in "classic", 38% and 21% in "adverse remodeling" and 74% and 10% in "overt dysfunction"., Conclusions: Most HCM patients die due to complications of their own disease, mainly in the context of HF. While SCD tends to be juvenile, HF related deaths often occur in age groups no longer amenable to cardiac transplant. Modes of death vary with the stage of disease, with SCD becoming less prevalent in more advanced phases, when competitive risk of HF becomes overwhelming., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: The effect of physiological circulatory changes during pregnancy on hypertrophic cardiomyopathy (HCM) has been reported with limited data. This study aimed to provide information regarding outcomes of pregnant women with HCM and to identify predictors of major adverse cardiac event (MACE)., Methods: A total of 45 pregnancies with HCM were retrospectively reviewed. The primary endpoint was a MACE that occurred within an 8‑week period after delivery, including maternal death, heart failure (HF), syncope, and malignant ventricular arrhythmias (VAs). Baseline and outcome data were analyzed for all patients. Patients with and without MACE were compared, and patients with obstructive HCM were compared with those who had non-obstructive HCM. The study population was divided into two subgroups of patients having or not having an implantable cardioverter defibrillator implantation (ICD)., Results: At least one MACE occurred in 11 patients (24.4%); six patients developed HF (13.3%), six had a ventricular tachyarrhythmia (13.3%), and two had syncope (4.4%). New York Heart Association functional class of ≥ II, presence of HF signs before pregnancy, increased left ventricular outflow tract (LVOT) gradient were significantly associated with MACE. Fatal VAs were seen during pregnancy in one of five HCM patients with ICD. In the ROC curve analysis, an LVOT gradient higher than 53.5 mm Hg predicted the presence of MACE with a sensitivity of 90.9% and a specificity of 73.5%. This study is the largest series in the literature representing pregnant women who had HCM and ICD., Conclusion: The current data suggest that HF and high LVOT gradients are important risk factors for the development of cardiac complications., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: Hypertrophic cardiomyopathy (HCM) can be associated with an abnormal exercise response. In adults with HCM, abnormal results on exercise stress testing are predictive of heart failure outcomes. Our goal was to determine whether an abnormal exercise response is associated with adverse outcomes in pediatric patients with HCM., Methods: In an international cohort study including 20 centers, phenotype-positive patients with primary HCM who were <18 years of age at diagnosis were included. Abnormal exercise response was defined as a blunted blood pressure response and new or worsened ST- or T-wave segment changes or complex ventricular ectopy. Sudden cardiac death (SCD) events were defined as a composite of SCD and aborted sudden cardiac arrest. Using Kaplan-Meier survival, competing outcomes, and Cox regression analyses, we analyzed the association of abnormal exercise test results with transplant and SCD event-free survival., Results: Of 724 eligible patients, 630 underwent at least 1 exercise test. There were no major differences in clinical characteristics between those with or without an exercise test. The median age at exercise testing was 13.8 years (interquartile range, 4.7 years); 78% were male and 39% were receiving beta-blockers. A total of 175 (28%) had abnormal test results. Patients with abnormal test results had more severe septal hypertrophy, higher left atrial diameter z scores, higher resting left ventricular outflow tract gradient, and higher frequency of myectomy compared with participants with normal test results ( P <0.05). Compared with normal test results, abnormal test results were independently associated with lower 5-year transplant-free survival (97% versus 88%, respectively; P =0.005). Patients with exercise-induced ischemia were most likely to experience all-cause death or transplant (hazard ratio, 4.86 [95% CI, 1.69-13.99]), followed by those with an abnormal blood pressure response (hazard ratio, 3.19 [95% CI, 1.32-7.71]). Exercise-induced ischemia was also independently associated with lower SCD event-free survival (hazard ratio, 3.32 [95% CI, 1.27-8.70]). Exercise-induced ectopy was not associated with survival., Conclusions: Exercise abnormalities are common in childhood HCM. An abnormal exercise test result was independently associated with lower transplant-free survival, especially in those with an ischemic or abnormal blood pressure response with exercise. Exercise-induced ischemia was also independently associated with SCD events. These findings argue for routine exercise testing in childhood HCM as part of ongoing risk assessment.

Background: Despite hypertrophic cardiomyopathy (HCM) being the most common inherited heart disease and conferring increased risk for heart failure (HF) and sudden cardiac death (SCD), risk assessment in HCM patients is still largely unresolved., Objectives: This study aims to synthesize and compare the prognostic impact of demographic, clinical, biochemical, and imaging findings in patients with HCM., Methods: The authors searched PubMed, Embase, and Cochrane Library for studies published from 1955 to November 2020, and the endpoints were: 1) all-cause death; 2) an arrhythmic endpoint including SCD, sustained ventricular tachycardia, ventricular fibrillation, or aborted SCD; and 3) a composite endpoint including (1) or (2) plus hospitalization for HF or cardiac transplantation. The authors performed a pairwise meta-analysis obtaining the pooled estimate separately for the association between baseline variables and study endpoints. A random-effects network meta-analysis was subsequently used to comparatively assess the prognostic value of outcome associates., Results: A total of 112 studies with 58,732 HCM patients were included. Among others, increased brain natriuretic peptide/N-terminal pro-B-type natriuretic peptide, late gadolinium enhancement (LGE), positive genotype, impaired global longitudinal strain, and presence of apical aneurysm conferred increased risk for the composite endpoint. At network meta-analysis, LGE showed the highest prognostic value for all endpoints and was superior to all other associates except New York Heart Association functional class >class II. A multiparametric imaging-based model was superior in predicting the composite endpoint compared to a prespecified model based on conventional risk factors., Conclusions: This network meta-analysis supports the development of multiparametric risk prediction algorithms, including advanced imaging markers additively to conventional risk factors, for refined risk stratification in HCM. (Long-term prognosis of hypertrophic cardiomyopathy according to genetic, clinical, biochemical and imaging findings: a systemic review and meta-analysis; CRD42020185219)., Competing Interests: Funding Support and Author Disclosures Dr Georgiopoulos was supported by a training grant from the European Association of Cardiovascular Imaging (training grant 2021). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)