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Competing Interests: Competing interests: None declared.

Competing Interests: Competing interests: None declared.

Background: Hypertrophic cardiomyopathy (HCM) is often concomitant with sleep-disordered breathing (SDB), which can cause adverse cardiovascular events. Although an appropriate approach to SDB prevents cardiac remodelling, detection of concomitant SDB in patients with HCM remains suboptimal. Thus, we aimed to develop a machine learning-based discriminant model for SDB in HCM., Methods: In the present multicentre study, we consecutively registered patients with HCM and performed nocturnal oximetry. The outcome was a high Oxygen Desaturation Index (ODI), defined as 3% ODI >10, which significantly correlated with the presence of moderate or severe SDB. We randomly divided the whole participants into a training set (80%) and a test set (20%). With data from the training set, we developed a random forest discriminant model for high ODI based on clinical parameters. We tested the ability of the discriminant model on the test set and compared it with a previous logistic regression model for distinguishing SDB in patients with HCM., Results: Among 369 patients with HCM, 228 (61.8%) had high ODI. In the test set, the area under the receiver operating characteristic curve of the discriminant model was 0.86 (95% CI 0.77 to 0.94). The sensitivity was 0.91 (95% CI 0.79 to 0.98) and specificity was 0.68 (95% CI 0.48 to 0.84). When the test set was divided into low-probability and high-probability groups, the high-probability group had a higher prevalence of high ODI than the low-probability group (82.4% vs 17.4%, OR 20.9 (95% CI 5.3 to 105.8), Fisher's exact test p<0.001). The discriminant model significantly outperformed the previous logistic regression model (DeLong test p=0.03)., Conclusions: Our study serves as the first to develop a machine learning-based discriminant model for the concomitance of SDB in patients with HCM. The discriminant model may facilitate cost-effective screening tests and treatments for SDB in the population with HCM., Competing Interests: Competing interests: YM received an unrestricted research grant from the Division of Cardiology, Internal Medicine III, Hamamatsu University School of Medicine, Astellas Pharma, Ono Pharmaceutical Co, Daiichi-Sankyo Co, Nippon Boehringer Ingelheim Co, Pfizer Japan, Takeda Pharmaceutical Co and Teijin Pharma. YM reports receipt of Scholarship funds or Donations Scholarship funds from Abbott Medical Japan and BIOTRONIK JAPAN., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Heart failure (HF) is one of the most common and lifestyle-limiting complications of hypertrophic cardiomyopathy (HCM). Prediction of worsening HF using clinical measures alone remains limited. Moreover, the mechanisms by which patients with HCM develop worsening HF have not been elucidated. Therefore, the aim of this study was to develop a plasma proteomics-based model to predict worsening HF among patients with HCM and to identify signalling pathways that are differentially regulated in those who subsequently develop worsening HF., Methods: In this multi-centre, prospective cohort study of 389 patients with HCM, plasma proteomics profiling of 4986 proteins was performed at enrolment. A proteomics-based random forest model was developed to predict worsening HF using data from one institution (training set, n=268). This model was externally validated in patients from a different institution (test set, n=121). Pathway analysis of proteins significantly dysregulated in patients who subsequently developed worsening HF compared with those who did not was executed, using a false discovery rate (FDR) threshold of <0.001., Results: Using the 11-protein proteomics-based model derived from the training set, the area under the receiver-operating characteristic curve to predict worsening HF was 0.87 (95% CI: 0.76 to 0.98) in the test set. Pathway analysis revealed that the Ras-MAPK pathway (FDR<0.00001) and related pathways were dysregulated in patients who subsequently developed worsening HF., Conclusions: The present study with comprehensive plasma proteomics profiling demonstrated a high accuracy to predict worsening HF in patients with HCM and identified the Ras-MAPK and related signalling pathways as potential underlying mechanisms., Competing Interests: Competing interests: Research grant and consultation fee from Bristol Meyers Squibb to YJS., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Competing interests: None declared.

Aims: Hypertrophic cardiomyopathy (HCM) is characterised by left ventricular hypertrophy (LVH), myocardial fibrosis, enhanced oxidative stress and energy depletion. Unbound/loosely bound tissue copper II ions are powerful catalysts of oxidative stress and inhibitors of antioxidants. Trientine is a highly selective copper II chelator. In preclinical and clinical studies in diabetes, trientine is associated with reduced LVH and fibrosis, and improved mitochondrial function and energy metabolism. Trientine was associated with improvements in cardiac structure and function in an open-label study in patients with HCM., Methods: The Efficacy and Mechanism of Trientine in Patients with Hypertrophic Cardiomyopathy (TEMPEST) trial is a multicentre, double-blind, parallel group, 1:1 randomised, placebo-controlled phase II trial designed to evaluate the efficacy and mechanism of action of trientine in patients with HCM. Patients with a diagnosis of HCM according to the European Society of Cardiology Guidelines and in New York Heart Association classes I-III are randomised to trientine or matching placebo for 52 weeks. Primary outcome is change in left ventricular (LV) mass indexed to body surface area, measured using cardiovascular magnetic resonance. Secondary efficacy objectives will determine whether trientine improves exercise capacity, reduces arrhythmia burden, reduces cardiomyocyte injury, improves LV and atrial function, and reduces LV outflow tract gradient. Mechanistic objectives will determine whether the effects are mediated by cellular or extracellular mass regression and improved myocardial energetics., Conclusion: TEMPEST will determine the efficacy and mechanism of action of trientine in patients with HCM., Trial Registration Numbers: NCT04706429 and ISRCTN57145331., Competing Interests: Competing interests: Relationships with industry are as follows: Univar Solutions B.V. has gifted the investigational medicinal product. Univar Solutions B.V. have had no role in trial design, the preparation or approval of this manuscript, and the decision to submit the manuscript for publication. Univar Solutions B.V. conducted a factual accuracy check of this manuscript, but any decisions to incorporate comments were made solely at the discretion of the authors. BR is advisor for Axcella Therapeutics and patent inventor of a new oxygen sensitive MRI approach USPTO, Serial No. 16/674,104, Nov 5, 2019 Serial No. GB 1818147.9, Nov 7, 2018. CAM has served as an advisor for AstraZeneca, Boehringer Ingelheim and Lilly Alliance, Novartis, PureTech Health and HAYA Therapeutics; and has received research support from Amicus Therapeutics, Guerbet Laboratories Limited and Roche., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

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.)

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.)

Objective: Hypertrophic cardiomyopathy (HCM) is a heterogeneous disease, likely encompassing several subtypes of disease with distinct biological mechanisms (ie, molecular subtypes). Current models based solely on clinical data have yielded limited accuracy in predicting the risk of major adverse cardiovascular events (MACE). Our aim in this study was to derive molecular subtypes in our multicentre prospective cohort of patients with HCM using proteomics profiling and to examine their longitudinal associations with MACE., Methods: We applied unsupervised machine learning methods to plasma proteomics profiling data of 1681 proteins from 258 patients with HCM who were prospectively followed for a median of 2.8 years. The primary outcome was MACE, defined as a composite of arrhythmia, heart failure, stroke and sudden cardiac death., Results: We identified four molecular subtypes of HCM. Time-to-event analysis revealed significant differences in MACE-free survival among the four molecular subtypes (p logrank =0.007). Compared with the reference group with the lowest risk of MACE (molecular subtype A), patients in molecular subtype D had a higher risk of subsequently developing MACE, with an HR of 3.41 (95% CI 1.54 to 7.55, p=0.003). Pathway analysis of proteins differentially regulated in molecular subtype D demonstrated an upregulation of the Ras/mitogen-activated protein kinase and associated pathways, as well as pathways related to inflammation and fibrosis (eg, transforming growth factor-β pathway)., Conclusions: Our prospective plasma proteomics study not only exhibited the presence of HCM molecular subtypes but also identified pathobiological mechanisms associated with a distinct high-risk subtype of HCM., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Reduced cardiac output (CO) has been considered crucial in symptoms' genesis in hypertrophic cardiomyopathy (HCM). Absolute value and temporal behaviour of O 2 -pulse (oxygen uptake/heart rate (VO 2 /HR)), and the VO 2 /work relationship during exercise reflect closely stroke volume (SV) and CO changes, respectively. We hypothesise that adding O 2 -pulse absolute value and kinetics, and VO 2 /work relationship to standard cardiopulmonary exercise testing (CPET) could help identify more exercise-limited patients with HCM., Methods: CPETs were performed in 3 HCM dedicated clinical units. We retrospectively enrolled non-end-stage consecutive patients with HCM, grouped according to left ventricle outflow tract obstruction (LVOTO) at rest or during Valsalva manoeuvre (72% of patients with LVOTO <30; 10% between 30 and 49 and 18% ≥50 mm Hg). We evaluated the CPET response in HCM focusing on parameters strongly associated with SV and CO, such as O 2 -pulse and VO 2 , respectively, considering their absolute values and temporal behaviour during exercise., Results: We included 312 patients (70% males, age 49±18 years). Peak VO 2 (percentage of predicted), O 2 -pulse and ventilation to carbon dioxide production (VE/VCO 2 ) slope did not change across LVOTO groups. Ninety-six (31%) patients with HCM presented an abnormal O 2 -pulse temporal behaviour, irrespective of LVOTO values. These patients showed lower peak systolic pressure, workload (106±45 vs 130±49 W), VO 2 (21.3±6.6 vs 24.1±7.7 mL/min/kg; 74%±17% vs 80%±20%) and O 2 -pulse (12 (9-14) vs 14 (11-17) mL/beat), with higher VE/VCO 2 slope (28 (25-31) vs 27 (24-31)) (p<0.005 for all). Only 2 patients had an abnormal VO 2 /work slope., Conclusion: None of the frequently used CPET parameters, either as absolute values or dynamic relationships, were associated with LVOTO. Differently, an abnormal temporal behaviour of O 2 -pulse during exercise, which is strongly related to inadequate SV increase, correlates with reduced functional capacity (peak and anaerobic threshold VO 2 and workload) and increased VE/VCO 2 slope, identifying more advanced disease irrespectively of LVOTO., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Competing interests: None declared.

We describe a patient with Fabry disease (FD) who initially presented with atrial fibrillation without left ventricular hypertrophy (LVH) 14 years before being correctly diagnosed with FD. In the interim, he survived a myocardial infarction complicated by ventricular fibrillation, and his severe LVH was misdiagnosed as sarcomeric hypertrophic cardiomyopathy. In the following 4 years, he developed proteinuric kidney disease, neuropathy, sensorineural hearing loss and gastrointestinal symptoms. The patient was eventually readmitted for an overt heart failure (HF) exacerbation and was seen by an HF cardiologist. The constellation of systemic findings led to further diagnostic testing, including an endomyocardial biopsy, tests to determine alpha-galactosidase A enzyme activity and α-galactosidase A gene (GLA) analysis. The results of the patient's tests were consistent with FD and he was started on enzyme replacement therapy. To our knowledge, this is the first detailed description of a late-onset phenotype of FD with c.146 G>C GLA variant. In addition, this case serves as a potent reminder to pay meticulous attention to 'red flags' accompanying LVH., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Sixty years ago, hypertrophic cardiomyopathy (HCM) was considered a rare lethal disease that affected predominantly young adults and for which there were few treatment options. Today, it is recognised to be a relatively common disorder that presents throughout the life course with a heterogeneous clinical phenotype that can be managed effectively in the majority of individuals. A greater awareness of the condition and less reluctance from healthcare practitioners to make the diagnosis, coupled with improvements in cardiac imaging, including greater use of artificial intelligence and improved yields from screening efforts, have all helped facilitate a more precise and timely diagnosis. This enhanced ability to diagnose HCM early is being paired with innovations in treatment, which means that the majority of patients receiving a contemporary diagnosis of HCM can anticipate a normal life expectancy and expect to maintain a good functional status and quality of life. Indeed, with increasing translation of molecular genetics from bench to bedside associated with a growing number of randomised clinical trials of novel therapies aimed at ameliorating or perhaps even preventing the disease, the next chapter in the story for HCM will provide much excitement and more importantly, offer much anticipated reward for our patients., Competing Interests: Competing interests: WEM has received advisory board fees from Pfizer, Alnylam and BMS. PME has received consultancy fees from Pfizer, BMS, DinaQor, Sanofi Genzyme, Sarepta, AstraZeneca and Novo Nordisk., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To evaluate the role of the ECG in the differential diagnosis between Anderson-Fabry disease (AFD) and hypertrophic cardiomyopathy (HCM)., Methods: In this multicentre retrospective study, 111 AFD patients with left ventricular hypertrophy were compared with 111 patients with HCM, matched for sex, age and maximal wall thickness by propensity score. Independent ECG predictors of AFD were identified by multivariate analysis, and a multiparametric ECG score-based algorithm for differential diagnosis was developed., Results: Short PR interval, prolonged QRS duration, right bundle branch block (RBBB), R in augmented vector left (aVL) ≥1.1 mV and inferior ST depression independently predicted AFD diagnosis. A point-by-point ECG score was then derived with the following diagnostic performances: c-statistic 0.80 (95% CI 0.74 to 0.86) for discrimination, the Hosmel-Lemeshow χ 2 6.14 (p=0.189) for calibration, sensitivity 69%, specificity 84%, positive predictive value 82% and negative predictive value 72%. After bootstrap resampling, the mean optimism was 0.025, and the internal validated c-statistic for the score was 0.78., Conclusions: Standard ECG can help to differentiate AFD from HCM while investigating unexplained left ventricular hypertrophy. Short PR interval, prolonged QRS duration, RBBB, R in aVL ≥1.1 mV and inferior ST depression independently predicted AFD. Their systematic evaluation and the integration in a multiparametric ECG score can support AFD diagnosis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

We herein report the case of a 53-year-old man who was historically diagnosed with hypertrophic cardiomyopathy (HCM) and was lost to follow-up, before presenting with end-stage heart failure. This was initially suspected as dilated cardiomyopathy and then 'burnt-out phase' of HCM but subsequently the underlying diagnosis was Fabry disease. Fabry disease is an uncommon lysosomal-storage disease due to reduced or absent activity of the alpha-galactosidase A enzyme. Cardiac involvement most frequently comprises left ventricular hypertrophy. Early treatment of the underlying condition with enzyme replacement therapy may prevent the progression to end-stage heart failure. Fabry disease should be considered in all patients presenting with a clinical phenotype of HCM and a historical diagnosis should be re-evaluated in light of new diagnostic tools. Untreated Fabry can progress to a 'burnt out' phase, whereby initial hypertrophy undergoes eccentric remodelling to a dilated, severely impaired left ventricle., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Genetic testing in hypertrophic cardiomyopathy (HCM) is a valuable tool to manage patients and their families. Genetic testing can help inform diagnosis and differentiate HCM from other disorders that also result in increased left ventricular wall thickness, thereby directly impacting treatment. Moreover, genetic testing can definitively identify at-risk relatives and focus family management. Pathogenic variants in sarcomere and sarcomere-related genes have been implicated in causing HCM, and targeted gene panel testing is recommended for patients once a clinical diagnosis has been established. If a pathogenic or likely pathogenic variant is identified in a patient with HCM, predictive genetic testing is recommended for their at-risk relatives to determine who is at risk and to guide longitudinal screening and risk stratification. However, there are important challenges and considerations to implementing genetic testing in clinical practice. Genetic testing results can have psychological and other implications for patients and their families, emphasising the importance of genetic counselling before and after genetic testing. Determining the clinical relevance of genetic testing results is also complex and requires expertise in understanding of human genetic variation and clinical manifestations of the disease. In this review, we discuss the genetics of HCM and how to integrate genetic testing in clinical practice., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Competing interests: None declared.

Objective: Up to 50% of patients with hypertrophic cardiomyopathy (HCM) show no disease-causing variants in genetic studies. TRIM63 has been suggested as a candidate gene for the development of cardiomyopathies, although evidence for a causative role in HCM is limited. We sought to investigate the relationship between rare variants in TRIM63 and the development of HCM., Methods: TRIM63 was sequenced by next generation sequencing in 4867 index cases with a clinical diagnosis of HCM and in 3628 probands with other cardiomyopathies. Additionally, 3136 index cases with familial cardiovascular diseases other than cardiomyopathy (mainly channelopathies and aortic diseases) were used as controls., Results: Sixteen index cases with rare homozygous or compound heterozygous variants in TRIM63 (15 HCM and one restrictive cardiomyopathy) were included. No homozygous or compound heterozygous were identified in the control population. Familial evaluation showed that only homozygous and compound heterozygous had signs of disease, whereas all heterozygous family members were healthy. The mean age at diagnosis was 35 years (range 15-69). Fifty per cent of patients had concentric left ventricular hypertrophy (LVH) and 45% were asymptomatic at the moment of the first examination. Significant degrees of late gadolinium enhancement were detected in 80% of affected individuals, and 20% of patients had left ventricular (LV) systolic dysfunction. Fifty per cent had non-sustained ventricular tachycardia. Twenty per cent of patients suffered an adverse cerebrovascular event (20%)., Conclusion: TRIM63 appears to be an uncommon cause of HCM inherited in an autosomal-recessive manner and associated with concentric LVH and a high rate of LV dysfunction., Competing Interests: Competing interests: JS-M, JPO, IG-D, IJC-R, MNC, DG-G, AL, LS and MO-G are employees of Health in Code SL. LM is a stakeholder and CEO of Health in Code SL., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Troponin and high signal intensity on T2-weighted (HighT2) cardiovascular magnetic resonance imaging (CMRi) are both markers of myocardial injury in hypertrophic cardiomyopathy (HCM). The interplay between exercise and disease development remains uncertain in HCM. We sought to assess the occurrence of postexercise troponin rises and its determinants., Methods: Multicentre project on patients with HCM and mutation carriers without hypertrophy (controls). Participants performed a symptom limited bicycle test with hs-cTnT assessment pre-exercise and 6 hours postexercise. Pre-exercise CMRi was performed in patients with HCM to assess measures of hypertrophy and myocardial injury. Depending on baseline troponin (< or > 13 ng/L), a rise was defined as a >50% or >20% increase, respectively., Results: Troponin rises occurred in 18% (23/127) of patients with HCM and 4% (2/53) in mutation carriers (p=0.01). Comparing patients with HCM with and without a postexercise troponin rise, maximum heart rates (157±19 vs 143±23, p=0.004) and maximal wall thickness (20 mm vs 17 mm, p=0.023) were higher in the former, as was the presence of late gadolinium enhancement (85% vs 57%, p=0.02). HighT2 was seen in 65% (13/20) and 19% (15/79), respectively (p<0.001). HighT2 was the only independent predictor of troponin rise (adjusted odds ratio 7.9; 95% CI 2.7 to 23.3; p<0.001)., Conclusions: Postexercise troponin rises were seen in about 20% of patients with HCM, almost five times more frequent than in mutation carriers. HighT2 on CMRi may identify a group of particularly vulnerable patients, supporting the concept that HighT2 reflects an active disease state, prone to additional injury after a short episode of high oxygen demand., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: In patients with hypertrophic cardiomyopathy (HCM), the role of small vessel disease and myocardial perfusion remains incompletely understood and data on absolute myocardial blood flow (MBF, mL/g/min) are scarce. We measured MBF using cardiovascular magnetic resonance fully quantitative perfusion mapping to determine the relationship between perfusion, hypertrophy and late gadolinium enhancement (LGE) in HCM., Methods: 101 patients with HCM with unobstructed epicardial coronary arteries and 30 controls (with matched cardiovascular risk factors) underwent pixel-wise perfusion mapping during adenosine stress and rest. Stress, rest MBF and the myocardial perfusion reserve (MPR, ratio of stress to rest) were calculated globally and segmentally and then associated with segmental wall thickness and LGE., Results: In HCM, 79% had a perfusion defect on clinical read. Stress MBF and MPR were reduced compared with controls (mean±SD 1.63±0.60 vs 2.30±0.64 mL/g/min, p<0.0001 and 2.21±0.87 vs 2.90±0.90, p=0.0003, respectively). Globally, stress MBF fell with increasing indexed left ventricle mass (R 2 for the model 0.186, p=0.036) and segmentally with increasing wall thickness and LGE (both p<0.0001). In 21% of patients with HCM, MBF was lower during stress than rest (MPR <1) in at least one myocardial segment, a phenomenon which was predominantly subendocardial. Apparently normal HCM segments (normal wall thickness, no LGE) had reduced stress MBF and MPR compared with controls (mean±SD 1.88±0.81 mL/g/min vs 2.32±0.78 mL/g/min, p<0.0001)., Conclusions: Microvascular dysfunction is common in HCM and associated with hypertrophy and LGE. Perfusion can fall during vasodilator stress and is abnormal even in apparently normal myocardium suggesting it may be an early disease marker., Competing Interests: Competing interests: SEP provides consultancy to Circle Cardiovascular Imaging (Calgary, Alberta, Canada)., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Objectives: N-terminal probrain natriuretic peptide (NT-proBNP) predicts mortality and the development of heart failure in hypertrophic cardiomyopathy (HCM). Mid-regional proatrial natriuretic peptide (MR-proANP) is a stable by-product of production of atrial natriuretic peptide. We sought to compare the prognostic value of MR-proANP and NT-proBNP in HCM., Methods: We prospectively enrolled a cohort of patients with HCM from different European centres and followed them. All patients had clinical, ECG and echocardiographic evaluation and measurement of MR-proANP and NT-proBNP at inclusion., Results: Of 357 patients enrolled, the median age was 52 (IQR: 36-65) years. MR-proANP and NT-proBNP were both independently associated with age, weight, New York Heart Association (NYHA) class, left ventricular ejection fraction (LVEF), wall thickness and left atrial dimension. During a median follow-up of 23 months, 32 patients had a primary end point defined as death (n=6), heart transplantation (n=8), left ventricular assist device implantation (n=1) or heart failure hospitalisation (n=17). Both NT-proBNP and MR-proANP (p<10 -4 ) were strongly associated with the primary endpoint, and the areas under the receiver operating characteristic (ROC) curves for both peptides were not significantly different. However, in a multiple stepwise regression analysis, the best model for predicting outcome was NYHA 1-2 vs 3-4 (HR=0.35, 95% CI 0.16 to 0.77, p<0.01), LVEF (HR=0.96, 95% CI 0.94 to 0.98, p=0.0005) and MR-proANP (HR=3.77, 95% CI 2.01 to 7.08, p<0.0001)., Conclusions: MR-proANP emerges as a valuable biomarker for the prediction of death and heart failure related events in patients with HCM., Competing Interests: Competing interests: RI has received research grant and honoraria for speaking, committees and advisory boards from Novartis, Servier, Bayer, Pfizer, Amgen. JGFC has received research grant and honoraria for speaking, committees and advisory boards from Amgen, AstraZeneca, BMS, GSK, J&J, Medtronic, Myokardia, Novartis, Novartis, Philips, Pharmacosmos, PharmaNord, Sanofi, Servier, Stealth Biopharmaceuticals, Torrent Pharmaceuticals and Vifor. CH has received proctor fees, speaker honoraria and fees for advisory board from Edwards Lifesciences, Boston Scientific, AstraZeneca, Bayer, Biotronic, Boehringer Ingelheim, Novartis, Pfizer, BMS, Daiichi-Sankyo and Bayer. MK has received honoraria, consultancy fees or speaker bureau fees from Novartis, Servier, MSD, BMS, Amgen, Sanofi, Novo Nordisk., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Competing interests: None declared.

Objective: In 2014, the European Society of Cardiology (ESC) recommended the use of a novel risk prediction model (HCM Risk-SCD) to guide use of implantable cardioverter defibrillators (ICD) for the primary prevention of sudden cardiac death (SCD) in patients with hypertrophic cardiomyopathy (HCM). We sought to determine the performance of HCM Risk-SCD by conducting a systematic review and meta-analysis of articles reporting on the prevalence of SCD within 5 years of evaluation in low, intermediate and high-risk patients as defined by the 2014 guidelines (predicted risk <4%, 4%-<6% and ≥6%, respectively)., Methods: The protocol was registered with PROSPERO (registration number: CRD42017064203). MEDLINE and manual searches for papers published from October 2014 to December 2017 were performed. Longitudinal, observational cohorts of unselected adult patients, without history of cardiac arrest were considered. The original HCM Risk-SCD development study was included a priori. Data were pooled using a random effects model., Results: Six (0.9%) out of 653 independent publications identified by the initial search were included. The calculated 5-year risk of SCD was reported in 7291 individuals (70% low, 15% intermediate; 15% high risk) with 184 (2.5%) SCD endpoints within 5 years of baseline evaluation. Most SCD endpoints (68%) occurred in patients with an estimated 5-year risk of ≥4% who formed 30% of the total study cohort. Using the random effects method, the pooled prevalence of SCD endpoints was 1.01% (95% CI 0.52 to 1.61) in low-risk patients, 2.43% (95% CI 1.23 to 3.92) in intermediate and 8.4% (95% CI 6.68 to 10.25) in high-risk patients., Conclusions: This meta-analysis demonstrates that HCM Risk-SCD provides accurate risk estimations that can be used to guide ICD therapy in accordance with the 2014 ESC guidelines., Registration Number: PROSPERO CRD42017064203;Pre-results., Competing Interests: Competing interests: MMA reports being supported by an unrestricted educational grant from Sanofi Genzyme, outside the submitted work. LM is an employee and a stakeholder of Health in Code SL. All other authors have nothing to disclose., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To identify electrocardiographic findings, especially deep Q and S waves in lead III, that differentiate athletes from patients with hypertrophic cardiomyopathy (HCM)., Methods: Digital ECGs of athletes and patients with HCM followed at the Stanford Center for Inherited Cardiovascular Disease were studied retrospectively. All patients with HCM had an echocardiogram performed. A multivariable logistic regression model was used to calculate ORs for various demographic and ECG characteristics. Linear regression was used to correlate ECG characteristics with echocardiogram findings., Results: We studied 1124 athletes and 240 patients with HCM. The average Q+S wave amplitude in lead III (III Q+S ) was significantly higher in patients with HCM compared with athletes (0.71±0.69 mV vs 0.21±0.17 mV, p<0.001). In patients with HCM, III Q+S directly correlated with interventricular septal (IVS) thickness on echocardiography (ρ=0.45, p<0.001). In a multivariable analysis adjusted for demographic and ECG characteristics, higher III Q+S values remained independently associated with HCM compared with athletes (OR=4.2 per 0.5 mV, p<0.001). In subgroup analyses of young patients, African-American subjects and subjects without left axis deviation (LAD), III Q+S remained associated with HCM. The addition of III Q+S >1.0 mV as an abnormal finding to the International Criteria for athletic ECG interpretation improved sensitivity from 64.2% to 70.4%, with a minimal decrease in specificity., Conclusion: Large Q and S waves in lead III distinguished athletes from patients with HCM, independent of axis and well-known ECG markers associated with HCM. The correlation between IVS thickness in patients with HCM and III Q+S suggests a partial explanation for this association., Competing Interests: Competing interests: VF: Partial owner, Cardiac Insight (Seattle, Washington). This company develops advanced body-worn sensing and computing technologies for cardiac diagnostics that uniquely enhance clinical efficacy. One of their products is the Cardea 20/20 ECG, which is designed to assess the cardiac risk evaluation of young athletes. EA: Founder, Personalis (Menlo Park, California). This company focuses on advanced genomic sequencing and analytics solutions to support the development of personalised therapeutics., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Aims: Amyloidosis is caused by deposition of abnormal protein fibrils, leading to damage of organ function. Hereditary amyloidosis represents a monogenic disease caused by germline mutations in 11 amyloidogenic precursor protein genes. One of the important but non-specific symptoms of amyloidosis is hypertrophic cardiomyopathy. Diagnostics of hereditary amyloidosis is complicated and the real cause can remain overlooked. We aimed to design hereditary amyloidosis gene panel and to introduce new next-generation sequencing (NGS) approach to investigate hereditary amyloidosis in a cohort of patients with hypertrophic cardiomyopathy of unknown significance., Methods: Design of target enrichment DNA library preparation using Haloplex Custom Kit containing 11 amyloidogenic genes was followed by MiSeq Illumina sequencing and bioinformatics identification of germline variants using tool VarScan in a cohort of 40 patients., Results: We present design of NGS panel for 11 genes ( TTR , FGA , APOA1 , APOA2 , LYZ , GSN , CST3 , PRNP , APP , B2M , ITM2B ) connected to various forms of amyloidosis. We detected one mutation, which is responsible for hereditary amyloidosis. Some other single nucleotide variants are so far undescribed or rare variants or represent common polymorphisms in European population., Conclusions: We report one positive case of hereditary amyloidosis in a cohort of patients with hypertrophic cardiomyopathy of unknown significance and set up first panel for NGS in hereditary amyloidosis. This work may facilitate successful implementation of the NGS method by other researchers or clinicians and may improve the diagnostic process after validation., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

A 10-year-old girl with attention-deficit hyperactivity disorder (ADHD) is diagnosed with hypertrophic cardiomyopathy. The stimulant medications used to control her ADHD pose possibly fatal risks to her cardiovascular health, so stimulant medication is stopped. Due to very poor quality of life off of medication, alternative therapies are used without improvement. The patient's caretakers decide that the benefits of stimulant medication outweigh the risks to the patient. The healthcare team clears the patient to be put back on stimulant medication with a signed waiver of liability by her caretakers., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Apical hypertrophic cardiomyopathy (ApHCM) is considered a 'benign' form of hypertrophic cardiomyopathy, with limited data on the long-term outcome. However, the clinical impact of atrial fibrillation (AF) in ApHCM is largely unknown. The hypothesis was that AF is common and has a prognostic implication in ApHCM., Methods: The occurrence of AF and outcome was assessed in 306 consecutive patients with ApHCM (68% male, 62±11 years)., Results: AF occurred in 77 patients with ApHCM (prevalence, 25.2%; annual incidence, 4.6%/year) and was independently predicted by old age and large left atrium (>45 mm). Among 70 AF patients indicated with anticoagulation, 53 patients (76%) received warfarin. During a follow-up of 5.5±2.0 years, the patients with AF had a higher incidence of all-cause death, cardiovascular death and strokes (11.7% vs 1.3%, 6.5% vs 0.9% and 19.5% vs 2.6%, respectively, all p<0.05) than those without AF. When adjusted by the age and gender, those with AF still had an increased risk for all-cause death (HR 6.58; 95% CI 1.65-26.16, p=0.007) and strokes (HR 5.13; 95% CI 1.85 to 14.18, p=0.002). AF was detected before the time of stroke in 8 (53%) out of 15 patients with both AF and stroke. In addition, six out of eight patients were on anticoagulation at the time of stroke. The cause of death was a stroke in three (33%) out of nine patients with AF., Conclusion: In patients with ApHCM, AF was common and was associated with a substantial risk for strokes and mortality suggesting that AF should be carefully managed in ApHCM., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Apical hypertrophic cardiomyopathy (Yamaguchi syndrome) is a rare subtype of hypertrophic cardiomyopathy. The syndrome is more common in Japan where it was first described. Outside Asia, it is a very rare cause of hypertrophic cardiomyopathy. Apical hypertrophic cardiomyopathy is usually detected incidentally and has a good long-term outcome. We present a case of apical hypertrophic cardiomyopathy in an African-American patient manifesting as atrioventricular nodal re-entrant tachycardia., Competing Interests: Competing interests: None declared., (2017 BMJ Publishing Group Ltd.)

Objective: Due to their unique pathophysiological profile, patients with hypertrophic cardiomyopathy (HCM) undergoing non-cardiac surgery require additional attention to perioperative management. We sought to compare perioperative outcomes of patients with HCM undergoing non-cardiac surgery with a matched group patients without HCM., Methods: This observational cohort study conducted at a tertiary care centre included patients with HCM (n=92, age 67 years, 54% men) undergoing intermediate-risk and high-risk non-cardiac surgeries between 1/2007 and 12/2013 (excluding <18 years, prior septal myectomy/alcohol ablation, low-risk surgery) who were 1:2 matched (based on age, gender, type and time of non-cardiac surgery) with patients without HCM (n=184, median age 65 years, 53% men). A composite endpoint (30-day postoperative death, myocardial infarction, stroke, in-hospital decompensated congestive heart failure (CHF) and rehospitalisation within 30 days) and postoperative atrial fibrillation (AF) were recorded., Results: There was a significantly lower incidence of intraoperative hypotension/tachycardia in patients with HCM versus those without HCM (p<0.001). At 30 days postoperatively, 42 (15%) patients had composite events. Rates of 30-day death, MI or stroke were very low in patients with HCM (5%). However, a significantly higher proportion of patients with HCM met the composite endpoint versus patients without HCM (20 (22%) vs 22 (12%), p=0.03), driven by decompensated CHF. On logistic regression, HCM, high-risk non-cardiac surgery, high anaesthesia risk score and intraoperative duration of hypotension were independently associated with 30-day composite events (p<0.05)., Conclusions: Patients with HCM undergoing high-risk and intermediate-risk non-cardiac surgeries have a low perioperative event rate, at an experienced centre. However, they have a higher risk of composite events versus matched patients without HCM., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

The burgeoning evidence of patients diagnosed with sigmoidal hypertrophic cardiomyopathy (HCM) later in life has revived the quest for distinctive features that may help discriminate it from more benign forms of isolated septal hypertrophy often labelled ventricular septal bulge (VSB). HCM is diagnosed less frequently than VSB at older ages, with a reversed female predominance. Most patients diagnosed with HCM at older ages suffer from hypertension, similar to those with VSB. A positive family history of HCM and/or sudden cardiac death and the presence of exertional symptoms usually support HCM, though they are less likely in older patients with HCM, and poorly investigated in individuals with VSB. A more severe hypertrophy and the presence of left ventricular outflow obstruction are considered diagnostic of HCM, though stress echocardiography has not been consistently used in VSB. Mitral annulus calcification is very prevalent in both conditions, whereas a restrictive filling pattern is found in a minority of older patients with HCM. Genetic testing has low applicability in this differential diagnosis at the current time, given that a causative mutation is found in less than 10% of elderly patients with suspected HCM. Emerging imaging modalities that allow non-invasive detection of myocardial fibrosis and disarray may help, but have not been fully investigated. Nonetheless, there remains a considerable morphological overlap between the two conditions. Comprehensive studies, particularly imaging based, are warranted to offer a more evidence-based approach to elderly patients with focal septal thickening., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: In hypertrophic cardiomyopathy (HCM), most of the factors associated with the risk of sudden cardiac death (SCD) are also involved in the pathophysiology of exercise limitation. The present multicentre study investigated possible ability of cardiopulmonary exercise test in improving contemporary strategies for SCD risk stratification., Methods: A total of 623 consecutive outpatients with HCM, from five tertiary Italian HCM centres, were recruited and prospectively followed, between September 2007 and April 2015. The study composite end point was SCD, aborted SCD and appropriate implantable cardioverter defibrillator (ICD) interventions., Results: During a median follow-up of 3.7 years (25th-75th centile: 2.2-5.1 years), 25 patients reached the end point at 5 years (3 SCD, 4 aborted SCD, 18 appropriate ICD interventions). At multivariate analysis, ventilation versus carbon dioxide relation during exercise (VE/VCO2 slope) remains independently associated to the study end point either when challenged with the 2011 American College of Cardiology Foundation/American Heart Association guidelines-derived score (C index 0.748) or with the 2014 European Society of Cardiology guidelines-derived score (C index 0.750). A VE/VCO2 slope cut-off value of 31 showed the best accuracy in predicting the SCD end point within the entire HCM study cohort (sensitivity 64%, specificity 72%, area under the curve 0.72)., Conclusions: Our data suggest that the VE/VCO2 slope might improve SCD risk stratification, particularly in those HCM categories classified at low-intermediate SCD risk according to contemporary guidelines. There is a need for further larger studies, possibly on independent cohorts, to confirm our preliminary findings., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Objective: While late gadolinium enhancement (LGE) in paediatric patients with hypertrophic cardiomyopathy (HCM) is reported as similar to adults, the relationship between LGE and ECG findings in paediatric patients is unknown. We sought to evaluate the relationship between LGE on cardiac MRI and LV precordial voltage on ECG., Methods: This was a retrospective analysis of paediatric patients with HCM aged 9-21 years with cardiac MRI and ECG completed within 60 days of each other. Demographic, MRI and ECG data were compared between patients with and without LGE. Maximal diastolic septal thickness, septal to free wall ratio and LGE presence were compared with LV precordial voltage (SV1, RV6 and SV1+RV6)., Results: This study included 37 patients (33 male). Mean age was 15.8±2.8 years. Mean maximal LV diastolic septal thickness was 22.1±7.9 mm. Mean septal to free wall ratio was 2.4±1.6 mm. LGE was present in 18 patients, with 16 isolated to the ventricular septum. Comparing patients with and without LGE, there was no difference in age (p=0.2) or body surface area (p=0.9). However, the presence of LGE was associated with significantly increased septal thickness (p=0.03), yet decreased voltages in SV1 (p=0.005), RV6 (p=0.005) and SV1+RV6 (p=0.002) despite increased septal dimensions., Conclusions: A significant inverse relationship exists between LGE presence and LV precordial voltage in this population. Unexpectedly low LV precordial voltages in patients with HCM may serve as a clinical surrogate marker for myocardial fibrosis and potential loss of viable myocardial tissue., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

A 34-year-old man was referred for progressive angina and exertional dyspnoea refractory to medical therapy, with a presumptive diagnosis of hypertrophic cardiomyopathy (HCM). Transthoracic echocardiography (TTE) revealed asymmetric septal hypertrophy without systolic anterior motion of the mitral valve leaflet and with no dynamic left ventricular outflow tract (LVOT) obstruction. However, the LVOT velocity was elevated at rest as well as with provocation, without the characteristic late peaking obstruction seen in HCM. Focused TTE to evaluate for suspected fixed obstruction demonstrated a subaortic membrane 2.2 cm below the aortic valve. Coronary CT angiography confirmed the presence of the subaortic membrane and was negative for concomitant coronary artery disease. Surgical resection of the subaortic membrane and septal myectomy resulted in significant symptomatic relief and lower LVOT velocities on postoperative TTE. This case reminds the clinician to carefully evaluate for alternative causes of LVOT obstruction, especially subaortic membrane, as a cause of symptoms mimicking HCM., (2015 BMJ Publishing Group Ltd.)

A woman in her late 50s experienced a witnessed, sudden out of hospital cardiac arrest. Initial workup included coronary angiography, transthoracic echocardiogram and a CT scan of the chest to rule out pulmonary embolus. She was subsequently discharged home without an implantable cardioverter defibrillator (ICD) or a life vest. On follow-up at another facility, an ICD was placed and a Holter monitor showed no ventricular ectopy. Further transthoracic echocardiographic images were obtained, which were suggestive of apical hypertrophic cardiomyopathy. A limited transthoracic echocardiogram with contrast was performed, which did not elucidate the hypertrophy. However, eccentric left ventricular apical wall hypertrophy was visualised by a coronary CT scan., (2015 BMJ Publishing Group Ltd.)

Objective: T wave inversion (TWI) has been associated with cardiomyopathies. The hypothesis of this study was that TWI has relevant clinical significance in peri-pubertal athletes., Methods: Consecutive male soccer players, aged 8-18 years, undergoing preparticipation screening between January 2008 and March 2009 were enrolled. Medical and family histories were collected; physical examinations, 12-lead ECGs and transthoracic echocardiogram (TTE) were performed. TWI was categorised by ECG lead (anterior (V1-V3), extended anterior (V1-V4), inferior (DII-aVF) and infero-lateral (DII-aVF/V4-V6/DI-aVL)) and by age., Results: Overall, 2261 (mean age 12.4 years, 100% Caucasian) athletes were enrolled. TWI in ≥2 consecutive ECG leads was found in 136 athletes (6.0%), mostly in anterior leads (126/136, 92.6%). TWI in anterior leads was associated with TTE abnormalities in 6/126 (4.8%) athletes. TWI in extended anterior (2/136, 1.5%) and inferior (3/136, 2.2%) leads was never associated with abnormal TTE. TWI in infero-lateral leads (5/136, 3.7%) was associated with significant TTE abnormalities (3/5, 60.0%), including one hypertrophic cardiomyopathy (HCM) and two LV hypertrophies. Athletes with normal T waves had TTE abnormalities in 4.4% of cases, including one HCM with deep Q waves in infero-lateral leads., Conclusions: In this broad population of peri-pubertal male athletes, TWI in anterior leads was associated with mild cardiac disease in 4.8% of cases, while TWI in infero-lateral leads revealed HCM and LV hypertrophy in 60% of cases. ECG identified all cases of HCM., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: Myocardial fibrosis identified by late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) in patients with hypertrophic cardiomyopathy (HCM) is associated with adverse cardiovascular events, but its value as an independent risk factor for sudden cardiac death (SCD) is unknown. We investigated the role of LGE-CMR in the risk stratification of HCM., Methods: We conducted a prospective cohort study in a tertiary referral centre. Consecutive patients with HCM (n=711, median age 56.3 years, IQR 46.7-66.6; 70.0% male) underwent LGE-CMR and were followed for a median 3.5 years. The primary end point was SCD or aborted SCD., Results: Overall, 471 patients (66.2%) had myocardial fibrosis (median 5.9% of left ventricular mass, IQR: 2.2-13.3). Twenty-two (3.1%) reached the primary end point. The extent but not the presence of fibrosis was a significant univariable predictor of the primary end point (HR per 5% LGE: 1.24, 95% CI 1.06 to 1.45; p=0.007 and HR for LGE: 2.69, 95% CI 0.91 to 7.97; p=0.073, respectively). However, on multivariable analysis, only LV-EF remained statistically significant (HR: 0.92, 95% CI 0.89 to 0.95; p<0.001). For the secondary outcome of cardiovascular mortality/aborted SCD, the presence and the amount of fibrosis were significant predictors on univariable but not multivariable analysis after adjusting for LV-EF and non-sustained ventricular tachycardia., Conclusions: The amount of myocardial fibrosis was a strong univariable predictor of SCD risk. However, this effect was not maintained after adjusting for LV-EF. Further work is required to elucidate the interrelationship between fibrosis and traditional predictors of outcome in HCM., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: The purpose of the present study was to determine the incidence of ventricular arrhythmias before and after alcohol septal ablation (ASA)., Background: In patients with hypertrophic obstructive cardiomyopathy (HOCM), gradient reduction by ASA is an alternative for surgical myectomy. However, concerns exist about whether the induction of a myocardial scar during ASA may create substrate for ventricular arrhythmias., Methods: The study group consisted of 44 patients in whom ASA was performed for symptomatic, drug-refractory hypertrophic cardiomyopathy. Continuous rhythm monitoring was obtained by implantable loop recorder (n=30) or pacemaker (n=14). Occurrence of ventricular and supraventricular arrhythmias before and after ASA was noted, retrospectively., Results: The ASA procedure was considered successful (resting gradient <30 mm Hg, and provoked gradient <50 mm Hg at 4 months in combination with NYHA Class functional status ≤2) in 30 (68%) patients. Rhythm monitoring before ASA was available in 28 patients. The median duration of rhythm monitoring after ASA was 3.0 years (IQR 1.3-4.3). Sustained VT/VF within 30 days after ASA occurred in three patients (7%), including 2 cases of procedural VF, while no VT/VF was observed before ASA (p=0.10). No sustained VT/VF was observed >30 days after ASA. No cardiac deaths occurred during follow-up., Conclusions: In a low-risk cohort of patients who underwent ASA, in which continuous rhythm monitoring was performed, sustained VT or VF within 30 days occurred in 3 patients (7%) while no VT/VF was observed before ASA. During long-term follow-up, no sustained VT or VF was observed >30 days after ASA., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)