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Abstract Hypertrophic cardiomyopathy (HCM) is an inherited disorder characterized by left ventricular hypertrophy and diastolic dysfunction, and increases the risk of arrhythmias and heart failure. Some patients with HCM develop a dilated phase of hypertrophic cardiomyopathy (D-HCM) and have poor prognosis; however, its pathogenesis is unclear and few pathological models exist. This study established disease-specific human induced pluripotent stem cells (iPSCs) from a patient with D-HCM harboring a mutation in MYBPC3 (c.1377delC), a common causative gene of HCM, and investigated the associated pathophysiological mechanisms using disease-specific iPSC-derived cardiomyocytes (iPSC-CMs). We confirmed the expression of pluripotent markers and the ability to differentiate into three germ layers in D-HCM patient-derived iPSCs (D-HCM iPSCs). D-HCM iPSC-CMs exhibited disrupted myocardial sarcomere structures and an increased number of damaged mitochondria. Ca2+ imaging showed increased abnormal Ca2+ signaling and prolonged decay time in D-HCM iPSC-CMs. Cell metabolic analysis revealed increased basal respiration, maximal respiration, and spare-respiratory capacity in D-HCM iPSC-CMs. RNA sequencing also showed an increased expression of mitochondrial electron transport system-related genes. D-HCM iPSC-CMs showed abnormal Ca2+ handling and hypermetabolic state, similar to that previously reported for HCM patient-derived iPSC-CMs. Although further studies are required, this is expected to be a useful pathological model for D-HCM.

Patients with hypertrophic cardiomyopathy (HCM) may progress to the dilated phase (DHCM). This study aimed to identify the predictive factors for DHCM progression, including left ventricular (LV) ejection fraction (LVEF < 50%) or decreased LV contraction (LVEF < 60%). The study included 291 patients enrolled in our hospital's HCM registry who were grouped based on their poststudy LVEF (LVEF of ≥60%, 50–59%, and <50%). Predictive factors of an LVEF of <50% or <60% were determined. Further, the effects of percutaneous transluminal septal myocardial ablation (PTSMA) on long-term systolic LV function and DHCM development were investigated. LVEF was ≥60%, 50–59%, and <50% in 239, 33, and 19 patients, respectively, during the follow-up period (mean: 64.9 months). Multivariate analyses indicated baseline atrial fibrillation (AF), nonsustained ventricular tachycardia (NSVT), and left ventricular diameter at end-systole (LVDs) as significant predictors of DHCM. Using a scoring method based on AF, NSVT, and LVDs, patients with 2 and 3 points had a significantly higher risk of developing DHCM. PTSMA in 78 HCM patients demonstrated no significant effect on long-term LVEF changes or DHCM development. We concluded that AF, NSVT, and LVDs are significant predictors of DHCM development. However, a validation study with a larger population is required. [ABSTRACT FROM AUTHOR]

Background: This study sought to develop an artificial intelligence-derived model to detect the dilated phase of hypertrophic cardiomyopathy (dHCM) on digital electrocardiography (ECG) and to evaluate the performance of the model applied to multiple-lead or single-lead ECG. Methods: This is a retrospective analysis using a single-center prospective cohort study (Shinken Database 2010–2017, n = 19,170). After excluding those without a normal P wave on index ECG (n = 1,831) and adding dHCM patients registered before 2009 (n = 39), 17,378 digital ECGs were used. Totally 54 dHCM patients were identified of which 11 diagnosed at baseline, 4 developed during the time course, and 39 registered before 2009. The performance of the convolutional neural network (CNN) model for detecting dHCM was evaluated using eight-lead (I, II, and V1-6), single-lead, and double-lead (I, II) ECGs with the five-fold cross validation method. Results: The area under the curve (AUC) of the CNN model to detect dHCM (n = 54) with eight-lead ECG was 0.929 (standard deviation [SD]: 0.025) and the odds ratio was 38.64 (SD 9.10). Among the single-lead and double-lead ECGs, the AUC was highest with the single lead of V5 (0.953 [SD: 0.038]), with an odds ratio of 58.89 (SD:68.56). Conclusion: Compared with the performance of eight-lead ECG, the most similar performance was achieved with the model with a single V5 lead, suggesting that this single-lead ECG can be an alternative to eight-lead ECG for the screening of dHCM.

We reviewed the long-term outcome of children with hypertrophic cardiomyopathy (HCM) based on the type. We reviewed the medical records of 100 patients (male 54 female 46) with HCM at our hospital between 1977 and 2015. The survival and cardiac event-free survival rates were calculated by the Kaplan–Meier method. The age at the time of the diagnosis ranged from 0 to 15 years with a median of 8 years. The number of patients with Noonan syndrome and hypertrophic obstructive cardiomyopathy (HOCM), idiopathic HCM (i-HCM), and secondary HCM (s-HCM) was 13, 13, 65, and 9 respectively. A dilated phase of HCM occurred in 24 patients. Nineteen (79 %) of the 24 patients died of heart failure, and two underwent a heart transplantation. Eight (33 %) of the 24 patients had s-HCM. The median age when a dilated phase occurred was 15 years old, and the median interval from the initial diagnosis to the dilated phase was 8 years. The median time from the diagnosis of a dilated phase to death was 1.6 years. Sudden death and implantable cardioverter defibrillator implantations occurred in 6 and 11 patients at around 15 years old, respectively. The 20-year survival rates were as follows: Noonan syndrome 84 %; HOCM 82 %; i-HCM 71 %; and s-HCM 17 %. Overall, the survival rates at 10, 20, and 30 years were 83 % (95 % confidence interval 73–89), 69 % (58–78), and 63 % (50–74), respectively. The overall cardiac event-free survival rates at 10, 20, and 30 years were 57 % (47–67), 39 % (31–50), and 32 % (21–44), respectively. The long-term outcome in children with HCM was poor, and the outcome of s-HCM was very poor. The occurrence of a dilated phase worsened the outcome in HCM patients. Sudden death and d-HCM often occurred at around 15 years old. [Display omitted] • The overall 30-year cardiac event free survival rate was 32 %. • The long-term outcome in children with hypertrophic cardiomyopathy was poor. • The median age when a dilated phase occurred was 15 years old. • Sudden death often occurred at around 15 years old. • The outcome of secondary hypertrophic cardiomyopathy was very poor. [ABSTRACT FROM AUTHOR]

Patients with hypertrophic cardiomyopathy (HCM) may progress to the dilated phase (DHCM). This study aimed to identify the predictive factors for DHCM progression, including left ventricular (LV) ejection fraction (LVEF < 50%) or decreased LV contraction (LVEF < 60%). The study included 291 patients enrolled in our hospital’s HCM registry who were grouped based on their poststudy LVEF (LVEF of ≥60%, 50–59%, and

Background: This study sought to develop an artificial intelligence-derived model to detect the dilated phase of hypertrophic cardiomyopathy (dHCM) on digital electrocardiography (ECG) and to evaluate the performance of the model applied to multiple-lead or single-lead ECG., Methods: This is a retrospective analysis using a single-center prospective cohort study (Shinken Database 2010-2017, n = 19,170). After excluding those without a normal P wave on index ECG (n = 1,831) and adding dHCM patients registered before 2009 (n = 39), 17,378 digital ECGs were used. Totally 54 dHCM patients were identified of which 11 diagnosed at baseline, 4 developed during the time course, and 39 registered before 2009. The performance of the convolutional neural network (CNN) model for detecting dHCM was evaluated using eight-lead (I, II, and V1-6), single-lead, and double-lead (I, II) ECGs with the five-fold cross validation method., Results: The area under the curve (AUC) of the CNN model to detect dHCM (n = 54) with eight-lead ECG was 0.929 (standard deviation [SD]: 0.025) and the odds ratio was 38.64 (SD 9.10). Among the single-lead and double-lead ECGs, the AUC was highest with the single lead of V5 (0.953 [SD: 0.038]), with an odds ratio of 58.89 (SD:68.56)., Conclusion: Compared with the performance of eight-lead ECG, the most similar performance was achieved with the model with a single V5 lead, suggesting that this single-lead ECG can be an alternative to eight-lead ECG for the screening of dHCM., Competing Interests: Dr. Suzuki received lecture fees from Daiichi Sankyo and Bristol-Myers Squibb. Dr. Yamashita received research funds and/or lecture fees from Daiichi Sankyo, Bayer Yakuhin, Bristol-Myers Squibb, Pfizer, Nippon Boehringer Ingelheim, Eisai, Mitsubishi Tanabe Pharm, Ono Pharmaceutical, and Toa Eiyo. J Motogi, T Umemoto, W Matsuzawa, T Takayanagi, A Hyodo, and K Satoh are employee at Nihon Kohden Corporation.The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Shinya Suzuki reports a relationship with Public Interest Incorporated Foundation The Cardiovascular Institute that includes: speaking and lecture fees. Takeshi Yamashita reports a relationship with Public Interest Incorporated Foundation The Cardiovascular Institute that includes: funding grants and speaking and lecture fees., (© 2023 The Author(s).)