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Background Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease, shows significant genetic and clinical heterogeneity, yet its molecular basis remains unclear. This study aims to uncover molecular insights behind HCM based on proteomic analysis. Methods We performed proteomic analysis on formalin-fixed paraffin-embedded septal tissue samples from 105 patients with obstructive HCM undergoing myectomy, including 35 with MYBPC3 and 35 with MYH7 mutations. The primary outcome was major adverse cardiovascular events (MACE), comprising all-cause mortality and other major cardiovascular events. Results We identified four molecular subtypes: 39 patients with subtype-I (S-I), 38 with S-II, 27 with S-III, and 1 with S-IV. During a median follow-up of 6.8 years, 28.6% of patients developed MACE. Among the subtypes, S-III exhibited the minimal fibrosis and the best clinical outcomes. S-II presented the most severe phenotype and poorest prognosis, characterized by activation of inflammatory and fibrotic pathways, along with downregulation of multiple metabolic processes. Compared to S-II, S-I displayed opposing pathway patterns and better outcomes, with a predominance of MYBPC3 mutation carriers. Beisides, we identified protein modules that were associated with genotypes and clinical features. MYH7-related modules were positively correlated with fibrosis and MACE, primarily enriched in inflammatory and fibrotic pathways. In contrast, MYBPC3-related modules were linked to better clinical outcomes, enriched in energy metabolism pathways. Conclusions This proteomic study revealed molecular mechanisms linking genotype, fibrosis and prognosis in HCM, and identified potential drivers of high-risk subtypes with severe phenotypes. These findings may guide future risk stratification and therapeutic target development. Graphical Abstract

Background The impact of septal myectomy on the progression of ascending aortic (AAo) dilation in patients with obstructive hypertrophic cardiomyopathy (HOCM) remains uncertain. This study aimed to investigate the relationship between septal myectomy and AAo dilation in HOCM patients. Methods A total of 69 patients with HOCM were enrolled. All the participants underwent sequential cardiac magnetic resonance scans at a mean interval of 5.13 ± 2.04 years, with each scan being more than 3 years apart. Results At baseline, 17 patients with HOCM (25%) exhibited AAo dilation (Indexed AAo dimension > 19 mm/m²). Age (OR 1.10, 95%CI: 1.01–1.019, P  = 0.026) and female (OR 4.80, 95%CI: 1.05–21.93, P  = 0.043) were independently associated with AAo dilation. In patients who underwent myectomy, the AAo dimension at follow-up was similar to that at baseline (32.47 ± 4.70 mm vs. 32.81 ± 5.06 mm, P  = 0.197). Furthermore, the rate of AAo dilation was lower in patients with myectomy compared to those without myectomy (-0.06 ± 0.38 mm/year vs. 0.18 ± 0.43 mm/year, P  = 0.016). Additionally, moderate or severe mitral regurgitation was significantly associated with AAo dilation rate (B = 0.273, P  = 0.032). Conclusions Myectomy in patients with HOCM was associated with the absence of progression of AAo dilatation.

Background Myocardial bridging (MB) is common in patients with hypertrophic cardiomyopathy (HCM). There are sparse data on the impact of MB on myocardial fibrosis in HCM. This study was designed to evaluate the relationship between MB and myocardial fibrosis in patients with obstructive HCM. Methods In this cohort study, retrospective data were collected from a high-volume HCM center. Patients with obstructive HCM who underwent septal myectomy and preoperative cardiac magnetic resonance (CMR) were screened from 2011 to 2018. Results Finally, 492 patients were included in this study, with an average age of 45.7 years. Of these patients, 76 patients had MB. MB occurred mostly in the left anterior descending artery (73/76). The global extent of late gadolinium enhancement (LGE) was correlated with the degree of systolic compression ( r  = 0.33, p  = 0.003). Multivariable linear regression analysis revealed that the degree of systolic compression was an independent risk factor for LGE ( β  = 0.292, p  = 0.007). The LGE fraction of basal and mid anteroseptal segments in patients with severe MB (compression ratio ≥ 80%) was significantly greater than that in patients with mild to moderate MB (compression ratio < 80%). During a median follow-up of 28 (IQR: 15–52) months, 15 patients died. Kaplan–Meier analysis did not identify differences in all-cause death (log-rank p  = 0.63) or cardiovascular death (log-rank p  = 0.72) between patients undergoing MB-related surgery and those without MB. Conclusions MB with severe systolic compression was significantly associated with a high extent of fibrosis in patients with obstructive HCM. Concomitant myotomy or coronary artery bypass grafting might provide excellent survival similar to that of patients without MB. Identification of patients with severe MB and providing comprehensive management might help improve the prognosis of patients with HCM.

Aims Chronic low‐grade inflammation, often observed in hypertrophic cardiomyopathy (HCM), promotes adverse ventricular remodelling. This study aimed to investigate the relationship between inflammatory markers and myocardial fibrosis (MF) in patients with HCM. Methods and results This study included 102 patients with complete baseline data who underwent septal myectomy. Myocardial samples were stained with Masson's trichrome and analysed to determine myocardial collagen content and MF levels. Plasma levels of inflammatory markers were measured using standard laboratory procedures. Univariate and multivariate logistic regression analyses were performed to explore the relationship between the inflammatory markers and MF. Among the 102 participants included in the analysis, the mean age was 48.9 years, with 69 [67.6%] being men. The overall MF ranged from 2.5% to 40.7% (mean = 15.2 ± 8.1%, median = 13.0%, IQR = 9.9%–18.4%). Participants were divided into two groups based on a median MF of 13%. The high MF group had a larger left atrial diameter and left ventricular ejection fraction. Levels of interleukin (IL)‐2, tumour necrosis factor (TNF)‐α and interferon (IFN)‐α were significantly higher in patients with high MF compared to those with low MF (2.3 vs. 4.0 pg/mL, 3.1 vs. 3.9 pg/mL, 4.2 vs.4.7 pg/mL, respectively; all P < 0.05). In multivariate models adjusted for age, sex and other clinical features, IL‐2, IL‐5 and TNF‐α, were correlated with increased interstitial MF [odds ratio (OR): 1.54, 95% confidence interval (CI): 1.10–2.14; OR: 1.42, 95% CI: 1.02–1.98; OR: 1.33, 95% CI: 1.04–1.70]. After additional adjustment for imaging indicators, IL‐2 and TNF‐α remained significant (OR: 1.49, 95% CI: 1.06–2.09, P = 0.021; OR:1.35, 95% CI: 1.01–1.80, P = 0.044). The correlation analysis between inflammation and replacement fibrosis assessed by CMR in 97 patients revealed that 72 (74.2%) showed late gadolinium enhancement (LGE). No significant correlation was found between inflammatory markers and the presence or extent of LGE. Conclusions Higher levels of IL‐2 and TNF‐α were associated with increased histopathological interstitial MF in patients with HCM. Given the gradual progression of MF in HCM, initiating anti‐inflammatory treatment in the early stages may delay its progression.

Background Type 2 diabetes mellitus is common in cardiovascular disease. It is associated with adverse clinical outcomes for patients who had undergone coronary artery bypass and valve operations. The aim of this study was to evaluate the impact of type 2 diabetes mellitus on the midterm outcomes of patients with hypertrophic cardiomyopathy who underwent septal myectomy. Methods We retrospectively analyzed the data of 67 hypertrophic cardiomyopathy patients with type 2 diabetes mellitus who underwent septal myectomy from two medical centers in China from 2011 to 2018. A propensity score–matched cohort of 134 patients without type 2 diabetes mellitus was also analyzed. Results During a median follow-up of 28.0 (interquartile range: 13.0–3.0) months, 9 patients died. The cause of death of all of these patients was cardiovascular, particularly sudden cardiac death in 3 patients. Patients with type 2 diabetes mellitus had a higher rate of sudden cardiac death (4.5% vs. 0.0%, p = 0.04). The Kaplan–Meier survival analysis revealed that the rates of predicted 3-year survival free from cardiovascular death (98.1% vs. 95.1%, p = 0.14) were similar between the two groups. However, the rates of predicted 3-year survival free from sudden cardiac death (100% vs. 96.7%, p = 0.01) were significantly higher in hypertrophic cardiomyopathy patients without type 2 diabetes mellitus than in those with type 2 diabetes mellitus. Furthermore, after adjustment for age and sex, only N-terminal pro-brain natriuretic peptide (hazards ratio: 1.002, 95% confidence interval: 1.000–1.005, p = 0.02) and glomerular filtration rate ≤ 80 ml/min (hazards ratio: 3.23, 95% confidence interval: 1.34–7.24, p = 0.047) were independent risk factors for hypertrophic cardiomyopathy patients with type 2 diabetes mellitus. Conclusions Hypertrophic cardiomyopathy patients with and without type 2 diabetes mellitus have similar 3-year cardiovascular mortality after septal myectomy. However, type 2 diabetes mellitus is associated with higher sudden cardiac death rate in these patients. In addition, N-terminal pro-brain natriuretic peptide and glomerular filtration rate ≤ 80 ml/min were independent risk factors among hypertrophic cardiomyopathy patients with type 2 diabetes mellitus.

Background Postoperative atrial fibrillation (POAF) is a common complication in patients with obstructive hypertrophic cardiomyopathy (HOCM) who undergo surgical myectomy. POAF is associated with poor outcome. The role of plasma big endothelin-1 level in predicting atrial fibrillation after surgical septal myectomy in HOCM patients has not well been studied. Methods A total of 118 patients with HOCM who underwent surgical septal myectomy were recruited in this study. Plasma big endothelin-1 level was measured. The heart rhythm was continuously monitored during hospital stay. Preoperative, intraoperative, and postoperative variables were collected. Results POAF developed among 26 of the 118 patients (22%) in this study. Compared with those without POAF, patients with POAF were significantly older (53.5 ± 10.6 vs. 47.3 ± 13.6 years, P  = 0.033), more likely to undergo mitral valve surgery (38.5% vs. 18.5%, P  = 0.032), and had higher plasma big endothelin-1 levels (0.41 ± 0.19 vs. 0.27 ± 0.14 pmol/l, P  = 0.001), longer hospital stay (9.1 ± 3.7 vs. 7.5 ± 2.8 days, P  = 0.022), larger preoperative left atria (48.0 ± 5.2 vs. 44.1 ± 5.9 mm; P  = 0.003). In the receiver operating characteristic curve analysis, the area under the curve for big endothelin-1 was 0.734 (95% CI, 0.634 to 0.834, P<0.001). In multivariate logistic regression analysis, preoperative big endothelin-1 level (OR 100.7, 95%CI: 5.0–2020.0, P  = 0.003) and left atrial diameter (OR 1.106, 95%CI: 1.015–1.205, P  = 0.022) were independent predictors of POAF. Conclusion Elevated preoperative plasma big endothelin-1 level is an independent predictor of POAF in HOCM patients undergoing surgical septal myectomy.

Obstructive hypertrophic cardiomyopathy (oHCM) and mitral valve (MV) prolapse (MVP) are the 2 conditions which could cause symptomatic heart failure and sudden cardiac death. The clinical characteristics and surgical outcomes of patients with oHCM and MVP have not been well reported. From April 2012 to February 2018, 84 patients with oHCM (28 patients with MVP and 56 gender- and age-matched patients without MVP) who underwent septal myectomy at our institution were enrolled in this study. Information on clinical characteristics and outcomes was obtained from electronic medical records and follow-up surveys. Compared with those without MVP, patients with MVP were more symptomatic (New York Heart Association class III to IV; 96% vs 77%), more often moderate-to-severe mitral regurgitation (86% vs 48%), atrial fibrillation (39% vs 11%) and higher incidence of nonsustained ventricular tachycardia (44% vs 15%). Twenty (71%) had MV repair and 8 (29%) had MV replacement. Compared with patients without MVP, those with MVP had a longer postoperative hospital stay (10.9 ± 6.4 vs 7.8 ± 2.8 days). None of the 84 study patients died during hospital or follow-up. At the most recent echocardiographic evaluation, left ventricular outflow tract gradient significantly decreased from 69.7 ± 35.4 millimeters of mercury to 7.3 ± 5.1 millimeters of mercury and the degree of mitral valve regurgitation improved from grade 2.43 ± 0.69 to grade 0.5 ± 0.69. In conclusion, MVP occurs rarely in oHCM, and was related to atrial fibrillation, ventricular arrhythmia and mitral regurgitation. Mitral valve surgery in combination with myectomy is effective and safe for patients with oHCM and MVP, relieving substantially left ventricular outflow tract gradients and mitral regurgitation.

The impact of mitral valve abnormality on the occurrence of non-sustained ventricular tachycardia (NSVT) in patients with hypertrophic cardiomyopathy (HC) has not been well determined. We sought to demonstrate the relation of mitral valve abnormalities with NSVT in patients with obstructive HC. Three hundred and sixteen adult patients with obstructive HC with at least 1 Holter electrocardiographic monitoring and cardiac magnetic resonance (CMR) from 2014 to 2018 were enrolled. CMR images and Holter electrocardiography were analyzed in all patients. NSVT occurred in 50 patients (16%). Compared with those without NSVT, anterior mitral leaflet and posterior mitral leaflet lengths was significantly increased in patients with NSVT (AML 32.0 ± 5.0mm vs. 26.1±4.8mm, p<0.001; PML 17.7±3.7mm vs. 15.2±2.7mm, p<0.001, respectively). Multivariate logistic regression analysis indicated that elongated AML and PML were significantly independent predictors of NSVT (AML: OR 1.261, 95%CI 1.156-1.375, p<0.001; PML: OR 1.126, 95%CI 1.001-1.265, p=0.047). Furthermore, the area under the receiver operating characteristic curve for AML was 0.812. At a cutoff valve of 27.5mm, AML length had a sensitivity of 86% and specificity of 65%. Elongated mitral leaflets independently correlated with NSVT in patients with obstructive HC. Furthermore, the morphological abnormalities of mitral valve could serve as a useful marker for improving risk stratification of SCD and may play a role in optimizing surgical strategy for patients with obstructive HC.

To assess the mid-term mortality and risk of atrial fibrillation (AF) in patients with hypertrophic cardiomyopathy (HC) and Wolff-Parkinson-White (WPW) syndrome, 40 patients with HC and WPW were enrolled in our center between 2010 and 2017. An age- and gender-matched comparison cohort of patients with HC without WPW (n = 160) was generated from the same center. The clinical profile and outcomes were assessed. Of 40 patients with WPW, 28 underwent accessory pathway (AP) elimination. Two patients (7%) had failed in AP elimination. During mid-term follow-up, 1 patient had an implantable cardioverter-defibrillator intervention. Fourteen patients had AF. A previous history of AF (hazard ratio [HR]: 4.69; 95% confidence interval [CI] 1.51 to 14.63) and left atrial dimension (HR: 1.12; 95% CI 1.03 to 1.23) at baseline were risk factors for AF occurrence during follow-up. The AP elimination significantly reduced risk for the incidence of AF (HR: 0.22; 95% CI 0.06 to 0.83). Compared with the control group, the prevalence of syncope and AF were significantly higher in the WPW group. During follow-up, no difference was identified in outcome measures consisting of all-cause death, cardiac transplantation, and implantable cardioverter-defibrillator intervention. A previous history of AF (HR: 5.20; 95% CI 2.63 to 10.30, p <0.001) and persistent existing WPW (HR: 3.64; 95% CI 1.63 to 8.11, p = 0.002) were independent risk factors for AF occurrence during follow-up in the entire cohort. In conclusion, although WPW was uncommon and might not be correlated with mid-term mortality in HC patients, WPW might increase the risk of AF occurrence. Additionally, AP elimination may reduce the risk of AF occurrence.

The motion of binary particles in three horizontal rotating drums with continuous rotational speed changes was studied based on the Discrete Element Method (DEM). Different simulation conditions were compared between two circular drums and an elliptical drum using the same number of physical properties for binary particles and drums, rotating at a speed series from 0.01 to 21.9 rad/s. By varying the rotational speed, four flow regimes were produced in the simulation. Flow regimes, velocity vectors, normal forces, and the number of contacts between 1 mm particles and 3 mm particles were comparatively analyzed, especially the particle velocity at transient changing rotational speeds. The results showed that four flow regimes were found at the same rotational speed for three different rotating drums, and normal forces were weakest for the cataracting regime; moreover, the three layers of particles were damaged when the rotational speed was suddenly decreased and the velocity direction of the particle motion was changed at the top of the particles’ bed. The maximum number of contacts was found with the rolling regime, based on the simulation results. The number of contacts of the major axis circular drum was smaller than for the minor axis at the same rotational speed, and the number of contacts of the elliptical drum was the largest among the three rotating drums.