OBJECTIVES:Cardiac involvement in idiopathic inflammatory myopathies (IIM) is rare but potentially severe. Anti-mitochondrial M2 antibody (AMA-M2) has been implicated in cardiac involvement, but the association remains underexplored. This study aims to evaluate the clinical, pathological and prognostic features of AMA-M2 IIM. METHODS:This historic prospective cohort included IIM patients hospitalized at Peking Union Medical College Hospital between 2008 and 2020. Outcomes were prospectively collected through the Prospective Registry Of MyositIS (PROMIS) registry. Cox regression models were employed to identify risk factors of cardiac involvement and mortality. RESULTS:Among 987 IIM patients, 55 (6%) were AMA-M2 positive. These patients exhibited higher rates of PM (56% vs 23.5%, P < 0.001), and elevated baseline gamma-glutamyl transferase (78.0 vs 35.0, P < 0.001) and alkaline phosphatase (85.0 vs 64.0, P < 0.001). Throughout disease courses, AMA-M2-positive patients had significantly higher rates of cardiac involvement (60% vs 12.9%, P < 0.001), including arrhythmias (56%), heart failure (44%) and pulmonary hypertension (31%). Some of the muscle biopsies showed features consistent with immune-mediated necrotizing myopathy, cardiac biopsies demonstrating structural degeneration with minimal inflammation and liver biopsies confirming early-stage primary biliary cholangitis (PBC). Multivariate Cox analysis identified AMA-M2 positivity as an independent risk factor for cardiac involvement (hazard ratio 3.156, P < 0.001). Despite frequent cardiac manifestations, long-term survival did not differ between AMA-M2-positive and -negative patients (mean survival: 103.9 months vs 98.0 months, P = 0.86). CONCLUSION:AMA-M2 positivity defines an IIM subgroup with significant cardiac involvement and an immune-mediated inflammatory muscle histology, but not necessarily worse long-term survival. These findings highlight the need for early recognition and tailored management of AMA-M2 IIM.

Background: Cardiac involvement in cryoglobulinemia (CG) is rare but potentially fatal, and its clinical spectrum remains poorly characterized. Methods: This retrospective study enrolled 11 patients with cardiac involvement among 885 patients with CG at Peking Union Medical College Hospital between January 2015 and March 2026. We analyzed its clinical characteristics, radiological features and management. Results: Among 885 CG patients, 11 (1.2%; 4 type I, 7 type II) had cardiac involvement. Cardiac symptoms included dyspnea (n = 6), chest tightness (n = 4), edema (n = 3), and orthopnea (n = 1). All patients had elevated N-terminal pro-B-type natriuretic peptide (median 29,799 pg/mL). Echocardiography, performed in all 11 patients, revealed left heart enlargement (n = 9), reduced left ventricular ejection fraction (n = 7), myocardial disease (n = 6), pericardial effusion (n = 4), and pulmonary hypertension (n = 3). Cardiac magnetic resonance in 5 of 11 patients showed non-ischemic late gadolinium enhancement in two cases. For first-line therapy, 6 of 11 patients received rituximab-based regimens, 3 of 11 received bortezomib-based regimens, and 1 of 11 received antiviral therapy with corticosteroids; 1 patient declined treatment. All 10 treated patients achieved initial cardiac improvement, with 5 relapsing and 2 dying during a median follow-up of 57 months (range 9-130 months). The estimated 4-year overall and progression-free survival rates were 77.9% (95% CI: 0.546-1.000) and 50.0% (95% CI: 0.269-0.929), respectively. Conclusions: Cardiac involvement in CG is rare and associated with diverse structural and functional abnormalities. Cardiac involvement should be considered in CG patients presenting with unexplained cardiac manifestations after excluding alternative causes. B-cell-targeted therapy induced an initial response, but relapse is common. Early intervention is essential given the substantial relapse burden and potential for severe morbidity.

Cardiomyopathies are major causes of heart failure and sudden cardiac death, but nationwide epidemiological data from China remain limited. Following the inclusion of several cardiomyopathies in the first national rare disease list in 2018, contemporary trends in hospitalization and in-hospital outcomes have not been systematically evaluated. This study aimed to characterize national hospitalization patterns for cardiomyopathies from 2018 to 2022. We conducted a nationwide retrospective study using the Hospital Quality Monitoring System (HQMS), which covers secondary and tertiary hospitals across 31 provinces. Cardiomyopathies were identified using National Clinical Version 2.0 codes. We assessed age- and sex-standardized hospitalization rates, regional variation, comorbidities, device use, intensive care unit (ICU) admission, in-hospital mortality, length of stay, and hospital costs. Temporal trends were analyzed using Joinpoint regression to estimate the average annual percent change (AAPC). A total of 1,935,421 hospitalizations from 943,178 unique patients were included. The standardized hospitalization rate increased from 151.55 to 206.23 per 1,000,000 population (AAPC = 7.68

AIM:Recent advancements have introduced cardiac myosin inhibitors (CMIs) that have demonstrated significant efficacy in obstructive hypertrophic cardiomyopathy (oHCM). This meta-analysis aims to synthesize the current understanding of the impact of CMIs on cardiac magnetic resonance (CMR) findings in patients with oHCM. MATERIAL AND METHODS:A search of the PubMed, Cochrane Library, and Embase databases was conducted from their inception until July 27, 2025. Random-effects models were used to pool mean differences with 95% confidence intervals. Both mavacamten and aficamten were included in all outcomes. RESULTS:Three randomised controlled trails (RCTs) involving 150 patients were included in this meta-analysis. This meta-analysis demonstrates a reduction in left ventricular mass index with CMIs compared to the placebo group (mean differences [MD]: -20.01 g/m2, 95% confidence interval [CI]: -29.77 to -10.26, P<0.0001, I2 = 67.7%). And CMIs can also reduce maximal left ventricular wall thickness (MD: -2.66 mm, 95% CI: -3.53 to -1.79, P<0.0001, I2 = 40.6%). Meanwhile, the pooled results demonstrate that CMIs reduce left atrial volume index (MD: -13.02, mL/m2 95% CI: -17.17 to -8.87, P<0.0001, I2 = 15.6%). However, the results do not show that CMIs improve late gadolinium enhancement (MD: 0.54 %, 95% CI: -0.48 to 1.56, P=0.2973, I2 = 0%). Similarly, there is no significant reduction in extracellular volume fraction (MD: 1.43 %, 95% CI: -0.02 to 2.88, P=0.0528, I2 = 0%). CONCLUSION:CMIs have shown efficacy in improving cardiac structure in oHCM. However, the impact on myocardial fibrosis remains unclear.

Background: Recent advancements have introduced novel cardiac myosin inhibitors (CMIs) that have demonstrated significant efficacy in treating hypertrophic cardiomyopathy (HCM). This meta-analysis aimed to clarify the current understanding of the impact of CMIs on echocardiographic cardiac structure and function in patients with HCM. Methods: A comprehensive search of the PubMed, Cochrane Library, and Embase databases was conducted from inception until September 14, 2025. The studies reporting the impact of CMIs on echocardiographic cardiac structure and function in HCM patients were included. Results: Ultimately, this meta-analysis included 10 studies: five randomized controlled trials (RCTs), three echocardiographic sub-studies derived from RCTs, and two long-term cohort studies. A total of 938 patients were enrolled in these studies. This meta-analysis revealed that CMIs significantly reduce interventricular septum thickness (mean difference (MD): –1.77, 95% confidence interval (CI): –3.30 to –0.23; p = 0.0240). CMIs were also shown to significantly reduce left ventricular mass index (MD: –18.15, 95% CI: –32.65 to –3.65; p = 0.0141). Moreover, the pooled results demonstrated that administering CMIs can significantly reduce left ventricular ejection fraction (MD: –3.22, 95% CI: –5.60 to –0.85; p = 0.0078). CMIs also significantly improved echocardiographic parameters of left ventricular diastolic function, such as the left atrial volume index (MD: –5.75, 95% CI: –7.87 to –3.64; p < 0.0001) and septal E/e′ ratio (MD: –3.80, 95% CI: –4.74 to –2.87; p < 0.0001). However, the results did not reveal an association between CMIs and the risk of atrial arrhythmias (risk ratio (RR): 0.98, 95% CI: 0.33 to 2.94; p = 0.9689). Conclusions: CMIs have shown great efficacy in improving left ventricular structure and diastolic function in HCM patients. Additionally, CMIs can reduce left ventricular ejection fraction. However, the impact of CMIs on the risk of atrial arrhythmias remains unclear. The PROSPERO Registration: CRD420251243904, https://www.crd.york.ac.uk/PROSPERO/view/CRD420251243904.

Background Long‐term efficacy and safety of mavacamten in Chinese patients with obstructive hypertrophic cardiomyopathy are unknown. Methods Patients who completed the 30‐week, double‐blind, placebo‐controlled treatment period in EXPLORER‐CN (A Study to Evaluate the Efficacy and Safety of Mavacamten in Chinese Adults With Symptomatic Obstructive HCM), with no active safety concerns, were eligible to enter the long‐term extension period to receive 48‐week mavacamten treatment. Patients previously on mavacamten continued mavacamten (dose at week 30; mavacamten–mavacamten group); patients previously on placebo received mavacamten (starting dose, 2.5 mg once daily; placebo–mavacamten group). Key efficacy end points included change from baseline in echocardiographic measures, New York Heart Association functional class, 23‐item Kansas City Cardiomyopathy Questionnaire Clinical Summary Score, and cardiac biomarkers through week 78. Analyses were descriptive; no between‐group hypothesis testing was performed. Results Seventy‐nine patients (mean age, 51.6 years; 27.8% women) entered the long‐term extension period (mavacamten–mavacamten, n=54; placebo–mavacamten, n=25). In the mavacamten–mavacamten group, numerical improvements in Valsalva and resting left ventricular outflow tract peak gradients were maintained through week 78 (mean change from baseline, −73.0 mm Hg [95% CI, −86.4 to −59.5]; and −56.3 mm Hg [95% CI, −67.1 to −45.5], respectively). Numerical improvements were also observed for other echocardiographic parameters, New York Heart Association class, Kansas City Cardiomyopathy Questionnaire Clinical Summary Score, and cardiac biomarkers through week 78. In the placebo–mavacamten group, numerical improvements with mavacamten in these parameters were noted from week 30 to week 78. Long‐term mavacamten treatment appeared well tolerated; left ventricular ejection fraction <50% was rare. Conclusions In this exploratory long‐term extension study, 78‐week mavacamten treatment appeared well‐tolerated and was associated with numerical improvements from baseline in echocardiographic parameters, New York Heart Association class, patient‐reported health status, and cardiac biomarkers in Chinese patients with obstructive hypertrophic cardiomyopathy. Registration URL: https://www.clinicaltrials.gov; Unique Identifier: NCT05174416.

Low QRS voltage relative to left ventricle (LV) thickness is one of the red flag characteristics in the diagnosis of cardiac amyloidosis, and it can be measured by specific indexes. Few studies have clearly defined the diagnostic threshold of voltage indexes for light chain amyloidosis cardiomyopathy (AL-CA) patients and other patients with LV hypertrophy. This case–control study analyzed electrocardiograms and echocardiograms of patients with AL-CA, hypertrophic cardiomyopathy (HCM), and hypertension left ventricular hypertrophy (HTN-LVH) seen at a single university center from 2008 to 2022. Low QRS voltage and three different precordial voltage indexes were evaluated. Diagnostic thresholds for rule-in and rule-out were calculated for AL-CA against each control group. A single voltage–mass ratio based on cross-sectional area (CSA) exhibited most accurate diagnostic accuracy, and the value of ≤1.72 aids the rule-in of AL-CA against other causes of left ventricular hypertrophy, providing a positive predictive value (PPV) of 86% versus HCM and 75% versus HTN-LVH.

Hematologic response is well established in systemic light chain (AL) amyloidosis treatment, but hepatic response patterns remain unclear. This study explored hepatic response dynamics in hepatic-involved patients with AL amyloidosis who achieved hematologic partial response within 24 months post-treatment. Using two- and four-level hepatic response criteria (two-level: hepatic organ response [hepatic OR], hepatic no response [hepatic NR]; four-level: hepatic complete response [hepaCR], hepatic very good partial response [hepaVGPR], hepatic partial response [hepaPR], hepatic no response [hepaNR]), responses were assessed at 3, 6, 12, and 24 months. Among 137 patients (median follow-up: 55.0 months), hepatic OR and ≥ hepaPR plateaued at 24 months, with hepatic OR achieved in 75.6

This study assessed mavacamten monotherapy efficacy and safety in an integrated analysis of four phase 3 studies: EXPLORER-HCM, the EXPLORER cohort of MAVA-LTE, VALOR-HCM and EXPLORER-CN. Mavacamten monotherapy was associated with improvements in left ventricular outflow tract gradients and symptoms in patients with obstructive hypertrophic cardiomyopathy; descriptive comparisons with patients receiving mavacamten plus beta-blockers or calcium-channel blockers suggested broadly similar trends in efficacy and adverse event rates. Reductions in left ventricular ejection fraction from baseline to week 128 of ≤8.8% were observed across treatment groups.

Background Cardiovascular diseases are often associated with altered protein subcellular localization. As a major cause of inherited cardiomyopathy, LMNA deficiency could trigger nuclear envelope rupture and broadly impair the localization of nuclear and cytoplasmic proteins. Systemic approaches to identify, dissect and manipulate the localization of endogenous proteins are important for mechanistic and therapeutic investigation. Method Proximity proteomics of the nuclear lamina was performed specifically in cardiomyocytes in Lmna-deficient murine models. AAV-mediated Cas9-based gene silencing and subcellular gene upregulation were conducted via the nuclear localization signal (NLS) and nuclear export signal (NES). Cas9-based somatic mutagenesis was supplemented with the single-strand DNA templates of AAV to achieve robust homology-directed repair (HDR) and targeted NLS knock-in, which translocated cytoplasmic proteins into nuclei. Result In vivo proximity proteomics detected increased epoxide hydrolase 2 (EPHX2) in cardiomyocyte nuclei in mice carrying germline or cardiac-specific Lmna truncating variants. This phenotype was associated with ruptured nuclear envelope. Cas9-mediated Ephx2 knockout in cardiomyocytes ameliorated cardiac dysfunction in Lmna-deficient mice. Strikingly, overexpression of NLS-EPHX2, but not NES-EPHX2, also mitigated cardiac dysfunction. The cardiac protective EPHX2 substrates, epoxyeicosatrienoic acids (EETs), did not alter upon NLS-EPHX2 overexpression. By contrast, the Lmna-related DNA damage marker γ-H2AX was reduced. The EPHX-D333A mutant lacking hydrolase activity recapitulated the effects of wildtype EPHX2 in nuclei. AAV-Cas9-based HDR achieved efficient NLS knock-in and EPHX2 nuclear translocation in more than 60% cardiomyocytes, which improved cardiac function. Conclusion Lmna deficiency leads to the nuclear translocation of EPHX2, which ameliorated cardiac dysfunction in a hydrolase-independent manner. AAV-HDR-mediated somatic gene editing provides an efficient approach to manipulate the subcellular localization of endogenous proteins in cardiomyocytes in vivo. ### Competing Interest Statement The authors have declared no competing interest. National Natural Science Foundation of China, 82570307 State Key Laboratory of Complex Severe and Rare Diseases, 2025-O-PY-002 Beijing Natural Science Foundation, F252059

Recurrent pericarditis (RP) remains challenging, especially in tuberculosis (TB)-endemic regions where empirical anti-TB therapy is often unnecessarily prolonged. We report a 35-year-old woman with three RP episodes over six months, presenting with pleuritic chest pain, elevated inflammatory markers, and moderate-to-large pericardial effusion. Extensive infectious (including TB), autoimmune, and malignancy workups were negative. Cardiac magnetic resonance revealed persistent pericardial late gadolinium enhancement despite clinical remission. Whole-exome sequencing identified a heterozygous MEFV c.442G>C (p.Glu148Gln) variant, suggesting an autoinflammatory predisposition. Although the patient finally achieved sustained symptom-free status for six months on a standardized low-dose colchicine regimen, still over 10% of patients have recurrent symptoms receiving colchicine in addition to conventional anti-inflammatory therapy with aspirin or ibuprofen. This case highlights the shifting paradigm from an infection-centered to an autoinflammatory framework for RP in TB-endemic countries, underscores the role of MEFV variants in idiopathic recurrent pericarditis, and illustrates the real-world gap between genetic insights and therapeutic accessibility to IL-1 inhibitors in resource-limited settings.

Cardiac amyloidosis (CA) is an under-recognized cause of left-ventricular hypertrophy (LVH) that is often misclassified as hypertrophic cardiomyopathy (HCM) or hypertensive heart disease (HHD). We aimed to develop and externally validate an AI model using electrocardiograms (ECG) and echocardiography to distinguish CA from other LVH aetiologies. A retrospective, multicenter study was conducted, with a derivation cohort collected from PUMCH (290 CA patients, 215 HCM patients, and 160 HHD patients) and an external validation cohort recruited from 10 other hospitals across China (126 CA patients, 240 HCM patients, and 190 HHD patients). Twenty-eight clinical, ECG, and echocardiographic predictors were included, and we selected the top 7 important features by recursive feature elimination strategy. The Super Learner model combines predictions from 11 machine learning models, and model performance was evaluated via macro-AUC, accuracy, precision, F1 score, and etc. We developed a simplified scoring system to diagnose CA, and classifying patients into three groups based on CA probability to minimize misdiagnosis risk. Ranking by feature importance, the top seven features were included and used for model construction, including Sokolow–Lyon index, interventricular septal thickness, systolic blood pressure, left-ventricular posterior wall thickness, tricuspid annular plane systolic excursion, average E/e′, and left-ventricular ejection fraction. The Super Learner model, combining Extra Trees, Histogram-based Gradient Boosting, LightGBM, and Multi-Layer Perceptron, achieved the highest AUC of 0.97 (95

Improvement of symptoms, physical function, and quality of life is one treatment goal for patients with obstructive hypertrophic cardiomyopathy (HCM). Mavacamten improved left-ventricular outflow tract gradients in Chinese patients with obstructive HCM in the EXPLORER-CN trial. We report here a detailed analysis of patient-reported health status per the 23-item Kansas City Cardiomyopathy Questionnaire (KCCQ-23) in Chinese patients after 78 weeks of mavacamten. Patients who completed the double-blind, placebo-controlled (DBPC) period of EXPLORER-CN with no active safety concerns could enter a long-term extension (LTE) period to receive mavacamten for 48 weeks at either the 30-week dose (mavacamten-mavacamten group) or a once-daily starting dose of 2.5 mg (subsequently adjusted via pharmacodynamics-based dose titration: placebo-mavacamten group). Health status endpoints included KCCQ-23 clinical summary score (CSS), overall symptom score (OSS), total symptom score (TSS), physical limitations score, and quality-of-life scores through week 78. Week 78 endpoint analyses were descriptive. In the DBPC period, 54 patients received mavacamten and 27 received placebo; of these, 54 and 25, respectively, entered the LTE period. KCCQ-23 CSS, OSS, and TSS improved with mavacamten and worsened with placebo during the DBPC period (mean change baseline to week 30: 5.7, 6.4, and 8.1, respectively [mavacamten-mavacamten group] and – 5.4, – 4.3, and – 4.8, respectively [placebo-mavacamten group]). CSS, OSS, and TSS continued to improve in the mavacamten-mavacamten group during the LTE period (mean change baseline to week 78: 7.1, 8.2, and 10.0, respectively). Scores improved in the placebo-mavacamten group after switching to mavacamten (mean change week 30 to week 78: 7.3, 9.5, and 5.7, respectively). Similar improvements in KCCQ-23 physical limitations and quality-of-life scores with mavacamten were observed throughout both study periods. Long-term mavacamten treatment for up to 78 weeks led to sustained improvements in patient-reported health status, supporting long-term treatment with mavacamten for Chinese patients with symptomatic obstructive HCM. ClinicalTrials.gov identifier NCT05174416.

The long-term prognosis of left ventricular noncompaction (LVNC) compared to dilated cardiomyopathy (DCM) remains inconclusive, as prior studies have frequently failed to adequately adjust for heart failure severity. We conducted a single-center, retrospective, comparative study enrolling 96 patients with dilated LVNC (dLVNC) and 437 patients with DCM diagnosed at Peking Union Medical College Hospital between January 2010 and December 2022. dLVNC was defined as meeting the Jenni criteria, with left ventricular ejection fraction (LVEF) ≤45% and increased left ventricular end-diastolic diameter (LVEDD). A 1:1 propensity score matching (PSM) was performed, with matching variables including sex, age, history of heart failure (HF) hospitalization, arrhythmia, LVEF, and LVEDD, resulting in 96 matched pairs. The primary endpoint was major adverse cardiovascular events (MACEs), comprising cardiovascular death or heart transplantation, HF hospitalization or cardiac resynchronization therapy implantation, severe arrhythmias, and systemic embolism. After a median follow-up of 5.46 (2.14–8.62) years in the dLVNC group and 5.26 (2.47–8.50) years in the DCM group, the Kaplan–Meier survival curves between the groups were highly overlapping and revealed no significant differences in MACEs (log-rank p = 0.88), all-cause mortality (log-rank p = 0.84), and individual components of MACEs. After adjusting for heart failure severity, dLVNC and DCM exhibit no substantial difference in long-term prognosis, and the morphological feature of excessive trabeculation itself does not independently increase the risk of adverse events.

Abstract Hypertrophic cardiomyopathy (HCM) is a prevalent inherited cardiovascular disorder characterized by left ventricular hypertrophy and constitutes the leading cause of exercise-induced sudden cardiac death in young individuals. Conventional therapeutic strategies, such as the use of β-blockers, calcium channel blockers, and septal reduction therapy, focus largely on symptomatic relief and often exhibit limited clinical efficacy. Recent years have witnessed significant progress across multiple therapeutic domains, encompassing general clinical management, pharmacotherapy, gene therapy, and invasive interventions. Emerging treatment modalities, including cardiac myosin inhibitors, myocardial metabolic modulators, anti-fibrotic agents, gene therapies, and interventional procedures, have shown promising potential. Concurrently, exercise management guidelines for patients with HCM have undergone progressive liberalization. These therapeutic innovations, together with optimized exercise strategies, may improve symptoms, prolong survival, and enhance quality of life. This review comprehensively summarizes current research regarding novel HCM treatment approaches—incorporating approved pharmaceuticals, preclinical findings, and clinical trial data—with the aim of facilitating continued development of HCM therapeutics.

Inflammation is a key contributor to cardiovascular disease (CVD), yet existing risk models such as Atherosclerotic Cardiovascular Disease Risk in China (China-PAR) and Pooled Cohort Equations (PCE) inadequately identify individuals at intermediate risk. We investigated whether incorporating the inflammatory chemokine CCL17 could improve cardiovascular risk prediction. In two prospective cohorts—the Shunyi Cohort (n = 706, China) and the UK Biobank (n = 36,097, UK)—baseline CCL17 levels were quantified, and major adverse cardiovascular events (MACEs) were tracked over follow-up. Elevated CCL17 levels were independently associated with increased risk of MACEs. Integrating CCL17 into existing models significantly improved discrimination and reclassification, particularly among intermediate-risk individuals (e.g., NRI: 15.1

BACKGROUND:Mavacamten, a first-in-class cardiac myosin inhibitor and the only approved cardiac myosin inhibitor worldwide, improved clinical symptoms and health status in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM) in phase 3 EXPLORER-HCM (Clinical Study to Evaluate Mavacamten [MYK-461] in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy; NCT03470545) and EXPLORER-CN (A Study to Evaluate the Efficacy and Safety of Mavacamten in Chinese Adults With Symptomatic Obstructive HCM; NCT05174416). OBJECTIVES:The purpose of this work was to study the effect of mavacamten on cardiac structure and function by cardiac magnetic resonance (CMR) imaging in Chinese participants in EXPLORER-CN. METHODS:Eligible patients with obstructive HCM underwent CMR imaging at screening and week 30. Change from baseline to week 30 in left ventricular (LV) mass index was analyzed as a prespecified secondary outcome. Prespecified exploratory outcomes included changes in cellular hypertrophy, cardiac structure and function, and myocardial fibrosis by CMR. RESULTS:Among 81 patients randomized, 58 patients (mean age 51.2 years, 74.1% men) with CMR data available were analyzed (mavacamten, n = 39; placebo, n = 19). After 30 weeks, greater reductions from baseline were observed (mean between-group difference) with mavacamten vs placebo in LV mass index (-30.8 g/m2 [95% CI: -41.5 to -20.1 g/m2]), maximal LV wall thickness (-3.5 mm [95% CI: -4.7 to -2.4 mm]), and maximal left atrial volume index (-18.3 mL/m2 [95% CI: -26.7 to -9.8 mL/m2]); all nominal P < 0.001. Reduction from baseline to week 30 in global mass of late gadolinium enhancement by 6 SDs was also observed with mavacamten vs placebo (mean between-group difference, -2.0 g [95% CI: -11.9 to 8.0 g]; nominal P = 0.007). CONCLUSIONS:At 30 weeks, improvements were observed in measures of cardiac structure and function, with reductions in indicators of myocardial fibrosis, in the mavacamten vs the placebo group. (A Study to Evaluate the Efficacy and Safety of Mavacamten in Chinese Adults With Symptomatic Obstructive HCM; NCT05174416).

Heart disease stands as the foremost global cause of mortality. In rodents, the heart possesses the remarkable ability for cardiac regeneration within the first 7 days post-birth. Furthermore, the transition to an oxygen-rich environment and altered nutrient availability trigger a profound shift in cardiac energy metabolism immediately after birth. Lactylation, which translates metabolic adjustments into enduring gene expression patterns, has been recognized for its role in this process. However, its role in heart development has remained unexplored. In this study, we conduct an integrated study combining global proteomics, lactylome, and genome-wide RNA sequencing to elucidate the role of lactylation throughout postnatal heart development. Our findings demonstrate a remarkable increase in non-histone lactylation levels as early as 1 week (1 w) to 6 weeks (6 w) postpartum and remained elevated from 6 months (6 m) onwards. However, the histone lactylation showed the opposite trend. Additionally, we propose that histone 4 lysine 12 lactylation (H4K12la) acts as a pivotal upstream regulatory element in the early postnatal mouse heart, from 1 w to 6 w postpartum. Our findings strongly suggest a significant connection between lactylation and postnatal cardiac development and highlight its involvement in gene expression regulation, thus offering potential mechanisms for targeting heart diseases.