Evidence map›Paper›PMID 42381624›Full record

Observational studyCirculation research2026

Proteogenomics of Hypertrophic Cardiomyopathy Reveals Subtype-Specific Therapy.

Ke Ma, Jie Yang, Hongchang Guo, Ping Li, Xiaowei Li, Zhujun Dong, Jing Zhang, Congcong Zhang, Pengli Yang, Chongpei Hua and 10 more

Registry-linked trialAbstract readMulticenter StudyObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in Circulation research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03076580 (An Integrative-omics Study to Identify New Biomarkers of Cardiomyopathy Patients in China), which is not on this map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03076580 unknown statusnot on this map

An Integrative-omics Study to Identify New Biomarkers of Cardiomyopathy Patients in China

TypeobservationalSponsorBeijing Institute of Heart, Lung and Blood Vessel DiseasesRan2015 to 2021Enrolled2,000ConditionsDilated Cardiomyopathy, Hypertrophic Cardiomyopathy, Arrhythmogenic Right Ventricular Cardiomyopathy, Left Ventricular Non-compaction
3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

20 authors.

Ke Ma *Beijing Anzhen Hospital, Capital Medical University, China (K.M., J.Y., H.G., P.L., Z.D., Jing Zhang, C.Z., P.Y., C.H., S.Z., G.L., J.D., Yang Li, Yulin Li).ORCID 0000-0001-6768-1259
Jie Yang *Beijing Anzhen Hospital, Capital Medical University, China (K.M., J.Y., H.G., P.L., Z.D., Jing Zhang, C.Z., P.Y., C.H., S.Z., G.L., J.D., Yang Li, Yulin Li).
Hongchang Guo *Beijing Anzhen Hospital, Capital Medical University, China (K.M., J.Y., H.G., P.L., Z.D., Jing Zhang, C.Z., P.Y., C.H., S.Z., G.L., J.D., Yang Li, Yulin Li).
Ping Li *Beijing Anzhen Hospital, Capital Medical University, China (K.M., J.Y., H.G., P.L., Z.D., Jing Zhang, C.Z., P.Y., C.H., S.Z., G.L., J.D., Yang Li, Yulin Li).
Xiaowei LiDepartment of Cardiology, The First Affiliated Hospital of Zhengzhou University, China (X.L., Jianchao Zhang, N.D., J.D.).
Zhujun DongBeijing Anzhen Hospital, Capital Medical University, China (K.M., J.Y., H.G., P.L., Z.D., Jing Zhang, C.Z., P.Y., C.H., S.Z., G.L., J.D., Yang Li, Yulin Li).ORCID 0009-0007-7297-7725
Jing ZhangBeijing Anzhen Hospital, Capital Medical University, China (K.M., J.Y., H.G., P.L., Z.D., Jing Zhang, C.Z., P.Y., C.H., S.Z., G.L., J.D., Yang Li, Yulin Li).
Congcong ZhangBeijing Anzhen Hospital, Capital Medical University, China (K.M., J.Y., H.G., P.L., Z.D., Jing Zhang, C.Z., P.Y., C.H., S.Z., G.L., J.D., Yang Li, Yulin Li).
Pengli YangBeijing Anzhen Hospital, Capital Medical University, China (K.M., J.Y., H.G., P.L., Z.D., Jing Zhang, C.Z., P.Y., C.H., S.Z., G.L., J.D., Yang Li, Yulin Li).ORCID 0009-0008-3780-8034
Chongpei HuaBeijing Anzhen Hospital, Capital Medical University, China (K.M., J.Y., H.G., P.L., Z.D., Jing Zhang, C.Z., P.Y., C.H., S.Z., G.L., J.D., Yang Li, Yulin Li).ORCID 0009-0003-1557-4840
Shuolin ZhuBeijing Anzhen Hospital, Capital Medical University, China (K.M., J.Y., H.G., P.L., Z.D., Jing Zhang, C.Z., P.Y., C.H., S.Z., G.L., J.D., Yang Li, Yulin Li).ORCID 0009-0001-2464-5255
Guoqing LiBeijing Anzhen Hospital, Capital Medical University, China (K.M., J.Y., H.G., P.L., Z.D., Jing Zhang, C.Z., P.Y., C.H., S.Z., G.L., J.D., Yang Li, Yulin Li).
Jianchao ZhangDepartment of Cardiology, The First Affiliated Hospital of Zhengzhou University, China (X.L., Jianchao Zhang, N.D., J.D.).
Ningyu DingDepartment of Cardiology, The First Affiliated Hospital of Zhengzhou University, China (X.L., Jianchao Zhang, N.D., J.D.).
Jizheng WangState Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Science and Peking Union Medical College, Beijing (J.W.).
Xin-Liang MaDepartment of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA (X.-L.M.).ORCID 0000-0002-9041-0876
Zhuofeng LinInnovation Center of Cardiometabolic Disease, Guangdong Medical University, Dongguan, China (Z.L.).ORCID 0000-0003-0136-3084
Jianzeng DongBeijing Anzhen Hospital, Capital Medical University, China (K.M., J.Y., H.G., P.L., Z.D., Jing Zhang, C.Z., P.Y., C.H., S.Z., G.L., J.D., Yang Li, Yulin Li).ORCID 0000-0001-7299-7805
Yang LiBeijing Anzhen Hospital, Capital Medical University, China (K.M., J.Y., H.G., P.L., Z.D., Jing Zhang, C.Z., P.Y., C.H., S.Z., G.L., J.D., Yang Li, Yulin Li).
Yulin LiBeijing Anzhen Hospital, Capital Medical University, China (K.M., J.Y., H.G., P.L., Z.D., Jing Zhang, C.Z., P.Y., C.H., S.Z., G.L., J.D., Yang Li, Yulin Li).ORCID 0000-0001-7909-0763

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundHypertrophic cardiomyopathy (HCM) is a heterogeneous disease with diverse prognosis. The underlying mechanisms remain unknown, resulting in limited risk stratification and therapeutic strategies. This study aimed to elucidate molecular subtypes of HCM through integrated proteogenomic analysis and explore subtype-specific therapeutic strategies.

methodsWe conducted an integrated proteogenomic analysis of 132 patients with HCM using myocardial samples, incorporating whole-exome sequencing, RNA sequencing, and proteomics. Unsupervised clustering was used to identify HCM subtypes, which were validated in heart tissues and human induced pluripotent stem cell-derived cardiomyocytes from 2 independent HCM subsets. Subtype-specific signatures and pathways were explored, and their causal link with HCM pathogenesis was established by genetic evidence. A subtype-specific drug was screened using in silico drug prediction, followed by in vitro and in vivo therapeutic effect assessments.

resultsIntegrated multi-omics analysis identified 2 proteome-based molecular subtypes, severe and mild. We identified 550 subtype-signature proteins, and enrichment analysis based on which revealed that the reduction in fatty acid metabolism and oxidative phosphorylation pathways in HCM versus healthy controls was predominantly driven by the severe subtype, with more severe clinical characteristics and poorer prognosis compared with the mild subtype. Validation in independent cohorts confirmed the robustness of the proteomic subtypes and their association with clinical severity. Additionally, key proteins in fatty acid oxidation and oxidative phosphorylation exhibited consistent expression differences among healthy controls and 2 HCM subtypes. Furthermore, genetic evidence established a causal link between reduced fatty acid oxidation and HCM pathogenesis. Baicalin, identified as a fatty acid oxidation facilitator, improved metabolic and hypertrophic phenotypes in severe subtype human induced pluripotent stem cell-derived cardiomyocytes and Myh6

conclusionsOur analysis demonstrates the metabolic heterogeneity of HCM and enables the development of risk stratification and subtype-specific therapeutic strategies. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03076580.

Indexed as

Cardiomyopathy, HypertrophicProteogenomicsAdultAnimalsFemaleHumansInduced Pluripotent Stem CellsMaleMiceMiddle AgedMultiomicsMyocytes, CardiacPhenotypecardiomyopathy, hypertrophicmetabolismprecision medicineproteogenomics

Identifiers

PMID42381624
PMCPMC13418873

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.