Share：
Share this content in WeChat
X
[Chinese] [PDF] 4 1
• Review •
Advances in precision medicine for dilated cardiomyopathy: Focusing on genetics and cardiac magnetic resonance imaging
KAISAIERJIANG Aisikaier  CHEN Xiuyu  ZHAO Shihua 

DOI:10.12015/issn.1674-8034.2025.11.033.


[Abstract] Dilated cardiomyopathy (DCM) is a major cause of heart failure and sudden cardiac death (SCD), with 30% to 40% of cases having a genetic basis. Studies demonstrate that specific genetic variants are significantly associated with malignant arrhythmias and adverse outcomes in patients. Traditional DCM diagnostic criteria, based on ventricular morphology and dysfunction, are inadequate for early subtyping and etiological differentiation. Recent breakthroughs in cardiac magnetic resonance (CMR) technology and genetic research have driven the evolution of DCM classification. The traditional "idiopathic vs. secondary" dichotomy is shifting towards a precision subtyping system based on underlying pathogenic mechanisms. This provides crucial evidence for SCD risk assessment and implantable cardioverter defibrillator (ICD) use in primary prevention. The integration of multi-dimensional data, including genotype, CMR phenotype, clinical information, and proteomics, analyzed through machine learning, is systematically reshaping DCM diagnosis, subtyping, risk stratification, and management strategies. This approach lays the groundwork for establishing an individualized "etiology-mechanism-phenotype" guided diagnostic and therapeutic model. However, the association between genotypes and CMR phenotypes has not been systematically established, and the precision subtyping of DCM along with SCD risk assessment system remain incomplete. This review focuses on recent advances in genetics and CMR in DCM and their clinical applications, analyzes current research limitations, and proposes future research directions to provide an evidence-based foundation for clinical decision-making.
[Keywords] dilated cardiomyopathy；magnetic resonance imaging；cardiac magnetic resonance；genotype；sudden cardiac death；risk stratification

KAISAIERJIANG Aisikaier   CHEN Xiuyu*   ZHAO Shihua  

Department of Magnetic Resonance Imaging, Fuwai Hospital, National Center for Cardiovascular Diseases of China, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China

Corresponding author: CHEN X Y, E-mail: cxy0202@126.com

Conflicts of interest   None.

Received  2025-09-16
Accepted  2025-10-29
DOI: 10.12015/issn.1674-8034.2025.11.033
DOI:10.12015/issn.1674-8034.2025.11.033.

[1]
MCKENNA W J, JUDGE D P. Epidemiology of the inherited cardiomyopathies[J]. Nat Rev Cardiol, 2021, 18(1): 22-36. DOI: 10.1038/s41569-020-0428-2.
[2]
FATKIN D, CALKINS H, ELLIOTT P, et al. Contemporary and future approaches to precision medicine in inherited cardiomyopathies: JACC focus seminar 3/5[J]. J Am Coll Cardiol, 2021, 77(20): 2551-2572. DOI: 10.1016/j.jacc.2020.12.072.
[3]
PINTO Y M, ELLIOTT P M, ARBUSTINI E, et al. Proposal for a revised definition of dilated cardiomyopathy, hypokinetic non-dilated cardiomyopathy, and its implications for clinical practice: a position statement of the ESC working group on myocardial and pericardial diseases[J]. Eur Heart J, 2016, 37(23): 1850-1858. DOI: 10.1093/eurheartj/ehv727.
[4]
ARBELO E, PROTONOTARIOS A, GIMENO J R, et al. 2023 ESC guidelines for the management of cardiomyopathies[J]. Eur Heart J, 2023, 44(37): 3503-3626. DOI: 10.1093/eurheartj/ehad194.
[5]
KAISAIERJIANG A, SA F, CHEN X Y, et al. The interpretation of 2023 ESC guidelines for the management of cardiomyopathies: classification innovation of non-dilated left ventricular cardiomyopathy[J]. Chin J Magn Reson Imag, 2025, 16(4): 1-5. DOI: 10.12015/issn.1674-8034.2025.04.001.
[6]
MCDONAGH T A, METRA M, ADAMO M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure[J]. Eur Heart J, 2021, 42(36): 3599-3726. DOI: 10.1093/eurheartj/ehab368.
[7]
GLIKSON M, NIELSEN J C, KRONBORG M B, et al. 2021 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy[J]. EP Eur, 2022, 24(1): 71-164. DOI: 10.1093/europace/euab232.
[8]
Correction to: 2023 focused update of the 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: developed by the task force for the diagnosis and treatment of acute and chronic heart failure of the European society of cardiology (ESC) with the special contribution of the heart failure association (HFA) of the ESC[J]. Eur Heart J, 2024, 45(1): 53. DOI: 10.1093/eurheartj/ehad613.
[9]
JORDAN E, PETERSON L, AI T, et al. Evidence-based assessment of genes in dilated cardiomyopathy[J]. Circulation, 2021, 144(1): 7-19. DOI: 10.1161/CIRCULATIONAHA.120.053033.
[10]
CABRERA-ROMERO E, OCHOA J P, BARRIALES-VILLA R, et al. Penetrance of dilated cardiomyopathy in genotype-positive relatives[J]. J Am Coll Cardiol, 2024, 83(17): 1640-1651. DOI: 10.1016/j.jacc.2024.02.036.
[11]
KHAN R S, PAHL E, DELLEFAVE-CASTILLO L, et al. Genotype and cardiac outcomes in pediatric dilated cardiomyopathy[J/OL]. J Am Heart Assoc, 2022, 11(1): e022854 [2025-09-15]. https://pubmed.ncbi.nlm.nih.gov/34935411/. DOI: 10.1161/JAHA.121.022854.
[12]
STROEKS S L V M, HELLEBREKERS D M E I, CLAES G R F, et al. Clinical impact of re-evaluating genes and variants implicated in dilated cardiomyopathy[J]. Genet Med, 2021, 23(11): 2186-2193. DOI: 10.1038/s41436-021-01255-1.
[13]
PARK H Y. Hereditary dilated cardiomyopathy: recent advances in genetic diagnostics[J]. Korean Circ J, 2017, 47(3): 291-298. DOI: 10.4070/kcj.2016.0017.
[14]
MAZZAROTTO F, OLIVOTTO I, WALSH R. Advantages and perils of clinical whole-exome and whole-genome sequencing in cardiomyopathy[J]. Cardiovasc Drugs Ther, 2020, 34(2): 241-253. DOI: 10.1007/s10557-020-06948-4.
[15]
MAZZAROTTO F, TAYAL U, BUCHAN R J, et al. Reevaluating the genetic contribution of monogenic dilated cardiomyopathy[J]. Circulation, 2020, 141(5): 387-398. DOI: 10.1161/CIRCULATIONAHA.119.037661.
[16]
MERLO M, CANNATÀ A, SINAGRA G. Dilated cardiomyopathy: a paradigm of revolution in medicine[J/OL]. J Clin Med, 2020, 9(11): 3385 [2025-09-15]. https://pubmed.ncbi.nlm.nih.gov/33105590/. DOI: 10.3390/jcm9113385.
[17]
SETTI M, MERLO M, GIGLI M, et al. Role of arrhythmic phenotype in prognostic stratification and management of dilated cardiomyopathy[J]. Eur J Heart Fail, 2024, 26(3): 581-589. DOI: 10.1002/ejhf.3168.
[18]
HEYMANS S, LAKDAWALA N K, TSCHÖPE C, et al. Dilated cardiomyopathy: causes, mechanisms, and current and future treatment approaches[J]. Lancet, 2023, 402(10406): 998-1011. DOI: 10.1016/S0140-6736(23)01241-2.
[19]
FATKIN D, HUTTNER I G, KOVACIC J C, et al. Precision medicine in the management of dilated cardiomyopathy: JACC state-of-the-art review[J]. J Am Coll Cardiol, 2019, 74(23): 2921-2938. DOI: 10.1016/j.jacc.2019.10.011.
[20]
ESCOBAR-LOPEZ L, OCHOA J P, MIRELIS J G, et al. Association of genetic variants with outcomes in patients with nonischemic dilated cardiomyopathy[J]. J Am Coll Cardiol, 2021, 78(17): 1682-1699. DOI: 10.1016/j.jacc.2021.08.039.
[21]
BARRIALES-VILLA R, OCHOA J P, LARRAÑAGA-MOREIRA J M, et al. Risk predictors in a Spanish cohort with cardiac laminopathies. The REDLAMINA registry[J]. Rev Esp Cardiol (Engl Ed), 2021, 74(3): 216-224. DOI: 10.1016/j.rec.2020.03.026.
[22]
GIGLI M, STOLFO D, GRAW S L, et al. Phenotypic expression, natural history, and risk stratification of cardiomyopathy caused by filamin C truncating variants[J]. Circulation, 2021, 144(20): 1600-1611. DOI: 10.1161/CIRCULATIONAHA.121.053521.
[23]
AKHTAR M M, LORENZINI M, PAVLOU M, et al. Association of left ventricular systolic dysfunction among carriers of truncating variants in filamin C with frequent ventricular arrhythmia and end-stage heart failure[J]. JAMA Cardiol, 2021, 6(8): 891-901. DOI: 10.1001/jamacardio.2021.1106.
[24]
SMITH E D, LAKDAWALA N K, PAPOUTSIDAKIS N, et al. Desmoplakin cardiomyopathy, a fibrotic and inflammatory form of cardiomyopathy distinct from typical dilated or arrhythmogenic right ventricular cardiomyopathy[J]. Circulation, 2020, 141(23): 1872-1884. DOI: 10.1161/CIRCULATIONAHA.119.044934.
[25]
VERSTRAELEN T E, VAN LINT F H M, BOSMAN L P, et al. Prediction of ventricular arrhythmia in phospholamban p.Arg14del mutation carriers-reaching the frontiers of individual risk prediction[J]. Eur Heart J, 2021, 42(29): 2842-2850. DOI: 10.1093/eurheartj/ehab294.
[26]
KUMAR S, BALDINGER S H, GANDJBAKHCH E, et al. Long-term arrhythmic and nonarrhythmic outcomes of lamin A/C mutation carriers[J]. J Am Coll Cardiol, 2016, 68(21): 2299-2307. DOI: 10.1016/j.jacc.2016.08.058.
[27]
HODGKINSON K A, HOWES A J, BOLAND P, et al. Long-term clinical outcome of arrhythmogenic right ventricular cardiomyopathy in individuals with a p.S358mutation in TMEML43 following implantable cardioverter defibrillator therapy[J/OL]. Circ Arrhythm Electrophysiol, 2016, 9(3): e003589 [2025-09-15]. https://pubmed.ncbi.nlm.nih.gov/26966288/. DOI: 10.1161/CIRCEP.115.003589.
[28]
HEY T M, RASMUSSEN T B, MADSEN T, et al. Pathogenic RBM20-variants are associated with a severe disease expression in male patients with dilated cardiomyopathy[J/OL]. Circ Heart Fail, 2019, 12(3): e005700 [2025-09-15]. https://pubmed.ncbi.nlm.nih.gov/30871348/. DOI: 10.1161/CIRCHEARTFAILURE.118.005700.
[29]
STROEKS S L V M, WANG P, MERLO M, et al. Impact of genotype-phenotype associations on prognosis in dilated cardiomyopathy[J/OL]. Eur J Heart Fail, 2025 [2025-09-15]. https://pubmed.ncbi.nlm.nih.gov/40938777/. DOI: 10.1002/ejhf.70040.
[30]
PALDINO A, FERRO M D, STOLFO D, et al. Prognostic prediction of genotype vs phenotype in genetic cardiomyopathies[J]. J Am Coll Cardiol, 2022, 80(21): 1981-1994. DOI: 10.1016/j.jacc.2022.08.804.
[31]
LAKDAWALA N K, TAYAL U. Genetic testing for dilated cardiomyopathy: old school is new school[J]. J Am Coll Cardiol, 2022, 80(12): 1127-1129. DOI: 10.1016/j.jacc.2022.07.010.
[32]
FINOCCHIARO G, MERLO M, SHEIKH N, et al. The electrocardiogram in the diagnosis and management of patients with dilated cardiomyopathy[J]. Eur J Heart Fail, 2020, 22(7): 1097-1107. DOI: 10.1002/ejhf.1815.
[33]
PRASAD S K, TAYAL U. The value of strain in familial dilated cardiomyopathy screening[J]. JACC Cardiovasc Imaging, 2020, 13(2Pt 2): 559-561. DOI: 10.1016/j.jcmg.2019.09.004.
[34]
ZHANG L X, CHEN Y, QI H C, et al. Research progress in the application of cardiac magnetic resonance imaging in dilated cardiomyopathy[J]. Chin J Magn Reson Imag, 2025, 16(3): 150-155. DOI: 10.12015/issn.1674-8034.2025.03.025.
[35]
HAMMERSLEY D J, MUKHOPADHYAY S, CHEN X Y, et al. Precision prediction of heart failure events in patients with dilated cardiomyopathy and mildly reduced ejection fraction using multi-parametric cardiovascular magnetic resonance[J]. Eur J Heart Fail, 2024, 26(12): 2553-2562. DOI: 10.1002/ejhf.3425.
[36]
KØBER L, THUNE J J, NIELSEN J C, et al. Defibrillator implantation in patients with nonischemic systolic heart failure[J]. N Engl J Med, 2016, 375(13): 1221-1230. DOI: 10.1056/NEJMoa1608029.
[37]
YAFASOVA A, BUTT J H, ELMING M B, et al. Long-term follow-up of DANISH (the Danish study to assess the efficacy of ICDs in patients with nonischemic systolic heart failure on mortality)[J]. Circulation, 2022, 145(6): 427-436. DOI: 10.1161/CIRCULATIONAHA.121.056072.
[38]
DONAL E, DELGADO V, BUCCIARELLI-DUCCI C, et al. Multimodality imaging in the diagnosis, risk stratification, and management of patients with dilated cardiomyopathies: an expert consensus document from the European Association of Cardiovascular Imaging[J]. Eur Heart J Cardiovasc Imaging, 2019, 20(10): 1075-1093. DOI: 10.1093/ehjci/jez178.
[39]
KLEM I, KLEIN M, KHAN M, et al. Relationship of LVEF and myocardial scar to long-term mortality risk and mode of death in patients with nonischemic cardiomyopathy[J]. Circulation, 2021, 143(14): 1343-1358. DOI: 10.1161/CIRCULATIONAHA.120.048477.
[40]
HOLMSTRÖM M, KIVISTÖ S, HELIÖ T, et al. Late gadolinium enhanced cardiovascular magnetic resonance of lamin A/C gene mutation related dilated cardiomyopathy[J/OL]. J Cardiovasc Magn Reson, 2011, 13(1): 30 [2025-09-15]. https://pubmed.ncbi.nlm.nih.gov/21689390/. DOI: 10.1186/1532-429X-13-30.
[41]
DI MARCO A, BROWN P F, BRADLEY J, et al. Improved risk stratification for ventricular arrhythmias and sudden death in patients with nonischemic dilated cardiomyopathy[J]. J Am Coll Cardiol, 2021, 77(23): 2890-2905. DOI: 10.1016/j.jacc.2021.04.030.
[42]
MIRELIS J G, ESCOBAR-LOPEZ L, OCHOA J P, et al. Combination of late gadolinium enhancement and genotype improves prediction of prognosis in non-ischaemic dilated cardiomyopathy[J]. Eur J Heart Fail, 2022, 24(7): 1183-1196. DOI: 10.1002/ejhf.2514.
[43]
LAKDAWALA N K, THUNE J J, COLAN S D, et al. Subtle abnormalities in contractile function are an early manifestation of sarcomere mutations in dilated cardiomyopathy[J]. Circ Cardiovasc Genet, 2012, 5(5): 503-510. DOI: 10.1161/CIRCGENETICS.112.962761.
[44]
XIANG X R, SONG Y Y, ZHAO K K, et al. Incremental prognostic value of left atrial and biventricular feature tracking in dilated cardiomyopathy: a long-term study[J/OL]. J Cardiovasc Magn Reson, 2023, 25(1): 76 [2025-09-15]. https://pubmed.ncbi.nlm.nih.gov/38057892/. DOI: 10.1186/s12968-023-00967-4.
[45]
RAAFS A G, VOS J L, HENKENS M T H M, et al. Left atrial strain has superior prognostic value to ventricular function and delayed-enhancement in dilated cardiomyopathy[J]. JACC Cardiovasc Imaging, 2022, 15(6): 1015-1026. DOI: 10.1016/j.jcmg.2022.01.016.
[46]
DE FRUTOS F, OCHOA J P, FERNÁNDEZ A I, et al. Late gadolinium enhancement distribution patterns in non-ischaemic dilated cardiomyopathy: genotype-phenotype correlation[J]. Eur Heart J Cardiovasc Imaging, 2023, 25(1): 75-85. DOI: 10.1093/ehjci/jead184.
[47]
STROEKS S L V M, WANG P, MERLO M, et al. Impact of genotype-phenotype associations on prognosis in dilated cardiomyopathy[J/OL]. Eur J Heart Fail, 2025 [2025-09-15]. https://pubmed.ncbi.nlm.nih.gov/40938777/. DOI: 10.1002/ejhf.70040.
[48]
JIANG X C, XU Y W, SUN J Y, et al. The phenotypic characteristic observed by cardiac magnetic resonance in a PLN-R14del family[J/OL]. Sci Rep, 2020, 10(1): 16478 [2025-09-15]. https://pubmed.ncbi.nlm.nih.gov/33020536/. DOI: 10.1038/s41598-020-73359-8.
[49]
AKHTAR M M, LORENZINI M, CICERCHIA M, et al. Clinical phenotypes and prognosis of dilated cardiomyopathy caused by truncating variants in the TTN gene[J/OL]. Circ Heart Fail, 2020, 13(10): e006832 [2025-09-15]. https://pubmed.ncbi.nlm.nih.gov/32964742/. DOI: 10.1161/CIRCHEARTFAILURE.119.006832.
[50]
AMIN R J, MORRIS-ROSENDAHL D, EDWARDS M, et al. The addition of genetic testing and cardiovascular magnetic resonance to routine clinical data for stratification of etiology in dilated cardiomyopathy[J/OL]. Front Cardiovasc Med, 2022, 9: 1017119 [2025-09-15]. https://pubmed.ncbi.nlm.nih.gov/36277766/. DOI: 10.3389/fcvm.2022.1017119.
[51]
TAYAL U, VERDONSCHOT J A J, HAZEBROEK M R, et al. Precision phenotyping of dilated cardiomyopathy using multidimensional data[J]. J Am Coll Cardiol, 2022, 79(22): 2219-2232. DOI: 10.1016/j.jacc.2022.03.375.
[52]
CHA M J, HONG Y J, PARK C H, et al. Utilities and limitations of cardiac magnetic resonance imaging in dilated cardiomyopathy[J]. Korean J Radiol, 2023, 24(12): 1200-1220. DOI: 10.3348/kjr.2023.0531.
[53]
TAO M, DHALIWAL S, GHOSALKAR D, et al. Utility of native T1 mapping and myocardial extracellular volume fraction in patients with nonischemic dilated cardiomyopathy: a systematic review and meta-analysis[J/OL]. Int J Cardiol Heart Vasc, 2024, 51: 101339 [2025-09-15]. https://pubmed.ncbi.nlm.nih.gov/38371310/. DOI: 10.1016/j.ijcha.2024.101339.
[54]
LI S, ZHOU D, SIRAJUDDIN A, et al. T1 mapping and extracellular volume fraction in dilated cardiomyopathy: a prognosis study[J]. JACC Cardiovasc Imaging, 2022, 15(4): 578-590. DOI: 10.1016/j.jcmg.2021.07.023.
[55]
ZHAO K D, CAO X S. Research progress of T1 mapping MRI in dilated cardiomyopathy[J]. Chin J Magn Reson Imag, 2024, 15(5): 204-208. DOI: 10.12015/issn.1674-8034.2024.05.033

PREV Advancements in the integration of artificial intelligence and imaging technology for the detection of metastatic cervical lymph nodes
NEXT Progress in non-invasive elastography techniques for the diagnosis and assessment of metabolic dysfunction-associated steatotic liver disease
  


LINK


Tel & Fax: +8610-67113815    E-mail: editor@cjmri.cn