Beyond morphology: A review of heterogeneous mechanisms and precision risk management in left ventricular non-compaction/left ventricular hypertrabeculation
Left ventricular non-compaction/left ventricular hypertrabeculation (LVNC/LVHT) has traditionally been regarded as a congenital cardiomyopathy caused by arrested myocardial compaction during embryogenesis. However, this classical concept is increasingly challenged by mounting clinical and basic evidence, in view of its marked heterogeneity in clinical presentation, imaging features, and genetic background. This review systematically synthesizes relevant research from recent years to propose that LVNC/LVHT is better understood not as a single discrete disease entity, but as a morphological endpoint resulting from diverse etiologies and mechanisms. This review critically appraises the phenotypic pitfalls of current imaging diagnostic criteria, highlighting the clinical dilemma of concurrent over-diagnosis and under-diagnosis that leads to inappropriate management. It then delineates two distinct pathogenic pathways: A developmental pathway associated with mutations in genes such as TAZ and MYH7 and dysregulation of signaling pathways including transforming growth factor-β and neuregulin 1–erythroblastic leukemia viral oncogene homolog; and an acquired/adaptive pathway linked to hemodynamic load-induced myocardial remodeling. Based on these insights, we propose an integrated classification framework subdividing LVNC/LVHT into development-driven, load-adaptive, and idiopathic benign trabeculation subtypes to resolve long-standing diagnostic confusion. We further introduce a multimodal risk stratification system incorporating cardiac structure and function, electrophysiology, genetics, circulating biomarkers, and systemic factors. This strategy aims to shift LVNC/LVHT management from a morphology-based, one-size-fits-all paradigm toward mechanism-guided, individualized precision care. Finally, we outline future directions, including validation of risk models, mechanistic studies, updated guidelines, and integration of artificial intelligence and multi-omics, to establish a novel precision diagnostic and therapeutic framework for LVNC/LVHT.
- Mirza H, Mohan G, Khan W, et al. A review of left ventricular non-compaction cardiomyopathy (LVNC). J Community Hosp Intern Med Perspect. 2022;12(6):51-63. doi: 10.55729/2000-9666.1120
- De Masi De Luca G, Brancati E, Sciarra L, et al. Left ventricular non-compaction, atrial fibrillation and ANK2 mutation in a young athlete. J Clin Med Res. 2025;17(1):60-65. doi: 10.14740/jocmr6126
- Beltrami M, Maestrini V, Baritussio A, et al. Left ventricular excessive trabeculation: pathophysiology, diagnostic challenges, and prognostic significance. Heart Fail Rev. 2026;31(1):80. doi: 10.1007/s10741-026-10649-9
- Pittorru R, De Lazzari M, Migliore F, et al. Left ventricular non-compaction: evolving concepts. J Clin Med. 2024;13(19):5674. doi: 10.3390/jcm13195674
- Huang X, Niu Q, Jiang Y. A review regarding the article “Advances and challenges in the diagnosis and management of left ventricular non-compaction in adults.” Curr Probl Cardiol. 2024;49(7):102582. doi: 10.1016/j.cpcardiol.2024.102582
- Ritter M, Oechslin E, Sütsch G, Attenhofer C, Schneider J, Jenni R. Isolated non-compaction of the myocardium in adults. Mayo Clin Proc. 1997;72(1):26-31. doi: 10.4065/72.1.26
- Jenni R, Oechslin E, Schneider J, Attenhofer Jost C, Kaufmann PA. Echocardiographic and pathoanatomical characteristics of isolated left ventricular non-compaction: a step towards classification as a distinct cardiomyopathy. Heart. 2001;86(6):666-671. doi: 10.1136/heart.86.6.666
- Petersen SE, Jensen B, Aung N, et al. Excessive trabeculation of the left ventricle: JACC: Cardiovascular Imaging expert panel paper. JACC Cardiovasc Imaging. 2023;16(3):408-425. doi: 10.1016/j.jcmg.2022.12.026
- Li D, Wang C. Advances in symptomatic therapy for left ventricular non-compaction in children. Front Pediatr. 2023;11:1147362. doi: 10.3389/fped.2023.1147362
- Mazzarotto F, Hawley MH, Beltrami M, et al. Systematic large-scale assessment of the genetic architecture of left ventricular non-compaction reveals diverse etiologies. Genet Med. 2021;23(5):856-864. doi: 10.1038/s41436-020-01049-x
- Bagnall RD, Singer ES, Wacker J, et al. Genetic basis of childhood cardiomyopathy. Circ Genom Precis Med. 2022;15(6):e003686. doi: 10.1161/circgen.121.003686
- McGurk KA, Qiao M, Zheng SL, et al. Genetic and phenotypic architecture of human myocardial trabeculation. Nat Cardiovasc Res. 2024;3(12):1503-1515. doi: 10.1038/s44161-024-00564-3
- Weiford BC, Subbarao VD, Mulhern KM. Non-compaction of the ventricular myocardium. Circulation. 2004;109(24):2965-2971. doi: 10.1161/01.cir.0000132478.60674.d0
- Aung N, Bartoli A, Rauseo E, et al. Left ventricular trabeculations at cardiac MRI: reference ranges and association with cardiovascular risk factors in UK Biobank. Radiology. 2024;311(1):e232455. doi: 10.1148/radiol.232455
- Ma YT, Wang LJ, Zhao XY, Zheng Y, Sha LH, Zhao XX. Can left ventricular entropy by cardiac magnetic resonance late gadolinium enhancement be a prognostic predictor in patients with left ventricular non-compaction? Diagn Interv Radiol. 2023;29(5):682-690. doi: 10.4274/dir.2023.221859
- Ross SB, Jones K, Blanch B, et al. A systematic review and meta-analysis of the prevalence of left ventricular non-compaction in adults. Eur Heart J. 2020;41(14):1428-1436. doi: 10.1093/eurheartj/ehz317
- Kazmirczak F, Martin CM, Shenoy C. Left ventricular non-compaction and cardiogenic shock. Circulation. 2020;141(8):696-701. doi: 10.1161/circulationaha.119.043716
- Wang J, Han Y, Chen Y. Discourage LVNC or revise the criteria of LVNC? JACC Cardiovasc Imaging. 2023;16(6):868. doi: 10.1016/j.jcmg.2023.03.024
- Casas G, Rodríguez-Palomares JF, Ferreira-González I. Left ventricular non-compaction: a disease or a phenotypic trait? Rev Esp Cardiol. 2022;75(12):1059-1069. doi: 10.1016/j.rec.2022.07.002
- Aung N, Doimo S, Ricci F, et al. Prognostic significance of left ventricular non-compaction: systematic review and meta-analysis of observational studies. Circ Cardiovasc Imaging. 2020;13(1):e009712. doi: 10.1161/circimaging.119.009712
- Arbelo E, Protonotarios A, Gimeno JR, et al. 2023 ESC guidelines for the management of cardiomyopathies. Eur Heart J. 2023;44(37):3503-3626. doi: 10.1093/eurheartj/ehad194
- Oechslin EN, Attenhofer Jost CH, Rojas JR, Kaufmann PA, Jenni R. Long-term follow-up of 34 adults with isolated left ventricular non-compaction: a distinct cardiomyopathy with poor prognosis. J Am Coll Cardiol. 2000;36(2):493-500. doi: 10.1016/S0735-1097(00)00755-5
- Protonotarios A, Elliott PM. Left ventricular non-compaction: have we reached the limits of conventional imaging? Eur Heart J. 2020;41(14):1437-1438. doi: 10.1093/eurheartj/ehz352
- De Lazzari M, Brunetti G, Frasson E, et al. Thinning of compact layer and systolic dysfunction in isolated left ventricular non-compaction: a cardiac magnetic resonance study. Int J Cardiol. 2024;397:131614. doi: 10.1016/j.ijcard.2023.131614
- Kim JH, Baggish AL, Levine BD, et al. Clinical considerations for competitive sports participation for athletes with cardiovascular abnormalities: a scientific statement from the American Heart Association and American College of Cardiology. J Am Coll Cardiol. 2025;85(10):1059-1108. doi: 10.1016/j.jacc.2024.12.025
- Rojanasopondist P, Nesheiwat L, Piombo S, Porter GA Jr, Ren M, Phoon CKL. Genetic basis of left ventricular non-compaction. Circ Genom Precis Med. 2022;15(3):e003517. doi: 10.1161/circgen.121.003517
- Ross SB, Singer ES, Driscoll E, et al. Genetic architecture of left ventricular non-compaction in adults. Hum Genome Var. 2020;7(1):33. doi: 10.1038/s41439-020-00120-y
- Siguero-Álvarez M, Salguero-Jiménez A, Grego-Bessa J, et al. A human hereditary cardiomyopathy shares a genetic substrate with bicuspid aortic valve. Circulation. 2023;147(1):47-65. doi: 10.1161/circulationaha.121.058767
- Fitzsimons LA, Kneeland-Barber DM, Hannigan GC, et al. Electrophysiological phenotyping of left ventricular non-compaction cardiomyopathy in pediatric populations: a systematic review. Physiol Rep. 2024;12(9):e16029. doi: 10.14814/phy2.16029
- Sharain K, Anavekar NS. Outcomes in left ventricular non-compaction: heterogeneity in results or heterogeneity in diagnosing a heterogeneous disease? Circ Cardiovasc Imaging. 2020;13(1):e010268. doi: 10.1161/circimaging.119.010268
- D’Silva A, Captur G, Bhuva AN, et al. Recreational marathon running does not cause exercise-induced left ventricular hypertrabeculation. Int J Cardiol. 2020;315:67-71. doi: 10.1016/j.ijcard.2020.04.081
- de la Chica JA, Gómez-Talavera S, García-Ruiz JM, et al. Association between left ventricular non-compaction and vigorous physical activity. J Am Coll Cardiol. 2020;76(15):1723-1733. doi: 10.1016/j.jacc.2020.08.030
- Ramazani N, Ivey B, Chakraborty S, et al. Left ventricular non-compaction cardiomyopathy: the tragedies & trabeculations of the architectural cardiac sponge. J Clin Med. 2026;15(5):2023. doi: 10.3390/jcm15052023
- Calvo Cuervo D. Comment on the ESC guidelines 2022 for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. Eur Cardiol. 2023;18:e01. doi: 10.15420/ecr.2022.48
- Casas G, Limeres J, Oristrell G, et al. Clinical risk prediction in patients with left ventricular myocardial non-compaction. J Am Coll Cardiol. 2021;78(7):643-662. doi: 10.1016/j.jacc.2021.06.016
- von Knobelsdorff-Brenkenhoff F, Schulz-Menger J. Cardiovascular magnetic resonance in the guidelines of the European Society of Cardiology: a comprehensive summary and update. J Cardiovasc Magn Reson. 2023;25(1):42. doi: 10.1186/s12968-023-00950-z
- Leiner T, Bogaert J, Friedrich MG, et al. SCMR position paper (2020) on clinical indications for cardiovascular magnetic resonance. J Cardiovasc Magn Reson. 2020;22(1):76. doi: 10.1186/s12968-020-00682-4
- Srivastava S, Yavari M, Al-Abcha A, Banga S, Abela G. Ventricular non-compaction review. Heart Fail Rev. 2022;27(4):1063-1076. doi: 10.1007/s10741-021-10128-3
- Grego-Bessa J, Gómez-Apiñaniz P, Prados B, Gómez MJ, MacGrogan D, de la Pompa JL. Nrg1 regulates cardiomyocyte migration and cell cycle in ventricular development. Circ Res. 2023;133(11):927-943. doi: 10.1161/circresaha.123.323321
- Rhee S, Paik DT, Yang JY, et al. Endocardial/endothelial angiocrines regulate cardiomyocyte development and maturation and induce features of ventricular non-compaction. Eur Heart J. 2021;42(41):4264-4276. doi: 10.1093/eurheartj/ehab298
- Wu T, Liang Z, Zhang Z, et al. PRDM16 is a compact myocardium-enriched transcription factor required to maintain compact myocardial cardiomyocyte identity in left ventricle. Circulation. 2022;145(8):586-602. doi: 10.1161/circulationaha.121.056666
- Li Y, Du J, Deng S, et al. The molecular mechanisms of cardiac development and related diseases. Signal Transduct Target Ther. 2024;9(1):368. doi: 10.1038/s41392-024-02069-8
- Lazarte J, Jurgens SJ, Choi SH, et al. LMNA variants and risk of adult-onset cardiac disease. J Am Coll Cardiol. 2022;80(1):50-59. doi: 10.1016/j.jacc.2022.04.035
- Bhaskaran A, Ben Yaou R, Helms AS, et al. Location of LMNA variants and clinical outcomes in cardiomyopathy. JAMA Cardiol. 2025;10(9):896-903. doi: 10.1001/jamacardio.2025.2069
- Zhu S, Chen Z, Zhu M, et al. Cardiolipin remodeling defects impair mitochondrial architecture and function in a murine model of Barth syndrome cardiomyopathy. Circ Heart Fail. 2021;14(6):e008289. doi: 10.1161/circheartfailure.121.008289
- Greenwell AA, Gopal K, Altamimi TR, et al. Barth syndrome-related cardiomyopathy is associated with a reduction in myocardial glucose oxidation. Am J Physiol Heart Circ Physiol. 2021;320(6):H2255-H2269. doi: 10.1152/ajpheart.00873.2020
- Pang J, Bao Y, Mitchell-Silbaugh K, Veevers J, Fang X. Barth syndrome cardiomyopathy: an update. Genes (Basel). 2022;13(4):656. doi: 10.3390/genes13040656
- Hirono K, Hata Y, Imamura T, et al. Determination of genotype and phenotypes in pediatric patients with biventricular non-compaction. J Am Heart Assoc. 2024;13(21):e035614. doi: 10.1161/jaha.124.035614
- Van Wauwe J, Mahy A, Craps S, et al. PRDM16 determines specification of ventricular cardiomyocytes by suppressing alternative cell fates. Life Sci Alliance. 2024;7(12):e202402719. doi: 10.26508/lsa.202402719
- Mikryukov AA, Mazine A, Wei B, et al. BMP10 signaling promotes the development of endocardial cells from human pluripotent stem cell-derived cardiovascular progenitors. Cell Stem Cell. 2021;28(1):96-111.e7. doi: 10.1016/j.stem.2020.10.003
- Feng W, Bais A, He H, et al. Single-cell transcriptomic analysis identifies murine heart molecular features at embryonic and neonatal stages. Nat Commun. 2022;13(1):7960. doi: 10.1038/s41467-022-35691-7
- Kodo K, Ong SG, Jahanbani F, et al. iPSC-derived cardiomyocytes reveal abnormal TGF-β signalling in left ventricular non-compaction cardiomyopathy. Nat Cell Biol. 2016;18(10):1031-1042. doi: 10.1038/ncb3411
- Sun B, Rouzbehani OMT, Kramer RJ, et al. Nonsense variant PRDM16-Q187X causes impaired myocardial development and TGF-β signaling resulting in non-compaction cardiomyopathy in humans and mice. Circ Heart Fail. 2023;16(12):e010351. doi: 10.1161/circheartfailure.122.010351
- Jang J, Bentsen M, Kim YJ, et al. Endocardial HDAC3 is required for myocardial trabeculation. Nat Commun. 2024;15(1):4166. doi: 10.1038/s41467-024-48362-6
- Chen S, Liang J, Yin J, et al. Contraction-induced endocardial id2b plays a dual role in regulating myocardial contractility and valve formation. Elife. 2025;13. doi: 10.7554/eLife.101151
- Ye S, Wang C, Xu Z, et al. Impaired human cardiac cell development due to NOTCH1 deficiency. Circ Res. 2023;132(2):187-204. doi: 10.1161/circresaha.122.321398
- Farah EN, Hu RK, Kern C, et al. Spatially organized cellular communities form the developing human heart. Nature. 2024;627(8005):854-864. doi: 10.1038/s41586-024-07171-z
- Chiang IK, Humphrey D, Mills RJ, et al. Sox7-positive endothelial progenitors establish coronary arteries and govern ventricular compaction. EMBO Rep. 2023;24(10):e55043. doi: 10.15252/embr.202255043
- Adao DMT, Ching C, Fish JE, Simmons CA, Billia F. Endothelial cell-cardiomyocyte crosstalk: understanding bidirectional paracrine signaling in cardiovascular homeostasis and disease. Clin Sci. 2024;138(21):1395-1419. doi: 10.1042/cs20241084
- Vignes H, Vagena-Pantoula C, Prakash M, et al. Extracellular mechanical forces drive endocardial cell volume decrease during zebrafish cardiac valve morphogenesis. Dev Cell. 2022;57(5):598-609.e5. doi: 10.1016/j.devcel.2022.02.011
- Liang J, Jiang P, Yan S, et al. Genetically encoded tension heterogeneity sculpts cardiac trabeculation. Sci Adv. 2025;11(10):eads2998. doi: 10.1126/sciadv.ads2998
- Wang J, Brown AL, Park SK, et al. Mechanically activated snai1b coordinates the initiation of myocardial delamination for trabeculation. Nat Commun. 2025;16(1):8363. doi: 10.1038/s41467-025-62285-w
- Di Gioia G, Crispino SP, Monosilio S, et al. Left ventricular trabeculation: arrhythmogenic and clinical significance in elite athletes. J Am Soc Echocardiogr. 2024;37(6):577-586. doi: 10.1016/j.echo.2024.03.003
- Amor-Salamanca A, Santana Rodríguez A, Rasoul H, et al. Role of TBX20 truncating variants in dilated cardiomyopathy and left ventricular non-compaction. Circ Genom Precis Med. 2024;17(2). doi: 10.1161/circgen.123.004404
- Visoiu IS, Jensen B, Rimbas RC, Mihaila-Baldea S, Nicula AI, Vinereanu D. How the trabecular layer impacts on left ventricular function. J Cardiol. 2025;85(1):17-27. doi: 10.1016/j.jjcc.2024.08.008
- Li RG, Li X, Morikawa Y, et al. YAP induces a neonatal-like pro-renewal niche in the adult heart. Nat Cardiovasc Res. 2024;3(3):283-300. doi: 10.1038/s44161-024-00428-w
- Boogerd CJ, Perini I, Kyriakopoulou E, et al. Cardiomyocyte proliferation is suppressed by ARID1A-mediated YAP inhibition during cardiac maturation. Nat Commun. 2023;14(1):4716. doi: 10.1038/s41467-023-40203-2
- Vaparanta K, Jokilammi A, Paatero I, et al. STAT5b is a key effector of NRG-1/ERBB4-mediated myocardial growth. EMBO Rep. 2023;24(5):e56689. doi: 10.15252/embr.202256689
- Liu J, Jin Y, Zuo S, et al. Dot1L promotes stress-induced cardiac hypertrophy in mice via Tbx6. Circ Res. 2025;137(4):496-512. doi: 10.1161/circresaha.124.324940
- Ramchand J, Podugu P, Obuchowski N, et al. Novel approach to risk stratification in left ventricular non-compaction using a combined cardiac imaging and plasma biomarker approach. J Am Heart Assoc. 2021;10(8):e019209. doi: 10.1161/jaha.120.019209
- Burns R, Young WJ, Aung N, et al. Genetic basis of right and left ventricular heart shape. Nat Commun. 2024;15(1):9437. doi: 10.1038/s41467-024-53594-7
- Kaski JP, Norrish G, Gimeno Blanes JR, et al. Cardiomyopathies in children and adolescents: aetiology, management, and outcomes in the European Society of Cardiology EURObservational Research Programme Cardiomyopathy and Myocarditis Registry. Eur Heart J. 2024;45(16):1443-1454. doi: 10.1093/eurheartj/ehae109
- Shah L, Tam I, Nosib S. Non-compaction cardiomyopathy, Becker muscular dystrophy, neuropathy and recurrent syncope. BMJ Case Rep. 2021;14(11):e244745. doi: 10.1136/bcr-2021-244745
- Kontorovich AR. Approaches to genetic screening in cardiomyopathies: practical guidance for clinicians. JACC Heart Fail. 2023;11(2):133-142. doi: 10.1016/j.jchf.2022.11.025
- Zhou D, Li S, Sirajuddin A, et al. CMR characteristics, gene variants and long-term outcome in patients with left ventricular non-compaction cardiomyopathy. Insights Imaging. 2021;12(1):184. doi: 10.1186/s13244-021-01130-2
- Alawani SS, Paul A, Krishna MR, Ahamed H. Familial left ventricular non-compaction cardiomyopathy due to a novel mutation in the MYH7 gene. Ann Pediatr Cardiol. 2021;14(4):544-546. doi: 10.4103/apc.APC_92_20
- Law JP, Pickup L, Pavlovic D, Townend JN, Ferro CJ. Hypertension and cardiomyopathy associated with chronic kidney disease: epidemiology, pathogenesis and treatment considerations. J Hum Hypertens. 2023;37(1):1-19. doi: 10.1038/s41371-022-00751-4
- Lai AC, Bienstock SW, Sharma R, et al. A personalized approach to chronic kidney disease and cardiovascular disease: JACC review topic of the week. J Am Coll Cardiol. 2021;77(11):1470-1479. doi: 10.1016/j.jacc.2021.01.028
- Gregor Z, Kiss AR, Grebur K, et al. MR-specific characteristics of left ventricular non-compaction and dilated cardiomyopathy. Int J Cardiol. 2022;359:69-75. doi: 10.1016/j.ijcard.2022.04.026
- Sigvardsen PE, Fuchs A, Kühl JT, et al. Left ventricular trabeculation and major adverse cardiovascular events: the Copenhagen General Population Study. Eur Heart J Cardiovasc Imaging. 2021;22(1):67-74. doi: 10.1093/ehjci/jeaa110
- Paluszkiewicz J, Milting H, Kałużna-Oleksy M, et al. Left ventricular non-compaction cardiomyopathy—still more questions than answers. J Clin Med. 2022;11(14). doi: 10.3390/jcm11144135
- Hsieh PN, Shen S, Chukwurah MI, et al. Athlete’s heart revisited: historical, clinical, and molecular perspectives. Circ Res. 2025;137(2):231-254. doi: 10.1161/circresaha.125.325638
- Martinez MW, Kim JH, Shah AB, et al. Exercise-induced cardiovascular adaptations and approach to exercise and cardiovascular disease: JACC state-of-the-art review. J Am Coll Cardiol. 2021;78(14):1453-1470. doi: 10.1016/j.jacc.2021.08.003
- Casavecchia G, Gravina M, Mautone F, et al. Left ventricle non-compaction phenotype: cause or consequence? J Cardiovasc Echogr. 2024;34(1):25-28. doi: 10.4103/jcecho.jcecho_30_22
- Di Lisi D, Macaione F, Damiani F, et al. What happened to the left ventricular non-compaction cardiomyopathy? To be or not to be: this is the question. Curr Probl Cardiol. 2024;49(11):102787. doi: 10.1016/j.cpcardiol.2024.102787
- Lander BS, Hoit BD. Is it finally time to untangle elite athletes from the controversial web of left ventricular trabeculations? J Am Soc Echocardiogr. 2024;37(6):587-590. doi: 10.1016/j.echo.2024.03.013
- Klaassen S, Kühnisch J, Schultze-Berndt A, Seidel F. Left ventricular non-compaction in children: the role of genetics, morphology, and function for outcome. J Cardiovasc Dev Dis. 2022;9(7):206. doi: 10.3390/jcdd9070206
- Vaidya VR, Lyle M, Miranda WR, et al. Long-term survival of patients with left ventricular non-compaction. J Am Heart Assoc. 2021;10(2):e015563. doi: 10.1161/jaha.119.015563
- Gao S, Zhang S, Wang Z, et al. Long-term prognosis of different subtypes of left ventricular non-compaction cardiomyopathy patients: a retrospective study in China. J Cardiovasc Dev Dis. 2023;10(9):369. doi: 10.3390/jcdd10090369
- Eichhorn C, Koeckerling D, Reddy RK, et al. Risk stratification in nonischemic dilated cardiomyopathy using CMR imaging: a systematic review and meta-analysis. JAMA. 2024;332(18):1535-1550. doi: 10.1001/jama.2024.13946
- Thomas JD, Edvardsen T, Abraham T, et al. Clinical applications of strain echocardiography: a clinical consensus statement from the American Society of Echocardiography developed in collaboration with the European Association of Cardiovascular Imaging of the European Society of Cardiology. J Am Soc Echocardiogr. 2025;38(11):985-1020. doi: 10.1016/j.echo.2025.07.007
- Topriceanu CC, Al-Farih M, Joy G, et al. The cardiovascular magnetic resonance phenotype of lamin heart disease. JACC Cardiovasc Imaging. 2025;18(6):644-660. doi: 10.1016/j.jcmg.2025.01.004
- Martínez-Tittonel LE, Ciorba FR, Bayona-Huguet X, Kaplinsky E. Left ventricular non-compaction cardiomyopathy: a review of the pathophysiology, epidemiology, diagnosis, genetics, and clinical management. J Pers Med. 2025;15(10):484. doi: 10.3390/jpm15100484
- Sanna GD, Piga A, Parodi G, et al. The electrocardiogram in the diagnosis and management of patients with left ventricular non-compaction. Curr Heart Fail Rep. 2022;19(6):476-490. doi: 10.1007/s11897-022-00580-z
- Jiang J, Zhang X, Yang K, et al. Clinical phenotypes across age groups and the predictive value of NT-proBNP for ventricular arrhythmias in left ventricular non-compaction: a multicenter cohort study. J Transl Med. 2026;24(1):264. doi: 10.1186/s12967-026-07714-0
- Yang ZG, Liu ZJ, Zhang XX, Wang L. Prognostic factors associated with left ventricular non-compaction: a PRISMA-compliant meta-analysis. Medicine. 2022;101(37):e30337. doi: 10.1097/MD.0000000000030337
- Wang F, Ye B, Fang L, et al. Serum metabolomic signatures integrating sphingosine-1-phosphate and tetrahydrocortisone improve prognostic assessment in non-ischemic cardiomyopathy. Metabolomics. 2026;22(4):108. doi: 10.1007/s11306-026-02497-3
- Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022;145(18):e895-e1032. doi: 10.1161/CIR.0000000000001063
- van der Lingen ACJ, Verstraelen TE, van Erven L, et al. Assessment of ICD eligibility in non-ischaemic cardiomyopathy patients: a position statement by the Task Force of the Dutch Society of Cardiology. Neth Heart J. 2024;32(5):190-197. doi: 10.1007/s12471-024-01859-7
- van der Heide MYC, Verstraelen TE, Wilde AAM. Personalized sudden cardiac death risk prediction in genetic heart diseases: beyond one-size-fits-all. Heart Rhythm. 2026;23(1):e62-e74. doi: 10.1016/j.hrthm.2025.07.041
- Grutters LA, Christiaans I. Cascade genetic counseling and testing in hereditary syndromes: inherited cardiovascular disease as a model: a narrative review. Fam Cancer. 2024;23(2):155-164. doi: 10.1007/s10689-023-00356-x
- Imai Y, Kusano K, Aiba T, et al. JCS/JCC/JSPCCS 2024 Guideline on Genetic Testing and Counseling in Cardiovascular Disease. Circ J. 2024;88(12):2022-2099. doi: 10.1253/circj.CJ-23-0926
- Giordano G, Proukhnitzky J, Fer F, et al. Family history of sudden cardiac death as a risk marker for ventricular arrhythmias in laminopathies. Europace. 2025;27(9). doi: 10.1093/europace/euaf202
- Gerard H, Iline N, Martel H, et al. Prognosis of adults with isolated left ventricular non-compaction: results of a prospective multicentric study. Front Cardiovasc Med. 2022;9:856160. doi: 10.3389/fcvm.2022.856160
- Grasso M, Bondavalli D, Vilardo V, et al. The new 2023 ESC guidelines for the management of cardiomyopathies: a guiding path for cardiologist decisions. Eur Heart J Suppl. 2024;26(suppl 1):i1-i5. doi: 10.1093/eurheartjsupp/suae002
- Liu L, Zeng R, Ding L, et al. ABLE-SCORE, a simplified risk score for major adverse cardiovascular outcomes in left ventricular hypertrabeculation: a multicenter longitudinal cohort study. BMC Med. 2024;22(1):439. doi: 10.1186/s12916-024-03666-8
- Femia G, Zhu D, Choudhary P, et al. Long term clinical outcomes associated with CMR quantified isolated left ventricular non-compaction in adults. Int J Cardiol. 2021;328:235-240. doi: 10.1016/j.ijcard.2020.12.017
- Llerena-Velastegui J, Velastegui-Zurita S, Santander-Fuentes C, et al. Advances and challenges in the diagnosis and management of left ventricular non-compaction in adults: a literature review. Curr Probl Cardiol. 2024;49(6):102571. doi: 10.1016/j.cpcardiol.2024.102571
- Llerena-Velastegui J, Lopez-Usina A, Mantilla-Cisneros C. Prevalence, clinical manifestations, and adverse outcomes of left ventricular non-compaction in adults: a systematic review and meta-analysis. Cardiol Res. 2024;15(5):377-395. doi: 10.14740/cr1673
- Monda E, Biagini E, Blom N, et al. Current management of transition and multidisciplinary care of patients with inherited and rare cardiomyopathies in Europe: results of the European Reference Network for rare and low prevalence complex diseases of the heart. Eur Heart J Qual Care Clin Outcomes. 2025;11(7):1155-1163. doi: 10.1093/ehjqcco/qcaf055
- Perpetua EM, Palmer R, Le VT, et al. JACC: Advances Expert Panel Perspective: Shared Decision-Making in Multidisciplinary Team-Based Cardiovascular Care. JACC Adv. 2024;3(7):100981. doi: 10.1016/j.jacadv.2024.100981
- Mastrodicasa D, van Assen M, Huisman M, et al. Use of AI in Cardiac CT and MRI: A Scientific Statement from the ESCR, EuSoMII, NASCI, SCCT, SCMR, SIIM, and RSNA. Radiology. 2025;314(1):e240516. doi: 10.1148/radiol.240516
- Alahwany SH, Kamel O, Abdelghany A, Ammar A. Leveraging artificial intelligence for risk stratification of inherited cardiomyopathies in under-resourced settings. Heart Rhythm O2. 2025;6(10):1659-1667. doi: 10.1016/j.hroo.2025.07.020
- Barón JR, Bernabé G, González-Férez P, García JM, Casas G, González-Carrillo J. Improving a deep learning model to accurately diagnose LVNC. J Clin Med. 2023;12(24):7633. doi: 10.3390/jcm12247633
- Bazoukis G, Tyrovolas K, Letsas KP, et al. Predictors of fatal arrhythmic events in patients with non-compaction cardiomyopathy: a systematic review. Heart Fail Rev. 2022;27(6):2067-2076. doi: 10.1007/s10741-022-10257-3
- Nemes A. Myocardial mechanics and associated valvular and vascular abnormalities in left ventricular non-compaction cardiomyopathy. J Clin Med. 2023;13(1):78. doi: 10.3390/jcm13010078
- Hesaraki M, Bora U, Pahlavan S, et al. A novel missense variant in actin binding domain of MYH7 is associated with left ventricular non-compaction. Front Cardiovasc Med. 2022;9:839862. doi: 10.3389/fcvm.2022.839862
- Rebs S, Sedaghat-Hamedani F, Kayvanpour E, et al. RBM20 variants disrupt Ca2+ handling and metabolism in dilated and non-compaction cardiomyopathy stem cell models. Signal Transduct Target Ther. 2026;11(1):276. doi: 10.1038/s41392-026-02838-7
- Rootwelt-Norberg C, Christensen AH, Skjølsvik ET, et al. Timing of cardioverter-defibrillator implantation in patients with cardiac laminopathies—external validation of the LMNA-risk ventricular tachyarrhythmia calculator. Heart Rhythm. 2023;20(3):423-429. doi: 10.1016/j.hrthm.2022.11.024
- Rodríguez-de-Vera JM, Bernabé G, García JM, Saura D, González-Carrillo J. Left ventricular non-compaction cardiomyopathy automatic diagnosis using a deep learning approach. Comput Methods Programs Biomed. 2022;214:106548. doi: 10.1016/j.cmpb.2021.106548
- Kawel-Boehm N. Assessing left ventricular trabeculation with cardiac MRI in the world’s largest population-based cohort study. Radiology. 2024;311(1):e240544. doi: 10.1148/radiol.240544
- Lai C, Yin M, Kholmovski EG, et al. Multimodal AI to forecast arrhythmic death in hypertrophic cardiomyopathy. Nat Cardiovasc Res. 2025;4(7):891-903. doi: 10.1038/s44161-025-00679-1
- van Assen M, Tariq A, Razavi AC, Yang C, Banerjee I, De Cecco CN. Fusion modeling: combining clinical and imaging data to advance cardiac care. Circ Cardiovasc Imaging. 2023;16(12):e014533. doi: 10.1161/circimaging.122.014533
- Kanemaru K, Cranley J, Muraro D, et al. Spatially resolved multiomics of human cardiac niches. Nature. 2023;619(7971):801-810. doi: 10.1038/s41586-023-06311-1
- Chen L, Hua K, Zhang N, et al. Multifaceted spatial and functional zonation of cardiac cells in adult human heart. Circulation. 2022;145(4):315-318. doi: 10.1161/circulationaha.121.055690
- Singh M, Kumar A, Khanna NN, et al. Artificial intelligence for cardiovascular disease risk assessment in personalised framework: a scoping review. EClinicalMedicine. 2024;73:102660. doi: 10.1016/j.eclinm.2024.102660
- Guigui SA, Horvath SA, Arenas IA, Mihos CG. Cardiac geometry, function and mechanics in left ventricular non-compaction cardiomyopathy with preserved ejection fraction. J Echocardiogr. 2022;20(3):144-150. doi: 10.1007/s12574-021-00560-7
- Islam R, Hong Z. YAP/TAZ as mechanobiological signaling pathway in cardiovascular physiological regulation and pathogenesis. Mechanobiol Med. 2024;2(4). doi: 10.1016/j.mbm.2024.100085
- Gorecka M, Bissell MM, Higgins DM, Garg P, Plein S, Greenwood JP. Rationale and clinical applications of 4D flow cardiovascular magnetic resonance in assessment of valvular heart disease: a comprehensive review. J Cardiovasc Magn Reson. 2022;24(1):49. doi: 10.1186/s12968-022-00882-0
- Hammaréus F, Trenti C, Björck HM, et al. Wall shear stress measured with 4D flow CMR correlates with biomarkers of inflammation and collagen synthesis in mild-to-moderate ascending aortic dilation and tricuspid aortic valves. Eur Heart J Cardiovasc Imaging. 2024;25(10):1384-1393. doi: 10.1093/ehjci/jeae130
- Sel K, Osman D, Zare F, et al. Building digital twins for cardiovascular health: from principles to clinical impact. J Am Heart Assoc. 2024;13(19):e031981. doi: 10.1161/jaha.123.031981
- Hirono K, Takarada S, Miyao N, et al. Thromboembolic events in left ventricular non-compaction: comparison between children and adults—a systematic review and meta-analysis. Open Heart. 2022;9(1):e001908. doi: 10.1136/openhrt-2021-001908
- Santos-Cantador J, Siguero-Álvarez M, de la Pompa JL. Patterning defects in mice with defective ventricular wall maturation and cardiomyopathy. J Cardiovasc Dev Dis. 2025;12(6):224. doi: 10.3390/jcdd12060224
- Mora-Ayestarán N, Ramos-Lopez N, Ochoa JP, et al. Left Ventricular Hypertrabeculation and Prognosis in Dilated Cardiomyopathy. Circulation. 2026;154(5):440-453. doi: 10.1161/circulationaha.125.078536
