Development and validation of a long-term prognostic prediction nomogram for ICM on the basis of polymorphism and plasma level of Mfn2

Abstract Objective To investigate the association between Mitofusin2 (Mfn2) genotype and its plasma levels with long-term prognosis of ischemic cardiomyopathy (ICM), and to establish and validate a predictive nomogram for long-term prognosis of ICM, thereby providing a theoretical basis for risk assessment of ICM. Methods This study included 1092 ICM patients who underwent follow-up at 3, 6, 12, 24, 36, 48, and 60 months after first diagnosed with ICM. Based on follow-up outcomes, patients were categorized into survival and death groups. All patients were randomly divided into a training set (n = 764) and a validation set (n = 328). Univariate Cox regression analysis was performed on the training set. Variables with P < 0.1 in univariate analysis underwent Lasso regression analysis. Multivariate Cox regression models were constructed using selected variables by lasso regression analysis.followed performed model validation. Performance was evaluated using ROC curves, calibration curves, and decision curve analysis (DCA). Results Multivariate Cox regression analysis revealed that plasma Mfn2 levels, heart rate, serum sodium, treatment with PCI or CABG, beta-blocker use, LVDD, and mutations at SNP loci rs1042842, rs2295281, and rs2236054 were independent predictors of long-term ICM prognosis ( P < 0.05). The nomogram constructed based on these findings demonstrated excellent discriminatory ability in both the training and validation cohorts (AUCs: 0.824 [1 year], 0.809 [3 years], and 0.877 [5 years] in the training set; and 0.808 (1 year), 0.767 (3 years), and 0.790 (5 years) in the validation set). The model demonstrated good consistency between observed and predicted values, indicating strong clinical usefulness. Conclusion Elevated plasma Mfn2 levels and genetic mutations at rs223605 may represent protective factors influencing long-term prognosis in ICM, whereas mutations at rs1042842 and rs2295281 may constitute risk factors for poor long-term outcomes in ICM.