Prognostic Value of Dynamic FDG PET-Derived Myocardial Glucose Metabolism in Ischemic Cardiomyopathy with Supportive External Gene-Expression Analysis

Figures

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  Figure 1. Kaplan–Meier curves for MACE-free survival stratified by myocardial glucose metabolism and metabolic heterogeneity. (A) Overall survival curves comparing low versus high MRGlu, categorized by the median value. (B) Among patients with low MRGlu, further stratification by metabolic heterogeneity using CoV (high vs. low, based on the median). (C) Among patients with high MRGlu, corresponding stratification by CoV (high vs. low, based on median). Abbreviations: MACE, major adverse cardiovascular event; CoV, coefficient of variation; MRGlu, myocardial metabolic rate of glucose.

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  Figure 2. Kaplan–Meier curves for MACE-free survival stratified into four metabolic phenotypes defined by global MRGlu and CoV: high MRGlu/high CoV, high MRGlu/low CoV, low MRGlu/high CoV, and low MRGlu/low CoV. The number-at-risk table below the plot indicates the number of patients remaining under observation and free of MACE at each specified follow-up time point. Abbreviations: MACE, major adverse cardiovascular event; CoV, coefficient of variation; MRGlu, myocardial metabolic rate of glucose.

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  Figure 3. Differential expression of glucose-handling genes in ischemic and dilated cardiomyopathy. Forest plot showing log2 fold change (±95% confidence interval) of key myocardial glucose-metabolism genes in ischemic cardiomyopathy (ICM; black) and dilated cardiomyopathy (DCM; gray) compared with non-failing hearts (NF). Abbreviations: AKT1, AKT serine/threonine kinase 1; DCM, dilated cardiomyopathy; HK1, hexokinase 1; HK2, hexokinase 2; ICM, ischemic cardiomyopathy; INSR, insulin receptor; IRS1, insulin receptor substrate 1; NF, non-failing heart; PFKM, phosphofructokinase, muscle type; PKM, pyruvate kinase M1/2; PRKAA1, protein kinase AMP-activated catalytic subunit alpha 1 (AMPKα1); SLC2A1, solute carrier family 2 member 1 (GLUT1); SLC2A4, solute carrier family 2 member 4 (GLUT4).

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  Figure 4. Heatmap of glucose-related gene expression in slow- and fast-progression heart failure. Each column represents a patient (numbers indicate sample ID), with the top horizontal bar denoting clinical group: blue for slow progression and orange for fast progression. Each row corresponds to a glucose metabolism-related gene. Values are shown as per-gene z-scores, with red indicating expression above the mean and blue indicating expression below the mean for that gene across all patients. Abbreviations: AKT1, AKT serine/threonine kinase 1; HK1, hexokinase 1; HK2, hexokinase 2; INSR, insulin receptor; IRS1, insulin receptor substrate 1; PFKM, phosphofructokinase, muscle type; PKM, pyruvate kinase M1/2; PRKAA1, protein kinase AMP-activated catalytic subunit alpha 1 (AMPKα1); SLC2A1, solute carrier family 2 member 1 (GLUT1); SLC2A4, solute carrier family 2 member 4 (GLUT4).

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  Figure 5. Expression of SLC2A1 (A), HK1 (B), IRS1 (C), and PKM (D) in slow- and fast-progression heart failure. Box–whisker plots showing expression levels in patients with slow progression (n = 9) and fast progression (n = 9) of heart failure. Boxes indicate the interquartile range (IQR) with the median indicated as a horizontal line; whiskers extend to the minimum and maximum observed values. The connector line with p value represents the result of the Mann–Whitney U test. Abbreviations: HK1, hexokinase 1; IRS1, insulin receptor substrate 1; PKM, pyruvate kinase M1/2; SLC2A1, solute carrier family 2 member 1 (GLUT1).

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  Figure 6. (A) Box–whisker plot of the composite 4-gene score in fast- and slow-progression heart failure. (B) Transplant-free survival stratified by high versus low composite 4-gene scores.