NPPB and heart failure: Critically, EFHD1 expression showed a significant negative correlation with clinical indicators of heart failure (NT-proBNP and E/e' ratio).<h4>Conclusion</h4>Our integrated analysis reveals CHCHD1 and EFHD1 as key mitochondrial genes linking mitochondrial dysfunction to immune dysregulation in HFpEF, offering new insights into its molecular mechanisms and potential therapeutic targets.