The Prognostic Value of TyG Index and Right Ventricular Function in HFpEF Patients With Chronic Kidney Disease

BACKGROUND: Right ventricular (RV) dysfunction and insulin resistance (IR) are associated with poor outcomes in heart failure with preserved ejection fraction (HFpEF). We hypothesized that the triglyceride-glucose (TyG) index, as a surrogate for IR, and RV function parameters would independently predict adverse outcomes in HFpEF, with potentially enhanced prognostic value in patients with chronic kidney disease (CKD), where RV impairment is more prevalent. METHODS: We prospectively enrolled 395 HFpEF patients admitted between October 2023 and October 2024. Two-dimensional RV free-wall longitudinal strain (2D-RVFWLS), three-dimensional RV ejection fraction (3D-RVEF), and TyG index were measured at baseline. The composite endpoint was cardiovascular (CV) death or HF rehospitalization. Multivariable Cox proportional hazards and Fine-Gray competing risk models were applied to identify predictors of adverse outcomes. Model performance was assessed using the C-index, category-free net reclassification improvement (cfNRI), and integrated discrimination improvement (IDI). RESULTS: In the overall cohort, lower 2D-RVFWLS and 3D-RVEF, along with higher TyG index, were associated with worse outcomes. RV dysfunction was more frequent and pronounced in the CKD group (lower absolute 2D-RVFWLS [16.7% vs. 19.5%, P<0.001]). During a median follow-up of 18.3 months, 158 patients experienced adverse outcomes. In multivariable Cox models, lower estimated glomerular filtration rate (eGFR) and smaller mitral E/A were independently associated with adverse outcomes. Adding the TyG index improved the base model (optimism-corrected ΔC-index = +0.013; apparent ΔC = +0.036), while the combination of TyG and 2D-RVFWLS achieved the highest predictive accuracy and significantly enhanced reclassification (cfNRI +0.362, IDI +0.396, both p < 0.001), particularly in the CKD subgroup. CONCLUSIONS: In HFpEF, the TyG index and 2D-RVFWLS provide independent prognostic value superior to 3D-RVEF. Their combination offers robust risk stratification, particularly for the vulnerable phenotype of HFpEF with CKD. TRIAL REGISTRATION: Retrospectively registered in the Chinese Clinical Trial Registry, registration number pending.