The Impact of Diabetes on Haemodynamic and Cardiometabolic Responses in Heart Failure With Preserved Ejection Fraction

Aims: Heart failure with preserved ejection (HFpEF) and diabetes mellitus (DM) commonly co-exist. However, it is unclear if DM modifies the haemodynamic and cardiometabolic phenotype in patients with HFpEF. We aimed to interrogate the haemodynamic and cardiometabolic effects of DM in HFpEF. Methods: We compared the haemodynamic and metabolic profiles of non-DM patients and patients with DM–HFpEF at rest and during exercise using right heart catheterisation and mixed venous blood gas analysis. Results: Of 181 patients with HFpEF, 37 (20%) had DM. Patients with DM displayed a more adverse exercise haemodynamic response vs HFpEF alone (mean pulmonary arterial pressure: 47 mmHg [interquartile range {IQR} 42–55] vs 42 [38–47], p<0.001; workload indexed pulmonary capillary wedge pressure indexed: 0.80 mmHg/W [0.44–1.23] vs 0.57 [0.43–1.01], p=0.047). HFpEF–DM patients had a lower mixed venous oxygen saturation at rest (70% [IQR 66–73] vs 72 [69–75], p=0.003) and were unable to enhance O₂ extraction to the same extent (Δ-28% [-33 to -15] vs -29 [-36 to -21], p=0.029), this occurred at a 22% lower median workload. Resting mixed venous lactate levels were higher in those with DM (1.5 mmol/L [IQR 1.1–1.9] vs 1 [0.9–1.3], p<0.001), and during exercise indexed to workload (0.09 mmol/L/W [0.06–0.13] vs 0.08 [0.05–0.11], p=0.018). Conclusion: Concurrent diabetes and HFpEF was associated with greater metabolic responses at rest, with enhanced wedge driven pulmonary hypertension and relative lactataemia during exercise without appropriate augmentation of oxygen consumption.