Pre-load Corrected Dynamic Starling Mechanism in Patients with Heart Failure with Preserved Ejection Fraction

The beat-to-beat dynamic Starling mechanism (DSM), the dynamic modulation of stroke volume (SV) due to breath-to-breath changes in left ventricular end-diastolic pressure (LVEDP), reflects ventricular-arterial coupling. The purpose of this study was to test whether LVEDP-SV relationship remained impaired in HFpEF patients after normalization of LVEDP. Right heart catheterization and model-flow analysis of the arterial pressure waveform were performed while preload was manipulated using lower body negative pressure to alter LVEDP. The DSM was compared at similar levels of LVEDP between HFpEF patients (N=10) and age-matched healthy controls (N=12): (HFpEF vs. controls: 10.9±3.8 vs. 11.2±1.3 mmHg, P=0.72). Transfer function analysis between diastolic pulmonary artery pressure (PAD) representing dynamic changes in LVEDP versus SV-index was applied to obtain gain and coherence of the DSM. The DSM gain was significantly lower in HFpEF patients than in the controls, even at a similar level of LVEDP (0.46±0.19 vs. 0.99±0.39 ml/m²/mmHg, P=0.0011). Moreover, the power spectral density of PAD, the input variability, was greater in the HFpEF group than the controls (0.75±0.38 vs. 0.28±0.26 mmHg2, P=0.003). Conversely, the power spectral density of SV-index, the output variability, was not different between the groups (P=0.77). There was no difference in the coherence, which confirms the reliability of the linear transfer function between the 2-groups (0.71±0.13 vs. 0.77±0.19, P=0.34). The DSM gain in HFpEF patients is impaired compared to age-matched controls even at a similar level of LVEDP, which may reflect intrinsic LV diastolic dysfunction and incompetence of ventricular-arterial coupling.

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