Congestive heart failure with preserved ejection fraction is associated with severely impaired dynamic Starling mechanism

Congestive heart failure with preserved ejection fraction is associated with severely impaired dynamic Starling mechanism. J Appl Physiol 110: 964-971, 2011. First published February 10, 2011; doi:10.1152/japplphysiol.00826.2010.- Sedentary aging leads to increased cardiovascular stiffening, which can be ameliorated by sufficient amounts of lifelong exercise training. An even more extreme form of cardiovascular stiffening can be seen in heart failure with preserved ejection fraction (HFpEF), which comprises ̃40̃50% of elderly patients diagnosed with congestive heart failure. There are two major interrelated hypotheses proposed to explain heart failure in these patients: 1) increased left ventricular (LV) diastolic stiffness and 2) increased arterial stiffening. The beat-to-beat dynamic Starling mechanism, which is impaired with healthy human aging, reflects the interaction between ventricular and arterial stiffness and thus may provide a link between these two mechanisms underlying HFpEF. Spectral transfer function analysis was applied between beat-to-beat changes in LV end-diastolic pressure (LVEDP; estimated from pulmonary artery diastolic pressure with a right heart catheter) and stroke volume (SV) index. The dynamic Starling mechanism (transfer function gain between LVEDP and the SV index) was impaired in HFpEF patients (n = 10) compared with healthy agematched controls (n = 12) (HFpEF: 0.23 ± 0.10 ml.m^-2.mmHg-1 and control: 0.37 ± 0.11 ml.m-2.mmHg^-1, means ± SD, P = 0.008). There was also a markedly increased (3-fold) fluctuation of LV filling pressures (power spectral density of LVEDP) in HFpEF patients, which may predispose to pulmonary edema due to intermittent exposure to higher pulmonary capillary pressure (HFpEF: 12.2 ± 10.4 mmHg² and control: 3.8 ± 2.9 mmHg², P = 0.014). An impaired dynamic Starling mechanism, even more extreme than that observed with healthy aging, is associated with marked breath-by-breath LVEDP variability and may reflect advanced ventricular and arterial stiffness in HFpEF, possibly contributing to reduced forward outputand pulmonary congestion.