Arterial Stiffening With Exercise in Patients With Heart Failure and Preserved Ejection Fraction

Abstract

BACKGROUND Aortic stiffening and reduced nitric oxide (NO) availability may contribute to the pathophysiology of heart failure with preserved ejection fraction (HFpEF). OBJECTIVES We assessed indices of arterial stiffness at rest and during exercise in subjects with HFpEF and hypertensive controls, to examine their relationship to cardiac hemodynamics and determine whether exertional arterial stiffening can be mitigated by inorganic nitrite. METHODS Twenty-two hypertensive controls and 98 HFpEF subjects underwent hemodynamic exercise testing with simultaneous expired gas analysis. Invasively measured radial artery pressure waveforms were converted to central aortic waveforms by transfer function to assess integrated measures of pulsatile aortic load, including arterial compliance, resistance, elastance, and wave reflection. RESULTS Arterial load and wave reflections were similar in HFpEF and controls at rest. During submaximal exercise, HFpEF subjects displayed reduced total arterial compliance and higher effective arterial elastance despite similar mean arterial pressures to controls. This was directly correlated with higher ventricular filling pressures and depressed cardiac output reserve (both p <0.0001). With peak exercise, increased wave reflections impaired compliance, resistance and elastance were observed. A subset of HFpEF subjects (n = 52) received sodium nitrite or placebo in a 1:1 double blind, randomized fashion. Compared to placebo, nitrite decreased aortic wave reflections at rest and improved arterial compliance, elastance, and improved central hemodynamics during exercise. CONCLUSION Abnormal pulsatile aortic loading during exercise occurs in HFpEF independent of hypertension, and is correlated with classical hemodynamic derangements that develop with stress. Inorganic nitrite mitigates arterial stiffening with exercise and improves hemodynamics, indicating that arterial stiffening with exercise is at least partially reversible. Further study is required to test effects of agents that target the NO pathway in reducing arterial stiffness in HFpEF.

Haemodynamic and metabolic phenotyping of hypertensive patients with and without heart failure by combining cardiopulmonary and echocardiographic stress test

“…These findings should be considered hypothesis‐generating and tested in more extensive, longitudinal trials evaluating the transition from HT to HFpEF. Alternative techniques should be performed to confirm our results, including the assessment of central aortic pressure, arterial stiffness and myocardial fibrosis . HFpEF represents a complex clinical syndrome to which different cardiovascular risk factors and diseases are related.…”

“…Systemic vascular resistance (SVR) was calculated as mean arterial pressure – measured as a function of HR – divided by CO and multiplied by 80 during each activity level . We assessed the pulsatile arterial load measuring pulse pressure (PP) and total arterial compliance index (TACI), which is a linear approximation of the pressure–volume relationship for the arterial system and was calculated as SV index/PP . We calculated the LVEDV/E/e′ ratio as a surrogate of LV compliance during exercise .…”

Brachial pulse pressure in acute heart failure. Results of the Heart Failure Registry

“…7 Similarly, in HFpEF, an altered ventricular-vascular coupling reserve may determine a lesser increase in LVEF and in PP amplitude compared to normal subjects. 33 Also, the presence of atrial fibrillation may at least in part contribute to a narrower PP in acute HF probably because of a reduction in atrial contribution to LV filling with a consequent further reduction in stroke volume. This may also explain the opposite negative prognostic behaviour of low PP and high pulse wave velocity, a direct measure of arterial stiffness, observed in patients with chronic HFrEF.…”

An integrative translational approach to study heart failure with preserved ejection fraction: a position paper from the Working Group on Myocardial Function of the European Society of Cardiology

“…Increased wall stress in turn raises end‐systolic elastance and volume sensitivity while transmitted pulsatile pressure evokes endothelial dysfunction (ED). Increased arterial stiffening with exercise has been recently shown in HFpEF . Measures of LVH, left atrial size, DD but also natriuretic peptides are age‐dependent, which suggests that ageing represents to some extent physiological HFpEF.…”