Arterial Stiffening With Exercise in HFpEF Patients

Study Questions:

Is arterial stiffness increased with exercise in patients with heart failure and preserved ejection fraction (HFpEF) compared to hypertensive controls without HF, and can this exertional arterial stiffening be mitigated by inorganic nitrite?


The study cohort was comprised of 98 HFpEF subjects and 22 hypertensive controls. All had hemodynamic assessment on supine exercise with simultaneous expired gas analysis. Radial artery pressure waveforms, measured invasively, were converted to central aortic waveforms by transfer function to assess integrated measures of pulsatile aortic load, including arterial compliance (total arterial compliance index, ml/mm Hg ∙ m2), resistance (SVRI, dyne-sec ∙ m2/cm5), elastance (Ea Indexed, mm Hg ∙ m2/ml), and wave reflection. The study investigators assessed the effects of sodium nitrite, a novel nitric oxide donor, on arterial load in HFpEF. Differences between HFpEF and controls at rest and exercise were tested using Chi square, Student’s t-test or Wilcoxon rank sum test.


Compared to controls, subjects with HFpEF were older and heavier. HFpEF subjects had higher N-terminal pro–B-type natriuretic peptide levels, increased E/e’ ratio, and higher right ventricular systolic pressure on echocardiography, consistent with increased filling pressures. Peak exercise capacity was roughly 40% lower in HFpEF subjects compared to controls (peak VO2 8.6 ± 2.3 vs. controls 14.8 ± 3.8 ml/min/kg, p < 0.0001). The arterial load and wave reflections were similar in both HFpEF and controls at rest, but on submaximal exercise (20 W), HFpEF subjects displayed reduced total arterial compliance (controls 0.70 ± 0.22 vs. HFpEF 0.50 ± 0.18, p = 0.0001) and higher effective arterial elastance (controls 2.64 ± 0.71 vs. HFpEF 3.26 ± 0.92, p = 0.004) 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 elastance (controls 2.45 ± 0.71 vs. HFpEF 3.16 ± 0.92, p = 0.003), resistance (controls 1473 ± 440 vs. HFpEF 1923 ± 494, p = 0.0007), and compliance (controls 0.77 ± 0.24 vs. HFpEF 0.55 ± 0.21, p = 0.0006). 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 (rest +0.06 ± 0.04, p = 0.1; exercise +0.10 ± 0.02, p = 0.0005), elastance (rest -0.13 ± 0.20, p = 0.5; exercise -0.38 ± 0.14, p = 0.008), and improved central hemodynamics during 20 W exercise.


The authors concluded that abnormal pulsatile aortic loading during exercise occurs in HFpEF independent of hypertension, and is correlated with classical hemodynamic derangements that develop with stress. They also concluded that inorganic nitrites ameliorate arterial stiffening with exercise and improve hemodynamics.


This is an important study because it suggests that arterial stiffening is a key factor in HFpEF patients. The findings of this study should result in the investigation of the utility of ‘destiffening’ agents in patients with HFpEF.

Clinical Topics: Anticoagulation Management, Diabetes and Cardiometabolic Disease, Geriatric Cardiology, Heart Failure and Cardiomyopathies, Noninvasive Imaging, Prevention, Acute Heart Failure, Heart Failure and Cardiac Biomarkers, Echocardiography/Ultrasound, Exercise, Hypertension

Keywords: Arterial Pressure, Blood Pressure, Cardiac Output, Compliance, Echocardiography, Exercise, Geriatrics, Heart Failure, Hypertension, Natriuretic Peptide, Brain, Peptide Fragments, Sodium Nitrite, Vascular Diseases, Vascular Stiffness

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