Sympathetic Neural Control at Rest and During the Cold Pressor Test in Patients With Heart Failure With Preserved Ejection Fraction

Abstract

Background: We tested the hypothesis that patients with heart failure with preserved ejection fraction (HFpEF) would have greater muscle sympathetic nerve activity (MSNA) at rest and sympathetic reactivity during a cold pressor test compared with non-heart failure controls. Further, given the importance of the baroreflex modulation of MSNA in the control of blood pressure (BP), we hypothesized that patients with HFpEF would exhibit a reduced sympathetic baroreflex sensitivity.

Methods: Twenty-eight patients with HFpEF and 44 matched controls (mean±SD: 71±8 versus 70±7 years; 9 men/19 women versus 16 men/28 women) were studied. BP, heart rate, and MSNA (microneurography) were measured during 6 to 10 minutes of supine rest and the 2-minute cold pressor test. Spontaneous sympathetic baroreflex sensitivity was assessed during supine rest.

Results: Patients with HFpEF had higher resting MSNA burst frequency (39±14 versus 31±12 bursts/min; P=0.020) and lower sympathetic baroreflex sensitivity (-2.83±0.76 versus -3.57±1.19 bursts/100 heartbeats/mm Hg; P=0.019) than controls, but burst incidence was not different between groups (56±19 versus 50±20 bursts/100 heartbeats; P=0.179). During the cold pressor test, increases in MSNA indices did not differ between groups (P=0.135-0.998), but patients had a smaller increase in diastolic BP (Δ4±6 versus Δ14±11 mm Hg; P<0.001) compared with controls.

Conclusions: Despite augmented resting MSNA burst frequency, burst incidence was not significantly different between groups, and sympathetic baroreflex sensitivity was reduced in patients with HFpEF. Furthermore, patients had preserved sympathetic reactivity but attenuated diastolic BP responses during the cold pressor test. These data suggest that, during physiological stress, sympathetic reactivity is intact, but the peripheral pathway for sympathetic vasoconstriction may be impaired in HFpEF.

Keywords: aged; baroreflex; heart failure; sympathetic nervous system.

Figure 1.

Muscle sympathetic nerve activity (MSNA) burst frequency (BF, A), burst incidence (BI, B), heart rate (HR, C), brachial systolic blood pressure (SBP, D), and brachial diastolic blood pressure (DBP, E) in patients with HFpEF and controls at rest in the supine position. Circles denote the individual value for each patient with HFpEF and matched control. Values are means ± standard deviation. (a) indicates P value from the Mann-Whitney Rank Sum test. Cohen’s d or Pearson correlation coefficients (r) indicate as the effect size. hbs, heartbeats.

Figure 2.

Sympathetic baroreflex sensitivity (sBRS) calculated from muscle sympathetic nerve activity burst incidence in patients with HFpEF and controls at rest in the supine position. Circles denote the individual value for each patient with HFpEF and each control subject. Values are means ± standard deviation. Cohen’s d indicates as the effect size. hbs, heartbeats.

Figure 3.

Original tracings of electrocardiogram (ECG), beat-by-beat blood pressure (BP) and muscle sympathetic nerve activity (MSNA) from one representative patient with HFpEF and one matched control during baseline and the cold pressor test (CPT).

Figure 4.

Changes (Δ) in muscle sympathetic nerve activity (MSNA) burst frequency (BF, A), burst incidence (BI, B), total activity (TA, C), heart rate (HR, D), brachial systolic blood pressure (SBP, E), and brachial diastolic blood pressure (DBP, F) in patients with HFpEF and controls from baseline to the cold pressor test. Circles denote the individual value for each patient with HFpEF and each control subject. Values are means ± standard deviation. (a) indicates P value from the Mann-Whitney Rank Sum test. Cohen’s d or Pearson correlation coefficients (r) indicate as the effect size. hbs, heartbeats; a.u., arbitrary units.