Normal sympathetic neural but blunted cardiovascular responses during static handgrip exercise in heart failure with preserved ejection fraction
Authors: Washio Takuro , Takeda Ryosuke , Hissen Sarah , Akins John , D'Souza Andrew , Manabe Kazumasa , Hearon Jr Christopher , MacNamara James , Sarma Satyam , Levine Benjamin , Fadel Paul , Fu Qi 
Published: May 2023

Background: Exercise intolerance is a hallmark of heart failure, which significantly impacts activities of daily living and quality of life. In heart failure with reduced ejection fraction, exercise intolerance is associated with sympathetic nervous system hyperactivity during exercise. Whether this is also true in heart failure with preserved ejection fraction (HFpEF) is unknown. Therefore, we hypothesized that patients with HFpEF would have augmented sympathetic neural responses to exercise. Methods: Thirty-four patients with HFpEF (19 women, 70±7 [SD] yrs) and 24 age-matched healthy controls (14 women, 70±6 yrs) were studied. Mean arterial pressure (MAP; finger photoplethysmography calibrated with brachial blood pressure [BP]), heart rate (HR; lead II electrocardiogram), cardiac output (CO; derived from the Windkessel model), total peripheral resistance (TPR=MAP/CO), and muscle sympathetic nerve activity (MSNA, microneurography) were measured during 3 min of supine baseline, static handgrip (SHG) exercise at 40% of maximal voluntary contraction (MVC) force until fatigue, and 2 min of post-exercise circulatory arrest (PECA). Sympathetic transduction was estimated using diastolic BP divided by MSNA burst incidence. Results: Patients with HFpEF had a smaller MVC (24±8 vs. 30±9 kg, P=0.020) and a shorter time to fatigue during SHG (162±67 vs. 210±80 sec, P=0.012) than controls. However, there were consistent results across subgroups analyzed according to matched MVC or time to fatigue during SHG. Baseline MSNA burst frequency was higher in HFpEF patients compared with controls (36±16 vs. 24±13 bursts/min,　 P=0.005); however, there were no differences in MSNA responses (Δ) to SHG and PECA between the groups (SHG peak: 19±14 in HFpEF vs. 19±12 bursts/min in controls, P=0.984; PECA: 8±13 vs. 6±7 bursts/minute, P=0.596). Increases in MAP, HR, and TPR from baseline to peak SHG were smaller in patients with HFpEF than in controls (all P<0.05), while the increase in CO was not different between the groups ( P=0.101). In contrast, ΔMAP, ΔHR and ΔCO from baseline to PECA were not different between the groups (all P>0.05), but ΔTPR remained lower in patients with HFpEF than controls ( P=0.023). The transduction of MSNA burst incidence into diastolic BP was lower in patients with HFpEF compared with controls throughout data collection ( P=0.010). Conclusions: Contrary to our hypothesis, patients with HFpEF have normal sympathetic neural reactivity during SHG exercise despite a higher baseline. The blunted pressor response may be attributed to impaired sympathetic transduction to stress rather than a change in sympathetic neural responsiveness during exercise in HFpEF. Supported by the National Institutes of Health (P01HL137630 and R01HL091078) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.