Evidence of an Exaggerated Muscle Metaboreflex Response in Heart Failure with Preserved Ejection Fraction
Authors: Clifton Heather Lynn , Ratchford Stephen M , Vranish Jennifer R , Trinity Joel D , Ryan John J , Richardson Russell S , Fadel Paul J , Sarma Satyam , Haykowsky Mark , Wray Walter 
Published: November 2023

BackgroundExercise intolerance is the primary chronic symptom in heart failure patients with preserved ejection fraction (HFpEF), and often persists even with optimized treatment. Though there are many mechanisms that may contribute to this deficit, disease‐related changes in the muscle metaboreflex may play a role. Indeed, it has been previously shown that in heart failure with reduced ejection fraction (HFrEF), input from group III/IV muscle afferents contributes to the development of fatigue and exercise intolerance. Therefore, the purpose of this study was to examine metaboreflex modulation of heart rate (HR) and mean arterial pressure (MAP) in HFpEF patients.MethodsEight HFpEF patients (6M, 2F; age 67 ± 4 yrs; BMI 35 ± 3 kg/m2; ejection fraction 63 ± 3%) and seven healthy controls (4M, 3F; age 59 ± 3 yrs; BMI 30 ± 1 kg/m2) participated in this study. Patients were studied under their normal pharmacotherapy. After 30 min of supine rest, participants performed 2 min of isometric handgrip exercise at 30% and 40% of maximal voluntary contraction (MVC), followed by 2 min of post‐exercise circulatory occlusion (PECO) to isolate the muscle metaboreflex response. HR (3‐lead ECG) and arterial blood pressure (Finapres Medical Systems BV) were measured continuously, and the last 30 sec of exercise and PECO was averaged to determine peak changes in HR and MAP.ResultsBaseline HR and MAP were not different between HFpEF and controls (70 ± 7 vs. 68 ± 5 bpm; 97 ± 4 vs. 103 ± 5 mmHg, respectively). At 30% MVC, comparable ΔHR were observed between groups during handgrip (6 ± 1 vs. 4 ± 2 bpm, HFpEF vs. control) and PECO (2 ± 1 vs. 2 ± 1 bpm, HFpEF vs. control). While ΔMAP was similar between groups during handgrip (15 ± 2 vs. 14 ± 3 mmHg, HFpEF vs. control), HFpEF patients exhibited a greater ΔMAP during PECO (16 ± 2 vs. 8 ± 3 mmHg, HFpEF vs. control, p<0.05). At 40% MVC, ΔHR was not significantly different between HFpEF and controls during handgrip (7 ± 3 vs. 12 ± 2 bpm, respectively) or PECO (1 ± 1 vs. 1 ± 2 bpm, respectively). Similarly, ΔMAP at 40% MVC was comparable between the groups during handgrip (24 ± 5 vs. 24 ± 2 mmHg, HFpEF vs. control), whereas there was a trend towards a greater ΔMAP during PECO in the HFpEF patients (24 ± 5 vs. 16 ± 3 mmHg, p=0.16).ConclusionsWhile the overall pressor response during handgrip was comparable between groups, a notable elevation in blood pressure was observed during PECO in the HFpEF patients. It is important to note that these differences occurred with the patients maintaining their normal pharmacotherapy, which often includes antihypertensive agents. These preliminary findings suggest that the muscle metaboreflex is exaggerated in patients with HFpEF, and this may be involved in the exercise intolerance observed in this patient population.Support or Funding InformationFunded in part by the National Institutes of Health (HL118313) and the U.S. Department of Veterans Affairs (RX001697, RX001418, E6910R)