Cardiac autonomic associations on exercise and ambulatory capacity in individuals with lower-extremity artery disease
Authors: Roque Marcal I , Cornelis N , Buys R , Fourneau I , Ciolac EG , Cornelissen V 
Published: May 2021

Abstract

Funding Acknowledgements
Type of funding sources: Foundation. Main funding source(s): This work was in part supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP #2019/19596-7), and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq #303399/2018-0).

OnBehalf
Exercise and Chronic Disease Research Laboratory - Bauru, Brazil; Research Group for Cardiovascular Rehabilitation - Leuven, Belgium.

INTRODUCTION
Lower-extremity artery disease (LEAD) characterized by progressive atherosclerotic build-up in leg arteries is becoming increasingly prevalent, affecting more than 200 million people worldwide. In line with other atherosclerotic disorders, LEAD is often associated with autonomic dysfunction as evidenced by a reduced heart rate variability (HRV). To date, little is known on the impact of cardiac autonomic function on exercise and ambulatory capacity.

PURPOSE
We aimed to investigate whether autonomic function is associated with ambulatory capacity and exercise capacity in patients with LEAD.

METHODS
Thirty-four patients (age≥17 years) diagnosed with LEAD (ankle brachial index: ABI ≤ 0.9 and/or 20% decrease after a maximal treadmill test) suffering from intermittent claudication (Rutherford I-III) were recruited in the PROSECO-IC trial. Patients were grouped based on beta-blocker medication (β-blocker and non β-blocker). Intervals between R waves (i-RR) obtained by heart rate (HR) signal were acquired beat-to-beat via a digital telemetry system (Polar®️ H10) during 15 min of supine rest and were used for 5-minute HRV analysis. Time domain indexes (mean i-RR, SNDD, pNN50%), and frequency domains (high frequency band (HF), low frequency (LF, very LF (VLF)) and the ratio (LF/HF). HRV was analyzed in absolute (abs), normalized (nu) and log units (log). Ambulatory capacity was assessed by means of a submaximal treadmill test, graded maximal treadmill test using Gardner protocol (GTM) and 6 minutes walking test (6MWT); exercise capacity was assessed by means of a graded maximal cardiopulmonary exercise test (HR, blood pressure (BP) and peak oxygen uptake (VO2peak)) at resting, 2 minutes, and peak of exercise.

RESULTS
Pearson test showed that sympathetic modulation indexes were moderate associated with pain free distance in GTM (LF/HF: r = 0.52, p = 0.04), and pain free time in 6MWT (LFlog: r=-0.62, p = 0.01; VLF: r=-0.52, p = 0.04), respectively, in patients without β-blocker. Similar HR associations with HRV (time and frequency domain) were observed during submaximal treadmill test and cardiopulmonary exercise test (p ≤ 0.05). Test-t demonstrated a significantly increased response intra-groups in HR and BP during both tests (p ≤ 0.05). Average BP were positive associated with the earlier stages of the cardiopulmonary test (resting to 2 min) with LFlog (r = 0.70, p= &lt;0.001) in β-blocker while non-β-blocker were associated from 2 min to peak with LFabs (r = 0.67, p= &lt;0.001) and LF/HF (r = 0.52, p = 0.03).

CONCLUSION
Sympathetic modulation was correlated with a longer pain free walking capacity in non-β-blockers. Yet, individuals treated by -β-blockers showed an earlier sympathetic modulation through exercise pressor response during the first stages of cardiopulmonary exercise compared to non-β-blockers with LEAD.