Central and peripheral determinants of impaired cardiorespiratory fitness in patients with symptomatic atrial fibrillation

Background

Cardiorespiratory fitness (CRF) measured by peak oxygen uptake (VO2peak) is often impaired in patients with atrial fibrillation (AF). The contribution of central cardiac versus peripheral abnormalities to lower CRF has not been established.

Purpose

To determine the relative central and peripheral contributors to impaired CRF in patients with AF.

Methods

Symptomatic AF patients referred for catheter ablation, underwent maximal cardiopulmonary exercise testing (CPET) on an upright cycle ergometer to determine VO2peak. Patients were dichotomised into low (<18mL/kg/min) and preserved (≥ 18mL/kg/min) CRF groups. To examine central and peripheral contributions, patients completed semi-supine exercise echocardiography with simultaneous gas exchange assessment (CPET-echo) to evaluate cardiac output (CO), heart rate (HR), stroke volume (SV) and arterial-venous oxygen difference (a-vO2) during exercise.

Results

A total of 105 patients were included (mean age 68±10 years; BMI 29±4kg/m2; 31% female). Fifty-eight patients were classified as preserved CRF (24.5 ± 5.8mL/kg/min), and 47 as low CRF (14.4. ± 2.35 mL/kg/min; p<0.001). Metabolic intensity during sub-maximal CPET-echo was similar between groups (RER 1.00±0.07 vs 1.02±0.09; p=0.2).

Exercise CO was lower in the low CRF group and remained independently associated with CRF status after adjustment for rhythm and sex (β = -1.32L/min, p= 0.030). This difference was driven by reduced peak HR (98.8 ± 23 vs 105 ± 17 bpm, p= 0.008), which remained independently associated with CRF status after adjustment (β = -10.3bpm, p = 0.007), whereas SV was not independently different (β = -1.4mL, p= 0.79).

Exercise a-vO2 difference was lower in the low CRF group (p= 0.004)). Haemoglobin concentration was independently associated with exercise a-vO2 difference (β = 0.89mL/dL per g/dL, p<0.001). In a multivariable analysis adjusted for age and sex, peripheral oxygen extraction explained 41.5% of the variance in oxygen uptake during CPET-echo, compared with 24.7% for heart rate and 23.4% for stroke volume.

Conclusion

Amongst patients with symptomatic AF, impaired CRF is largely a consequence of impaired O₂ extraction in the periphery in addition to blunted cardiac output. This limitation is a consequence of lower O₂ carrying capacity, in addition to potential abnormalities in skeletal muscle. Therapeutic interventions that improve these components may reduce exertional symptoms in this cohort.