Endothelial dysfunction and exercise performance in lone atrial fibrillation or associated with hypertension or diabetes: different results with cardioversion

Abstract

Endothelial dysfunction and underperfusion of exercising muscle contribute to exercise intolerance, hyperventilation, and breathlessness in atrial fibrillation (AF). Cardioversion (CV) improves endothelial function and exercise performance. We examined whether CV is equally beneficial in diabetes and hypertension, diseases that cause endothelial dysfunction and are often associated with AF. Cardiopulmonary exercise and pulmonary and endothelial (brachial artery flow-mediated dilation) function were tested before and after CV in patients with AF alone ( n = 18, group 1) or AF with hypertension ( n = 19, group 2) or diabetes ( n = 19, group 3). Compared with group 1, peak exercise workload, O₂consumption (V̇o₂), O₂pulse, aerobic efficiency (ΔV̇o₂/ΔWR), and ratio of brachial diameter changes to flow changes (Δ D/ΔF) were reduced in group 2 and, to a greater extent, in group 3; exercise ventilation efficiency (V̇e/V̇co₂slope) and dead space-to-tidal volume ratio (Vd/Vt) were similar among groups. CV had less effect on peak workload (+7% vs. +18%), peak V̇o₂(+12% vs. +17%), O₂pulse (+33% vs. +50%), ΔV̇o₂/ΔWR (+7% vs. +12%), V̇e/V̇co₂slope (−6% vs. −12%), Δ D/ΔF (+7% vs. +10%), and breathlessness (Borg scale) in group 2 than in group 1 and was ineffective in group 3. The antioxidant vitamin C, tested in eight additional patients in each cohort, improved flow-mediated dilation in groups 1 and 2 before, but not after, CV and was ineffective in group 3, suggesting that the oxidative injury is least in lone AF, greater in hypertension with AF, and greater still in diabetes with AF. Comorbidities that impair endothelial activity worsen endothelial dysfunction and exercise intolerance in AF. The advantages of CV appear to be inversely related to the extent of the underlying oxidative injury.