Sympathetic Neural Overdrive and Diminished Exercise Capacity in Reduced Ejection Fraction Heart Failure Related to Anthracycline- Based Chemotherapy.

Abstract

Cardiotoxicity is the most worrying cardiovascular alteration in patients treated with chemotherapy. To improve the understanding regarding the cardiotoxicity, we studied whether: 1) patients with cardiac dysfunction related to anthracycline-based chemotherapy have augmented sympathetic nerve activity and decreased exercise capacity and 2) these responses are similar to those observed in patients with heart failure caused by other etiologies. Sixteen patients with heart failure with reduced ejection fraction related to anthracycline-based chemotherapy with or without chest radiation (HFrEFCA), 10 patients with heart failure with reduced ejection not related to cancer therapy (HFrEF), and 16 age-and body mass index (BMI)-matched healthy controls were studied. Left ventricular ejection fraction (LFEF, Echocardiography), peak oxygen consumption (peak V̇O2, cardiopulmonary exercise test), muscle sympathetic nerve activity (MSNA, microneurography) and forearm blood flow (FBF, venous occlusion plethysmography) were measured. We found that peak oxygen consumption peak V̇O2 and LVEF were significantly reduced in patients with HFrEFCA compared to controls (P<0.0001) but similar to those found in HFrEFCA patients. The sympathetic nerve activity burst frequency and incidence were significantly higher in patients with HFrEFCA than in controls (P<0.0001). No differences were found between HFrEF and HFrEFCA patients. Peak V̇O2 was inversely associated with MSNA burst frequency (r=-0.53, P=0.002) and burst incidence (r=-0.38, P=0.01), and directly associated with LVEF (r=0.71, P<0.0001). Taken together, we conclude that patients who develop heart failure due to anthracycline-based chemotherapy have sympathetic neural overdrive and reduced exercise capacity. In addition, these physiological changes are similar to those observed in patients with HFrEF.