TY - JOUR
T1 - Sympathetic neural overdrive and diminished exercise capacity in reduced ejection fraction heart failure related to anthracycline-based chemotherapy
AU - Rodrigues, Amanda G.
AU - Sales, Allan R.K.
AU - Faria, Diego
AU - Fonseca, Silvia M.R.
AU - Bond, Marina M.K.
AU - Jordão, Camila P.
AU - de Souza, Francis R.
AU - Bittar, Cristina S.
AU - Dos Santos, Marília H.H.
AU - Sarmento, Adriana O.
AU - Negrao, Marcelo V.
AU - Hajjar, Ludhmila A.
AU - Negrão, Carlos E.
AU - Filho, Roberto Kalil
N1 - Publisher Copyright:
Copyright © 2023 the American Physiological Society.
PY - 2023/11
Y1 - 2023/11
N2 - 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 control subjects were studied. Left ventricular ejection fraction (LVEF, echocardiography), peak oxygen consumption (peak V_ O2, 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 V_ O2 and LVEF were significantly reduced in patients with HFrEFCA compared with that of control subjects (P < 0.0001) but similar to those found in patients with HFrEFCA. The sympathetic nerve activity burst frequency and incidence were significantly higher in patients with HFrEFCA than that in control subjects (P < 0.0001). No differences were found between patients with HFrEF and HFrEFCA. Peak V_ O2 was inversely associated with MSNA burst frequency (r ¼ -0.53, P ¼ 0.002) and burst incidence (r ¼ -0.38, P ¼ 0.01) and directly associated with LVEF (r ¼ 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.
AB - 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 control subjects were studied. Left ventricular ejection fraction (LVEF, echocardiography), peak oxygen consumption (peak V_ O2, 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 V_ O2 and LVEF were significantly reduced in patients with HFrEFCA compared with that of control subjects (P < 0.0001) but similar to those found in patients with HFrEFCA. The sympathetic nerve activity burst frequency and incidence were significantly higher in patients with HFrEFCA than that in control subjects (P < 0.0001). No differences were found between patients with HFrEF and HFrEFCA. Peak V_ O2 was inversely associated with MSNA burst frequency (r ¼ -0.53, P ¼ 0.002) and burst incidence (r ¼ -0.38, P ¼ 0.01) and directly associated with LVEF (r ¼ 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.
KW - chemotherapy
KW - exercise capacity
KW - heart failure
KW - sympathetic nerve activity
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U2 - 10.1152/ajpheart.00476.2023
DO - 10.1152/ajpheart.00476.2023
M3 - Article
C2 - 37682239
AN - SCOPUS:85184908583
SN - 0193-1849
VL - 325
SP - H1126-H1132
JO - American Journal of Physiology - Endocrinology and Metabolism
JF - American Journal of Physiology - Endocrinology and Metabolism
IS - 5
ER -