Carlos Eduardo Negrão

Long-term breast cancer (BC) survivors previously treated with doxorubicin- and trastuzumab-based chemotherapy show reduced muscle metaboreflex activation, which partly explains attenuated pressor and sympathetic neural responses to exercise in this population. Importantly, these findings shed light on the blunted exercise-induced blood pressure increase observed in long-term BC survivors.

Patients with long COVID, even 2 yr after SARS-CoV-2 infection, exhibited sympathetic neural overdrive, aortic stiffening, endothelial dysfunction, cardiac morphofunctional changes, diminished aerobic exercise capacity, increased circulating endothelial cell-derived EVs, decreased antioxidant activity, and increased oxidant activity. Moreover, we showed that the reduced aerobic exercise capacity was associated with sympathetic neural outflow, vascular dysfunction, cardiac morphofunctional alterations, and increased circulating oxidative stress.

Background Evidence on the safety and anti-ischemic effects of exercise-based cardiac rehabilitation (ECR) in patients with refractory angina (RA) remains limited. Objective To evaluate the safety and efficacy of a 12-week ECR program in patients with RA, focusing on improvements in symptoms, functional capacity, and ischemic burden assessed by exercise stress echocardiography (ESE). Methods This was a prospective, single-center, randomized controlled trial evaluating a 12-week ECR program in patients with RA. Forty-five patients were randomized to either the rehabilitation group (RG), receiving ECR, or the control group (CG), receiving medical treatment (MT) alone. Outcomes included mortality, cardiovascular events, anginal symptoms, and parameters from ESE and cardiopulmonary exercise testing (CPET). Statistical significance was set at p < 0.05. Results In ESE, exercise duration was significantly greater in RGpost (after ECR) compared to RGpre (before ECR) (∆ = 63.24 ± 19.87 s; p < 0.01). Angina quantification was lower in RGpost than in RGpre, CGpost (after MT alone), and CGpre (before MT alone) (∆ = –1.64 ± 0.48 n, p < 0.01; –3.10 ± 0.97 n, p < 0.01; and –2.73 ± 0.92 n, p = 0.01, respectively). The angina threshold was higher in RGpost than in RGpre and CGpost (∆ = 89.66 ± 33.16 s, p = 0.04; and 111.76 ± 42.25 s, p = 0.04, respectively). Improvement in ischemic burden on ESE was demonstrated by increased time to ischemic threshold in RGpost compared to RGpre, CGpost, and CGpre (∆ = 83.23 ± 21.84 s, p < 0.01; 98.44 ± 35.11 s, p = 0.03; and 109.34 ± 34.00 s, p < 0.01, respectively). In CPET, RGpost showed increased exercise duration (∆ = 104.54 ± 28.09 s, p < 0.01) and distance covered (∆ = 131.23 ± 30.48 m, p < 0.01) compared to RGpre. No significant differences in VO2 were observed between groups. Two patients in the CG group died. One patient in the RG group experienced prolonged angina during training. No significant differences in major cardiovascular events were observed between groups. Conclusion The 12-week ECR-program was safe and effective in improving exercise duration, distance covered and ischemic burden on ESE in patients with RA.

Resumo Fundamento As evidências sobre a segurança e os efeitos anti-isquêmicos da reabilitação cardíaca baseada em exercício (RCE) em pacientes com angina refratária (AR) ainda são limitadas. Objetivo Avaliar a segurança e a eficácia de um programa de RCE de 12 semanas em pacientes com AR, com foco na melhora dos sintomas, da capacidade funcional e da carga isquêmica avaliada por ecocardiografia de estresse com exercício (EEE). Métodos Estudo prospectivo, randomizado, controlado, e unicêntrico, que avaliou um programa de RCE de 12 semanas em pacientes com AR. Quarenta e cinco pacientes foram randomizados para o grupo de reabilitação (GR), que recebeu RCE, ou para o grupo controle (GC), que recebeu apenas tratamento médico. Os desfechos avaliados incluíram mortalidade, eventos cardiovasculares, sintomas anginosos e parâmetros da EEE e do teste cardiopulmonar de exercício (TCPE). O nível de significância estatística adotado foi p < 0,05. Resultados Na EEE, a duração do exercício foi significativamente maior no GRpós (após a RCE) em comparação com GRpré (antes da RCE) (∆ = 63,24 ± 19,87 s; p < 0,01). A quantificação de angina foi menor no GRpós em comparação ao GRpré, ao GCpós (após tratamento médico isolado) e ao GCpré (antes do tratamento médico isolado) (∆ = –1,64 ± 0,48 n, p < 0,01; -3,10 ± 0,97 n, p < 0,01; e -2,73 ± 0,92 n, p = 0,01, respectivamente). O limiar de angina foi maior em GRpós em comparação ao GRpré e ao GRpós (∆ = 89,66 ± 33,16 s, p = 0,04; e 111,76 ± 42,25 s, p = 0,04, respectivamente). A melhora na carga isquêmica na EEE foi demonstrada pelo aumento do tempo até o limiar isquêmico GRpós em comparação ao GCpré, e ao GCpré e GRpós (∆ = 83,23 ± 21,84 s, p < 0,01; 98,44 ± 35,11 s, p = 0,03; e 109,34 ± 34,00 s, p < 0,01, respectivamente). No TCPE, o GRpós apresentou aumento na duração do exercício (∆ = 104,54 ± 28,09 s; p < 0,01) e na distância percorrida (∆ = 131,23 ± 30,48 m; p < 0,01) em comparação ao GRpré. Não foram observadas diferenças significativas no VO2 entre os grupos. Dois pacientes do grupo CG faleceram. Um paciente do GR apresentou angina prolongada durante o treinamento. Não houve diferenças significativas nos eventos cardiovasculares maiores entre os grupos. Conclusão O programa de RCE de 12 semanas foi seguro e eficaz na melhora da duração do exercício, da distância percorrida e da carga isquêmica na EEE em pacientes com AR.

Partial coherence analysis has been instrumental in demonstrating, for the first time, that cerebral blood velocity (CBv) is continuously influenced, not only by fluctuations in mean arterial pressure but also muscle sympathetic nervous activity (MSNA), leading to similar dynamic responses at rest and during different sympathoexcitatory maneuvers in healthy subjects. Modeling the temporal relationship between MSNA and CBv opens new opportunities for advancing knowledge regarding the role of the sympathetic nervous system in the regulation of cerebral circulation in health and disease.

Purpose Central and peripheral chemoreceptors are hypersensitized in patients with heart failure with reduced ejection fraction. Whether this autonomic alteration occurs in patients with heart failure with preserved ejection fraction (HFpEF) remains little known. We test the hypothesis that the central and peripheral chemoreflex control of muscle sympathetic nerve activity (MSNA) is altered in HFpEF. Methods Patients aged 55–80 years with symptoms of heart failure, body mass index ≤ 35 kg/m², left ventricular ejection fraction > 50%, left atrial volume index > 34 mL/m², left ventricular early diastolic filling velocity and early diastolic tissue velocity of mitral annulus ratio (E/e′ index) ≥ 13, and BNP levels > 35 pg/mL were included in the study (HFpEF, n = 9). Patients without heart failure with preserved ejection fraction (non-HFpEF, n = 9), aged-paired, were also included in the study. Peripheral chemoreceptors stimulation (10% O₂ and 90% N₂, with CO₂ titrated) and central chemoreceptors stimulation (7% CO₂ and 93% O₂) were conducted for 3 min. MSNA was evaluated by microneurography technique, and forearm blood flow (FBF) by venous occlusion plethysmography. Results During hypoxia, MSNA responses were greater (p < 0.001) and FBF responses were lower in patients with HFpEF (p = 0.006). Likewise, MSNA responses during hypercapnia were higher (p < 0.001) and forearm vascular conductance (FVC) levels were lower (p = 0.030) in patients with HFpEF. Conclusions Peripheral and central chemoreflex controls of MSNA are hypersensitized in patients with HFpEF, which seems to contribute to the increase in MSNA in these patients. In addition, peripheral and central chemoreceptors stimulation in patients with HFpEF causes muscle vasoconstriction.

Long-term Hodgkin lymphoma (HL) survivors have impaired muscle blood flow responses during mental stress and decreased maximal aerobic capacity. Supervised aerobic exercise training combined with local strength exercises restores muscle blood flow responses during mental stress and maximal aerobic capacity in these survivors. These findings provide evidence of safety and effectiveness of exercise training in HL survivors. Moreover, they highlight the importance of exercise training in the treatment of this set of patients.

Background: COVID-19 has become a dramatic health problem during this century. In addition to high mortality rate, COVID-19 survivors are at increased risk for cardiovascular diseases 1-year after infection. Explanations for these manifestations are still unclear but can involve a constellation of biological alterations. We hypothesized that COVID-19 survivors compared with controls exhibit sympathetic overdrive, vascular dysfunction, cardiac morpho-functional changes, impaired exercise capacity, and increased oxidative stress. Methods: Nineteen severe COVID-19 survivors and 19 well-matched controls completed the study. Muscle sympathetic nerve activity (microneurography), brachial artery flow-mediated dilation and blood flow (Doppler-Ultrasound), carotid-femoral pulse wave velocity (Complior), cardiac morpho-functional parameters (echocardiography), peak oxygen uptake (cardiopulmonary exercise testing), and oxidative stress were measured ~3 months after hospital discharge. Complementary experiments were conducted on human umbilical vein endothelial cells cultured with plasma samples from subjects. Results: Muscle sympathetic nerve activity and carotid-femoral pulse wave velocity were greater and brachial artery flow-mediated dilation, brachial artery blood flow, E/e′ ratio, and peak oxygen uptake were lower in COVID-19 survivors than in controls. COVID-19 survivors had lower circulating antioxidant markers compared with controls, but there were no differences in plasma-treated human umbilical vein endothelial cells nitric oxide production and reactive oxygen species bioactivity. Diminished peak oxygen uptake was associated with sympathetic overdrive, vascular dysfunction, and reduced diastolic function in COVID-19 survivors. Conclusions: Our study revealed that COVID-19 survivors have sympathetic overactivation, vascular dysfunction, cardiac morpho-functional changes, and reduced exercise capacity. These findings indicate the need for further investigation to determine whether these manifestations are persistent longer-term and their impact on the cardiovascular health of COVID-19 survivors.