ABC | Volume 112, Nº3, March 2019

Brief Communication Ribeiro et al Beta-blocker effect on substrate oxidation during exercise in heart failure Arq Bras Cardiol. 2019; 112(3):304-308 obtained frommedical records. The study was performed in a cross-over design, all patients participated in the same exercise sessions in random order (generated by randomizer.org ), and every single session being separated by one week (5 weeks for complete protocol). No changes in medication were made during the evaluations. The protocol was accepted by the Ethics Committee of the Montreal Heart Institute (08‑1023), all procedures in agreement with Helsinki declaration and written informed consent was obtained from all patients. Maximal cardiopulmonary exercise test Maximal cardiopulmonary exercise testing was performed according to previously published methodology. 7-9 In short, the maximal exercise protocol was performed on a cycle ergometer (Ergoline 800S, Bitz, Germany), speed was settled at 60 RPM, and the power was increased by 10 W every minute until exhaustion. Gas exchanges variables were measured breath by breath during testing and then averaged every 15s. Peak power output (PPO) was defined as the power output reached the last fully completed stage. Electrocardiographic activity was monitored continuously using an 8-lead ECG (Marquette, Missouri, USA). HIIE sessions The exercise sessions were based on previously published methodology in patients with HFrEF. 7 HIIE protocols were all prescribed at 100% PPO, based on CPET and differed in interval duration (30 seconds for protocols A and B vs 90 seconds for protocols C and D) and type of recovery (active recovery at 50% of PPO for protocols B and D vs passive recovery [0% of PPO] for protocols A and C). The exercise time and recovery were designed as 1:1 ratio. Each patient exercised for a maximal time of 30 min or until exhaustion due to fatigue, dyspnea, dizziness, or inability to maintain pedal cadence at 60 rpm. 7 Substrate oxidation and energy expenditure calculation EE was calculated usingWeir equation. 10 Substrate oxidation (CHO and lipid) was calculated from gas exchange using the Frayn equation 11 (in g/min) and with a respiratory exchange ratio values (in %) using a table of non-protein respiratory quotient. 12 Statistical analysis Results are expressed as mean ± SD for clinical characteristics and described as n (%) for beta blocker regimen (Table 1). This is an exploratory analysis from our previous studies, 7-9 all HIIE sessions that lasted more than 10 min of exercise were included. The substrates were compared in two time-points: rest and end of 10 min, both averages of 3 min measurements. EE (Kcal/min; EE), CHO and lipid oxidation, in g/min and total contribution (%), were compared during HIIE protocols using a two-way ANOVA for beta‑blocker type and time factors. The Bonferroni post‑hoc test with a p value ≤ 0.05 was used. Student`s t-test was used to compare the exercise total time between types of beta-blocker. All analyses were performed using IBM SPSS Statistics software, version 21 and Statview. Results The patients’ characteristics are described in Table 1, two patients were excluded for this analysis because did not achieve the minimum of 10 min exercise. Both groups were similar for clinical characteristics, except for systolic and diastolic blood pressures. Total exercise time was not different between the beta-blockers types (non-vasodilating group = 1377 ± 505 s; vasodilating group = 1371 ± 503 s; p = 0.962). Also, no differences were found for EE for group or interaction (group p = 0.203; time p < 000.1 and interaction p = 0.867). Differences in CHO (mg/min*Kg -1 and %; p =0.012 and p = 0.0006) and lipids (mg/min*Kg -1 and %; p = 0.0017 and p = 0.0083) were found for group and time analysis, and interaction was found just for CHO (mg/min*Kg -1 ; p = 0.03) (Figure 1). Discussion Our results showed a different effect on substrate oxidation depending on the type of beta-blocker generation. We believe that the decision of beta-blocker use can benefit the substrate oxidation during exercise and can be chosen accordingly with patients’ necessity. Because of their effect on alfa1 – adrenergic receptors, vasodilating beta-blockers like carvedilol could benefit CHO oxidation, as shown in our results for absolute and relative values, comparing to non‑vasodilation beta-blockers. Because these blocking agents can have a different effect on the circulatory and respiratory systems, previously they were known to potentially reduce exercise capacity in heart failure patients. 13 Recent evidence has shown some improvement, with a different combination of drugs, vasodilating beta-blockers demonstrated positive effect increasing insulin sensitivity comparing to non-vasodilating ones 14 and probably remodelling substrate oxidation. According to literature, HIIE requires greater energetic demand from the muscular system, 15 and therefore should be accompanied by higher CHO oxidation. The increasing use of HIIE in a clinical context is due to its superiority compared to continuous exercise training to improve VO 2peak , with similar effects on left ventricular function, safety and exercise compliance. 6,16 In our previous work, 9 we showed substrate oxidation differences between HIIE protocols, and the individual variances lead us to explore the potential muscle metabolism differences that could be related to beta- blocker use. Also, there is still little data available on substrate oxidation and the effect of pharmacological agents in heart failure patients, 3 especially during high-intensity exercise, so we believe we are providing interesting initial data to raise interest on the subject. The major limitation of our study is the sample size, but we believe appropriate for a pilot study to encourage further investigation. Also, because of the lack of a placebo group, we cannot investigate the actual effect of beta‑blocker on substrate oxidation, but differences between different regimens. Since more than 90% of our HFrEF patients are under some beta-block medication, we did not consider the possibility to suspend or change patients’ medication. 305