BLOOD PRESSURE AND HEART RATE EFFECTS OF ANODAL TDCS ON LEFT TEMPORO-INSULAR CORTEX DURING CONSTANT AEROBIC EXERCISE IN HEART FAILURE PATIENTS
DOI: Pending DOI
Synopsis
Problem: Patients with HFrEF face significant hemodynamic risks during aerobic exercise, requiring strategies to ensure safe training.
Methods: In a double-blind, randomized, controlled trial, 22 HFrEF patients received active anodal tDCS over the left temporo-insular area (2 mA, 20 min) or sham stimulation during a single session of continuous aerobic exercise.
Results: Active tDCS significantly attenuated systolic blood pressure (SBP) at the end of exercise compared to sham (122±16 vs 140±19 mmHg, p=0.04). No significant differences were observed in diastolic blood pressure or heart rate between groups.
Conclusion: Acute left temporo-insular tDCS prevents excessive SBP elevation during exercise in HFrEF patients, potentially reducing cardiac afterload during physical exertion.
Background
Heart failure with reduced ejection fraction (HFrEF) is characterized by limited functional capacity due to impaired cardiac function, autonomic dysfunction, and inflammatory alterations1. Exercise-based rehabilitation is a cornerstone of HFrEF treatment, with strong evidence for functional improvement and reduced readmission2. However, barriers such as low adherence and resistance to improvement remain significant3. Studies in healthy volunteers have explored transcranial direct current stimulation (tDCS) effects on performance and hemodynamics4-6. Okano et al.4 found that anodal temporo-insular tDCS in amateur cyclists reduced perceived exertion and delayed cardiac vagal withdrawal during incremental exercise. Farinatti et al.6 reported increased post-exercise hypotension after tDCS over the perceptual area in healthy subjects. Given the hemodynamic risks of aerobic exercise in HFrEF patients, monitoring is essential for safe training. Therefore, this study aimed to evaluate the acute hemodynamic response to anodal temporo-insular tDCS during a single session of continuous aerobic exercise in patients with HFrEF. We hypothesized that stimulation attenuates blood pressure and heart rate responses to physical exertion in this population.
Methods
This is a double-blind, randomized, controlled study and part of the ELETRIC trial⁷. It was conducted at the cardiopulmonary physiology laboratory of Hospital Universitário Getúlio Vargas (UFAM, Manaus, Brazil), approved by the ethics committee (IRB#64652122.0.0000.5020) and registered in the Brazilian Clinical Trials Registry (#RBR-10w787j6). Volunteers were evaluated by a cardiologist and underwent a symptom-limited cardiopulmonary exercise test using a HandyMet metabolic cart (MDI, Brazil) and a CG 4 electromagnetic cycle ergometer (Inbramed, Brazil) following guidelines⁸. The workload at the anaerobic threshold was selected for exercise. After 2 adaptation sessions, outcomes were assessed in the third session. The exercise protocol consisted of 5min rest, 5min warm-up, 15min exercise at the anaerobic threshold and/or Borg 3 (moderate intensity), and 5min active cool-down on the cycle ergometer (Inbramed, Brazil). Anodal tDCS using a Focus Research device (NKL, Brazil) was applied over the left temporo-insular area with the cathodic electrode on the right supraorbital area (Figure 1) at 2mA for 20min, with a 30s ramp-up and ramp-down (during warm-up and exercise). Sham used a 30s ramp-up, 1 min of stimulation, then ramp-down. Systolic and diastolic blood pressure by aneroid sphygmomanometer and heart rate by finger pulse oximeter (Nonin, USA) were assessed. Statistical analysis: independent t-test, chi-square, ANOVA two-way mixed with Tukey's post hoc test (Jamovi and GraphPad Prism 9.0 were used), and p < 0.05 was accepted as statical significant.
Results
A total of 146 volunteers were contacted, of whom 27 were selected. Ultimately, 22 volunteers participated in the study and were divided into Sham (n=10) and tDCS (n=12) groups. Both the volunteer and the therapist were blinded. Volunteers had the following characteristics: age (Sham: 54±13 years; tDCS: 55±8 years, p=0.870), women (Sham: 30%; tDCS: 42%, p=0.571), BMI (Sham: 30.4±2.9 kg/m²; tDCS: 27.9±3.9 kg/m², p=0.107), LVEF (Sham: 34±6%; tDCS: 30±9%, p=0.107), VO2peak (Sham: 22.3±8.5 ml·kg⁻¹·min⁻¹; tDCS: 27±6.8 ml·kg⁻¹·min⁻¹, p=0.151), peak workload (Sham: 90.8±26.6 W; tDCS: 95.2±29.5 W, p=0.722), 6MWT (Sham: 494±64 m; tDCS: 461±99 m, p=0.368), NYHA III (Sham: 80%; tDCS: 59%, p=0.277). Patients showed no differences in comorbidities. There were also no differences in medication use. All patients were using beta-blockers, and sacubitril-valsartan was very common (Sham: 70%; tDCS: 75%, p=0.793). During training, a lower systolic blood pressure (SBP) was observed at the end of exercise, with a significant interaction (p=0.04, η²p=0.12; moderate to large effect size). The Sham group reached 140±19 mmHg of SBP, while the tDCS group reached 122±16 mmHg of SBP. Interestingly, resting SBP values were 110±11 mmHg in the Sham group and 109±15 mmHg in the tDCS group. Regarding diastolic blood pressure, there was no change at the end of exercise between groups. For heart rate, a similar increase was observed between groups, with no detectable impact of tDCS. Exercise workload was similar between groups, with a mean of 40±16 W in the Sham group and 42±16 W in the tDCS group (p=0.789).
Discussion
This is the first study to evaluate BP and HR behavior during physical exercise in patients with HFrEF during tDCS stimulation. The study demonstrated that left temporo-insular anode stimulation can prevent a large increase in SBP during continuous aerobic exercise. Integrative physiology studies have shown that there is an interaction of peripheral type III/IV receptors in the pressor response during physical exercise and central mediation of various areas of the central nervous system, mainly the left insula9,10. Evidence shows that the peripheral system is important in pressor hyperactivity during exercise in patients with HF11. The current study likely can regulate peripheral activation, even with patients using drugs that control BP behavior. Even though there was no negative behavior with the use of tDCS during exercise, it is still not known whether the pressor response effect is positive in this type of patient. We know that lower BP may be due to decreased cardiac output or vascular resistance, and to evaluate this question, further studies will be necessary8. However, due to the lack of symptomatology or BP increase followed by a pressure drop (common in output alterations), this was not observed in the study. Finally, one hypothesis that can be postulated is that the lack of BP increase during submaximal exercise may be a strategy to reduce the impact of afterload and decrease cardiac O₂ consumption in patients with coronary artery disease, favoring higher training loads in this population.
Disclosures
The authors declare no financial disclosures
References
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