Marlus Karsten

Multiparametric comparison of CARvedilol, vs. NEbivolol, vs. BIsoprolol in moderate heart failure: The CARNEBI trial

BACKGROUND Several β-blockers, with different pharmacological characteristics, are available for heart failure (HF) treatment. We compared Carvedilol (β1-β2-α-blocker), Bisoprolol (β1-blocker), and Nebivolol (β1-blocker, NO-releasing activity). METHODS Sixty-one moderate HF patients completed a cross-over randomized trial, receiving, for 2 months each, Carvedilol, Nebivolol, Bisoprolol (25.6 ± 12.6, 5.0 ± 2.4 and 5.0 ± 2.4 mg daily, respectively). At the end of each period, patients underwent: clinical evaluation, laboratory testing, echocardiography, spirometry (including total DLCO and membrane diffusion), O2/CO2 chemoreceptor sensitivity, constant workload, in normoxia and hypoxia (FiO2=16%), and maximal cardiopulmonary exercise test. RESULTS No significant differences were observed for clinical evaluation (NYHA classification, Minnesota questionnaire), laboratory findings (including kidney function and BNP), echocardiography, and lung mechanics. DLCO was lower on Carvedilol (18.3 ± 4.8*mL/min/mmHg) compared to Nebivolol (19.9 ± 5.1) and Bisoprolol (20.0 ± 5.0) due to membrane diffusion 20% reduction (*=p<0.0001). Constant workload exercise showed in hypoxia a faster VO2 kinetic and a lower ventilation with Carvedilol. Peripheral and central sensitivity to CO2 was lower in Carvedilol while response to hypoxia was higher in Bisoprolol. Ventilation efficiency (VE/VCO2 slope) was 26.9 ± 4.1* (Carvedilol), 28.8 ± 4.0 (Nebivolol), and 29.0 ± 4.4 (Bisoprolol). Peak VO2 was 15.8 ± 3.6*mL/kg/min (Carvedilol), 16.9 ± 4.1 (Nebivolol), and 16.9 ± 3.6 (Bisoprolol). CONCLUSIONS β-Blockers differently affect several cardiopulmonary functions. Lung diffusion and exercise performance, the former likely due to lower interference with β2-mediated alveolar fluid clearance, were higher in Nebivolol and Bisoprolol. On the other hand, Carvedilol allowed a better ventilation efficiency during exercise, likely via a different chemoreceptor modulation. Results from this study represent the basis for identifying the best match between a specific β-blocker and a specific HF patient.

Muscular pre-conditioning using light-emitting diode therapy (LEDT) for high-intensity exercise: a randomized double-blind placebo-controlled trial with a single elite runner

Abstract Recently, low-level laser (light) therapy (LLLT) has been used to improve muscle performance. This study aimed to evaluate the effectiveness of near-infrared light-emitting diode therapy (LEDT) and its mechanisms of action to improve muscle performance in an elite athlete. The kinetics of oxygen uptake (VO2), blood and urine markers of muscle damage (creatine kinase – CK and alanine), and fatigue (lactate) were analyzed. Additionally, some metabolic parameters were assessed in urine using proton nuclear magnetic resonance spectroscopy (1H NMR). A LED cluster with 50 LEDs (λ = 850 nm; 50 mW 15 s; 37.5 J) was applied on legs, arms and trunk muscles of a single runner athlete 5 min before a high-intense constant workload running exercise on treadmill. The athlete received either Placebo-1-LEDT; Placebo-2-LEDT; or Effective-LEDT in a randomized double-blind placebo-controlled trial with washout period of 7 d between each test. LEDT improved the speed of the muscular VO2 adaptation (∼−9 s), decreased O2 deficit (∼−10 L), increased the VO2 from the slow component phase (∼+348 ml min−1), and increased the time limit of exercise (∼+589 s). LEDT decreased blood and urine markers of muscle damage and fatigue (CK, alanine and lactate levels). The results suggest that a muscular pre-conditioning regimen using LEDT before intense exercises could modulate metabolic and renal function to achieve better performance.

Relationship between inspiratory muscle capacity and peak exercise tolerance in patients post-myocardial infarction

OBJECTIVE The study objective was to evaluate inspiratory muscle endurance in patients post-myocardial infarction without respiratory muscle weakness and its correlation with peak exercise capacity. METHODS Ten patients who recently had a myocardial infarction (recent infarction group [RIG]), 9 patients who less recently had a myocardial infarction (less recent infarction group [LIG]), and 12 healthy subjects (control group [CG]) underwent a cardiopulmonary exercise test and respiratory endurance protocol. Analysis of variance with post hoc Dunn comparisons was used to contrast performances on all tests, and Pearsons correlation was used to determine associations between variables. RESULTS The RIG presented lower maximal incremental pressure and oxygen consumption than the CG (P < .01). There was a positive correlation between peak oxygen uptake and both maximal inspiratory pressure (.68, P < .001) and maximal incremental pressure (.65, P < .001) in the RIG. CONCLUSION The RIG showed lower maximal incremental pressure, which is related to peak exercise capacity. This novel relationship in functional capacity can indicate the need to improve muscle endurance in these patients even in the absence of inspiratory muscle weakness.

Respiratory muscle endurance is limited by lower ventilatory efficiency in post-myocardial infarction patients

Background Reduced respiratory muscle endurance (RME) contributes to increased dyspnea upon exertion in patients with cardiovascular disease. Objective The objective was to characterize ventilatory and metabolic responses during RME tests in post-myocardial infarction patients without respiratory muscle weakness. Method Twenty-nine subjects were allocated into three groups: recent myocardial infarction group (RG, n=9), less-recent myocardial infarction group (LRG, n=10), and control group (CG, n=10). They underwent two RME tests (incremental and constant pressure) with ventilatory and metabolic analyses. One-way ANOVA and repeated measures one-way ANOVA, both with Tukey post-hoc, were used between groups and within subjects, respectively. Results Patients from the RG and LRG presented lower metabolic equivalent and ventilatory efficiency than the CG on the second (50± 06, 50± 5 vs. 42± 4) and third part (50± 11, 51± 10 vs. 43± 3) of the constant pressure RME test and lower metabolic equivalent during the incremental pressure RME test. Additionally, at the peak of the incremental RME test, RG patients had lower oxygen uptake than the CG. Conclusions Post-myocardial infarction patients present lower ventilatory efficiency during respiratory muscle endurance tests, which appears to explain their inferior performance in these tests even in the presence of lower pressure overload and lower metabolic equivalent.

Influência da força muscular respiratória pré-operatória na evolução clínica após cirurgia de revascularização do miocárdio

The aim of this study was to assess whether preoperative respiratory muscle strength: a) is related to other preoperative risk factors and b) represents a higher risk to postoperative pulmonary complications (PPC), higher time under mechanical ventilation (MV), intensive care unit (ICU) and hospitalization, after myocardial revascularization surgery. Twenty-four patients were studied and, after the analysis of preoperative measures taken, divided into two groups: G1, with maximum inspiratory pressure (MIP) over 70% predicted value (n=13, 54%); and G2, with MIP below 70% predicted value (n=11, 46%). At the statistical analysis, significance level was set at 5% (p 0.05). Almost half of G2 patients, who had lower MIP, also presented maximum expiratory pressure (MEP) below predicted value. As for time under MV, postoperative ICU and in-hospital times, besides number of PPC, no statistical differences were found between the groups. When compared to G1, G2 patients showed higher relative risk to developing postoperative pulmonary complications.

Avaliação da frequência cardíaca à medida de pressão expiratória máxima estática e à manobra de Valsalva em jovens saudáveis

BACKGROUND The measure of the maximal expiratory pressure (MEP) has some contraindications, as it is believed that the responses obtained in this measure are similar to the Valsalva maneuver (VM). OBJECTIVE The main purpose of this study was to evaluate the heart rate responses (HR) during the MEP and the VM measures in healthy young men into different postures aiming to identify whether and in which situation the MEP reproduces the responses obtained in the VM. Additionally we aim to estimate the workload realized during the maneuvers. METHOD Twelve healthy young men were evaluated, instructed and familiarized with the maneuvers. The VM was characterized by an expiratory effort (40 mmHg) against a manometer for 15 seconds. The MEP measure has been performed according to the American Thoracic Society. Both measures were performed at sitting and supine positions. ANOVA two-way with Holm-Sidak post-hoc test (p<0.05) was used to analyse the heart rate variation (∆HR); Valsalva index (VI); MEP index (MEPI), and the estimated workload of the maneuvers (Wtotal, Wisotime, Wtotal/∆HRtotal and Wisotime/∆HRisotime ). RESULTS The ∆HR during the maneuvers was not influenced by the supine and sitting positions. However, the ∆HR during the VM and VI were higher (supine: 47±9 bpm, 2.3±0.2; sitting: 41±10 bpm, 2.0±0.2, respectively) than ∆HR during the MEP and MEPI values (supine: 23±8 bpm, 1.5±0.2; sitting 24±8 bpm, 1.6±0.3, respectively) (p<0.001). The estimated workload of the maneuvers was statistically different (p<0.001) between the maneuvers, except to Wtotal/∆HR. CONCLUSIONS In the studied conditions the MEP does not reproduces the HR response observed in the VM in healthy young men.

Pressão expiratória positiva nas vias aéreas não reproduz as respostas de frequência cardíaca à manobra de Valsalva em homens jovens saudáveis

The expiratory positive airway pressure (EPAP) is a therapeutic resource that comprises an inspiration followed by expiration against resistance. During its application there were adjustments in the cardiovascular system, similar to those observed during the Valsalva maneuver (VM). The aim of this study was to analyze the heart rate (HR) response to VM and to different ways of EPAP application to identify if and in which condition this technique reproduces the HR response observed in the VM, in apparently healthy young men. Ten subjects (24±3 years, 25±3 kg/m2) performed randomly the VM and EPAP procedures on different days. The expiratory effort in VM was sustained for 15 s (oral pressure of 40 mmHg [53.4cm H2O]). Two EPAP techniques were employed (alone and therapeutic) against three pressure levels (10, 15 and 20 cmH2O), randomly applied. The maneuvers were repeated three times with five minutes interval. It was considered the greatest value of HR variation (DHR) for each maneuver analysis. Were used the Shapiro-Wilk test to analyze the data distribution and the ANOVA for repeated measures, with Fishers post-hoc, considering α<0.05. The DHR values observed in VM were higher (p<0.05) than those found in the different EPAP techniques, regardless the pressure level employee. The EPAP application, in these three level pressures, generates less cardiac overload and does not reproduce HR responses observed in the VM.

Circulatory and Ventilatory Power: Characterization in Patients with Coronary Artery Disease

Background Circulatory power (CP) and ventilatory power (VP) are indices that have been used for the clinical evaluation of patients with heart failure; however, no study has evaluated these indices in patients with coronary artery disease (CAD) without heart failure. Objective To characterize both indices in patients with CAD compared with healthy controls. Methods Eighty-seven men [CAD group = 42 subjects and healthy control group (CG) = 45 subjects] aged 40–65 years were included. Cardiopulmonary exercise testing was performed on a treadmill and the following parameters were measured: 1) peak oxygen consumption (VO2), 2) peak heart rate (HR), 3) peak blood pressure (BP), 4) peak rate-pressure product (peak systolic HR x peak BP), 5) peak oxygen pulse (peak VO2/peak HR), 6) oxygen uptake efficiency (OUES), 7) carbon dioxide production efficiency (minute ventilation/carbon dioxide production slope), 8) CP (peak VO2 x peak systolic BP) and 9) VP (peak systolic BP/carbon dioxide production efficiency). Results The CAD group had significantly lower values for peak VO2 (p < 0.001), peak HR (p < 0.001), peak systolic BP (p < 0.001), peak rate-pressure product (p < 0.001), peak oxygen pulse (p = 0.008), OUES (p < 0.001), CP (p < 0.001), and VP (p < 0.001) and significantly higher values for peak diastolic BP (p = 0.004) and carbon dioxide production efficiency (p < 0.001) compared with CG. Stepwise regression analysis showed that CP was influenced by group (R2 = 0.44, p < 0.001) and VP was influenced by both group and number of vessels with stenosis after treatment (interaction effects: R2 = 0.46, p < 0.001). Conclusion The indices CP and VP were lower in men with CAD than healthy controls.

Effects of carvedilol on oxygen uptake and heart rate kinetics in patients with chronic heart failure at simulated altitude

Background: The response to moderate exercise at altitude in heart failure (HF) is unknown. Methods and results: We evaluated 30 HF patients, (NYHA I-III, 25 M/5 F; 59 ± 10 years; LVEF = 39.6 ± 7.1%), in stable clinical conditions, treated with carvedilol at the maximal tolerated dose. We performed a maximal cardiopulmonary exercise test (CPET) with ramp protocol at sea level to evaluate patients’ performance and two moderate intensity constant workload CPETs (50% of peak workload) at sea level (normoxia) and simulated altitude (hypoxia). Oxygen uptake ( V · O 2 ) and heart rate (HR) on-kinetics at constant workload were assessed calculating the time constant (τ) with a monoexponential equation. V · O 2 and HR were higher in hypoxia (0.944 ± 0.233 vs 1.031 ± 0.264 l/min; 100 ± 23 vs 108 ± 22 bpm; p < 0.001). On-kinetics showed a different behavior of τ being V · O 2 faster in hypoxia (67.1 ± 23.0 vs. 56.3 ± 19.7 s; p = 0.026) and HR faster in normoxia (49.3 ± 19.4 vs. 62.2 ± 22.5 s; p = 0.018). Ten patients, who lowered oxygen kinetics in hypoxia, had greater HR increase during maximal CPET suggesting lower functional betablockade. The higher τ of V · O 2 in hypoxia is likely to be due to a peripheral effect of carvedilol mediated either by β- or α-receptor. Conclusion: HF patients performing moderate exercise at 2000 m simulated altitude have 20% V · O 2 increase without trouble at the beginning of exercise when treated with carvedilol.