Ioannis D. Laoutaris

Inspiratory muscle training using an incremental endurance test alleviates dyspnea and improves functional status in patients with chronic heart failure.

Background The benefits of inspiratory muscle training (IMT) in patients with chronic heart failure (CHF) have been inadequately studied. Design and methods Using a prospective, age and sex-matched controlled study, we investigated 35 patients with moderate to severe CHF (NYHA class II–III and left ventricular ejection fraction 24.4 ± 1.3% [mean ± SEM]). An incremental respiratory endurance test using a fixed respiratory workload was provided by software with an electronic mouth pressure manometer interfaced with a computer. The training group (n = 20) exercised at 60% of individual sustained maximal inspiratory pressure (SMIP) and the control group (n = 15) at 15% of SMIP. All patients exercised three times weekly for 10 weeks. Pulmonary function, exercise capacity, dyspnea and quality of life were assessed, pre- and post-training. Results The training group significantly increased both maximum inspiratory pressure (Pimax), (111 ± 6.8 versus 83 ± 5.7cmH2O, P<0.001), and SMIP (527822 ± 51358 versus 367360 ± 41111 cmH2O/sec × 10-1, P < 0.001). Peak VO2 increased after training (17.8 ± 1.2 versus 15.4 ± 0.9 ml/kg/min, P< 0.005), as did the six-minute walking distance (433 ± 16 versus 367 ± 22 meters, P < 0.001). Perceived dyspnea assessed using the Borg scale was reduced for both the treadmill (12.7 ± 0.57 versus 14.2 ± 0.48, P < 0.005) and the walking (9 ± 0.48 versus 10.5 ± 0.67, P< 0.005) exercise tests and the quality of life score was also improved (21.1 ± 3.5 versus 25.2 ± 4, P < 0.01). Resting heart rate was significantly reduced with training (77 ± 3.3 versus 80 ± 3beats/min, P < 0.05). The control group significantly increased Pimax (86.6 ± 6.3 versus 78.4 ± 6.9cmH2O, P < 0.05), but decreased SMIP (274972 ± 32399 versus 204661 ± 37184cmH2O/sec × 101, P < 0.005). No other significant effect on exercise capacity, heart rate, dyspnea, or quality of life was observed in this group. Conclusion Inspiratory muscle training using an incremental endurance test, successfully increases both inspiratory strength and endurance, alleviates dyspnea and improves functional status in CHF.

Benefits of physical training on exercise capacity, inspiratory muscle function, and quality of life in patients with ventricular assist devices long-term postimplantation

Background: Capacity to exercise may not be fully restored in patients with heart failure even in the long term after ventricular assist device (VAD) implantation. The benefits of exercise training in patients with VAD are unknown. Design and methods: Fifteen patients, aged 38.3 ± 15.9 years, bridged to heart transplantation with left ventricular assist device or biventricular assist device were randomized at a ratio of 2 : 1 to a training group (TG, n = 10) or a control group (n = 5), 6.3 ± 4 months after implantation. Both the groups were advised to walk 30–45 min/day. TG also underwent moderate-intensity aerobic exercise using a bike or treadmill for 45 min, three to five times a week, combined with high-intensity inspiratory muscle training using a computer-designed software to respiratory exhaustion, two to three times a week for 10 weeks. The patients were tested using cardiopulmonary exercise testing, 6-min walk test, spirometry and electronic pressure manometer for inspiratory muscle strength (Pimax) and endurance (sustained Pimax) measurement. Quality of life was assessed with the Minnesota Living with Heart Failure questionnaire. Results: TG improved peak oxygen consumption (19.3 ± 4.5 vs. 16.8 ± 3.7 ml/kg per min, P = 0.008) and VO2 at ventilatory threshold (15.1 ± 4.2 vs. 12 ± 5.6 ml/kg per min, P = 0.01), whereas the ventilation/carbon dioxide slope decreased (35.9 ± 5.6 vs. 40 ± 6.5, P = 0.009). The 6-min walk test distance increased (527 ± 76 vs. 462 ± 88 m, P = 0.005) and quality of life was improved (38.2 ± 11.6 vs. 48.9 ± 12.8, P = 0.005), as well as Pimax (131.8 ± 33 vs. 95.5 ± 28cmH2O, P = 0.005), sustained Pimax (484 ± 195 vs. 340 ± 193cmH2O/s/10 3 , P = 0.005), and inspiratoty lung capacity (2.4 ± 0.9 vs. 1.7 ± 0.7 L, P = 0.008) were improved. No significant changes were noted in the control group. Conclusion: Our findings indicate that exercise training may improve the functional status of VAD recipients even at a later period after implantation and thus, may have additional importance in cases of destination therapy.

Immune response to inspiratory muscle training in patients with chronic heart failure.

Background The effects of inspiratory muscle training on plasma cytokines, C-reactive protein and the soluble apoptosis mediators Fas and Fas ligand in chronic heart failure are unknown. Design and methods Thirty-eight patients with chronic heart failure, age 57 ± 2 years, New York Heart Association classification II-III, were assigned to either a high intensity training group (n = 15, age 53±2 years) exercised at 60% of sustained maximal inspiratory pressure, or a low intensity training group (n = 23, age 59 ± 2 years), exercised at 15% of sustained maximal inspiratory pressure, three times per week for 10 weeks. Patients in the high intensity training group and low intensity training group were matched for age, sex and New York Heart Association functional class. Plasma levels of tumor necrosis factor (TNF)-α, soluble TNF receptor I, interleukin-6, C-reactive protein, soluble apoptosis mediators Fas and Fas ligand were measured at baseline and at post-inspiratory muscle training. Pulmonary function was assessed by spirometry, exercise capacity by a cardiopulmonary exercise test and the 6 min walk test, whereas dyspnea by the Borg scale after the 6 min walk test. Results High intensity training group improved inspiratory muscle strength (105.1 ± 4.9 vs. 79.8 ± 4.7 cmH2O, P < 0.001), sustained maximal inspiratory pressure (504.5 ± 39.7 vs. 312.5 ± 26.5cmH2O/s/103, P<0.001), forced vital capacity (98.9 ± 3.9 vs. 96 ± 3.3%, P<0.05), peak Vo2 (19.4 ± 1.2 vs. 17.3 ± 0.9 ml/kg per min, P<0.01), 6 min walk test distance (404.3 ± 11.9 vs. 378.2 ± 10.4 m, P<0.01) and dyspnea (8.0 ± 0.4 vs. 9.2 ± 0.4, P<0.01). Circulating TNF-α, soluble TNF receptor I, interleukin-6, C-reactive protein, soluble apoptosis mediators Fas and Fas ligand were not significantly altered. Low intensity training group increased only the inspiratory muscle strength (90.3 ± 5.9 vs. 80.2 ± 5cmH2O, P<0.01). Comparison between groups was significant for soluble TNF receptor I change (high intensity training group, 5.8 ± 0.49 vs. 6.1 ± 0.42; low intensity training group, 8.4 ± 0.6 vs. 7.8 ± 0.6, P<0.01). Conclusion A high intensity inspiratory muscle training program resulted in improvement in functional status of chronic heart failure patients compared with low intensity inspiratory muscle training. Improvement in exercise capacity was not associated with an anti-inflammatory effect, although a beneficial influence on soluble TNF receptor I was recorded. Possible reasons include inadequate level of muscle mass exercise and the low pretraining New York Heart Association class. Eur J Cardiovasc Prev Rehabil 14:679-685

Effects of inspiratory muscle training on autonomic activity, endothelial vasodilator function, and N-terminal pro-brain natriuretic peptide levels in chronic heart failure.

PURPOSE To assess the effects of inspiratory muscle training (IMT) on autonomic activity, endothelial function, and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in patients with chronic heart failure. METHODS Using age- and sex-matched controlled study, 23 patients (mean left ventricular ejection fraction 29 ± 2%) were assigned to either a high-intensity training group (n = 14), New York Heart Association (NYHA) class II (n = 9)/III (n = 5), or a low-intensity training group (n = 9), NYHA class II (n = 6)/III (n = 3), exercising at 60% and 15% of sustained maximum inspiratory pressure (SPImax), respectively, 3 times per week for 10 weeks. Before and following IMT, patients underwent cardiopulmonary exercise testing and dyspnea evaluation on exertion. Sympathovagal balance was assessed by heart rate variability (HRV) from 24-hour electrocardiogram and endothelial function, using venous occlusion plethysmography. Serum levels of NT-proBNP were determined. RESULTS High-intensity training group improved maximum inspiratory pressure (PImax, 105.4 ± 5.3 vs 79.1 ± 5 cm H2O, P = .001), SPImax (511 ± 42 vs 308 ± 28 cm H2O/sec/103, P = .001), peak oxygen consumption (19 ± 1.2 vs 17.1 ± 0.7 mL.kg−1min−1, P = .01) and dyspnea (17.6 ± 0.2 vs 18.1 ± 0.1, P = .02). Endothelium-dependent vasodilation, HRV, and NT-proBNP levels were not altered. Low-intensity training group increased only the PImax (97.6 ± 11.3 vs 84.2 ± 8.7 cm H2O, P = .03). CONCLUSIONS Improvement in dyspnea and exercise tolerance after IMT were not associated with changes in markers of HRV, endothelial function, and NT-proBNP in patients with mild to moderate chronic heart failure. Further studies on the effects of IMT in advanced heart failure would be worthwhile.

Benefits of combined aerobic/resistance/inspiratory training in patients with chronic heart failure. A complete exercise model? A prospective randomised study ☆

BACKGROUND We hypothesised that combined aerobic training (AT) with resistance training (RT) and inspiratory muscle training (IMT) could result in additional benefits over AT alone in patients with chronic heart failure (CHF). METHODS Twenty-seven patients, age 58 ± 9 years, NYHA II/III and LVEF 29 ± 7% were randomly assigned to a 12-week AT (n=14) or a combined AT/RT/IMT (ARIS) (n=13) exercise program. AT consisted of bike exercise at 70-80% of max heart rate. ARIS training consisted of AT with RT of the quadriceps at 50% of 1 repetition maximum (1RM) and upper limb exercises using dumbbells of 1-2 kg as well as IMT at 60% of sustained maximal inspiratory pressure (SPI(max)). At baseline and after intervention patients underwent cardiopulmonary exercise testing, echocardiography, evaluation of dyspnea, muscle function and quality of life (QoL) scores. RESULTS The ARIS program as compared to AT alone, resulted in additional improvement in quadriceps muscle strength (1RM, p=0.005) and endurance (50%1 RM × number of max repetitions, p=0.01), SPI(max) (p<0.001), exercise time (p=0.01), circulatory power (peak oxygen consumption × peak systolic blood pressure, p=0.05), dyspnea (p=0.03) and QoL (p=0.03). CONCLUSIONS ARIS training was safe and resulted in incremental benefits in both peripheral and respiratory muscle weakness, cardiopulmonary function and QoL compared to that of AT. The present findings may add a new prospective to cardiac rehabilitation programs of heart failure patients whilst the clinical significance of these outcomes need to be addressed in larger randomised studies.

Combined aerobic/inspiratory muscle training vs. aerobic training in patients with chronic heart failure: The Vent-HeFT trial: a European prospective multicentre randomized trial

Vent‐HeFT is a multicentre randomized trial designed to investigate the potential additive benefits of inspiratory muscle training (IMT) on aerobic training (AT) in patients with chronic heart failure (CHF).

Thyroid hormone signalling is altered in response to physical training in patients with end-stage heart failure and mechanical assist devices: potential physiological consequences?

OBJECTIVES The present study investigated the potential of the failing myocardium of patients with ventricular assist devices (VAD) to respond to physiological growth stimuli, such as exercise, by activating growth signalling pathways. This may be of therapeutic relevance in identifying novel pharmacological targets for therapies that could facilitate recovery after VAD implantation. METHODS Twenty-two patients bridged to heart transplantation (HTx) with VAD were included in the study. A group of patients underwent moderate intensity aerobic exercise (GT), while another group of patients did not receive exercise training (CG). Thyroid hormone receptor alpha1 (TRα1) protein and total (t) and phosphorylated (p) protein kinase B (Akt) and c-Jun N-terminal kinase (JNK) kinase signalling were measured in myocardial tissue by western blotting at pre-VAD and pre-HTx period. In addition, Thyroid hormone (TH) levels were measured in plasma. RESULTS Peak oxygen consumption (VO2) at pre-HTx period was higher in patients subjected to training protocol [18.0 (0.8) for GT when compared with 13.7 (0.7) for CG group, P = 0.002]. N-terminal-prohormone of brain natriuretic peptide (NT-proBNP) levels were 1068 (148) for CG vs 626 (115) for GT group, P = 0.035. A switch towards up-regulation of physiological growth signalling was observed: the ratio of p-Akt/t-Akt was 2-fold higher in GT vs CG, P < 0.05 while p-JNK/t-JNK was 2.5-fold lower (P < 0.05) in GT vs CG, in pre-HTx samples. This response was accompanied by a 2.0-fold increase in TRα1 expression in pre-HTx samples with concomitant increase in circulating T3 in GT vs CG, P < 0.05. No differences in peak VO2, NT-proBNP, T3, TRα1, p/t-AKT and p/t-JNK were found between groups in the pre-VAD period. CONCLUSIONS The unloaded failing myocardium responded to physical training by enhancing thyroid hormone signalling. This response was associated with an up-regulation of Akt and suppression of JNK activation.

Incremental Value of N-terminal Pro–Brain Natriuretic Peptide Over Left Ventricle Ejection Fraction and Aerobic Capacity for Estimating Prognosis in Heart Failure Patients

BACKGROUND N-terminal pro-brain natriuretic peptide (NT-proBNP) plasma levels have been associated with indices of left ventricular (LV) function and aerobic capacity in heart failure. METHODS We prospectively followed-up 149 patients with impaired left ventricular function for 30 +/- 10 months. During this period, 22 patients died and 5 underwent heart transplantation. Blood samples for NT-proBNP assessment were taken at baseline and before cardiopulmonary exercise to estimate peak oxygen consumption (Vo(2)). LV cavity diameter, left atrial size and LV ejection fraction (LVEF) were measured by echocardiography. RESULTS NT-proBNP plasma levels >1,164 pg/ml showed 85% sensitivity and 82% specificity for detecting Vo(2)<14 ml/kg/min (area under the curve [AUC] = 90%, p < 0.001). Patients above this cutoff showed a 13.6-fold greater hazard ratio compared with those with values below this cutoff (p < 0.001). NT-proBNP plasma levels of >760 pg/ml showed 77% sensitivity and 69% specificity for detecting LVEF <28% (AUC = 77%, p < 0.001). Patients with values above this cutoff showed a 15.85-fold greater hazard ratio compared to those with values below this cutoff (p < 0.001). The addition of NT-proBNP to an assessment model that includes peak Vo(2), LVEF and New York Heart Association (NYHA) classification can significantly improve predictive ability. CONCLUSIONS Assessment of NT-proBNP should be performed to detect candidates for heart transplantation because of the useful prognostic information that it can provide.

High plasma adiponectin is related to low functional capacity in patients with chronic heart failure

We evaluated the association between plasma adiponectin and functional capacity in patients with chronic heart failure (CHF). Similarly to NT-proBNP, plasma adiponectin was elevated in CHF compared to healthy controls. Adiponectin correlated inversely with peak oxygen consumption and 6-minute walking distance and was able to identify CHF patients with impaired exercise capacity. Our findings support a role of adiponectin as an index of heart failure severity.

Effects of Inspiratory Muscle Training in Patients With Chronic Heart Failure

We read with interest the article by Chiappa et al. ([1][1]) reporting on the improvement in limb blood flow and attenuation of inspiratory muscle (IM) metaboreflex after inspiratory muscle training (IMT), explaining an IMT-induced increase in peak oxygen consumption (Vo2) and decrease in