Blunted peripheral blood supply and underdeveloped skeletal muscle in Fontan patients: The impact on functional capacity.

Changes in circulatory physiology are common in Fontan patients due to suboptimal cardiac output, which may reduce the peripheral blood flow and impair the skeletal muscle. The objective of this study was to investigate the forearm blood flow (FBF), cross-sectional area (CSA) of the thigh and functional capacity in asymptomatic clinically stable patients undergoing Fontan surgery. Thirty Fontan patients and 27 healthy subjects underwent venous occlusion plethysmography, magnetic resonance imaging of the thigh musculature and maximal cardiopulmonary exercise testing. Muscle sympathetic nerve activity (MSNA), norepinephrine measures, cardiovascular magnetic resonance, handgrip strength and 6-minute walk test were also performed. Fontan patients have blunted FBF (1.59 ± 0.33 vs 2.17 ± 0.52 mL/min/100 mL p < 0.001) and forearm vascular conductance (FVC) (1.69 ± 0.04 vs 2.34 ± 0.62 units p < 0.001), reduced CSA of the thigh (81.2 ± 18.6 vs 116.3 ± 26.4 cm2p < 0.001), lower peak VO2 (29.3 ± 6 vs 41.5 ± 9 mL/kg/min p < 0.001), walked distance (607 ± 60 vs 701 ± 58 m p < 0.001) and handgrip strength (21 ± 9 vs 30 ± 8 kgf p < 0.001). The MSNA (30 ± 4 vs 22 ± 3 bursts/min p < 0.001) and norepinephrine concentration [265 (236-344) vs 222 (147-262) pg/mL p = 0.006] were also higher in Fontan patients. Multivariate linear regression showed FVC (β = 0.653; CI = 0.102-1.205; p = 0.022) and stroke volume (β = 0.018; CI = 0.007-0.029; p = 0.002) to be independently associated with reduced CSA of the thigh adjusted for body mass index. The CSA of the thigh adjusted for body mass index (β = 5.283; CI = 2.254-8.312; p = 0.001) was independently associated with reduced peak VO2. Patients with Fontan operation have underdeveloped skeletal muscle with reduced strength that is associated with suboptimal peripheral blood supply and diminished exercise capacity.

Turquetto ALR ，Dos Santos MR ，Sayegh ALC ，de Souza FR ，Agostinho DR ，de Oliveira PA ，Dos Santos YA ，Liberato G ，Binotto MA ，Otaduy MCG ，Negrão CE ，Canêo LF ，Jatene FB ，Jatene MB ... -  《-》

Aerobic exercise and inspiratory muscle training increase functional capacity in patients with univentricular physiology after Fontan operation: A randomized controlled trial.

The effect of exercise training and its mechanisms on the functional capacity improvement in Fontan patients (FP) are virtually unknown. This trial evaluated four-month aerobic exercise training and inspiratory muscle training on functional capacity, pulmonary function, and autonomic control in patients after Fontan operation. A randomized controlled clinical trial with 42 FP aged 12 to 30 years and, at least, five years of Fontan completion. Twenty-seven were referred to a four-months supervised and personalized aerobic exercise training (AET) or an inspiratory muscle training (IMT). A group of non-exercise (NET) was used as control. The effects of the exercise training in peak VO2; pulmonary volumes and capacities, maximal inspiratory pressure (MIP); muscle sympathetic nerve activity (MSNA); forearm blood flow (FBF); handgrip strength and cross-sectional area of the thigh were analyzed. The AET decreased MSNA (p = 0.042), increased FBF (p = 0.012) and handgrip strength (p = 0.017). No significant changes in autonomic control were found in IMT and NET groups. Both AET and IMT increased peak VO2, but the increase was higher in the AET group compared to IMT (23% vs. 9%). No difference was found in the NET group. IMT group showed a 58% increase in MIP (p = 0.008) in forced vital capacity (p = 0.011) and forced expiratory volume in the first second (p = 0.011). No difference in pulmonary function was found in the AET group. Both aerobic exercise and inspiratory muscle training improved functional capacity. The AET group developed autonomic control, and handgrip strength, and the IMT increased inspiratory muscle strength and spirometry. ClinicalTrials.gov Identifier: NCT02283255.

Turquetto ALR ，Dos Santos MR ，Agostinho DR ，Sayegh ALC ，de Souza FR ，Amato LP ，Barnabe MSR ，de Oliveira PA ，Liberato G ，Binotto MA ，Negrão CE ，Canêo LF ，Trindade E ，Jatene FB ，Jatene MB ... -  《-》

Impaired Pulmonary Function is an Additional Potential Mechanism for the Reduction of Functional Capacity in Clinically Stable Fontan Patients.

Turquetto ALR ，Canêo LF ，Agostinho DR ，Oliveira PA ，Lopes MICS ，Trevizan PF ，Fernandes FLA ，Binotto MA ，Liberato G ，Tavares GMP ，Neirotti RA ，Jatene MB ... -  《-》

Resistance training improves cardiac output, exercise capacity and tolerance to positive airway pressure in Fontan physiology.

Subjects with Fontan-type circulation have no sub-pulmonary ventricle and thus depend exquisitely on the respiratory bellows and peripheral muscle pump for cardiac filling. We hypothesised that resistance training to augment the peripheral muscle pump might improve cardiac filling, reduce inspiratory-dependence of IVC return to the heart and thus improve exercise capacity and cardiac output on constant positive airway pressure (CPAP). Eleven Fontan subjects (32+/-2 years, mean+/-SEM) had cardiac magnetic resonance imaging (MRI) and exercise testing (CPET); six underwent 20 weeks of high-intensity resistance training; others were non-exercising controls. After training, CPET was repeated. Four trainers had MRI with real-time flow measurement at rest, exercise and on CPAP in the trained state and following a 12-month detrain. In the trained state, muscle strength increased by 43% (p=0.002), as did total muscle mass (by 1.94 kg, p=0.003) and peak VO2 (by 183 ml/min, p=0.02). After detraining, calf muscle mass and peak workload had fallen significantly (p<0.03 for both) as did peak VO2 (2.72 vs. 2.18 l/min, p<0.001) and oxygen pulse, a surrogate for SV (16% lower, p=0.005). Furthermore after detraining, SV on MRI decreased at rest (by 11 ml, p=0.01) and during moderate-intensity exercise (by 16 ml, p=0.04); inspiratory-dependent IVC blood return during exercise was 40% higher (p=0.02). On CPAP, cardiac output was lower in the detrained state (101 vs. 77 ml/s, p=0.03). Resistance muscle training improves muscle mass, strength and is associated with improved cardiac filling, stroke volume, exercise capacity and cardiac output on CPAP, in adults with Fontan-type circulation.

Cordina RL ，O'Meagher S ，Karmali A ，Rae CL ，Liess C ，Kemp GJ ，Puranik R ，Singh N ，Celermajer DS ... -  《-》

Hemodynamic causes of exercise intolerance in Fontan patients.

Exercise intolerance is frequent among Fontan patients and an important determinant for quality of life. This study investigated the hemodynamic causes of impaired exercise capacity in Fontan patients with particular focus on the influence of stroke volume index (SVI) and heart rate (HR). In 38 Fontan patients, peak oxygen consumption (VO2), SVI and HR were recorded during incremental load exercise test and compared with 19 age and gender matched controls. SVI (ml/m(2)) was lower in patients than controls during warm-up (28[26-31] vs. 35[30-39], p=0.0093), at submaximal (40[37-43] vs. 55[51-59], p<0.0001) and at maximal exercise (38[35-40] vs. 54[51-58], p<0.0001). Similarly, HR (% of expected maximum) was lower in patients at warm-up (45[43-48]% vs. 64[57-64]%, p<0.0001), submaximal (71[68-75]% vs 85[82-88]%, p<0.0001) and maximal exercise (84[80-88]% vs. 97[95-99]%, p<0.0001). Furthermore, SVI dropped 14% (from 44[41-48] to 38[35-40] ml/m(2)) in Fontan patients from the peak plateau to maximal exercise vs. 5% (from 57[53-61] to 54[51-58] ml/m(2)) in controls, p<0.0001. The low SVI and HR explained 67% and 20% of the difference in peak VO2 between Fontan patients and controls respectively. SVI decreased significantly in Fontan patients near the end of maximal effort exercise. The low SVI at maximal exercise was the most important hemodynamic factor limiting exercise capacity in Fontan patients, whereas chronotropic impairment had a smaller impact. The low SVI and HR at maximal exercise accounted for the difference in peak VO₂ between Fontan patients and controls in this study. http://www.cvk.sum.dk/CVK/Home/English.aspx (protocol nr: H-3-2010-045).

Hebert A ，Jensen AS ，Mikkelsen UR ，Idorn L ，Sørensen KE ，Thilen U ，Hanseus K ，Søndergaard L ... -  《-》