Influence of 24 h Simulated Altitude on Red Blood Cell Deformability and Hematological Parameters in Patients with Fontan Circulation.

Patients with Fontan circulation are particularly dependent on low pulmonary vascular resistance because their lungs are passively perfused. Hypoxia drives pulmonary vasoconstriction; thus, red blood cell (RBC) deformability and stability of hematological parameters might be of particular importance, because alterations during hypoxia might further influence circulation. This study aimed to measure respective parameters in patients with Fontan circulation exposed to normobaric hypoxia. A total of 18 patients with Fontan circulation (16 to 38 years) were exposed to normobaric hypoxia (15.2% ambient oxygen). Blood samples were taken in normoxia, after 24 h in hypoxia, and 60 min after return to normoxia. Blood count, RBC age distribution, EPO, RBC deformability, marker of RBC nitric oxide, oxidative state, and RBC ATP were measured. Hypoxia increased oxidative stress in RBC, but without affecting RBC deformability. RBC age distribution remained unaffected, although EPO concentrations increased, followed by a rise in reticulocyte count at an already high hematocrit. NO metabolism was not affected by hypoxia. Modest normobaric hypoxia for 24 h did not impair RBC deformability in patients with Fontan circulation; however, the oxidative system seemed to be stressed. Given the high baseline Hct in these patients, hypoxia-induced erythropoiesis could adversely affect rheology with more prolonged hypoxia exposure.

Adequate exercise response at artificial altitude in Fontan patients.

Purpose: For Fontan-palliated patients, altitude exposure is still a part of discussion since the extent of hypoxic pulmonary vasoconstriction potentially resulting in decreasing cardiac output (Qc), especially during physical exercise, is still unclear. We investigated the effects of normobaric hypoxia (15.2% O2) simulating 2,500 m above sea level on cardiopulmonary and metabolic parameters and the benefit of daily physical activity (PA) on hypoxic exercise capacity. Methods: A total of 21 Fontan patients (14-31 years) and 20 healthy controls performed cardiopulmonary exercise tests on a bicycle ergometer in normoxia and hypoxia until subjective exhaustion, measuring capillary lactate (cLa) every 2 min. In between, participants underwent an activity tracking over 5 days with a triaxial accelerometer. Results: Hypoxic exercise was well tolerated by Fontan patients, and no adverse clinical events were observed. Fontan patients showed reduced physical capacity under both conditions compared to controls (63% normoxia, 62% hypoxia), but the relative impairment due to hypoxia was similar for both (≈10%). Up to workloads of 2 W/kg oxygen uptake ( V . O2) and heart rate (HR) developed similarly in patients and controls. cLa increased faster in relation to workload in Fontan patients, but remained significantly lower at peak workload (normoxia 3.88 ± 1.19 mmol/l vs. 7.05 ± 2.1 mmol/l; hypoxia 4.01 ± 1.12 mmol/l vs. 7.56 ± 1.82 mmol/l). Qc was diminished but could be increased similar to controls. Fontan patients with higher PA levels showed a higher V . O2peak in hypoxia. Conclusion: Exercise during short-time artificial altitude exposure seems to be safe for young Fontan patients. Further studies are needed to validate longer exposure under real conditions. V . O2, HR, and Qc might not be a limiting factor for exercise until workloads of 2 W/kg. Higher daily PA levels might improve physical capacity under altitude conditions.

Systemic ventricular function in Fontan patients at rest and after exercise at altitude.

Objective: Physical activity at high altitude is expected to pose risks for patients with Fontan circulation and to impair systemic ventricular function. This study aims to determine the effect of high-altitude hypoxia on ventricular function in Fontan patients at rest and after exercise. We hypothesize that systemic ventricular function deteriorates under hypoxic conditions in Fontan patients. Methods: In this prospective study, 21 Fontan patients (NYHA class I-II) and 21 age-, gender- and body mass index-matched healthy controls were enrolled (median age 17.9 and 16.9 years). Transthoracic echocardiography was performed at rest, after peak (PE) and after continuous exercise (CE) in normoxia and hypoxia at simulated altitude (2,500 m above sea level). The effect of hypoxia on echocardiographic parameters was quantified by linear mixed-effects models and the difference between normoxia and hypoxia (Δ= hypoxia-normoxia). Results: At rest, cardiac output (CO) estimated by outflow tract velocity time integral × heart rate and annular plane systolic excursion (APSE) were lower in hypoxia compared to normoxia in Fontan patients (CO: Δ = -12.0%, n.s.; APSE: Δ = -9.6%, p < 0.001), an increase was observed in controls (CO: Δ = 8.5%, n.s.; APSE: Δ = 2.5%, n.s.). Other parameters of systolic and diastolic function did not show relevant changes. After exercise under hypoxic conditions, Fontan patients did not show relevant deterioration of systolic function compared to normoxia. Late, active diastolic filling reflected by A-wave velocity remained unchanged in Fontan patients, but increased in controls. Under hypoxic conditions, CO and workload were higher after CE than PE in Fontan patients (CO: PE Δ = 1,530 vs. CE 1630), whereas controls showed higher work load and CO estimates after PE than CE as expected (CO: PE Δ = 2,302 vs. CE 2149). Conclusion: Fontan patients clinically tolerated short-term altitude exposure up to two hours and exercise and showed no consistent deterioration of systolic systemic ventricular function, but parameters of myocardial contractility, heart rate and cardiac output did not increase as observed in controls. This is likely to be multifactorial and may include intrinsic cardiac dysfunction as well as preload inadequacy and the lack of augmented atrial contraction. CE may be better tolerated than PE.

Physical activity and heart rate monitoring in Fontan patients - Should we recommend activities in higher intensities?

OBJECTIVE: Exercise capacity is impaired in Fontan palliated patients. The change in daily activity behaviour with an increase in sedentary lifestyle results in low physical activity levels. This might have a greater impact on patients with chronic heart disease in contrast to healthy controls. For a better understanding, we compared data from cardiopulmonary exercise testing (CPET) with heart rates and physical activity in daily life. METHODS: 21 Fontan patients and 20 age, sex and BMI matched controls underwent CPET and 5 days of daily life activity tracking with a triaxial accelerometer (wGT3x-BT, Actigraph) including heart rate monitoring with an optical heart rate sensor. RESULTS: 27% of our Fontan teenagers and 71% of the Fontan adults reached the specific WHO recommendations for moderate to vigorous physical activity (MVPA) during everyday life (EDL), without differences to controls. There was a strong correlation between MVPA and [Formula: see text] for all Fontan patients (p = 0.0035, Pearson r = 0.788). Daily MVPA correlated to peak oxygen uptake and lactate production. Up to workloads of 2 W/kg and in daily life heart rates in Fontan patients were similar to controls. CONCLUSIONS: Daily MVPA is alarmingly low without any differences between Fontan patients and controls. Heart rate behaviour was similar and does not seem to be a limiting factor for physical activity in daily life. Higher intensity activities should be implemented regularly in EDL for Fontan patients. Proof is needed as to whether sports in moderate or possibly even in vigorous activity (e.g. high-intensity interval training) improve exercise capacity the most.

Altered Hemorheology in Fontan Patients in Normoxia and After Acute Hypoxic Exercise.

BACKGROUND: The Fontan circulation is a unique palliation procedure for several congenital heart defects. Impaired exercise capacity has previously been demonstrated in these patients and also a higher risk for cardiopulmonary mortality. Hemorheology was shown to affect cardiopulmonary capacity and in turn to be affected by regular exercise and hypoxia but none of these have been investigated in Fontan patients so far. The aim of this study was to detect general differences in hemorheology in normoxia as well as possible altered hemorheological responses to hypoxia exposure and hypoxic exercise between Fontan patients and healthy controls. METHODS AND FINDINGS: 26 Fontan patients and 20 healthy controls performed an acute exercise test (AET) on a bicycle ergometer under hypoxia with ambient 15.2% oxygen saturation (sO2). Blood samples were taken at rest in normoxia (T0), at rest in hypoxia (T1), after maximum exhaustion in hypoxia (T2), and after 50 min recovery in normoxia (T3). Hemorheological and blood parameters were investigated. Additionally, arterial stiffness was tested at T0. Red blood cell (RBC) deformability, NOx, erythropoietin (EPO) concentration, RBC count, hemoglobin (Hb) concentration and hematocrit (hct) were significantly increased in Fontan patients compared to controls. Same was observed for arterial stiffness. No changes were observed for RBC aggregation, fibrinogen concentration, free radical levels and vascular endothelial growth factor (VEGF). Hypoxia exposure did not change parameters, whereas exercise in hypoxia increased aggregation and hct significantly in both groups. Fontan patients showed significantly increased aggregation-disaggregation balance compared to controls. CONCLUSION: Acute hypoxia exposure and exercise under hypoxia might have similar impact on hemorheology in Fontan patients and controls and was clinically well tolerated. Nevertheless, exercise alters aggregation and possibly hemodynamics which requires special attention in Fontan patients.