Prognostic value of maximal and submaximal exercise performance in fontan patients < 15 years of age

Developmen

Oxygen uptake efficiency slope is strongly correlated to VO2peak long-term after arterial switch operation

After the arterial switch operation (ASO) for transposition of the great arteries (TGA), many patients have an impaired exercise tolerance. Exercise tolerance is determined with cardiopulmonary exercise testing by peak oxygen uptake (VO2peak). Unlike VO2peak, the oxygen uptake efficiency slope (OUES) does not require a maximal effort for interpretation. The value of OUES has not been assessed in a large group of patients after ASO. The purpose of this study was to determine OUES and VO2peak, evaluate its interrelationship and assess whether exercise tolerance is related to ventricular function after ASO. A cardiopulmonary exercise testing, assessment of physical activity score and transthoracic echocardiography (fractional shortening and left/right ventricular global longitudinal peak strain) were performed to 48 patients after ASO. Median age at follow-up after ASO was 16.0 (IQR 13.0-18.0) years. Shortening fraction was normal (36 +/- 6%). Left and right global longitudinal peak strain were reduced: 15.1 +/- 2.4% and 19.5 +/- 4.5%. This group of patients showed lower values for all cardiopulmonary exercise testing parameters compared to the reference values: mean VO2peak% 75% (95% CI 72-77) and mean OUES% 82(95% CI 77-87); without significant differences between subtypes of TGA. A strong-to-excellent correlation between the VO2peak and OUES was found (absolute values: R = 0.90, p < 0.001; normalized values: R = 0.79, p < 0.001). No correlation was found between cardiopulmonary exercise testing results and left ventricle function parameters. In conclusion, OUES and VO2peak were lower in patients after ASO compared to reference values but are strongly correlated, making OUES a valuable tool to use in this patient group when maximal effort is not achievable.Cardiolog

3-Month enalapril treatment in pediatric fontan patients with moderate to good systolic ventricular function

Many Fontan patients with and without systolic ventricular dysfunction are being treated with angiotensin-converting enzyme (ACE) inhibitors, despite its effectiveness remaining unclear. In the present study, we evaluated the short-term effect of enalapril on exercise capacity, vascular and ventricular function in pediatric Fontan patients with moderategood systolic ventricular function. Fontan patients between 8 and 18 years with moderategood systolic ventricular function and without previous ACE inhibitor treatment were included and were treated with enalapril for 3 months. During the first 2 weeks, the dosage was titrated according to systolic blood pressure (SBP). Exercise tests, ventricular function assessed by echocardiography, arterial stiffness measurements, and plasma levels of N-terminal pro-B-type natriuretic peptide assessed before and after a 3-month enalapril treatment period was compared. A total of 28 Fontan patients (median age 13.9 years, 6 to 15 years after Fontan operation) completed the study with a mean dosage of 0.3 +/- 0.1 mg/ kg/d. A total of 6 patients (21 %) experienced a significant drop in SBP and 6 others (21%) experienced other adverse events. Enalapril treatment lowered the SBP (from 110 to 104 mmHg, p = 0.003) and levels of N-terminal pro-B-type natriuretic peptide (from 80 to 72 ng/L, p = 0.036). However, enalapril treatment did not improve exercise capacity, ventricular function, or arterial stiffness. In conclusion, short-term ACE inhibition has no beneficial effect in Fontan patients with moderate-good systolic ventricular function. (C) 2021 The Authors. Published by Elsevier Inc.Thoracic Surger

4D flow cardiovascular magnetic resonance derived energetics in the Fontan circulation correlate with exercise capacity and CMR-derived liver fibrosis/congestion

Aim This study explores the relationship between in vivo 4D flow cardiovascular magnetic resonance (CMR) derived blood flow energetics in the total cavopulmonary connection (TCPC), exercise capacity and CMR-derived liver fibrosis/congestion. Background The Fontan circulation, in which both caval veins are directly connected with the pulmonary arteries (i.e. the TCPC) is the palliative approach for single ventricle patients. Blood flow efficiency in the TCPC has been associated with exercise capacity and liver fibrosis using computational fluid dynamic modelling. 4D flow CMR allows for assessment of in vivo blood flow energetics, including kinetic energy (KE) and viscous energy loss rate (EL). Methods Fontan patients were prospectively evaluated between 2018 and 2021 using a comprehensive cardiovascular and liver CMR protocol, including 4D flow imaging of the TCPC. Peak oxygen consumption (VO2) was determined using cardiopulmonary exercise testing (CPET). Iron-corrected whole liver T1 (cT1) mapping was performed as a marker of liver fibrosis/congestion. KE and EL in the TCPC were computed from 4D flow CMR and normalized for inflow. Furthermore, blood flow energetics were compared between standardized segments of the TCPC. Results Sixty-two Fontan patients were included (53% male, 17.3 +/- 5.1 years). Maximal effort CPET was obtained in 50 patients (peak VO2 27.1 +/- 6.2 ml/kg/min, 56 +/- 12% of predicted). Both KE and EL in the entire TCPC (n = 28) were significantly correlated with cT1 (r = 0.50, p = 0.006 and r = 0.39, p = 0.04, respectively), peak VO2 (r = - 0.61, p = 0.003 and r = - 0.54, p = 0.009, respectively) and % predicted peak VO2 (r = - 0.44, p = 0.04 and r = - 0.46, p = 0.03, respectively). Segmental analysis indicated that the most adverse flow energetics were found in the Fontan tunnel and left pulmonary artery. Conclusions Adverse 4D flow CMR derived KE and EL in the TCPC correlate with decreased exercise capacity and increased levels of liver fibrosis/congestion. 4D flow CMR is promising as a non-invasive screening tool for identification of patients with adverse TCPC flow efficiency.Cardiovascular Aspects of Radiolog

Cardiac autonomic nervous activity in patients with transposition of the great arteries after arterial switch operation

BackgroundA chronic imbalance of the autonomic nervous system(ANS) may contribute to long term complications in different congenital heart diseases. The purpose of this study was to determine whether the ASN plays a role in the long-term outcome of patients with Transposition of great arteries(TGA) after arterial switch operation(ASO) as its contribution is as yet not clear.MethodsThe ANS activity was evaluated non-invasively in 26 TGA patients and 52 age-appropriate healthy subjects combining impedance cardiography and electrocardiography. Heart rate, pre-ejection period(sympathetic activity parameter) and respiratory sinus arrhythmia and the root of the mean square of successive normal-to-normal interval differences(parasympathetic activity parameter) were measured during 5 different daily activities(sleep, sitting, active sitting, light and moderate/vigorous physical activity). Whether the ANS activity was related to ventricular function, exercise test performance or clinical outcome in the patient group was also analyzed.ResultsCompared to healthy subjects: heart rate was significantly lower in TGA patients at rest and during quiet and active sitting; sympathetic activity was significantly reduced in patients during physical activity; and the parasympathetic activity was higher in TGA patients while quiet and active sitting. In the patient group a significant positive correlation between 4-chamber longitudinal strain and parasympathetic activity during 3 different daily activities was found.ConclusionsThe sympathetic nervous system response to physical activity is reduced in TGA patients after ASO. Additionally, we observed a positive correlation between better left ventricular function and higher parasympathetic activity that could be in line with the known protective effect of a higher vagal activity.</p

Extracardiac conduit adequacy along the respiratory cycle in adolescent Fontan patients

OBJECTIVES: Adequacy of 16-20mm extracardiac conduits for adolescent Fontan patients remains unknown. This study aims to evaluate conduit adequacy using the inferior vena cava (IVC)-conduit velocity mismatch factor along the respiratory cycle.METHODS: Real-time 2D flow MRI was prospectively acquired in 50 extracardiac (16-20mm conduits) Fontan patients (mean age 16.9 +/- 4.5 years) at the subhepatic IVC, conduit and superior vena cava. Hepatic venous flow was determined by subtracting IVC flow from conduit flow. The cross-sectional area (CSA) was reported for each vessel. Mean flow and velocity was calculated during the average respiratory cycle, inspiration and expiration. The IVC-conduit velocity mismatch factor was determined as follows: V-conduit/V-IVC where V is the mean velocity.RESULTS: Median conduit CSA and IVC CSA were 221 mm(2) (Q1-Q3 201-255) and 244 mm(2) (Q1-Q3 203-265), respectively. From the IVC towards the conduit, flow rates increased significantly due to the entry of hepatic venous flow (IVC 1.9, Q1-Q3 1.5-2.2) versus conduit (3.3, Q1-Q3 2.5-4.0 1/min, P < 0.001). Consequently, mean velocity significantly increased (IVC 12 (Q1-Q3 11-14 cm/s) versus conduit 25 (Q1-Q3 17-31 cm/s), P < 0.001), resulting in a median IVC-conduit velocity mismatch of 1.8 (Q1-Q3 1.5-2.4), further augmenting during inspiration (median 2.3, Q1-Q3 1.8-3.0). IVC-conduit mismatch was inversely related to measured conduit size and positively correlated with conduit flow. The normalized IVC-conduit velocity mismatch factor during expiration and the entire respiratory cycle correlated with peak VO2 (r = -0.37, P = 0.014 and r = -0.31, P = 0.04, respectively).CONCLUSIONS: Important blood flow accelerations are observed from the IVC towards the conduit in adolescent Fontan patients, which is related to peak VO2. This study, therefore, raises concerns that implanted 16-20mm conduits have become undersized for older Fontan patients and future studies should clarify its effect on long-term outcome.Thoracic Surger

Haemodynamic performance of 16-20-mm extracardiac Goretex conduits in adolescent Fontan patients at rest and during simulated exercise

OBJECTIVES: To date, it is not known if 16-20-mm extracardiac conduits are outgrown during somatic growth from childhood to adolescence. This study aims to determine total cavopulmonary connection (TCPC) haemodynamics in adolescent Fontan patients at rest and during simulated exercise and to assess the relationship between conduit size and haemodynamics. METHODS: Patient-specific, magnetic resonance imaging-based computational fluid dynamic models of the TCPC were performed in 51 extracardiac Fontan patients with 16-20-mm conduits. Power loss, pressure gradient and normalized resistance were quantified in rest and during simulated exercise. The cross-sectional area (CSA) (mean and minimum) of the vessels of the TCPC was determined and normalized for flow rate (mm(2)/l/min). Peak (predicted) oxygen uptake was assessed. RESULTS: The median age was 16.2 years (Q1-Q3 14.0-18.2). The normalized mean conduit CSA was 35-73% smaller compared to the inferior and superior vena cava, hepatic veins and left/right pulmonary artery (all P = 1.0 at rest and >= 3.0 mmHg during simulated exercise were observed in patients with a conduit CSA = 125 mm(2)/l/min. Normalized TCPC resistance correlated with (predicted) peak oxygen uptake. CONCLUSIONS: Extracardiac conduits of 16-20 mm have become relatively undersized in most adolescent Fontan patients leading to suboptimal haemodynamics