Open Field Exercise Testing in Pediatric Congenital Heart Disease Patients: A Subsumption of Cardiovascular Parameters

Congenital heart disease patients often suffer from congestive heart failure or reduced physical exercise capacity [1]. Both situations are associated with a substantial morbidity and mortality in affected children [2]. While patients and parents easily recognize acute congestive heart failure due to new onset of symptoms, chronic congestive heart failure remains challenging to stratify as symptoms progress constantly and most patients are well adapted to their individual limits. It is crucial to catch the slow deterioration of physical exercise capacity in time to treat chronic congestive heart failure [3]. In addition, a reduced cardiovascular fitness, reflected by the lower \(\dot{V}{O}_{2}peak\) values, represents an individual cardiovascular risk factor. In particular, a reduced \(\dot{V}{O}_{2}peak\) at a young age seems to be hard to compensate throughout the adolescent and young adulthood period. This points to the importance of an early recognition of these parameters in young children with congenital heart disease, to provide the possibility for early intervention [4, 5].

Besides clinical examination, symptom-based classification systems [6, 7] and imaging techniques, such as MRI, CT and echocardiography, were performed. As a possible influence of baseline systolic or diastolic function may significantly influence the physical exercise capacity, echocardiographic parameters were taken to evaluate this possible confounder [8]. Furthermore, two main methods are used to grade heart failure in children. The first method is the measurement of brain natriuretic peptide (proBNP) levels [9, 10]. However, studies indicated that using proBNP as a prognostic value in adults cannot be equally applied to pediatric patients [7]. Moreover, venous blood sampling represents an invasive diagnostic tool and can be difficult and traumatizing for the child. The second method for a reliable assessment of congestive heart failure is cardiopulmonary exercise testing (CPET) [11]. This method is also considered the gold standard [12]. The peak oxygen uptake (\(\dot{V}{O}_{2}peak\)) [13] as well as the oxygen uptake efficiency slope (OUES) [14], a surrogate parameter for \(\dot{V}{O}_{2}peak\), are important prognostic parameters in patients with congenital heart disease [15]. Typically, CPET has been performed on a bicycle or a treadmill [16] and it is a suitable diagnostic tool for adults and older children. However, specific reasons complicate these methods for use in young children. First, peak cardiopulmonary performance in children under the age of 8 years is difficult to achieve: on a bicycle because of weak leg muscle strength [17] and on a treadmill due to the unfamiliar exercise form and the fear to fall. Secondly, body size may limit the bicycle method [18].

The currently introduced method by Schöffl et al. [18] uses mobile cardiopulmonary exercise equipment with a protocol tailored to young children and closes that diagnostic gap. While average values for healthy children have already been established, this study evaluates a typical range of performance parameters in patients with congenital heart disease. Values are tested according to the reported protocol in terms of the individual anatomy and objective and subjective degree of congestive heart failure. The results should enable physicians to better assess the individual performance of children with congenital heart disease.

During the period of 2021–2022, children aged 4–8 years with common congenital heart defects [Tetralogy of Fallot (TOF), Transposition of the great arteries (TGA), and after univentricular palliation (TCPC)] were included. These common, complex groups of CHD with symptomatic patients were selected based on clinical need according to the assessment of cardiovascular fitness and performance.

Voluntary participants were recruited consecutively with inclusion of children meeting the inclusion criteria. Written informed consent was obtained from each child and the respective parent using age-appropriate consent forms. This prospective investigator-initiated study was approved by the Ethics Committee of the University of Erlangen-Nuremberg (159_19B) and the Heart Center Leipzig (063/20-ek).

Before cardiopulmonary exercise testing, a thorough clinical examination was performed to rule out contraindications like an acute infection or other non-cardiac preexisting medical conditions. We obtained each patient’s history, an ECG, an echocardiography (including the baseline measurements for evaluation of systolic and diastolic cardiac function), a standardized questionnaire to evaluate subjective physical exercise capacity and a proBNP level. The mobile cardiopulmonary exercise testing device (Cortex Metamax 3B, Cortex Biophysik GmbH, Leipzig, Germany) was fitted to each child using a backpack that could be adapted accordingly to the respective size of each child. A respiratory mask for children (Hans Rudolph, Shawnee, Kansas, USA) was adapted using standard headgear. A Custo ECG 3-lead monitoring was installed.

All tests were performed on flat ground, either gravel or asphalt. A physician accompanied the children for instructions, motivation, and safety monitoring. The outdoor running protocol consisted of 2 min of slow walking, 2 min of slow jogging, 2 min of fast jogging, and a maximum of 2 min of maximum-speed running as previously described by Schöffl et al. [18]. Before each step, the children received instructions about the aimed speed and were then allowed to set the running speed for each exercise according to their capabilities. During the fastest stage, children were instructed to run as fast as possible for as long as possible and received verbal encouragement. The test ended with a recovery period of 3–5 min of slow walking.

A trained study nurse was at the exercise site to monitor the cardiopulmonary exercise testing recordings.

After test completion, values were analyzed using the Metasoft Studio software (Cortex Metamax 3B, Cortex Biophysik GmbH, Leipzig, Germany). Graphs were averaged over 20 data points. The following parameters were recorded constantly throughout the exercise test: oxygen uptake (\(\dot{V}{O}_{2}\)) as well as CO₂ elimination (\(\dot{VC}{O}_{2})\), heart rate, respiratory exchange ratio (RER = \(\dot{\dot{V}{CO}_{2}/}\)/\(\dot{V}{O}_{2}/\)), oxygen pulse (O₂pulse = \(\dot{V}{O}_{2}/\)HR), minute ventilation (\(\dot{V}E\)) and the time of each test (exercise time). First ventilatory threshold (VT1) was calculated using the v-slope method [19] and second ventilatory threshold (VT2) was calculated according to Binder et al. [20]. Oxygen uptake efficiency slope was displayed as the slope of \(\dot{V}{O}_{2}\) on the y-axis plotted against the logarithm of minute ventilation on the x-axis (\(\dot{V}{O}_{2}\) a*log V \({}^{ \cdot }{\text{E}}\)þb, a representing oxygen uptake efficiency slope in l/min). All OUES values were calculated from the onset of cardiopulmonary exercise testing to VT2 and were thus only reported in children having achieved VT2. Physiological criteria for having reached exhaustion included two criteria: peak HR ≥ 195/min, and/or RER at \(\dot{V}{O}_{2}peak\) ≥ 1.0 [21].

Statistical analysis was calculated using SPSS V27 (IBM, Armonk, New York, USA). Comparisons of normally distributed CPET data between sexes were performed using two-sided T-test. For the comparison of the datasets for the patient characteristics, ANOVA testing was used. Differences in \(V{O}_{2} peak\)/OUES/kg values between TOF, TGA and TCPC patients were also compared using ANOVA testing. To evaluate the correlation between age and \(V{O}_{2} peak\)/OUES/kg, linear regression was performed. Pearson correlation coefficients were calculated to examine for possible associations between echocardiographic measurements and \(V{O}_{2} peak\)/OUES/kg values. Data are presented as mean values and were considered statistically significant with p < 0.05.

The current study presents cardiovascular performance parameters for young children from 4 to 8 years with congenital heart disease, using an 8-min open-field cardiopulmonary exercise testing protocol. In recently published studies [18, 21], it has been shown that the 8-min open-field testing can be regarded as a new method capable of sufficiently performing cardiopulmonary exercise testing even when used in very young children. The presented data can underline the feasibility of the test for young children with congenital heart disease, as 97% of tests could be successfully completed.

As there are currently only reported values of the 8-min open-field-testing protocol for healthy children, the current data shall help physicians to interpret the cardiovascular performance of children with congenital heart disease.

Typical ranges of \(\dot{V}{O}_{2}peak\) are depicted in Fig. 1 compared to the limits of healthy children. Overall, lower \(V{O}_{2}peak\) values can be observed in congenital heart disease patients. Yet, a substantial number of patients with TGA or TOF seem to be able to reach normal \(V{O}_{2}peak\) limits.

As shown in Tables 2, 3, and 4, it seems that TCPC patients show the lowest \(V{O}_{2}peak\) values compared to patients with Tetralogy of Fallot and children with TGA. The statistical comparison between the individual groups can underline the evidence of our assumption (comparing TGA and TCPC: p = 0.008; TOF and TCPC: p = 0.021). With regard to other protocols for cardiopulmonary exercise testing, these findings are in accordance with the current literature [15]. With this in mind, the currently depicted 8-min open-field cardiopulmonary exercise testing seems to provide good quality data for CPET in young children with congenital heart disease.

Apart from the diagnosis, we identified no other influences on the \(\dot{V}{O}_{2}peak\) values recorded in this study. In particular, there was no significant influence of cardiac function, evaluated by echocardiography, on CPET performance parameters. And in consistency with previous studies in healthy children, who, according to Kalden et al. [21], showed no significant differences of \(\dot{V}{O}_{2}peak\) between healthy boys and girls in this range of age, the current data seem to underline these findings. We assume that differences in cardiopulmonary performance between sexes become visible only in older children and therefore, cannot be demonstrated in our study population of children of prepubertal age [16].

Consequently, the presented formulas to estimate an expectable \(V{O}_{2} peak\)/OUES/kg in a certain type of CHD are calculated independent of sex. While the type of congenital heart disease seems to predict a certain level of \(V{O}_{2}peak\), the current study could not demonstrate any influence of echocardiographic parameters on \(V{O}_{2}peak\). It is likely that several factors influence the \(V{O}_{2}peak\). As a result, it cannot be expected that there is a significant influence of a single echocardiographic finding that might be found in a relatively small patient cohort.

It has to be stated that CPET measurements, like the \(V{O}_{2}peak,\) differ with regard to the applied CPET protocol. For example, \(V{O}_{2}peak\) is about 10% higher on a treadmill than on a cycle ergometer [12, 22]. Therefore it has to be kept in mind that the ranges reported in this study are linked to the reported CPET protocol. A comparison to other common protocols, with regard to maximum values, is difficult as mostly the percentage of really young children in these studies is limited [23, 24].

Finally, the study’s findings shall help physicians interpret the individual performance of young children with congenital heart disease and evaluate the patient for heart failure on the one hand side and to guide physical training to improve the cardiovascular risk profile in congenital heart disease patients on the other hand side.

This study presents cardiovascular performance parameters of children aged 4–8 years with congenital heart disease tested in a newly developed outdoor running protocol for CPET.

In this study, only voluntary participants were included. Therefore, the possibility of a selection bias leading to an underrepresentation of children with high limitations of cardiopulmonary performance cannot be excluded. Almost exclusively Caucasian participants were included, limiting the applicability of results to children from other ethnic groups.