A retrospective observational study was conducted in Fontan patients referred to the Pediatric Cardiology Department in National Heart Hospital in Sofia, Bulgaria. This is the only center in the country involved in the surgical treatment of congenital heart defects. Patients aged 8y-18y with functionally univentricular heart who had undergone the Fontan procedure and had CPET were investigated. Exclusion criteria from the study were patients less than 8 or above 18 years of age and a submaximal effort test. Data were collected over a one-year period, from August 2021 to August 2022, involving the patients that met the inclusion criteria (11 out of 19 patients). Simultaneously, 11 age-matched healthy patients from outpatient visits were selected for comparison. Additional factors assessed included ventricular morphology (right, left), ventricular dysfunction and more than moderate atrioventricular valve regurgitation, evaluated by echocardiography. The Ethics Committee in our institution approved the study protocol and waived the need for patient consent due to the study’s retrospective nature.

The authors reviewed patients’ medical files for baseline characteristics and anatomic details. We defined the primary outcome of interest: peak VO₂, a direct measurement of cardiorespiratory fitness ^[12]. Secondary outcomes included peak work rate, peak heart rate, peak oxygen pulse, oxygen consumption (VO₂) at ventilatory anaerobic threshold (VAT), minute ventilation/carbon dioxide production slope (VE/VCO₂ slope) at VAT, oxygen saturation at rest and at peak exercise. Peak VO₂, VO₂ at VAT, work rate and heart rate are also expressed as a percentage of predicted normal values in order to eliminate sex, height and weight differences ^[13–14].

Transthoracic echocardiography was performed using Philips Epic 7c ultrasound system with X5-1 transducer. We graded atrioventricular valve regurgitation (AVVR) according to the American Society of Echocardiography recommended criteria: none to trivial, 0; mild, 1; mild to moderate, 2; moderate to severe, 3; and severe, 4 ^[15]. Ventricular dysfunction was assessed by the modified Simpson method using 4 chamber frames at end systole and end diastole, and was classified as follows: mildly abnormal, 41–51%; moderately abnormal, 30–40%; severely abnormal, <30% ^[16–17].

All patients underwent CPET on an electrically braked cycle ergometer (Lode Corival; Lode BV, Groningen, The Netherlands). Meanwhile, VO₂ was measured using a commercial, breath-by-breath gas analysis system (Ultima-CPX, MGC Diagnostics Corp., St. Paul, Minnesota). A RAMP protocol was used, in which the patient should maintain a pedaling speed of about 60/minute. After an initial warm-up period of 2–3 minutes, the pedal resistance is gradually increased at a rate, based on the patient’s age, weight, gender, and level of fitness so that they reach peak exertion in 8–12 minutes. Anaerobic threshold was calculated using the V-slope method (170029). Oxygen pulse - a surrogate for stroke volume - was measured by dividing absolute oxygen uptake by heart rate. Also, VE/VCO₂ slope was assessed at VAT. Blood pressure was measured every 2 minutes with an automatic cuff and a 12-lead ECG was obtained throughout the whole exercise. A maximal effort test was defined as peak respiratory exchange ratio (RER)³ 1.05.

The authors used descriptive statistics to provide frequencies and percentages for categorical variables and medians, and interquartile ranges for continuous variables. We used the students t-test to compare variables between Fontan patients and healthy patients. Normality was checked based on the normal Q-Q plot and histogram. Gender, age at Fontan, age at CPET, ventricular dominance, pulmonary vasodilator therapy, more than moderate AVVR and ventricular dysfunction were assessed for linearity with peak VO₂. Out of the 7 independent variables only gender and ventricular dominance were significantly linearly related. A multiple regression was run to predict peak VO₂ from gender and ventricular dominance. A value of P£0.05 indicated statistical significance. We used IBM SPSS Statistics 24 (IBM Corp., Armonk, N.Y., USA) for statistical analysis.

We had 19 Fontan patients who were referred to the Pediatric Cardiology Department in National Heart Hospital in Sofia, Bulgaria between August, 2021 and August, 2022. A total of 11 patients were included in the study, regarding the including criteria. Fontan patients’ characteristics are summarized in Table 1.

It is accurate to note that Only 1 patient (9.1%) had more than moderate AVVR and none of the observed patients had neither moderate, nor severe ventricular dysfunction and this may explain the fairly preserved numbers compared to larger registries. Hereby, we should mention that low burden of ventricular dysfunction in this group might bias results toward better exercise outcomes.

All of the single ventricle patients had an extracardiac Fontan procedure. Comparison between Fontan patients and healthy subjects is presented in Table 2. Age at CPET, body mass index and gender distribution were similar between the two groups for the purposes of objectivity.

All of the study subjects achieved maximal effort test. Exercise capacity in our Fontan cohort was reduced compared to healthy peers - patients after Fontan palliation had lower peak VO₂ (23.1 ml/kg/min vs. 30.1 ml/kg/min, P=0.046), percent-predicted peak VO₂ (52% vs. 76%, P<0.001), percent-predicted peak work (56% vs. 82%, P<0.001), percent-predicted peak VO₂ at VAT (37% vs. 48%, P=0.04), resting saturation (93% vs. 97%, P<0.001) and saturation at peak work (84% vs. 95%, P<0.001). None of the patients exhibited ECG abnormalities and one Fontan patients had an abnormal blood pressure response. Comparison of CPET parameters between the two groups is demonstrated in Table 3.

A multiple regression was run to predict peak VO₂ from gender and ventricular dominance. The multiple regression model statistically significantly predicted peak VO₂, F (2, 8) = 12.998, P = 0.003, adj. R2= .71. Both gender and ventricular dominance added statistically significantly to the prediction, P=0.003. Male Fontan patients exhibited higher peak VO₂ of 11.925 ml/kg/min. Peak VO₂ for patients with left ventricular dominance was 7.738 ml/kg/min, greater than patients with right ventricular dominance. Regression coefficients and standard errors can be found in Table 4.

Some limitations are worth noting. A RAMP protocol was used via cycle ergometer, which means that obtained peak VO₂ is lower than uphill treadmill running. Cycle ergometry was used mainly because of the relatively young patients age. Another limitation is the single-center, retrospective, non-randomized design of the study. Also, the small sample size in this research may limit the ability to observe significant differences.