Virtual Reality Exercise Alleviates Postprandial Vascular and Metabolic Impairment in Adolescents With Congenital Heart Disease: A Randomized Controlled Crossover Trial

Author's summary

Adolescents with congenital heart disease (CHD) experienced impaired vascular and metabolic responses after a high-fat meal and prolonged sitting. A single session of virtual reality (VR) exergaming preserved endothelial function, reduced systolic blood pressure, and attenuated postprandial metabolic impairment. VR exergaming may provide an engaging and feasible alternative to traditional exercise for adolescents with CHD to protect vascular health. Incorporating VR-based exercise into pediatric cardiac rehabilitation programs could enhance adherence and clinical outcomes, although further trials are needed.

Abstract

Background and Objectives

Adolescents with congenital heart disease (CHD) are at increased cardiovascular risk, exacerbated by high-fat meals (HFMs) and sedentary behavior. While exercise is recommended to mitigate this risk, adherence can be challenging. Virtual reality (VR) exergaming has emerged as a potentially motivating alternative. This study examined whether a single session of VR exergaming could attenuate vascular and metabolic impairment induced by an HFM and prolonged sitting in adolescents with CHD.

Methods

In a randomized crossover design, 10 adolescents with CHD (mean age, 12.6±3.3 years) completed 2 trials after an HFM with 4 hours of sitting: (1) 30 minutes of VR cycling, and (2) uninterrupted sitting. Vascular and metabolic markers were assessed at baseline and 4 hours, including flow-mediated dilation (FMD), augmentation index (AIx), carotid-femoral pulse wave velocity, blood pressure (BP), glucose, lipids, and triglyceride-glucose index (TyG).

Results

FMD was preserved in the VR trial and decreased in the sitting trial, with a significant interaction (p=0.008). Systolic BP showed a significant interaction (p=0.022), with reductions observed only after VR exercise. AIx was significantly lower in the VR trial compared with sitting (p=0.002), but no interaction was observed. The postprandial increase in TyG index was attenuated in the VR trial (interaction p=0.040).

Conclusions

A single session of VR exergaming attenuated vascular and metabolic impairment induced by an HFM and prolonged sitting in adolescents with CHD. These findings suggest that VR exergaming may serve as an alternative to traditional exercise for vascular health in CHD.

Graphical Abstract

INTRODUCTION

Congenital heart disease (CHD) occurs in approximately 9 out of every 1,000 live births, and advances in medical and surgical care have enabled the majority of affected patients to survive into adolescence and adulthood.¹⁾,²⁾ Despite improved survival rates, adolescents with CHD remain at high risk of developing cardiovascular (CV) disease,³⁾ due not only to residual structural defects but also to persistent vascular abnormalities, such as endothelial dysfunction and increased arterial stiffness, which are contributors to CV risks.⁴⁾

In addition to these factors, lifestyle risk factors may further elevate CV risk in this population. High-fat meal (HFM) consumption and prolonged sedentary behavior are well-established risk factors associated with increased CV risk. The combination of an HFM and prolonged sitting may further exacerbate vascular and metabolic impairment. Even a single HFM can acutely impair vascular function by reducing nitric oxide bioavailability and increasing oxidative stress,⁵⁾ while prolonged sitting worsens endothelial function and arterial stiffening.⁶⁾,⁷⁾ These behaviors are commonly observed in adolescents with CHD, often influenced by parental overprotection, low self-efficacy, and physical limitations.⁸⁾,⁹⁾

Aerobic exercise has been shown to attenuate postprandial vascular impairment in healthy individuals.¹⁰⁾,¹¹⁾,¹²⁾ However, adolescents with CHD may face barriers to engaging in traditional exercise programs due to low exercise confidence, fear of overexertion, and limited accessibility. Virtual reality (VR) exergaming represents an engaging and immersive alternative to traditional exercise, combining physical activity with interactive, game-like environments to enhance motivation and adherence.¹³⁾,¹⁴⁾,¹⁵⁾ Evidence suggests that VR interventions can reduce anxiety and improve emotional well-being in children with CHD and related conditions,¹⁶⁾,¹⁷⁾ while recent meta-analyses support their potential to improve functional capacity in cardiac rehabilitation.¹⁸⁾ Taken together, these findings position VR exergaming as a promising strategy for addressing both physiological and psychological needs in this population. This study aimed to evaluate whether a single session of VR exergaming could attenuate vascular and metabolic impairment induced by an HFM and prolonged sitting in adolescents with CHD.

METHOD

Ethical statement

This study was approved by the Institutional Review Board (IRB) of the University of Seoul (IRB No. 2023-11-003). Before participation, all participants and their guardians provided written informed consent after receiving detailed information regarding the study’s purpose and procedures.

Study participants

Ten adolescents with CHD (5 boys, 5 girls; mean age: 12.6±3.3 years; body mass index [BMI]: 18.9±2.4 kg/m²) were recruited through an open call on the official website of the Korean Congenital Heart Disease Patient Group. Eligible participants were adolescents aged between 9 and 23 years, in accordance with the Framework Act on Youth in Korea. The participants’ descriptive characteristics are presented in Table 1. All had complex congenital heart defects and had undergone one to 3 prior cardiac surgeries. Participants were excluded if they had any evidence of cognitive impairment, physical activity restrictions, or if they were currently engaged in regular exercise training. All participants were classified as the New York Heart Association Functional Class I. Three patients were taking CV-related medications, such as aspirin, an angiotensin-converting enzyme inhibitor or an angiotensin II receptor blocker (ARB), and an anticoagulant.

Table 1. Demographic characteristics of patients with congenital heart disease (n=10).

Variables		Value
Sex (male/female)		5/5 (50%/50%)
Age (years)		12.6±3.3
Height (cm)		152.3±12.0
Weight (kg)		44.2±10.4
Body mass index (kg/m2)		18.9±2.4
Body fat (%)		24.2±7.0
Lean body mass (kg)		17.8±4.8
Glucose (mg/dL)		102.5±4.2
Total cholesterol (mg/dL)		140.0±33.0
Triglyceride (mg/dL)		101.3±37.8
Low-density lipoprotein cholesterol (mg/dL)		64.6±28.7
High-density lipoprotein cholesterol (mg/dL)		55.0±12.1
Leisure time moderate to vigorous physical activity (MET-minute/week)		160 [0.0–390.0]
Sitting time (hour/day)		9.9±1.2
Type of underlying heart disease
	Atrioventricular septal defect	1 (10)
	Double outlet right ventricle	1 (10)
	Functional single ventricle	2 (20)
	Persistent truncus arteriosus	1 (10)
	Pulmonary atresia with intact ventricular septum	1 (10)
	Pulmonary atresia with ventricular septal defect	1 (10)
	Tetralogy of fallot	2 (20)
	Transposition of great arteries	1 (10)
Number of cardiac surgeries
	1	5 (50)
	2	2 (20)
	3	3 (30)
NYHA functional classification
	NYHA I	10 (100)
	NYHA II–IV	0 (0)
Types of medications prescribed
	Aspirin	2 (20)
	ACEI/ARB	1 (10)
	Anticoagulant	2 (20)

Values are presented number (%), mean ± standard deviation, or median [interquartile range].

ACEI = angiotensin-converting enzyme inhibitor; ARB = angiotensin II receptor blocker; NYHA = New York Heart Association.

Study design

Using a randomized crossover design, participants were assigned to 1 of 2 trials first: (1) the 30-minute VR exergaming trial, in which they engaged in VR exercise following an HFM, or (2) the sitting trial, in which they remained sedentary following an HFM. After completing the first trial, participants underwent a washout period of at least 3 days before switching to the opposite trial.¹⁹⁾ The overall study design is illustrated in Figure 1.

Figure 1. Experimental design. Participants completed 2 postprandial trials in a randomized crossover design: (1) VR exercise and (2) seated rest, separated by a 3-day washout. All variables were measured at the time points indicated by arrows, with blood markers and FMD assessed only at baseline and 4 hours post-meal.

FMD = flow-mediated dilation; VR = virtual reality.

To minimize potential confounding factors affecting vascular and metabolic function, participants were instructed to abstain from caffeine for 12 hours and vigorous exercise for 24 hours before each trial. On the experimental day, participants arrived in a fasted state (≥8 hours), and all experimental days were conducted in a controlled laboratory environment.²⁰⁾ At the beginning of each trial, participants rested in a seated position for 10–15 minutes, after which baseline measurements were collected. Then, they consumed a standardized HFM over 20 minutes, with meal composition adapted from previous studies.¹⁰⁾,²¹⁾ The 2 meal options, a Korean beef bulgogi Hamburger set (1,088 kcal, 16.7 g saturated fat) and a boneless chicken set (1,097 kcal, 17.2 g saturated fat), were matched in total caloric and saturated fat content to ensure consistency across trials. Following the meal, participants engaged in the assigned intervention.

In the VR exergame trial, participants first rested for 30 minutes postprandially before performing 30 minutes of VR-based exercise while wearing a head-mounted display. The VR exercise session was conducted using VZfit Play (VirZoom, Cambridge, MA, USA), a system that integrates an accelerometer sensor with a stationary bike pedal, allowing interactive cycling movements combined with upper-body motion. Using real-time heart rate (HR) monitoring (Hicardi+ H100, DongA ST Inc., Seoul, Korea) during VR exercise to track electrocardiographic data and exercise intensity, it was found that the mean HR and rating of perceived exertion were 161±10 bpm (60–80% of HR reserve) and 14–16, respectively, indicating moderate-to-vigorous intensity physical activity. In the sitting trial, participants remained seated for 4 consecutive hours without engaging in any physical activity. They were permitted to read or use their mobile phones but were restricted from any other activities except bathroom breaks.

Measurements

Anthropometric measurements and physical activity assessments were conducted during the participants’ first experimental visit. Height, weight, body fat percentage, and skeletal muscle mass were measured using an automatic extensometer (BSM330, InBody, Seoul, Korea) and a bioelectrical impedance analyzer (InBody620, InBody, Seoul, Korea). Physical activity levels were evaluated using the Global Physical Activity Questionnaire, which assessed moderate-to-vigorous physical activity and sedentary time.⁸⁾,⁹⁾ In addition, endothelial function and metabolic markers were assessed at baseline and 4 hours after an HFM, whereas arterial stiffness and hemodynamic markers were assessed at baseline and again at 2, 3, and 4 hours.

Endothelial function

Brachial artery flow-mediated dilation (FMD) was assessed according to the guidelines established by Thijssen et al.²²⁾ The right brachial artery was imaged 2–3 cm proximal to the antecubital fossa using a high-resolution ultrasound system (Arietta 60; Hitachi Aloka Medical, Tokyo, Japan) equipped with a 9–14 MHz linear transducer (L441, Hitachi Aloka Medical). After a 1-minute recording of the resting brachial artery diameter and blood velocity, a blood pressure (BP) cuff was inflated to 220 mmHg on the forearm for 5 minutes to induce forearm ischemia. Upon deflation, reactive hyperemia was induced, and brachial artery diameter and blood velocity were continuously recorded for 3 minutes. Brachial artery diameter and blood velocity were analyzed using an automated analysis program (FMD Studio, Rome, Italy; Quipu s.r.l., Pisa, Italy). The FMD response (% FMD) was calculated as a percent change in peak diameter (post-cuff deflation) relative to resting diameter (before cuff deflation). The shear rate was calculated as a product of blood velocity and 8 divided by resting diameter. All measurements were obtained by the same trained investigator who was blinded to the experimental groups.

Arterial stiffness

Arterial stiffness was assessed using 2 parameters: the carotid-femoral pulse wave velocity (cfPWV) and the radial artery augmentation index (AIx). cfPWV was measured using SphygmoCor (AtCor Medical, Sydney, Australia) in accordance with the Clinical Application of Arterial Stiffness, Task Force III guidelines.²³⁾ The pulse wave transit time (Δt) was determined using the foot-to-foot method, measuring the time delay between the systolic upstrokes of the carotid and femoral pulse waveforms. AIx was measured from the right radial artery using applanation tonometry (Millar Instruments, Houston, TX, USA). A continuous pulse wave was recorded for at least 10 seconds, and the central arterial waveform (AIx) was calculated using an automated transfer function algorithm.

Blood pressure and heart rate

BP and HR were measured from the left brachial artery using an automatic BP monitor (HEM-7080IC, OMRON DALIAN CO., Dalian, China). Measurements were taken twice, with at least a one-minute interval between each measurement, and the average of the 2 readings was used for analysis. If the difference between the first and second systolic BP measurements exceeded 10 mmHg, an additional measurement was taken. In such cases, the average of the 2 lowest values was used for final analysis.

Metabolic blood markers

Postprandial metabolic markers were assessed using capillary blood sampling from the left fingertip, which was disinfected with an alcohol swab before collection. Blood samples were analyzed using an automated blood analyzer (LABGEO PT10; Samsung, Suwon, Korea) to measure glucose levels, triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and total cholesterol (TC). The triglyceride-glucose index (TyG) was calculated using the following equation: TyG = ln [TG × (Glucose/2)].

Randomization and sample size

As no prior studies have examined the acute effects of exercise or HFM consumption in adolescents with CHD, the sample size was estimated from Kranen et al.,²⁴⁾ who reported an acute effect of moderate-intensity aerobic exercise on FMD in adolescents (Cohen’s d=0.66). Based on the corresponding F-test effect size of f=0.33, a 2-factor (trial × time) repeated-measures analysis of variance (ANOVA) with α=0.05, power (1−β)=0.80, and a correlation among repeated measures of 0.60 indicated that 18 observations were required (G*Power 3.1.9.2). Correlation among repeated measures was set to 0.60 due to the nature of the cross-over design, in which the same participants complete both trials. Considering the cross-over design and potential dropout rate of 10%, the total sample size was set at 10 participants (20 observations).

Statistical analysis

All data are presented as mean ± standard deviation or median [interquartile range], as appropriate. Normality was assessed using the Shapiro–Wilk test.

The effects of VR exercise and sitting conditions on vascular and metabolic function were examined using a 2-way repeated-measures ANOVA, with trial (condition) and time (measurement time points) as factors. When a significant interaction was detected, post-hoc analyses were performed using Bonferroni correction or Tukey’s HSD test, depending on data characteristics. In the absence of a significant interaction, post-hoc tests were conducted only for significant main effects. Changes from baseline (Δ) between the 2 conditions were compared using paired t-tests. All analyses were performed using IBM SPSS Statistics version 28.0 (IBM Corp., Armonk, NY, USA), with statistical significance set at p<0.05.

RESULTS

Comparisons of changes in FMD between the VR exercise trial and the sitting trial are presented in Table 2 and Figure 2. As shown in Table 2, resting and peak brachial artery diameters increased significantly over time in both trials (p<0.001, p=0.033), with no significant trial × time interactions. FMD showed a significant interaction effect (p=0.008), with higher postprandial values observed in the VR exercise trial compared to the sitting trial (8.22±2.47% vs. 5.86±2.47%, p=0.005). Resting shear rate and shear rate area under the curve did not differ significantly between trials or over time.

Table 2. Comparisons of changes in brachial artery flow-mediated dilation responses between VR exercise trial and Sitting trial.

Variables	VR exercise trial		Sitting trial		p value
	Baseline	Post-4 hours	Baseline	Post-4 hours	Time	Trial	Interaction
Rest diameter (mm)	3.07±0.38	3.11±0.39†	3.00±0.40	3.15±0.42†	<0.001	0.690	0.118
Peak diameter (mm)	3.28±0.44	3.36±0.40†	3.23±0.48	3.33±0.41	0.033	0.243	0.833
Resting shear rate (/s)	286.6±125.4	370.4±78.9	312.0±104.0	406.6±143.9	0.113	0.542	0.851
Shear rate AUC	19,437±7,353	22,450±8,637	20,942±6,275	24,543±6,412	0.137	0.447	0.884
FMD (%)	6.80±2.30	8.22±2.37*	7.03±2.87	5.86±2.47	0.880	0.040	0.008

Values are presented as mean ± standard deviation.

Shear rate AUC: shear rate area-under-the-curve above the baseline of the shear rate stimulus from release of the arterial occlusion to peak vasodilation.

AUC = area-under-the-curve; FMD = flow-mediated dilation; VR exercise trial = virtual reality-based exercise trial.

^*p<0.05 vs. Sitting trial, ^†p<0.05 vs. baseline.

Figure 2. Changes in FMD after a high-fat meal in VR exercise trial and Sitting trial. Data are mean ± standard deviation.

FMD = flow-mediated dilation; VR = virtual reality, Δ FMD = changes in flow-mediated dilation.

As shown in Table 3, HR increased significantly after the HFM in both trials (p<0.001), with a greater increase observed in the VR exercise trial. Systolic blood pressure decreased significantly only at 3 hours postprandially in the VR exercise trial (107±8 mmHg → 100±6 mmHg, p<0.05), whereas diastolic blood pressure and mean blood pressure showed modest time-related changes with limited between-trial differences. AIx decreased significantly in both trials, with a greater reduction observed in the VR exercise trial (p=0.037 and p=0.002 for time and trial, respectively). Although cfPWV showed a significant trial effect, post-hoc comparisons did not reveal significant differences between trials at any time point.

Table 3. Comparisons of changes in heart rate, brachial blood pressure, and arterial stiffness between the VR exercise trial and Sitting trial.

Variable	VR exercise trial				Sitting trial				p value
	Baseline	Post-2 hours	Post-3 hours	Post-4 hours	Baseline	Post-2 hours	Post-3 hours	Post-4 hours	Time	Trial	Interaction
HR (beats/minutes)	76±14	101±13*†§∥	93±16*†‡∥	87±15*†‡§	75±11	86±11†	80±15	83±12	<0.001	<0.001	0.003
SBP (mmHg)	107±8	102±6	100±6*†	104±9	107±11	106±10	108±11	109±10	0.099	0.080	0.022
DBP (mmHg)	67±6	62±6*	64±5*	64±5	69±8	69±6	69±8	67±7	0.056	0.020	0.303
MBP (mmHg)	81±6	75±4*	76±5*	77±6	82±9	81±7	82±8	81±7	0.059	0.030	0.176
PP (mmHg)	40±6	41±8	36±4	40±6	38±5	37±7	39±7	42±9	0.116	0.851	0.088
AIx	11.1±7.4	2.9±10.1*†	5.1±7.9†	5.3±7.6*†	12.0±8.0	8.5±7.9	9.6±5.2	11.2±5.8	0.037	0.002	0.179
AIx@75	11.2±9.2	14.3±12.3	12.6±10.4	8.1±10.4	10.8±8.9	11.7±10.3	11.8±7.9	12.3±7.9	0.430	0.935	0.108
cfPWV	5.2±0.9	5.2±1.0	5.0±0.7	5.0±0.7	5.3±0.9	5.5±0.8	5.4±0.5	5.4±1.0	0.738	<0.001	0.672

Values are presented as mean ± standard deviation.

AIx = augmentation index; AIx@75 = augmentation index at heart rate 75 bpm; cfPWV = carotid-femoral pulse wave velocity; DBP = diastolic blood pressure; HR = heart rate; MBP = mean blood pressure; PP = pulse pressure; SBP = systolic blood pressure; VR exercise trial = virtual reality-based exercise trial.

^*p<0.05 vs. Sitting trial, ^†p<0.05 vs. baseline, ^‡p<0.05 vs. post-2 hours, ^§p<0.05 vs. post-3 hours, ^∥p<0.05 vs. post-4 hours.

Glucose, TG, and TyG index increased significantly over time following the HFM in both the VR exercise and sitting trials (all p<0.05 for time effect). The TyG index showed a significant trial × time interaction (p=0.040), with a smaller postprandial increase observed in the VR exercise trial compared to the sitting trial. TC, LDL-C, and HDL-C showed no significant interaction effects, although LDL-C and HDL-C decreased significantly over time (p=0.021 and p=0.029, respectively) (Table 4).

Table 4. Comparison of changes in glucose, cholesterol after a high-fat meal between the VR exercise trial and Sitting trial.

Variables	VR exercise trial		Sitting trial		p value
	Baseline	Post-4 hours	Baseline	Post-4 hours	Time	Trial	Interaction
Glucose (mg/dL)	102±6	110±7*	103±4	117±10*	<0.001	0.071	0.149
TG (mg/dL)	105±49	173±104*	101±38	219±124*	0.005	0.099	0.097
TyG index	8.5±0.4	9.0±0.5*	8.5±0.4	9.3±0.6*	<0.001	0.177	0.040
TC (mg/dL)	136±24	140±28	140±33	143±35	0.054	0.386	0.764
LDL-C (mg/dL)	63±18	54±20	62±29	52±24	0.021	0.682	0.884
HDL-C (mg/dL)	52±8	50±13	55±12	48±13	0.029	0.911	0.105

Values are presented as mean ± standard deviation.

HDL-C = high-density lipoprotein cholesterol; LDL-C = low-density lipoprotein cholesterol; TC = total cholesterol; TG = triglyceride; TyG = triglyceride-glucose index; VR exercise trial = virtual reality-based exercise trial.

^*p<0.05 vs. baseline.

DISCUSSION

To our knowledge, this is the first study to investigate the acute effects of VR-based exercise on postprandial vascular and metabolic responses following an HFM combined with prolonged sitting in adolescents with CHD.

VR exergaming preserved FMD compared with a significant postprandial reduction in the sitting trial, consistent with previous findings in healthy populations showing that postprandial hyperlipidemia and inactivity impair endothelial function through reduced nitric oxide bioavailability and increased oxidative stress.²¹⁾ The protective effect observed in the present study aligns with studies reporting that acute aerobic exercise mitigates postprandial endothelial dysfunction,¹⁰⁾,²¹⁾,²⁵⁾ likely via shear-stress—induced eNOS activation, nitric oxide production, and suppression of oxidative stress. Our findings extend this evidence by showing, for the first time, that VR exercise yields similar vascular benefits in CHD adolescents.

VR exergaming also led to a greater reduction in AIx compared to sitting, suggesting improved wave reflection and central hemodynamics, whereas cfPWV did not differ between trials. This supports the view that large-artery stiffness requires longer-term training to change. In CHD, vascular benefits from exercise may be driven more by enhanced peripheral circulation and microvascular recruitment than by central stiffness adaptations, given the frequent presence of impaired microvascular function and reduced skeletal muscle perfusion in this population.²⁶⁾,²⁷⁾,²⁸⁾ Such peripheral vasodilatory responses could explain the AIx improvements observed, aligning with prior evidence that aerobic exercise promotes vascular relaxation and reduces wave reflection.²⁹⁾

Regarding metabolic responses, VR exergaming attenuated the postprandial rise in the TyG index, a marker of insulin resistance linked to cardiometabolic risk. This effect may reflect enhanced skeletal muscle glucose uptake and lipid metabolism during and after exercise, potentially mediated by increased lipoprotein lipase activity and improved insulin signaling. Adolescents with CHD, particularly those with Fontan physiology, often present with unfavorable body composition, including increased fat mass and reduced muscle mass despite normal BMI,³⁰⁾ which may heighten vulnerability to postprandial metabolic disturbances. The observed vascular and metabolic benefits support VR exergaming as a novel strategy to address both physiological and behavioral needs in this population.

Adolescents with CHD often face barriers to participating in conventional exercise programs due to physical limitations, fear of overexertion, and low motivation. VR exergaming offers an engaging, interactive, and adaptable alternative that can be implemented in clinical or home-based settings to promote physical activity. The observed acute benefits on vascular and metabolic function provide a rationale for incorporating VR-based exercise into lifestyle recommendations for this population.

We acknowledged several methodological limitations to our study. First, although we employed a crossover design to reduce inter-individual differences, the sample size was relatively small, which may limit generalizability and the ability to conduct subgroup analyses by CHD diagnosis type. Second, the intervention involved only a single acute VR exergaming session, so the long-term effects of regular participation remain unknown. Third, metabolic markers were assessed using capillary blood sampling; therefore, this methodological consideration should be taken into account when interpreting the findings. Finally, although participants maintained their usual medications, we cannot exclude the possibility that vascular responses in this acute setting were influenced by potential effects of cardiac conditions, prior cardiac surgery, or drugs such as aspirin, ACE inhibitors/ARBs, or anticoagulants.

In conclusion, a single session of VR exergaming attenuated postprandial endothelial dysfunction, reduced AIx, and blunted the rise in TyG index induced by an HFM and prolonged sitting in adolescents with CHD. VR exergaming represents a promising, accessible, and engaging strategy to counteract acute vascular and metabolic insults in this vulnerable population.