Children with repaired CHD have impaired cardiorespiratory fitness

Children with surgically corrected congenital heart disease (CHD) have a significantly reduced cardiorespiratory fitness (CRF) compared with controls in a meta-analysis and meta-regression.

In the meta-analysis of 45 studies comprising 2,536 children with CHD (60 percent male) and 3,108 healthy controls (57 percent male), children with CHD had significantly lower peak oxygen uptake (V̇O_2peak) than controls (standardized mean difference [SMD], -1.13; p<0.0001), which represents a large-sized negative effect. [Trends Cardiovasc Med 2025;35:417-426]

In individuals with CHD, impaired V̇O_2peak is an independent predictor of long-term mortality, morbidity, heart failure, and quality of life (QoL). [Eur J Prev Cardiol 2022;29:513-533; Int J Cardiol 2016;203:1052-1060] Hence, it has become the key parameter for evaluating CRF and is used as a marker of functional status, the researchers noted.

“Reduced saturation during exercise, chronotropic impairment, and early onset of anaerobic threshold (AT) are likely to play a role in this impairment,” the investigators said.

More profound effect

Participants with univentricular hearts (UVHs) had the most pronounced effect (SMD, -1.61; p<0.0001). “While this group of patients may maintain daily activity levels comparable to their healthy peers at a young age, their impaired fitness may limit their ability to engage in sports and predispose them to a more sedentary lifestyle, factors well known to further decrease long-term cardiovascular health,” the investigators explained.

This finding thus holds significant clinical relevance, particularly in this patient subgroup, because a decline in V̇O_2peak is strongly associated with the need for heart transplantation, as well as increased mortality. [Open Heart 2018;5:e000812]

“[E]arly reductions and/or declines in V̇O_2peak during follow-up should be closely monitored as they may inform clinical decision-making, such as re-intervention planning or optimizing heart failure therapy,” the researchers said.

Other subgroups

Large-sized differences were also observed between the subgroups of children with tetralogy of Fallot (TOF; SMD, -1.07; p<0.0001), biventricular hearts (BVHs; SMD, -0.96; p<0.0001), and ventricular septal defect (VSD; SMD, -0.83; p<0.0001) and their respective controls. In the subgroup of patients with transposition of the great arteries (TGA), the difference relative to controls was moderate-sized (SMD, -0.79; p<0.0001).

These effect sizes translated to weighted MDs of 7.6, 7, 5.6, and 6.3 mL/kg/min for the respective TOF, BVH, VSD, and TGA subgroups (vs their respective controls).

Moreover, the UVH subgroup exhibited significantly poorer V̇O_2peak than the BVH (p<0.0001), TOF (p=0.005), VSD (p=0.01), and TGA (p=0.001) subgroups.

According to the investigators, the reduced CRF among children with TOF underlines the importance of close monitoring of pulmonary regurgitation and right ventricular (RV) function. “Timely intervention, such as pulmonary valve replacement before severe RV remodeling, may help preserve V̇O_2peak and prevent further decline, though additional research is needed to confirm this hypothesis.”

Of note as well was the large-sized CRF impairment among children with VSD, which, according to the researchers, may be considered a simple CHD with the potential for full anatomical repair. They said that the impairment may have been due to inactivity and potential deconditioning. “Since recommendations for sports are generally unrestricted for children with VSD, they could benefit from intensive sport programmes that have been shown to increase CRF in healthy subjects.”

Meta-regression

Without stratifying by subgroup, the overall meta-regression analysis identified reduced oxygen saturation at peak exercise (SpO_2peak), peak heart rate (HR_peak), oxygen (O₂) pulse, and AT as potential determinants of CRF impairment.

“SpO_2peak was … the most explanatory for the extent of the impairment,” the researchers said. SpO_2peak accounted for 48 percent of the variance (p=0.003). This was followed by HR_peak (19 percent; p=0.006), onset of AT (16 percent; p=0.001), and O₂ pulse (5 percent; p<0.05).

“[I]t is not surprising that HR_peak and O₂ pulse, surrogate measures of stroke volume, were associated with CRF. In [this] analysis, HR_peak appeared to be a stronger determinant of CRF than O₂ pulse,” they noted. “This may be because, in younger individuals, increasing HR is the primary mechanism for augmenting cardiac output during exercise, rather than increasing stroke volume.”

The association between V̇O_2peak and O₂ pulse may be attributed to the association between V̇O_2peak and HR_peak, as O₂ pulse is calculated by dividing absolute V̇O_2peak by HR_peak, the investigators explained.

Early onset of AT, a well-documented phenomenon in CHD patients, may indicate physical deconditioning secondary to sedentary behaviour, which is common among children with CHD. [Curr Respir Med Rev 2011;7:87-96; Neth Heart J 2009;17:385-392; Pediatr Res 2021;89:1650-1658; Curr Opin Cardiol 2022;37:91-98]

Early CRF monitoring recommended

“[D]espite advancements in medical care, children with surgically corrected CHD often experience reduced CRF, which is associated with negative long-term health outcomes,” the investigators noted. Evidence shows that children with CHD have a higher mortality risk during childhood compared with their healthy counterparts, and that CHD severely impairs QoL. [J Am Heart Assoc 2020;9:e017704; J Am Coll Cardiol 2021;77:2219-2235; J Pediatr 2015;166:119-124.e1]

In the 44 studies that reported the participants’ exact ages, the weighted mean age at cardiopulmonary exercise testing was 13.2 years. Forty-two studies reported V̇O_2peak indexed for weight; across these studies, the weighted mean V̇O_2peak was 34 mL/kg/min, which was lower than that of controls (42.7 mL/kg/min).

“[T]his meta-analysis shows that CRF is already substantially impaired in children with surgically corrected CHD and several isolated subgroups. In the context of a shuttle run test, it would mean that, on average, a child with surgically corrected CHD can only reach about half the stages that their healthy peers would achieve,” the investigators said.

Taken together, the study establishes diagnosis-specific benchmarks for CRF impairments and provides grounds for future studies investigating the causes of impaired CRF, they noted. “Since CRF is an important predictor of mortality, morbidity, and QoL in patients with CHD, clinical follow-up should focus on monitoring CRF from an early age.”