Early diagnosis, along with advancements in medical and surgical management, has significantly increased the survival of patients with congenital heart disease, enabling most to reach adulthood. Nevertheless, their lifespan remains shorter than that of the general population. Long-term follow-up of these patients has introduced challenges such as functional assessment for surgical indications and escalation to alternative therapeutic options. 

Given this context, it is essential to develop tools that allow precise risk stratification for each patient. Reduced exercise capacity is linked to poorer outcomes, not only in the general population but also in conditions like heart failure or pulmonary hypertension. Among patients with congenital heart disease, exercise testing provides an objective evaluation of functional capacity and correlates not only with symptoms but also with prognosis. 

The study presented here seeks to analyze the association between exercise capacity and mortality in a cohort of adult patients with congenital heart disease included in the Swedish National Registry. Additionally, a secondary aim is to identify mortality predictors within this population. 

The wide variability in outcomes and prognosis associated with different types of congenital heart disease complicates the identification of universal parameters for early detection of patients likely to experience unfavorable progression. Various factors may serve as risk indicators, and this study evaluates several of them. Functional capacity is often used as a criterion for invasive strategies, making its correlation with prognosis crucial to supporting clinical decisions. 

This retrospective observational study analyzes data from the SWEDCON (Swedish Registry of Congenital Heart Disease), which encompasses all seven healthcare regions in Sweden. The study included patients over 18 years of age with congenital heart diseases of varying complexity. Data from their first exercise test and clinical assessment were collected. Patients without clinical data within two years of the exercise test were excluded. Exercise capacity was assessed through cycle ergometer tests conducted between 1990 and 2017. Predicted maximal exercise capacity, measured by workload, was calculated based on sex, age, and height using formulas proposed by Brudin et al. The classification according to the percentage of predicted maximal workload achieved was as follows: good exercise capacity (>70% of predicted value), moderately reduced exercise capacity (50-70% of predicted value), and severely reduced exercise capacity (<50% of predicted value). 

A total of 3,721 patients were included in the analysis, with a mean age of 27 years (20.8-41) and 44.6% female representation. The cohort was predominantly composed of patients with congenital heart diseases of moderate complexity (52%), although most were in NYHA Class I. The mean exercise capacity was 77% ± 20%, with differences noted across various congenital heart diseases: higher in moderate complexity lesions and lower in severe cases. The mean follow-up duration was 9.4 years, during which 5.8% of the patients died. Deceased patients were generally older, had worse exercise capacity, experienced greater symptom burden, used more medications, and were in higher NYHA classes. 

Kaplan-Meier survival curves demonstrated that survival was directly proportional to exercise capacity: 91% for the group achieving >70% of predicted maximal workload, 80% for those achieving 50-70%, and 67% for those achieving <50%. In summary, reduced exercise capacity was significantly associated with lower survival rates. 

The secondary objective involved identifying mortality predictors through univariable and multivariable Cox regression analyses. Univariable analysis revealed that moderately and severely reduced exercise capacity increased mortality risk by 2-6 times (HR 2.3; 95% CI: 1.7-3.2; p < .001) and (HR 5.6; 95% CI: 4.0-7.9; p < .001), respectively, compared to patients with good exercise capacity. Other factors associated with higher mortality included advanced age, higher NYHA class, lower self-reported physical activity, presence of symptoms, pacemaker use, increased cardiovascular medication, and ventricular dysfunction. In multivariable analysis, congenital heart disease complexity combined with moderately or severely reduced exercise capacity was associated with a 2-3 times greater mortality risk. 

Based on these findings, the authors concluded that reduced exercise capacity, along with greater congenital heart disease complexity, is associated with increased mortality risk. Prospective studies are needed to validate these results. 

COMMENTARY: 

The significance of this study lies in its large sample size and adequate follow-up duration, establishing it as the most comprehensive investigation into the relationship between exercise capacity and mortality among patients with congenital heart disease. Consequently, the study provides sufficient statistical power to establish mortality as a robust primary outcome and achieve statistical significance. Additionally, the inclusion of patients from centers with varying levels of specialization and congenital heart disease complexity enhances the study’s external validity and facilitates the generalization of its findings to different clinical settings. 

Although this study utilized peak workload as the measure of exercise capacity, this parameter demonstrates a strong correlation with peak oxygen consumption, which is more commonly employed in clinical practice. The findings align with previous studies analyzing the functional capacity and prognosis of specific congenital heart disease subgroups. 

Another notable conclusion of the study is the tendency to perform exercise tests primarily on patients with more complex congenital heart diseases. However, as highlighted in other research, mortality among patients with less complex congenital heart diseases remains higher than that of the general population. Therefore, emphasizing the potential benefit of exercise testing in this patient group is crucial. 

Key limitations of the study include its retrospective nature and potential variability in exercise test protocols over the years covered by the registry. As noted by the authors, the underrepresentation of exercise testing in patients with less complex congenital heart diseases—who exhibit lower mortality rates than those with more complex lesions—might have underestimated the role of exercise capacity in predicting mortality. 

In congenital heart disease patients, quality of life and functional capacity are pivotal in evaluating the success of interventions. Functional capacity quantification is often challenging, particularly in this patient population. The NYHA classification provides a subjective evaluation of functional capacity, which correlates well with exercise limitations in these patients. However, compared to objective exercise capacity measures, it tends to underestimate the degree of limitation. Patients with congenital heart disease often have reduced awareness of their exercise limitations, likely due to the gradual onset and early development of these limitations. This phenomenon is particularly notable in patients with right-sided heart lesions, who often report minimal symptoms until advanced stages, potentially impacting surgical decisions, exercise prescriptions, and prognostic outcomes. 

In conclusion, incorporating objective measures of exercise capacity into follow-up assessments and integrating these findings into clinical decision-making is essential for managing patients with congenital heart diseases of any complexity. This is especially pertinent given that studies such as the one presented demonstrate a significant association between easily accessible parameters like exercise capacity and patient mortality. Designing prospective studies to confirm these results and integrate exercise testing into routine follow-up protocols for these patients would be highly beneficial. 

REFERENCE: 

Wikner A, Sandström A, Rinnström D, Wiklund U, Christersson C, Dellborg M, et al.; Impaired exercise capacity and mortality risk in adults with congenital heart disease. JACC: Advances. 2023 Feb 21;2(5):100422. doi:10.1016/j.jacadv.2023.100422