Introduction
Coarctation of the aorta (CoA) is a common congenital aortic lesion, which accounts for 5–10% of all congenital heart defects [
1]. Untreated CoA may lead to morbidity and death early in life as a result of hypertension, congestive cardiac failure, myocardial infarction, stroke, infective endocarditis and aortic rupture [
1]. Furthermore, despite timely repair, patients with CoA require life-long follow-up due to an increased risk of cardiovascular morbidity and mortality [
1‐
3].This is largely due to CoA-associated hypertension which may be present in up to 68% at long-term follow-up [
1,
3].
Reduced exercise capacity is a common finding in adults with congenital heart disease (CHD) and has been related to cardiovascular morbidity and mortality in this population [
2,
3]. Subjective appraisal of exercise performance by CoA patients themselves is usually good. However, self-reported physical fitness is notoriously unreliable and frequently not in line with the actual physical fitness of the patient. Objective data on exercise capacity in patients after repair of coarctation are scarce [
3]. A large number of CoA patients are normotensive at rest, but might develop hypertension during exercise [
1,
4,
5]. Several studies have also shown a relationship between exercise-induced hypertension and systemic hypertension in CoA patients, suggesting that exercise-induced hypertension may be a predictor for the development of chronic hypertension and cardiovascular events in long-term follow-up [
2,
4,
6,
7]. Hypertension has serious consequences for the future cardiovascular health since it may lead to atherosclerosis, coronary artery disease, stroke, left ventricular (LV) dysfunction, heart failure, and death [
1,
3,
6]. Timely identification of patients at risk for hypertension is of great importance to initiate early intervention strategies and reduce the risk of hypertension related cardiovascular sequelae [
1,
2,
4]. This study sought to assess exercise capacity and blood pressure response in adult patients long-term after CoA repair in relation to left ventricular and vascular function.
Discussion
Although self-reported exercise capacity in CoA patients tends to be good, objective data on exercise capacity after CoA repair are scarce [
2,
3]. We found that exercise capacity is well preserved in adult CoA patients long-term after successful repair of coarctation of the aorta. However, exercise hypertension occurred in over two-thirds of CoA patients, and is strongly related to systemic hypertension. Despite a high rate of hypertension, cardiac function seems to be preserved during exercise.
Overall, CoA patients showed a good exercise capacity compared to controls. Peak oxygen uptake was similar between CoA patients and controls, as is in line with an earlier study by Balderston et al., who studied exercise capacity in 31 children after surgical repair of CoA [
19]. Their cohort of patients with a mean age of 11 years showed a VO
2peak of 48 ± 1.4 ml/kg/min compared to a VO
2peak of 41 ± 12.0 ml/kg/min in our cohort with a mean age of 29.8 years, both with a VO
2peak predicted value of > 85% (89% vs 96%, respectively). In contrast, Buys et al. found impaired exercise capacity and lower VO
2peak in a large group of adults treated for CoA in childhood [
2]. A recent study on CPET in children with CHD by Amedro et al. also showed decreased VO
2peak in a large cohort of CHD-patients with a mean age of 12 years [
20]. A subanalysis showed a significantly lower VO
2peak/kg for CoA patients compared to controls. However, CoA patients still reached 95% of the predicted VO
2peak/kg [
20].
Patients with CHD have been shown to experience a decline in exercise capacity from puberty, whereas VO
2peak continues to increase and VO
2peak/kg remains stable in healthy adolescents during this period [
21]. A retrospective cohort study by Diller et al. showed dramatically lower VO
2peaky during cardiopulmonary exercise testing in patients with adult CHD [
22]. In multivariate analysis, decrease in VO
2peak/kg was identified as a strong predictor for hospitalization or death during follow-up. However, Diller et al. showed that the degree of exercise intolerance is related to the underlying anatomical features [
22]. A smaller subanalysis showed that patients with repaired CoA demonstrated the highest VO
2peak values compared to patients with other complex CHD. Decrease in VO
2peak after anatomically successful repair was explained by associated lesions or late repair of CHD and therefore longer exposure to altered cardiovascular dynamics [
3,
22]. The differences in reported exercise capacity might be explained by the heterogeneity in age, age at time of repair and associated lesions of the assessed study populations.
Increase of oxygen uptake during exercise is achieved through increased cardiac output (heart rate × stroke volume) and mixed arteriovenous oxygen difference, of which heart rate is the strongest contributor to the increased oxygen transport [
18] Our patients showed a significantly lower peak heart rate than healthy controls and chronotropic incompetence was seen in 9% of CoA patients. Chronotropic incompetence has been strongly associated with increased risk of adverse cardiovascular outcomes and sudden death [
18]. Although the underlying mechanisms for chronotropic incompetence in heart disease are not fully understood, reduced beta-receptor sensitivity or downregulation of beta-receptors as a result of chronic increased catecholamine levels have been implicated in patients with heart failure [
18,
23]. Sino-atrial dysfunction has also been observed after cardiac surgery in patients with Tetralogy of Fallot [
24]. Chronotropic incompetence after cardiac surgery might be explained by post-operative scarring of the myocardium. However, none of our patients with chronotropic incompetence had undergone open heart surgery, suggesting involvement of a more generalized arterio-ventricular pathophysiology.
Over two-thirds (68%) of CoA patients were hypertensive during exercise. This finding is in line with a recent study in children and adolescents after CoA repair [
25]. Exercise hypertension is a strong predicator for systemic hypertension and cardiovascular events in long-term follow-up [
2,
7]. Hypertension is a well-known long-term complication of CoA, even after surgical or endovascular repair. Reduced aortic compliance, abnormal baroreceptor function, and altered wall-shear stress dynamics have all been implicated in the development of CoA-associated hypertension [
1,
2]. In a retrospective cohort study comparing CPET outcomes in normotensive and hypertensive CoA patients, Buys et al. showed that age was the only significant predictor for progression of exercise-induced hypertension to systemic hypertension [
2]. Early detection and treatment of hypertension is essential in preventing long-term complications such as atherosclerosis, coronary and cerebral artery disease, heart failure, and death [
26]. According to the recently updated guidelines of the European Society of Hypertension, patients with hypertension after CoA repair should be treated as particularly high risk patients, who require aggressive treatment with anti-hypertensive medication (beta-blockers or calcium channel blockers) and/or re-intervention in the case of rest- or restenosis [
27]. As exercise-induced hypertension may precede systemic hypertension, regular follow-up of CoA patients, including CPET, is strongly recommended even long-term after successful repair [
26,
27].
In regard to the results of this study, several limitations should be discussed. The relatively small sample size and low inclusion rate (31%) limits generalization of the results and may have obscured further differences and associations. Furthermore, the inclusion rate for the study was relatively low (31%), as a large number of CoA patients did not agree to undergo CPET in a study setting. This may have resulted in some degree of selection bias in the study. The control group consisted of age- and gender-matched reference values rather than actual control group participants. Nevertheless, these controls may provide a better comparison of CoA patients to a healthy standard than actual control participants, as exercise capacity can vary widely within a healthy population. Furthermore, as a large number of patients in our cohort were already hypertensive, comparison of patients with hypertension with patients with exercise hypertension only was not possible.
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