Coarctation of the aorta (CoA), first described over 200 years ago, has for long been considered as a simple mechanical obstruction caused by a segmental narrowing of the aortic arch.1 It was only in the last decades that staggering results revealed that, beyond the anatomical malformation, CoA answers for a systemic vasculopathy with irreversible effects on endothelial function, arterial stiffness and left ventricular remodeling.2^-4 As a result, although resection of the coarcted segment may prevent patients from dying by age of 30, even after this procedure, subjects remain at higher risk of hypertension and premature cardiovascular death.5^,6

This challenging phenomenon has led to an intense search for predictors of worse prognosis in repaired patients. In this direction, some have claimed that late repair is among the main risk factor for all-cause mortality in subjects undergoing resection of aorta coarctation.7 Importantly, late correction frequently occurs as a result of an underdiagnosis rate of over 62%, placing CoA as the most frequently misdiagnosed critical congenital heart disease.8 Besides, recoarctation occurs in one-third of patients, leading to a regression of the benefits of first surgical correction and, often, requiring reintervention. This complication demands a life-long surveillance by regular echocardiography in repaired patients.5 Finally, hypertension stands as the main complication in repaired subjects, hence representing a known risk factor for cardiovascular disease from an early age, with important long-term repercussions on mortality.9^-11

In this study, we retrospectively analyzed data of patients operated for CoA at a tertiary care hospital. The main goals of this study were: (i) to register the frequency of common clinical signs at diagnosis; (ii) to describe the course of echocardiographic parameters before and during the follow-up of coartectomized subjects; (iii) to analyze the clinical prognosis of patients according to baseline characteristics, occurrence of recoarctation and associated malformations. A total of 417 patient-years follow-up was studied, revealing hypothesis-generating results.

We identified 72 patients who underwent CoA surgical correction at the HC-UNICAMP between June 1996 and November 2016. Patients were followed for a mean time of 5.82 years, ranging from 0 to 20 years. The mean age at surgery was 5.64 ± 1.31 years, ranging from 0.1 to 27 years, and 51.6% of patients were operated in their first year of life. Demographic data is summarized in Table 1.

At diagnosis, 51 (87.9%) patients had a heart murmur and 23 (48.9%) had no palpable pulse in the lower limbs. Out of the 18 electrocardiographic tests performed, 12 (67%) patients with LV overload were detected, and of 14 patients who underwent complementary cardiovascular imaging investigation beyond echocardiogram, two (14%) had a chest X-ray, one (7%) had a chest computed tomography and six (43%) underwent computed tomography angiography. Besides, among those taking antihypertensive medications at baseline (58%), the most frequent classes were thiazide diuretics (35.6%), beta-blockers (27.1%) and inhibitor of angiotensin-converting enzyme inhibitors (22%). Use of vasodilators (5.1%) and angiotensin receptor blocker (1.7%) were far less common (Table 2).

At baseline, the mean peak DAG was 55 mmHg, and 19 (78%) of patients had LV hypertrophy. The most common echocardiographic findings were bicuspid aortic valve (BAV) (32.8%), persistent arterial duct (31%) and interventricular communication (19%). Mitral valve insufficiency was present in 13.8% of patients. Noteworthy, pulmonary artery hypertension occurred in 12.1% of patients. Less common findings are summarized in Table 3.

All patients underwent surgical correction of CoA by left thoracotomy followed by end-to-end anastomosis. The mean time of surgery and hospitalization was 2.3 hours and 10 days, respectively, and mean cross-clamping time was 15.9 minutes. Of 51 patients operated, three patients had chylothorax, with no other surgical complications being reported. Among those who did not have recoarctation during follow-up, surgical correction greatly decreased peak DAG (54 vs 13 mmHg; p < 0.001) and symptoms (60 vs 4.5%; p < 0.001), but not hypertension (58 vs 38%; p = 0.17) (Figure 1). Besides, a significant reduction in LVM, LVEDD, LVESD, PW, ARD and LAD was observed in these patients when compared to baseline values (Figure 2 and Table 4).

Figure 1

Figure 2

Importantly, during follow-up, 16 (27.6%) patients had recoarctation (Figure 3). The mean follow-up period before detection of recoarctation was 5.6 years, and half of the cases occurred after 3.6 years of follow-up. Last recoarctation event was identified after 15 years of follow-up. Overall, patients with recoarctation were more likely to be symptomatic (4.5 vs 64%; p < 0.001) and hypertensive (38 vs 78%; p = 0.011) when compared to those without recoarctation (Table 5). In addition, compared to baseline, there was no significant change in peak gradient or in LVM (Table 5).

Figure 3

Noteworthy, patients with BAV at diagnosis had comparable results with controls during follow-up. Also, age at surgery and gender did not affect the outcomes (data not shown).

In this case series, we evaluated data from 72 patients operated for coarctation of the aorta and followed for up to 20 years in tertiary hospital in Brazil. Our main objectives were to identify the most frequent clinical findings that could benefit from early diagnosis, to describe the course of echocardiographic measures following surgical correction, and to detect the occurrence of recoarctation and its impact on prognosis. Our main findings were the following: (i) heart murmur is present in most patients; (ii) in addition to peak DAG, LV mass and diameters also decreased after surgical correction; (iii) recoarctation is a late finding in operated subjects and significantly impacts prognosis.

In our study, most patients who underwent CoA surgical correction had systolic heart murmur with posterior radiation at diagnosis, and half of them had hypertension, cardiac symptoms, and no palpable pulse in the lower limbs. Of note, these findings were achieved by proper physical examination and history-taking, which can guide complementary investigation focused on early diagnosis. Yet, half of patients were lately diagnosed in our follow-up, which is in accordance with previous large population-based studies showing late diagnosis rates of over 62%.8

Whether late correction constitutes an independent risk factor for poor prognosis remains a matter of debate, with some suggesting a relationship of late correction with re-coarctation rates6 and others with long-term cardiovascular mortality. In our study, neither re-coarctation nor clinical outcomes differed in a significant manner between age groups. Still, an earlier surgical treatment of comorbidities that are known to have an impact on cardiovascular mortality would presumably improve long-term survival. This hypothesis is supported by the absence of LV hypertrophy and cardiac symptoms in operated patients in our analysis.

It is of note that more than one third of patients remained hypertensive after surgical correction. This finding is in accordance with previous studies suggesting hypertension as the main late complication in operated patients, even in the absence of residual obstruction.9^,11 Although the exact mechanism for this phenomenon remains unclear, a role of arterial stiffness, endothelial dysfunction and altered autonomic cardiac modulation has been proposed.

In this matter, post-coartectomy subjects have impaired endothelial function, which, in turn, increases peripheral vascular resistance, leading to increased blood pressure.10 Moreover, coarctation leads to deposition of collagen and depletion of smooth muscle in the aortic wall. This negatively affects aortic distensibility and the sensitivity of aortic arch baroreceptors, thereby impairing arterial compliance with substantial effects on blood pressure.15^,16 Finally, it has been conjectured that hypertension results from compensatory sympathetic stimuli in response to acute unloading of the baroreceptors following surgery.10 Importantly, these features are not prevented by surgical correction, reinforcing that coarctation is a generalized vasculopathy far beyond the narrowing of the aortic arch.

Our study found a high prevalence of LV hypertrophy at baseline, which markedly decreased after surgical correction. Noteworthy, in coarctation, an increase in LV mass occurs in spite of elevated blood pressure, which may be explained by the “ventricular-arterial coupling” hypothesis, that postulates that aortic stiffness increases wave reflection pressure, leading to LV afterload.17 Importantly, such phenomenon leads to diastolic dysfunction and changes in LV morphology, which are partially reversed by surgery, as demonstrated in the present study and in previous ones.4^,18^-20 In fact, in our follow-up we found a significant reduction of indexed LV diameters, LV mass and posterior wall thickness in operated patients who did not manifest recoarctation.

Finally, pulmonary hypertension occurred in 12% of patients in our follow-up, which is in accordance with previous studies. Mechanistically, it is assumed that endothelial dysfunction and arterial stiffness are the most likely causes of pulmonary hypertension in these patients, though a role for vascular reactivity has been also proposed.20 Moreover, BAV was the most common associated malformation in our analysis, which is in agreement with previous studies showing a common genetic mutation for both congenital heart diseases.21 Noteworthy, it has been proposed that such phenomenon would lead to greater hemodynamic changes, which could plausibly lead to worsen prognosis.22 In our study, patients with isolated and complex coarctation had comparable results, although larger studies are required to correctly address this issue.

Coarctectomy improves cardiac symptoms and LV hypertrophy, with a slight effect on the incidence of hypertension. Age at surgical repair and complex malformations were not related to a worse prognosis. In our study, recoarctation had a negative impact on the benefit of surgery in one-third of patients, which reinforces the need for lifelong surveillance by echocardiography.