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1 Introduction

Aortic coarctation is an uncommon but partially reversible cause of secondary hypertension. In this chapter, we will discuss the pathophysiology, epidemiology, and clinical presentation. We will review the known mechanisms for hypertension development in coarctation. Finally, we will consider medical, surgical, and interventional treatment strategies for coarctation and their effects on hypertension and overall prognosis.

2 Epidemiology and Associations

Aortic coarctation is defined as a narrowing or stenosis in an aortic segment. Most commonly, discrete coarctation is focal and juxtaductal, near the insertion of the ligamentum arteriosum in the upper segment of the descending thoracic aorta (i.e., aortic isthmus). Other anatomic presentations of coarctation include diffuse aortic arch hypoplasia, abdominal aortic stenosis, and even aortic atresia when the obstruction is absolute (Fig. 16.1).

Fig. 16.1
figure 1

Classification of coarctation of the aorta. (a) Coarctation can be (i) preductal, occurring proximal to the ductus arteriosus (DA); (ii) juxtaductal, occurring at the level of the DA; and (iii) postductal, occurring distal to the DA. (b) Aortic arch interruption is essentially a complete form of coarctation, in which there is a gap between the ascending and descending thoracic aorta. The interruption can be (i) distal to the left subclavian artery, (ii) between the left carotid and left subclavian arteries, and (iii) between the innominate and left carotid arteries. Printed with permission from artist Mr. Talmur Ahmed

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Coarctation represents 6–8% of congenital heart defects (CHD) with an incidence of 1 in 2500 live births and a male-to-female predominance of about 1.5–1 [1]. It can occur either as an isolated lesion or in association with bicuspid aortic valve (BAV), Turner’s syndrome, patent ductus arteriosus (PDA), mitral valve abnormalities, ventricular septal defect (VSD), and additional left heart obstructive lesions (e.g., Shone’s complex or hypoplastic left heart syndrome) [2,3,4,5,6]. Abdominal aortic coarctation also referred to as midaortic syndrome typically includes aortic hypoplasia, and it is associated with renal artery stenosis [7]. The term simple coarctation implies an absence of additional intracardiac pathology (other than BAV or PDA), whereas complex coarctation is associated with additional forms of CHD.

3 Histology and Genetics

Morphologically, the tissue ridge (often circumferential) that comprises focal coarctation intrudes into the aortic lumen leading to obstruction. While there remains controversy as to its development, there are several hypotheses including (1) hemodynamic effects in development from low flow state and (2) abnormal migration of ductal tissue [2].

The hemodynamic hypothesis considers abnormal ductal flow and/or unfavorable angulation of ductal insertion to the isthmus during fetal development that leads to coarctation upon ductal closure at birth [2]. A mechanism of medial infolding and migration of ductal tissue with surrounding secondary cystic medial necrosis has been supported by pathology specimens finding a sling of ductal tissue at the isthmus and even in hypoplastic arch tissue [6].

Several studies have focused on the maldevelopment of neural crest cells that could broadly tie in coarctation with the company that it keeps (e.g., outflow tract and noncardiac vascular anomalies) [8, 9]. The Notch signaling pathway appears to have an important role in cardiovascular development. Defects in the Notch pathway have been linked with neural crest abnormalities and cardiovascular defects in both mice and humans, including aortic arch malformations [10].

4 Mechanism of Hypertension Development

When the degree of aortic obstruction is significant, areas below the level of coarctation see decreased blood pressure and perfusion relative to proximal arterial beds. In discrete juxtaductal coarctation, this leads to reduced blood pressure to abdominal organs including the kidneys and lower extremities in comparison to the upper extremities, coronary arteries, and cerebral vasculature. The lack of renal blood flow leads to activation of the renin-angiotensin system (RAS) thereby increasing peripheral afterload and intrarenal sodium uptake (Fig. 16.2).

Fig. 16.2
figure 2

Mechanism of hypertension in patients with coarctation of the aorta. (1) The narrowed aorta results in decreased blood flow distal to the obstruction, which leads to hypoperfusion of the organs, including the kidneys. The kidneys respond by activating the renin-angiotensin-aldosterone axis to normalize blood pressure. This results in normalization of blood pressure in the lower extremities with adequate perfusion of the organs but at the expense of increased blood pressure in the upper body. (2) The narrowed aorta also forces the left ventricle to contract more forcefully to maintain cardiac output, thus increasing systolic pressure in the left ventricle and proximal aorta

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To some extent the body can mitigate hypoperfusion by development of collaterals later in life that arise from above the coarctation segment and provide perfusion past the obstruction. There are two anatomic sources of collateral circulation that can develop (1) anterior circulation, bilateral internal mammary arteries connecting to external iliacs via epigastric arteries, and (2) posterior circulation, thyrocervical arteries to descending aorta via intracostal arteries [11]. There is considerable variation in collateral development that is not well understood.

There are two proposed mechanisms of hypertension development in coarctation: (1) direct consequence of mechanical obstruction and (2) maladaptation of the RAS [2]. The mechanical obstruction of coarctation may mandate a higher blood pressure to allow for systemic flow through the increased systemic vascular resistance (SVR) inherent in aortic obstruction or from small-caliber collateral vessels. Based on this mechanism, the treatment of secondary hypertension would be resection of the coarctation to allow unhindered aortic flow. However, this mechanism alone does not adequately explain the variability in hypertension reduction after coarctation repair or the late hypertension that can develop in patients years later [12]. In addition, the severity of obstruction does not always correlate with hypertension severity [2].

This humoral theory of RAS activation secondary to renal underperfusion is conjectured to be the primary mechanism of late hypertension and vascular abnormalities in coarctation patients [2]. Animal studies transplanting one kidney proximal to the coarctation segment demonstrate significant reduction in SVR and blood pressure [12, 13]. This explains why measured SVR is often increased even distal to the obstruction. Nonetheless, human and animal studies of coarctation have not consistently documented increased renin levels [14].

5 Clinical Presentation and Diagnosis

It is the specifics of (1) coarctation location (e.g., arch, juxtaductal, or abdominal); (2) severity of stenosis, ranging from mild obstruction to total occlusion with thoracic collaterals; and (3) concomitant cardiac and vascular abnormalities that dictate the age of clinical presentation and severity of illness. Symptoms can range from patients being asymptomatic with a murmur to a constellation of hypertension, claudication, hypertensive headaches, and congestive heart failure. In cases where the coarctation segment involves the left subclavian artery ostium, reversal of left vertebral flow at high outputs can lead to subclavian steal syndrome.

Most coarctation patients will be diagnosed in childhood based on physical exam, clinical symptoms, or as part of a secondary hypertension work-up. There are some patients with a combination of minimal symptoms, adequate collateral development, and/or inadequate access to informed health care who are not diagnosed until much later in life. Patients with inadequate collateral development across the coarctation will be more symptomatic with greater propensity for distal hypoperfusion. Abdominal aortic coarctation nearly always is diagnosed in neonatal period and can present with life-threatening neonatal hypertension.

One notable extracardiac vascular association of coarctation is the increased incidence of saccular berry aneurysms (3–5%) in the circle of Willis. This coupled with upper extremity and cerebrovascular hypertension creates the potential for aneurysmal rupture, which can be fatal or result in a debilitating stroke. Any suggestive neurologic symptoms (e.g., acute severe headache or sudden neurologic loss) should trigger evaluation for this condition by CT, MRI, or angiography. Given the clinical association, many advocate routine lifetime screening for cerebral aneurysms, even in the absence of symptoms.

A thorough cardiovascular exam should assess for evidence of LV pressure overload/hypertrophy through a prominent LV point of maximal impulse, decreased ventricular compliance via the presence of an S4, severe obstructive coarctation with or without collateral flow by the presence of systolic and/or continuous murmurs on the front chest, back, or abdomen. As BAV is found in 80% of coarctation patients, there may be signs of the bicuspid valve including a systolic click and a murmur of regurgitation or stenosis. Pulses should be palpated in all extremities and may be absent or diminished in the femoral artery, dorsalis pedis, and posterior tibialis. Simultaneous pulse measurement of brachial and femoral artery can reveal a brachiofemoral delay implying obstruction to lower extremity blood flow.

All patients presenting with hypertension or prehypertension, especially at an early age, should have four-extremity blood pressure measurements upon initial evaluation. In patients without significant aortic obstruction or vascular disease, the principle of pressure amplification ensures that the lower extremities have higher blood pressure readings than upper extremities. In patients with coarctation or obstructive peripheral vascular disease, noninvasive assessment of lower extremity blood pressure can be reduced to absent. In general, four-extremity blood pressure should also help rule out aortic arch involvement of the coarctation if both upper extremity blood pressures are equal. However, there is a higher incidence in coarctation of anomalous right subclavian artery from descending aorta (~5%) compared to standard population. In the absence of aortic imaging, this can make it challenging for the unaware clinician to distinguish juxtaductal coarctation from arch hypoplasia.

Aortic imaging is crucial for coarctation diagnosis and evaluation including echocardiography, CT, and MRI, though classic rib notching and thoracic collaterals and aortic patterns from pre- and post-stenotic dilation can be appreciated on chest X-ray. Echocardiography will reveal associated congenital heart defects in addition to visualizing bicuspid aortic valves with corresponding aortopathy of the root and ascending aorta. In adults, suprasternal notch views of the aortic arch and descending aorta can help visualize the juxtaductal region on 2D echo and quantify coarctation gradients using continuous-wave Doppler. In general, peak gradients from echo overestimate the gradients achieved by extremity blood pressures or in the catheterization laboratory. When coarctation is severe, pulse-wave Doppler of the abdominal aorta can display a dulled systolic peak and increased diastolic flow.

6 Medical Therapy in Repaired Coarctation

There are a few studies with conflicting findings to guide treatment of early or late hypertension in repaired coarctation patients [15,16,17]. Prior to coarctation repair, blood pressure control can be challenging and require polypharmacy. Blood pressure treatment may be limited by underperfusion below the coarctation level, leading to symptoms such as claudication or signs of underperfusion of abdominal organs.

Given the presumed mechanisms of hypertension development in coarctation, it is not surprising that ACE inhibitors, ARBs, and beta blockers are often first-line therapies. In two open-label prospective trials, enalapril and candesartan were slightly more effective in lowering blood pressure and reducing LV mass index compared to atenolol [16, 17]. In another study, metoprolol was more effective than candesartan to effectively lower blood pressure [15]. As such there is no definitive evidence as to the choice of antihypertensive. Similar to the state of affairs in hypertension as a whole, the goal to treat high blood pressure may supersede choice of therapeutics.

7 Surgical and Interventional Treatment of Coarctation

In adults, the majority of patients followed with aortic coarctation have either unrepaired disease with a new diagnosis or recurrent coarctation with prior repair. Indications for treatment include a gradient or blood pressure differential ≥20 mmHg or a peak gradient <20 mmHg in the presence of significant collaterals. Additional considerations include symptoms related to coarctation, upper extremity hypertension, hypertensive response to exercise, and pathologic left ventricular hypertrophy [18, 19]. The European Society of Cardiology guidelines provide a Class IIb recommendation for treatment when the aortic narrowing is ≥50% of the aortic diameter at the diaphragm, regardless of pressure gradient or the presence of hypertension [19, 20].

Both surgical and interventional approaches are viable therapies for coarctation; the choice of modality depends on patient age and size, technical suitability, concomitant cardiovascular abnormalities, and institutional experience [20]. In neonates, surgery remains the standard of care with operative survival ~99%. In children, stenting is possible when the aorta can accommodate a stent that maybe expanded to larger adult diameters in the future. In adults, stenting and surgery are considered depending on the anatomic details and comorbid conditions though coarctation surgery in adults does have higher perioperative risk. Surgical repair has been shown to have 91% survival at 20 years when surgery is performed <14 yo and 79% survival when >14 yo [21].

There are multiple surgical approaches that have been used to repair coarctation (Fig. 16.3)—each technique has pros and cons (Fig. 16.4a) [22]. Crafoord first performed aortic resection with end-to-end anastomosis in 1944 though recurrence rates were over 50% [20, 23]. This technique was later modified by Amato in 1977 to include a broader longitudinal resection and extended anastomosis. In many modern-day institutions, extended end-to-end repair remains the preferred surgical technique with low mortality and low restenosis rates of 4–11% [22, 24].

Fig. 16.3
figure 3

Different types of surgical repair for aortic coarctation. (a) End-to-end anastomosis. The coarctation segment is resected and the aorta is reapproximated. (b) Patch augmentation. The aorta is incised longitudinally and covered with a patch of polytetrafluoroethylene. (c) Interposition graft. (d) Ascending-to-descending aorta bypass graft. (e) Subclavian flap. After performing an extended aortotomy, the left subclavian artery is sewn over the isthmus of the aorta. (f) Extended aortic arch repair. This is done when there is severe transverse arch hypoplasia. Permission to use illustrations obtained from Dr. J. P. M. Hamer at the University of Groningen, The Netherlands

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Fig. 16.4
figure 4

Prognosis of patients with coarctation of the aorta. (a) Type of aortic coarctation repair stratified by decade. (b) Long-term survival rates of patients with aortic coarctation repair (~70%) vs. age- and sex-matched population (~90%). (c) Comparison of hypertension pre- and postoperatively at various time intervals of follow-up. Permission to use figures obtained from Brown ML et al (2013) J Am Coll Cardiol 62(11):1020–1025

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Additional surgical methods include aortic patch augmentation described by Vosschulte in 1961 which allows for the resection of longer coarctation segments with low recoarctation rates of 5–12% [25]. However, there is an increased risk of aneurysm formation along the patch in 18–50% of patients [22]. Subclavian flap repair was developed by Waldhausen and Nahrwold in 1966 that uses left subclavian tissue to augment the lumen. This negates the need for patch material, however does leave the scepter of subclavian steal or arm claudication in the future [26]. Interposition grafts (either homografts or Dacron based) were used as early as 1951 by Gross. There are inherent limitations to growth with this technique in children, and there is a risk of aneurysm formation at the suture lines of the graft [22]. Still this technique is used successfully in adults [27]. Ascending-to-descending aorta bypass grafts can intuitively avoid the complication of recoarctation; however this technique does entail its own concerns of long-term graft patency [28].

While balloon angioplasty remains a feasible option for focal coarctation, there are higher rates of recurrence (50% vs. 21%) compared to surgery [29]. Other publications have found balloon angioplasty of discrete coarctation to be a durable therapy with reported follow-up from 8 to 15 years in small prospective cohorts [30, 31]. Compared to angioplasty alone, stenting helps prevent elastic recoil of the aorta, requires less aortic overexpansion in treatment (thus decreasing risk of aneurysm formation), and still allows the possibility of future re-dilation [32,33,34,35]. In many institutions, covered stents have become a preferred strategy over bare metal stents [36]. The aortic covering can help mitigate many aortic wall complications (e.g., intimal tear or intramural hematoma). In the USA, the Cheatham Platinum (CP) stent (NuMED, Hopkinton, NY) has been approved by the FDA in 2016 for treatment of aortic coarctation (Fig. 16.5).

Fig. 16.5
figure 5

(a–d) Interventional repair of coarctation with covered CP stent. Once the stent is put in position and fully dilated, normal blood flow is restored. An alternative to stent placement is balloon dilation, which is preferred in children and neonates due to concerns about stent size—smaller stents cannot undergo serial dilation to keep pace with somatic growth, and larger stents may not fit into the femoral artery of smaller patients

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There is limited prospective data comparing surgery with stenting [32, 37, 38]. Several cohorts and one meta-analysis have suggested comparable rates of procedural success with overall reduction in periprocedural morbidity and length of hospital stay tempered by slight increase in rates of restenosis or reintervention [39,40,41]. The Congenital Cardiovascular Interventional Study Consortium has published the largest prospective comparisons of stent, balloon, and surgery [20, 42]. Stenting had a lower short-term complication rate (12.5%) compared to surgery (25%) and balloon angioplasty (44%). Complications include moderate or severe re-obstruction, aortic wall injury, and stent fracture. Total re-interventions were higher with stenting compared to other modalities though the majority of these were staged interventions for further stent expansion in native coarctation [20].

8 Hypertension After Coarctation Treatment

Surgical or interventional repair remains the mainstay treatment for native or recurrent coarctation. These interventions change the natural history of disease with improved survival and decreased vascular complications of MI and stroke though life expectancy curves of even repaired coarctation remain below in those of age- and gender-matched population (Fig. 16.4b) [2, 43, 44]. Its effects on hypertension, however, are more complex.

Both surgical and interventional repair of coarctation have been shown to decrease hypertension in the short-to-medium term or make it more manageable with pharmacotherapy (Fig. 16.4c) [45,46,47]. While preprocedural hypertension will regress or improve, especially if coarctation repair is performed earlier in life, many patients remain at risk for developing systemic arteriopathy including late hypertension [21, 48, 49].

After surgical or interventional repair, one national cohort study suggested a 20-year freedom from hypertension of only 51% and 79%, respectively [50]. Coarctation had a statistically significant odds ratio of 15.7 for late development of hypertension and 6.6 for stroke (Fig. 16.6) [48]. In Hager et al. cohort study of nearly 500 operated patients, prevalence of hypertension was over 50%, most related to duration of follow-up, as nearly all patients >55 yo were hypertensive [51, 52].

Fig. 16.6
figure 6figure 6

The age group distribution of the number (a) and the incidence (b) of patients with coarctation of the aorta and systemic hypertension. (c) The age group distribution of cerebrovascular accident (CVA). Permission to use figures obtained from Wu MH et al (2015) Am J Cardiol 116(5):779–784

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Even in adult patients who had successful coarctation repair with “normal range” resting blood pressures, accentuated systolic blood pressure and pulse pressure response was observed during daytime activities with higher LV mass measurements [53]. This was determined to be partly secondary to upper limb conduit artery dysfunction, finding a reduced brachial artery vascular response to both endothelium-dependent flow-mediated dilation and glyceryl trinitrate administration compared to age- and gender-matched controls. Even in normotensive patients after coarctation repair, vascular studies have suggested a shift in the relationship between vascular resistance and central venous pressure, suggesting a reset of the integrated cardiopulmonary-arterial baroreflex [54].

Another potential contributor to development of late hypertension in treated coarctation may be residual juxtaductal coarctation gradient or mild transverse aortic arch hypoplasia (TAA). Cases of de novo coarctation or repaired coarctation with residual gradients have found stenting to eliminate even mild coarctation (clinical gradient of ~20 mmHg) to help reduce systolic blood pressure in the medium term [47, 51].

After repair, a number of patients will appear to have TAA on imaging in the absence of any resting arm-leg gradient. While traditionally this is considered benign, there is one study linking it to late hypertension with an odds ratio 6.4 [55]. It is not known whether the operative risks of a more aggressive surgical arch reconstruction would ameliorate this increased risk of late hypertension.

This potential for late hypertension and late vascular complications demands careful monitoring and follow-up of all coarctation patients. Early emphasis of lifestyle modifications including optimal weight, diet, and aggressive pharmacologic treatment of coarctation should be the mainstay. Management of other reversible risk factors such as smoking cessation and hyperlipidemia should be emphasized from an early age.

Conclusion

Aortic coarctation remains a rare but important secondary cause of hypertension. The diagnosis should be considered and can be excluded through simple physical examination and confirmed through vascular and cardiac imaging techniques. Surgical and interventional repair of aortic coarctation is corrective with good medium- and long-term outcomes. While coarctation repair will ameliorate hypertension, these patients remain at risk for the development of late hypertension and future vascular abnormalities. All coarctation patients should receive lifelong care and risk factor modification.