What is coarctation of the aorta, particularly in patients with Ehlers-Danlos syndrome (EDS)?

Coarctation of the Aorta

Coarctation of the aorta is a congenital narrowing of the aorta, typically occurring just distal to the left subclavian artery at the ligamentum arteriosum, causing upper extremity hypertension and lower extremity hypoperfusion that requires lifelong surveillance even after successful repair. 1

Definition and Anatomic Features

Coarctation consists of short-segment narrowing in the region of the ligamentum arteriosum adjacent to the origin of the left subclavian artery. 1 In some cases, narrowing extends to the aortic arch or isthmus. 1 The lesion manifests as either a discrete stenosis or a hypoplastic segment, with more distal locations termed mid-aortic syndrome requiring different management. 1

• An intrinsic abnormality in the aortic wall predisposes to dissection or rupture in the ascending aorta or at the coarctation site itself. 1
• Extensive collateral vessels may develop proximal to the obstruction, which can reduce the measured gradient and mask the true severity of obstruction. 1

Associated Cardiac and Vascular Lesions

Bicuspid aortic valve occurs in 50-85% of coarctation patients and requires concurrent surveillance. 1 This is the most common associated lesion and has significant implications for long-term management.

Additional associated conditions include: 1

• Subaortic stenosis
• Mitral valve abnormalities (including parachute mitral stenosis)
• Ventricular septal defect
• Circle of Willis cerebral artery aneurysms (10% prevalence) 1
• Ascending aortic aneurysms 1

Coarctation may be associated with Turner syndrome, occurring in 7-18% of Turner syndrome patients, with up to 12.6% of females with coarctation having Turner syndrome. 1

Clinical Presentation and Physical Examination

Unrepaired Coarctation

The pathognomonic finding is brachial-femoral pulse delay with decreased amplitude or absent femoral pulses compared to brachial pulses. 1 This reflects the hemodynamic obstruction and should be assessed in every patient with systemic hypertension. 1

Hypertension is present in the right arm relative to the lower extremities, unless anomalous origin of the right subclavian artery is present. 1 The left subclavian artery may be close to the narrowing and thus may or may not show hypertension. 1

Blood pressure findings: 1

• Supine bilateral arm (brachial artery) pressures should be measured
• Prone right or left supine leg (popliteal artery) pressures should be measured
• A pressure differential >20 mmHg between upper and lower extremities suggests significant coarctation

Auscultatory findings: 1

• Murmur or bruit in the left interscapular position (from coarctation or collaterals)
• Continuous murmurs over parasternal areas (mammary arteries) if collaterals present
• Continuous murmurs around left scapula if collaterals present
• Periscapular collaterals may be palpable
• Parasternal and apical systolic ejection sound (suggests associated bicuspid aortic valve)
• Systolic crescendo-decrescendo murmur (left ventricular outflow tract obstruction)
• Early diastolic decrescendo murmur (aortic regurgitation)

Carotid pulsations may be hyperdynamic. 1

Symptoms

Mild cases may remain undetected until adulthood. 1 Symptoms reflect: 1

• Pre-stenotic hypertension: headache, nosebleeds, exertional headaches 1
• Post-stenotic hypoperfusion: abdominal angina, claudication, leg fatigue 1

The natural course without treatment is driven by hypertension-related complications including heart failure, intracranial hemorrhage, premature coronary/cerebral artery disease, and aortic rupture/dissection. 1 Mean age of death if untreated is 34 years. 2

Diagnostic Evaluation

Initial Assessment

Every patient with systemic arterial hypertension should have brachial and femoral pulses palpated simultaneously to assess for brachial-femoral delay. 1 This is a Class I recommendation with Level of Evidence C. 1

Blood pressure measurements at both arms and one lower extremity are mandatory in all coarctation patients. 1, 3

Imaging Modalities

Initial imaging and hemodynamic evaluation by transthoracic echocardiography (TTE), including suprasternal notch acoustic windows, is the first-line diagnostic tool. 1 TTE demonstrates: 1

• The coarctation on suprasternal notch view of aortic arch and proximal descending aorta
• Color flow imaging and Doppler velocity across the coarctation
• A diastolic tail in the descending thoracic aorta or abdominal diastolic antegrade flow suggests significant narrowing 1
• Left ventricular hypertrophy (marker of disease severity) 1

Every patient with coarctation (repaired or not) should have at least one cardiovascular MRI or CT scan for complete evaluation of the thoracic aorta and intracranial vessels. 1 This is a Class I recommendation with Level of Evidence B. 1

CMR and cardiac CT are the preferred imaging techniques for depicting the narrowing and surrounding anatomy necessary for interventional decision-making. 1, 3 These modalities: 1

• Visualize the entire thoracic aorta
• Define coarctation anatomy and assess for arch hypoplasia
• Identify collateral vessels
• Detect aneurysms and associated aortic pathology
• Evaluate for bicuspid aortic valve and ascending aortic dilation

Hemodynamic Criteria for Significant Coarctation

Significant coarctation is defined by: 1, 3

• Peak-to-peak invasive gradient >20 mmHg, OR
• Peak-to-peak gradient <20 mmHg with anatomic imaging evidence of significant coarctation plus radiological evidence of significant collateral flow 1

• 50% narrowing relative to aortic diameter at the diaphragm level 1, 3

Important caveat: In the presence of collaterals or decreased left ventricular function, gradients or ankle-brachial index may underestimate severity. 1

Additional Diagnostic Studies

Electrocardiogram: 1

• May demonstrate left ventricular hypertrophy with secondary ST-T wave abnormalities
• Occasionally shows right ventricular conduction delay

Chest X-ray: 1

• Prominent curvilinear shadow along mid-right sternal border (dilated ascending aorta)
• "3 sign" from indentation at coarctation site
• Rib notching on underside of ribs 3-9 from collateral vessels

Special Consideration: Ehlers-Danlos Syndrome

While the provided evidence does not specifically address coarctation in Ehlers-Danlos syndrome (EDS), the general principles apply with heightened concern for aortic wall integrity. The intrinsic aortic wall abnormality in coarctation predisposes to dissection or rupture 1, which would be compounded by the connective tissue fragility in EDS, particularly vascular EDS. These patients would require even more vigilant surveillance and potentially earlier intervention thresholds, though specific guidelines for this population are not established in the current evidence.

Treatment Indications and Approaches

Indications for Intervention

Intervention is indicated in patients with hypertension and an increased non-invasive gradient between upper and lower limbs (decreased ankle-brachial index) confirmed with invasive peak-to-peak measurement >20 mmHg. 1, 3 This is a Class I recommendation. 1

Intervention is also indicated with peak-to-peak gradient <20 mmHg when anatomic imaging shows significant coarctation with radiological evidence of significant collateral flow. 1

Endovascular treatment should be considered in hypertensive patients with >50% narrowing relative to aortic diameter at the diaphragm, even if invasive peak-to-peak gradient is <20 mmHg, when technically feasible. 1, 3 This is a Class IIa recommendation. 1

Endovascular treatment should be considered in normotensive patients with invasive peak-to-peak gradient >20 mmHg, when technically feasible. 1, 3

Treatment Modalities by Age and Anatomy

For older children (>25 kg) and adults, covered stenting is the first-choice treatment for native coarctation and re-coarctation. 1, 3 Transcatheter treatment is preferred when technically feasible. 1, 4

Surgical repair is the treatment of choice in neonates, infants, and young children. 4 Surgical options include: 1

• Subclavian flap aortoplasty
• Resection with end-to-end anastomosis (simple or extended)
• Patch aortoplasty
• Interposition grafting
• Bypass grafting (ascending to descending aorta conduit in complex cases)

The choice between percutaneous catheter intervention versus surgical repair should be determined by consultation with a team of adult congenital heart disease cardiologists, interventionalists, and surgeons. 1

Medical Management

Hypertension should be controlled with beta-blockers, ACE inhibitors, or angiotensin-receptor blockers as first-line medications. 1 The choice may be influenced by aortic root size and presence of aortic regurgitation. 1

Hypertension in coarctation patients should be treated according to standard ESC or ACC/AHA hypertension guidelines. 1

Long-Term Complications and Follow-Up

Post-Repair Complications

Hypertension remains an important complication even after successful treatment and is more common when initial repair is performed in adulthood. 1

Right arm 24-hour ambulatory blood pressure measurement or exercise tests better detect hypertension than office measurements alone. 1, 3 This is critical because exercise-induced hypertension may be present despite normal resting blood pressures. 1

Late complications requiring surveillance: 1

• Recurrent stenosis/re-coarctation (occurs in ~10% after surgical repair, ~8% after balloon dilation) 1
• Aneurysm or pseudoaneurysm formation (particularly with patch repairs) 1
• Rupture
• Persistent or recurrent hypertension
• Aortic dissection

Lifelong Surveillance Requirements

All coarctation patients require lifelong follow-up regardless of treatment success. 1, 3 This is a Class I recommendation with Level of Evidence B. 1

Imaging of the aorta with CMR or cardiac CT every 3-5 years is required, adjusted to previous imaging findings, clinical status, and type of intervention. 1, 3 This documents post-repair or post-interventional complications including re-coarctation, aneurysms, pseudoaneurysms, and dissection. 1

Surveillance for bicuspid aortic valve dysfunction and ascending aortic dilation is required in coarctation patients. 3 When bicuspid aortic valve is present with maximum aortic diameter >40 mm, serial TTE imaging after 1 year, then every 2-3 years if stable, is recommended. 1

Screening for intracranial aneurysms by MRA or CTA may be reasonable, though routine screening in asymptomatic patients currently lacks strong evidence. 1, 3 The prevalence of intracranial aneurysms is 10% in coarctation patients. 1

Cardiovascular Risk Stratification

Patients with coarctation continue to have reduced life expectancy and increased risk of cardiovascular sequelae despite adequate relief of stenosis. 4 Long-term risks include: 1

• Heart failure
• Premature coronary artery disease
• Cerebrovascular disease and stroke
• Aortic complications (dissection, rupture)

Intensive follow-up of left ventricular function, valvular function, blood pressure, and anatomy of the heart and aorta is critical in coarctation management. 4

Key Clinical Pitfalls

Collateral vessels can reduce the measured gradient and mask severity of obstruction 1, leading to underestimation of disease. Always correlate hemodynamic data with anatomic imaging.

Decreased left ventricular function can also cause gradients or ankle-brachial index to underestimate severity. 1 Do not rely solely on gradient measurements in these patients.

The location of coarctation relative to the left subclavian artery determines which arm will be hypertensive. 1 Always measure blood pressure in both arms and at least one leg.

Anomalous origin of the right subclavian artery can alter the typical blood pressure pattern. 1 Be aware of this anatomic variant when interpreting blood pressure differentials.

Patch repairs carry particular risk of repair-site para-anastomotic aneurysms or pseudoaneurysms. 1 These patients require especially vigilant imaging surveillance.