Housecalls hero

Coarctation of the Aorta
December  2019

A 38-year-old female applied for life insurance. At age 28 she underwent successful stenting for an aortic coarctation. A regular follow-up by transthoracic echocardiography four and six years after stenting revealed a small intrastent gradient of 14 mm Hg. But very recently this gradient increased to 26 mm Hg, then two months later to 30 mm Hg. There was no associated cardiac defect and no left ventricular hypertrophy. The left ventricular ejection fraction was normal at 60% with a pulmonary artery systolic pressure in normal range as well.

She remains asymptomatic, her BP is normal at 110/78 mm Hg without treatment. The BMI is 22.3, and labs are within normal limits. 

What is coarctation of the aorta and what are the mortality implications?
Coarctation of the aorta (CoA) is a congenital cardiac defect leading to a narrowing of the descending aorta, which is typically located at the insertion of the ductus arteriosus just distal to the left subclavian artery at the level of the aortic isthmus. However, it is more likely to represent a spectrum of aortic narrowing from a discrete entity to tubular hypoplasia, with many variations seen between these two extremes.

Etiology
The etiology of CoA remains unclear. The primary mechanism is thought to be medial thickening and intimal hyperplasia that leads to the formation of a posterolateral ridge that encircles the aortic lumen, resulting in the CoA segment.

Another theory is that of aberrant ductal tissue residing in the wall of the fetal thoracic aorta and abnormal intrauterine blood flow through the aortic arch. A genetic predisposition is also
suggested by reports of CoA occurring in family members and by its association with Turner syndrome.

Pathophysiology
CoA does not cause a hemodynamic problem in utero, as two-thirds of the combined cardiac output flows through the patent ductus arteriosus (PDA) into the descending thoracic aorta,
bypassing the site of constriction at the isthmus.

During the neonatal period, when the PDA and foramen ovale (between the right and left atria) begin to close, the bloodflow that must cross the narrowed aortic segment to reach the lower
extremities steadily increases. As this occurs the hemodynamic changes may range from mild systolic hypertension to severe heart failure depending upon the severity of the coarctation and
the presence of other associated lesions.

At birth, the left ventricular afterload increases because of outflow tract obstruction resulting in increased systolic pressure in the left ventricle and proximal aorta.

Several compensatory mechanisms arise to surmount the left ventricular outflow tract obstruction. These include left ventricular myocardial hypertrophy, which maintains normal systolic function and ejection fraction, and the development of collateral blood flow involving the intercostal, internal mammary and scapular vessels, which circumvent the stenotic lesion (Figure 1).

Figure 1 - Cardiac MRI of a 53-year-old patient
with severe coarctation and evidence of
collateral flow.
Source: Marc G Cribbs Coarctation: a review www.USCjournal.com













Although CoA can be an isolated congenital heart disease, it is commonly found in other congenital syndromes and cardiovascular anomalies. The most common cardiovascular
malformation associated with CoA is bicuspid aortic valve (BAV), occurring in more than 50% of cases.

Other defects like atrial septal defect, ventricular septal defect, atrioventricular canal
defect, aortic stenosis, transposition of the great arteries, patent ductus arteriosus and hypoplastic left heart syndrome occur less frequently.

The most important non-cardiac lesion is cerebral aneurysm, which is present in up to 10% of patients.

Epidemiology
CoA is the fifth-most common congenital heart defect, accounting for 6% to 8% of live births with congenital heart disease. The estimated incidence is 1 in 2500 births, occurring more commonly
in males than females (59% versus 41%).

Clinical presentation
The clinical presentation and exam findings are variable based on patient’s age. Typically, earlier presentation corresponds to severe disease.

Younger children: Newborns and neonates are usually asymptomatic right after birth as the PDA helps perfuse the lower body irrespective of severity of CoA. Neonates with severe/critical CoA develop signs and symptoms of cardiogenic shock as the ductus arteriosus closes after birth. Clinically, babies may show absent/feeble femoral pulse, delayed capillary refill, feeding problems, decreased responsiveness, metabolic acidosis, mesenteric ischemia, myocardial depression, etc.

Older pediatric patients are usually diagnosed due to weak femoral pulse, upper extremity hypertension, a systolic murmur over upper sternal border with radiation to the back and upperlower extremity systolic blood pressure gradient. 

Newborn pulse oximetry screening is a great tool in detecting cases of critical congenital heart disease in newborns, although its utility is limited in patients with pure CoA and a closed PDA due to lack of blood mixing/shunting.

Adolescents and adults: Almost always these patients are diagnosed with CoA during workup of systemic hypertension or heart murmur. Clinical signs may include upper extremity
hypertension, weak femoral pulse, arm-leg systolic blood pressure gradient (>20 mmHg is significant), a systolic murmur on the back from flow through the coarctation segment or a continuous murmur from the collateral flow around the coarctation site. Intercostal pulses from collateral vessels are a pathognomonic sign.

Patients may also complain of frequent headaches from systemic hypertension and lower limb claudication from chronic hypoperfusion. If the collateral circulation around the coarctation
site is significant then distal pulses may be adequate and arm-leg blood pressure gradient may not be significant.

Diagnostic evaluation

EKG may be normal or demonstrate evidence of left ventricular hypertrophy from chronic left ventricular pressure overload.

Chest X-ray in adults may show a normal cardiac contour. Double contouring of the descending aorta known as the “3 sign” beneath the aortic notch is characteristic and represents narrowing of the aorta at the level of CoA and dilatation of the aorta pre- and post-CoA. Rib notching of the posterior fourth to eighth ribs caused by the dilated intercostal collateral arteries can be visible in patients with longstanding severe CoA.

Fetal echocardiography has advanced significantly during the past couple of decades to allow us to make prenatal diagnosis of CoA and avoid a cardiovascular catastrophe after birth.

Transthoracic echocardiography (TTE) is the primary imaging modality for suspected CoA. It has the capacity to provide us with diagnosis, to assess severity and to detect associated cardiac defects.

Cardiac magnetic resonance imaging (cMRI) or computed tomography angiography (CTA) clearly defines the location and severity of CoA as well as collateral vessels. cMRI is a preferred non-invasive, advanced imaging modality for patients with CoA since it does not include any exposure to ionizing radiation but provides excellent image resolution. This makes it ideal for initial imaging and serial follow-ups. 

Furthermore, cMRI angiography with gadolinium-enhanced contrast provides excellent visualization of extracardiac vasculature and allows for optimal three-dimensional reconstruction as needed. Utilization of phase contrast flow analysis helps to assess peak gradient across the coarctation site. If cMRI is ontraindicated, 

CTA imaging may be used to diagnose CoA.

Catheter angiography is currently limited to coronary angiography before intervention/surgery and when catheter-based intervention such as balloon dilatation and/or stenting is considered.

Natural history
We know from postmortem reports prior to the availability of operative repair that average survival age of individuals with unoperated CoA was approximately 35 years of age, with 75
percent mortality by 46 years of age.

Approximately one-quarter will die from aortic dissection or rupture, one quarter will die from heart failure, one-quarter will die from intracranial hemorrhage, and the remainder will die from
other complications.

Treatment
Indications for intervention: According to the most recent recommendations for the management of CoA issued by the American Heart Association/American College of Cardiology and the European Society of Cardiology, corrective intervention should be performed in patients with CoA with any of the following:
  • Critical CoA
  • CoA gradient >20 mm Hg
  • Radiologic evidence of clinically significant collateral flow
  • Systemic hypertension attributable to CoA
  • Heart failure attributable to CoA
These guidelines stress that correction of coarctation should be performed as early as possible (optimally early in childhood) to reduce long-term morbidity, to prevent the development of
chronic systemic hypertension and to improve survival.

Treatment options: Surgical repair, transcatheter balloon angioplasty (BA) and transcatheter stent implantation are treatment modalities available for management of CoA. The preferred treatment option depends on the anatomy of the coarctation, the age of the patient, the size of the patient and other comorbidities.

Surgical options, depending on the lesion, include subclavian artery patch aortoplasty, patch aortoplasty, bypass of the coarctation, tube graft replacement, aneurysm replacement, twostage
combined bicuspid valve surgery and arch and descending aorta replacement or ascending aorta–to–descending aorta bypass. Endovascular balloon dilatation and stent placement has
been used successfully and is becoming a less invasive alternative to conventional open surgical procedures except for neonates and infants less than four months old.

All three treatment modalities show significant improvement in systolic blood pressure and peak pressure gradient. The rate of acute complications is lower after stent implantation compared to
BA or surgery. However, planned re-intervention is more likely in stented patients. Stent implantation and surgery achieve superior hemodynamic results over BA.

Long-term cardiovascular complications
Major long-term complications following CoA repair include recoarctation (restenosis after an initially successful dilatation or operative repair), aortic aneurysm, systemic hypertension and
intracranial aneurysms.

Recoarctation rate is approximately:
  • 5% to 15% after surgery
  • Up to 50% in neonates and young infants, 20% to 30% in older children and 8% in adolescents and adults after balloo angioplasty
  • After stenting intermediate outcomes are promising.
Catheter-based intervention is preferred over surgical repair of recoarctation because mortality for reoperation is higher than for primary repair.

Aortic aneurysm may develop at the site of prior coarctation following surgery, BA or stent implantation. Its incidence after surgical repair or BA ranges from less than one percent to nine
percent and is generally treated surgically.

Systemic hypertension is more common in patients whose repair was performed after 20 years of age compared with those who were corrected in early childhood. The risk of hypertension
increases over time in all patients and, associated with left ventricular hypertrophy, is among the factors that contribute to premature death from coronary and cerebrovascular disease in patients with repaired CoA. Thus, it is paramount to control hypertension with medical treatment.

Intracranial aneurysms are associated with CoA in up to 10% of patients. This fact may justify routine screening for cerebrovascular aneurysms.

Whether the patient has undergone a surgical or transcatheter treatment, lifelong follow-up care is required to detect long-term complications.

Prognosis
The estimated 10-year survival following CoA repair is greater than 90%.

In a single-center series of 819 patients (mean age at repair 17.2±13.6 years) who underwent surgical repair of isolated CoA at the Mayo Clinic between 1946 and 2005, the survival rates at 10, 20 and 30 years after primary repair were 93%, 86% and 74%,
respectively.

In an earlier report from the same center, the most common cause of late death was coronary artery disease, followed by sudden death, heart failure, cerebrovascular accident and ruptured aortic aneurysm.

Data on long-term prognosis after transcatheter intervention are more limited. In a report of intermediate outcomes in patients enrolled in the Coarctation of the Aorta Stent Trial (COAST)-I trial, five-year freedom from reintervention was 75 percent.

Factors associated with decreased survival include older age at initial repair (i.e., older than 20 years) and preoperative hypertension.

After reintervention for restenosis, aneurysm or pseudoaneurysm, ML Brown et. al. showed that survival was 97% at five and 10 years respectively, and there was no difference in survival between operative and endovascular patients at 10 years (99% versus 91%, respectively).

Recently, A Sanchez Recalde et. al., in a retrospective study in Spain, found that the standardized mortality ratio (SMR) in the cohort of patients with aortic coarctation was 3.25 (Figure 2). The main independent predictors of death in this multivariate analysis were: left ventricular dysfunction, severe pulmonary arterial hypertension, and aortic wall aneurysms. SMR was 1.75 in patients with no risk factors, similar to the reference population.

Figure 2 - Age at diagnosis-, sex- and time of follow-up-adjusted Standardized Mortality Ratio
(SMR) in adults with aortic coarctation 
Source: Sanchez Recalde A et al Risk factors for excess mortality in adults with coarctation of the aorta; https://academic.oup.comeurheartj › article › suppl_1 › ehy565.2113

Returning to the case
First, this young woman underwent the repair of her CoA at 28 years old, which is usually not a favorable predictor of survival, but fortunately she is asymptomatic. And more importantly, she
has no hypertension, no heart failure, no aortic aneurysm and no arterial pulmonary hypertension.

However, the peak pressure gradient through the stent has steadily increased over the years, reaching 30 mm Hg on the latest transthoracic echocardiograpy. This is suspicious for a
recoarctation which may require a reintervention. It appears prudent to delay any offer pending resolution of the increasing gradient.

References
  • Brown ML, Burkhart HM, Connolly HM, et al. Coarctation of the aorta: lifelong surveillance is mandatory following surgical repair. J Am Coll Cardiol 2013; 62:1020.
  • Cohen M, Fuster V, Steele PM, et al. Coarctation of the aorta. Long-term follow-up and prediction of outcome after surgical correction. Circulation 1989; 80:840.
  • Forbes TJ, Moore P, Pedra CA, et al. Intermediate follow-up following intravascular stenting for treatment of coarctation of the aorta. Catheter Cardiovasc Interv 2007; 70:569.
  • Cribbs MG Coarctation: a review www.USCjournal.com Stout KK, Daniels CJ, Aboulhosn JA, et al. 2018 AHA/ACC Guideline for the Management of Adults With Congenital Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical
  • Practice Guidelines. J Am Coll Cardiol 2019; 73:e81.
  • Meadows J, Minahan M, McElhinney DB, et al. Intermediate Outcomes in the Prospective,
  • Multicenter Coarctation of the Aorta Stent Trial (COAST). Circulation 2015; 131:1656.
  • Holzer R, Qureshi S, Ghasemi A, et al. Stenting of aortic coarctation: acute, intermediate, and longterm results of a prospective multiinstitutional registry--Congenital Cardiovascular Interventional Study Consortium (CCISC). Catheter Cardiovasc Interv 2010; 76:553.
  • Brown ML, Burkhart HM et al Late outcomes of reintervention on the descending aorta after repair of aortic coarctation Circulation 2010; 122[suppl 1]:S81–S84.
  • Agarwala BN et al Uptodate Management of coarctation of aorta; last updated 01.10.2019
  • Sanchez Recalde A et al Risk factors for excess mortality in adults with coarctation of the aorta; https://academic.oup.com › eurheartj › article › suppl_1 › ehy565.2113