A 15-year-old boy with neurofibromatosis-1 (NF-1) was recognized to have severe hypertension when being screened for a school athletic team. His blood pressure was 225/110 mmHg. His only complaint was lower extremity fatigue with modest physical activity. A continuous systolic bruit that did not vary with respiration was noted in his epigastrium. There was a femoral-radial artery pulse delay. He had palpable pedal pulses, with good capillary fill in his toes. The left border of cardiac dullness was 8 cm to the left of the mid-sternal line with a sustained apical impulse. There were no cardiac murmurs. An electrocardiogram documented mild left ventricular hypertrophy. His chest film revealed a slightly enlarged heart. There was no ribnotching to suggest collateral vessels due to a thoracic aortic coarctation. His basic blood chemistries and urinalysis were normal. Prior to his referral to our hospital he had undergone an attempted percutaneous transluminal angioplasty (PTA) of the right renal artery. Failure of the renal PTA and refractory hypertension led to his admission for further study and therapy.

Question 1

What would be the definitive manner of imaging his aorta and its branches?

A.  Ultrasonography

B.  Computed tomographic arteriography (CTA) C.  Magnetic resonance angiography (MRA)

D.  Conventional arteriography (Digital subtraction angiography)

Conventional aortography was chosen to best define his vascular anatomy because of its greater definition of small arteries. It documented an abdominal aortic narrowing beginning at the CA level and extending below the renal arteries, as well as ostial narrowings of both renal arteries, the celiac artery (CA) and superior mesenteric artery (SMA) (Fig. 30.1).

J.C. Stanley ( )

Section of Vascular Surgery, Department of Surgery, University of Michigan Cardiovascular Centre, University of Michigan Medical School, Ann Arbor, MI, USA

Deep abdominal ultrasonography prior to his referral had documented abnormal midabdominal aortic, bilateral renal artery, CA, and SMA velocities, all of which exceeded 300 cm/s, compared to a 125 cm/s velocity in the infrarenal aorta. The anatomic detail of the splanchnic and renal circulation revealed by ultrasonography was limited. Similarly, an MRA obtained before the failed PTA did not clearly delineate the suspected anatomic extent of his aortic branch narrowings.

Question 2

What are the preferred treatment options in managing this patient’s aortic disease?

A.  Thoracoabdominal bypass B.  Patch aortoplasty

C.  Aggressive medical therapy with a polypharmacy including ACE inhibitors and diuretics

D.  Percutaneous ballon angioplasty with stenting

E.  A thoracoabdominal bypass was performed with a 16 mm ePTFE graft.

Question 3

How would you treat the bilateral renal and splanchnic arterial stenotic disease in this patient?

A.  Aortic implantation of the normal renal and mesenteric arteries beyond their stenotic segments

B.  Renal or mesenteric bypasses with an internal artery graft C.  Renal or mesenteric bypasses with a vein graft

D.  Balloon angioplasty

The left renal artery and SMA distal to their proximal stenotic segments were transected, spatulated, and reimplanted onto the adjacent infrarenal aorta. The right renal artery was reconstructed with an iliorenal bypass.

Question 4

How would you treat the renal and splanchnic arterial disease?

A.  At the same time the aortic coarctation is being repaired? B.  At a different time than the aortic repair?

C.  BWith anti-inflammatory agents (immunosuppressants)? D.  With anti-thrombotic agents (ASA, clopidogrel)?

Treatment of the renal artery and SMA narrowings occurred at the same time as the aortic repair.

pressure elevations refractory to simple drug interventions should raise the suspicion of a secondary form of hypertension. Furthermore, the presence of NF-1 and its known association with arterial stenoses would raise a suspicion of the midaortic syndrome. These later patients often have coexisting splanchnic and renal artery occlusive disease.

Aortic Coarctation Character: An earlier collective review of 119 patients identified suprarenal coarctations in 11%, intrarenal coarctations in 54%, infrarenal coarctations in 25%, and diffuse aortic hypoplasia in 12%.8 A contemporary series of 53 patients from the University of Michigan, revealed 69% suprarenal, 23% intrarenal, and 8% infrarenal abdominal aortic coarctations. The latter reflects a more contemporary classification of aortic coarctation, based upon the most superior level of the narrowing.17 Indeed, it is the most cephalic extent of the disease that defines the complexity of the aortic reconstruction, with considerable differences if the CA and SMA are involved, compared to the renal arteries alone. Most aortic coarctations are diminutive vessels, often with an hour-glass narrowing representing a lack of growth in developmental lesions or circumferential contraction in cases of an inflammatory aortitis. Such morphologic changes are best identified by detailed imaging. [Q1]

AssociatedRenalandSplanchnicArterialDisease:Nearly80%ofpatientswithabdominal aortic developmental lesions have been reported to have renal artery stenoses,8 a finding consistent with the recent Michigan series in which 87% had renal artery narrowings orocclusions.17 Splanchnicarterialocclusivediseasehasbeenpreviouslyreportedtoaffect 22% of patients with abdominal aortic coarctations.8 The true incidence of splanchnic arterial involvement may be much greater, in that lateral aortograms were not routinely obtained in evaluating many of these patients. The more complete imaging in the recent Michigan series revealed 62% to have CA or SMA stenoses and occlusions, with both vessels involved in 82% of these cases.17 Suprarenal or infrarenal coarctations, when distant from the CA and SMA, are less likely to be associated with stenotic branch disease, compared to more centrally located abdominal aortic coarctations. Presence of these branch narrowings are best defined by detailed imaging. [Q1]

Pathogenesis: Many abdominal aortic coarctations appear related to events occurring around the 25th day of fetal development. At that time the two embryonic dorsal aortas fuse and lose their intervening wall to form a single vessel. Overfusion of the two embryonic dorsal aortae or their failure to fuse with subsequent obliteration of one of these vessels would predictably result in an aortic narrowing.23 Developmental overfusion of the two primitive dorsal aortas receives support in patients with decreased aortic diameters who have single origins of the lumbar arteries.17,24

Multiple renal arteries to one or both kidneys in nearly half of the patients exhibiting suprarenal and intrarenal abdominal aortic coarctations exceeds the 25–35% observed in the general population and also supports a developmental etiology of these narrowings.8,16 Normal aortic development occurs at approximately the same embryonic time that the multiple metanephric arteries involute, leaving a single renal artery. Dominance of this single renal artery is alleged to result from its obligate hemodynamic advantage over adjacent metanephric vessels. It is likely that if aortic narrowings exist, flow disturbances will occur in the vicinity of this principle renal artery and diminish its hemodynamic advantage, allowing persistence of adjacent metanephric channels. The fact that aortic narrowings distant from the renal arteries are less likely to be associated with multiple renal arteries lends further credence to this developmental hypothesis.8,16,17,25

Viral-mediated events may impede transition of fetal mesenchymal tissue to vascular smooth muscle or alter its organization and growth in utero, and also result in developmental aortic narrowings. Certain viruses, including rubella, are cytocidal and inhibitory to cell replication, with intimal fibroplasia and aortic hypoplasia occurring as a consequence.26–29 In fact, fibroproliferative intimal disorders have been documented in the aorta and large elastic arteries of 16.5% of patients exhibiting the congenital rubella syndrome.28

Patients with NF-1 exhibit an unusually high frequency of arterial abnormalities, includingdevelopmentalabdominalaorticcoarctationsandrenalarterystenoses.30 Because of the protean nature of NF-1 and infrequent genetic analyses of patients with abdominal aortic coarctation, the exact frequency of this disease among these individuals is unknown. Nevertheless, 29% of the recent Michigan series’ patients carried a diagnosis of NF-1.17 The primary vascular pathology in neurofibromatosis appears to be related to abnormal smooth muscle growth, not entrapment or invasion of the arterial wall by neural elements.31,32 Similar events may affect patients with the Alagille syndrome,33 and Williams’ syndrome.34

Panaortitis with adventitial or periadventitial fibrosis and associated inflammatory cell infiltrates, suggesting an active or chronic aortitis, is another well recognized cause of abdominal aortic coarctations. The proposition that most abdominal aortic coarctations are a variant of an inflammatory aortitis like Takayasu’s disease is quite controversial and not supported by histological findings.21,35 This cause of aortic narrowings, suspected in only 8% of the recent Michigan series,17 is encountered much more often in the subcontinent populations of Asia and South America.

Clinical Manifestations: Most patients with midaortic syndrome present with uncontrolled hypertension due to suprarenal or intrarenal aortic coarctations, and coexisting renal artery stenoses in many cases. Changes in pulsatile flow and pressure across renal stenoses or aortic narrowings are responsible for renin-angiotensin system activation and subsequent blood pressure elevations. This form of renovascular hypertension is usually resistant to simple pharmacologic control. An occasional patient reports exercise-related lower extremity fatigue, but true claudication is rare. Associated splanchnic arterial occlusive disease affects a majority of those aortic narrowings, yet symptomatic intestinal ischemia is very uncommon.17,36 In the recent Michigan series, more than half the patients manifest splanchnic occlusive lesions, yet only 6% experienced intestinal angina.17

Abdominal aortic coarctations usually cause signs or symptoms during the first or second decade of life, yet an earlier review noted that patients had reached a mean age of 22 years before the diagnosis was actually confirmed.8 Untreated, this entity has been associated with stroke, progressive left ventricular hypertrophy with congestive heart failure and flash pulmonary edema, and less often with renal insufficiency.37 In one review, 55% of untreated patients died at a mean age of 34 years.8

Clear anatomic imaging is essential to establishing a correct diagnosis of midaortic syndrome. [Q1] Deep abdominal ultrasonography may provide evidence of narrowed vessels with documented increases in velocity blood flow. Ultrasonography may useful for screening, but it is inadequate at providing precise information about the character and location of stenotic disease in small arteries. [Q1:A] MRA is noninvasive and may give an accurate accounting of aortic and aortic branch disease. However, a severe stenosis may be suggested by MRA when such is not present, because of the phase-drop out phenomenon

associated with turbulent blood flow. This often occurs in the face of arterial tortuosity, without the presence of an actual arterial narrowing. [Q1: C] Thus, either multi-slice CTA or catheter-related conventional digital subtraction arteriography are the favored examinations when assessing the disease pattern in patients with midaortic syndrome. [Q1: B, D] Treatment Options: The two procedures most commonly performed in treating aortic coarctations remain open interventions.17 Patch aortoplasty, when technically feasible has recently become a common means of treating isolated abdominal aortic coarctations. [Q2: B] Thoracoabdominal bypass may be favored in certain patients having too narrow or too lengthy of a coarctation segment to allow easy placement of a patch, as well as in certain

patients having complex disease affecting the renal and splanchnic arteries. [Q2: A] Thoracoabdominal bypass grafts usually originate from the distal thoracic aorta above

the diaphragm or from the supraceliac aorta at the diaphragmatic hiatus, being passed behind the left kidney to the distal aorta.17 In some patients, aortic exposure may be facilitated by a thoracoabdominal incision through the left sixth or seventh intercostals space extending from the posterior axillary line across the costal margin, onto the abdomen, in either an oblique fashion to the right of the umbilicus or as a midline incision to just above the pubis. In younger children and adolescents, a transverse supraumbilical abdominal incision has been used most often, extending laterally to the posterior axillary lines, combined with medial rotation of the viscera, allowing access to the abdominal aorta from its supraceliac level at the aortic hiatus to the origin of the iliac arteries. [Q2: A]

Dacron graft knitted or woven thoracoabdominal grafts have been used in the distant past, with expanded Teflon grafts used more often in recent years because of their greater stability regarding postimplantation dilatation.17 Graft diameter should be chosen to be as big as possible, short of being so large that excessive luminal thrombus would accumulate. In children, the intent is to oversize grafts compared to the aorta, with anticipated growth otherwise resulting in a graft too small to maintain normal distal pressures and flow. In the ideal circumstance, oneshould use agraftwhosesize would not representa kineticenergyconsuming constriction as the patient grows into maturity. This means having a conduit at least 60% or 70% the size of the adult aorta. This translates into using 8–12 mm grafts in young children, 12–16 mm grafts for early adolescents, and 14–20 mm grafts in late adolescents and adults.17 In the very young child, use of large conduits may not be possible. Graft length is considered a non-issue in older children and adolescents, with axial growth from the diaphragm to pelvis being minimal after age 9 or 10 in late childhood. [Q2: A]

Patch aortoplasty is usually undertaken when the coarctation segment is short and has a largeenoughdiametertoallowcompletionofananastomosiswithoutanoverlapofsutures from the opposing sides of the patch.17 Whenever possible, patches in children should be made sufficiently large enough, similar to thoracoabdominal graft sizing, so as to not be constrictive with growth into adulthood, yet not so generous as to risk development of an extensive lining of unstable thrombus. Expanded Teflon graft material is again favored over-fabricated Dacron graft material, because of the latter’s propensity for dilatation years after implantation. [Q2: B]

Endoluminal stenting of select abdominal aortic coarctations may be considered in some patients. [Q2: C] Current endovascular technologies appear to allow the safe treatment of focal stenoses, excluding tight fibrotic narrowings, remote from the CA, SMA, and renal arteries. Percutaneous transluminal angioplasty of an abdominal

aortic coarctation was first reported in 1983.13 Subsequent case reports described the transition to stenting in these cases.1,6 In fact, early and late failures of balloon angioplasty alone suggest that stent placement is necessary to overcome the significant recoil of these often hypoplastic and highly fibrotic aortic narrowings.7,10,17,38 The authors remain cautious at accepting the long-term benefits of endoluminal treatment of abdominal aortic coarctation in any patient, except adults with very focal narrowings distant from their renal arteries. Given the high frequency with which the renal and splanchnic arteries are affected in abdominal aortic coarctation, especially in the younger-growing patient, the number of lesions amenable to endovascular repair may be limited. [Q2: C]

Reoperations after repairs of abdominal aortic coarctation are infrequent, but may be required for anastomotic narrowings or if a patient outgrows the adequacy of the primary procedure. The fact that nearly 10% of the currently reported cases in the Michigan series required late secondary operations supports the importance of life-long follow-up of these patients.17 Aneurysmal aortic deterioration in the region of a patch in one of the patients in that series, many years after the initial reconstruction and 2 years after she completed her only pregnancy, deserves note. The effect of gestational hormones and blood pressure increases during pregnancy may be relevant, in that pregnancy-related aortic diameter increases of 1.5 cm or more have been observed at the site of thoracic aortic coarctation repairs in nearly 10% of those undergoing such an intevervention.39 Although this finding may not be directly extrapolated to abdominal aortic coarctation repairs, it does justify close surveillance of those patients who subsequently become pregnant. [Q5]

Division and reimplantation of the normal renal artery beyond an ostial stenosis onto the adjacent aorta become an important means of renal revascularization in these patients.17,37 [Q3: A] In these circumstances, the transected renal artery is usually spatulated anteriorly and posteriorly to create a generous anastomotic orifice. An oval aortotomy is best made with an aortic punch, being a little more than twice the diameter of the renal artery being implanted. This will provide a sufficiently large anastomosis so an anastomotic narrowing would not evolve as the child grows. These anastomoses are usually performed using interrupted monofilament sutures in young patients. However, a continuous suture is often used in older adolescents with large renal arteries. Most implantations of the renal artery are into a normal infrarenal segment of the aorta. Medial mobilization of the kidney may be necessary to ensure that there is no tension on the implanted renal artery. Implantation of a renal artery branch or accessory renal artery into a nondiseased adjacent main or segmental renal artery also involves spatulation of the segmental vessel and completion of the anastomosis using monofilament sutures. Implantation of a renal artery into the superior mesenteric artery may be undertaken when implantation elsewhere is deemed hazardous. [Q3: A]

Aortorenalbypasswiththeinternaliliacarteryusedasafreegrafthasbecomepreferred when a bypass is required.17,37 [Q3: B] The excised internal iliac artery usually includes its inferior branches, which are incised to create a large common orifice for the aortic anastomosis. Distal anastomoses from the renal artery to the graft are completed after spatulation of both the iliac artery and renal artery to increase the anastomotic circumference. Such ovoid anastomoses were less likely to develop late strictures and are usually completed

with interrupted sutures in very young children, although a continuous suture may be used in reconstructing larger renal arteries. Aortorenal bypasses with vein grafts were standard during the first decade of this experience, but because more than half these conduits undergo aneurysmal deterioration, they have not been favored during the past 25 years.17,36 However, when no other alternative exists vein grafts may be used with a knitted Dacron sleeve placed about them so as to limit the expected graft expansion. [Q3: C]

Irreparable renal disease is often the reason for performance of a nephrectomy. Nonsalvageable kidneys exist when radionuclide renal imaging confirms marked loss of renal function to less than 10% of total renal function, associated with diminutive-sized kidneys 2–3 cm in length due to loss of parenchymal tissue. Irreparable renal disease also includes kidney’s exhibiting multiple intrarenal aneurysms not amenable to any form of open reconstruction, in situ or ex vivo. In the aforenoted circumstances, and in the presence of a normal contralateral kidney, nephrectomy is reasonable.

The role of PTA in treating pediatric renovascular hypertension remains controversial. Failure after PTA for developmental disease might be anticipated, given the excessive elastic tissue in many stenoses, which would predictably contribute to early post-dilation recoil, as well as the minute caliber of these diseased vessels that might lead to their disruption.37 Nevertheless, a small number of recent reports suggest success with catheterbasedinterventions.20 Itisofnotethatifthediseasebeingtreatedisaquiescentinflammatory aortoarteritis, then more salutary outcomes might follow PTA than would be the case if developmentally hypoplastic renal arteries are being treated. However, even in the former setting, recurrent stenoses are frequent. [Q3: D]

Simultaneous or staged aortic and visceral artery reconstructions depend on the clinical relevance of the nonaortic disease as well as the proximity of the aortic reconstruction to the affected aortic branches. [Q4] Certainly, renal artery stenoses and secondary renovascular hypertension justify an aggressive reconstructive approach. A mandate to reconstruct the CA or SMA applies only to symptomatic cases. Nevertheless, a relative indication to prophylactically reconstruct these vessels exists when performance of an aortoplasty or renal revascularization would make a subsequent CA or SMA revascularization exceedingly difficult. [Q4: A] When the aortic reconstruction was distant from the CA or SMA, such as with thoracoabdominal bypass, a concomitant splanchnic revascularization is less likely to be performed. [Q4: B]

Long-term follow-up of patients undergoing surgical treatment of their abdominal aortic coarctation is warranted. At a minimum, noninvasive assessments of lower extremity blood flow with exercise ankle-brachial indices are recommended. [Q5: A] Imaging with MRA studies or CTA should be obtained if any evidence of diminished blood flow exists. [Q5: B, C] More detailed imaging with conventional arteriography is appropriate if blood pressure increases occur in those who have undergone concomitant renal artery reconstructions or whose renal blood flow is dependent upon their aortic reconstruction. [Q5: D]

Abdominal aortic coarctation represents a complex vascular disease, often complicated by coexisting renal and splanchnic arterial disease. Individualized treatment is dependent on the pattern of the anatomic lesions, patient age, and anticipated growth potential. Salutary outcomes following carefully performed operative therapy are anticipated in more than 90% of patients.