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Ann Thorac Surg 1999;67:1861-1863
© 1999 The Society of Thoracic Surgeons

Aortic dissection in Marfan’s syndrome

^a The Oxford Heart Centre, John Radcliffe Hospital, Oxford, England, United Kingdom

Address reprint requests to Dr Westaby, The Oxford Heart Centre, John Radcliffe Hospital, Headley Way, Headington, Oxford, OX3 9DU England

Presented at the Aortic Surgery Symposium VI, April 30–May 1, 1998, New York, NY.

	Abstract

Top Abstract Introduction Structure and functional changes... Surgery for acute type... References

 
Background. Aortic dissection is the most frequent cause of premature death in Marfan’s syndrome. Low-risk elective surgery of the abnormal aortic root has the potential to prevent this complication.

Methods. We examine genetic, structural, and pathophysiological mechanisms of aortic dissection and discuss the surgical methods used when dissection occurs.

Results. Abnormal fibrillin disturbs the functional relationship between blood flow and vascular endothelial cell response (mechanotransduction). Decreased arterial distensibility also decreases aortic wall stress, thereby predisposing to dissection in the weakened arterial wall. Radical root and wall surgery and lifelong beta-blockade are required after aortic dissection.

Conclusions. Detailed lifelong medical and surgical treatment can greatly prolong life in Marfan’s syndrome. Elective aortic root replacement is paramount in preventing aortic dissection and avoiding subsequent problems in the distal aorta.

	Introduction

Top Abstract Introduction Structure and functional changes... Surgery for acute type... References

 
Marfan’s syndrome is a well-defined genetic defect (chromosome 15q) with both a structural and functional propensity for aortic dissection. Severe elastic fiber degeneration occurs because mutant fibrillin is unable to bind calcium. Sinus dilatation and increased wall stiffness elevate pulse pressure on the structurally attenuated aortic wall. Impaired mechanotransduction (nitric oxide production) causes failure of flow-mediated vaso-dilation with increased wall stress and cardiac workload.

Prevention of aortic dissection is paramount for the Marfan patient. Lifelong ß-blockade and elective aortic root replacement (at 5.0 cm) transform the long-term outlook. Surgical risk and valve-related morbidity are low in specialist centers. Radical root replacement with open arch repair is required for dissection patients, but event-free survival is limited by distal aneurysm formation. Surgery for extensive arch and thoracoabdominal aneurysms carries the risk of cerebral injury, paraplegia, and renal failure. Evolving techniques are improving survival in these taxing operations.

The outlook for patients with Marfan’s syndrome is transformed by elective aortic root replacement [1]. With current methods, this can be performed with <2% 30-day mortality. Aortic root dilatation begins in infancy with a maximal rate of diameter increase during the ages of 6–14 years. After this, root enlargement slows, but the increase in radius and decreased wall thickness causes mural stress to rise dramatically. The mean root diameter for any given body surface area in Marfan’s syndrome is at or above the 95th percentile for normal subjects. Beta adrenergic blockade retards the rate of dilatation and risk of dissection by reducing wall stress. Data from the Johns Hopkins Hospital and the University of Tennessee show the rate of dilatation to be between 0.7 to 1.1 mm per year in treated patients verses 2.1 ± 1.6 mm per year in a control group [2].

Considerable energy has been expended in deciding the root diameter at which surgery should be undertaken. Aortic regurgitation seldom begins under 6 cm, but many patients suffer catastrophic acute type A dissection in a smaller root [3]. Given the safety of elective root replacement, the low risk of bleeding or thromboembolism with modern bileaflet valves, and survival of > 75% at 20 years (from early series), we suggest root surgery when the diameter reaches 5.0 cm [4]. Risk factors for hospital mortality are poor functional class (NYHA III–IV) and urgent surgery, both through late presentation or delayed operation. The outstanding problems for Marfan’s patients are failure to recognize the syndrome (and begin beta-blockade), failure to perform radical root replacement (Fig 1), unknown durability of the valve sparing operation, and late events if the patient survives acute dissection [5].

View larger version (80K): [in this window] [in a new window]   Fig 1. (A) Fifteen cm aortic aneurysm extending around the arch. (B) Massive chronic thoracoabdominal aneurysm after acute type A dissection in a patient with Marfan’s syndrome.

	Structure and functional changes in the Marfan aorta

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Considerable pleomorphism in Marfan’s syndrome occurs through variable expression of the fibrillin gene on chromosome 15q. This produces a phenotypic continuum blurring into the general population and accounting for cardiovascular anomalies in patients without ocular or skeletal expression [6]. The fibrillin monomer (a fundamental component of the elastic fiber) is a 42-amino acid pleated structure whose integrity depends on calcium binding by cysteine’s disulfide bonds [7]. Mutant fibrillin disintegrates through inability to bind calcium when cysteine is replaced by other amino acids.

Only small discontinuous segments of elastic laminae are found in the media with wide interlamellar spaces and loss of connections. Bundles of microfibils in various stages of elastic fiber assembly fail to merge into solid fibers (Grade III or IV medial degeneration) [8].

Endothelial cells lay down fibrillin microfibrils in the vascular subendothelium. Abnormal fibrillin causes a disturbed functional relationship between blood flow and vascular endothelial cell responses (mechanotransduction). In normal subjects, increased flow and pharmacological stimuli activate endothelial cell nitric oxide synthetase causing vasodilatation. In Marfan’s syndrome, the abnormal endothelial structural components cannot convert physical forces to nitric oxide production, resulting in failure of flow-mediated vasodilatation. Impaired mechanotransduction contributes to decreased arterial distensibility, and increases in pulse wave velocity, reflected wave pressure, and aortic wall stress. Together, these cause an increase in cardiac workload. Differences in the ratio of elastic to collagen fibers affect aortic wall stiffness (less elastin, stiffer aorta). Intravascular ultrasound measurements in the Marfan patient show changes in ascending aortic diameter (from diastole to systole) to be significantly reduced with increased pulse pressure on the thin aortic wall during systole [9]. Marfan patients consequently have both a structural and functional propensity towards aortic dissection.

	Surgery for acute type A dissection

Top Abstract Introduction Structure and functional changes... Surgery for acute type... References

 
Conservative operations with glue repair or valve resuspension are unacceptable in the Marfan patient. Failure to exclude the aortic sinuses results in aneursymal dilatation and the need for early reoperation [10]. Valve sparing operations have been used in dissection patients, but without extensive experience (in elective operations), the extra time and judgment required may prejudice survival. Together with the uncertain durability of the Marfan valve suspended in a tube graft, these factors mitigate against valve preservation after dissection in most centers.

The immediate priority in surgery for acute type A dissection is survival, and we consider the best chance of this to be through aortic root replacement. The coronary ostia are mobilized completely from the aortic wall and implanted into a valved conduit. We replace the aorta to the root of the innominate artery with an oblique open distal anastomosis, which includes the inferior aspect of the aortic arch [11]. Gelatine Resorcine-Formol glue is used to reconstitute the dissected distal aorta and coronary buttons [12]. There is no place for repair with a cross-clamp in place. This will not eliminate the distal dissection and risks aortic rupture from the cross-clamp site. If the aortic root is replaced during cooling (with a cross-clamp in place), the site of clamping must be excised during the open distal anastomosis.

Even after uneventful recovery from dissection repair, the outlook for these patients is dismal when compared with that after elective root replacement [13]. Persistence of the aortic false lumen with perceptible flow in 85% of patients presents a constant risk for aneurysm formation, reoperation, or sudden death [14].

Those who have undergone inappropriate root operation (valve replacement alone or supracoronary graft insertion and separate valve replacement) often develop aneursymal dilatation within a few years of surgery. The patient is kept on a beta-blocker with continuous surveillance of the whole aorta by magnetic resonance imaging or computed tomographic scan. Progressive expansion of a thin-walled arch or descending false channel eventually causes back pain, recurrent laryngeal nerve palsy, and tracheo-bronchial compression. Dilatation to 15 cm or more may occur within 2 years of acute dissection despite satisfactory blood pressure control.

Whether the second operation is performed via sternotomy or thoracotomy, there are significant risks from femoral arterial perfusion [15]. These include retrograde cerebral embolism from thrombus within the thoracoabdominal aorta or failure to perfuse the brachiocephalic arteries from this route. Consequently, we now cannulate the aorta as close to the arch as possible and use the main pulmonary artery for venous return. This method has substantially reduced our incidence of cerebral injury in operations on the arch and descending aorta.

For combined arch and descending thoracic replacement (via left thoracotomy), we replace the arch first using hypothermic circulatory arrest then cannulate the graft to reperfuse the coronary, carotid, and anterior spinal arteries. The descending thoracic or thoracoabdominal aorta is then replaced without time constraint, allowing implantation of intercostal vessels to reduce the risk of paraplegia. For complete thoracoabdominal replacement, separate balloon cannulae are used to perfuse the renal and visceral arteries.

	References

Top Abstract Introduction Structure and functional changes... Surgery for acute type... References

 

1. Gott V.C., Pyeritz R.E., Cameron D.E., Green P.S., McKusick V.A. Composite graft repair of Marfan’s aneurysms of the ascending aorta: results in 100 patients. Ann Thorac Surg 1991;52:38-45.[Abstract]
2. Salim M.A., Alpert B.S., Ward J.C., Pyeritz R.E. Effect of beta-adrenergic blockade on aortic root rate of dilation in Marfan’s syndrome. Am J Cardiol 1994;74:629-633.[Medline]
3. Shores J., Berger K.R., Murphy E.A., Pyeritz R.E. Progression of aortic dilation and benefit of long term beta-adrenergic blockade in Marfan’s syndrome. N Engl J Med 1994;330:1335-1341.[Abstract/Free Full Text]
4. Svensson L.G., Crawford E.S., Coselli J.S., et al. Impact of cardiovascular operation on survival in the Marfan patient. Circulation 1989;80:1233-1242.
5. David T.E., Feindel C.M. An aortic valve sparing operation for patients with aortic incompetence and aneurysms of the ascending aorta. J Thorac Cardiovasc Surg 1995;109:345-352.[Abstract/Free Full Text]
6. Dietz H.C., Pyeritz R.E. Mutations in the human gene for fibrillin-1 (FBNI) in the Marfan syndrome and related disorders. Hum Mol Genet 1995;4:1799-1809.[Abstract]
7. Sakai L.Y., Keene D.R., Glanville R.W., Bachinger H.P. Purification and partial characterization of fibrillin, a cysteine rich structural component of corrective tissue microfibrils. J Biol Chem 1991;266:147-163.
8. Hollister D.W., Godfrey M., Sakai L.Y., Pyeritz R.E. Immunohistological abnormalities of the microfibrillar-fibre system in the Marfan Syndrome. N Engl J Med 1990;323:152-160.[Abstract]
9. Robicsek F., Thubrikar M.J. Hemodynamic considerations regarding the mechanism and prevention of aortic dissection. Ann Thorac Surg 1994;58:1247-1253.[Abstract]
10. Carrel T., Pasic M., Jenni R., et al. Reoperations after operation on the thoracic aorta: etiology, surgical techniques and prevention. Ann Thorac Surg 1993;56:259-265.[Abstract]
11. Heinemann M., Laas J., Jurman M., et al. Surgery extended into the aortic arch in acute type A dissection. Circulation 1991;84(Suppl 3):25-30.
12. Westaby S., Katsumata T., Freitas E. Aortic value conservation in acute type A dissection. Ann Thorac Surg 1997;64:1108-1112.[Abstract/Free Full Text]
13. Smith J.A., Fann J.I., Miller D.C., et al. Surgical management of aortic dissection in patients with Marfan’s syndrome. Circulation 1994;90(Suppl 2):235-242.
14. Moore N.R., Parry A.J., Westaby S., et al. Fate of the native aorta after repair of acute type A dissection; a magnetic resonance imaging study. Heart 1996;75:62-66.[Abstract/Free Full Text]
15. Westaby S., Katsumata T. Proximal aortic perfusion for complex arch and descending aortic disease. J Thorac Cardiovasc Surg 1998;115:162-167.[Abstract/Free Full Text]

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