By James H Black III
Patients with connective tissue disorders have benefitted tremendously from the advent of modern molecular biology research including mapping of the human genome and refinement of modern surgical techniques. Indeed, the 19th and most of the 20th century historical outlook of patients with aortic catastrophes thought secondary to inborn genetic causes was bleak, and life expectancy was severely limited – often less than 40 years of age. The modern era has brought a longer lifespan to many connective tissue disorder patients and a new appreciation of the late affects of their vasculopathy, particularly outside the aortic root.
While clustering of aneurysms within a family pedigree is not infrequent and may account for 10–20% of aneurysms, several connective tissue disorders affecting the arterial tree have emerged with a studied natural history, a defined basis for genetic inheritance, and sufficiently understood pathophysiologic mechanisms to guide treatment. These “heritable disorders of connective tissue” have severe vascular manifestations and include commonly:
- Marfan Syndrome
- Vascular Type Ehlers-Danlos Syndrome
- Loeys-Dietz Syndrome
- Familial thoracic aortic aneurysm and dissection
Identification of these connective tissue disorder patients during initial evaluation is key to devising treatment strategies that mitigate acute presentations, reduce future events in contiguous aortic segments, and avoid the need for secondary intervention. Medium-sized arteries (usually the branches of aorta) are more commonly affected in Vascular Type Ehlers-Danlos Syndrome and uniquely in the cervical arteries of Loeys-Dietz Syndrome, versus the large vessel aortopathy of Marfan Syndrome, Loeys-Dietz Syndrome, and familial thoracic aortic aneurysm and dissection. Vascular Type Ehlers-Danlos Syndrome patients with acute presentations are among the most difficult to manage, and percutaneous endovascular embolisation is our preferred management technique. Open surgical reconstructions and large diameter sheath insertions are at best difficult and hazardous, leading to great anxiety concerning vascular isolation, dissection, and clamping. If confronted with vascular disintegration, proximal ligation and extra-anatomic bypass or direct reconstruction under permissive hypotension (SBP 60–80mmHg) may be the only surgical option.
Patients with familial thoracic aortic aneurysm and dissection have few distinct physical findings other than livedo reticularis versus the skeletal height, arm-span, and facial features of Marfan Syndrome and Loeys-Dietz Syndrome. As the presentation of familial thoracic aortic aneurysm and dissection tends to be later than Marfan Syndrome and Loeys-Dietz Syndrome, often in the 50–60 year old, TEVAR may be a suitable option. Although more difficult to diagnose and thus limiting reporting, concerns of retrograde aortic dissection and secondary catastrophe after TEVAR in familial thoracic aortic aneurysm and dissection have not emerged. If identified, screening for abdominal aortic aneurysm and descending thoracic aortic aneurysm is recommended for first degree family members.
It is important to note that all approved stent grafts excluded patients with connective tissue disorders, due to concerns that the persistent radial force of the implants or insertion techniques could promulgate vascular injury. For patients with Marfan Syndrome and the more aggressive Loeys-Dietz Syndrome, proper identification has several important implications for management of the thoracoabdominal aortic territory. Firstly, the natural history of patients with Marfan Syndrome and Loeys-Dietz Syndrome who undergo surveillance with elective aortic root replacement is excellent and approaches the general population, with few late downstream aortic events. However, when dissection occurs and is repaired, the natural history of secondary aortic intervention, usually for thoracic aortic aneurysm, is dramatically unravelled, with the time to the next aortic procedure averaging only 2–3 years. The performance of stent-grafts, in both acute and chronic dissection of the descending thoracic aorta for Marfan Syndrome, has been encumbered by many device related issues. In a study of several hundred TEVARs for type B dissection by Dong in 2009 (Circulation), the authors stated “the most common complication in Marfan Syndrome was retrograde aortic dissection.” Retrograde aortic dissection carries a need for emergent proximal surgery and mortality ranges from 20 to 60%. In a related study, 33% of Marfan Syndrome developed new entry tears at the zone of deployment, either proximally and distally, with a mortality of 30%.
Importantly, device oversizing bore no relevance to tear events suggesting the underlying aortopathy was operant. Even with initial success, the late aortic dilation has been documented in many Marfan Syndrome series with secondary interventions required in close to 50% of patients within a year. Mortality may also plague those secondary interventions and conversions due to the complexity of multiple dissection lumens.
The cardinal manifestations of the various connective tissue disorders require practitioner awareness so prudent application of modern treatment paradigms can be achieved. While endovascular therapy has yet to have a clearly defined long-term role in many connective tissue disorders, undoubtedly in instances of vascular rupture endovascular technology may be life-saving and serve as a “bridge” to definitive surgery in centres with established expertise in conventional surgical solutions.
James H Black III is the Bertram M Bernheim Research associate professor of Surgery, Johns Hopkins Hospital, Baltimore, USA.
