Aortic root and arch dilation

Aortic root and arch dilatation.

Preliminary studies suggest a link between aortic root and arch dilatation with thoracic outlet vein compression, the MTHFR mutation, as well as hypermobility syndromes.

At present we are investigating the hypothesis that catecholamine and/or inflammatory responses and baroreceptor signaling from vascular compression syndromes, particularly thoracic outlet syndrome are responsible for the dilatation.

It is thought we can halt the progression of the dilatation by removing the inflammatory responses by dealing with the genetic problems of the MTHFR mutation and the mechanical sources in the thoracic outlet. Trials are well underway using angiotensin-renin blockers in stabilizing this dilatation.

The last couple of years has been eye-opening for me as I have been working with a cardiologist looking at causes of migraine. There have been many spin-offs as there is very strong evidence that migraine (especially with aura) is associated with a defect in a gene which has been implicated in a wide range of medical conditions, including chronic fatigue, fibromyalgia, deep vein thrombosis and a myriad of conditions where the collagen, the building structure in our body is affected. This may manifest in common things such as varicose veins and dupuyrtrens contracture. It probably is also the cause of other problems such as gout, and I have a suspicion that it may be the underlying culprit in osteoporosis and diverticular disease, diseases where problems occur in the collagen tissue.

Having this mutation puts you at increased risk for all these, and then what happens is basically affected by what you do with yourself through life, eg periods of excess stress, or accidents, or poor lifestyle- especially smoking.   Increasingly there is evidence that all these issues are bound together as inflammatory processes, with your DNA determining what diseases you develop.

There is a condition where the aorta leading from the heart is affected as the collagen tissue is degenerate, causing dilation, and if not managed correctly, it could lead to rupture of the aorta or heart failure. All studies I have found have been in patients with Marfan’s syndrome, where progressive enlargement of the aortic root, leading to dissection, is the main cause of death. Research suggests that this root enlargement is caused by excessive signalling by transforming growth factor b (TGF-b ) that can be mitigated by treatment with TGF-b -blockers, particularly angiotensin 11-receptor blockers (ARBs.) (1)

People with hypermobility, with increased stretch of blood vessels (or compression), causes increased baroreceptor signalling (ref Prof Pete Smith). A lot of mast cells are around major key branch points (including the root of the aorta) and histamine is a co-factor in sensory nerve activation thresholds. As yet, we don’t know why, there is an increased propensity to dilate at those points.

At this stage it seems apparent that elevated homocysteine, which is a common accompaniment of the MTHFR mutation is one of the risks for developing this dilatation. We believe that it is the defect in the collagen caused by multiple gene mutations that underlies the whole process. In ongoing studies here on thoracic outlet compression, there appears to be an association with inflammatory processes from this and a higher risk of developing aortic dilatation.

Research has demonstrated that a type of blood pressure tablet, the ARBs, seem to slow the progress of this dilatation, and early studies would suggest there is actual repair, possibly at a DNA level. So this is where we start in practice, to stop the process using a combination of ARB (eg Atacand or Micardis) and vitamin B12 which appears to improve function of the defective enzyme in the MTHFR pathway. Traditional management in Marfan’s has been with b-blockers, and in progressive disease, the combination of ARB and  b-blocker appears to be synergistic. (3)

There are guidelines for the dilatation, which do not include the current research, but do suggest that the echocardiogram be checked yearly, or twice yearly if the aortic root has enlarged to 4.5 cm at which time you would need a specialist opinion. The yearly echocardiogram should be done on the same machine and if there is progression despite treatment, I would recommend an earlier referral as this association with elevated homocysteine is as yet unexplored territory and the management at research level. The dilating aorta can be surgically corrected if necessary, but we hope to stop this being required by halting and hopefully reversing the process, something that is looking promising with early research results.


  1. Brooke,B.,Habashi,J., Judge, D., Patel,N., Loeys, B., Dietz, H.:Angiotensin11 Blockade and Aortic Root Dilation in Marfan’s Syndrome: 2008, N Engl J Med
  2. Braverman,A.: Medical Management of Thoracic Aortic Aneurysm Disease, 2012: Journal of Thoracic and Cardiovascular Surgery
  3. Lee, S., Oh, J., Ko, Y., Lee, S., Chang,B., Lee, D., Kwak, Y., Choi, D.:The Beneficial Effect of Renin-Angiotensin-Aldosterone System Blockade in Marfan Syndrome Patients after Aortic Root Replacement: 2016. Yonsei Med J.

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