Invited Commentary

Abstract

The goal of thoracic aortic replacement is to prevent aortic rupture or dissection, both of which can be fatal. Unfortunately, the main tool we have to guide our decision making (aortic diameter) is neither sensitive nor specific for predicting these potentially fatal outcomes. Recent evidence has demonstrated that a large percentage of patients present with type A aortic dissection at smaller aortic diameters. International Registry of Acute Aortic Dissections data demonstrated that 40% of patients had aortic dissection at diameters less than 5 cm [1Pape L.A. Tsai T.T. Isselbacher E.M. et al.Aortic diameter >or = 5.5 cm is not a good predictor of type A aortic dissection: observations from the International Registry of Acute Aortic Dissection (IRAD).Circulation. 2007; 116: 1120-1127Crossref PubMed Scopus (565) Google Scholar], whereas another study showed that 87% of patients without a connective tissue disorder experienced dissection at less than 5.5 cm [2Kim E.K. Choi S.H. Sung K. et al.Aortic diameter predicts acute type A aortic dissection in patients with Marfan syndrome but not in patients without Marfan syndrome.J Thorac Cardiovasc Surg. 2014; 147: 1505-1510Abstract Full Text Full Text PDF PubMed Scopus (41) Google Scholar]. One third of patients with ACTA2 mutations experience dissection at less than 5 cm [3Regaldo E.S. Guo D. Prakash S. et al.Aortic disease presentation and outcome associated with ACTA2 mutations.Circ Cardiovasc Genet. 2015 Mar 10; ([Epub ahead of print])Google Scholar]. We replace aortas to prevent complications of aneurysms, but clearly, using current guidelines, we are not 100% successful at our intended goal. Operating at smaller diameters in everyone is not the answer, because many patients whose aortas would never undergo dissection would be subject to the risks of a major operation with potential complications. Thus we need a way to identify the specific patients who are at highest risk for experiencing dissection at smaller aortic diameters. In this article, Dr Ziganshin and his colleagues at Yale [4Ziganshin B.A. Bailey A.E. Coons C. et al.Routine genetic testing for thoracic aortic aneurysm and dissection in a clinical setting.Ann Thorac Surg. 2015; 100: 1604-1612Abstract Full Text Full Text PDF PubMed Scopus (99) Google Scholar] have tried to identify these patients by bringing routine genetic testing to their clinic. Using whole-exome sequencing, the authors examined 21 genes known to be associated with thoracic aortic aneurysms and dissections in patients presenting to their clinic. The majority of patients (72.5%) had no mutations in the 21 genes studied. However, the remainder of the patients had either known or unstudied mutations in these 21 genes. Although at first glance this may seem a low yield, as a pilot or proof of feasibility study these results are meaningful. First, identification of certain genetic mutations altered the clinical management of select patients, namely, more frequent follow-up and earlier prophylactic operations. Second, this study will allow investigators to link the rate of aneurysmal progression to specific genetic mutations, thus further identifying mutations that put patients at higher risk of accelerated aneurysmal growth and dissection. Third, the article identified novel genetic variants in genes known to be associated with thoracic aortic aneurysms and dissections. Finally, and perhaps most importantly, this study made the formidable translational leap of bringing our basic science knowledge to everyday clinical practice, with the hope of solving a common clinical problem. Limitations of this study include the cost, time delay, and reimbursement for whole-exome sequencing. Additionally, only a select set of genes was tested, and it is likely that there are many other genes associated with thoracic aortic aneurysms and dissections. Finally, the impact of the interaction of environmental factors on genetically susceptible individuals was not assessed and remains difficult to elucidate. Is it time to bring routine genetic testing to all patients in the surgical thoracic aorta surgery clinic? Unfortunately, with the limitations listed here, as well as others, probably not just yet. However, the work by Dr Ziganshin and his group in this study has laid the foundation for hopefully making genetics a part of our diagnostic assessment and risk stratification of patients with thoracic aortic conditions in the near future. Routine Genetic Testing for Thoracic Aortic Aneurysm and Dissection in a Clinical SettingThe Annals of Thoracic SurgeryVol. 100Issue 5PreviewHereditary factors play an important etiologic role in thoracic aortic aneurysm and dissection (TAAD), with a number of genes proven to predispose to this condition. We initiated a clinical program for routine genetic testing of individuals for TAAD by whole exome sequencing (WES). Here we present our initial results. Full-Text PDF