A Journey Through The Thoracic Aorta: From Root To Arch

Abstract

This thesis investigated the clinical and pathological outcomes of disease of the aortic valve and the ascending aorta, including the aortic root. Purpose: The aortic valve and proximal aorta are the anatomical origin of the systemic circulation and pathology in this area can be catastrophic. Despite this, there is limited knowledge of the pathophysiology of proximal aortic aneurysms and patient outcomes for treatment strategies of aortic valve disease. The purpose of this thesis is to strengthen the knowledge of pathology affecting the thoracic aorta so that it can help guide clinical management in the future. Aims: This thesis aims to investigate the effects of pathology on the aortic valve and thoracic ascending aorta through determination of: 1. The pathophysiology of proximal aortic aneurysms, specifically focusing on evaluating aortic root and ascending aortic aneurysm in relation to (a) histology (Chapter 2) and (b) propensity to aortic rupture in pigs in-vitro (Chapter 3) and in-vivo (Chapter 4) models; and 2. Comparing SAVR & TAVR in relation to (a) clinical outcomes (Chapter 5) and (b) patient-related outcomes (Chapter 6). Methods: Chapter 2, focused on histological analysis of aneurysmal aortas, and involved laboratory preparation of human aneurysmal and non-aneurysmal tissue and analysis utilizing histological and immunohistochemistry techniques. Chapter 3, which focused on a laboratory pig model in ascending aorta and aortic root rupture, involved laboratory preparation of pig non-aneurysmal samples, and utilised a unique pressure testing apparatus, to determine the maximal stress the root and ascending aorta can withstand prior to rupture. This was a pilot study for Chapter 4. Chapter 4, which focused on a live pig model in ascending aorta and aortic root rupture, involved placement of live pigs on cardiopulmonary bypass, and determination of maximal aortic pressures prior to rupture or failure of the aorta clinically and radiologically using 4D flow MRI. This ruptured tissue was then analysed utilising histological and immunohistochemistry techniques. Chapter 5 which focused on clinical outcomes of aortic valve surgery, utilised the ANZSCTS national database from Monash Health, incorporating data collection and analysis from 2001 to 2019. Chapter 6 which focused on the patient-related outcomes following aortic valve surgery, involved the use of validated questionnaires of patients over a 12-month period following their surgery. Specific outcomes measured included frailty, depression, angina, and quality of life. Results and Discussion: Chapter 2, 3, and 4 focus on the comparisons in structure between two anatomical regions of the aorta, while Chapter 5 and 6 focus on comparisons in approach between two methods of aortic valve replacement. All Chapters give us valuable knowledge as to how we can manage aortic pathology not only during surgery, but also during the patient’s perioperative journey. The aortic root is the most susceptible region of the thoracic aorta and is predisposed to progression of pathology and rupture in clinical testing. The aortic root is more vulnerable to high pressures, further exacerbated by aneurysmal changes, supported by both microscopic and macroscopic characteristics, while the ascending aorta retains its resilience in comparison. This identified a difference between the aortic root and ascending aorta not only in known anatomical and physiological form, but in each areas ability to maintain its integrity in severe stress and aneurysmal pathological change. With respect to outcomes post aortic valve replacement, the ANZSCTS database showed no difference in composite endpoints of mortality and stroke between Surgical aortic valve replacement (SAVR) and Transcatheter aortic valve replacement (TAVR), while the degree of morbidity (complete heart block requiring pacemaker and vascular complications) was more prevalent in TAVR groups. In contrast, quality of life, depression, angina, and frailty consecutively measured over 12 months, showed significant improvement in both SAVR and TAVR groups, and an obvious benefit to these measures in all patients requiring intervention for aortic stenosis. When these two groups (SAVR and TAVR) were matched, clinically relevant preoperative variables were identified as being predictive of early mortality. Conclusions: The aortic root differs to the ascending aorta under maximal stress and in response to pathological change. Following further clinical testing and human trials, consideration should be for surgical management of these structures as separate entities. Transcatheter approaches are evolving with improved outcomes in large scale randomised trials supported by our findings of composite primary end points, as well as comparable improvement in quality of life, angina, depression, and frailty with surgical groups. Clinically significant morbidity in the form of vascular and electrophysiological complications remain high, and this should be a focus of ongoing long term clinical trials before an absolute incorporation of this technique for all patients with aortic stenosis. Recommendations: This unique analysis offers a new perspective of root and ascending aorta dilatation with strong clinical implications. These two structures deserve new and different management. National databases reporting on outcomes in aortic valve surgery should consider combining databases regardless of transcatheter or open surgical approach, to allow for a comprehensive and accurate representation of morbidity and mortality outcomes. Longer term analysis of these morbidity results should guide clinical guidelines as to the appropriate use of these techniques in aortic valve disease, and the utilisation of combined surgical and physician teams in performing these procedures.