Dataset Information

Protocol for a randomised controlled trial for Treatment in Thoracic Aortic Aneurysm: Surgery versus Surveillance (TITAN: SvS).

ABSTRACT:

Introduction

Ascending thoracic aortic aneurysm (ATAA) is an asymptomatic condition that can lead to catastrophic events of rupture or dissection. Current guidelines are based on limited retrospective data and recommend surgical intervention for ATAA with a diameter of greater or equal to 5.5 cm. Treatment in Thoracic Aortic Aneurysm: Surgery versus Surveillance is the first prospective, multicentre, randomised controlled trial that compares outcomes of patients undergoing early elective ascending aortic surgery to patients undergoing medical surveillance.

Methods and analysis

Patients between the ages of 18 and 80 with an asymptomatic ATAA between 5.0 cm and 5.4 cm in diameter are eligible for randomisation to early surgery or surveillance. Patients in the surgery group will be followed at 1 month after discharge, then annually for a minimum of 2 years and up to 5 years. Patients in the surveillance group will be followed annually from their index clinic visit for a minimum of 2 years and up to 5 years. The primary outcome is all-cause mortality at follow-up. A sample size of 618 subjects (309 in each group) will achieve an 80% power at a 0.047 significance level.

Ethics and dissemination

This study has received Ottawa Health Science Network Research Ethics Board approval (Protocol 20180007-01H), which was most recently updated on 25 November 2020. The Research Ethics Board have granted approval to the study at 14 participating institutions, including the Ottawa Health Science Network Research Ethics Board. On completion of data analysis, the result of the trial will be presented at national and international conferences, and published in relevant journals, regardless of the finding of the trial.

Trial registration number

NCT03536312.

SUBMITTER: Guo MH

PROVIDER: S-EPMC8160193 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Thoracic aortic aneurysms result from dysregulated remodeling of the vascular extracellular matrix, which may occur as a result of altered resident cellular function. The present study tested the hypothesis that aortic fibroblasts undergo a stable change in cellular phenotype during thoracic aortic aneurysm formation.Primary murine aortic fibroblasts were isolated from normal and thoracic aortic aneurysm-induced aortas (4 weeks post induction with 0.5 mol/L CaCl(2) 15 minutes) by the outgrowth method. Normal and thoracic aortic aneurysm cultures were examined using a focused polymerase chain reaction array to determine fibroblast-specific changes in gene expression in the absence and presence of biological stimulation (endothelin-1, phorbol-12-myristate-13-acetate, angiotensin-II). The relative expression of 38 genes, normalized to 4 housekeeping genes, was determined, and genes displaying a minimum 2-fold increase/decrease or genes with significantly different normalized cycle threshold values were considered to have altered expression.At steady state, thoracic aortic aneurysm fibroblasts revealed elevated expression of several matrix metalloproteinases (Mmp2, Mmp11, Mmp14), collagen genes/elastin (Col1a1, Col1a2, Col3a1, Eln), and other matrix proteins, as well as decreased expression of Mmp3, Timp3, and Ltbp1. Moreover, gene expression profiles in thoracic aortic aneurysm fibroblasts were different than normal fibroblasts after equivalent biological stimuli.This study demonstrated for the first time that isolated primary aortic fibroblasts from thoracic aortic aneurysm-induced mice possess a unique and stable gene expression profile, and when challenged with biological stimuli, induce a transcriptional response that is different from normal aortic fibroblasts. Together, these data suggest that aortic fibroblasts undergo a stable phenotypic change during thoracic aortic aneurysm development, which may drive the enhancement of extracellular matrix proteolysis in thoracic aortic aneurysm progression.