Registry of Aortic Diseases to Model Adverse Events and Progression (ROADMAP) in Uncomplicated Type B Aortic Dissection: Study Design and Rationale

PURPOSE To describe the design and methodological approach of a multicenter, retrospective study to externally validate a clinical and imaging-based model for predicting the risk of late adverse events in patients with initially uncomplicated type B aortic dissection (uTBAD). MATERIALS AND METHODS The Registry of Aortic Diseases to Model Adverse Events and Progression (ROADMAP) is a collaboration between 10 academic aortic centers in North America and Europe. Two centers have previously developed and internally validated a recently developed risk prediction model. Clinical and imaging data from eight ROADMAP centers will be used for external validation. Patients with uTBAD who survived the initial hospitalization between January 1, 2001, and December 31, 2013, with follow-up until 2020, will be retrospectively identified. Clinical and imaging data from the index hospitalization and all follow-up encounters will be collected at each center and transferred to the coordinating center for analysis. Baseline and follow-up CT scans will be evaluated by cardiovascular imaging experts using a standardized technique. RESULTS The primary end point is the occurrence of late adverse events, defined as aneurysm formation (≥6 cm), rapid expansion of the aorta (≥1 cm/y), fatal or nonfatal aortic rupture, new refractory pain, uncontrollable hypertension, and organ or limb malperfusion. The previously derived multivariable model will be externally validated by using Cox proportional hazards regression modeling. CONCLUSION This study will show whether a recent clinical and imaging-based risk prediction model for patients with uTBAD can be generalized to a larger population, which is an important step toward individualized risk stratification and therapy.Keywords: CT Angiography, Vascular, Aorta, Dissection, Outcomes Analysis, Aortic Dissection, MRI, TEVAR© RSNA, 2022See also the commentary by Rajiah in this issue

Gene Expression Changes in Rats with Diastolic Dysfunction Induced by Diabetes and Hypertension, and in Humans with Diastolic Heart Failure

Current therapies for heart failure are administered across a heterogeneous spectrum of disease etiology and phenotype. Standard treatments for systolic heart failure are not efficacious for patients with diastolic heart failure, raising the possibility that as of yet unidentified mechanisms are responsible for disease pathogenesis. We observed that diabetic rats treated with Angiotensin II infusion developed cardiac hypertrophy, fibrosis, and impaired diastolic function. Using a systems biology approach, we identified (a) changes in the cardiac transcriptome of rats in response to diabetes and hypertension; (b) the subset of genes that were simultaneously regulated in both the heart and whole blood of rats exposed to diabetes and hypertension; and (c) differentially expressed genes in whole blood of patients with diastolic heart failure compared to those with systolic heart failure and controls. In each experiment, we identified differential expression of functionally related groups of genes, suggesting coordinated regulation of multiple genes. Protein processing, extracellular matrix remodeling and inflammation were three of the dominant processes in cardiac tissue of diabetic hypertensive rats that were simultaneously regulated in whole blood. Extracellular matrix protein 1, transforming growth factor beta family members, and angiopoietin-like four were identified as part of a panel of extracellular matrix mediators that were coordinately regulated in both tissues. Gene expression profiles in blood of patients with diastolic heart failure allowed us to study networks and relationships of interactions that may not have been available from the study of single targets. A panel of eleven candidate markers was identified, including several that participate in cytoskeletal rearrangement or cell adhesion (plexin C1, transgelin 2, ninein, villin 2, and dock 2), and others involved in protein processing (ubiquitination factor E4B, myotubularin related protein 3, presenilin 1). These sets of experiments contribute to the literature regarding the myocardial effects of diabetes and hypertension and provide novel insight into the coordinated regulation of genes in the heart and blood in response to cardiovascular stress. The list of top candidate genes identified from the blood of patients with diastolic heart failure may have clinical utility as disease biomarkers.Ph

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

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