The CardiOvascular Remodeling Following Endovascular Aortic Repair (CORE) Study

NCT02735720 | Terminated

• 1 other identifier: CORE01
• Study Type: observational
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

The use of TEVAR is increasing rapidly and patients even in younger patients. However, current endografts are several orders of magnitude stiffer than the native aorta. Pre-clinical and clinical studies have reported acute aortic stiffening after TEVAR resulting in hypertension, elevated pulse pressure, cardiac remodeling, reduced coronary perfusion, and finally, heart failure. These effects are markedly profound in young patients, as their hearts and aortas are more compliant. Previous studies on adverse cardiovascular remodeling have important limitations, such as retrospective design, use of echocardiography (with low reproducibility and high operator-dependency), and mixed populations. A systematic assessment of the deleterious effects of TEVAR is still missing. The objective of this study is to perform a prospective, non-randomized controlled, study in which blood pressure, heart rate, ECG, echocardiography, CT, MRI, intra-luminal hemodynamic assessment, computational modeling and biomarkers are used to assess cardiovascular remodeling following TEVAR. This study targets patients with thoracic aortic aneurysms (TAA) or penetrating aortic ulcers (PAU) treated with TEVAR. A control group will consist of TAA and PAU subjects who do not require endovascular treatment. The specific aims of the study include: 1) Quantification of cardiovascular remodeling following TEVAR in TAA or PAU patients. 2) Validation of computational modeling of thoracic aortic hemodynamics following TEVAR using the above clinical measurements. Once validated, computational analyses will be performed to virtually assess the impact of more compliant endografts on cardiac and aortic hemodynamics. 3) Investigation of diagnostic accuracy of ECG, BNP, NT-pro-BNP and Troponin T, for cardiac remodeling compared to MRI, the reference method. This study will assess the impact of thoracic aortic stent grafts on the cardiovascular system through non-invasive measurements. Although there are no direct benefits for the enrolled subjects, future aortic patients might benefit from better patient management with improved aortic endograft designs and long-term outcomes.

Conditions

Thoracic Aortic Aneurysm

Keywords

thoracic endovascular aortic repair; endograft; cardiac remodelling; thoracic aortic aneurysm; penetrating aortic ulcer; MRI

Outcome Measures

Primary Outcomes (1)

• Changes in left ventricular mass (g), quantified with cardiac MRI

  This will be quantified in grams.

  1 year

Secondary Outcomes (9)

• Diagnostic accuracy of ECG for cardiac remodelling compared to MRI

  1 year

• Diagnostic accuracy of ECG alone, and in combination with BNP, NT-pro-BNP, and Troponin T for cardiac remodelling compared to MRI

  1 year

• Validation of computational modelling of thoracic aortic hemodynamics (i.e. velocity, flow, and pressure) following TEVAR against intra-luminal pressures and MRI.

  1 year

• Early-to-late atrial filling ratios measured through cardiac MRI

  1 year

• Aortic flow (ml/min) measured through cardiac MRI

  1 year

Study Arms (2)

TEVAR group

Adult patients whose clinician's are managing their thoracic aortic aneurysms or with penetrating aortic ulcers with TEVAR. Standard work-up examinations for TEVAR will be collected, consisting of computed tomography (CT), echocardiography, blood pressure, heart rate, ECG and blood tests. Prior to the TEVAR procedure, a non-invasive MRI scan and blood samples will be acquired. Intraoperative pressure measurements will be collected during the TEVAR. One year following TEVAR, the subject will undergo a second non-invasive MRI study in addition to the standard clinical imaging follow-up CT-scan. Measurements of blood pressure, heart rate, ECG, and blood testing will also be repeated at follow-up.

Other: TEVAR; Other: Non-TEVAR medical treatment

Non-TEVAR medical treatment group

Adult patients whose clinician's are managing their thoracic aortic aneurysms or with penetrating aortic ulcers with pharmacological treatment alone. Patients with stable thoracic aortic aneurysms or with penetrating aortic ulcers not requiring aortic repair are monitored in the outpatient clinic as standard of care. The investigators will collect blood pressures and heart rates in these patients, which are acquired as standard of care. In addition, in this study, these subjects will undergo an ECG, blood testing and one non-invasive MRI scan at baseline. One year after baseline, this group will undergo a second non-invasive MRI study, with subsequent blood pressure and heart rate measurements, ECG and blood testing.

Other: Non-TEVAR medical treatment

Interventions

TEVAR OTHER

Thoracic endovascular aortic repair, which includes the implantation of stent-graft in the thoracic aorta to repair the lesion. This may be done with a variety of stent-graft brands and types. The type and brand of stent-graft is left to the discretion of the care taking physician.

TEVAR group

Non-TEVAR medical treatment OTHER

Any clinical management by physicians caring for these patients. This includes whatever blood pressure and heart rate medication is prescribed by the treating physician, without any surgery. The type and dosage of medication is left to the discretion of the care taking physician.

Non-TEVAR medical treatment group; TEVAR group

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

The patient population will consist of adult patients with descending thoracic aortic aneurysms or with penetrating aortic ulcers managed with TEVAR (TEVAR group, n=12) or with optimal medical treatment alone (control group, n=12) at the University of Michigan Health System.

You may qualify if:

• Adults with descending thoracic aortic aneurysms or with penetrating aortic ulcers.
• Subject willing to return for one year follow up and comply with protocol requirements.

You may not qualify if:

• Ejection fraction \< 35%; LV wall motion abnormality
• Poor renal function (estimated glomerular filtration rate (eGFR) \< 60 mL/min/173 m2)
• Pregnancy
• Connective tissue disorder
• Significant valve, lung or congenital heart disease
• History of cardiac or aortic surgery
• Expected cardiac or aortic surgery within the study period
• Standard MRI contraindications (pacemakers, non-compatible metal implants, and claustrophobia)

Sponsors & Collaborators

• University of Michigan: lead

Study Sites (1)

Department of Cardiac Surgery, University of Michigan Health System

Ann Arbor, Michigan, 48109, United States

Location

Related Publications (7)

• Takeda Y, Sakata Y, Ohtani T, Tamaki S, Omori Y, Tsukamoto Y, Aizawa Y, Shimamura K, Shirakawa Y, Kuratani T, Sawa Y, Yamamoto K, Mano T, Komuro I. Endovascular aortic repair increases vascular stiffness and alters cardiac structure and function. Circ J. 2014;78(2):322-8. doi: 10.1253/circj.cj-13-0877. Epub 2013 Nov 29.

  PMID: 24292128 BACKGROUND

• Tzilalis VD, Kamvysis D, Panagou P, Kaskarelis I, Lazarides MK, Perdikides T, Prassopoulos P, Boudoulas H. Increased pulse wave velocity and arterial hypertension in young patients with thoracic aortic endografts. Ann Vasc Surg. 2012 May;26(4):462-7. doi: 10.1016/j.avsg.2011.06.021. Epub 2012 Jan 27.

  PMID: 22284778 BACKGROUND

• Roccabianca S, Figueroa CA, Tellides G, Humphrey JD. Quantification of regional differences in aortic stiffness in the aging human. J Mech Behav Biomed Mater. 2014 Jan;29:618-34. doi: 10.1016/j.jmbbm.2013.01.026. Epub 2013 Feb 9.

  PMID: 23499251 BACKGROUND

• Coogan JS, Humphrey JD, Figueroa CA. Computational simulations of hemodynamic changes within thoracic, coronary, and cerebral arteries following early wall remodeling in response to distal aortic coarctation. Biomech Model Mechanobiol. 2013 Jan;12(1):79-93. doi: 10.1007/s10237-012-0383-x. Epub 2012 Mar 14.

  PMID: 22415052 BACKGROUND

• Nauta FJ, Kamman AV, Ibrahim EH, Agarwal PP, Yang B, Kim K, Williams DM, van Herwaarden JA, Moll FL, Eagle KA, Trimarchi S, Patel HJ, Figueroa CA. Assessment of CardiOvascular Remodelling following Endovascular aortic repair through imaging and computation: the CORE prospective observational cohort study protocol. BMJ Open. 2016 Nov 17;6(11):e012270. doi: 10.1136/bmjopen-2016-012270.

  PMID: 27856475 RESULT

• van Bakel TMJ, Arthurs CJ, Nauta FJH, Eagle KA, van Herwaarden JA, Moll FL, Trimarchi S, Patel HJ, Figueroa CA. Cardiac remodelling following thoracic endovascular aortic repair for descending aortic aneurysms. Eur J Cardiothorac Surg. 2019 Jun 1;55(6):1061-1070. doi: 10.1093/ejcts/ezy399.

  PMID: 30535179 RESULT

• van Bakel TMJ, Burris NS, Patel HJ, Figueroa CA. Ascending aortic rupture after zone 2 endovascular repair: a multiparametric computational analysis. Eur J Cardiothorac Surg. 2019 Sep 1;56(3):618-621. doi: 10.1093/ejcts/ezy458.

  PMID: 30608518 RESULT

Related Links

• Computational lab where computational modeling will be conducted

Biospecimen

Retention: SAMPLES WITH DNA

Blood testing will include complete blood count with platelets (including white blood cells, hemoglobine, hematocrit, red blood cells), a basic metabolic panel (including sodium, potassium, glucose, and calcium. Cardiac biomarkers testing will include natriuretic peptide (BNP), amino-terminal pro-BNP (NT-pro-BNP) and Troponin T. The investigators will not determine DNA of the patients.

MeSH Terms

Conditions

Aortic Aneurysm, Thoracic; Penetrating Atherosclerotic Ulcer

Interventions

Endovascular Aneurysm Repair

Condition Hierarchy (Ancestors)

Aortic Aneurysm; Aneurysm; Vascular Diseases; Cardiovascular Diseases; Aortic Diseases; Acute Aortic Syndrome; Arteriosclerosis; Arterial Occlusive Diseases

Intervention Hierarchy (Ancestors)

Endovascular Procedures; Vascular Surgical Procedures; Cardiovascular Surgical Procedures; Surgical Procedures, Operative; Blood Vessel Prosthesis Implantation; Vascular Grafting; Minimally Invasive Surgical Procedures; Prosthesis Implantation

Study Officials

• Alberto C Figueroa, PhD

  Departments of Biomedical Engineering and Surgery, University of Michigan, USA

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 1 Year
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 28, 2016
• First Posted: April 13, 2016
• Study Start: March 14, 2017
• Primary Completion: February 21, 2020
• Study Completion: February 21, 2020
• Last Updated: June 6, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)