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The CardiOvascular Remodeling Following Endovascular Aortic Repair (CORE) Study (CORE)

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ClinicalTrials.gov Identifier: NCT02735720
Recruitment Status : Recruiting
First Posted : April 13, 2016
Last Update Posted : April 17, 2018
Sponsor:
Information provided by (Responsible Party):
Alberto Figueroa, University of Michigan

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.


Condition or disease Intervention/treatment
Thoracic Aortic Aneurysm Other: TEVAR Other: Non-TEVAR medical treatment

  Show Detailed Description

Study Type : Observational [Patient Registry]
Estimated Enrollment : 24 participants
Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 1 Year
Official Title: The CardiOvascular Remodeling Following Endovascular Aortic Repair (CORE) Study
Actual Study Start Date : March 14, 2017
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : June 2019

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
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
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.

Other: Non-TEVAR medical treatment
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

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
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.




Primary Outcome Measures :
  1. Changes in left ventricular mass (g), quantified with cardiac MRI [ Time Frame: 1 year ]
    This will be quantified in grams.


Secondary Outcome Measures :
  1. Diagnostic accuracy of ECG for cardiac remodelling compared to MRI [ Time Frame: 1 year ]
    A standard 12-lead ECG will be obtained and left ventricular hypertrophy will be assessed (i.e. QRS complex widening, abnormal ST segments or T waves).

  2. Diagnostic accuracy of ECG alone, and in combination with BNP, NT-pro-BNP, and Troponin T for cardiac remodelling compared to MRI [ Time Frame: 1 year ]

    A standard 12-lead ECG will be obtained and left ventricular hypertrophy will be assessed (i.e. QRS complex widening, abnormal ST segments or T waves).

    Cardiac biomarkers BNP, NT-pro-BNP, and Troponin T will be quantified in blood samples.


  3. Validation of computational modelling of thoracic aortic hemodynamics (i.e. velocity, flow, and pressure) following TEVAR against intra-luminal pressures and MRI. [ Time Frame: 1 year ]
    Hemodynamics (i.e. velocity in ml/min, flow in mm3/min, and pressure in mmHg) measured with intraluminal catheters and MRI will be used to create and validate patient-specific computational models. Subsequently, the impact of more compliant stent-grafts on aortic hemodynamics will be assessed.

  4. Early-to-late atrial filling ratios measured through cardiac MRI [ Time Frame: 1 year ]
    Early-to-late atrial filling ratios of the left atrium will be quantified using cardiac MRI.

  5. Aortic flow (ml/min) measured through cardiac MRI [ Time Frame: 1 year ]
    Aortic flow (ml/min) will be quantified using phase-contrast MRI at the intersections of the ascending aorta, all arch branches, proximal descending aorta, and distal descending aorta.

  6. Myocardial strain (%) using MRI sequences. [ Time Frame: 1 year ]
    Strain-encoding (SENC) or conventional tagged images will be used to quantify cardiac strain (%) at the basal, mid-ventricular, and apical short-axis slices, as well as in a 4-chamber slice.

  7. Central aortic pulse wave velocity using phase-contrast MRI. [ Time Frame: 1 year ]
    Phase-contrast MRI measurements will be acquired at different levels of the thoracic aorta using through-plane velocity-encoding and in an oblique sagittal view (in-plane velocity-encoding) to estimate the aortic vessel wall stiffness via PWV (cm/s) measurements.

  8. Myocardial perfusion using MRI perfusion sequences. [ Time Frame: 1 year ]
    Myocardial perfusion images will be acquired after administration of gadolinium-based contrast agent under pharmacological stress. The investigators will determine perfusion defects as well as the myocardium contrast uptake (ml/min/g) and contrast washout curves.

  9. Aortic strain (%) using MRI sequences. [ Time Frame: 1 year ]
    Cine images will be used to measure strain (%) of the thoracic aorta through measurements in the ascending aorta just distal to the coronary branches and proximal to the celiac trunk.


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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02735720


Contacts
Contact: Nickole Garvey, RN,BSN,CCRP (734) 232-6737 ngarvey@med.umich.edu
Contact: Theodorus MJ van Bakel, MD 7345481660 vanbakel@med.umich.edu

Locations
United States, Michigan
Department of Cardiac Surgery, University of Michigan Health System Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Theodorus van Bakel, MD    734-548-1660    vanbakel@med.umich.edu   
Contact: Alberto Figueroa, PhD    734-7638680    figueroc@med.umich.edu   
Sub-Investigator: Foeke J Nauta, MD         
Principal Investigator: Alberto C Figueroa, PhD         
Sub-Investigator: Arnoud V Kamman, MD         
Sub-Investigator: El-Sayed H Ibrahim, PhD         
Sub-Investigator: Prachi P Agarwal, MD         
Sub-Investigator: Bo Yang, MD         
Sub-Investigator: Karen Kim, MD         
Sub-Investigator: David M Williams, MD         
Sub-Investigator: Joost A van Herwaarden, MD, PhD         
Sub-Investigator: Frans L Moll, MD, PhD         
Sub-Investigator: Kim A Eagle, MD         
Sub-Investigator: Santi Trimarchi, MD, PhD         
Sub-Investigator: Himanshu J Patel, MD         
Sub-Investigator: Theodorus MJ van Bakel, MD         
Sponsors and Collaborators
University of Michigan
Investigators
Principal Investigator: Alberto C Figueroa, PhD Departments of Biomedical Engineering and Surgery, University of Michigan, USA

Additional Information:
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Alberto Figueroa, Principal Investigator, University of Michigan
ClinicalTrials.gov Identifier: NCT02735720     History of Changes
Other Study ID Numbers: CORE01
First Posted: April 13, 2016    Key Record Dates
Last Update Posted: April 17, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Alberto Figueroa, University of Michigan:
thoracic endovascular aortic repair
endograft
cardiac remodelling
thoracic aortic aneurysm
penetrating aortic ulcer
MRI

Additional relevant MeSH terms:
Aneurysm
Aortic Aneurysm
Aortic Aneurysm, Thoracic
Vascular Diseases
Cardiovascular Diseases
Aortic Diseases