The CardiOvascular Remodeling Following Endovascular Aortic Repair (CORE) Study
| Status: | Not yet recruiting |
|---|---|
| Conditions: | Cardiology, Cardiology |
| Therapuetic Areas: | Cardiology / Vascular Diseases |
| Healthy: | No |
| Age Range: | 18 - 99 |
| Updated: | 4/21/2016 |
| Start Date: | April 2016 |
| End Date: | June 2019 |
| Contact: | Nickole Garvey, RN,BSN,CCRP |
| Email: | ngarvey@med.umich.edu |
| Phone: | (734) 232-6737 |
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.
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.
Patient Population and Clinical Measurements:
The Frankel Cardiovascular Center at the University of Michigan Health System (UMHS) is a
regional center with expertise in managing a large variety of aortic diseases. Only adult
patients (age between 18-99 years) will be included. Patients will be included regardless of
race or ethnicity. The patient population consists of:
1. Patients with a descending thoracic aortic aneurysm (TAA). TAA is defined by a
balloon-like dilatation of the thoracic aorta. Such a dilatation may grow and
eventually rupture, associated with high mortality. In the United States, more than
10,000 patients die every year due to a ruptured aneurysm. Current United States
guidelines state that when the diameter of a TAA in patients with no connective tissue
disorder is larger than 55-60 mm, aortic repair is recommended. To date, TEVAR is the
first choice of therapy unless the anatomy is unsuitable or the patient has a
connective tissue disorder.
2. Patients with a penetrating aortic ulcer (PAU). PAU is a chronic aortic condition,
defined by an ulcer-like disruption of the inner aortic wall. Up to 28% of patients
with a PAU may have or may develop an aortic aneurysm. Treatment with TEVAR is
recommended for these patients, especially when patients are complicated by aortic
growth or rupture.
Study Design:
TEVAR Group. In this study, the investigators target both TAA and PAU treated with TEVAR.
Patients are to be identified in the clinic setting. Patients who are planned for treatment
TEVAR for TAA and PAU (based on their treating physician's decision) will be given
information about this observational study. Results for the standard work-up examinations
for TEVAR, which consist of computed tomography (CT), echocardiography, blood (BP) and heart
(HR) measurements, and electrocardiogram (ECG) will be collected. Once patient consent is
confirmed, and prior to the TEVAR procedure, this study will include a non-invasive MRI scan
and a blood collection for the biomarker data, in addition to the standard of care. In this
study, during the TEVAR procedure, intraluminal pressure measurements will be conducted
using the catheters and guidewires that will be already in place for the deployment of the
endograft. This study will neither delay or modify their endovascular procedure. One year
(between a window of 275 - 455 days) following the TEVAR procedure, the subject will undergo
and a second non-invasive MRI study in addition to the standard clinical imaging follow-up.
During this follow-up imaging, the patients will also undergo BP and HR measurements, ECG
and blood tests.
Control Group. Patients with a stable TAA or PAU who do not require surgery are monitored in
the outpatient clinic as standard of care. In this study, these patients will be given
information about our study and will be asked to be included in our investigation. Once
consent of the patients is confirmed, participants will undergo BP and HR measurements, ECG,
blood tests, and one non-invasive MRI scan, at baseline. One year (between a window of 275 -
455 days) after baseline, the participants will undergo additional observations;
non-invasive MRI study, BP and HR measurements, ECG and blood tests.
Clinical Measurements:
BP, HR, ECG, and blood- tests will be collected by trained personnel on all at baseline, and
at one year (between a window of 275 - 455 days) follow-up.
- BP and HR will be measured per standard protocol.
- ECG will consist of a standard 12 lead ECG.
- Standard blood tests include complete blood count with platelets (including white blood
cells, hemoglobin, hematocrit, red blood cells), a basic metabolic panel (including
sodium, potassium, glucose, and calcium. Cardiac biomarkers tests include natriuretic
peptide (BNP), amino-terminal pro-BNP (NT-pro-BNP) and Troponin T.
Echocardiography - Preoperative echocardiography is standard of care in all patients
requiring TEVAR. The obtained echocardiographic measurements in these patients will be
collected and compared to the preoperative MRI data.
Intraluminal pressures - During TEVAR, an angiography will be performed as standard of care.
In this study, intraluminal pressure measurements will be conducted in the TEVAR group,
using the catheters and guidewires that will be already in place for the deployment of the
endograft, as is commonly done at the UMHS.
MRI - This study will employ the following clinical and (FDA/IRB approved) research MRI
sequences to assess multiple signs of cardiovascular remodeling:
Clinical sequences:
1. Phase-contrast MRI measurements will be acquired on different cross-sections of the
aorta (through-plane velocity-encoding). Images will also be captured in an oblique
sagittal view (in-plane velocity-encoding) to estimate the aortic vessel wall stiffness
via pulse wave velocity measurements. Velocity-encoded phase-contrast MRI images will
be acquired across the mitral valve to evaluate the left ventricular (LV) diastolic
function through the measurement of early-to-atrial ratios. Myocardial perfusion images
will be acquired after administration of gadolinium based contrast agent under
pharmacological stress.
2. Cine measurements will include LV volume, LV wall volume and left atrial volume.
3. Tag-MRI will measure different components of myocardial strain in standard short-axis
and four-chamber views.
Research sequences:
1. Strain encoding sequences will measure cardiac- and aortic strain. This sequence is IRB
approved: IRBMED # 2004-0452.
2. Steady state free precession sequences will measure strain of the thoracic aorta
through cine measurements in the ascending aorta just distal to the coronary branches
and just proximal to the celiac trunk. The sequence is obtained in accordance within
FDA safety guidelines and with FDA approved MRI machines. It is easily reproducible and
quantifiable and confirms to all MRI safety parameters in the United States.
All these measurements are non-invasive and therefore do not impose additional risk or
burden to the patient. Contrast will be administered, except for those patients with poor
renal function (eGFR<60). The total anticipated scan time is approximately 1 hour.
Computational Modeling - Using the imaging and clinical data, simulations of blood flow and
pressure will be performed using computational fluid dynamics (CFD) techniques and the
High-Performance Computer cluster "Flux" at the University of Michigan. Highly detailed
descriptions of velocity, flow, pressure, wall shear stress and other hemodynamically
significant quantities will be obtained. The results of these non-invasive simulations will
be compared against the clinical measurements (BP, HR, echocardiography, MRI, and
intraluminal pressures) to calibrate this tool. Once calibrated, computational analyses will
be performed to virtually assess the impact of more compliant endografts on cardiac and
aortic hemodynamics.
Statistical Analysis - Statistical analysis will include descriptive and comparative
analysis of both clinical measurements and data acquired from computational modeling. In
analysis, participants will be grouped by TEVAR or Control group. Sub-analysis will include
grouping by endograft length, gender, and age. The patients identifying information and
protected health data will be dealt with based on HIPAA guidelines.
Preliminary echocardiographic data of TAA patients treated with TEVAR at the University of
Michigan Health System revealed an average LV mass increase of 39% (P = 0.047) at 1-year
follow-up. Power analysis for a Mann-Whitney U test, based on these preliminary data,
calculated that for a significant threshold of 5% (P < 0.05, two-sided test) a total sample
size of 20 patients (α = 0.05, power = 97%) would be needed to observe a significant effect
of TEVAR on LV mass increase. To ensure a margin of error, the investigators aim to include
12 TEVAR patients and 12 control patients.
To sum up, the end-goal of this study is to assess the impact of TEVAR on adverse
cardiovascular remodeling through imaging and computation. This impact remains unclear and
may carry important implications for patient management and future endograft design. The
additional measurements required for this study are almost risk-free for all included
participants. 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.
The Frankel Cardiovascular Center at the University of Michigan Health System (UMHS) is a
regional center with expertise in managing a large variety of aortic diseases. Only adult
patients (age between 18-99 years) will be included. Patients will be included regardless of
race or ethnicity. The patient population consists of:
1. Patients with a descending thoracic aortic aneurysm (TAA). TAA is defined by a
balloon-like dilatation of the thoracic aorta. Such a dilatation may grow and
eventually rupture, associated with high mortality. In the United States, more than
10,000 patients die every year due to a ruptured aneurysm. Current United States
guidelines state that when the diameter of a TAA in patients with no connective tissue
disorder is larger than 55-60 mm, aortic repair is recommended. To date, TEVAR is the
first choice of therapy unless the anatomy is unsuitable or the patient has a
connective tissue disorder.
2. Patients with a penetrating aortic ulcer (PAU). PAU is a chronic aortic condition,
defined by an ulcer-like disruption of the inner aortic wall. Up to 28% of patients
with a PAU may have or may develop an aortic aneurysm. Treatment with TEVAR is
recommended for these patients, especially when patients are complicated by aortic
growth or rupture.
Study Design:
TEVAR Group. In this study, the investigators target both TAA and PAU treated with TEVAR.
Patients are to be identified in the clinic setting. Patients who are planned for treatment
TEVAR for TAA and PAU (based on their treating physician's decision) will be given
information about this observational study. Results for the standard work-up examinations
for TEVAR, which consist of computed tomography (CT), echocardiography, blood (BP) and heart
(HR) measurements, and electrocardiogram (ECG) will be collected. Once patient consent is
confirmed, and prior to the TEVAR procedure, this study will include a non-invasive MRI scan
and a blood collection for the biomarker data, in addition to the standard of care. In this
study, during the TEVAR procedure, intraluminal pressure measurements will be conducted
using the catheters and guidewires that will be already in place for the deployment of the
endograft. This study will neither delay or modify their endovascular procedure. One year
(between a window of 275 - 455 days) following the TEVAR procedure, the subject will undergo
and a second non-invasive MRI study in addition to the standard clinical imaging follow-up.
During this follow-up imaging, the patients will also undergo BP and HR measurements, ECG
and blood tests.
Control Group. Patients with a stable TAA or PAU who do not require surgery are monitored in
the outpatient clinic as standard of care. In this study, these patients will be given
information about our study and will be asked to be included in our investigation. Once
consent of the patients is confirmed, participants will undergo BP and HR measurements, ECG,
blood tests, and one non-invasive MRI scan, at baseline. One year (between a window of 275 -
455 days) after baseline, the participants will undergo additional observations;
non-invasive MRI study, BP and HR measurements, ECG and blood tests.
Clinical Measurements:
BP, HR, ECG, and blood- tests will be collected by trained personnel on all at baseline, and
at one year (between a window of 275 - 455 days) follow-up.
- BP and HR will be measured per standard protocol.
- ECG will consist of a standard 12 lead ECG.
- Standard blood tests include complete blood count with platelets (including white blood
cells, hemoglobin, hematocrit, red blood cells), a basic metabolic panel (including
sodium, potassium, glucose, and calcium. Cardiac biomarkers tests include natriuretic
peptide (BNP), amino-terminal pro-BNP (NT-pro-BNP) and Troponin T.
Echocardiography - Preoperative echocardiography is standard of care in all patients
requiring TEVAR. The obtained echocardiographic measurements in these patients will be
collected and compared to the preoperative MRI data.
Intraluminal pressures - During TEVAR, an angiography will be performed as standard of care.
In this study, intraluminal pressure measurements will be conducted in the TEVAR group,
using the catheters and guidewires that will be already in place for the deployment of the
endograft, as is commonly done at the UMHS.
MRI - This study will employ the following clinical and (FDA/IRB approved) research MRI
sequences to assess multiple signs of cardiovascular remodeling:
Clinical sequences:
1. Phase-contrast MRI measurements will be acquired on different cross-sections of the
aorta (through-plane velocity-encoding). Images will also be captured in an oblique
sagittal view (in-plane velocity-encoding) to estimate the aortic vessel wall stiffness
via pulse wave velocity measurements. Velocity-encoded phase-contrast MRI images will
be acquired across the mitral valve to evaluate the left ventricular (LV) diastolic
function through the measurement of early-to-atrial ratios. Myocardial perfusion images
will be acquired after administration of gadolinium based contrast agent under
pharmacological stress.
2. Cine measurements will include LV volume, LV wall volume and left atrial volume.
3. Tag-MRI will measure different components of myocardial strain in standard short-axis
and four-chamber views.
Research sequences:
1. Strain encoding sequences will measure cardiac- and aortic strain. This sequence is IRB
approved: IRBMED # 2004-0452.
2. Steady state free precession sequences will measure strain of the thoracic aorta
through cine measurements in the ascending aorta just distal to the coronary branches
and just proximal to the celiac trunk. The sequence is obtained in accordance within
FDA safety guidelines and with FDA approved MRI machines. It is easily reproducible and
quantifiable and confirms to all MRI safety parameters in the United States.
All these measurements are non-invasive and therefore do not impose additional risk or
burden to the patient. Contrast will be administered, except for those patients with poor
renal function (eGFR<60). The total anticipated scan time is approximately 1 hour.
Computational Modeling - Using the imaging and clinical data, simulations of blood flow and
pressure will be performed using computational fluid dynamics (CFD) techniques and the
High-Performance Computer cluster "Flux" at the University of Michigan. Highly detailed
descriptions of velocity, flow, pressure, wall shear stress and other hemodynamically
significant quantities will be obtained. The results of these non-invasive simulations will
be compared against the clinical measurements (BP, HR, echocardiography, MRI, and
intraluminal pressures) to calibrate this tool. Once calibrated, computational analyses will
be performed to virtually assess the impact of more compliant endografts on cardiac and
aortic hemodynamics.
Statistical Analysis - Statistical analysis will include descriptive and comparative
analysis of both clinical measurements and data acquired from computational modeling. In
analysis, participants will be grouped by TEVAR or Control group. Sub-analysis will include
grouping by endograft length, gender, and age. The patients identifying information and
protected health data will be dealt with based on HIPAA guidelines.
Preliminary echocardiographic data of TAA patients treated with TEVAR at the University of
Michigan Health System revealed an average LV mass increase of 39% (P = 0.047) at 1-year
follow-up. Power analysis for a Mann-Whitney U test, based on these preliminary data,
calculated that for a significant threshold of 5% (P < 0.05, two-sided test) a total sample
size of 20 patients (α = 0.05, power = 97%) would be needed to observe a significant effect
of TEVAR on LV mass increase. To ensure a margin of error, the investigators aim to include
12 TEVAR patients and 12 control patients.
To sum up, the end-goal of this study is to assess the impact of TEVAR on adverse
cardiovascular remodeling through imaging and computation. This impact remains unclear and
may carry important implications for patient management and future endograft design. The
additional measurements required for this study are almost risk-free for all included
participants. 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.
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)
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