The Cardiovascular Implications of Thoracic Endovascular Aortic Repair: how aortic stenting impacts LV function and coronary artery ow

David P Stonko (  dstonko1@jhmi.edu ) Johns Hopkins https://orcid.org/0000-0002-2804-2857 Hossam Abdou R. Adams Cowley Shock Trauma Center, University of Maryland Medical System Joseph Edwards R. Adams Cowley Shock Trauma Center, University of Maryland Medical System Noha N Elansary R. Adams Cowley Shock Trauma Center, University of Maryland Medical System Eric Lang R. Adams Cowley Shock Trauma Center, University of Maryland Medical System Caitlin W Hicks Johns Hopkins Hospital, Department of Vascular and Endovascular Therapy https://orcid.org/00000001-7638-1936 Jonathan J Morrison (  jonathan.morrison@som.umaryland.edu ) R. Adams Cowley Shock Trauma Center, University of Maryland Medical System https://orcid.org/0000-0001-7462-8456

. This follows teleologically because the heart must work against a non-complaint stented aortic system, and must, therefore, compensate over time. These changes extend to even young patients treated with thoracic endovascular aortic repair (TEVAR) for trauma, where there is no underlying aortic pathology, and where increased quality of life years are at risk (Youssef et. al 2020). In the longer term, increased aortic stiffness secondary to stent grafts leads to heart failure in as many as 40% of patients, and is believed to contribute substantially to the long-term Despite the increasing use of aortic endografts, little is known about the impact on the heart. These include the biomechanical effect on the left ventricle, the effects on afterload andor contractility, andor the impact on coronary ow that results from changes in afterload or and diastolic lling. There is a critical need for to better understanding the changes to central hemodynamics imposed by aortic stenting, particularly in TEVAR) ( Little WC 1985). Observing left ventricular PV loops and measuring coronary and aortic ow directly during and immediately after endovascular aortic stent-grafting would provide a comprehensive understanding of the acute cardiovascular implications of aortic stenting and may provide insight into therapeutic strategies. Avenues to reverse these changes would lead to the possibility of preventing the long-term cardiovascular complications that can occur secondary to aortic stent grafting.
The goal of this study is to utilize a large animal model of cardiovascular physiology to capture left ventricular and coronary ow physiologic changes associated with TEVAR. Using left ventricular PV loop analysis, along with direct measurement of coronary and aortic ow, we seek to understand cardiac physiologic changes associated with TEVAR in order to develop strategies to prevent long-term LV changes and improve outcomes after TEVAR. 1. Anesthetize the animal with telazol (5mg/kg) and xylazine (2mg/kg) at appropriate doses.

Reagents
2. Transport the animal to the procedure area.
3. Place the animal under iso urane targeting 1.0 MAC by facemask. Transition to generally 10 ccs/kg TV, RR of 12-14 initially but to a target of pCO2 30-45 and an FiO2 of 40% but adjusted appropriately as needed.
4. Place the animal in sternal recumbency and intubate the animal with a 7.0 endotracheal tube.

Turn the animal into dorsal recumbency and restrain.
6. Place all venous and arterial catheters using US guidance, and place all monitoring devices. Includes: -place a 7 fr sheath in 2 of the following: either carotid or right brachial artery through which we will place the PV Loop through one and place a pig-tail catheter for angiography above the TEVAR through the other.

[DS1] [HA2]
-place a 7 fr sheath in either jugular down to the RA to be able to obtain central venous gases (and labs).
-place a 7 fr sheath in the other carotid or either brachial artery, and through this place an aortic pressure probe (which will remain proximal to the TEVAR graft) -place a 7 fr sheath in the right or left jugular for central venous pressure probe -place an at least 7 fr sheath in left femoral vein through which we will hemorrhage and later resuscitate[HA3] [DS4] .
-place a 10 fr sheath in right femoral artery for TEVAR deployment later[DS5] -also place EKG leads, oxygen saturation probe, rectal temperature probe and a bovie pad (after shaving).
7. Perform a lower abdominal laparotomy for cystostomy (place a foley catheter into the bladder) to facilitate bladder drainage. 8. Perform a left anterolateral thoracotomy. Place the 3 or 4mm ow probe around the coronary ow probe and add ultrasound jelly to the probe. 10. Perform a TIMEOUT. Con rm all line placements, con rm all sheaths work (drawback and ush), con rm uids are ready, that the timer is ready and reset, that data is being transduced through LabChart through appropriately labeled channels and saved. Con rm ventilatory settings. 11. Con rm uoroscopically that all catheters and devices are appropriately positioned.
3. Get baseline blood resistivity, enter value into the PV catheter system control.
Throughout baseline, stent and observation periods use the following guidelines for physiologic control of the animal: -Treat glucose < 65 with 1 amp D50 -for pH < 7.2 give on ampule of bicarbonate -treat pCO2 as necessary with MV changes -during resuscitation, treat sustained MAP < 65 after starting uids with pressor, rst line is norepinephrine.
III. Perform TEVAR 1. Con rm access with pigtail in aorta proximal to left subclavian, and that all lines and ports ush.
2. Place Amplatz wire into ascending aorta from femoral artery access. 1. Obtain a VBG and ABG at the start of this period, then every hour and at the end of this period.
2. Con rm ventilatory stability with each set of labs.
3. Ends with chem8, VBG, ABG, and troponin. Obtain full thickness heart tissue and place in formalin.
Obtain 5 tubes of blood, spin down and pipet off serum; place serum in -5 deg C freezer.
[DS1]an entire second paper here could done be: test for endoleaks using various imaging mechanisms once in post op monitoring phase. Since we will be in this phase for so long we can image the TEVAR stent several ways and see which is best (IA vs IV, on table CT vs DSA, etc) and this will not even increase the length of study for each pig.

Troubleshooting
Time Taken Estimated 2 hours for instrumentation, followed by one hour of baseline, then one hour for stenting, and 3 hours of monitoring for a total estimated minimum of 7 hours per animal. With the possibility of postoperative monitoring up to a total of 24-hours per animal.

Anticipated Results
We will rst provide baseline characteristics regarding the animals including weight, sex and animal type (these will be Yorkshire swine).
The main section of the anticipated results are two-fold. The rst is an assessment of LV functional changes associated with TEVAR. This would ultimately look like the following table. Baseline values here represent values obtained from animals in other studies. These are all continuous data points and would be presented as means and standard deviations. These would be compared using 2-tailed, paired t-tests from baseline to stenting, and from stenting to post-stenting periods. This would allow us to test if there are changes to LV contractility, afterload or preload before, during and after TEVAR. We may consider dividing the post-stenting period into shorter phases (e.g., 1-, 2-and 3-hour post-stenting) and compare how the data trend over time post-TEVAR.
The second part of the results will describe how coronary ow changes during each of these time periods.
We will examine total left coronary ow over time, peak coronary ow during each cardiac cycle, and will also examine whether there are changes to retrograde vs antegrade ow patterns.
Lastly, we will utilize the computed cardiac output, venous and arterial blood gases to compute changes in coronary ow as they relate to CO and LV functional parameters. Similarly, we will compute the oxygen utilization per cc blood ow and calculate how this changes in relation to CO and LV function. Figure 1 Study timing and overview for each phase of the trial.