Evaluation of Hemodynamic Parameters Following Transjugular Intrahepatic Portosystemic Shunt (TIPS)

Study Overview
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Brief Summary
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During a TIPS procedure, a shunt or stent (mesh tube) is passed down the jugular vein (the vein above the collarbone in the neck) using fluoroscopy (real time x-rays) guidance. Then, a stent is inserted between the portal vein (vein that carries blood from the intestines into the liver) to a hepatic vein (vein that carries blood away from the liver back to the heart). This means that blood that would usually gets filtered through the liver is now bypassing the liver and going directly to the heart. Because more blood will be flowing to the heart, the heart needs to be strong enough to handle the extra volume. This study is being done to determine the impact of the TIPS procedure on cardiac (heart) function by collecting data (heart pressures) during the TIPS procedure. Immediately after TIPS and at standard follow-up time points, labs and transthoracic echocardiograms (TTE or echo) will also be collected. The device(s) used in this study are neither the intervention studied nor the experimental variable of interest. Devices are commercially available and used, and procedures are performed, in accordance with the institution's standard of care.

Detailed Description
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The long-term goal of this proposal is to improve survival in patients with end stage liver disease following TIPS placement. Given that the most common indications for TIPS placement are also defining features of decompensated cirrhosis, specifically hemorrhage and refractory ascites, the overall health of this patient population is extraordinarily complex. One notable circulatory impact of cirrhosis is the increase in total blood volume in concert with a disproportionate increase in splanchnic blood volume. Therefore, at the time of TIPS placement, a patient may experience a marked increase in central blood volume that may lead to cardiac dysfunction. Considering that a central feature of cirrhotic cardiomyopathy is attenuated response to stress, it is conceivable that some perioperative cardiovascular complications could be attributed to the patient's baseline health rather than an isolated effect of the procedure alone. By instituting measures to identify patients that may be at increased risk for an adverse outcome, this proposal hopes to offer a new paradigm for managing TIPS patients in the acute postoperative setting. Therefore, the purpose of this study is to derive better correlates between non-invasive and invasive measurements of cardiac function.

Official Title
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Evaluation of Hemodynamic Parameters Following Transjugular Intrahepatic Portosystemic Shunt (TIPS)

Conditions
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Refractory Ascites

Intervention / Treatment
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* Procedure: Study - Transjugular Intrahepatic Portosystemic Shunt (TIPS)
* Procedure: Control - Transjugular Intrahepatic Portosystemic Shunt (TIPS)


Participation Criteria
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Eligibility Criteria
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OVERALL INCLUSION ≥ 18 years Patients with indications as established by the ACR-SIR-SPR practice parameters:: prophylaxis against recurrent variceal bleed in high-risk patients portal hypertensive gastropathy or intestine-opathy refractory ascites hepatic hydrothorax hepatopulmonary syndrome hepatorenal syndrome decompression of portosystemic collaterals prior to abdominal surgical procedures Technically successful creation of a TIPS shunt, defined as creation of a portosystemic shunt with post TIPS creation portosystemic gradient of ≤ 12 mmHg STUDY ARM INCLUSION: • All patients undergoing elective TIPS who meet at least one of the criteria: Right atrial pressure (RAP) ≥ 15mm Hg; OR Change in RAP ≥ 10mm Hg; OR Peak systolic velocity ratio (PSRV) pressure ≥ 46mm Hg CONTROL ARM INCLUSION: • Patients undergoing elective TIPS for control of refractory ascites who do not meet at least one of the criteria outlined above for the study arm. Historical controls: we will use data collected form our own recent institutional review. EXCLUSION All patients who do not exhibit alterations in invasive RAP or PRVS measurements as listed in Inclusion Criteria and do not meet criteria for participation as a control subject (i.e. are not undergoing elective TIPS for control of refractory ascites). Admitted for GI bleed. Budd-Chiari syndrome. TIPS in setting of mesenteric vein thrombosis.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: All patients undergoing TIPS will have the following hemodynamic measurements obtained: systolic, diastolic and mean RAP; systolic, diastolic and mean right ventricular pressure (RSV). Peak systolic right ventricular (PSRV) pressure will serve as surrogate for pulmonary artery pressure (PAP). There are 2 groups in this project. Subjects will be enrolled in 1 of the 2 groups based on their heart pressure measurements (high or normal). If a subject does not meet criteria for 1 of the 2 groups, they will not be in the study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study - Transjugular Intrahepatic Portosystemic Shunt (TIPS)<br>Right Atrial Pressure (RAP) ≥ 15mmHg or change in RAP ≥ 10 mmHg or Peak Systolic Right Ventricular (PSRV) Pressure ≥ 46 mmHg | Procedure: Study - Transjugular Intrahepatic Portosystemic Shunt (TIPS)<br>* Prior to and 1-3 days after the TIPS procedure, the following blood tests are done for research purposes: Brain Natriuretic Peptide (BNP); Endothelin-1; Tumor Necrosis Factor-alpha (TNF-a); Endothelial Nitric Oxide Synthase (eNOS). Subjects with abnormal heart pressures during TIPS will have a right heart catheterization (RHC) to monitor heart function, blood flow, and pressures in and around the heart. The subject will be admitted to the Cardiovascular Intensive Care Unit and have a TTE all of which are standard of care. Routine follow-up visits will occur in IR Clinic at 2 Weeks (± 3 days), 4-6 weeks and 4-6 months. Visits will include: blood draws for research related blood tests as listed above; standard of care ultrasound of the abdomen; TTEs; and for at least one year, routine lab testing, imaging, medications, and subject overall condition will be assessed for long term outcomes. Diagnostic RHC will be done as needed per standard of care.<br>* Other names: Research Blood Tests;|
| Active Comparator: Control - Transjugular Intrahepatic Portosystemic Shunt (TIPS)<br>Normal hemodynamic parameters | Procedure: Control - Transjugular Intrahepatic Portosystemic Shunt (TIPS)<br>* Subject's with normal heart pressures who are having elective (planned in advance and not due to an emergency) TIPS due to refractory ascites (fluid build up in the belly that does not go away or comes back shortly after being removed). Prior to and 1-3 days after the TIPS procedure, the following blood tests are done for research purposes: Brain Natriuretic Peptide (BNP); Endothelin-1; Tumor Necrosis Factor-alpha (TNF-a); Endothelial Nitric Oxide Synthase (eNOS). The subject will be admitted to the hospital after TIPS for standard of care monitoring. Routine follow-up visits will occur in IR Clinic at 2 Weeks (± 3 days), 4-6 weeks and 4-6 months. Visits will include: blood draws for research related blood tests as listed above; standard of care ultrasound of the abdomen; and for at least one year, routine lab testing, imaging, medications, and subject overall condition will be assessed for long term outcomes.<br>* Other names: Research Blood Tests;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiac related events | any cardiac event to include, heart failure, heart attack, pulmonary hypertension | from insertion of TIPS to 2 years post TIPS | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical success | No further need for paracentesis or thoracentesis at 6 months | 6 months after TIPS placement | 
| Overall survival | evaluation of overall survival from time of TIPS placement to death | all patients will be followed for 2 years after TIPS placement | 
| Complications | Any peri or post procedural TIPS related events including liver failure, need for re-intervention, etc. | from insertion of TIPS to 2 years post TIPS | 
| TIPS patency | evaluation of how long the TIPS remains patent without need for further intervention | from insertion of TIPS to 2 years post TIPS | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TIPS, Hemodynamic, Ascites, Hepatic, Hydrothorax