Tonometry(1) and Duplex Ultrasound(2) to Predict CV Events in to be Treated Patients With an AAA

Study Overview
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Brief Summary
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Abdominal aortic aneurysm (AAA) is a common vascular disease and associated with risk of rupture, but also with a high cardiovascular (CV) event rate. A key difficulty in AAA is predicting these life-threatening complications, which are strongly linked to vascular health. In 2013, the SMART risk score was developed to calculate the risk of the patients for recurrent vascular events based on clinical characteristics. Recently, a novel, easy to perform, non-invasive test of endothelial function (the carotid artery reactivity (CAR) test), reflecting target organ damage, has been introduced. The CAR is a simple, quick (5-min), non-invasive test that uses ultrasound to examine the carotid artery in response to sympathetic stimulation by placing one hand in cold water. This test shows strong agreement with both coronary and aortic responses to sympathetic stimulation and predicted CV-events in patients with peripheral arterial disease. The aim of this prospective 2-year follow-up study is to investigate the predictive capacity of the CAR-test for development of CV-events after elective AAA repair in comparison to the SMART risk score. Secondary objectives are to investigate the predictive capacity of arterial stiffness measurements and the post-operative CAR-test for development of CV-events and to evaluate health status scores to provide insight if these scores can support clinical decision making.

Detailed Description
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The investigators will include 194 patients with an AAA who will be scheduled for repair. Participants will be recruited from all collaborating hospitals (currently Radboudumc, Rijnstate, CWZ) after providing written informed consent. In this observational, prospective study, a total of 194 patients who are going to be treated for their AAA will be included. Baseline patient characteristics will be registered, including traditional risk factors and CV-history. In addition to regular care of measuring AAA diameter progression (in mm/year), we will perform the CAR-test (10-min) and non-invasive arterial stiffness measures (PWA and PWV) with the SphygmoCor device (10-min). Furthermore, the investigators will ask patients to complete a questionnaire about the quality of their life. A second questionnaire tries to clarify the disease experience of the patients. Both questionnaires will be asked to be completed at the start, 6-8 weeks after repair, after one year and after two years of repair. Subsequently, the investigators will record major adverse cardiovascular events (MACE) according to the International Classification of Disease-10. Registration of MACE will be performed using hospital-records and following international guidelines. Across a 2-year follow-up, by means of regular follow-up appointments, the investigators will examine the ability of the CAR parameter and arterial stiffness parameters to predict CV-events.

Official Title
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Tonometry(1) and Duplex Ultrasound(2) to Predict Cardiovascular Events in to be Treated Patients With an Abdominal Aortic Aneurysm (One-Two-Treat Trial)

Conditions
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Abdominal Aortic Aneurysm, Cardiovascular Events

Intervention / Treatment
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* Diagnostic Test: Carotid Artery Reactivity test (CAR test)
* Diagnostic Test: Arterial Stiffness


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female at least 18 years old; Informed consent form understood and signed and patient agrees to follow- up visits; Has an infrarenal or juxtarenal abdominal aortic aneurysm (AAA), scheduled for elective repair (i.e open repair, EVAR, FEVAR and CHEVAR) according to standard practice; Exclusion Criteria: Life expectancy < 2 years; Psychiatric or other condition that may interfere with the study; Participating in another clinical study, interfering on outcomes; Increased risk for coronary spasms (score Rose-questionnaire ≥2; Presence of Raynaud's phenomenon, Marfan syndrome, chronic pain syndrome at upper extremity(s), presence of an AV fistula or shunt, open wounds to the upper extremity(s), and/or scleroderma associated with placing the hand in ice water; Recent (<3 months) presence of angina pectoris, myocardial infarction, cerebral infarction, and/or heart failure, or PAD treatment.

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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Arms and Interventions

| Intervention/Treatment |
| --- |
|Diagnostic Test: Carotid Artery Reactivity test (CAR test)|The CAR test will be applied to stimulate the sympathetic nervous system. This thermal stimulus is known to elevate blood pressure via sympathetic pathways, so it can be used to study the vascular response to sympathetic activation. The participant will submerge their left hand in a bucket of ice water (approximately 4 degrees celcius) for 3 minutes, which is reported to be sufficient to induce a maximal dilation in the common carotid artery. At baseline and every minute after the hand is submerged in ice water, the blood pressure will be measured to check whether a sympathetic stimulation is achieved.|
|Diagnostic Test: Arterial Stiffness|The SphygmoCor device will be used to non-invasively measure arterial stiffness parameters using applanation tonometry. For Pulse Wave Analyses (PWA), the radial waveform will be recorded. Approximately 10 waveforms are averaged, resulting in several non-invasive parameters: Peripheral pressure parameters Central and abdominal aneurysm pressure parameters (derived using a transfer function) Cardiac output parameters (sub-endocardial viability ratio (SEVR), Ejection Duration (ED)) Pulse wave velocity will be performed by recording the waveforms of the carotid and femoral artery sequentially. The travelled distance will be measured according to the current guidelines and entered in the program. The program will calculate the PWV based on 10 ECG triggered waveform of each artery.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major Adverse Cardiovascular Events (MACE) | Incidence of MACE, including myocardial infarction, cerebral infarction, heart failure, rupture, and peripheral vascular disease | 2-year follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SMART Risk score | Second Manifestations of ARTerial disease risk score is developed to determine the risk of recurrent vascular events based on clinical characteristics of the patients | Baseline | 
| CAR-test results | Percentage of vasodilation/vasoconstriction to the CAR test at the common carotid artery at baseline | Baseline and 6-weeks after operation | 
| CAR-test results | Magnitude of the blood flow and perfusion response | Baseline and 6-weeks after operation | 
| CAR-test results | Timing of the blood flow and perfusion response | Baseline and 6-weeks after operation | 
| CAR-test results | Blood pressure responses | Baseline and 6-weeks after operation | 
| CAR-test results | Heart rate responses | Baseline and 6-weeks after operation | 
| CAR-test results | Changes after treatment | Baseline and 6-weeks after operation | 
| SphygmoCor parameters | Peripheral pressure measurements (PWA) | Baseline, 6-weeks, 1 year and 2 year after operation | 
| SphygmoCor parameters | Central pressure measurements (derived using a transfer function, PWA) | Baseline, 6-weeks, 1 year and 2 year after operation | 
| SphygmoCor parameters | Abdominal pressure measurements (derived using a transfer function, PWA) | Baseline, 6-weeks, 1 year and 2 year after operation | 
| SphygmoCor parameters | SEVR | Baseline, 6-weeks, 1 year and 2 year after operation | 
| SphygmoCor parameters | ED | Baseline, 6-weeks, 1 year and 2 year after operation | 
| SphygmoCor parameters | PWV | Baseline, 6-weeks, 1 year and 2 year after operation | 
| SphygmoCor parameters | Change in Peripheral pressure measurements (PWA) after treatment | Baseline and 6-weeks after operation | 
| SphygmoCor parameters | Change in Central pressure measurements (derived using a transfer function, PWA) after treatment | Baseline and 6-weeks after operation | 
| SphygmoCor parameters | Change in Abdominal pressure measurements (derived using a transfer function, PWA) after treatment | Baseline and 6-weeks after operation | 
| SphygmoCor parameters | Change in SEVR after treatment | Baseline and 6-weeks after operation | 
| SphygmoCor parameters | Change in ED after treatment | Baseline and 6-weeks after operation | 
| SphygmoCor parameters | Change in PWV after treatment | Baseline and 6-weeks after operation | 
| Score EQ-5D questionnaire | Patient reported outcomes measured by the general health questionnaire | Baseline, 6-weeks, 1 year and 2 year after operation | 
| Score IPQ-K questionnaire | Patient reported outcomes measured by the disease perception questionnaire | Baseline, 6-weeks, 1 year and 2 year after operation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Functional Response, Abdominal Aortic Aneurysm, Cardiovascular Events