Multidisciplinary Analysis by Morphological and Mechanical Evaluation of the Aortic Wall in Patients Undergoing Cardiac Surgery.

Multidisciplinary Analysis by Morphological and Mechanical Evaluation of the Aortic Wall in Patients With Aortic Disease, Undergoing Aortic Cardiac Surgery, vs Patients Without Aortic Disease

Surgical indication in patients suffering from Ascending aorta aneurysm is currently based mainly on the maximum diameter of the aortic dilatation and on the yearly growth rate. Several clinical preoperative patients characteristics have been, potentially, correlated to impaired mechanical characteristics of aortic wall, and therefore to an increased risk of rupture and or dissection. On other hands, such suppositions have been never confirmed, as a full characterization of the mechanical behaviour of the ascending aortic tissue, especially in case of aneurysm, has not been fully clarified yet. Objective of this observational study is to better elucidate, using direct in vivo evaluation, the mechanical characteristics of the aortic wall in patients with ascending aorta diseases. Our study will have a further peculiar characteristic as we have the intention of compare such mechanical characteristics to those of patients, without known aortic diseases, undergoing heart transplantation. Potential correlation between, directly measured mechanical characteristics of the aortic wall, and preoperative parameters (anagraphic patients characteristics, clinical data and diagnostic tests) will be also investigated.

Study Overview

• Status: Recruiting
• Conditions: Aortic Aneurysm; Aortic Aneurysm and Dissection

Detailed Description

1. Patients selection All patients undergoing cardiac surgery procedures requiring ascending aorta replacement could be enrolled in the study, providing that they will sign the specific informed consent. In these patients (Group A), at surgery, following routine collection of specimens for standard histological and/or biochemical evaluation, all residual specimens are collected, stored, and sent for anonymous mechanical tests at the Department of Civil Engineering of the University of Pavia for the full protocol of the tests). There will be no specific contraindication to patient inclusion in the study except in case of high biological hazard (i.e. HCV+ patients). Patient inclusion in the study and specimen collection, therefore, will not interfere in any way with the diagnostic and therapeutic decision-making process. As a control group, we will also enroll, pending specific consensus, patients undergoing heart transplantation. In this group of patients (Group B), once the cardiotomy is completed, selected specimens of the removed ascending aorta will be stored and sent to the Department of Engineering of the University of Pavia using the same protocol. Group B could also include specimens from donor's hearts, harvested at the time of transplantation.

2. Specimen's Collection and preparation Once the selected portion of the ascending aorta is removed, according to the surgical procedure, specimens for routine investigations are collected and prepared for histological evaluation as per the current protocol. The residual portion is divided into specimens, which will be identified according to the orientation and the anatomical position as A1, A2, and A3 (anterior portion respectively from the ST junction to the tubular portion and finally to the distal portion close to the innominate artery) and P1, P2 (posterior portion respectively from the proximal portion to the distal portion).

   Once all specimens are identified, they will be stored in isotonic physiological solution and kept in a refrigerator at 4°C until mechanical testing will be performed. They will be all collected in one single box identified with a numerical progressive code (i.e. P1, P2, etc) without any further information regarding the patient's characteristics. Patient data and their correlation to the progressive code will be only available in the specific database, which will be under the direct responsibility of the principal investigator of the study .

3. Mechanical Properties Analysis Mechanical uniaxial tensile ultimate stress test are performed on the fresh "ex vivo" sample within 24 hours from the harvesting. Briefly, from the full cylinder, a number of samples with a dog-bone shape and a length/width ratio of at least 4:1 are prepared. Samples are divided and identified according the region of the aortic wall (anterior/greater curvature and posterior/lesser curvature). The number of samples obtained from each patient are related to the original dimension of the harvested aortic cylinder and usually ranged from 2 to 13. The dog-bone shape allowed a central narrow region, identified by two black markers. Before mechanical tests, the thickness of each samples of aortic wall (awTK) is accurately measured with a dedicated calibre. Tests are, then, performed using a MTS insight testing system 10 kN (MTS system corporation) using uniaxial circumferential and/or longitudinal force. Each test is identified according the region of the aorta where the specimen was harvested and the direction of the applied force. Three ultimate mechanical properties parameters will be measured : Peak Strain (Pstr) as the maximum strain before specimen rupture (marker of aortic wall elasticity); Peak Stress (PS) as the maximum stress before specimen rupture (marker of aortic wall strength) and Maximum Elastic Modulus (EM) as the maximum slope of stress/strain curve (marker of aortic wall stiffness or resistance to deformation).
4. Statistical analysis Based on a previous series of test and on the standard deviation obtained for the three main mechanic parameters measured: Peek Strain, Peek stress and Elastic modulus (0.11 mm, 0.756 MPa and 17.88 MPa respectively) we calculated a sample size of 22 patients each groups to detect a difference equal to 1sd with a power of (90% error and 0.5% error ). Furthermore, based on the number of patients undergoing ascending aortic surgery at our Division in the last three years (nearly 100py), and on the patients characteristics (age, gender, presence of bicuspid aortic valve), we aim to collect at least 60-80 patients in one year, and to identify, with significant statistical power, potential mechanical characteristics differences related to gender, age >70 years and the presence of native bicuspid valve.

Summary of description of statistical analysis:

Statistical analysis will be performed using MedCalc Statistical Software. Continuous variables will be tested for normality of distribution using a Kolmogorov-Smirnov tests. According to the result of the normal distribution, continuous variables will be then summarized as mean plus/minus SD or median [IQR]. Differences between two groups (i.e. female/male, below/above 70 yo, bicuspid/tricuspid native aortic valve) will be compared trough the unpaired t-test and analysis of variance (with Bonferroni test) or Mann-Whitney U-test and Kruskal-Wallis in case of parametric or non parametric distribu tion respectively (p<0.05 was considered statistically significant). The statistic relations between different continuous variables (i.e mechanical tests and age, extension of aortic dilatation, extension of indexed aortic dilatation, preoperative TTE calculated aortic elasticity etc etc, will be evaluated by mean of a linear regression analysis, using the Pearson's correlation coefficent (r) and assuming as significant a p value <0.005. Finally a multivariate regression models (forward stepwise) will be carried out to identify the predictors of a severely impaired mechanical properties (i.e. Peek Strain and Peek Stress <25th percentile and Elastic Modulus >75th percentile).

• Study Type: Observational
• Enrollment (Estimated): 250

Contacts and Locations

• Study Contact: Name: Pasquale Totaro, MD; Phone Number: 3283678762; Email: p.totaro@matteo.pv.it

Study Locations

• Italy
  • Lombardy
    • Pavia, Lombardy, Italy, 27100
      • Recruiting
      • Fondazione IRCCS Policlinico San Matteo di Pavia
      • Contact: Pasquale Totaro, MD; Phone Number: 3283678762; Email: p.totaro@matteo.pv.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

The primary study population consisted of patients referred for ascending aortic/aortic root dilation surgery. The study evolved to include control groups including patients with acute aortic dissection and patients without aortic disease undergoing heart transplantation.

Description

Inclusion Criteria:

• Patients undergoing surgery including ascending aorta replacement at our Department and/or heart transplantation

Exclusion Criteria:

• Patients with biological hazard (HBC/HIV +)

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
2 main groups: Diseased Aorta and non-diseased aorta; Diseased aorta included patients with chronic aortic aneurysm and patients with aortic dissection. Control group included non diseased aorta undergoing surgery for heart transplantation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of extreme aortic wall fragility in relation to demographic or pathological characteristics of the enrolled patients.	The execution of the above tests, and the following analysis and post-processing of the tests response will allow the characterization of ultimate mechanical properties using three main parameters: Peak Strein (the maximum strein before specimen rupture); Peak Stress (the maximum stress before specimen rupture); Maximum Elastic Modulus (the maximum slope of the stress-strain curve The identification of extreme aortic wall fragility will be based primarily on extreme values of the first two parameters (<25th percentile). For the third parameter, both extreme values (<25th and >75th percentile) will be considered. As a further parameter of fragility, an abnormal increase in intra-patient variability will also be considered, in case of the possibility of multiple tests.	Perioperative (Within 24 hours from surgery)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ex-vivo evaluation of mechanical properties of aortic wall in patients with and without aortic diseases undergoing cardiac surgery procedure.	Uniaxial and biaxial tensile tests to failure of fresh specimens collected during cardiac surgery and transferred (within 24 hours) to the Department of Civil Engineering and Architecture of the University of Pavia. The execution of the above tests, and the following analysis and post-processing of the tests response will allow the characterization of ultimate mechanical properties using three main parameters: Peak Strein (the maximum strein before specimen rupture); Peak Stress (the maximum stress before specimen rupture); Maximum Elastic Modulus (the maximum slope of the stress-strain curve) . Test results will ultimately be correlated with patient demographics and specific disease patterns (e.g. presence and extent of aortic dilation, combined aortic valve disease, acute aortic dissection). The final aim of the study is the potential identification of predictive factors for increased risk of acute aortic events.	Perioperative (within 24 hours from surgery)
Ex vivo evaluation of aortic wall mechanical characteristics in patients with and without aortic disease.	Fresh aortic wall samples taken during surgery are sent within 24 hours at the Department of Civil Engineering and Architecture of the University of Pavia where uniaxial and biaxial mechanical test at rupture are completed. The execution of the above tests, and the following analysis and post-processing of the tests response will allow the characterization of ultimate mechanical properties using three main parameters: Peak Strein (the maximum strein before specimen rupture, expressed as mm-mm); Peak Stress (the maximum stress before specimen rupture, expressed as MPa); Maximum Elastic Modulus (the maximum slope of the stress-strain curve, expressed as a ratio mm-mm/MPa). The test results will then be correlated with the patients' demographic characteristics and with the characteristics of the disease to highlight potential predictors of greater fragility of the aortic wall and increased risk of acute events.	Perioperative (Without 24 hours from surgery)

Collaborators and Investigators

• Sponsor: Fondazione IRCCS Policlinico San Matteo di Pavia

Study record dates

Study Major Dates

• Study Start (Actual): March 24, 2015
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: February 3, 2026
• First Submitted That Met QC Criteria: February 12, 2026
• First Posted (Actual): February 19, 2026

Study Record Updates

• Last Update Posted (Actual): February 19, 2026
• Last Update Submitted That Met QC Criteria: February 12, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Dissection, Blood Vessel; Acute Aortic Syndrome; Vascular Diseases; Cardiovascular Diseases; Aortic Diseases; Aneurysm; Aortic Aneurysm; Aortic Dissection
• Other Study ID Numbers: APA

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No