On the prospect of serum exosomal miRNA profiling and protein biomarkers for the diagnosis of ascending aortic dilatation in patients with bicuspid and tricuspid aortic valve.

Background: To determine the impact of circulating miRNA and protein activity on the severity of ascending aortic dilatation in patients with bicuspid (BAV) and tricuspid aortic valve (TAV). Methods: By reverse transcription polymerase chain reaction, exosomal circulating expression levels (versus healthy aorta) of miRNAs and absolute levels of transforming growth factor β (TGF-β), matrix metalloproteinases (MMP-2, -3 and -9), tissue inhibitors (TIMP-1, -2, -3 and -4), and soluble receptors for advanced glycation end products AGEs (sRAGE) were evaluated in ascending dilated aortas of 71 patients with different valve morphotype. Results: Less-dilated ascending aorta exhibited a specific miRN…

Predicting LVOT Obstruction in Transcatheter Mitral Valve Replacement for Failed Surgical Annuloplasty

Three-dimensional parametric modeling of bicuspid aortopathy and comparison with computational flow predictions

Bicuspid aortic valve (BAV)-associated ascending aneurysmal aortopathy (namely "bicuspid aortopathy") is a heterogeneous disease making surgeon predictions particularly challenging. Computational flow analysis can be used to evaluate the BAV-related hemodynamic disturbances, which likely lead to aneurysm enlargement and progression. However, the anatomic reconstruction process is time consuming so that predicting hemodynamic and structural evolution by computational modeling is unfeasible in routine clinical practice. The aim of the study was to design and develop a parametric program for three-dimensional (3D) representations of aneurysmal aorta and different BAV phenotypes starting from s…

Corrigendum to Patterns of ascending aortic dilatation and predictors of surgical replacement of the aorta: A comparison of bicuspid and tricuspid aortic valve patients over eight years of follow-up “J Mol Cell Cardiol. 2019 Oct;135:31–39. PMID: 31348923” (Journal of Molecular and Cellular Cardiology (2019) 135 (31–39), (S0022282819300495), (10.1016/j.yjmcc.2019.07.010))

The authors regret that the author name of Romano and Raffa are incorrect. The corrected author's name are Romano G and Raffa GM. The authors would like to apologise for any inconvenience caused.

Patient-Specific Analysis of Ascending Thoracic Aortic Aneurysm with the Living Heart Human Model

In ascending thoracic aortic aneurysms (ATAAs), aneurysm kinematics are driven by ventricular traction occurring every heartbeat, increasing the stress level of dilated aortic wall. Aortic elongation due to heart motion and aortic length are emerging as potential indicators of adverse events in ATAAs

In Vivo Strain Analysis of Dilated Ascending Thoracic Aorta by ECG-Gated CT Angiographic Imaging

Accurate assessment of aortic extensibility is a requisite first step for elucidating the pathophysiology of an ascending thoracic aortic aneurysm (ATAA). This study aimed to develop a framework for the in vivo evaluation of the full-field distribution of the aortic wall strain by imaging analysis of electrocardiographic- (ECG) gated thoracic data of 34 patients with ATAA. Seven healthy controls (i.e., non-aneurysmal aorta) from patients who underwent ECG-gated CT angiography for coronary artery diseases were included for comparison. To evaluate the systolic function, ECG-gated computed tomography (CT) angiography was used to generate patient-specific geometric meshes of the ascending aorta…

Statistical shape analysis of ascending thoracic aortic aneurysm: Correlation between shape and biomechanical descriptors

An ascending thoracic aortic aneurysm (ATAA) is a heterogeneous disease showing different patterns of aortic dilatation and valve morphologies, each with distinct clinical course. This study aimed to explore the aortic morphology and the associations between shape and function in a population of ATAA, while further assessing novel risk models of aortic surgery not based on aortic size. Shape variability of n = 106 patients with ATAA and different valve morphologies (i.e., bicuspid versus tricuspid aortic valve) was estimated by statistical shape analysis (SSA) to compute a mean aortic shape and its deformation. Once the computational atlas was built, principal component analysis (PCA) allow…

Echocardiography to estimate high filling pressure in patients with heart failure and reduced ejection fraction

Aims: Echocardiographic assessment of left ventricular filling pressures is performed using a multi-parametric algorithm. Unselected sample of patients with heart failure with reduced ejection fraction (HFrEF) patients may demonstrate an indeterminate status of diastolic indices making interpretation challenging. We sought to test improvement in the diagnostic accuracy of standard and strain echocardiography of the left ventricle and left atrium (LA) to estimate a pulmonary capillary wedge pressure (PCWP) > 15 mmHg in patients with HFrEF. Methods and results: Out of 82 consecutive patients, 78 patients were included in the final analysis and right heat catheterization, and echocardiogram…

On the severity of aortic stenosis in ascending aortic aneurysm: A computational tool to examine ventricular-arterial interaction and aortic wall stress

Abstract An ascending thoracic aortic aneurysm (ATAA) is a life-threatening cardiovascular consequence of vessel dilatation that portends adverse events and death. From a clinical perspective, ATAA should not be treated as an isolated disease, and surgery is often carried out in the presence of AS, aortic insufficiency or a calcified valve leaflet. Aortic stenosis (AS) is common in ATAAs and leads to both vessel rigidity and left ventricular (LV) impairment. In this study, lumped-parameter modeling and computational analysis were used to assess the change in the wall shear stress (WSS) and intramural wall stress of patient-specific ATAA models with different degrees of AS (i.e., mild to sev…

Ascending Aorta Resection and End-to-End Anastomosis: Redistribution of Wall Shear Stress Induced by a Bioprosthetic Heart Valve

Although aortic resection and end-to-end anastomosis are applied to repair ascending aortic aneurysm, there is a lack of information on the late risk of post-operative complications, such as aortic dissection and aneurysmal re-dilatation. It is recognized that altered hemodynamic forces exerted on an aortic wall play an important role on dissection and aneurysm formation. We present a case in which the hemodynamic forces were investigated prior and after repair of an ascending aorta treated by resection with end-to-end anastomosis and a bioprosthetic heart valve. Post-operative wall shear stress was redistributed uniformly along the vessel circumference, and this may suggest a reduced risk …

Patterns of ascending aortic dilatation and predictors of surgical replacement of the aorta: A comparison of bicuspid and tricuspid aortic valve patients over eight years of follow-up

Abstract Background Predictors of thoracic aorta growth and early cardiac surgery in patients with bicuspid aortic valve are undefined. Our aim was to identify predictors of ascending aorta dilatation and cardiac surgery in patients with bicuspid aortic valve (BAV). Methods Forty-one patients with BAV were compared with 165 patients with tricuspid aortic valve (TAV). All patients had LV EF > 50%, normal LV dimensions, and similar degree of aortic root or ascending aorta dilatation at enrollment. Patients with more than mild aortic stenosis or regurgitation were excluded. A CT-scan was available on 76% of the population, and an echocardiogram was repeated every year for a median time of 4 ye…

Computational fluid dynamics of the ascending aorta before the onset of type A aortic dissection.

We performed a pre-dissection computational fluid analysis of an ascending aortic aneurysm associated with unicuspid aortic valve. The analysis showed an abnormal helical flow pattern inside the aneurysm and an increased wall stress on the right postero-lateral wall of the ascending aorta. These values were largely higher than the theoretical cut-off for aortic wall dissection, their topographic distribution followed the intimal tear site as subsequently diagnosed by computed tomography scan and confirmed during the operation for dissection repair.

Shear Stress and Aortic Strain Associations With Biomarkers of Ascending Thoracic Aortic Aneurysm

This study aims to investigate the association of wall shear stress (WSS) and aortic strain with circulating biomarkers including matrix metalloproteinases (MMP), tissue inhibitors of metalloproteinase (TIMP), and exosomal level of microRNA (miRNA) in ascending aortic aneurysms of patients with bicuspid or tricuspid aortic valve.A total of 76 variables from 125 patients with ascending aortic aneurysms were collected from (1) blood plasma to measure plasma levels of miRNAs and protein activity; (2) computational flow analysis to estimate peak systolic WSS and time-average WSS (TAWSS); and (3) imaging analysis of computed tomography angiography to determine aortic wall strain. Principal compo…

Early distal remodeling after elephant trunk repair of thoraco-abdominal aortic aneurysms

Hemodynamic alterations occur when the elephant trunk (ET) technique is adopted to treat extensive aortic aneurysms. In planning the 2nd stage operation to complete ET repair, surgeons must weigh an adequate recovery time after initial surgery against the risk of postoperative ET-related complications. The purpose of this study was to understand the mechanistic link between the flow alteration caused by the ET graft and the development of premature aortic rupture before the 2nd stage operation. Specifically, fluid-structure interaction (FSI) analysis was performed using the CT imaging data of aorta at different stages of ET repair, and then computational variables were compared to those obs…

Identification of circumferential regional heterogeneity of ascending thoracic aneurysmal aorta by biaxial mechanical testing

Abstract Ascending thoracic aortic aneurysm (ATAA) in patients with bicuspid aortic valve (BAV) can present an asymmetrical aortic dilatation compared with patients with tricuspid aortic valve (TAV). This pattern of aneurysm dilatation led us to hypothesize that biomechanical differences likely induced by regional heterogeneity of material properties can underlie the observed asymmetric enlargement discrepancies between BAV ATAA and TAV ATAA. This study aimed to characterize the mechanical properties and associated aortic tissue stiffness changes along the circumferential direction of aortic rings collected from surgically-repaired patients with ATAA. Biaxial material testing was performed …

Patients with bicuspid aortic valve are likely to receive an aortic valve prosthesis during prophylactic resection of their ascending aortic aneurysm.

This study aims to evaluate whether thepresence or discovery of a BAV under ATAA repair would impactthe decision-making of the surgical procedure choice.

Peripheral Artery Disease and Continuous Flow Left Ventricle Assist Device: An Engaging Complement Analysis May Help to Guide Treatment

Use of continuous flow left ventricle assist device (CF-LVAD) in advanced heart failure (HF) patients results in clinically relevant improvements in survival, functional capacity, and quality of life. Peripheral artery disease (PAD) can occur in patients with CF-LVAD due to the high rate of concomitance between risk factors for atherosclerosis and HF. Diagnosis of PAD can be difficult in the specific setting of a patient supported by this kind of device because of the marked alteration in waveform morphology and velocity created by the artificial physiology of an LVAD. We report the case of a 53-year-old man with HF secondary to ischemic cardiomyopathy supported by the HeartWare HVAD as bri…

Biomechanical implications of excessive endograft protrusion into the aortic arch after thoracic endovascular repair

Endografts placed in the aorta for thoracic endovascular aortic repair (TEVAR) may determine malappositioning to the lesser curvature of the aortic wall, thus resulting in a devastating complication known as endograft collapse. This premature device failure commonly occurs in young individuals after TEVAR for traumatic aortic injuries as a result of applications outside the physical conditions for which the endograft was designed. In this study, an experimentally-calibrated fluid-structure interaction (FSI) model was developed to assess the hemodynamic and stress/strain distributions acting on the excessive protrusion extension (PE) of endografts deployed in four young patients underwent TE…

On the role of material properties in ascending thoracic aortic aneurysms

One of the obstacles standing before the biomechanical analysis of an ascending thoracic aortic aneurysm (ATAA) is the difficulty in obtaining patient-specific material properties. This study aimed to evaluate differences on ATAA-related stress predictions resulting from the elastostatic analysis based on the optimization of arbitrary material properties versus the application of patient-specific material properties determined from ex-vivo biaxial testing. Specifically, the elastostatic analysis relies the on the fact that, if the aortic wall stress does not depend on material properties, the aorta has to be statistically determinate. Finite element analysis (FEA) was applied to a group of …

Computational modeling of bicuspid aortopathy: Towards personalized risk strategies.

This paper describes current advances on the application of in-silico for the understanding of bicuspid aortopathy and future perspectives of this technology on routine clinical care. This includes the impact that artificial intelligence can provide to develop computer-based clinical decision support system and that wearable sensors can offer to remotely monitor high-risk bicuspid aortic valve (BAV) patients. First, we discussed the benefit of computational modeling by providing tangible examples of in-silico software products based on computational fluid-dynamic (CFD) and finite-element method (FEM) that are currently transforming the way we diagnose and treat cardiovascular diseases. Then…

An In Vitro Phantom Study on the Role of the Bird-Beak Configuration in Endograft Infolding in the Aortic Arch.

Purpose: To assess endograft infolding for excessive bird-beak configurations in the aortic arch in relation to hemodynamic variables by quantifying device displacement and rotation of oversized stent-grafts deployed in a phantom model. Methods: A patient-specific, compliant, phantom pulsatile flow model was reconstructed from a patient who presented with collapse of a Gore TAG thoracic endoprosthesis. Device infolding was measured under different flow and pressure conditions for 3 protrusion extensions (13, 19, and 24 mm) of the bird-beak configuration resulting from 2 TAG endografts with oversizing of 11% and 45%, respectively. Results: The bird-beak configuration with the greatest protr…

Prognostic Value of the 6-Min Walk Test After Open-Heart Valve Surgery: EXPERIENCE OF A CARDIOVASCULAR REHABILITATION PROGRAM

PURPOSE: This single-center retrospective analysis aimed to evaluate the prognostic relevance of 6-min walk test (6MWT) in patients admitted to an in-hospital cardiovascular rehabilitation program after open-heart valve surgery. METHODS: One hundred one patients able to perform a 6MWT within the first week of admission (time after surgery: 16 ± 8 d) were included (age 68 ± 11 y; 55% female; median left ventricular ejection fraction 55% [interquartile range: 50-60]; 51% after aortic valve surgery). Study endpoints were cardiovascular death and the combined outcome of cardiovascular death/cardiac hospitalization. Univariate and multivariate analyses were performed to analyze predictive value …

Simulation study of transcatheter heart valve implantation in patients with stenotic bicuspid aortic valve

Bicuspid aortic valve (BAV) anatomy has routinely been considered an exclusion in the setting of transcatheter aortic valve implantation (TAVI) because of the large dimension of the aortic annulus having a more calcified, bulky, and irregular shape. The study aims to develop a patient-specific computational framework to virtually simulate TAVI in stenotic BAV patients using the Edwards SAPIEN 3 valve (S3) and its improved version SAPIEN 3 Ultra and quantify stent frame deformity as well as the severity of paravalvular leakage (PVL). Specifically, the aortic root anatomy of n.9 BAV patients who underwent TAVI was reconstructed from pre-operative CT imaging. Crimping and deployment of S3 fram…

Transcatheter Heart Valve Implantation in Bicuspid Patients with Self-Expanding Device

Bicuspid aortic valve (BAV) patients are conventionally not treated by transcathether aortic valve implantation (TAVI) because of anatomic constraint with unfavorable outcome. Patient-specific numerical simulation of TAVI in BAV may predict important clinical insights to assess the conformability of the transcathether heart valves (THV) implanted on the aortic root of members of this challenging patient population. We aimed to develop a computational approach and virtually simulate TAVI in a group of n.6 stenotic BAV patients using the self-expanding Evolut Pro THV. Specifically, the structural mechanics were evaluated by a finite-element model to estimate the deformed THV configuration in …

Constitutive modeling of ascending thoracic aortic aneurysms using microstructural parameters.

Ascending thoracic aortic aneurysm (ATAA) has been associated with diminished biomechanical strength and disruption in the collagen fiber microarchitecture. Additionally, the congenital bicuspid aortic valve (BAV) leads to a distinct extracellular matrix structure that may be related to ATAA development at an earlier age than degenerative aneurysms arising in patients with the morphological normal tricuspid aortic valve (TAV). The purpose of this study was to model the fiber-reinforced mechanical response of ATAA specimens from patients with either BAV or TAV. This was achieved by combining image-analysis derived parameters of collagen fiber dispersion and alignment with tensile testing dat…

Should subcutaneous implantable cardioverter-defibrillators be implanted in patients who are candidates for continuous flow left ventricular assist device?

Deep learning approach for the segmentation of aneurysmal ascending aorta.

Diagnosis of ascending thoracic aortic aneurysm (ATAA) is based on the measurement of the maximum aortic diameter, but size is not a good predictor of the risk of adverse events. There is growing interest in the development of novel image-derived risk strategies to improve patient risk management towards a highly individualized level. In this study, the feasibility and efficacy of deep learning for the automatic segmentation of ATAAs was investigated using UNet, ENet, and ERFNet techniques. Specifically, CT angiography done on 72 patients with ATAAs and different valve morphology (i.e., tricuspid aortic valve, TAV, and bicuspid aortic valve, BAV) were semi-automatically segmented with Mimic…

In Silico Shear and Intramural Stresses are Linked to Aortic Valve Morphology in Dilated Ascending Aorta

Objective/Background: The development of ascending aortic dilatation in patients with bicuspid aortic valve (BAV) is highly variable, and this makes surgical decision strategies particularly challenging. The purpose of this study was to identify new predictors, other than the well established aortic size, that may help to stratify the risk of aortic dilatation in BAV patients.Methods: Using fluid-structure interaction analysis, both haemodynamic and structural parameters exerted on the ascending aortic wall of patients with either BAV ( n = 21) or tricuspid aortic valve (TAV; n = 13) with comparable age and aortic diameter (42.7 +/- 5.3 mm for BAV and 45.4 +/- 10.0 mm for TAV) were compared…