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.

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 fr…

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…

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…

Computational analysis to predict false-lumen perfusion and outcome of type B aortic dissection.

We have attempted to identify potential predictors foracute and late aortic events starting from admission computed tomographic images.

Molecular Analysis With 16S rRNA PCR/Sanger Sequencing and Molecular Antibiogram Performed on DNA Extracted From Valve Improve Diagnosis and Targeted Therapy of Infective Endocarditis: A Prospective Study

Abstract Background Molecular analysis (MA) on heart valve (HV) improves the microbiologic diagnosis of infectious endocarditis (IE). The main drawback of MA is the lack of antimicrobial susceptibility information. Methods We conducted a prospective cohort observational study of consecutive adult patients from April 2012 to May 2021 who underwent valve surgery at our hospital. The performance of MA, blood cultures (BC) and valve cultures (VC), and the diagnostic and therapeutic impact of MA were evaluated. Molecular antibiogram results were compared to culture-based antimicrobial susceptibility testing (AST). Results A total of 137 patients with definite IE and 52 patients with no IE were e…

Simulation of left ventricular outflow tract (LVOT) obstruction in transcatheter mitral valve-in-ring replacement.

Left ventricular outflow tract (LVOT) obstruction is a feared complication of transcatheter mitral valve replacement (TMVR). This procedure leads to an elongation of LVOT in the left ventricle (namely, the neoLVOT), ultimately portending hemodynamic impairment and death. This study sought to understand the biomechanical implications of LVOT obstruction in two patients who underwent TMVR as an "off-label" application of the Edwards SAPIEN 3 (S3) Ultra transcatheter heart valve (THV). A computational framework of TMVR was developed to assess the neoLVOT area and quantify the sub-aortic flow structure. We observed that the annuloplasty ring serves as the key anchor zone of S3 Ultra THV. A good…

A strange pneumonia

We report the case of a 62-year-old man with non-ST elevation myocardial infarction complicated by partial rupture of the antero-lateral papillary muscle in which severe mitral regurgitation with lateralized direction towards the right pulmonary veins gave unilateral pulmonary oedema, resembling an acute pneumonia.Unilateral pulmonary oedema is a rare entity, more frequently appearing as opacity of the right lung and always associated with severe mitral regurgitation. It is very important to suspect and promptly recognize unilateral pulmonary oedema because initial misdiagnosis leads to a delay in the initiation of appropriate treatment and to an increased risk of mortality.

Atlas-Based Evaluation of Hemodynamic in Ascending Thoracic Aortic Aneurysms

Atlas-based analyses of patients with cardiovascular diseases have recently been explored to understand the mechanistic link between shape and pathophysiology. The construction of probabilistic atlases is based on statistical shape modeling (SSM) to assess key anatomic features for a given patient population. Such an approach is relevant to study the complex nature of the ascending thoracic aortic aneurysm (ATAA) as characterized by different patterns of aortic shapes and valve phenotypes. This study was carried out to develop an SSM of the dilated aorta with both bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV), and then assess the computational hemodynamic of virtual models ob…

Long-term functional and psychological recovery in a population of acute respiratory distress syndrome patients treated with VV-ECMO and in their caregivers.

Background Acute respiratory distress syndrome (ARDS) survivors are affected with long-term physical/mental impairments, with improvements limited mostly to the first year after intensive care (ICU) discharge. Furthermore, caregivers of ICU patients exhibit psychological problems after family-member recovery. We evaluated the long-term physical and mental recovery of ARDS survivors treated with veno-venous extracorporeal membrane oxygenation (VV-ECMO), and the long-term psychological impact on their caregivers. Methods Single-center prospective evaluation of a retrospective cohort of 75 ARDS patients treated with VV-ECMO during a seven-year period (25.10.2009-11.08.2016). Primary outcomes w…

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…

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…

Usefulness of regional right ventricular and right atrial strain for prediction of early and late right ventricular failure following a left ventricular assist device implant: A machine learning approach

Background: Identifying candidates for left ventricular assist device surgery at risk of right ventricular failure remains difficult. The aim was to identify the most accurate predictors of right ventricular failure among clinical, biological, and imaging markers, assessed by agreement of different supervised machine learning algorithms. Methods: Seventy-four patients, referred to HeartWare left ventricular assist device since 2010 in two Italian centers, were recruited. Biomarkers, right ventricular standard, and strain echocardiography, as well as cath-lab measures, were compared among patients who did not develop right ventricular failure (N = 56), those with acute–right ventricular fail…

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 …

Shear stress alterations in the celiac trunk of patients with a continuous-flow left ventricular assist device as shown by in-silico and in-vitro flow analyses

Background The use of left ventricular assist devices (LVADs) to treat advanced cardiac heart failure is constantly increasing, although this device leads to high risk for gastrointestinal bleeding. Methods Using in-silico flow analysis, we quantified hemodynamic alterations due to continuous-flow LVAD (HeartWare, Inc., Framingham, MA) in the celiac trunk and major branches of the abdominal aorta, and then explored the relationship between wall shear stress (WSS) and celiac trunk orientation. To assess outflow from the aortic branch, a 3-dimensional-printed patient-specific model of the celiac trunk reconstructed from an LVAD-supported patient was used to estimate echocardiographic outflow …

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.

Haemodynamic predictors of a penetrating atherosclerotic ulcer rupture using fluid-structure interaction analysis

We present preliminary data on the flow-induced haemodynamic and structural loads exerted on a penetrating atherosclerotic aortic ulcer (PAU). Specifically, one-way fluid-structure interaction analysis was performed on the aortic model reconstructed from a 66-year-old male patient with a PAU that evolved into an intramural haematoma and rupture of the thoracic aorta. The results show that elevated blood pressure (117 mmHg) and low flow velocity at the aortic wall (0.15 m/s(2)) occurred in the region of the PAU. We also found a low value of time-averaged wall shear stress (1.24 N/m(2)) and a high value of the temporal oscillation in the wall shear stress (oscillatory shear index = 0.13) in t…

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 fluid dynamics simulation to evaluate aortic coarctation gradient with contrast-enhanced CT

Coarctation of aorta (CoA) is a narrowing of the aorta leading to a pressure gradient (Delta P) across the coarctation, increased afterload and reduced peripheral perfusion pressures. Indication to invasive treatment is based on values of maximal (systolic) trans-coarctation Delta P. A computational fluid dynamic (CFD) approach is herein presented for the non-invasive haemodynamic assessment of Delta P across CoA. Patient-specific CFD simulations were created from contrast-enhanced computed tomography (CT) and appropriate flow boundary conditions. Computed Delta P was validated with invasive intravascular trans-CoA pressure measurements. Haemodynamic indices, including pressure loss coeffic…

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…

Predicting Outcome of Aortic Dissection with Patent False Lumen by Computational Flow Analysis

Although Type B aortic dissection (AoD) has better in-hospital survival than Type A AoD, the short- and long term outcome for patients remains challenging, with 50–80% deaths at 5-years. Dissection-related complications include rapid aortic expansion, impending rupture, and malperfusion syndromes. We aimed to assess hemodynamic implications of patients with patent false lumen (FL) of dissected aorta. Computational fluid dynamic analyses were performed on patient-specific aortic geometries reconstructed from computed tomography scans of 25 patients with AoDs, who were admitted in our hospital from 2007 to 2013. We used the development of acute complications and chronic aneurysmal evolution a…

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 …

Difference in hemodynamic and wall stress of ascending thoracic aortic aneurysms with bicuspid and tricuspid aortic valve.

The aortic dissection (AoD) of an ascending thoracic aortic aneurysm (ATAA) initiates when the hemodynamic loads exerted on the aneurysmal wall overcome the adhesive forces holding the elastic layers together. Parallel coupled, two-way fluid–structure interaction (FSI) analyses were performed on patient-specific ATAAs obtained from patients with either bicuspid aortic valve (BAV) or tricuspid aortic valve (TAV) to evaluate hemodynamic predictors and wall stresses imparting aneurysm enlargement and AoD. Results showed a left-handed circumferential flow with slower-moving helical pattern in the aneurysm's center for BAV ATAAs whereas a slight deviation of the blood flow toward the anterolater…

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…

Combination of aztreonam, ceftazidime–avibactam and amikacin in the treatment of VIM-1 Pseudomonas aeruginosa ST235 osteomyelitis

Abstract We describe a challenging case of patient with metallo-beta-lactamase-producing Pseudomonas aeruginosa sternal osteomyelitis following aortic valve replacement with biological prosthesis. The strain exhibited a multidrug-resistance phenotype carrying the blaVIM-1 gene and belonged to the high-risk clone sequence type ST235. The patient was successfully treated with surgical debridement plus antibiotic therapy with ceftazidime/avibactam, aztreonam, and amikacin. Time-kill curves showed that this triple antibiotic combination at 1 × MIC was strongly synergic after 8 h, achieving 99.9% killing and maintaining this until 48 h.

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…

Modeling Right Ventricle Failure After Continuous Flow Left Ventricular Assist Device: A Biventricular Finite-Element and Lumped-Parameter Analysis

The risk of right ventricle (RV) failure remains a major contraindication for continuous-flow left ventricular assist device (CF-LVAD) implantation in patients with heart failure. It is therefore critical to identify the patients who will benefit from early intervention to avoid adverse outcomes. We sought to advance the computational modeling description of the mechanisms underlying RV failure in LVAD-supported patients. RV failure was studied by computational modeling of hemodynamic and cardiac mechanics using lumped-parameter and biventricular finite element (FE) analysis. Findings were validated by comparison of bi-dimensional speckle-tracking echocardiographic strain assessment of the …

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…