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Thoracic Aortic Disease: From Bench to Bedside

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A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: closed (30 April 2023) | Viewed by 44390

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Special Issue Editors

Dr. Stefano Nistri

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Guest Editor

CMSR Veneto Medica-Cardiology Service, Altavilla Vicentina, Italy
Interests: valvular heart disease; diseases of the aorta; hypertrophic cardiomyopathy; diastolic function; definition of normalcy; primary care cardiology; preclinical left ventricular dysfunction; chronic heart failure; echocardiography; guidelines implementation

Prof. Dr. Betti Giusti

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Guest Editor

Department of Experimental and Clinical Medicine, University of Florence, Atherothrombotic Diseases Center, Careggi University Hospital, Florence, Italy
Interests: ischemic stroke; atherothrombotic diseases; aortopathies; metabolomics; lipoproteomics; genomics; transcriptomics; genetic risk factors

Prof. Dr. Guglielmina Pepe

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Department of Experimental and Clinical Medicine (DMSC),Tuscany CRR Marfan Syndrome and Related Disorders, University of Florence, Careggi University Hospital, Florence, Italy
Interests: hereditary thoracic aortic aneurysms and dissections; inherited connective tissue disorders; congenital heart diseases; molecular mechanisms underlying hereditary diseases; genotype-phenotype correlation; clinical, biochemical and genetic biomarkers; early diagnosis comorbidities; guidelines implementation
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Dear Colleagues,

The thoracic aorta is a complex structure that can be involved in a variety of pathological processes, resulting in a wide spectrum of either acute or chronic disorders. Aneurysm of the thoracic aorta is the most common of these disorders, and is commonly encountered in outpatient, non-referral settings. The clinical cardiologist is thus called to a substantial number of actions aimed not only at proper anatomical definition and quantitation, but, even more importantly, at accurately defining the etiology and pathogenesis of the aortic aneurysm in an individual patient. Such a complex diagnostic work-out relies on simple medical actions (e.g., family history-taking), but also on the integration of refined imaging modalities and clinico-genetic evaluations.

This Special Issue is thus aimed at providing clinical cardiologists, but also internists and general practitioners (usually the first to encounter patients with thoracic aortic aneurysms) with a summary of updated evidence to support an appropriate referral pattern. We will examine multiple etiologies, their biomolecular and pathogenetic backgrounds, the utilization of different imaging modalities, their integration in a multimodal approach, as well as precise clinical approaches for timely follow-up strategies—including medical therapies and address to interventions. Moreover, problems related to the definition of normalcy/abnormalcy, and the potential implications for physical activities and sport, should be considered. Similarly, the strategies to be utilized in patients after an acute thoracic aortic syndrome will be analyzed, together with the needs of their relatives for clinical and genetic screenings.

The unique profile of this Special Issue will be constituted by its main aim: to provide clinicians practicing in primary care or non-referral settings with updated knowledge on diseases of the thoracic aorta by experts in the multiple fields involved in research and assistance of these relatively common patients.

Dr. Stefano Nistri
Prof. Dr. Betti Giusti
Prof. Dr. Guglielmina Pepe
Guest Editors

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Keywords

aneurysm
aorta, thoracic
aortic aneurysm
aortic dissection
aortic ulcer
aortic wall
athletes
bicuspid aortic valve
cardiac surgical indications
computed tomography
coronary angiography
diagnostic imaging
echocardiography/ultrasound
exome sequencing
familial
aortic aneurysm
first-degree relatives
gene
genetic
genome-wide
growth/dilation rate
histopathology
intramural hematoma
linkage analysis
magnetic resonance
mutation
natural history
next-generation sequencing
non-syndromic aortic aneurysm/dissecting
normalcy
pedigree
relatives
screening
screening aortic aneurysm
siblings
sporadic thoracic aorta
syndromic aortic aneurysm
trans-thoracic, transesophageal
whole exome
whole genome
X-ray

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Published Papers (12 papers)

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Research

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10 pages, 886 KiB

Open AccessArticle

Aortic Dilatation in Pediatric Patients with Bicuspid Aortic Valve: How the Choice of Nomograms May Change Prevalence

by Gaia Spaziani, Francesca Bonanni, Francesca Girolami, Elena Bennati, Giovanni Battista Calabri, Chiara Di Filippo, Giulio Porcedda, Silvia Passantino, Stefano Nistri, Iacopo Olivotto and Silvia Favilli

Diagnostics 2023, 13(8), 1490; https://doi.org/10.3390/diagnostics13081490 - 20 Apr 2023

Cited by 1 | Viewed by 1963

Abstract

Background: Aortic dilation (AoD) is commonly reported in patients with bicuspid aortic valve (BAV) and has been related to flow abnormalities and genetic predisposition. AoD-related complications are reported to be extremely rare in children. Conversely, an overestimate of AoD related to body size may lead to excess diagnoses and negatively impact quality of life and an active lifestyle. In the present study, we compared the diagnosis performance of the newly introduced Q-score (based on a machine-learning algorithm) versus the traditional Z-score in a large consecutive pediatric cohort with BAV. Materials and methods: Prevalence and progression of AoD were evaluated in 281 pediatric patients ages > 5 and < 18 years at first observation, 249 of whom had isolated BAV and 32 had BAV associated with aortic coarctation (CoA–BAV). An additional group of 24 pediatric patients with isolated CoA was considered. Measurements were made at the level of the aortic annulus, Valsalva sinuses, sinotubular aorta, and proximal ascending aorta. Both Z-scores using traditional nomograms and the new Q-score were calculated at baseline and at followup (mean 4.5 years). Results: A dilation of the proximal ascending aorta was suggested by traditional nomograms (Z-score > 2) in 31.2% of patients with isolated BAV and 18.5% with CoA–BAV at baseline and in 40.7% and 33.3%, respectively, at followup. No significant dilation was found in patients with isolated CoA. Using the new Q-score calculator, ascending aorta dilation was detected in 15.4% of patients with BAV and 18.5% with CoA–BAV at baseline and in 15.8% and 3.7%, respectively, at followup. AoD was significantly related to the presence and degree of aortic stenosis (AS) but not to aortic regurgitation (AR). No AoD-related complications occurred during the followup. Conclusions: Our data confirm the presence of ascending aorta dilation in a consistent subgroup of pediatric patients with isolated BAV, with progression during followup, while AoD was less common when CoA was associated with BAV. A positive correlation was found with the prevalence and degree of AS, but not with AR. Finally, the nomograms used may significantly influence the prevalence of AoD, especially in children, with a possible overestimation by traditional nomograms. This concept requires prospective validation in long-term followup. Full article

(This article belongs to the Special Issue Thoracic Aortic Disease: From Bench to Bedside)

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22 pages, 2518 KiB

Open AccessArticle

Use of Anti-Thrombotic Drugs and In-Hospital Mortality in Acute Aortic Dissection Patients

by Kensuke Hori, Nagisa Morikawa, Eiki Tayama and Yoshihiro Fukumoto

Diagnostics 2022, 12(10), 2322; https://doi.org/10.3390/diagnostics12102322 - 26 Sep 2022

Cited by 2 | Viewed by 1907

Abstract

Acute aortic dissection occurs due to a primary tear in the aortic intima, with blood from the aortic lumen entering the adjacent diseased media. In the clinical setting, practitioners often hesitate before the use of anti-thrombotic drugs in the acute phase of aortic dissection. Therefore, we examined the clinical course in patients who had already received antithrombotic therapies at the onset of acute aortic dissection, and who were given anti-thrombotic drugs in the acute phase during hospitalization. We retrospectively enrolled 685 consecutive patients with acute aortic dissection (type A/B: 454/231), who were transferred to Kurume University Hospital from 2004 to 2020. In types A and B, there were no significant differences between in-hospital mortality with or without antithrombotic therapies at the onset (14.3% vs. 16.4%, p = 0.66 in type A, 2.6% vs. 7.3%, p = 0.29 in type B). Patients in type A who survived more than a day and were treated with anti-thrombotic drugs during hospitalization had significantly lower in-hospital mortality compared with those who received no anti-thrombotic drugs in the acute phase (2.2% vs. 16.1%, p < 0.001), while there was no significant difference between in-hospital mortality in the two type-B groups (2.4% vs. 4.9%, p = 0.48). Although there were variations in response among patients with acute aortic dissection, anti-thrombotic drugs did not worsen in-hospital mortality for patients with acute aortic dissection, indicating that medical staff should not hesitate to administer anti-thrombotic drugs if indicated. Full article

(This article belongs to the Special Issue Thoracic Aortic Disease: From Bench to Bedside)

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Review

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18 pages, 2366 KiB

Open AccessReview

Coarctation of the Aorta: Diagnosis and Management

by Sadaf Raza, Suneil Aggarwal, Petra Jenkins, Ahmed Kharabish, Shehab Anwer, Damien Cullington, Julia Jones, Jaspal Dua, Vasileios Papaioannou, Reza Ashrafi and Sarah Moharem-Elgamal

Diagnostics 2023, 13(13), 2189; https://doi.org/10.3390/diagnostics13132189 - 27 Jun 2023

Cited by 13 | Viewed by 8702

Abstract

Coarctation of the aorta (CoA) accounts for approximately 5–8% of all congenital heart defects. Depending on the severity of the CoA and the presence of associated cardiac lesions, the clinical presentation and age vary. Developments in diagnosis and management have improved outcomes in this patient population. Even after timely repair, it is important to regularly screen for hypertension. Patients with CoA require lifelong follow-up with a congenital heart disease specialist as these patients may develop recoarctation and complications at the repair site and remain at enhanced cardiovascular risk throughout their lifetime. Full article

(This article belongs to the Special Issue Thoracic Aortic Disease: From Bench to Bedside)

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14 pages, 1642 KiB

Open AccessReview

Thoracic Aorta: Anatomy and Pathology

by Cira Rosaria Tiziana di Gioia, Andrea Ascione, Raffaella Carletti and Carla Giordano

Diagnostics 2023, 13(13), 2166; https://doi.org/10.3390/diagnostics13132166 - 25 Jun 2023

Cited by 8 | Viewed by 5386

Abstract

The aorta is the largest elastic artery in the human body and is classically divided into two anatomical segments, the thoracic and the abdominal aorta, separated by the diaphragm. The thoracic aorta includes the aortic root, the ascending aorta, the arch, and the descending aorta. The aorta’s elastic properties depend on its wall structure, composed of three distinct histologic layers: intima, media, and adventitia. The different aortic segments show different embryological and anatomical features, which account for their different physiological properties and impact the occurrence and natural history of congenital and acquired diseases that develop herein. Diseases of the thoracic aorta may present either as a chronic, often asymptomatic disorder or as acute life-threatening conditions, i.e., acute aortic syndromes, and are usually associated with states that increase wall stress and alter the structure of the aortic wall. This review aims to provide an update on the disease of the thoracic aorta, focusing on the morphological substrates and clinicopathological correlations. Information on anatomy and embryology will also be provided. Full article

(This article belongs to the Special Issue Thoracic Aortic Disease: From Bench to Bedside)

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12 pages, 2203 KiB

Open AccessReview

The Role of Genetic Testing in Patients with Heritable Thoracic Aortic Diseases

by Emanuele Monda, Michele Lioncino, Federica Verrillo, Marta Rubino, Martina Caiazza, Alfredo Mauriello, Natale Guarnaccia, Adelaide Fusco, Annapaola Cirillo, Simona Covino, Ippolita Altobelli, Gaetano Diana, Giuseppe Palmiero, Francesca Dongiglio, Francesco Natale, Arturo Cesaro, Eduardo Bossone, Maria Giovanna Russo, Paolo Calabrò and Giuseppe Limongelli

Diagnostics 2023, 13(4), 772; https://doi.org/10.3390/diagnostics13040772 - 17 Feb 2023

Cited by 8 | Viewed by 1891

Abstract

Heritable thoracic aortic disease (HTAD) is a term used to define a large group of disorders characterized by the occurrence of aortic events, mainly represented by aneurysm or dissection. These events generally involve the ascending aorta, although the involvement of other districts of the aorta or peripheral vessels may occur. HTAD can be classified as non-syndromic if the disorder is limited to the aorta, and syndromic when associated with extra-aortic features. About 20–25% of patients with non-syndromic HTAD exhibit a family history of aortic disease. Thus, a careful clinical evaluation of the proband and the first-degree family members is required to differentiate familial and sporadic cases. Genetic testing is essential since it allows confirmation of the etiological diagnosis of HTAD (particularly in patients with a significant family history) and may guide family screening. In addition, genetic diagnosis significantly impacts patients’ management since the different conditions significantly differ with respect to natural history and treatment strategies. The prognosis in all HTADs is determined by the progressive dilation of the aorta, potentially leading to acute aortic events, such as dissection or rupture. Moreover, the prognosis varies according to the underlying genetic mutations. This review aims to describe the clinical characteristics and natural history of the most common HTADs, with particular emphasis on the role of genetic testing in risk stratification and management. Full article

(This article belongs to the Special Issue Thoracic Aortic Disease: From Bench to Bedside)

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16 pages, 2506 KiB

Open AccessReview

The Role of Multimodality Imaging Approach in Acute Aortic Syndromes: Diagnosis, Complications, and Clinical Management

by Francesco Perone, Marco Guglielmo, Michele Coceani, Lucia La Mura, Ilaria Dentamaro, Jolanda Sabatino and Alessia Gimelli

Diagnostics 2023, 13(4), 650; https://doi.org/10.3390/diagnostics13040650 - 9 Feb 2023

Cited by 8 | Viewed by 2915

Abstract

Acute aortic syndromes are life-threatening conditions with high morbidity and mortality. The principal pathological feature is acute wall damage with possible evolution towards aortic rupture. Accurate and timely diagnosis is mandatory to avoid catastrophic consequences. Indeed, misdiagnosis with other conditions mimicking acute aortic syndromes is associated with premature death. In this view, cardiovascular imaging is necessary for the correct diagnosis and management. Echocardiography, computed tomography, magnetic resonance imaging, and aortography allow for diagnosis, guarantee immediate treatment, and detect associated complications. Multimodality imaging is essential in the diagnostic work-up to confirm or rule out acute aortic syndromes. The aim of this review is to highlight the contemporary evidence on the role of single cardiovascular imaging techniques and multimodality imaging in the diagnosis and management of acute aortic syndromes. Full article

(This article belongs to the Special Issue Thoracic Aortic Disease: From Bench to Bedside)

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33 pages, 1634 KiB

Open AccessReview

Tracking an Elusive Killer: State of the Art of Molecular-Genetic Knowledge and Laboratory Role in Diagnosis and Risk Stratification of Thoracic Aortic Aneurysm and Dissection

by Rosina De Cario, Marco Giannini, Giulia Cassioli, Ada Kura, Anna Maria Gori, Rossella Marcucci, Stefano Nistri, Guglielmina Pepe, Betti Giusti and Elena Sticchi

Diagnostics 2022, 12(8), 1785; https://doi.org/10.3390/diagnostics12081785 - 22 Jul 2022

Cited by 11 | Viewed by 3414

Abstract

The main challenge in diagnosing and managing thoracic aortic aneurysm and dissection (TAA/D) is represented by the early detection of a disease that is both deadly and “elusive”, as it generally grows asymptomatically prior to rupture, leading to death in the majority of cases. Gender differences exist in aortic dissection in terms of incidence and treatment options. Efforts have been made to identify biomarkers that may help in early diagnosis and in detecting those patients at a higher risk of developing life-threatening complications. As soon as the hereditability of the TAA/D was demonstrated, several genetic factors were found to be associated with both the syndromic and non-syndromic forms of the disease, and they currently play a role in patient diagnosis/prognosis and management-guidance purposes. Likewise, circulating biomarker could represent a valuable resource in assisting the diagnosis, and several studies have attempted to identify specific molecules that may help with risk stratification outside the emergency department. Even if promising, those data lack specificity/sensitivity, and, in most cases, they need more testing before entering the “clinical arena”. This review summarizes the state of the art of the laboratory in TAA/D diagnostics, with particular reference to the current and future role of molecular-genetic testing. Full article

(This article belongs to the Special Issue Thoracic Aortic Disease: From Bench to Bedside)

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13 pages, 1058 KiB

Open AccessReview

Bicuspid Aortic Valve in Children and Adolescents: A Comprehensive Review

by Gaia Spaziani, Francesca Girolami, Luigi Arcieri, Giovanni Battista Calabri, Giulio Porcedda, Chiara Di Filippo, Francesca Chiara Surace, Marco Pozzi and Silvia Favilli

Diagnostics 2022, 12(7), 1751; https://doi.org/10.3390/diagnostics12071751 - 20 Jul 2022

Cited by 9 | Viewed by 4166

Abstract

Bicuspid aortic valve (BAV) is the most common congenital heart defect. Prevalence of isolated BAV in the general pediatric population is about 0.8%, but it has been reported to be as high as 85% in patients with aortic coarctation. A genetic basis has been recognized, with great heterogeneity. Standard BAV terminology, recently proposed on the basis of morpho-functional assessment by transthoracic echocardiography, may be applied also to the pediatric population. Apart from neonatal stenotic BAV, progression of valve dysfunction and/or of the associated aortic dilation seems to be slow during pediatric age and complications are reported to be much rarer in comparison with adults. When required, because of severe BAV dysfunction, surgery is most often the therapeutic choice; however, the ideal initial approach to treat severe aortic stenosis in children or adolescents is not completely defined yet, and a percutaneous approach may be considered in selected cases as a palliative option in order to postpone surgery. A comprehensive and tailored evaluation is needed to define the right intervals for cardiologic evaluation, indications for sport activity and the right timing for intervention. Full article

(This article belongs to the Special Issue Thoracic Aortic Disease: From Bench to Bedside)

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14 pages, 2059 KiB

Open AccessReview

Thoracic Aortic Dilation: Implications for Physical Activity and Sport Participation

by Emanuele Monda, Federica Verrillo, Marta Rubino, Giuseppe Palmiero, Adelaide Fusco, Annapaola Cirillo, Martina Caiazza, Natale Guarnaccia, Alfredo Mauriello, Michele Lioncino, Alessia Perna, Gaetano Diana, Antonello D’Andrea, Eduardo Bossone, Paolo Calabrò and Giuseppe Limongelli

Diagnostics 2022, 12(6), 1392; https://doi.org/10.3390/diagnostics12061392 - 4 Jun 2022

Cited by 14 | Viewed by 4349

Abstract

Thoracic aortic dilatation is a progressive condition that results from aging and many pathological conditions (i.e., connective tissue, inflammatory, shear stress disorders, severe valvular heart disease) that induce degenerative changes in the elastic properties, leading to the loss of elasticity and compliance of the aortic wall. Mild aortic root enlargement may be also observed in athletes and is considered as a normal adaptation to regular exercise training. On the other hand, high-intensity physical activity in individuals with a particular genetic substrate, such as those carrying gene variants associated with Marfan syndrome or other inherited aortopathies, can favor an excessive aortic enlargement and trigger an acute aortic dissection. The evaluation of the aortic valve and aortic root diameters, as well as the detection of a disease-causing mutation for inherited aortic disease, should be followed by a tailored decision about sport eligibility. In addition, the risk of aortic complications associated with sport in patients with genetic aortic disease is poorly characterized and is often difficult to stratify for each individual athlete. This review aims to describe the relationship between regular physical activity and aortic dilation, focusing on patients with bicuspid aortic valve and inherited aortic disease, and discuss the implications in terms of aortic disease progression and sport participation. Full article

(This article belongs to the Special Issue Thoracic Aortic Disease: From Bench to Bedside)

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14 pages, 1949 KiB

Open AccessReview

Adventitial Fibroblasts in Aortic Aneurysm: Unraveling Pathogenic Contributions to Vascular Disease

by Cameron D. A. Mackay, Anshul S. Jadli, Paul W. M. Fedak and Vaibhav B. Patel

Diagnostics 2022, 12(4), 871; https://doi.org/10.3390/diagnostics12040871 - 31 Mar 2022

Cited by 15 | Viewed by 4249

Abstract

Aortic aneurysm (AA) is a degenerative vascular disease that involves aortic dilatation, and, if untreated, it can lead to rupture. Despite its significant impact on the healthcare system, its multifactorial nature and elusive pathophysiology contribute to limited therapeutic interventions that prevent the progression of AA. Thus, further research into the mechanisms underlying AA is paramount. Adventitial fibroblasts are one of the key constituents of the aortic wall, and they play an essential role in maintaining vessel structure and function. However, adventitial fibroblasts remain understudied when compared with endothelial cells and smooth muscle cells. Adventitial fibroblasts facilitate the production of extracellular matrix (ECM), providing structural integrity. However, during biomechanical stress and/or injury, adventitial fibroblasts can be activated into myofibroblasts, which move to the site of injury and secrete collagen and cytokines, thereby enhancing the inflammatory response. The overactivation or persistence of myofibroblasts has been shown to initiate pathological vascular remodeling. Therefore, understanding the underlying mechanisms involved in the activation of fibroblasts and in regulating myofibroblast activation may provide a potential therapeutic target to prevent or delay the progression of AA. This review discusses mechanistic insights into myofibroblast activation and associated vascular remodeling, thus illustrating the contribution of fibroblasts to the pathogenesis of AA. Full article

(This article belongs to the Special Issue Thoracic Aortic Disease: From Bench to Bedside)

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Other

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8 pages, 649 KiB

Open AccessCase Report

Asymptomatic Aortic Stenosis in an Older Patient: How the Geriatric Approach Can Make a Difference

by Alberto Finazzi, Adriana Antonella Bruni, Stefano Nistri and Giuseppe Bellelli

Diagnostics 2023, 13(5), 909; https://doi.org/10.3390/diagnostics13050909 - 27 Feb 2023

Cited by 2 | Viewed by 1538

Abstract

We present a case report of an older patient with aortic stenosis who was managed before and after transcatheter aortic valve implantation by a team of cardiologists but without the support of a geriatrician. We first describe the patient’s post-interventional complications from a geriatric perspective and afterwards, discuss the unique approach that the geriatrician would have provided. This case report was written by a group of geriatricians working in an acute hospital, along with a clinical cardiologist who is an expert in aortic stenosis. We discuss the implications for modifying conventional practice in tandem with existing literature. Full article

(This article belongs to the Special Issue Thoracic Aortic Disease: From Bench to Bedside)

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4 pages, 2678 KiB

Open AccessInteresting Images

Delayed Aortic Valve Perforation Caused by Blunt Trauma

by Kazuya Tateishi, Chantal Y. Asselin, Elie M. Elmann and Joseph De Gregorio

Diagnostics 2023, 13(3), 549; https://doi.org/10.3390/diagnostics13030549 - 2 Feb 2023

Cited by 2 | Viewed by 2223

Abstract

Traumatic aortic regurgitation (AR) is a rare complication of blunt chest trauma. We described the case of a 35-year-old male who presented to our hospital with shortness of breath 7 years after sustaining blunt chest trauma associated with a motorcycle accident. Transthoracic and transesophageal echocardiogram detected severe AR with two separate jets. The patient was diagnosed with congestive heart failure due to severe AR, and surgical aortic valve replacement was performed. A large perforation of the right coronary cusp likely sustained during the initial blunt chest trauma injury was confirmed surgically. As AR caused by blunt chest trauma can gradually worsen, it is necessary to confirm if there is a history of trauma in patients with severe AR of unknown origin. Full article

(This article belongs to the Special Issue Thoracic Aortic Disease: From Bench to Bedside)

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