Long-term outcomes in heritable thoracic aortic disease.

Heritable aortic aneurysm is an increasingly recognized cause of morbidity and mortality. Whilst Marfan syndrome (MFS) is well-known, the clinical presentation and prognosis of more newly described genetic syndromes is less familiar to clinicians. There is a particular lack of knowledge regarding clinical outcomes for non-syndromal heritable aortic disease.

Novel insights into bicuspid aortic valve (BAV) aortopathy: Long non-coding RNAs TUG1 and MIAT are differentially expressed in BAV ascending aortas.

Background: Whilst a combination of genetically mediated vulnerability and hemodynamic insult is suspected to contribute to bicuspid aortic valve (BAV) aortopathy, the underlying pathophysiological mechanisms are poorly understood.

Methods: Utilizing RT-qPCR, we compared the expression of 28 potentially relevant long non-coding RNA (lncRNA) in aortic tissue from BAV patients undergoing aortic surgery for aortopathy, to healthy controls. Relative lncRNA expression was measured using ΔΔCT, with fold-change calculated as RQ=2.

Models of cardiovascular surgery biobanking to facilitate translational research and precision medicine.

Biobanking in health care has evolved over the last few decades from simple biological sample repositories to complex and dynamic units with multi-organizational infrastructure networks and has become an essential tool for modern medical research. Cardiovascular tissue biobanking provides a unique opportunity to utilize cardiac and vascular samples for translational research into heart failure and other related pathologies. Current techniques for diagnosis, classification, and treatment monitoring of cardiac disease relies primarily on interpretation of clinical signs, imaging, and blood biomarkers.

Oxidative stress in genetically triggered thoracic aortic aneurysm: role in pathogenesis and therapeutic opportunities.

The primary objective of this review was to explore the contribution of oxidative stress to the pathogenesis of genetically-triggered thoracic aortic aneurysm (TAA). Genetically-triggered TAAs manifest substantial variability in onset, progression, and risk of aortic dissection, posing a significant clinical management challenge. There is a need for non-invasive biomarkers that predict the natural course of TAA and therapeutics that prevent aneurysm progression.

The Role of Inflammation and Myeloperoxidase-Related Oxidative Stress in the Pathogenesis of Genetically Triggered Thoracic Aortic Aneurysms.

Genetically triggered thoracic aortic aneurysms (TAAs) are usually considered to exhibit minimal levels of inflammation. However, emerging data demonstrate that specific features of an inflammatory response can be observed in TAA, and that the extent of the inflammatory response can be correlated with the severity, in both mouse models and in human studies. Myeloperoxidase (MPO) is a key mediator of the inflammatory response, via production of specific oxidative species, e.

The RNA-binding fragile-X mental retardation protein and its role beyond the brain.

It is well-established that variations of a CGG repeat expansion in the gene FMR1, which encodes the fragile-X mental retardation protein (FMRP), cause the neurocognitive disorder, fragile-X syndrome (FXS). However, multiple observations suggest a general and complex regulatory role of FMRP in processes outside the brain: (1) FMRP is ubiquitously expressed in the body, suggesting it functions in multiple organ systems; (2) patients with FXS can exhibit a physical phenotype that is consistent with an underlying abnormality in connective tissue; (3) different CGG repeat expansion lengths in FMR1 result in different clinical outcomes due to different pathogenic mechanisms; (4) the function of FMRP as an RNA-binding protein suggests it has a general regulatory role. This review details the complex nature of FMRP and the different CGG repeat expansion lengths and the evidence supporting the essential role of the protein in a variety of biological and pathological processes.

Epigenetic influences on genetically triggered thoracic aortic aneurysm.

Genetically triggered thoracic aortic aneurysms (TAAs) account for 30% of all TAAs and can result in early morbidity and mortality in affected individuals. Epigenetic factors are now recognised to influence the phenotype of many genetically triggered conditions and have become an area of interest because of the potential for therapeutic manipulation. Major epigenetic modulators include DNA methylation, histone modification and non-coding RNA.

Angiotensin, transforming growth factor β and aortic dilatation in Marfan syndrome: Of mice and humans.

Marfan syndrome is consequent upon mutations in , which encodes the extracellular matrix microfibrillar protein fibrillin-1. The phenotype is characterised by development of thoracic aortic aneurysm. Current understanding of the pathogenesis of aneurysms in Marfan syndrome focuses upon abnormal vascular smooth muscle cell signalling through the transforming growth factor beta (TGFβ) pathway.

Multi-Velocity Encoding Four-Dimensional Flow Magnetic Resonance Imaging in the Assessment of Chronic Aortic Dissection.

Background: Chronic descending thoracic aortic dissection (CDTAD) following surgical repair of ascending aortic dissection requires long-term imaging surveillance. We investigated four-dimensional (4D)-flow magnetic resonance imaging (MRI) with a novel multi-velocity encoding (multi-VENC) technique as an emerging clinical method enabling the dynamic quantification of blood volume and velocity throughout the cardiac cycle.

Methods: Patients with CDTAD (n = 10; mean age, 55.

ARHGAP18 Protects Against Thoracic Aortic Aneurysm Formation by Mitigating the Synthetic and Proinflammatory Smooth Muscle Cell Phenotype.

Rationale: Thoracic aortic aneurysm (TAA) is a potentially lethal condition, which can affect individuals of all ages. TAA may be complicated by the sudden onset of life-threatening dissection or rupture. The underlying mechanisms leading to TAA formation, particularly in the nonsyndromal idiopathic group of patients, are not well understood.

Management of aortic regurgitation and bilateral carotid occlusion in severe Takayasu arteritis.

We present a patient with Takayasu arteritis and severe aortic valve regurgitation and bilateral carotid artery occlusions, who underwent aortic valve replacement and aorto-bicarotid bypass. The management of the cardiovascular manifestations of Takayasu arteritis is reviewed.

Familial non-syndromal thoracic aortic aneurysms and dissections - Incidence and family screening outcomes.

Background: Non-syndromal thoracic aortic aneurysm and dissection (ns-TAAD) is a genetic aortopathy, with uncertain incidence. This study documented the incidence of ns-TAAD and outcomes of family screening over 15years.

Methods: Consecutive series of 2385 patients with aortic disease in prospective registry (2000 to 2014), including 675 undergoing surgery.

Nonsyndromic Thoracic Aortic Aneurysm and Dissection: Outcomes With Marfan Syndrome Versus Bicuspid Aortic Valve Aneurysm.

Background: Genetic aortopathy (GA) underlies thoracic aortic aneurysms (TAA) in younger adults. Comparative survival and predictors of outcomes in nonsyndromic TAA (NS-TAA) are incompletely defined compared to Marfan syndrome (MFS) and bicuspid aortic valve (BAV).

Objectives: The study sought to compare survival and clinical outcomes for individuals with NS-TAA, MFS, and BAV.

MRI in Chronic Aortic Dissection: A Systematic Review and Future Directions.

The acute event of thoracic aortic dissection carries with it high mortality and morbidity. Despite optimal initial surgical or medical management strategies, the risk of further complications in the long-term, including aneurysmal dilatation and false lumen (FL) expansion, are not insignificant. Adequate follow-up of such conditions requires dedicated imaging where relevant prognostic indicators are accurately assessed.

Long Term Outcomes Following Freestyle Stentless Aortic Bioprosthesis Implantation: An Australian Experience.

Background: The Freestyle stentless bioprosthesis (FSB) has been demonstrated to be a durable prosthesis in the aortic position. We present data following Freestyle implantation for up to 10 years post-operatively and compare this with previously published results.

Methods: A retrospective cohort analysis of 237 patients following FSB implantation occurred at five Australian hospitals.

Adjustment and Coping Mechanisms for Individuals with Genetic Aortic Disorders.

Background: Advances in diagnosis and management of Genetic Aortic (GA) Disorders have improved prognosis for affected individuals, yet many do not adhere to key management recommendations, and some may experience clinically significant levels of psychological distress. These issues are often not communicated to treating clinicians. Poor adjustment and coping may adversely impact on prognosis, but little is known about the processes contributing to negative outcomes.

The freestyle aortic bioprosthesis: a systematic review.

Background: The Medtronic Freestyle bioprosthesis (FSB) provides an alternative to other prostheses for both aortic valve and aortic root surgery. This paper is a systematic review of the post-operative outcomes in patients with aortic valve and/or aortic root disease following FSB implantation.

Methods: Electronic databases were searched for primary analysis, prospective randomised studies comparing the FSB with an alternative aortic prosthesis were included.

Replacement of the aortic root with a composite valve-graft conduit: risk factor analysis in 246 consecutive patients.

Background: Composite valve-graft (CVG) replacement of the aortic root is a well-studied and recognised treatment for various aortic root conditions, including valvular disease with associated aortopathy. There have been few previous studies of the procedure in large numbers in an Australian setting.

Method: From January 2006 to June 2013, 246 successive patients underwent CVG root replacements at our institution.

Clinical utility of magnetic resonance imaging in the follow-up of chronic aortic type B dissection.

Several imaging modalities are utilised in the assessment of disease progression in chronic aortic dissection. We present the case of a 66 year-old male who underwent ascending aorta repair for Stanford type A aortic dissection. On follow-up the persisting dissection of the descending thoracic aorta was observed to regress on magnetic resonance imaging (MRI).

Perturbations of mechanotransduction and aneurysm formation in heritable aortopathies.

Thoracic aortic aneurysm and dissection in young and middle aged patients is increasingly recognised as due to genetic aortopathy. Mutations in multiple genes affecting proteins in the extracellular matrix, microfibrillar structure, the endothelium and cell signalling pathways have been associated with thoracic aortic disease. The TGFß signalling pathway appears to play a key role in mediating abnormal aortic growth and aneurysm formation.