Cardiogenetics: genetic testing in the diagnosis and management of patients with aortic disease

Abstract

Thoracic aortic aneurysm and aortic dissection have a potent genetic underpinning with 20% of individuals having an affected relative. Heritable thoracic aortic diseases (HTAD) may be classified as syndromic (including Marfan syndrome, Loeys-Dietz syndrome, vascular Ehlers-Danlos syndrome and others) or non-syndromic (without recognisable phenotypes) and relate to pathogenic variants in multiple genes affecting extracellular matrix proteins, transforming growth factor-beta (TGF-β) signalling and smooth muscle contractile function. Clinical and imaging characteristics may heighten likelihood of an underlying HTAD. HTAD should be investigated in individuals with thoracic aortic aneurysm or aortic dissection, especially when occurring in younger individuals, in those with phenotypic features and in those with a family history of aneurysm disease. Screening family members for aneurysm disease is important. Consultation with a medical geneticist and genetic testing of individuals at increased risk for HTAD is recommended. Medical management and prophylactic aortic surgical thresholds are informed by an accurate clinical and molecular diagnosis.

Using a new selective antegrade cerebral perfusion technique for ascending aorta and aortic arch repair

“…Группа B включает наличие расслоения в нисходящей аорте (дистальнее отхождения левой подключичной артерии), без участия восходящей аорты или дуги аорты. Она включает в себя DeBakey типа III без ретроградного продолжения в восходящий отдел аорты [2,6,7,10].…”

“…Если РА проходит через все три слоя, то формируется полный разрыв стенки, что приводит к массивному кровотечению. Смертность в результате разрыва составляет 80%, а половина пациентов умирают на догоспитальном этапе [3,[6][7][8][9][10].…”

“…В 50% случаев у женщин моложе 40 лет расслоение возникает именно во время беременности. Наиболее высокая частота РА приходится на III триместр беременности [2][3][4][5][6][7]. Аортиты, закрытые травмы грудной клетки, атеросклероз аорты в сочетании с гипертонической болезнью и токсикоз беременных также сопровождаются расслоением и даже разрывом аневризмы аорты в качестве осложнения [2,4,5].…”

Drug Repurposing Patent Applications October–December 2020

“…The inventors compared it (at oral doses of 90 mg/ kg) with Gilead's candidate Ask1 inhibitor selonsertib (now presumably discontinued) in the commonly used rabbit model of NASH; edaravone was superior in reducing NASH scores (the sum of the scores of steatosis, inflammation, and cell ballooning), elevated liver enzymes, and histopathology. 17 However, the spectrum of vascular malformations extends beyond aneurysms. In earlier work the inventors examined four generations of a family suffering from what they named multiorgan venous and lymphatic defect (MOVLD) syndrome.…”

Heartbeat: Recreational substance use and risk of premature atherosclerotic cardiovascular disease

“…Our series of review articles on Cardiogenetics continues in this issue of Heart with a detailed and practical approach to genetic testing in the diagnosis and management of patients with aortic disease by Thakker and Braverman. 8 Now that genetic testing for inherited aortopathies is widely available it is important to recognise, as the authors conclude, that "Genetic testing can establish a specific diagnosis in about 25% of cases of familial Figure 3 Four steps for the improvement of the quality of bystander intervention. if successfully implemented, these steps have the potential to increase survival following sudden cardiac death in people of all socioeconomic positions.…”