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Marfan's syndrome presenting as an ascending aortic dissection : A Case Study
Abstract
672 Marfan’s syndrome presenting as an ascending aortic dissection : A Case Study R. Kurup ∗ , D. Ross Westmead Hospital, NSW, Australia A 28-year-old presented to hospital with syncope. He was markedly hypotensive, and cyanotic and an urgent echocardiogram showed a large global pericardial effusion with tamponade and the patient underwent an emergency pericardiocentesis. 600mls of haemorrhagic pericardial fluid was drained with immediate improvement in haemodynamics. A transthoracic echocardiogram post procedure revealed an ascending aortic aneurysm, dissection flap and also severe aortic regurgitation (Picture A). An urgent CT aortogram confirmed the ascending aortic aneurysm with a Stanford Type A dissection flap (Picture B), and the patient was taken for an emergency Bentall’s procedure (Picture C). The patient displayed phenotypic characteristics suspicious for Marfan’s syndrome, so genetic testing was undertaken which came back heterozygous for the c.7870 7874delAACAC variant in exon 63 of the FBN1 gene associated with Marfan’s. Histopathological analysis of the aortic root revealed cystic medical degeneration and blood in the layers of the aortic wall (Picture D). Conclusion: Non-traumatic aortic dissections leading to acute aortic regurgitation in a young individual should prompt investigation for connective tissue diseases.
http://dx.doi.org/10.1016/j.hlc.2015.06.675 673 Navigating uncharted waters: novel echocardiography techniques for non-invasive in-vivo assessment of contractile function in adult zebrafish and its potential applications for research in cardiovascular genetics L. Wang 1,2,∗ , S. Kesteven 1 , M. Imtiaz 1 , I. Martin 1 , M. Feneley 1,2 , D. Fatkin 1,2 1 Victor
Chang Cardiac Research Institute, Darlinghurst, NSW, Australia 2 St Vincent’s Hospital, Darlinghurst, NSW, Australia Introduction: The zebrafish (Danio rerio) heart consists of an atrium and ventricle, and is a useful vertebrate model for investigating genetic determinants of myocardial
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dysfunction as well as cardiac regeneration. Although zebrafish larvae are transparent, allowing real-time video analysis of contractile function, adult zebrafish are nontransparent. Echocardiography is an established means of non-invasive serial monitoring of cardiac function in humans, and translation of this technique in adult zebrafish may allow repeated in-vivo measurements of cardiac function. Zebrafish echocardiography, however, requires overcoming important limitations including: the small size of the adult zebrafish heart (1.0mmx1.5mm), the need for studies to be conducted under water, and standardising anaesthesia to limit effects on cardiac function. Only three published studies exist describing this technique, which are limited by small sample size. Methods: Using a Vevo®2100 ultrasound system (50MHz probe, B-mode frame rate 250-500fps, image resolution 30μm), we applied various techniques of assessing systolic function (e.g. two-dimensional fractional shortening and area change, and strain, left ventricular outflow tract velocity time integral), as well as diastolic measurements (E/A, E/é). Results: We were able to translate techniques used in human echocardiography such as fractional area change, Mmode excursion distances, diastology and novel methods of speckle tracking, and have validated these findings in a population of wild-type zebrafish of various ages. Conclusion: Echocardiography in adult zebrafish is a useful tool for non-invasive assessment of myocardial contractile function. Our dataset of wild-type fish will provide a normal reference range, against which future zebrafish models of myocardial dysfunction can be compared. http://dx.doi.org/10.1016/j.hlc.2015.06.676 674 Potential role of multiple mutations altering thoracic aortic aneurysm formation E. Robertson 1,2,∗ , Y. Lu 1 , M. Kekic 1 , B. Hambly 1 , R. Jeremy 1,2 1 University
of Sydney, NSW, Australia Prince Alfred Hospital, Camperdown, NSW, Australia
2 Royal
There are several genes that are implicated in thoracic aortic aneurysm formation, including FBN1, TGFBR1&2, Col3A1 & 5A2, and MYH11. We hypothesised that due to the population incidence of these mutations, ‘double-hit’ mutations may occur and could possibly result in an altered clinical phenotype when compared with the single gene mutation. Genomic DNA analysis of 16 genes implicated in thoracic aortic aneurysm was performed on ten patients with inherited thoracic aortic aneurysm disease. Of the patients analysed, one patient (P1) was identified as having a mutation in both MYH11 (c.2517G.C (pW839C)) and FBN1 (splice donor site c.4210+1G>A). Another patient (P2) was identified as having both COL5A (c.3794A>G (pD1265G)) and FBN1 (c.5861T>G (p.F1954C)). All mutations were predicted by PolyPhen to be deleterious. Pedigrees for P1 and P2 are shown in figures 1 and 2 respectively. M1 has Marfan Syndrome (MFS) and developed progressive aortic dilatation requiring prophylactic surgery at 37 years of age. P1 also has MFS, however, aortic dilatation occurred at a much younger age, with prophylactic
672 Marfan’s syndrome presenting as an ascending aortic dissection : A Case Study R. Kurup ∗ , D. Ross Westmead Hospital, NSW, Australia A 28-year-old presented to hospital with syncope. He was markedly hypotensive, and cyanotic and an urgent echocardiogram showed a large global pericardial effusion with tamponade and the patient underwent an emergency pericardiocentesis. 600mls of haemorrhagic pericardial fluid was drained with immediate improvement in haemodynamics. A transthoracic echocardiogram post procedure revealed an ascending aortic aneurysm, dissection flap and also severe aortic regurgitation (Picture A). An urgent CT aortogram confirmed the ascending aortic aneurysm with a Stanford Type A dissection flap (Picture B), and the patient was taken for an emergency Bentall’s procedure (Picture C). The patient displayed phenotypic characteristics suspicious for Marfan’s syndrome, so genetic testing was undertaken which came back heterozygous for the c.7870 7874delAACAC variant in exon 63 of the FBN1 gene associated with Marfan’s. Histopathological analysis of the aortic root revealed cystic medical degeneration and blood in the layers of the aortic wall (Picture D). Conclusion: Non-traumatic aortic dissections leading to acute aortic regurgitation in a young individual should prompt investigation for connective tissue diseases.
http://dx.doi.org/10.1016/j.hlc.2015.06.675 673 Navigating uncharted waters: novel echocardiography techniques for non-invasive in-vivo assessment of contractile function in adult zebrafish and its potential applications for research in cardiovascular genetics L. Wang 1,2,∗ , S. Kesteven 1 , M. Imtiaz 1 , I. Martin 1 , M. Feneley 1,2 , D. Fatkin 1,2 1 Victor
Chang Cardiac Research Institute, Darlinghurst, NSW, Australia 2 St Vincent’s Hospital, Darlinghurst, NSW, Australia Introduction: The zebrafish (Danio rerio) heart consists of an atrium and ventricle, and is a useful vertebrate model for investigating genetic determinants of myocardial
S403
.. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. ..
dysfunction as well as cardiac regeneration. Although zebrafish larvae are transparent, allowing real-time video analysis of contractile function, adult zebrafish are nontransparent. Echocardiography is an established means of non-invasive serial monitoring of cardiac function in humans, and translation of this technique in adult zebrafish may allow repeated in-vivo measurements of cardiac function. Zebrafish echocardiography, however, requires overcoming important limitations including: the small size of the adult zebrafish heart (1.0mmx1.5mm), the need for studies to be conducted under water, and standardising anaesthesia to limit effects on cardiac function. Only three published studies exist describing this technique, which are limited by small sample size. Methods: Using a Vevo®2100 ultrasound system (50MHz probe, B-mode frame rate 250-500fps, image resolution 30μm), we applied various techniques of assessing systolic function (e.g. two-dimensional fractional shortening and area change, and strain, left ventricular outflow tract velocity time integral), as well as diastolic measurements (E/A, E/é). Results: We were able to translate techniques used in human echocardiography such as fractional area change, Mmode excursion distances, diastology and novel methods of speckle tracking, and have validated these findings in a population of wild-type zebrafish of various ages. Conclusion: Echocardiography in adult zebrafish is a useful tool for non-invasive assessment of myocardial contractile function. Our dataset of wild-type fish will provide a normal reference range, against which future zebrafish models of myocardial dysfunction can be compared. http://dx.doi.org/10.1016/j.hlc.2015.06.676 674 Potential role of multiple mutations altering thoracic aortic aneurysm formation E. Robertson 1,2,∗ , Y. Lu 1 , M. Kekic 1 , B. Hambly 1 , R. Jeremy 1,2 1 University
of Sydney, NSW, Australia Prince Alfred Hospital, Camperdown, NSW, Australia
2 Royal
There are several genes that are implicated in thoracic aortic aneurysm formation, including FBN1, TGFBR1&2, Col3A1 & 5A2, and MYH11. We hypothesised that due to the population incidence of these mutations, ‘double-hit’ mutations may occur and could possibly result in an altered clinical phenotype when compared with the single gene mutation. Genomic DNA analysis of 16 genes implicated in thoracic aortic aneurysm was performed on ten patients with inherited thoracic aortic aneurysm disease. Of the patients analysed, one patient (P1) was identified as having a mutation in both MYH11 (c.2517G.C (pW839C)) and FBN1 (splice donor site c.4210+1G>A). Another patient (P2) was identified as having both COL5A (c.3794A>G (pD1265G)) and FBN1 (c.5861T>G (p.F1954C)). All mutations were predicted by PolyPhen to be deleterious. Pedigrees for P1 and P2 are shown in figures 1 and 2 respectively. M1 has Marfan Syndrome (MFS) and developed progressive aortic dilatation requiring prophylactic surgery at 37 years of age. P1 also has MFS, however, aortic dilatation occurred at a much younger age, with prophylactic