Images in Cardiovascular Medicine Quadricuspid Aortic Valve and Anomalous Systemic Venous Connection in a Patient With Cat-Eye Syndrome Jasper Jan Brugts, MD, PhD, MSc; Judith Anne Adriane Ellen Cuypers, MD; Peter Polak, MD, PhD; Mohamed Ouhlous, MD, PhD; Pieter van de Woestijne, MD, PhD; Marja Wessels, MD, PhD; Jolien Roos-Hesselink, MD, PhD
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35-year-old female patient was admitted to the hospital after an accidental car crash. Medical history noted anal surgery for rectovaginal fistula at young age. She complained of dyspnea on exertion for several years. On physical examination, a diastolic murmur at the left second intercostal space was noted. No relevant abnormalities were seen in blood results, ECG, and x-ray. Echocardiography demonstrated a normal left ventricular function with severe aortic regurgitation and mild dilatation of the ascending aorta (39 mm). Transesophageal echocardiography confirmed a quadricuspid aortic valve (Figure 1A–1C). A contrast computed tomography scan revealed a double vena cava inferior system, hemiazygos, persisting vena cava superior, and aneurysmatic coronary sinus with a quadricuspid aortic valve (Figure 2A– 2D). She was referred to the clinical geneticist for syndrome diagnosis. On physical examination, she showed bilateral preauricular pits and an asymmetric face. The combination of external ear abnormalities, anal surgery, and a congenital heart defect suggested the diagnosis of cat-eye syndrome. Single-nucleotide polymorphism array analysis confirmed a nonmosaic 22q11.1q11.21 quadrisomy in leukocytes. The patient underwent aortic valve replacement (Figure 1D) with a St. Jude mechanoprothesis. Cat-eye syndrome is a rare chromosomal disorder named after the typical eye abnormalities, coloboma, which are not always present. Other anomalies include anal atresia with fistula, preauricular tags or pits, renal malformations, and frequent occurrence of congenital heart defects. Associated findings in cat-eye syndrome may vary greatly in range and severity. Cat-eye syndrome is caused by a small supernumerary chromosome derived from the proximal part of chromosome 22, which typically is bicentric and bisatellited and often present in a mosaic state.1,2 Different types of congenital heart defects are reported in patients with cat-eye syndrome, although particularly totally anomalous pulmonary venous return and tetralogy of Fallot are associated. A quadricuspid aortic valve is an extremely rare congenital malformation with an estimated incidence of 0.003% to 0.043% of all congenital heart disease, with only scarce descriptions in literature.3–6 It can appear as an isolated
congenital anomaly but may also be associated with other cardiac malformations. Furthermore, it should be realized that it is part of a continuum of dysmorphic aortic valves.4 For example, the functional bicuspid valve with double raphe also can be a congenital quadricuspid valve of origin.4 In quadricuspid aortic valves, the most common complications include regurgitation and coronary artery anomalies.3–6 The mechanism causing valvular incompetence is incompletely understood. The functional aspect of the quadricuspid valve is represented mainly by pure insufficiency.6 The anatomic abnormalities of the cusps could induce unequal shear stress, leading to fibrosis and incomplete coaptation.6 However, insufficiency is also observed in cases of quadricuspid valve with 4 equal cusps.6 As in bicuspid valves, regurgitation of an abnormal aortic valve may also occur as a result of a prolapse of the cusps, or it can be associated with aortic root dilatation.6 Aortic root dilatation in patients with quadricuspid aortic valves also is observed.6 In bicuspid aortic valves, the dilatation of the proximal ascending aorta is observed secondary to abnormalities of the aortic media. Whether this is the case in our patient with a quadricuspid valve cannot be confirmed.3–6 The natural history of a quadricuspid aortic valve is progression to valve regurgitation in varying severity, which is rare before adulthood and mainly occurs later in life.3–6 The diagnosis is commonly made between the fifth and sixth decades and is more frequently in male patients.3–6 Diagnosis of quadricuspid aortic valve is usually made noninvasively by transthoracic echocardiography. In our case, the quadricuspid aortic valve showed mild ascending aortic dilation but no coronary anomalies. Because of the symptomatic severe regurgitation, we operated on our patient. Currently, she is doing well with normal function of the mechanoprothesis. In the absence of hemodynamic consequences, the additional anomalous systemic venous connections, which are also rare, were not corrected. The occurrence of a quadricuspid valve in combination with anomalous systemic venous connections is an unusual new observation in a patient with cat-eye syndrome and, to the best of our knowledge, has not been reported before in the literature.
From Department of Cardiology, Thoraxcenter (J.J.B., J.A.A.E.C., J.R.-H.), Department of Radiology (M.O.), Department of Cardiothoracic Surgery (P.v.d.W.), and Department of Clinical Genetics (M.W.), Erasmus MC, Rotterdam, The Netherlands; and Department of Cardiology, St. Anna Ziekenhuis, Geldrop, The Netherlands (P.P.). Correspondence to Jasper Jan Brugts, MD, PhD, MSc, Department of Cardiology, Erasmus MC Thoraxcenter, ‘s Gravendijkwal 230, 3015CE Rotterdam, The Netherlands. E-mail [email protected] (Circulation. 2015;131:1225-1227. DOI: 10.1161/CIRCULATIONAHA.114.013290.) © 2015 American Heart Association, Inc. Circulation is available at http://circ.ahajournals.org
DOI: 10.1161/CIRCULATIONAHA.114.013290
Downloaded from http://circ.ahajournals.org/ at CONS CALIFORNIA DIG LIB on April 9, 2015 1225
1226 Circulation March 31, 2015
Disclosures None.
References 1. Rosias PPR, Sijstermans JMJ, Theunissen PMVM, Pulles CFM, de Die CEM, Engelen JJM, van der Meer SB. Phenotypic variability of the cat eye syndrome: case report and review of literature. Genetic Counseling. 2001;12: 273–282. 2. Raca G, Schimmenti L, Martin CL. Intra-chromosomal duplications of 22q11 are not a common cause of isolated coloboma and coloboma with other limited features of cat eye syndrome. Am J Med Genet Part A. 2008;146A:401–404.
3. Goubeia S, Martins JD, Costa G, Parames F, Freitas I, Rebelo M, Trigo C, Pinto FF. Quadricuspid aortic valve: a 10 year case series and literature review. Rev Port Cardiol. 2011;30:849–854. 4. Brugts JJ, Kurvers M, Kofflard MJ. Bicuspid aortic valve with vertical opening and double raphe. Eur Heart J Cardiovasc Imaging. 2012;13:123. doi: 10.1093/ejechocard/jer229. 5. Godefroid O, Colles P, Vercauteren S, Louagie Y, Marchandise B. Quadricuspid aortic valve: a rare etiology of aortic regurgitation. Eur J Echocardiogr. 2006;7:168–170. doi: 10.1016/j.euje.2005.03.011. 6. Barbosa MM, Motta MS. Quadricuspid aortic valve and aortic regurgitation diagnosed by Doppler echocardiography: report of two cases and review of the literature. J Am Soc Echocardiogr. 1991;4:69–74.
Figure 1. Transesophageal 2-dimensional echocardiographic images and a perioperative image of the quadricuspid aortic valve. A, Transesophageal echocardiographic image of the short-axis aortic valve demonstrating a quadricuspid aortic valve (diastolic still frame with closed aortic valve). B, Transesophageal echocardiographic image of the short-axis aortic valve demonstrating a quadricuspid aortic valve (systolic still frame with open aortic valve). C, Transesophageal echocardiographic image of the short-axis aortic valve with color Doppler flow demonstrating a severe aortic valve insufficiency resulting from central malcoaptation. Transthoracic echocardiography measured a vena contracta of 8 mm and pressure half-time of 378 milliseconds. D, Perioperative photograph of the true quadricuspid aortic valve.
Downloaded from http://circ.ahajournals.org/ at CONS CALIFORNIA DIG LIB on April 9, 2015
Brugts et al Quadricuspid Aortic Valve and Cat-Eye Syndrome 1227
Figure 2. Computed tomography (CT) images of the thorax and abdomen. A, CT thorax coronal plane image demonstrating the persisting left superior vena cava (single white asterisk) and dilated coronary sinus (double white asterisk). B, CT thorax transverse plane image demonstrating the arteria lusoria (white star). C, CT thorax transverse plane image demonstrating the vena azygos at thoracic level (solid white circle). D, CT abdomen transverse plane image demonstrating the double inferior vena cava (white arrows).
Downloaded from http://circ.ahajournals.org/ at CONS CALIFORNIA DIG LIB on April 9, 2015
Quadricuspid Aortic Valve and Anomalous Systemic Venous Connection in a Patient With Cat-Eye Syndrome Jasper Jan Brugts, Judith Anne Adriane Ellen Cuypers, Peter Polak, Mohamed Ouhlous, Pieter van de Woestijne, Marja Wessels and Jolien Roos-Hesselink Circulation. 2015;131:1225-1227 doi: 10.1161/CIRCULATIONAHA.114.013290 Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 2015 American Heart Association, Inc. All rights reserved. Print ISSN: 0009-7322. Online ISSN: 1524-4539
The online version of this article, along with updated information and services, is located on the World Wide Web at: http://circ.ahajournals.org/content/131/13/1225
Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in Circulation can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office. Once the online version of the published article for which permission is being requested is located, click Request Permissions in the middle column of the Web page under Services. Further information about this process is available in the Permissions and Rights Question and Answer document. Reprints: Information about reprints can be found online at: http://www.lww.com/reprints Subscriptions: Information about subscribing to Circulation is online at: http://circ.ahajournals.org//subscriptions/
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A
35-year-old female patient was admitted to the hospital after an accidental car crash. Medical history noted anal surgery for rectovaginal fistula at young age. She complained of dyspnea on exertion for several years. On physical examination, a diastolic murmur at the left second intercostal space was noted. No relevant abnormalities were seen in blood results, ECG, and x-ray. Echocardiography demonstrated a normal left ventricular function with severe aortic regurgitation and mild dilatation of the ascending aorta (39 mm). Transesophageal echocardiography confirmed a quadricuspid aortic valve (Figure 1A–1C). A contrast computed tomography scan revealed a double vena cava inferior system, hemiazygos, persisting vena cava superior, and aneurysmatic coronary sinus with a quadricuspid aortic valve (Figure 2A– 2D). She was referred to the clinical geneticist for syndrome diagnosis. On physical examination, she showed bilateral preauricular pits and an asymmetric face. The combination of external ear abnormalities, anal surgery, and a congenital heart defect suggested the diagnosis of cat-eye syndrome. Single-nucleotide polymorphism array analysis confirmed a nonmosaic 22q11.1q11.21 quadrisomy in leukocytes. The patient underwent aortic valve replacement (Figure 1D) with a St. Jude mechanoprothesis. Cat-eye syndrome is a rare chromosomal disorder named after the typical eye abnormalities, coloboma, which are not always present. Other anomalies include anal atresia with fistula, preauricular tags or pits, renal malformations, and frequent occurrence of congenital heart defects. Associated findings in cat-eye syndrome may vary greatly in range and severity. Cat-eye syndrome is caused by a small supernumerary chromosome derived from the proximal part of chromosome 22, which typically is bicentric and bisatellited and often present in a mosaic state.1,2 Different types of congenital heart defects are reported in patients with cat-eye syndrome, although particularly totally anomalous pulmonary venous return and tetralogy of Fallot are associated. A quadricuspid aortic valve is an extremely rare congenital malformation with an estimated incidence of 0.003% to 0.043% of all congenital heart disease, with only scarce descriptions in literature.3–6 It can appear as an isolated
congenital anomaly but may also be associated with other cardiac malformations. Furthermore, it should be realized that it is part of a continuum of dysmorphic aortic valves.4 For example, the functional bicuspid valve with double raphe also can be a congenital quadricuspid valve of origin.4 In quadricuspid aortic valves, the most common complications include regurgitation and coronary artery anomalies.3–6 The mechanism causing valvular incompetence is incompletely understood. The functional aspect of the quadricuspid valve is represented mainly by pure insufficiency.6 The anatomic abnormalities of the cusps could induce unequal shear stress, leading to fibrosis and incomplete coaptation.6 However, insufficiency is also observed in cases of quadricuspid valve with 4 equal cusps.6 As in bicuspid valves, regurgitation of an abnormal aortic valve may also occur as a result of a prolapse of the cusps, or it can be associated with aortic root dilatation.6 Aortic root dilatation in patients with quadricuspid aortic valves also is observed.6 In bicuspid aortic valves, the dilatation of the proximal ascending aorta is observed secondary to abnormalities of the aortic media. Whether this is the case in our patient with a quadricuspid valve cannot be confirmed.3–6 The natural history of a quadricuspid aortic valve is progression to valve regurgitation in varying severity, which is rare before adulthood and mainly occurs later in life.3–6 The diagnosis is commonly made between the fifth and sixth decades and is more frequently in male patients.3–6 Diagnosis of quadricuspid aortic valve is usually made noninvasively by transthoracic echocardiography. In our case, the quadricuspid aortic valve showed mild ascending aortic dilation but no coronary anomalies. Because of the symptomatic severe regurgitation, we operated on our patient. Currently, she is doing well with normal function of the mechanoprothesis. In the absence of hemodynamic consequences, the additional anomalous systemic venous connections, which are also rare, were not corrected. The occurrence of a quadricuspid valve in combination with anomalous systemic venous connections is an unusual new observation in a patient with cat-eye syndrome and, to the best of our knowledge, has not been reported before in the literature.
From Department of Cardiology, Thoraxcenter (J.J.B., J.A.A.E.C., J.R.-H.), Department of Radiology (M.O.), Department of Cardiothoracic Surgery (P.v.d.W.), and Department of Clinical Genetics (M.W.), Erasmus MC, Rotterdam, The Netherlands; and Department of Cardiology, St. Anna Ziekenhuis, Geldrop, The Netherlands (P.P.). Correspondence to Jasper Jan Brugts, MD, PhD, MSc, Department of Cardiology, Erasmus MC Thoraxcenter, ‘s Gravendijkwal 230, 3015CE Rotterdam, The Netherlands. E-mail [email protected] (Circulation. 2015;131:1225-1227. DOI: 10.1161/CIRCULATIONAHA.114.013290.) © 2015 American Heart Association, Inc. Circulation is available at http://circ.ahajournals.org
DOI: 10.1161/CIRCULATIONAHA.114.013290
Downloaded from http://circ.ahajournals.org/ at CONS CALIFORNIA DIG LIB on April 9, 2015 1225
1226 Circulation March 31, 2015
Disclosures None.
References 1. Rosias PPR, Sijstermans JMJ, Theunissen PMVM, Pulles CFM, de Die CEM, Engelen JJM, van der Meer SB. Phenotypic variability of the cat eye syndrome: case report and review of literature. Genetic Counseling. 2001;12: 273–282. 2. Raca G, Schimmenti L, Martin CL. Intra-chromosomal duplications of 22q11 are not a common cause of isolated coloboma and coloboma with other limited features of cat eye syndrome. Am J Med Genet Part A. 2008;146A:401–404.
3. Goubeia S, Martins JD, Costa G, Parames F, Freitas I, Rebelo M, Trigo C, Pinto FF. Quadricuspid aortic valve: a 10 year case series and literature review. Rev Port Cardiol. 2011;30:849–854. 4. Brugts JJ, Kurvers M, Kofflard MJ. Bicuspid aortic valve with vertical opening and double raphe. Eur Heart J Cardiovasc Imaging. 2012;13:123. doi: 10.1093/ejechocard/jer229. 5. Godefroid O, Colles P, Vercauteren S, Louagie Y, Marchandise B. Quadricuspid aortic valve: a rare etiology of aortic regurgitation. Eur J Echocardiogr. 2006;7:168–170. doi: 10.1016/j.euje.2005.03.011. 6. Barbosa MM, Motta MS. Quadricuspid aortic valve and aortic regurgitation diagnosed by Doppler echocardiography: report of two cases and review of the literature. J Am Soc Echocardiogr. 1991;4:69–74.
Figure 1. Transesophageal 2-dimensional echocardiographic images and a perioperative image of the quadricuspid aortic valve. A, Transesophageal echocardiographic image of the short-axis aortic valve demonstrating a quadricuspid aortic valve (diastolic still frame with closed aortic valve). B, Transesophageal echocardiographic image of the short-axis aortic valve demonstrating a quadricuspid aortic valve (systolic still frame with open aortic valve). C, Transesophageal echocardiographic image of the short-axis aortic valve with color Doppler flow demonstrating a severe aortic valve insufficiency resulting from central malcoaptation. Transthoracic echocardiography measured a vena contracta of 8 mm and pressure half-time of 378 milliseconds. D, Perioperative photograph of the true quadricuspid aortic valve.
Downloaded from http://circ.ahajournals.org/ at CONS CALIFORNIA DIG LIB on April 9, 2015
Brugts et al Quadricuspid Aortic Valve and Cat-Eye Syndrome 1227
Figure 2. Computed tomography (CT) images of the thorax and abdomen. A, CT thorax coronal plane image demonstrating the persisting left superior vena cava (single white asterisk) and dilated coronary sinus (double white asterisk). B, CT thorax transverse plane image demonstrating the arteria lusoria (white star). C, CT thorax transverse plane image demonstrating the vena azygos at thoracic level (solid white circle). D, CT abdomen transverse plane image demonstrating the double inferior vena cava (white arrows).
Downloaded from http://circ.ahajournals.org/ at CONS CALIFORNIA DIG LIB on April 9, 2015
Quadricuspid Aortic Valve and Anomalous Systemic Venous Connection in a Patient With Cat-Eye Syndrome Jasper Jan Brugts, Judith Anne Adriane Ellen Cuypers, Peter Polak, Mohamed Ouhlous, Pieter van de Woestijne, Marja Wessels and Jolien Roos-Hesselink Circulation. 2015;131:1225-1227 doi: 10.1161/CIRCULATIONAHA.114.013290 Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 2015 American Heart Association, Inc. All rights reserved. Print ISSN: 0009-7322. Online ISSN: 1524-4539
The online version of this article, along with updated information and services, is located on the World Wide Web at: http://circ.ahajournals.org/content/131/13/1225
Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in Circulation can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office. Once the online version of the published article for which permission is being requested is located, click Request Permissions in the middle column of the Web page under Services. Further information about this process is available in the Permissions and Rights Question and Answer document. Reprints: Information about reprints can be found online at: http://www.lww.com/reprints Subscriptions: Information about subscribing to Circulation is online at: http://circ.ahajournals.org//subscriptions/
Downloaded from http://circ.ahajournals.org/ at CONS CALIFORNIA DIG LIB on April 9, 2015
