TGFBR1 Rare Variant Associated With Thoracic Aortic Aneurysm, Double Chamber Left Ventricle, Coronary Anomaly, and Inducible Ventricular Tachycardia (2020)

HomeCirculation: Cardiovascular ImagingVol. 13, No. 6TGFBR1 Rare Variant Associated With Thoracic Aortic Aneurysm, Double Chamber Left Ventricle, Coronary Anomaly, and Inducible Ventricular Tachycardia Free AccessCase ReportPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissionsDownload Articles + Supplements ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toSupplemental MaterialFree AccessCase ReportPDF/EPUBTGFBR1 Rare Variant Associated With Thoracic Aortic Aneurysm, Double Chamber Left Ventricle, Coronary Anomaly, and Inducible Ventricular Tachycardia Katia Bravo-Jaimes, MD, Naddi B. Marah, MD, Deepa Raghunathan, MD, Steven Napierkowski, MD, Ijeoma A. Ekeruo, MD, Danai Kitkungvan, MD, Dianna M. Milewicz, MD, PhD, Richard W. Smalling, MD, PhD and Siddharth K. Prakash, MD, PhD Katia Bravo-JaimesKatia Bravo-Jaimes Division of Cardiology (K.B.-J., N.B.M., D.R., S.N., I.A.E., D.K., R.W.S., S.K.P.), Department of Internal Medicine, McGovern Medical School, University of Texas Health Science Center at Houston. , Naddi B. MarahNaddi B. Marah Division of Cardiology (K.B.-J., N.B.M., D.R., S.N., I.A.E., D.K., R.W.S., S.K.P.), Department of Internal Medicine, McGovern Medical School, University of Texas Health Science Center at Houston. , Deepa RaghunathanDeepa Raghunathan Division of Cardiology (K.B.-J., N.B.M., D.R., S.N., I.A.E., D.K., R.W.S., S.K.P.), Department of Internal Medicine, McGovern Medical School, University of Texas Health Science Center at Houston. , Steven NapierkowskiSteven Napierkowski Division of Cardiology (K.B.-J., N.B.M., D.R., S.N., I.A.E., D.K., R.W.S., S.K.P.), Department of Internal Medicine, McGovern Medical School, University of Texas Health Science Center at Houston. , Ijeoma A. EkeruoIjeoma A. Ekeruo Division of Cardiology (K.B.-J., N.B.M., D.R., S.N., I.A.E., D.K., R.W.S., S.K.P.), Department of Internal Medicine, McGovern Medical School, University of Texas Health Science Center at Houston. , Danai KitkungvanDanai Kitkungvan Division of Cardiology (K.B.-J., N.B.M., D.R., S.N., I.A.E., D.K., R.W.S., S.K.P.), Department of Internal Medicine, McGovern Medical School, University of Texas Health Science Center at Houston. , Dianna M. MilewiczDianna M. Milewicz Division of Medical Genetics (D.M.M., S.K.P.), Department of Internal Medicine, McGovern Medical School, University of Texas Health Science Center at Houston. , Richard W. SmallingRichard W. Smalling Division of Cardiology (K.B.-J., N.B.M., D.R., S.N., I.A.E., D.K., R.W.S., S.K.P.), Department of Internal Medicine, McGovern Medical School, University of Texas Health Science Center at Houston. and Siddharth K. PrakashSiddharth K. Prakash Siddharth Prakash, MD, PhD, McGovern Medical School at the University of Texas at Houston, 6431 Fannin St, MSB 6.106, Houston, TX 77030. Email E-mail Address: [email protected] Division of Cardiology (K.B.-J., N.B.M., D.R., S.N., I.A.E., D.K., R.W.S., S.K.P.), Department of Internal Medicine, McGovern Medical School, University of Texas Health Science Center at Houston. Division of Medical Genetics (D.M.M., S.K.P.), Department of Internal Medicine, McGovern Medical School, University of Texas Health Science Center at Houston. Originally published2 Jun 2020https://doi.org/10.1161/CIRCIMAGING.119.010084Circulation: Cardiovascular Imaging. 2020;13:e010084A 45-year-old woman with a heterozygous TGFBR1 variant (c.725G>T, p.Trp242Leu), aortic root aneurysm, multiple transient ischemic attacks, and surgical patent foramen ovale closure presented for evaluation of palpitations and decreased exercise tolerance. Physical exam revealed features observed in Marfan syndrome, including a high-arched palate, down-slanting palpebral fissures, joint hypermobility, and positive wrist and thumb signs, but no specific features of Loeys-Dietz syndrome.1 A holosystolic murmur was audible at the cardiac apex.A transthoracic echocardiogram showed normal biventricular size and function, bileaflet mitral valve prolapse with moderate mitral regurgitation, aortic root enlargement with a maximum diameter of 4.3 cm at the sinuses of Valsalva, and a normally structured aortic valve. An outpouching in the inferolateral wall was suspicious for a possible left ventricular (LV) aneurysm (Movie I in the Data Supplement). Head to pelvis magnetic resonance angiography revealed an aberrant right subclavian artery but no other aneurysms or dissections. Cardiac magnetic resonance imaging demonstrated a LV end-diastolic volume index of 95 mL/m2 and LV ejection fraction of 55%. A broad-necked outpouching measuring 6.0 by 1.9 centimeters was visible in the inferolateral LV with a muscular ridge that partially separated the outpouching from the LV cavity (Figure 1, Movies II through IV in the Data Supplement). The myocardium at the basal and distal segments of the outpouching displayed normal characteristics and preserved contractility, but the interposed myocardium was thin and hypokinetic with subendocardial late gadolinium enhancement (Figure 1C). A 24-hour Holter monitor detected multiple premature ventricular contractions with occasional bigeminy and trigeminy in association with presyncopal symptoms.Download figureDownload PowerPointFigure 1. Cardiac magnetic resonance images showing the accessory chamber. A, Long axis view. B, Short axis view. C, Subendocardial delayed enhancement (arrows). A indicates accessory chamber; L, left ventricle; and R, right ventricle.Beta blockers, losartan, and rivaroxaban were prescribed. To evaluate the myocardial late gadolinium enhancement and ventricular arrhythmia, an electrophysiology study, selective coronary angiography and ventriculography were performed. Sustained monomorphic ventricular tachycardia with right bundle branch morphology and superior axis was induced by ventricular extrastimulus testing (Figure 2). Therefore, an implantable cardioverter defibrillator was placed. Selective coronary angiography identified normal origins of the right and left coronary arteries without angiographic evidence of stenosis (Figure 3; Movie V in the Data Supplement). The left coronary artery bifurcated into a type 1 dual left anterior descending system. The circumflex artery (LCX) was absent, but the right coronary artery gave rise to a large posterolateral branch that supplied the inferolateral wall. Ventriculograms with selective injections into both chambers clearly demonstrated a smaller, accessory contractile chamber that communicated with the left ventricular outflow tract and confirmed that overall LV contractility was normal (Figure 4; Movie VI in the Data Supplement).Download figureDownload PowerPointFigure 2. Intracardiac electrogram showing inducible monomorphic ventricular tachycardia.Download figureDownload PowerPointFigure 3. Selective coronary angiography demonstrating dual left anterior descending coronary arteries. A, Shows the 2 left anterior descending (LAD) arteries (yellow and blue arrows) in the right anterior oblique view. B, Shows the 2 LAD arteries (yellow and blue arrows) in the left anterior oblique view. C, Shows the right coronary artery with the posterior lateral branch supplying the lateral aspect.Download figureDownload PowerPointFigure 4. Left ventriculogram with a pigtail catheter in the accessory chamber. A and B, Show still-frame images in diastole and systole, respectively, in the right anterior oblique view. C and D, Show images in diastole and systole, respectively, in the left anterior oblique view. These images show normal contractility of the accessory chamber. A indicates accessory chamber; and LV, left ventricle.Double chamber left ventricle (DCLV) is a rare myocardial developmental defect in which the LV is divided into a primary chamber and an accessory chamber or outpouching by abnormal muscular tissue. The accessory chamber may be located in the inferolateral wall or adjacent to the apex.2 Cardiac magnetic resonance plays a pivotal role to differentiate DCLV from similar malformations, such as congenital ventricular aneurysms or diverticula. Aneurysms characteristically exhibit dyskinesis, and diverticula typically have narrower openings with preserved and synchronous contractility.3Selective coronary angiography is indicated to define coronary anatomy and to exclude ischemia, but cardiac magnetic resonance can provide more robust information about the volume and contractility of the accessory chamber. Anomalous origin of the LCX from the right coronary artery or anomalous arteries to the accessory chamber have been previously described in DCLV. We observed a type 1 dual left anterior descending system that has not been previously reported. Altered perfusion because of the coronary anomaly may have contributed to the development of scar in the inferolateral myocardium.DCLV has been implicated in fatal ventricular arrhythmias, but the prognosis is not well defined.4 Implantable cardioverter defibrillator therapy is not usually indicated for primary prevention in asymptomatic patients. In this case, the presence of symptoms, late gadolinium enhancement, and inducible ventricular tachycardia were sufficient to warrant implantable cardioverter defibrillator implantation.To our knowledge, the coexistence of TGFBR1 variants with DCLV, coronary anomalies, and inducible ventricular tachycardia has not been previously reported. Additional studies will determine if these complications are also found in individuals with Loeys-Dietz syndrome caused by TGFBR1 mutations.Sources of FundingThis study was funded in part by a grant from the NIH (R01HL137028).DisclosuresNone.FootnotesThe Data Supplement is available at https://www.ahajournals.org/doi/suppl/10.1161/CIRCIMAGING.119.010084.Siddharth Prakash, MD, PhD, McGovern Medical School at the University of Texas at Houston, 6431 Fannin St, MSB 6.106, Houston, TX 77030. Email siddharth.k.[email protected]tmc.eduReferences1. Loeys BL, Chen J, Neptune ER, Judge DP, Podowski M, Holm T, Meyers J, Leitch CC, Katsanis N, Sharifi N, et al. A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2.Nat Genet. 2005; 37:275–281. doi: 10.1038/ng1511CrossrefMedlineGoogle Scholar2. Masci PG, Pucci A, Fontanive P, Coceani M, Marraccini P, Lombardi M. Double-chambered left ventricle in an asymptomatic adult patient.Eur Heart J Cardiovasc Imaging. 2012; 13:E1–E3. doi: 10.1093/ejechocard/jer242CrossrefMedlineGoogle Scholar3. Hemmers T, Schwaiger M, Stern H. Double chambered left ventricle in cardiac magnetic resonance imaging.Heart. 2006; 92:1401. doi: 10.1136/hrt.2005.079699CrossrefMedlineGoogle Scholar4. Sharma S, Dinwoodey DI, Chaudhry GM, Labib SB. Congenital double-chambered left ventricle presenting as monomorphic ventricular tachycardia.CASE (Phila). 2019; 3:51–55. doi: 10.1016/j.case.2018.11.008MedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetails June 2020Vol 13, Issue 6 Advertisement Article InformationMetrics © 2020 American Heart Association, Inc.https://doi.org/10.1161/CIRCIMAGING.119.010084PMID: 32482137 Originally publishedJune 2, 2020 Keywordsischemic attack, transientrivaroxabanLoeys-Dietz syndromeanomalous left coronary arterytachycardia, ventricularheart defects, congenitalmitral valve prolapsePDF download Advertisement SubjectsCongenital Heart Disease