A 6-month-old infant boy presented with symptomatic heart failure. Dilated cardiomyopathy was found in association with a mutation in TTN. Structural heart disease included novel septation of the left ventricle with a fenestrated membrane resulting from aberrant congenital mitral valve apparatus formation. (Level of Difficulty: Advanced.)

Ballweg, Jean A.

Khandalavala, Karl R.

Radio, Stanley J.

Robinson, Jeffrey A.

English

University of Nebraska Medical Center Research: DigitalCommons@UNMC

University of Nebraska Medical Center DigitalCommons@UNMC Journal Articles: Pediatrics Pediatrics 2021 Intraventricular Septation in the Context of Dilated Cardiomyopathy Associated With TTN Mutation Karl R. Khandalavala University of Nebraska Medical Center Jean A. Ballweg University of Nebraksa Medical Center Stanley J. Radio University of Nebraska Medical Center, sradio@unmc.edu Jeffrey A. Robinson University of Nebraska Medical Center, jeffrey.robinson@unmc.edu Tell us how you used this information in this short survey. Follow this and additional works at: https://digitalcommons.unmc.edu/com_peds_articles  Part of the Pediatrics Commons Recommended Citation Khandalavala, Karl R.; Ballweg, Jean A.; Radio, Stanley J.; and Robinson, Jeffrey A., "Intraventricular Septation in the Context of Dilated Cardiomyopathy Associated With TTN Mutation" (2021). Journal Articles: Pediatrics. 35. https://digitalcommons.unmc.edu/com_peds_articles/35 This Article is brought to you for free and open access by the Pediatrics at DigitalCommons@UNMC. It has been accepted for inclusion in Journal Articles: Pediatrics by an authorized administrator of DigitalCommons@UNMC. For more information, please contact digitalcommons@unmc.edu. IMAGING VIGNETTECLINICAL VIGNETTEIntraventricular Septation in the Contextof Dilated Cardiomyopathy AssociatedWith TTN MutationKarl R. Khandalavala, BS,a Jean A. Ballweg, MD,b,c Stanley J. Radio, MD,d Jeffrey A. Robinson, MDb,cABSTRACTA 6-month-old infant boy presented with symptomatic heart failure. Dilated cardiomyopathy was found inassociation with a mutation in TTN. Structural heart disease included novel septation of the left ventricle with afenestrated membrane resulting from aberrant congenital mitral valve apparatus formation. (Level of Difficulty:Advanced.) (J Am Coll Cardiol Case Rep 2021;3:1674–1676) © 2021 Published by Elsevier on behalf of theAmerican College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license(http://creativecommons.org/licenses/by-nc-nd/4.0/).CASE PRESENTATIONA previously healthy 6-month-old full-term infant boy was brought to an emergency department with a 2-dayhistory of vomiting, pallor, and poor feeding. Upon transfer to a tertiary pediatric referral center, his bloodpressure (BP) was 85/39 mmHg, pulse 145 beats/min, respirations 36/min, weight 6.4 kg (1st percentile), andlength 69 cm (50th percentile). Significant physical examination findings included a gallop rhythm, hepato-megaly, and low-set ears with fatty and thickened helices. A chest x-ray demonstrated massive cardiomegalywith increased pulmonary vascular markings (Supplemental Figure 1). The presenting electrocardiogramdemonstrated normal sinus rhythm, nonspecific interventricular block, right ventricular hypertrophy, and T-wave inversion in the inferior leads (Supplemental Figure 2). An echocardiogram demonstrated dilated car-diomyopathy with severe left ventricular dilation, systolic dysfunction (Supplemental Tables 1 to 3), and theunique finding of a septating band within the left ventricle (LV) (Figures 1A and 1B). This was further charac-terized as a multiply fenestrated membrane. Multiple left ventricular thrombi were noted, both within the trueleft ventricular cavity and within the false chamber. Genetic studies indicated a titin (TTN) mutation–associated dilated cardiomyopathy (1G) (Supplemental Table 4).Despite maximal pharmacologic therapy for systolic failure, left ventricular ejection fraction remaineddepressed, and orthotopic cardiac transplantation was performed. Gross pathologic examination of the nativeexplanted heart revealed severe biventricular dilation and hypertrophy, as well as interstitial fibrosis withmyocytolysis. Within the LV, there was endocardial fibroelastosis with a “sheetlike” partition consisting ofpartially fenestrated fibromyxomatous tissue that was intertwined with and extended from the chordaeISSN 2666-0849 https://doi.org/10.1016/j.jaccas.2021.09.002From the aCollege of Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA; bDivision of Cardiology,Department of Pediatrics, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA; cThe Dr. C. C.and Mabel L. Criss Heart Center, Children’s Hospital and Medical Center, Omaha, Nebraska, USA; and the dDepartment ofPathology, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA.The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information,visit the Author Center.Manuscript received June 1, 2021; revised manuscript received August 17, 2021, accepted September 2, 2021.J A C C : C A S E R E P O R T S VO L . 3 , N O . 1 5 , 2 0 2 1ª 2 0 2 1 P U B L I S H E D B Y E L S E V I E R O N B E H A L F O F T H E AM E R I C A N C O L L E G E O FC A R D I O L O G Y F O UN DA T I O N . T H I S I S A N O P E N A C C E S S A R T I C L E U N D E R T H EC C B Y - N C - N D L I C E N S E ( h t t p : / / c r e a t i v e c o mm o n s . o r g / l i c e n s e s / b y - n c - n d / 4 . 0 / ) .tendineae of the mitral valve to an area of noncompaction-like change of the leftventricular endomyocardium (Figure 1C). Histologic examination confirmed endo-cardial fibroelastosis (EFE) (Figures 1D and 1E). In addition, features of a dilated car-diomyopathy, including subendocardial myocytolysis, interstitial fibrosis, and T cell(CD3þ) lymphocyte infiltration were observed. The septating band itself consisted ofvalve tissue components, including fibromyxomatous stroma and minimal collagenwith decreased amounts of elastin relative to normal chordae tendineae or valveleaflets.DISCUSSIONWithin current published reports, this case is not consistent with typical classifications of intraventricularfindings such as intramyocardial delamination, congenital diverticula, congenital aneurysms, or EFE. FailureFIGURE 1 Novel Intraventricular Septation in Multiple Imaging Modalities(A) 2-dimensional (2D) image by transthoracic echocardiogram in the 4-chamber view, demonstrating severe dilation of the left ventricle withthe mitral valve apparatus and intraventricular septation seen. (B) 2D image by transthoracic echocardiogram in the subcostal coronal view,demonstrating the fenestrated left ventricular septation within the severely dilated left ventricle. (C) Cross-section on gross examination ofthe explanted heart. Corresponding plane of dissection demonstrating left ventricle (LV), right ventricle (RV), and ventricular septum (VS)with endocardial fibroelastosis (EFE) (black arrows) and “apron” (blue star). Apical mural thrombus is also present (yellow arrow). (D)Microscopic section of the ventricular myocardium on Verhoeff-Van Gieson stain at 10 magnification, demonstrating EFE of VS highlightedas black region (yellow arrow). (E) Microscopic cross-section of the delaminated ventricular apron on Movat stain at 20 magnification,demonstrating thin strands of elastin (black) with prominent sea-green to blue myxomatous stroma.AB BR E V I A T I O N SAND ACRONYM SBP = blood pressureEFE = endocardialfibroelastosisLV = left ventricleTTN = titin geneJ A C C : C A S E R E P O R T S , V O L . 3 , N O . 1 5 , 2 0 2 1 Khandalavala et alN O V E M B E R 3 , 2 0 2 1 : 1 6 7 4 – 1 6 7 6 Novel Intraventricular Septation1675of myocardial delamination has been implicated in congenital valvular conditions such as Ebstein’s anomalybut does not result in defects containing multiple myocardial layers (1). Congenital LV diverticula and aneu-rysms involve dilations of the left ventricle wall that contain all three layers of the ventricular wall contractingsynchronously within the heart, which was not observed in this case (2). The pathologic specimen containedfeatures of EFE, which is generally limited to the endocardial layer but was observed here as a separateintracavity sheet or septation (3).The case presentation, echocardiographic imaging, and gross pathologic changes fail to meet the diagnosticcriteria for any known condition. The presence of EFE raises an interesting question about the functionalconsequences of this finding within the dilated cardiomyopathy diagnosis. Early identification of significantanatomic abnormalities, as observed in this case, may have an impact on clinical management. These patientsmay be at greater risk for medical treatment failure and require early cardiac transplantation.FUNDING SUPPORT AND AUTHOR DISCLOSURESThe authors have reported that they have no relationships relevant to the contents of this paper to disclose.ADDRESS FOR CORRESPONDENCE: Dr Jeffrey A. Robinson, Pediatric Cardiology, Dr. C.C. and Mabel L. CrissHeart Center, Children’s Hospital & Medical Center, 8200 Dodge Street, Omaha, Nebraska 68114-4113, USA.E-mail: jrobinson@ChildrensOmaha.org.RE F E RENCE S1. Osiro S, Tiwari KJ, Mathenge N, Rodriguez JR,Tubbs RS, Loukas M. When lithium hurts: a look atEbstein anomaly. Cardiol Rev. 2013;21:257–263.2. Hamaoka K, Onaka M, Tanaka T, Onouchi Z.Congenital ventricular aneurysm and diverticulumin children. Pediatr Cardiol. 1987;8:169–175.3. Weixler V, Hammer PE, Marx GR, Emani SM, DelNido PJ, Friehs I. Flow disturbances and progres-sion of endocardial fibroelastosis: a case report.Cardiovasc Pathol. 2019;42:1–3.KEY WORDS congenital heart disease,dilated cardiomyopathy, endocardialfibroelastosis, intraventricular septation,titin geneAPPENDIX For supplemental figuresand tables, please see the online version of thispaper.Khandalavala et al J A C C : C A S E R E P O R T S , V O L . 3 , N O . 1 5 , 2 0 2 1Novel Intraventricular Septation N O V E M B E R 3 , 2 0 2 1 : 1 6 7 4 – 1 6 7 61676

Intraventricular Septation in the Context of Dilated Cardiomyopathy Associated With TTN Mutation

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Intraventricular Septation in the Context of Dilated Cardiomyopathy Associated With TTN Mutation

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