Utility of Three-Dimensional Printed Model in Biventricular Repair of Complex Congenital Cardiac Defects: Case Report and Review of Literature

Heterotaxy is a rare syndrome associated with cardiac complexity, anatomic variability and high morbidity and mortality. It is often challenging to visualize and provide an accurate diagnosis of the cardiac anatomy prior to surgery with the use of conventional imaging techniques. We report a unique case demonstrating how the use of three-dimensional (3D) cardiac printed model allowed us to better understand the anatomical complexity and plan a tailored surgical approach for successful biventricular repair in a patient with heterotaxy syndrome.


Introduction
Heterotaxy syndrome is a rare disorder characterized by abnormal lateralization and isomerism of thoraco-abdominal organs across the left-right axis of the body [1][2][3][4]. It is often associated with complex cardiac anatomy, which can include right or left atrial isomerism, ambiguous atrial anatomy, cardiac malposition, common atrioventricular (AV) valve defects, and abnormalities in pulmonary and/or systemic venous connections [5]. The complexity and the severity of the associated defects in heterotaxy syndrome determines the surgical decision for univentricular versus biventricular repair. (Surgical management with univentricular or biventricular repair in patients with heterotaxy syndrome is typically determined by the complexity and severity of the associated cardiac defects) [2]. Given the complex cardiac anatomy associated in heterotaxy syndrome, several tools are used to define the anatomy prior to surgical intervention, including echocardiography, computerized tomography (CT), and Magnetic Resonance Imaging (MRI), but anatomy is often confirmed intraoperatively [2,5]. In order to minimize uncertainty in defining the patient's anatomy, we utilized 3D-printed cardiac model for pre-surgical planning and familiarize ourselves with the procedures to be performed. To our knowledge, this is the first reported case using 3D printed cardiac model to plan a unique biventricular repair using a Warden-like procedure in a patient with heterotaxy syndrome and complex cardiac anatomy.

Case Presentation
The patient is a 5-month-old male who was diagnosed with multiple congenital anomalies including heterotaxy syndrome, polysplenia, intestinal malrotation, absent septum pellucidum, cleft lip and palate, small left kidney with hydronephrosis and right inguinal hernia at birth. His post-natal echocardiogram revealed mesocardia with apex to the left, midline liver, atrial situs ambiguous with a common atrium and ipsilateral pulmonary veins (left pulmonary veins draining into the left-sided atrium and right pulmonary veins draining into the right-sided atrium), D-looped ventricles, normally related great arteries (A,D,S), interrupted inferior vena cava (IVC) with hemiazygos continuation to the left superior vena cava (SVC) draining into the left and anterior aspect of the common atrium, hepatic veins draining to the common atrium, a partial AV canal, small anterior muscular ventricular septal defect (VSD), and a moderate sized patent ductus arteriosus (PDA) [6]. Genetic testing detected an interstitial deletion on chromosome 20. The cardiology and cardiovascular surgical team decided to medically manage him with diuretics with a plan for surgical repair at 4 to 6 months of age.
At three and a half months of age, the patient underwent elective cleft lip and palate repair where he experienced acute hypoxemic respiratory failure and cardiorespiratory arrest, as well as multiple failed attempts at extubation. Cardiac computerized tomography angiography (CTA) confirmed the cardiac anatomy previously seen on post-natal echocardiogram (Figures 1 and 2). It also revealed an anomalous origin of an accessory left pulmonary artery (LPA) arising from the proximal right pulmonary artery (RPA), which resulted in severe compression of the left mainstem bronchus against the descending aorta, forming a partial left pulmonary artery sling [6]. Given his complex medical history and cardiac anatomy, a three-dimensional (3D) cardiac printed model was used to further delineate his cardiac anatomy and determine the safest plan for surgical intervention.
The DICOM (Digital Imaging and Communications in Medicine) files from CTA were imported into the segmentation software. Mimics Medical 23 software was used for 3D segmentation. The resulting 3D segmented virtual model was converted to a STL (Stereolithography or Standard Tessellation Language) file that is compatible with 3D printing. The heart model design was then printed using Stratasys J750 printer to generate the flexible cardiac model. Loose powder present at the end of the building process was vacuumed off to reveal the final product. Figures 3 and 4 show the pre-operative 3D cardiac model of this patient.    Upon examination of the cardiac model, the surgical decision was to perform a complex biventricular surgical repair. At the age of 5 months, the patient underwent partial AV canal repair with closure of mitral valve cleft. A modified Warden procedure was performed. As previously planned on the 3D model, a large systemic venous baffle was created to drain systemic venous circulation into the right atrium. The base of LSVC, left-sided atrial appendage and right-sided atrial appendage were fashioned to form the posterior wall of the baffle. The joint of the LSVC to the left atrium was closed with a pericardial patch. A 30-degree CardioCel patch was used to form the anterior wall of the systemic venous baffle. With that, the LSVC and hemiazygos vein that carries the flow from the IVC was directed into the right atrium. The mitral cleft was closed with an interrupted 6-0 Prolene sutures. To create an atrial septum, a CardioCel bovine pericardial patch was used. The patch was started from the posterior and inferior portion of the left atrium and the suture line was carried out anteriorly. This method allowed us to move toward the space of tissue between the mitral valve and the tricuspid valve. Then, the same patch was turned to the superior portion to create an interatrial septum which was missing in this patient. At the end of the procedure, separation between the right atrium from the left atrium was obtained, incorporating the four pulmonary veins communicating with the mitral valve, and the hepatic veins together with blood coming from the superior vein baffle communicating with the tricuspid valve.
Normal biventricular size and systolic function with no evidence of significant intracardiac shunt was obtained on cardiac MRI performed 5 weeks postoperatively. His postoperative course from the cardiac perspective remained uneventful until discharge [6]. Figures 5 and 6 show the post-operative CT imaging of the patient. Figure 7 compares the preoperative 3D cardiac anatomy and the postoperative 3D cardiac anatomy to demonstrate the baffle connection from left SVC to left-sided atrial appendage and the right-sided atrial appendage.

Discussion
Historically, heterotaxy patients have had poor surgical outcomes associated with high morbidity and mortality due to structural abnormalities of systemic and pulmonary venous connections, increased incidence of single ventricle physiology, pulmonary and aortic outflow obstruction, arrhythmias and infections associated with splenic dysfunction [1,5,[7][8][9][10][11][12][13]. Important principles of cardiac repair in heterotaxy syndrome include division of extracardiac communication, intracardiac separation of venous return between pulmonary and systemic circulation, and the use of baffles and an atrial switch with patches in isomeric cardiac repair [14]. Patients with single ventricle physiology often require multi-step palliation with a Blalock-Taussig shunt and bidirectional Glenn/Kawashima procedure to direct systemic flow to the pulmonary circulation prior to a Fontan procedure, which is considered the definitive intervention [15]. Biventricular repair is considered in heterotaxy patients with adequate biventricular volume, function, and favorable anatomy between AV valves and ventricles [1,5,14]. The surgical techniques described in the literature include intra-atrial and interventricular redirection, AV valve repair and the use of baffles to direct systemic venous return to the right atrium [4,15].
In recent years, 3D printing has been increasingly used in the surgical field, especially for reconstructive surgeries in craniomaxillofacial [16,17], orthopedics [18], and congenital heart diseases to minimize surgical complications. In congenital heart defect surgery, specifically for biventricular repairs, 3D printed cardiac models, in conjunction with other imaging modalities, have helped in pre-surgical planning by defining the relationship of the ventricles, VSD morphology, and the VSD relation to the outflow tracts. This is crucial in determining the feasibility of a biventricular surgical approach [19][20][21][22][23][24][25][26][27]. 3D printed cardiac models have also played a pivotal role in changing the surgical plan from conservative management to biventricular repair, single ventricle palliation to biventricular repair, or modifying the entire surgical approach for biventricular repair [28].
In addition, 3D printed heart models have helped reduce communication barriers between patients, their families, and physicians. It aids in the education of cardiac anatomy, pathology, surgical procedures, and post-operative progress [22,29]. These heart models also help strengthen relationships among medical providers as they promote constructive discussions between surgeons and cardiologists [19,30]. Therefore, given the complex anatomy and risks involved in this case, the team decided to utilize 3D printing to: (1) familiarize themselves with the anatomy, evaluate techniques and procedures, (2) for-mulate a novel surgical approach, and (3) counsel and educate patients and their families pre-and post-operatively.
From extensive literature review, there are 14 reports of successful biventricular repair using 3D printed cardiac models in complex congenital heart disease (Table 1). Two prior reports in the literature demonstrate the use of 3D printed cardiac models in defining complex cardiac anatomy and pre-surgical planning for biventricular repair in patients with heterotaxy syndrome [27,28]. However, neither of these reports described the novel surgical approach used in this case -the "modified Warden procedure"-which involved creating a baffle with the right-sided and left-sided atrial appendages to direct left sided systemic venous return to the right sided atrium. Heterotaxy syndrome with partial LPA sling, partial AV canal with a common atrium, atrial situs ambiguous, interrupted IVC, VSD, and PDA Agarwal A. discussed the use of 3D cardiac modeling to explore the possibility of biventricular repair in a 4-year-old patient with heterotaxy syndrome as well as its importance in the planning of her complex cardiac surgery [27]. Valverde et al. performed a study to investigate the impact of 3D cardiac models on the surgical planning of patients with complex cardiac anatomy. They reported the positive influence of 3D cardiac model on the management plan of a 34-year-old patient with heterotaxy syndrome [28].
The remaining reports discussed biventricular repair in various other complex cardiac anatomy, and the benefits of 3D cardiac modeling in visualizing complex cardiac anatomy which helped simplify decisions related to surgical options. Riesenkampff et al. produced 11 cardiac models of patients with complex anatomy to investigate the possibility of biventricular repair. There was a unanimous agreement among physicians that these models improved their understanding of the pathology, and helped streamline discussions regarding surgical options for the patients [19]. Valverde et al. described biventricular repair in a 1.5-year-old male with transposition of the great arteries, subaortic VSD, and severe pulmonary stenosis. His 3D cardiac model allowed surgeons to make a decision between the Nikaidoh procedure or the Rastelli repair, and helped them anticipate procedural complications [31]. A case reported by Farooqi et al. involved a seven-year-old male with double outlet right ventricle (DORV) who had previously undergone a bidirectional Glenn procedure. A cardiac model allowed them to visualize the surgical approach and identify a possible baffle position for VSD repair [20]. Garekar et al. printed five cardiac models with different anatomy to study potential surgical options in each case. Three of the five cases underwent successful biventricular repair and surgeons reported a high level of accuracy between the cardiac model and the patients' anatomy as observed in the operating theatre [21]. Kappanayil et al. also discussed five cases of complex cardiac anatomy, four of which were previously refused surgery due to high mortality and unpredictable outcomes. Of the five cases, three underwent biventricular repairs after using their cardiac models for anatomical understanding and pre-surgical planning [22]. Anwar et al. used a cardiac model to study relationships of anatomical structures, identify a potential baffle pathway, and for pre-surgical planning in an 8-month-old male with situs inversus, dextrocardia, DORV, and L-malposed great arteries [23]. Bhatla et al. described two separate cases of biventricular repair after viewing each patient's specific cardiac anatomy on a cardiac model. For both cases, the models helped define the spatial relationship between the anatomical structures. They also assisted surgeons in the evaluation of different surgical options and helped them arrive at the most appropriate surgical approach [24,32]. Hoashi et al. printed 20 cardiac models of patients with congenital heart diseases to assess its utility in preoperative surgical simulation. The team found 3D cardiac models very helpful in educating and preparing young surgeons with no prior experience for biventricular repair or neonatal open-heart surgery [25]. Vettukattil et al. described cardiac models for five cases, three of which underwent biventricular repair. These models made the complex anatomy easier to understand, and demonstrated the anatomy precisely which helped in identifying a surgical plan [26].
As evident from the table and previous reported cases, 3D-printed models have helped in understanding the anatomy, spatial relationships of important and adjoining structures, deciding between surgical options, as well as surgical simulations and for educational purposes.
Despite the benefits of 3D printing, the high costs involved in the initial set-up can prevent widespread use of the technology [22,[33][34][35]. Use of 3D printing is also limited due to the long processing time needed to print a model. This is dependent on the type of printer, availability of materials, and complexity of pathology to be printed [33,34]. In terms of technical limitations, 3D printed cardiac models do not showcase the dynamic changes that occur during a cardiac cycle which is essential for the understanding of pathophysiology in congenital heart diseases [28,36]. There can also be instances where internal structures like atrioventricular valves, semilunar valves or papillary muscles are not appropriately captured due to blood pooling and the limitations of the imaging technology, resulting in models that are difficult to analyze [30,37]. Lastly, materials currently used to produce 3D cardiac models are unable to replicate tissue texture and properties of the layers of the heart, hence limiting the experience of surgical simulation [30,34].
However, its ability to provide tactile experience, valuable information for pre-surgical planning, and improve patient communication proves that it has the potential to be a useful tool in the future of congenital heart surgery [22].

Conclusions
This case highlights the use of a 3D-printed model in helping plan a unique surgical approach to achieve a successful biventricular repair in a patient with heterotaxy syndrome. 3D printing is proving to be an integral tool in understanding the anatomical complexity, planning the surgical approach, and achieving successful outcomes for patients with complex congenital heart defects.