Author + information
- Received October 5, 2015
- Revision received December 30, 2015
- Accepted January 8, 2016
- Published online April 1, 2016.
- Kanwal M. Farooqi, MDa,b,∗ (, )
- Omar Saeed, MDc,
- Ali Zaidi, MDc,
- Javier Sanz, MDd,
- James C. Nielsen, MDb,e,
- Daphne T. Hsu, MDf and
- Ulrich P. Jorde, MDc
- aDivision of Pediatric Cardiology, University Hospital, Rutgers–New Jersey Medical School, Newark, New Jersey
- bDivision of Pediatric Cardiology, Mount Sinai Medical Center, Icahn School of Medicine at Mount Sinai, New York, New York
- cDivision of Cardiology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York
- dZena and Michael A. Wiener Cardiovascular Institute and Marie-Josée and Henry R. Kravis Center for Cardiovascular Health, Icahn School of Medicine at Mount Sinai, New York, New York
- eDivision of Pediatric Cardiology, Stonybrook University Medical Center, Stonybrook, New York
- fDivision of Pediatric Cardiology, Children’s Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, New York
- ↵∗Reprint requests and correspondence:
Dr. Kanwal M. Farooqi, Rutgers–New Jersey Medical School, 185 South Orange Avenue, MSB-F512, Newark, New Jersey 07103.
As the population of adults with congenital heart disease continues to grow, so does the number of these patients with heart failure. Ventricular assist devices are underutilized in adults with congenital heart disease due to their complex anatomic arrangements and physiology. Advanced imaging techniques that may increase the utilization of mechanical circulatory support in this population must be explored. Three-dimensional printing offers individualized structural models that would enable pre-surgical planning of cannula and device placement in adults with congenital cardiac disease and heart failure who are candidates for such therapies. We present a review of relevant cardiac anomalies, cases in which such models could be utilized, and some background on the cost and procedure associated with this process.
The size of the adult population with congenital heart disease (CHD) has surpassed that of the pediatric population with CHD (1,2). This improvement in survival reflects the success of innovations in congenital heart surgery. However, approximately one-quarter of these adults with congenital heart disease (ACHD) will progress to heart failure (HF) by 30 years of age (3). HF has been documented in 22% of patients with d-transposition of the great arteries (d-TGA) who have had a Mustard procedure, 32% of patients with l-transposition of the great arteries (l-TGA), and 40% of patients who have had a Fontan procedure (4).
Ventricular assist devices (VAD) have evolved from large pulsatile volume displacement pumps with limited durability (averaging 12 to 18 months) to small continuous flow left ventricular assist devices lasting nearly 10 years in individual cases (5,6). The most recent continuous flow left ventricular assist device models are comparable in size to a golf ball and weigh <300 g; dual implantation procedures have been performed to provide biventricular support (7). However, the utilization of VADs in patients with CHD remains rare due to the highly variable anatomy and complex physiology in this population (8).
Three-dimensional (3D) printing is an emerging technology that enables creation of physical anatomic models from a patient’s imaging datasets. Such a model allows the surgeon direct visualization of a patient’s 3D cardiac anatomy before entering the operating room, thus facilitating planning of device and cannula placement in adults with complex congenital lesions. The goal of the present article is to review the application of 3D printing to facilitate durable mechanical circulatory support (MCS) in some representative congenital defects that we believe are well suited for this technology.
The Failing Systemic Right Ventricle
d-TGA after atrial switch procedure
d-TGA refers to the congenital cardiac malformation in which there is ventriculoarterial discordance (9). In other words, the aorta arises from the right ventricle (RV) and the pulmonary artery from the left ventricle (LV) (Figure 1A). These neonates are cyanotic at birth, and an atrial septostomy is often needed to allow mixing of 2 otherwise separate and parallel circuits (10). It is now standard of care to perform an arterial switch operation within the first few weeks of life to establish normal connections of the ventricles and great arteries (11). This surgery consists of the pulmonary artery and aorta being disconnected, just above the semi-lunar valves, and then reanastomosed with the RV and LV, respectively, allowing the LV to remain as the systemic ventricle. The coronary arteries are also surgically repositioned with the aorta.
Before this approach, an atrial switch procedure, which consisted of surgically rerouting the systemic and pulmonary venous return to the LV and RV, respectively, was used to treat these patients. The venous return was directed to the contralateral atrioventricular valve by creating atrial baffles, with autologous tissue in the Senning procedure or synthetic material in the Mustard procedure (Figure 1B) (12,13). Despite anatomically corrected blood flow, these patients are at high risk for HF due to the RV serving the systemic circulation, with approximately 30% developing clinical HF by 40 years of age. Once symptoms of HF develop, 1-year mortality approaches 50% (4,14,15).
There have been only a few reports addressing the application of MCS in patients with d-TGA and a failing systemic RV after an atrial switch procedure (16–20). Maly et al. (19) reported on a small series of patients who had a HeartMate II VAD (Thoratec Corporation, Pleasanton, California) implanted as a bridge to transplantation. Three patients survived to undergo a heart transplant, whereas 2 died on post-operative days 30 and 502 from pump thrombosis and progressive HF, respectively. The investigators concluded that the use of the VAD as a bridge to transplant is a suitable approach in these patients with severe RV failure. One of the patients in a report by Menachem et al. (17) had undergone a Mustard procedure at 3.5 years of age. After developing severe right ventricular dysfunction with recurrent episodes of ventricular tachycardia, a HeartMate II VAD was placed, and the patient subsequently underwent successful cardiac transplantation. Of note, the pre-peritoneal pocket was created in the right upper abdomen, with the pump outflow graft oriented in the right upper abdomen and coursed through the right chest for anastomosis to the ascending aorta. These reports illustrate the potential utility of durable MCS in patients with d-TGA.
l-transposition of the great arteries
In patients with l-TGA, the RV is leftward and posterior, and there is atrioventricular discordance as well as ventriculoarterial discordance (21). This anatomic arrangement results in deoxygenated blood traveling from the right atrium to the right-sided LV and then to the pulmonary artery. The oxygenated blood from the pulmonary veins arrives in the left atrium and then is routed to a left-sided RV and finally to the aorta (Figure 2). Because the oxygenated and deoxygenated blood flow is directed appropriately, this malformation is referred to as “congenitally corrected.” However, as in d-TGA after atrial switch, the morphological RV is responsible for supporting the systemic circulation. In a series of patients with l-TGA, 25% of those without associated lesions and 67% of patients with associated lesions developed HF by 45 years of age (22,23). Approximately 13% of these adults will go on to require heart transplantation (23). A few reports have described their experience with MCS in these patients (16–18). Two subjects in the aforementioned series by Menachem et al. (17) were patients with l-TGA. One patient with situs inversus underwent placement of a HeartMate II VAD as destination therapy. The cardiac apex was at the right axillary line, requiring rotation of the anterior aspect of the VAD by 180 degrees. This procedure allowed placement of the apical cannula in the systemic RV. The power source was also switched to arise from the left upper abdomen. The patient did well in the early post-operative period but died of subdural and subarachnoid hemorrhage. The other patient developed advanced cardiomyopathy and had refractory ventricular arrhythmia with declining functional status. Due to progressive symptoms and dependence on inotropic support, she was listed for transplantation but was highly allosensitized and so was considered for VAD placement. She underwent placement of a HeartWare VAD (HeartWare Inc., Framingham, Massachusetts) for refractory HF. The procedure was done through a median sternotomy, and once the device was connected to the systemic RV, the HVAD outflow cannula was directed toward the leftward pleural space because of the leftward aorta. This patient did well and was discharged on oral diuretic agents.
Barriers to VAD placement in d-TGA and l-TGA
There are numerous anatomic factors that may play a role in complicating VAD placement in patients with a systemic RV. The right ventricular apex is not as well developed as the left ventricular apex, and thus there may be more difficulty identifying the ideal site of inflow cannula insertion. In patients with severe HF, the right ventricular dilation may cause distortion of the ventricle, further making this delineation challenging. The presence of trabeculations and the moderator band, specific to the RV, introduce possible sources of inflow obstruction, especially if placed as traditionally done at the ventricular “dimple.” Most groups perform an aggressive resection of these structures to avoid this complication and place the cannula more posteriorly (18). Rotation of the VAD by 180 degrees in patients with l-TGA may make posterior placement simpler (17). Extensive scarring of the mediastinum and abnormal hemodynamics offer further challenges to VAD placement (24,25).
Although patients with both d-TGA and l-TGA experience systemic RV failure, the anatomic location of the ventricle is very different. In patients with d-TGA, the RV is anterior and rightward as in a normal heart, whereas in l-TGA, it is leftward and posterior, in the usual left ventricular position. In these patients, placement of a VAD in the right abdomen instead of the left can cause compression of right-sided structures, which must be monitored in the postoperative setting (26). These anatomic considerations again highlight the uniqueness of these patients. During consideration for VAD placement in patients who have had an atrial switch procedure, care must be taken to assess for baffle leaks or obstruction that might result in cyanosis or inadequate flow. Interestingly, an aspect in which placement of a right-sided VAD is somewhat less complicated seems to be the lack of subsequent failure of the opposite ventricle (ie, LV). Remarkably, the LV seems to be less susceptible to the post-VAD changes that often cause right ventricular failure in patients after left ventricular assist device placement in the LV (17).
HF after Fontan palliation
The Fontan palliation is a surgical option offered to patients whose anatomy is not amenable to support a 2-ventricle circulation. In most cases, 1 of the ventricles is severely underdeveloped and unable to support either the pulmonary or systemic circulation. This palliation allows systemic venous return to be diverted directly to the pulmonary arteries, rendering the single ventricle solely responsible for pumping oxygenated blood to the systemic circulation (27). The CHDs that warrant such an intervention are numerous and include hypoplastic left heart syndrome, tricuspid atresia, and double inlet LV. The interventions consist of a 3-stage palliation that is completed at approximately 3 years of age. Once complete, the venous blood flow is provided passively to the pulmonary arteries by direct surgical anastomosis, from the superior and inferior vena cava. The functional ventricle, either a morphological RV or LV (which varies depending on the patient’s diagnosis), supplies the systemic blood flow. Although this innovative surgical approach offers survival to patients whose demise was previously inevitable, the Fontan procedure continues to be considered a palliation rather than a cure and is associated with long-term morbidity (28). Incidence of Fontan failure is approximately 30% at 20-year follow-up, suggesting that earlier options for appropriate treatment of HF need to be identified for these patients (29). Common morbidities in this population include an increased risk of thromboembolism, protein-losing enteropathy, plastic bronchitis, bleeding complications, atrial arrhythmias, and liver cirrhosis (30,31).
In patients with a failing Fontan circulation, poor nutritional status and organ dysfunction make them imperfect candidates for a much-needed cardiac transplantation. A handful of groups have reported on VAD placement, into either the right-sided circulation or the systemic ventricle, to rehabilitate these patients (32–35). A Berlin Heart (Berlin Heart GmbH, Berlin, Germany) was inserted into the right-sided circulation in a case reported by Prêtre et al. (32). Although the patient had good systolic function of the systemic ventricle and atrioventricular valve, he displayed signs of right atrial dilation, arrhythmia, and renal and hepatic failure. To create an inflow and outflow site, the cavopulmonary anastomosis was taken down, and 2 new “chambers” were surgically created. The inflow cannula was connected to the chamber that received systemic venous flow. This was separated from the pulmonary artery to which the outflow cannula was connected. The cannulas were then connected at the skin to a Berlin Heart. This patient recovered remarkably with improvement in organ function and resolution of ascites. He underwent a transplant 13 months later. In patients with poor systemic ventricular function, left VAD placement with the inflow cannula placed in the ventricle and outflow into the ascending aorta has been reported, with good outcomes (34). Clearly, the approach to MCS placement in these patients must be individualized. As the few reported cases illustrate, approach to cannula and device placement is heavily dependent on the source of HF as well as the specific congenital malformation.
Barriers to VAD placement in Fontan circulation
In patients with a univentricular circulation, the clinical status will govern the anatomic placement of the VAD. In patients with good systemic ventricular function, surgical considerations include the method of separation of the systemic venous and pulmonary circulation with takedown of the cavopulmonary anastomosis. Before the patient is taken to the operating room, the presence of Fontan circuit leaks or stenosis must be assessed, as well as any stenosis of the pulmonary arteries.
The variable approaches to device and cannula placement in patients with ACHD and HF highlight the challenge of application of MCS in these patients. 3D printing is a technique that can offer additional anatomic information to aid in pre-surgical planning and in effect decrease some of the potential difficulty associated with offering VAD therapies in this population.
The ABCs of 3D Printing
The technology of 3D printing, also referred to as rapid prototyping, additive manufacturing, or stereolithography, was first patented in 1986 by Charles Hull. The process of creating a 3D physical structure by using a 3D printer involves first creating a virtual 3D object from a 3D image dataset, using a method called segmentation. This 3D file can then be translated into a physical 3D object by using various techniques depending on the type of printer used (Central Illustration). Printers using fusion deposition modeling, for example, use a nozzle to extrude thin layers of a liquefied thermoplastic sequentially onto a platform. Stereolithographic printers utilize a laser beam directed at a basin of liquid photopolymer to sequentially solidify layers onto a platform, which is slowly raised.
The capabilities of printers vary widely in terms of the largest size model that may be printed (build volume), layer resolution, material used for printing, and support material solubility. Support material is printed with the model to protect any overhanging parts from collapsing before solidifying. Some printers have the ability to print in different colors within the same model, which can be useful, for example, when printing tumors within the myocardium (36). Specialties ranging from orthopedics to cardiology are applying this technology to create patient-specific models to aid in pre-surgical planning (37–39).
3D printing in HF patients without CHD
In patients with HF without CHD, a 3D printed model can also be useful in planning surgical management. In adults with mitral valvulopathy, a 3D printed model of the valve can be used to assess the specific mechanism of regurgitation (40,41). In patients with aortic stenosis who are candidates for transcatheter aortic valve replacement, the left ventricular outflow tract can be printed for pre-procedural planning (42).
3D printing in HF patients with CHD
Applications in pediatric patients with CHD include visualizing intracardiac spatial anatomy for repair of a double outlet RV, ventricular septal defects, and tetralogy of Fallot with major aortopulmonary collateral arteries (43–45). Interestingly, there is a report of the technology being used in development of an axial flow VAD more than a decade ago (46).
With the number of adults with CHD and HF undoubtedly set to increase over time, strong consideration must be given to methods that will allow us to more readily offer therapies such as MCS. We are hopeful that the approach of creating 3D printed patient-specific cardiac models in these patients will narrow the wide gap between patients with and without CHD being offered these potentially life-extending therapies.
Clinical examples of patients with ACHD-HF and 3D printed cardiac models
A 36-year-old male patient with d-TGA had undergone a Mustard procedure at 5 years of age. A pulmonary venous baffle revision was performed 2 years later to relieve a baffle obstruction. The patient underwent pacemaker placement for sick sinus syndrome at 15 years of age. He had a history of an embolic cerebrovascular accident with residual right-sided weakness. He developed gradual severe RV failure and was classified as New York Heart Association functional class III at the time a cardiac magnetic resonance scan was performed. The magnetic resonance angiography image dataset was used to create the virtual 3D model (Materialise, Leuven, Belgium), which was subsequently printed on a desktop 3D printer (Mojo, Stratasys, Eden Prairie, Minnesota). The pulmonary venous baffle anatomy was isolated and printed, which included the severely dilated systemic RV (Figure 3).
Interestingly, this patient had a HeartWare VAD placed in the systemic RV before the 3D printed model was created, as a bridge to transplant. There was special attention paid to the positioning of the inflow cannula in the systemic RV to avoid flow obstruction from heavy trabeculations or tricuspid valve tissue. Although the 3D model was not available before implantation, it could assist in placement of the inflow cannula to avoid interference from nearby structures and maintain optimal ventricular unloading. Unfortunately, the patient died of sepsis and multiorgan failure 247 days after placement of the VAD.
A 51-year-old patient with l-TGA and mild to moderate systemic atrioventricular valve regurgitation demonstrated clinical signs of HF for about 1 year. He reported dyspnea on exertion, palpitations, fatigue, and lower extremity edema. His comorbidities include hyperlipidemia and type 2 diabetes mellitus. The systemic RV was severely hypertrophied, moderately dilated, and had moderate systolic and diastolic dysfunction. The patient underwent a cardiac computed tomography scan that was used to create the virtual 3D model (Materialise), which was subsequently printed on a desktop 3D printer (Mojo) (Figure 4).
A 37-year-old patient with a diagnosis of tricuspid atresia and d-TGA had undergone Fontan palliation at 7 years of age. Due to atrial arrhythmias, she required a Maze procedure with epicardial pacemaker placement. At 28 years of age, she underwent an extracardiac Fontan revision but continued to have significant ascites and atrial arrhythmias. She underwent a cardiac computed tomography scan that was used to create the virtual 3D model (Materialise), which was subsequently printed on a desktop 3D printer (Mojo) (Figure 5).
Choice of source image dataset
The choice of source image dataset is dependent on multiple factors. A cardiac computed tomography scan is able to provide images with high spatial resolution acquired in a short period of time. However, obtaining images with good blood-to-myocardium contrast requires administration of nephrotoxic iodinated contrast and exposure of the patient to radiation. Magnetic resonance lacks radiation exposure and can offer good blood-to-myocardium distinction with or without contrast. The study is much longer, however, and often requires sedation for younger patients. A good quality model can be created from either type of 3D dataset, and specific attention must be given to the study that the patient would tolerate best and therefore result in the best image dataset.
Cost of creating models
The cost of creating a 3D-printed cardiac model is affected by the post-processing software, personnel needed to perform the segmentation, the 3D printer, and material costs. The printer we used was the Mojo, a desktop printer which costs approximately $5,000. The material cost for this printer is typically about $5 per cubic inch for an acrylonitrile butadiene styrene plastic. The range of cost for 3D printers starts at a few hundred dollars but can easily reach more than $100,000 for larger industrial size printers (47,48).
To reduce material use, 3D cardiac models can be printed on a smaller scale. The models printed for our patients were 33% of the full heart size and used a range of 0.4 to 0.7 in3 of material.
The Future of 3D printing
3D printing has proven to be a promising technology, with exciting potential applications for medicine. It provides the opportunity to hold physical replicas of a patients’ anatomy in our hand before entering the operating room. In patients in need of MCS, it may soon be possible to print a patient-specific life-size cardiac model and subsequently print a functioning VAD personalized to that patient’s anatomy. In the realm of bioprinting, which involves laying down live cells on a scaffold, the possibilities seem to stretch as far as the imagination. Considering that the overall response to this technology from the medical community, especially surgeons, has been positive, the main barriers to more widespread use are largely technical (i.e. access to postprocessing software, knowledge of skillful post-processing, availability of good image datasets, access to a 3D printer). With the enthusiasm for this technology comes the need for standardization of technique, establishment of clinical utility, and increases in accessibility. These are hurdles that are not insignificant and with the steep increase in research being done we will hopefully make further strides in this field in the near future.
Funding for the three-dimensional printer used to create the models was provided by the Congenital Heart Defect Coalition. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- adult with congenital heart disease
- congenital heart disease
- dextro-transposition of the great arteries
- heart failure
- levo-transposition of the great arteries
- left ventricle
- mechanical circulatory support
- right ventricle
- ventricular assist device
- Received October 5, 2015.
- Revision received December 30, 2015.
- Accepted January 8, 2016.
- American College of Cardiology Foundation
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