Pediatric Cardiac Tumors
Pediatric cardiac tumors are extremely rare. Rhabdomyomas are the most common tumors in infancy and fetal life, followed by intra pericardial teratoma. Fibromas present in early childhood and myxomas are primarily seen in the adolescent and adult population. Patients with cardiac tumors can be asymptomatic or may present with arrhythmia, heart failure, or sudden death. Echocardiography is the primary modality for initial evaluation of symptomatic patients. Cardiac magnetic resonance imaging provides further characterization of cardiac masses and tumors for diagnostic purposes. The treatment varies from conservative management to surgical resection. Due to the potential of tumor regression, most patients with rhabdomyoma undergo conservative management. Surgical intervention may be indicated depending if patients are symptomatic or significant obstruction to flow and distortion of valve function is present. Fibromas are more often resected because they do not regress and have a strong association with ventricular arrhythmias. Intrapericardial teratomas are the second most common fetal tumor; the results of post-natal resection are excellent. The presence of hydrops in fetal life predicts a poor outcome. Cardiac myxomas are the most common adult tumors. Although resection can be achieved with low morbidity, the incidence of recurrence is highest among all tumors. The long term survival after tumor resections are excellent. The long-term functional performance may be affected by residual atrioventricular valve insufficiency, ventricular aneurysms, and global myocardial reserve.
The epidemiological data on the prevalence of cardiac tumors is based on post mortem autopsy studies. Nadas and Ellison reported the prevalence of pediatric cardiac tumors (primary and metastatic) to be 0.027% in 11,000 pediatric autopsies. In a review of 22 series based on autopsies, McAllister et al reported a frequency of 0.021% across all age groups. The prevalence rates in autopsy studies are inherently flawed by a high referral bias; and thus, the true population based prevalence of pediatric cardiac tumors remains largely unknown.
Pediatric cardiac tumors are extremely rare, and the vast majority are benign. Over a period of fifteen years, 27,640 pediatric patients were assessed for cardiac disease at The Hospital for Sick Children, Toronto. The incidence of primary cardiac tumors was 0.2%. The incidence was 0.06% in the first five-year cohort and it increased to 0.32% in the final five-year cohort. The higher incidence rate in the latter cohort was attributed to the development and enhancement of non- invasive imaging modalities. In a multicenter study of 14,000 fetal patients, the prevalence of fetal cardiac tumors was 0.14%. The most common indication for a fetal echocardiogram was the presence of a cardiac mass on obstetrical ultrasound. The higher fetal prevalence as compared to the pediatric autopsy studies highlight probable in-utero demise or the natural post-natal regression that occurs with certain primary cardiac tumor subtypes.
Malignant tumors of the heart constitute approximately 10% of all pediatric tumors. Secondary metastasis or contiguous spread to the heart constitutes the most common malignant tumors.
Nomenclature and Classification
As described in Chapter 2 of the Pediatric and Congenital Cardiac Section of this STS E-Book, both The International Paediatric and Congenital Cardiac Code (IPCCC) and the Eleventh Version of the International Classification of Diseases (ICD-11) provide the following definition :
- Congenital cardiac tumor is defined as a congenital malformation consisting of growth of abnormal tissue within the heart.
Tumors can arise from the endocardium, myocardium, blood vessels and pericardium. The most common benign tumors of the heart are rhabdomyoma, fibroma, teratoma and myxoma. The frequency of pediatric cardiac tumors varies across the fetal, neonatal and pediatric age spectrum. The tumors differ in their predilection for the location in the heart; the ventricles are the most common site. Malignant tumors of the heart mostly occur due to metastatic or contiguous spread and are more common than primary malignant tumors. The most common primary malignant tumors of the heart are sarcomas (rhabdomyosarcoma and angiosarcoma).
These are benign tumors that arise from the cardiac myocyte and constitute the most common pediatric cardiac tumors. Rhabdomyomas constitute approximately 40-60% of pediatric cardiac tumors; the frequency is higher in the fetal and early infancy period. Approximately, 50-80% of the children with a diagnosis of rhabdomyoma have a diagnosis of Tuberous Sclerosis. Tuberous Sclerosis is characterized by benign lesions in the brain, kidney, and lungs. It is an autosomal dominant disorder characterized mutations in the TSC-1 and TSC-2 genes. The presence of multiple lesions in the heart is highly suggestive of a diagnosis of Tuberous Sclerosis and may herald the diagnosis before neurologic or cutaneous manifestations appear.
Rhabdomyomas are histologically hamartomas that present as well circumscribed solitary or multiple nodules within the heart. Histologically, these are enlarged myocytes with clear cytoplasm that stain strongly with periodic Acid-Schiff stain indicating the presence of abundant intracellular glycogen. Although, it can occur anywhere within the heart, it has a high predilection for the ventricular cavity and septum.
Maternal hormones may be responsible for their progression during fetal life and most rhabdomyoma will be evident as a rounded, homogenous and hyperechoic mass on fetal echocardiography by the late second or third semester.
Fibroma is composed of fibroblasts or myofibroblasts in a collagen matrix. They are the second most common tumor encountered in surgical series and present in early childhood. They can growth to become quite large in size and replace functioning myocardium. The most common site of occurrence is the ventricular free wall, although they may occur in the ventricular septum. They are associated with Gorlin syndrome which is characterized by skeletal abnormalities and a predisposition to neoplasms.
Fibromas are histologically hamartomas that present as a mural, whitish circumscribed mass. Histologically, they are composed of spindle cells in a loose matrix that are not encapsulated and extend into the surrounding myocardium.
Myxomas are the most common primary cardiac tumor seen in the adult population. They are most commonly seen in the adolescent pediatric population. They are located in the left atrium in 90% of the cases. Although most tumors are sporadic; they can be associated with Carney or familial syndrome.
Histologically, they are composed of mesenchymal elements in a gelatinous stroma. They arise from the endothelium and present as exophytic masses projecting into the left atrial cavity. At their base, they are frequently attached by a stalk to the fossa ovalis. They can have friable papillary fronds on the surface which makes them susceptible to embolization.
Teratomas are germ cell tumors that commonly presently as an intra-pericardial mass. They are the second most common tumor encountered in fetal and infant series of cardiac tumors. The intrapericardial teratoma is usually located on the right side and displaces the heart structures posteriorly and to the left. They are attached by a pedicle to one of the great arteries and can grow quite large in size.
Histologically they are composed of primitive primordial germ cell remnants and contain immature endothelial and mesenchymal elements. They can grow to become quite large in size and are characterized by a multilobular and cystic appearance.
Although, teratoma can originate within the ventricular myocardium, they are extremely rare.
Pathophysiology and Clinical Presentation
The age of the patient and the tumor characteristics (location and size) determines the primary presentation and symptoms. The histology of the lesion does not impact the presenting symptoms significantly in most of the cases.
Patient with cardiac tumors can become symptomatic during fetal life or early infancy. The rhabdomyoma and intra pericardial teratoma primarily present during fetal life and early infancy. Cardiac symptoms from rhabdomyoma arise due to obstruction of ventricular blood flow by the tumor or infiltration of ventricular tissue. During the fetal life, these hemodynamic lesions lead to fetal hydrops and demise. The tumor may distort the atrioventricular valve causing stenosis or regurgitation; it may further obstruct the right or left outflow tract of the heart leading to cyanosis or congestive heart failure. The heart failure could be compounded by the progressive growth of the tumor that may replace functioning ventricular mass. Tumor cells may provide an alternate pathway across the atrioventricular junction leading to pre-excitation and atrial arrhythmias.
Fetal and infant intrapericardial teratoma present as a multi-loculated mass attached to the great vessels that compresses the surrounding heart structures. The majority of these teratomas are located anteriorly and rightwards of the heart. Their location leads to compression on the cardiac chambers and great vessels (Video 1). Pericardial effusion is rarely associated with other cardiac tumors. However, it is generally present with this tumor, secondary to rupture of cystic areas or obstruction of cardiac and pericardial lymphatics. The pericardial fluid can compress the atria and vena cava and lead to cardiac tamponade.
Video 1: Intrapericardial Teratoma - CT angiogram animation from posterior to anterior through the coronal plane demonstrating large heterogeneous mass arising from the right anterosuperior mediastinum containing primarily soft-tissue densities, fatty components and a small area of peripheral calcification consistent with a teratoma. There is compression of the right atrial mass.
Sudden cardiac arrest from ventricular arrhythmia may be the first presenting symptom due to tumor infiltration of the myocardium. The mechanism of ventricular arrhythmias is mostly consistent with a re-entry phenomenon. Fibromas can increase in size significantly and their proximity to the coronary arteries and atrioventricular grove makes surgical excision challenging. In the largest pediatric series of patients undergoing surgery for fibroma, ventricular arrhythmias were present in 90% of patients.
Atrial myxomas are rare in the pediatric population. They are associated with tumor embolization into the systemic and pulmonary circulation. In addition, constitutional symptoms of fatigue, fever and chills may be encountered due to systemic release of inflammatory mediators from the tumor. Large left atrial tumors can prolapse through the mitral valve and lead to mitral stenosis or regurgitation due to valve distortion (Video 2,3).
Video 2: Left Atrial Myxoma - Apical view of the left ventricular inflow demonstrates a heterogenous mass attached to the interatrial septum. The mass protrudes into the left ventricle through the mitral valve during diastole.
Video 3: Left Atrial Myxoma - Color flow Doppler imaging demonstrates mild to moderate valve insufficiency from its posterior aspect, presumably from the presence of the tumor mass preventing adequate coaptation.
The gold standard of diagnosing a particular cardiac tumor is obtaining histological tissue for pathological examination. Obtaining a tissue diagnosis requires an invasive surgical or catheter based approach, with its attendant morbidity. The approach to the diagnosis of a particular tumor type has evolved in the present era; it is based upon indirect clinical and probabilistic findings on imaging studies, which can point to a specific type of tumor. These findings include location, morphology, dimensions, extension, presence of infiltration, and any signs that may allow characterization, such as presence of adipose tissue, necrosis, hemorrhage, vascularization, calcifications, and myxoid tissue. The specific tumor diagnosis can also be made due to the presence of associated syndromes. The syndromes associated with primary cardiac tumors include Tuberous Sclerosis (rhabdomyoma), Gorlin’s syndrome (Fibroma) and Carney syndrome complex (myxoma). Asymptomatic tumors may be diagnosed during systemic evaluation of these syndromes.
The primary imaging modality for diagnosis and serial follow up of patients with primary cardiac tumors are echocardiography and magnetic resonance imaging. The finding of cardiomegaly may be apparent on a chest x-ray. Similarly, the presence of arrhythmias, chamber enlargement or hypertrophy on an electrocardiogram may prompt additional imaging studies. The primary role of computerized axial tomography and cardiac catheterization is to define coronary compression or involvement by the tumor. Due to the concerns of ionizing radiation in the pediatric population, their use has been supplemented by the above-mentioned diagnostic modalities. Magnetic Resonance Imaging (MRI) can be a useful adjunct that contributes information regarding perturbation of valve function, degree of outflow obstruction, and extent of myocardial effacement.
A fetal echocardiogram may be obtained due to family history, dysrhythmia or an abnormality on the obstetric ultrasound such as hydrops or suspected cardiac mass. Although, cardiac tumors may be diagnosed as early as 20 weeks of gestation, the diagnosis requires that they be of sufficient size. If the mass is not apparent at earlier ultrasounds, echocardiograms at late second or early third semesters should detect cardiac rhabdomyoma or teratoma as they increase in size during gestation. The fetal echocardiogram can define hemodynamic disturbances, determine prognosis, guide therapeutic interventions and define the best prenatal and delivery management strategy.
Echocardiography is the first diagnostic modality utilized for detecting cardiac masses due to its wide availability and applicability. Two-dimensional and M-mode echocardiography delineates the location, characteristics, and relationship of the tumor with surrounding cardiac structures (Video 4, 5). It allows the identification of pericardial effusions and helps guide therapeutic interventions. Doppler and color flow echocardiography illustrate the hemodynamic consequences of the tumor due to inflow or outflow obstruction across the atrioventricular or semilunar valves.
Video 4: Left Ventricular Rhabdomyoma - Parasternal long axis view of the left ventricular outflow tract shows a pedunculated mass directly below the aortic valve.
Video 5: Left Ventricular Rhabdomyoma - Parasternal short axis view of the aortic valve shows the cross section area of the mass in relation to the left ventricular outflow tract.
Due to its limited field of view that may further be hampered by poor acoustic windows, echocardiogram has limited ability to elaborate on soft tissue characteristics. Contrast enhancement, three dimensional studies and transesophageal echocardiography may better illustrate the characteristics and relationships of the tumor, but cannot provide definitive histological diagnosis and has been supplemented by magnetic resonance imaging. The main utility of echocardiography is serial imaging of these lesions without the need for radiation or use of iodinated or gadolinium enhanced contrast.
Magnetic Resonance Imaging
Cardiac MR is often the preferred imaging modality for cardiac masses because of its superior soft-tissue characterization and high temporal resolution. Cardiac MRI offers a non- noninvasive alternative for comprehensive cardiac assessment including tissue characteristics, tumors size, extent and physiological impact. The main advantage over EKG gated CT imaging is the absence of ionizing radiation which is particularly desirable in the pediatric population. The main disadvantage is the time required for image acquisition and the potential need for general anesthesia in smaller children. MRI characteristics of the common cardiac tumors (fibromas and rhabdomyomas) are illustrated in Figure 1 and 2.
In a multicenter study utilizing pre-defined diagnostic criteria, MRI was able to predict the primary histologic diagnosis in 97% of the cases. Of the 78 cases, 76 (97%) were correctly diagnosed, with 43 (55%) having a single correct diagnosis, and 33 (42%) having the correct diagnosis as part of a differential diagnosis. However, MRI was unable to exclude malignancy in certain highly vascular tumors and authors cautioned on relying on MRI based criteria alone. The accuracy of achieving a single correct diagnosis improved with obtaining a complete study based upon well-established protocols. The MRI characteristics of cardiac tumors are illustrated in Table 1.
Homogenous, intramyocardial or intracavitary
Left ventricle, predilection for outflow tract
Solitary, multiple in Tuberous Sclerosis
Left ventricle, free wall or septum
Left atrium, attached to atrial septum
Solitary, multiple in Carney Syndrome
Intra pericardial compression of right atrium
MDE; Myocardial Delayed Enhancement, FPP; First Pass Perfusion
Natural History Without Treatment
Cardiac rhabdomyomas cells lose their ability to divide after birth and tend to regress thereafter. In a natural history study of 33 patients with cardiac rhabdomyoma, spontaneous regression occurred in all except two patients that subsequently required intervention for outflow tract obstruction. Although, the incidence of tumors in the right or left ventricular outflow tract was reported to be 28% in a large series; obstructive symptoms were present in only 11%. The long-term outcome of conservatively and surgically managed infants was similar in this series. Although rhabdomyomas regress in the majority of patients, progressive development of neurologic and renal complications impacts long term survival in children with Tuberous Sclerosis.
Fibromas are slow growing tumors and are associated with progressive heart failure and outflow tract obstruction. Fibromas have the highest association with ventricular arrhythmias. Spontaneous regression in fibromas is rare, although they may remain quiescent for years and are incidentally discovered in adulthood.
Teratomas are the second most common neonatal tumor and are associated with a high incidence of fetal hydrops and neonatal pericardial effusion. The intrapericardial teratomas can significantly increase in size and require early fetal or neonatal intervention. There are rare reports of malignant transformation in teratomas.
Cardiac myxomas are associated with obstructive, constitutional and embolic symptoms. Untreated sarcomas have a poor outcome with 10% percent survival at one year.
History of Surgery for This Anatomic Defect
De-Senac’s asserted in 1783 that “the heart is an organ too noble to be attacked by a primary tumor”. However, the assertion was contradicted by earlier and subsequent reports of cardiac tumors. The first description of a tumor mass in the heart was made by Colombo in 1562 in the text ‘De Re Anatomica’ followed by Malpighi, who in 1666 wrote a dissertation entitled “De polypo cordis”.
A more detailed medical report of a primary cardiac tumor was written in 1835 by Albas who described a myocardial fibroma on a postmortem exam.18 In 1936, Barnes used an electrocardiogram and biopsy of a peripheral metastatic lesion to diagnose a primary tumor of the heart in a living patient. Goldberg et al. used angiography to establish the diagnosis of a cardiac tumor in the early 1950s. This patient and another, reported in the same year by Bahnson, underwent attempted resection. Both procedures resulted in postoperative deaths. The first report of successful surgical management was reported by Bahnson and Newman in 1954 utilizing inflow occlusion.
The first successful resection of a primary cardiac tumor utilizing cardiopulmonary bypass was performed by Craaford in 1954. Through a left thoracotomy under fibrillatory arrest, a left atrial myxoma was resected in a 40-year-old woman who was initially referred for atypical mitral stenosis. In the earlier era, the great majority of cardiac tumors were discovered at postmortem examination. The end of the 1960s brought the advent of echocardiography and an exponential rise in the diagnosis of cardiac masses. The understanding of the natural history and improvement in cardiac imaging allowed a tailored approach to the management of cardiac tumors.
Pre-Surgical Decision Making and Indications for Surgery
The guiding surgical principles in tumor resection are; 1) radical resection whenever feasible 2) tumor reduction as a palliative therapy when radical resection is not feasible 3) reconstruction of the affected structures 4) disposition to implant assist devices when necessary to facilitate perioperative recovery. The radical resections should avoid crossing the atrioventricular groove, preserve the papillary muscle architecture and identify and maintain perfusion through the major branch coronary arteries.
The indications for surgery have been inconsistent across studies; the decision has been based upon symptoms, “hemodynamic impairment” or physiological compromise. Symptoms such as heart failure and cyanosis arise due to hemodynamically significant obstructive inflow or outflow tract lesions, replacement of cardiac mass by tumor or onset of medically resistant ventricular arrhythmias. The presence of physiological compromise implies that there is ductal dependent blood flow, hypotension, acidosis or the need for mechanical ventilation. These physiological indicators and symptoms constitute a definite indication for surgical intervention. “Hemodynamic impairment” has been defined by the presence of hemodynamically significant lesion in the right or left outflow tract defined by imaging modalities. The degree of hemodynamic impairment/ outflow tract obstruction that can be safely observed is unclear from studies. The outflow gradients in the majority of the surgically operated cases were in the mild to moderate ranges and would not have met criteria for catheter intervention if this was primarily valvar stenosis.,, In the absence of symptoms, hemodynamically significant lesions in the outflow tract should be closely observed if the natural history is to regress over time. An aggressive strategy may be justified for histological lesions with no potential for regression.
Among patients presenting diagnosed with rhabdomyoma, surgery was required in 3% to 23 % of the total patient cohort., The overwhelming majority of surgeries were performed in the neonatal and early infancy period. In the earlier era, the thresholds for surgical interventions were lower and the presence of symptomatic or asymptomatic hemodynamically significant outflow tract gradient was the primary indication. A hemodynamically significant RVOT or LVOT gradient was identified by a peak gradient ranging from 20 to 50mmHg.,,The subsequent updates from the same institutions have reported a much lower incidence of surgery as the regressive nature of these tumors was recognized. Asymptomatic outflow tract lesions could be safely observed without increase in mortality.
Symptomatic obstructive rhabdomyomas in the left or right ventricular outflow tract lesions can be completely excised or partially if there are concerns of residual cardiac myocardial reserve. The residual tumor generally demonstrates involution over time. The right ventricular outflow obstruction can also be palliated with shunts or ductal stents while allowing the tumor to regress. The most challenging group is neonates with giant infiltrative rhabdomyoma that replace cardiac mass or result in obliteration of ventricular cavity. Case reports have advocated subtotal resection, transplantation or single ventricle palliative strategies.
The most common arrhythmias noted were supraventricular with accessory pathways. The majority of these arrhythmias tend to resolve as the tumor regresses; medical treatment should be considered and surgical or invasive catheter based reserved for highly symptomatic patients.
Fibromas present with progressive growth in early childhood; however, they tend to become quiescent with age. The most common indication for intervention is based upon electrocardiographic evidence of ventricular arrhythmia. In a review of 20 pediatric patients from Boston Children’s Hospital, ventricular arrhythmias were the primary indication in 90% of patients. The ventricular arrhythmias considered an indication for surgery included:
- ventricular fibrillation,
- sustained ventricular tachycardia,
- non-sustained ventricular tachycardia, and
- low grade ventricular arrhythmia such as frequent ectopic ventricular beats.
In an earlier review of this cohort evaluating the predisposition of the lesion to ventricular arrhythmias, half of the patients presented with sudden death or hemodynamically unstable ventricular tachycardia as a presenting symptom. The surgical cohort represented 77% (20/26) of the total number of patients followed for fibromas, indicating a high rate for intervention for this benign lesion.
In a second surgical series of 18 patients (adult and pediatric) from The Mayo Clinic, the most common of indication of surgery was the presence of symptoms. Symptoms were present in 72% of the patients and included dyspnea, syncope, easy fatigability, congestive heart failure and sudden death. Asymptomatic patients were considered for surgery if the tumor was large at initial presentation or showed progressive growth. The rationale to operate on asymptomatic patients was to prevent the risk of sudden death from ventricular arrhythmia and prevent cardiac deformity and preserve atrioventricular valve function from enlarging tumors. Although a bias towards surgery in asymptomatic patients is observed, this is still controversial.
The recent series from experienced centers have shown the feasibility of complete or near complete excision of the tumor, even if they were initially referred for transplantation. However, if the tumor excision would result in significant detriment in cardiac function, partial resection resulted in reliable relief of symptoms and favorable long-term outcome. The residual tumor has not shown to increase over time. Cardiac transplantation has been described for progressive cardiac dysfunction following radical resections; this approach is challenged by excellent long-term results by the subtotal resection approach.
Cardiac myxomas are the most common tumors in the adult population and often present in the older pediatric population. The largest pediatric experience of 18 patients was reported in a Multicenter European Congenital Association Study. All of the myxomas occurred in the left atrium and were associated with symptoms and findings in approximately half of the patients. The major indication for surgery was hemodynamic impairment due to obstruction of the left atrioventricular valve inflow and symptoms of congestive heart failure. Surgery is, however, even recommended for asymptomatic patients due to its propensity for peripheral embolization.
In the largest review of patients with atrial myxomas across all age groups from The Mayo Clinic, the risk of recurrence was 5%. The risk factors for recurrence were younger patients, smaller tumor size and ventricular origin and the recommendation was complete resection preferably with surrounding endocardial resection.
Intra-pericardial tumors are best managed by complete surgical resection. Surgery is indicated in all patients due to high incidence of symptoms and small potential of malignant degeneration. Although, postnatal resection results in excellent outcomes, prenatal diagnosis often culminates in death. Tumor growth in the fetus is rapid and associated with decline in cardiac output, hydrops and death.
Fetal management depends upon the gestational age and presence or absence of hydrops. If no hydropic changes are seen, then the fetus can be can be delivered close to term with post- natal resection. Early hydrops before 28 weeks is associated with a poor outcome and often results in fetal demise. If early hydrops is associated with a small tumor and large pericardial effusion, in utero pericardiocentesis can potentially delay the progression of hydrops. The only successful reported case of surgical resection at 24 weeks had the following recommendations for fetal resection 1) increasing tumor size with declining cardiac output 2) resection prior to the onset of hydrops to avoid operating on a potentially unstable fetus. If there is rapid increase in tumor size or development of late hydrops, the fetus can be delivered with subsequent tumor resection, especially in late third trimester. The EXIT (ex utero intrapartum therapy) procedure may be utilized if there are concerns about circulatory instability during transition from fetal to postnatal life. It enables surgeons to perform the procedure procedures under controlled conditions, while the fetus remains on utero-placental bypass.
Surgical Approaches for This Anatomical Defect
The standard surgical technique for resection of rhabdomyoma involves median sternotomy, aortic bicaval cannulation, cardiopulmonary bypass and aortic cross clamping. Since the approach (transventricular, transatrial or transaortic) is determined by the location of the tumor; appropriate imaging and precise tumor localization is essential. Individual tailored approaches are employed but aimed at curative resection. However, the guiding principle is the immediate relief of the significant hemodynamic lesions with preservation of the remaining heart function structure and function; total resection is a secondary aim. If the anticipated curative resection would involve papillary muscles, affect coronary artery flow, and result in significant myocardial resection, partial resection is performed. The involution of the remaining tumor burden has been observed in most cases.
Most of the lesions presenting for surgery are exophytic and protrude into the outflow tract. The left ventricular outflow tract lesions can be exposed through an aortotomy with traction of the leaflets providing exposure to the tumor. These are commonly attached to the anterosuperior aspect of the interventricular septum just beneath the aortic valve or from attachments to the region of aortic–mitral continuity. The exposure is generally limited due to the small size of the annulus but securing it with a suture and gentle traction provided sufficient exposure to initiate the resection. The tumor can then be removed in its entirety or in several pieces to avoid inadvertent damage to surrounding vital structures. A left ventriculotomy should be avoided and if additional exposure is required, an antegrade approach through the mitral valve should be employed. The approach to right ventricular tumors is facilitated by the availability of right ventricular incision if antegrade or retrograde approaches through the tricuspid or pulmonary valve do not provide adequate exposure.
These procedures are performed through a median sternotomy, aortic and bicaval cannulation and cardiopulmonary bypass with moderate hypothermia. The two largest series differ in their approach towards cardioplegic arrest in the contemporary era. The proponents of cardioplegic arrest advocate optimal conditions for resection, accurate tumor resection, preservation of surrounding structures and cardiac repair. In the contemporary experience from Boston Children’s Hospital, tumor resection was performed with heart beating or under conditions of fibrillatory arrest. The absence of cardioplegic arrest allowed improved identification of the coronary arteries that needed to be preserved.
The epicardial incision is made along the long axis of the tumor and parallel to any significant coronary arteries. The tumor has a typical whitish fibrous texture that renders itself to enucleation. Since it is a benign tumor, there is no need to resect any margin of myocardium. There is frequent entry into the ventricular cavity that can be closed directly in the majority of cases. The tumor bed is obliterated in multiple layers with pledgeted sutures and the epicardial surface is approximated with fine sutures. Care is taken to avoid kinking the coronary vessels along their epicardial course. If the tumor involves the interventricular septum, resection can be achieved and the defect can be closed in layers in the majority of the patients. A prosthetic patch may be utilized for epicardial and septal closures if the defect is large.
Challenging situations arise if the tumor is in close proximity to the atrioventricular groove or the major coronary arteries. In these instances, a near total resection is performed and a small rim of tumor if left behind to avoid impingement of these structures. The second scenario may involve distortion of the papillary muscles with pre-operative mitral valve insufficiency or the muscles are splayed after the resection. In the majority of the patients, standard repair techniques for the mitral valve can be applied and replacement may be unnecessary. The greatest challenge from an anatomic location involves the presence of the tumor in the superior septum and crux of the heart posteriorly (Video 6, 7). The left coronary artery runs in close proximity and sub-total resection might be a better option. Excellent long-term results have been achieved through this conservative approach.
Video 6: Left Ventricular Fibroma - Parasternal short axis view of the aortic valve shows the cross section area of the mass in relation to the left ventricular outflow tract.
Video 7: Left Ventricular Fibroma - Color flow Doppler imaging demonstrates that the outlet portion of the ventricle is spared with moderate mitral regurgitation.
The standard operative approach is through median sternotomy utilizing cardiopulmonary bypass with aortic and bicaval cannulation and cardioplegic arrest after aortic cross clamp. Manipulation of the heart should be avoided before aortic cross clamp to prevent tumor embolization. The left atrial tumors could be approached through a left atrial, right atrial and trans-septal incision or through a bi-atrial incision parallel to the atrioventricular groove. The principles guiding the surgical approach to atrial myxomas proposed by Jones et al. are (1) allow minimal manipulation of the tumor, (2) provide adequate exposure for complete resection of the tumor, (3) allow inspection of all four heart chambers, (4) minimize recurrence, and (5) be safe and efficacious.
The bi-atrial approach is often advocated over the uni-atrial approach due to improved visualization of the tumor base; it simultaneously allows inspection for fragments or concomitant synchronous tumor in all cardiac chambers. The drawback is a higher incidence of post-operative atrial arrhythmias. In the contemporary era with transesophageal echocardiography, either approach yields a satisfactory result with low recurrence rates., The ventricular myxomas are rare, tend to occur towards the apex and have a higher recurrence rate due to the difficult access and inability to obtain adequate margins.
The extent of resection of the tumor base is dictated by location of the tumor. If the tumor is attached to the atrial septum or atrial free wall, the tumor should be excised at least a 5mm endocardial button. Some authors advocate a full thickness resection of the atrial septum with direct suture or patch closure. If the tumor is located adjacent to the mitral or tricuspid valve or atrioventricular groove, endocardial resection may not be feasible and resection of the base of the stalk will have to be performed. Fulguration of the base with cautery, cryoablation and phenol may be used to prevent tumor recurrence.
The intra-pericardial teratoma is best approached through a median sternotomy. After draining the pericardial fluid, a multi-cystic encapsulated mass is encountered with limited attachments to the surrounding structures. The blood supply of the teratoma originates from a vascular pedicle that arises from the aortic root and should be carefully controlled. Cardiopulmonary bypass is rarely required; however, case reports have reported its use secondary to aortic adhesions or loss of control of vascular pedicle from the aorta. The availability of cardiopulmonary bypass on stand-by is a safe option.
Short Term Outcomes and Complications of Surgery
Short Term Outcomes
The largest series of pediatric cardiac tumors in the United States was reported after a review of the Pediatric Cardiac Care Consortium database. In this surgical cohort of 120 patients, the early operative mortality was 7.9%. The European Congenital Heart Surgeons Association Study reviewed 83 patients with benign cardiac tumors that underwent surgery between 1990 and 2005. The reported operative mortality was 2.4%. The most common tumors in these databases were rhabdomyoma. The largest single institutional pediatric series report excellent outcomes of surgery with morality rates ranging from 0 to 5%.,,
The majority of the reported deaths were in neonates and infants with rhabdomyoma and fibroma. The mortality in these patients was attributed to inadequate post-resection myocardial functional reserve and myocardial ischemia from coronary artery injury.
The relative size of the tumor is the most important determinant of perioperative mortality. The higher relative size of the tumor in the younger age group affected mortality more significantly than the patient age or size. The relative size of the tumor was described by the ratio of tumor diameter (DT) and estimated cardiac weight (CW). The higher tumor to cardiac size ratio (DT/CW) leads to poor cardiac output after resection. Initially, this subset of patients may be best managed by subtotal resections, palliative approaches or rarely transplantation. Irrespective of the DT/CW, the presence of fibroma in the ventricular septum has been correlated with a poorer outcome than other locations in the heart. The second most common mode of death is perioperative coronary artery injury or ischemia from tumor compression. Patients with tumors involving the superior interventricular septum and crux of the heart are the most vulnerable due to the close proximity of the left main coronary artery.
The early surgical outcomes of surgery for myxoma and intrapericardial teratoma have been excellent.
Although the complication rate was 29% in the European Congenital Heart Association Study, most complications were benign. The most serious complications were low cardiac output, valvular insufficiency and arrhythmias. The incidence of low cardiac output requiring ECMO was reported to be around 5%. Low cardiac output was seen in infants with relatively sized tumors. Mitral or tricuspid insufficiency occurred due to the location of the tumor near the atrioventricular valve or due to splaying of the papillary muscle after resection of large fibromas or rhabdomyoma. Conventional mitral valve repair techniques make mitral valve replacement rare. The highest incidence of post-operative arrhythmias is seen after resection of atrial myxoma, especially after a biatrial approach.
Long Term Outcomes and Complications of Surgery
Kaplan-Meier analysis estimated a survival of 93% for all benign pediatric tumors at 20 years in the European Congenital Heart Surgeons Study. Malignancy, early post- operative complications, and transplant were identified as negative predictors of long-term outcome. Similar long-term outcomes have been reported by single institutional series that evaluated the entire broad spectrum of pediatric cardiac tumors.
Single institutional studies of surgical therapy for cardiac fibroma report excellent survival with no late death reported., Although the surgical outcomes of pediatric patients with cardiac rhabdomyoma are excellent; the frequent association with Tuberous Sclerosis affects long term outcome. The most common cause of death in this cohort is renal disease, brain tumors, and lymphangiomyomatosis of the lung. Although, the outcomes of rhabdomyoma and fibroma are excellent in the surgically treated patients, there may be significant pre surgical attrition, conferring a higher mortality rate for the overall cohort. This fact is borne out by two meta-analyses of patients with cardiac fibroma and rhabdomyoma., In the largest series of surgically treated myxomas in adults, the survival is similar to age matched general population; the data is limited to case series in the pediatric population.
The recurrence for rhabdomyoma and fibroma after surgical resection is extremely rare. The partial excision of the tumor was followed by complete regression in the majority of the patients with rhabdomyoma. Although the single institution series from the United States reported an aggressive approach with complete or near complete resection; there was no difference in recurrence when compared to contemporary series where partial resection was carried out. The risk of recurrence for myxoma was reported at 5.6% from the Mayo Clinic, the incidence was highest within the first four years. The presence of Carney syndrome, ventricular location, small size and younger age was associated with tumor recurrence.
Although limited information is available on long term functional class; 20% of surviving patients with complete resection of fibroma were in NYHA Class II or above. The potential explanation for this functional impairment is related to atrioventricular valve insufficiency, impaired ejection fraction and ventricular aneurysms. The occurrence of atrioventricular valve insufficiency is reported in up to 20% of the population and is generally the most common indication for repeat surgical intervention., Although, the ejection fraction may be impaired after large tumor resections from loss of cardiac mass or ventricular wall aneurysms; this detriment in quality of life and functional outcome is offset by the avoidance of cardiac transplantation in these selected patients.
The tumor serves as a suitable substrate for surgical intervention to eliminate arrhythmias. Despite the absence of intraoperative mapping in most of the patients; complete control of ventricular arrhythmia was observed in two large series.,, The primary mechanism of ventricular arrhythmia was a re-entry phenomenon. The beneficial effect was also observed in partial resection due to reduced arrhythmogenic substrate.
Future Directions in the Management of This Defect
Everolimus is a mammalian target of rapamycin (mTOR) inhibition that has demonstrated efficacy in treating subependymal giant cell astrocytomas (SEGAs) and other manifestations of tuberous sclerosis complex (TSC). Giant rhabdomyoma in the pre-natal and neonatal period represents a significant management challenge. Although natural regression is observed in the majority, hydrops and acute hemodynamic effects can develop, which necessitate intervention. Recent case reports of low dose Everolimus in hemodynamically significant lesions have reported regression in excess of the expected natural history. Everolimus is a Class C agent during pregnancy due to miscarriage reported in animals. Successful pregnancy with Everolimus based immunosuppression has been reported in selected renal transplant patients. The safety profile of this agent will continue to be examined; however, if could potentially affect fetal and neonatal survival in large tumors by promoting tumor regression in late pregnancy.
Although ventricular fibromas may continue to increase in size in children, they tend to become quiescent beyond that age group. Ventricular arrhythmias may be present in patients with ventricular fibroma. Surgical indications have included:
- high grade (ventricular fibrillation/tachycardia) arrhythmias that present with sudden death or hemodynamic alterations, and
- low grade arrhythmias (non-sustained ventricular tachycardia or frequent premature ventricular contractions) with associated symptoms.
Clinical predictors of the development of ventricular arrhythmia and the degradation of low-grade ventricular arrhythmia into high grade arrhythmia are not defined; this uncertainty has led certain authors to propose surgery in asymptomatic individuals. There is a potential need for clinical, echocardiographic and electrocardiographic scoring systems to improve patient selection.
The outcomes of post-natal resection of teratoma are excellent. The outcome during fetal life depends upon the presence of hydrops. The presence of hydrops in the third trimester can be managed by delivery and surgical excision with acceptable results. With improvement in patient selection and surgical techniques, fetal surgery in the second trimester with total or subtotal resection could potentially improve outcome in specialized centers and thereby favorably impact the future of children with these fetal tumors.
- Nadas AS, Ellison RC. Cardiac tumors in infancy. Am J Cardiol. 1968;21(3):363-6. [PMID:4866645]
- McAllister HA. Primary tumors of the heart and pericardium. Pathol Annu. 1979;14 Pt 2:325-55. [PMID:232754]
- Beghetti M, Gow RM, Haney I, et al. Pediatric primary benign cardiac tumors: a 15-year review. Am Heart J. 1997;134(6):1107-14. [PMID:9424072]
- Holley DG, Martin GR, Brenner JI, et al. Diagnosis and management of fetal cardiac tumors: a multicenter experience and review of published reports. J Am Coll Cardiol. 1995;26(2):516-20. [PMID:7608458]
- Uzun O, Wilson DG, Vujanic GM, et al. Cardiac tumours in children. Orphanet J Rare Dis. 2007;2:11. [PMID:17331235]
- Webb DW, Thomas RD, Osborne JP. Cardiac rhabdomyomas and their association with tuberous sclerosis. Arch Dis Child. 1993;68(3):367-70. [PMID:8466239]
- Uzun O, McGawley G, Wharton GA. Multiple cardiac rhabdomyomas: tuberous sclerosis or not? Heart. 1997;77(4):388. [PMID:9155628]
- Nathan M, Fabozzo A, Geva T et al. Successful surgical management of ventricular fibromas in children. J Thoracic Cardiovas Surg. 2014;148: 2602-2608
- Beroukhim RS, Prakash A, Buechel ER, et al. Characterization of cardiac tumors in children by cardiovascular magnetic resonance imaging: a multicenter experience. J Am Coll Cardiol. 2011;58(10):1044-54. [PMID:21867841]
- Pennell DJ, Sechtem UP, Higgins CB, et al. Clinical indications for cardiovascular magnetic resonance (CMR): Consensus Panel report. Eur Heart J. 2004;25(21):1940-65. [PMID:15522474]
- Hoffmann U, Globits S, Schima W, et al. Usefulness of magnetic resonance imaging of cardiac and paracardiac masses. Am J Cardiol. 2003;92(7):890-5. [PMID:14516903]
- O'Donnell DH, Abbara S, Chaithiraphan V, et al. Cardiac tumors: optimal cardiac MR sequences and spectrum of imaging appearances. AJR Am J Roentgenol. 2009;193(2):377-87. [PMID:19620434]
- Sciacca P, Giacchi V, Mattia C, et al. Rhabdomyomas and tuberous sclerosis complex: our experience in 33 cases. BMC Cardiovasc Disord. 2014;14:66. [PMID:24884933]
- Nield LE, Mendelson M, Ahmad N, et al. Clinical review of obstructive primary cardiac tumors in childhood. Congenit Heart Dis. 2014;9(3):244-51. [PMID:23962026]
- Miyake CY, Del Nido PJ, Alexander ME, et al. Cardiac tumors and associated arrhythmias in pediatric patients, with observations on surgical therapy for ventricular tachycardia. J Am Coll Cardiol. 2011;58(18):1903-9. [PMID:22018302]
- Columbus MR. Venice: N Beui;1559. Anatomica De Re. Book XV;p. 269.
- Forrester JM. Malpighi's De polypo cordis: an annotated translation. Med Hist. 1995;39(4):477-92. [PMID:8558994]
- Barnes AR, Beaver DC, Snell AM. Primary sarcoma of heart: report of a case with electrocardiographic and pathological studies. Am Heart J. 1934;9: 480
- GOLDBERG HP, GLENN F, DOTTER CT, et al. Myxoma of the left atrium; diagnosis made during life with operative and post-mortem findings. Circulation. 1952;6(5):762-7. [PMID:12988355]
- Bahnson HT, Newman EV. Diagnosis and surgical removal of intracavity myxoma of the right atrium. Bull Johns Hopkins Hosp. 1953;93:150
- Chitwood WR. Clarence Crafoord and the first successful resection of a cardiac myxoma. Ann Thorac Surg. 1992;54(5):997-8. [PMID:1417305]
- Delmo Walter EM, Javier MF, Sander F, et al. Primary Cardiac Tumors in Infants and Children: Surgical Strategy and Long-Term Outcome. Ann Thorac Surg. 2016;102(6):2062-2069. [PMID:27344282]
- Padalino MA, Vida VL, Boccuzzo G, et al. Surgery for primary cardiac tumors in children: early and late results in a multicenter European Congenital Heart Surgeons Association study. Circulation. 2012;126(1):22-30. [PMID:22626745]
- Freedom RM, Lee KJ, MacDonald C, et al. Selected aspects of cardiac tumors in infancy and childhood. Pediatr Cardiol. 2000;21(4):299-316. [PMID:10865003]
- Black MD, Kadletz M, Smallhorn JF, et al. Cardiac rhabdomyomas and obstructive left heart disease: histologically but not functionally benign. Ann Thorac Surg. 1998;65(5):1388-90. [PMID:9594871]
- Günther T, Schreiber C, Noebauer C, et al. Treatment strategies for pediatric patients with primary cardiac and pericardial tumors: a 30-year review. Pediatr Cardiol. 2008;29(6):1071-6. [PMID:18600370]
- Padalino MA, Vida VL, Bhattarai A, et al. Giant intramural left ventricular rhabdomyoma in a newborn. Circulation. 2011;124(20):2275-7. [PMID:22083149]
- Demkow M, Sorensen K, Whitehead BF, et al. Heart transplantation in an infant with rhabdomyoma. Pediatr Cardiol. 1995;16(4):204-6. [PMID:7567670]
- Cho JM, Danielson GK, Puga FJ, et al. Surgical resection of ventricular cardiac fibromas: early and late results. Ann Thorac Surg. 2003;76(6):1929-34. [PMID:14667615]
- Valente M, Cocco P, Thiene G, et al. Cardiac fibroma and heart transplantation. J Thorac Cardiovasc Surg. 1993;106(6):1208-12. [PMID:8246562]
- Shah IK, Dearani JA, Daly RC, et al. Cardiac Myxomas: A 50-Year Experience With Resection and Analysis of Risk Factors for Recurrence. Ann Thorac Surg. 2015;100(2):495-500. [PMID:26070596]
- Nassr AA, Shazly SA, Morris SA, et al. Prenatal management of fetal intrapericardial teratoma: a systematic review. Prenat Diagn. 2017;37(9):849-863. [PMID:28695637]
- Fagiana AM, Barnett S, Reddy VS, et al. Management of a fetal intrapericardial teratoma: a case report and review of the literature. Congenit Heart Dis. 2010;5(1):51-5. [PMID:20136858]
- Rychik J, Khalek N, Gaynor JW, et al. Fetal intrapericardial teratoma: natural history and management including successful in utero surgery. Am J Obstet Gynecol. 2016;215(6):780.e1-780.e7. [PMID:27530489]
- Jones DR, Warden HE, Murray GF, et al. Biatrial approach to cardiac myxomas: a 30-year clinical experience. Ann Thorac Surg. 1995;59(4):851-5; discussion 855-6. [PMID:7695408]
- Bielefeld KJ, Moller JH. Cardiac tumors in infants and children: study of 120 operated patients. Pediatr Cardiol. 2013;34(1):125-8. [PMID:22735896]
- Linnemeier L, Benneyworth BD, Turrentine M, et al. Pediatric cardiac tumors: a 45-year, single-institution review. World J Pediatr Congenit Heart Surg. 2015;6(2):215-9. [PMID:25870340]
- Torimitsu S, Nemoto T, Wakayama M, et al. Literature survey on epidemiology and pathology of cardiac fibroma. Eur J Med Res. 2012;17:5. [PMID:22472419]
- Shepherd CW, Gomez MR, Lie JT, et al. Causes of death in patients with tuberous sclerosis. Mayo Clin Proc. 1991;66(8):792-6. [PMID:1861550]
- Verhaaren HA, Vanakker O, De Wolf D, et al. Left ventricular outflow obstruction in rhabdomyoma of infancy: meta-analysis of the literature. J Pediatr. 2003;143(2):258-63. [PMID:12970643]
- Franz DN, Belousova E, Sparagana S, et al. Long-Term Use of Everolimus in Patients with Tuberous Sclerosis Complex: Final Results from the EXIST-1 Study. PLoS One. 2016;11(6):e0158476. [PMID:27351628]
- Breathnach C, Pears J, Franklin O, et al. Rapid regression of left ventricular outflow tract rhabdomyoma after sirolimus therapy. Pediatrics. 2014;134(4):e1199-202. [PMID:25180276]
- Carta P, Zanazzi M, Minetti EE. Unplanned pregnancies in kidney transplanted patients treated with everolimus: three case reports. Transpl Int. 2015;28(3):370-2. [PMID:25363420]
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