Left Ventricular Inflow Tract Obstruction Secondary to a Myxoma in a Dog

Introduction

Tumors involving the heart occur infrequently in dogs, accounting for an incidence of only 0.19%.¹ The most common primary cardiac tumor in dogs is hemangiosarcoma, followed by aortic body tumors.^1–3 The most common metastatic cardiac tumors reported in dogs are hemangiosarcoma, adenocarcinoma, osteosarcoma, mastocytoma, lymphoma, and various other sarcomas.¹ Cardiac tumors may occur at either intracavitary or intramural locations. In dogs, most primary intracavitary and valvular tumors are located in the right side of the heart.^1–3 Primary tumors located in the left-sided chambers and valves are very uncommon.⁴ Myxomas located in the left cardiac chambers are commonly reported in humans; however, to the authors' knowledge, only myxomas involving the right-sided chambers and tricuspid valve have been reported in dogs.^2,5,6–8 The clinical signs caused by cardiac tumors are more closely related to their anatomic location and associated hemodynamic disturbances than their histologic type.^6,9,10 When left ventricular tumors are predominantly intramural in location, they often do not cause symptoms, but they may produce conduction disturbances, arrhythmias, or they may interfere with ventricular function.^4,9,10 When the tumor has a significant valvular component, left ventricular inflow or outflow tracts can be obstructed, resulting in findings consistent with aortic or mitral stenosis.^4,10 This report describes development of a left ventricular inflow tract obstruction secondary to a myxoma in a dog.

Case Report

A 4 yr old, 11 kg, male fox terrier was referred to the Murcia University Veterinary Teaching Hospital with a 1 mo history of cough and exercise intolerance. Furosemide (1 mg/kg per os [PO] q 12 hr) had been administered for 2 days before admittance.

On physical examination, the dog was alert, in good body condition, and had a mild expiratory dyspnea when handled (respiratory rate was 40 breaths/min). The femoral pulses were weak, rapid, markedly irregular, and accompanied by pulse deficits. Thoracic auscultation revealed harsh lung sounds bilaterally, a very rapid and irregular cardiac rhythm, and a grade 4/6 pansystolic murmur, which was loudest over the mitral valve region. The electrocardiogram showed atrial fibrillation with a ventricular rate between 180 and 220 beats/min. Systemic systolic blood pressure (Doppler method) was 130 mm Hg.

Thoracic radiographs revealed a left-sided cardiac enlargement that was predominately left atrial enlargement (vertebral heart size, 15.0; reference range, 9.7 ± 0.5), causing elevation of the caudal portion of the trachea and the carina, mild left mainstem bronchus compression, pulmonary congestion, and mild pulmonary interstitial edema (Figures 1A and B).¹¹ Results of a complete blood count and biochemical parameters were within normal limits.

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Transthoracic two-dimensional (2D) echocardiography (Figures 2A–C) revealed a homogenous, echodense mass involving the mitral valve, chordae tendinae, and the posteromedial papillary muscle, inducing stenosis of the mitral orifice. A right parasternal, short-axis, transmitral M-mode view showed a thickened mitral valve and anterior motion of the posterior mitral leaflet during diastole (Figure 3). Left ventricular M-mode measurements were within normal limits¹² (Table 1). Severe, left atrial enlargement was measured by the 2D short-axis view¹³ (Table 1). Pulmonic, aortic, and tricuspid blood flow patterns and velocities (pulsed-wave Doppler echocardiography), recorded from standard positions, were within normal limits.¹⁴ Color flow mapping revealed an area of diastolic flow convergence with a red to blue aliased signal proximal to the valve, with turbulence developing at the valve orifice, extending into the ventricular inlet. Also, a mild, systolic, mitral regurgitation was present. Peak filling velocity (Figure 4) obtained via continuous-wave Doppler echocardiography recorded from the left apical four-chamber position was 2.27 m/s in early diastole (reference range, 0.73 ± 0.11 m/s). The maximum, instantaneous, diastolic Doppler pressure gradient was 20.61 mm Hg, the deceleration time was 586 msec (reference range, 81 ± 17 msec), and the half-time pressures ranged from 180 to 250 msec (reference range, 10–52 msec). ^2,14–16

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Table 1 Left Ventricular M-mode Measurements and Two-Dimensional Left Atrium-Aorta Ratio

EPSS, E-point septal separation; IVSTd, diastolic interventricular septal dimension; IVSTs, systolic interventricular septal dimension; LA/AO, left atrium-aorta ratio, LVIDd, diastolic left ventricular internal dimension; LVIDs, systolic left ventricular internal dimension; LVWd, diastolic left ventricular free wall dimension; LVWs, systolic left ventricular free wall dimension; SF, shortening fraction

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A tentative diagnosis of a cardiac tumor causing left ventricular inflow tract obstruction was made. The dog was prescribed a sodium-restricted diet, benazepril (0.5 mg/kg PO q 24 hr), furosemide (1 mg/kg PO q 12 hr), and digoxin (0.0055 mg/kg PO q 12 hr) and was discharged from the hospital. Follow-up examinations of the dog were performed 1 mo, 2 mo, and 6 mo after diagnosis, showing improvement of clinical findings, but similar echocardiographic features.

The dog subsequently presented to the referring veterinarian for several episodes of alveolar pulmonary edema. The referring veterinarian increased the dose of furosemide to 2 mg/kg PO q 8 hr and prescribed pimobendan (0.25 mg/kg PO q 12 hr) and spironolactone (1 mg/kg PO q 24 hr) in addition to the previously prescribed medications. Eleven months after being diagnosed, the dog was euthanized at the owner's request because of recurrent congestive heart failure.

On postmortem examination, the gross appearance of the skin, head, and abdominal organs were unremarkable. The lungs showed severe congestion and edema. Grossly, the heart had a severely dilated left atrium and pulmonary veins. Inside the left atrium, a severely stenotic atrioventricular orifice was noted, due to involvement of the mitral valve leaflets with a mass, resulting in thickened and fused mitral valve leaflets (Figure 5). A longitudinal section through the left ventricle showed a white-yellow mass (1.5 cm × 2 cm × 1.5 cm), involving the posterior papillary muscle and chordae tendinae of the mitral valve (Figure 6). Tissue samples from the heart, lungs, regional lymph nodes, liver, spleen, and kidneys were fixed in 10% formalin and embedded in paraffin. Sections (4 μm thick) were prepared for routine hematoxylin and eosin staining. Additional sections of the cardiac mass were also stained by alcian blue (pH 2.5) and toluidine blue. Selected, serial sections of the tumor were immunostained using the labeled avidin-biotin complex (ABC) method^a and the following antibodies were used: cytokeratin^b (marker for epithelial cells, prediluted); vimentin^c (marker for mesenchymal cells, 1:100); α-smooth muscle actin^d (marker for smooth muscle cells and myofibroblasts, 1:100); and CD31 (marker for endothelial cells, 1:50)^e. Pretreatment with 0.1% pronase for 10 min was performed for cytokeratin. The sections were heated with an autoclave for 10 min at 121°C (to reproduce antigen retrieval) in either a citrate buffer at pH 6 for vimentin and α-smooth muscle actin or in EDTA at pH 9 for CD31.

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Histologically, signs of congestion and edema were observed in the lungs. No tumor lesions were observed in the tracheobronchial lymph nodes, lungs, and abdominal organs. The cardiac mass was composed of an abundant basophilic myxoid matrix, rich in acid mucopolysaccharides (Figure 7) that were stained by both alcian blue and toluidine blue. Stellate- to spindle-shaped cells with small, hyperchromatic nuclei were observed in the myxoid matrix. Metaplastic cartilagenous foci were frequently observed. Both cell populations were strongly positive for vimentin, but only a proportion of the cells were positive for α-smooth muscle actin, confirming the mesenchymal nature of the neoplastic cells (Figure 8). Neoplastic cells did not stain for CD31, thus ruling out a vascular tumor (e.g., hemangioma, hemagiosarcoma). CD31-positive inmunostaining was observed on the endothelial cells from the endocardium and endothelial cells of vessels in the tumor. The histochemical and immohistochemical findings confirmed the diagnosis of a myxoma.

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Discussion

Left ventricular inflow tract obstruction is a rare condition in dogs, usually caused by congenital mitral valve malformation.^14,16,17 To the authors' knowledge, a myxoma causing left ventricular mitral stenosis has not been reported in dogs. In this case, a mass outside the heart was not detected on either gross or microscopic examination and thus, a primary cardiac myxoma could be considered. Cardiac myxoma is a benign, endocardial neoplasm originating from multipotential mesenchymal cells in the subendocardial layer. They are capable of differentiating into various cell types.¹⁸ Myxoma is the most common primary cardiac tumor in adult human patients, but is extremely rare in animals.⁵ In dogs, the first case was reported by Roberts (1959), followed by sporadic reports thereafter.^2,4,6–8 In humans, cardiac myxomas usually develop in the atria, mainly from the interatrial septum in the left atrium. Myxomas are detected in the ventricles and mitral valve less frequently.^5,9,10,19 In dogs, cardiac myxomas have been reported in the right side of the heart, some of them involving the tricuspid valve and right ventricular outflow tract.^2,4,6–8 To the authors' knowledge, this is the first report in dogs of a myxoma involving the left side of the heart. In both humans and dogs, myxomas are generally polypoid, often pedunculated, round or oval, have a smooth or gently lobulated surface, are white-gray, yellow, or brown in color, and range in size from 1 to 15 cm in diameter.^4–8 In this case, the mass was not pedunculated and the size was 1.5 cm × 2 cm × 1.5 cm. The histopathologic findings of an abundant extracellular matrix containing acid mucopolysaccharides and the homotypic characteristics of spindle and stellate cells pointed to the diagnosis of a myxoma.^5–8,18 This supposition was confirmed in the case presented herein by the strong positive immunoreactivity for vimentin in the immunohistochemical analysis.

The rate of growth of myxomas is unknown, but generally they appear to grow rather quickly.^5,20 Nonetheless, in one human patient, a left atrial myxoma did not change in appearance over a period of 28 mo.²¹ In the case described herein, the echocardiographic appearance of the mass was similar at 2 mo, 6 mo, and 11 mo after diagnosis.

The clinical features of cardiac myxomas are determined by their location, size, and mobility. Most human patients present with one or more of the triad of constitutional, embolic, and intracardiac obstruction symptoms.^5,9,10 Constitutional symptoms (i.e., fatigue, fever, myalgia arthralgia, weight loss, and anemia), which can mimic symptoms of endocarditis, rheumatologic disorders, and/or malignancy, are believed to be caused by inflammatory mediators such as interleukin-6 released by the tumor.^5,22 Mitral valve myxoma differs slightly from that of other cardiac myxomas in that it has a lower incidence of constitutional manifestations.²³ Systemic embolization occurs in left-sided myxomas in 30–45% of human patients, mainly to the cerebral, visceral, and coronary arteries or even to the abdominal aorta.^5,9 Depending on their location and size, myxomas commonly give rise to signs of ventricular inflow obstruction, mimicking the clinical picture of mitral valve or tricuspid valve stenosis and associated insufficiency.^9,10,19 In dogs with cardiac myxomas, signs of right-sided heart failure and right ventricular outflow tract obstruction with associated exertional syncope have been reported at initial presentation.^2,4,6–8 In addition, emboli from the tumor have been found in pulmonary arteries.^2,6,7 The dog of this report only presented with clinical manifestations related to left ventricular inflow tract obstruction with left-sided congestive heart failure.

In humans, noninvasive diagnosis and localization of cardiac myxomas is commonly made by transesophageal echocardiography because it allows for a very early detection of small valvular tumors and may help characterize their location and echostructure better than transthoracic echocardiography.^5,9,19,23 Other noninvasive techniques such as computed tomography and magnetic resonance imaging may offer some advantages, such as the detection of very small mass and differentiation of tissue composition of the tumors.^5,9

Detection of a mass affecting the mitral valve and papillary muscles in the dog described in this report was easily achieved noninvasively by means of transthoracic 2D echocardiography. In dogs, the differential diagnoses of a mass affecting the mitral valve should include myxomatous degeneration (endocardiosis), endocarditis vegetations, and tumors.²⁴ Mitral endocardiosis appears as variable degrees of valvular thickening, commonly associated with valvular prolapse. In addition, mitral regurgitation, but not stenosis, of the left ventricular inflow characterizes mitral endocardiosis. When mitral endocarditis is present, typical locations of mitral vegetations are over the leading valve edge on the low pressure side (i.e., the atrial side).²⁴

Echocardiographic appearance of valvular myxomas in humans is variable, but a homogeneous, echodense mass is a common presentation, similar to that found in this clinical case.^5,10,19 In this case, long- and short-axis standard transthoracic echocardiography views allowed the authors to obtain images of cardiac structures as well as the mass, which were in agreement with postmorten images. Also, a reduced diastolic mitral valve excursion and a small mitral valve orifice due to the mass were also seen. The mitral M-mode echocardiographic findings presented in this clinical case, consisting of a reduced rate of diastolic closure of the anterior mitral leaflet and anterior motion of the posterior mitral leaflet during diastole, have been reported to be characteristic of mitral obstruction.^16,17 The hemodynamic consequences of mitral inflow obstruction and regurgitation, evaluated by Doppler echocardiography in the dog described in this report, were similar to those reported in both human patients with mitral myxoma and dogs with congenital mitral stenosis.^10,16,17,19 The spectral Doppler features in patients with mitral stenosis reveal a high peak transmitral gradient and a prolonged pressure half-time.^14,16,17 Because heart rate determines the length of the diastolic filling period, variations in filling caused by atrial fibrillation may influence transmitral pressure gradients and pressure half-times, as was observed in this case.^14,17

The treatment of choice for myxomas in humans is complete surgical removal. It may be curative, although recurrences within a few months to several years after the initial surgical excision have also been reported.^5,9 Either mechanical damage to a heart valve or adhesion of the tumor to valve leaflets may call for valve repair by annuloplasty or replacement with a prosthetic valve.^5,9 In the dog in this case, the myxoma involved the mitral valve, papillary muscles, and chordate. Thus, only standard treatment of left congestive heart failure was recommended.

Conclusion

Although myxomas are rarely reported in dogs and have never been reported in the left side of the heart, this report demonstrates that myxomas may occur in this location in the dog. A myxoma should be a differential for a left-sided cardiac mass, especially masses involving the mitral valve, which may cause mitral stenosis and associated clinical signs.