Supravalvular Mitral Stenosis in a Cat

Case Report

A 3-year-old, 4-kg, castrated male domestic shorthair cat was presented to the University of Minnesota Veterinary Teaching Hospital (UMVTH) for evaluation of respiratory distress. The cat had a 1-month history of labored breathing and intermittent coughing. His appetite had been decreased for the previous month, and he had been completely anorectic for several days prior to presentation.

On physical examination, the patient was quiet, alert, and responsive. He was in normal body condition. Respiratory rate was 100 breaths per minute, with increased inspiratory and expiratory effort. Lung sounds were muffled on auscultation, though an expiratory wheeze could be heard when he became agitated. Heart rate was 180 beats per minute and regular. A grade 3/6 holosystolic murmur with point of maximal intensity over the left caudal parasternal region could be heard. All other physical examination findings were normal.

Thoracic radiographs showed moderate pleural effusion and a severe, diffuse alveolar infiltrate. The cardiac silhouette was somewhat obscured by the fluid but appeared moderately to severely enlarged relative to the thorax.

Thoracocentesis was performed, and 165 mL of slightly hemorrhagic, milky effusion was removed. Fluid analysis revealed 11.6 × 10³ nucleated cells/μL, 17.4 × 10³ red blood cells/μL, and a total protein of 3.2 g/dL. The nucleated cells were 95% normal small lymphocytes and 5% macrophages. Abundant extracellular lipid droplets consistent with chylomicrons were present. The fluid was not evaluated for cholesterol and triglyceride concentrations, as the visualization of chylomicrons on microscopy is considered specific for chylous effusions.¹ A complete blood count was within reference ranges. A serum biochemical profile showed a very slight increase in aspartate aminotransferase (44 U/L; reference range, 9 to 37 U/L) and a moderate increase in glucose (255 mg/dL; reference range, 64 to 145 mg/dL), which was attributed to a stress response. A urinalysis was normal.

The cat was placed in an oxygen cage and treated with furosemide^a (16 mg intravenously [IV], q 4 hours) and 2% nitroglycerin ointment^b (0.25 inch topically applied to the hairless areas of alternating pinnae, tid). Respiratory rate decreased to <40 breaths per minute over 24 hours, and the furosemide dosage was decreased (10 mg IV, tid).

Two-dimensional echocardiography showed pleural and pericardial effusion and severe left atrial enlargement. Pericardial effusion was considered moderate but not of sufficient magnitude to necessitate pericardiocentesis. The left auricle extended approximately two-thirds the length of the left ventricle toward the left ventricular apex. A perforate membrane that divided the atrium into two chambers [Figures 1A, 1B] was visualized just proximal to the mitral valve. Color-flow Doppler interrogation revealed high-velocity blood flow through a single aperture in the membrane [Figure 2]. Peak blood-flow velocity through the aperture measured 2.2 meters per second with continuous-wave Doppler. Using the modified Bernoulli equation (pressure gradient = 4 × V²),² this indicated a peak pressure difference of 19.4 mm Hg between the two atrial chambers (normal peak left atrial systolic pressure, 5 to 12 mm Hg).³ Mild mitral valve regurgitation was also observed during color-flow Doppler interrogation, accounting for the systolic murmur heard in this cat. The anterior leaflet of the mitral valve was elongated, while the posterior leaflet was short and difficult to visualize. There was increased thickness of the chordae tendineae. No other abnormalities were noted on echocardiographic examination. A diagnosis of supravalvular mitral stenosis (SMS) and mitral valve dysplasia with resultant congestive heart failure was made on the basis of echocardiography, radiography, pleural fluid analysis, and physical examination findings.

Radiographs that were taken 48 hours after admission showed resolution of pleural effusion. A mild, diffuse, interstitial pulmonary infiltrate persisted. There was moderate enlargement of the cardiac silhouette relative to the thorax on the lateral view and marked left atrial enlargement on the dorsoventral view.

The owners were offered surgical correction of the defect, but they opted instead for medical management of congestive heart failure. The cat was discharged 3 days after admission and was given furosemide (6.25 mg per os [PO], bid), enalapril^c (1.25 mg PO, sid), and aspirin^d (5 mg total dose PO, q 72 hours) for prophylaxis of thromboembolic complications associated with the greatly enlarged left atrium.⁴ This is a much lower aspirin dose than the typically recommended dosages for prophylaxis of thromboembolism in cats (25 mg/kg body weight or 81 mg total dose PO, q 72 hours).⁴ The authors currently use this lower aspirin dose at the UMVTH based on studies that suggest that very low doses of aspirin selectively inhibit platelet production of thromboxane A₂, while sparing endothelial production of prostaglandin I₂ (PGI₂). Thromboxane A₂ promotes platelet aggregation and vasoconstriction, whereas PGI₂ causes vasodilatation and decreases platelet aggregation.⁵⁶

Ten months after initial diagnosis, the owners reported that the cat had a good appetite and was generally quite active, although he tired more easily than prior to the onset of clinical signs. Periodic adjustments of the diuretic dose had been necessary to control increases in respiratory rate and radiographic signs of congestive heart failure.

Discussion

Malformation of the mitral valve complex was the most common cardiac anomaly found in a large survey of feline congenital defects.⁷ Gross abnormalities included enlarged annulus; short, thick leaflets; short and stout or long and thin chordae tendineae; upward malposition of atrophic or hypertrophic papillary muscles; insertion of one papillary muscle directly onto one or both leaflets; diffuse, endocardial fibrosis; and enlargement of the left atrium and ventricle.⁷⁸ However, clinical recognition of all forms of mitral valve stenosis, including SMS, is quite uncommon in cats. A review of the literature revealed only one other report of SMS in the cat.⁹

In humans, SMS is also very rare and is frequently associated with multiple defects of the mitral valve apparatus, similar to those described above.¹⁰¹¹ In addition to SMS, the cat in this report had mild mitral regurgitation, thick chordae tendineae, and short posterior and long anterior mitral valve leaflets, which indicated that abnormalities of the mitral valve apparatus were also present. Embryologically, the mitral and tricuspid valves are derived primarily from the ventricular walls, with a small contribution from the endocardial cushions, through infolding of the endomyocardial tissue. Congenital abnormalities may occur as a result of abnormal development during this process of diverticulation and undermining.¹²¹³

Supravalvular mitral stenosis must be differentiated from cor triatriatum sinister (CTS), another rare defect that causes membranous division of the left atrium.^14–17 Supravalvular mitral stenosis can be distinguished from CTS by the location of the membrane relative to the left auricle. In SMS, the left auricle is proximal to the dividing membrane and connects to the enlarged proximal left atrial chamber. This was seen quite dramatically in this patient. In CTS, the left auricle is distal to the dividing membrane and connects to the distal left atrial chamber.¹⁴¹⁵ Cor triatriatum sinister is thought to result from incomplete incorporation of the embryological pulmonary venous chamber into the developing left atrium.¹² Both CTS and SMS cause left ventricular inflow obstruction, which may result in signs of pulmonary hypertension and congestive heart failure, including pulmonary edema, pleural effusion, and pericardial effusion.

Pleural effusion may result from right, left, or bilateral heart failure. The veins of the visceral pleura drain into the pulmonary veins; therefore, left heart failure resulting in elevated left atrial pressure may lead to the formation of pleural effusion. Venous return from the parietal pleura drains into the systemic venous circuit; thus, right heart failure may also result in pleural effusion.¹⁸ Clinically significant pericardial effusion is quite rare in cats. However, in one study, congestive heart failure was the most common pathological diagnosis resulting in mild pericardial effusion in cats; that study included two cases with mitral valve malformations.¹⁹ Any disease process resulting in excessive fluid retention, such as congestive heart failure, may potentially result in pericardial effusion.²⁰

Although surgery was declined in the case of this report, SMS represents a potentially correctable congenital cardiac defect. Successful surgical correction of CTS in a kitten has been described.¹⁶ While SMS is rare, it should be included in the list of differential diagnoses for congenital and acquired cardiac defects in young cats, especially because it is potentially surgically correctable.