History

A 16-year-old 3.8-kg (8.4-lb) castrated male domestic shorthair cat was evaluated for recent-onset labored breathing, hyporexia, and progressive weight loss. A heart murmur was documented 10 years earlier. The cat had not undergone any prior cardiovascular testing or received any cardiac medications.

Clinical and Gross Findings

On physical examination, respiratory distress was noted along with a grade 3/6 left parasternal systolic murmur. Moderate generalized cachexia and thyroid gland enlargement were evident. Focused thoracic ultrasonography revealed pleural effusion and an enlarged left atrium. Oxygen and furosemide were administered, and 180 mL of translucent, pink pleural effusion was removed via thoracocentesis. Clinicopathologic analyses performed on an in-house analyzer^a following IV administration of furosemide (5.5 mg/kg [2.5 mg/lb]) revealed no abnormalities except for hyperlactatemia (2.7 mmol/L; reference range, 0.0 to 2.0 mmol/L) and high BUN concentration (29 mg/dL; reference range, 12.0 to 28.0 mg/dL). Electrocardiography and echocardiography were performed after 12 hours of treatment with oxygen and additional IV administration of furosemide (2 mg/kg [0.9 mg/lb]). At this time, infrequent cardiac arrhythmias and an S4 gallop were detected in addition to the cardiac murmur. Ventricular premature depolarizations were detected by ECG. Serum total thyroxine concentration was 0.4 μg/dL (reference range, 0.8 to 4.7 μg/dL).

Echocardiographic results included left ventricular (LV) dilation with an area of focal thinning and hypokinesis of the LV free wall (LVFW). There was marked left atrial and right heart enlargement. The base of the interventricular septum in diastole was thickened. The cat was discharged from the hospital, and the client was instructed to administer furosemide, clopidogrel, pimobendan, and lisinopril. Although treatment improved the cat's condition initially, the cat was euthanized (via IV injection of pentobarbital sodium and phenytoin sodium solution) because of dyspnea with recurrent pleural effusion 3 weeks later.

On necropsy, the abdomen and thorax contained a marked amount of translucent, straw-colored fluid. The left thyroid gland contained a well-delineated mass (3 × 2 × 1 cm). The LV was markedly dilated with a bulbous region at the apex (lower third of the LV) where the myocardium was paper thin (Figure 1). The basilar portion of the LV was eccentrically dilated, and the right ventricle (RV) was unremarkable. The heart weighed 28 g, and the heart-to-body weight ratio was 0.74% (in clinically normal cats, the mean ± SD heart-to-body weight ratio is 0.58% ± 0.1%¹). There was mild hydropericardium. The liver was diffusely enlarged and dark reddish brown (consistent with chronic passive congestion).

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Gross images of the left ventricle (LV; A and B) and an opened cross section through the LV along the long axis (C) in the heart of a 16-year-old cat that was evaluated because of respiratory distress, including open-mouthed breathing. A heart murmur was documented 10 years earlier. Notice that the bulbous region at the apex is sharply demarcated from the upper portion of the LV. The LV is severely eccentrically dilated.

Citation: Journal of the American Veterinary Medical Association 255, 9; 10.2460/javma.255.9.1023

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Formulate differential diagnoses from the history, clinical findings, and Figure 1—then turn the page→

Histopathologic Findings

Histologic examination of sections of the LVFW in the apical region revealed almost complete loss of cardiac myocytes with a thin remnant of fibrovascular tissue between the endo- and epicardium. At the interface of fibrovascular tissue and remaining myocardium in the more basilar portion of the LVFW, there was scattered cardiac myocyte degeneration with sarcoplasmic vacuolization and occasional contractile fiber fragmentation (Figure 2). The transition area had multifocal regions of myocardial loss with replacement fibrosis. There was no evidence of myocardial inflammation microscopically. Extensively, the liver had moderate sinusoidal dilation with mild fibrosis that surrounded the central vein and extended into the sinusoids. There was mild to moderate multifocal lymphoplasmacytic interstitial nephritis. The thyroid gland nodule was well delineated from and mildly compressed the normal gland parenchyma and was composed of numerous variably sized areas of colloid containing epithelial cell-lined follicles. In addition, within the tumor there were multiple large epithelial cell-lined cysts, which contained large quantities of eosinophilic proteinaceous fluid (consistent with a cystadenoma).

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Photomicrographs of sections of the heart from the cat in Figure 1. A—Low-magnification view of the transition of the basilar region of the LV to the apical portion of the LV. Notice the loss of cardiac myocytes with replacement by fibrovascular tissue (asterisk). H&E stain; bar = 1 mm. B—View of the same region in panel A following trichrome staining. The green regions (asterisk) are composed of fibrous tissue and are contrasted with the purple regions of myocardium. Trichrome stain; bar = 1 mm. C—Higher-magnification view of the interface between the remaining myocardium and fibrovascular tissue. The cardiac myocytes (left side of image) have variable size and angular shape (arrow) along with sarcoplasmic vacuolation. H&E stain; bar = 100 μm. D—View of the same region in panel C following trichrome staining. The purple staining of the myocardium highlights the variable size of the cells. On the right side of the image, there is poorly arranged fibrous tissue with numerous small-caliber vessel profiles and adipocytes representative of all of the region that underwent cardiac myocyte loss. Trichrome stain; bar = 100 μm. E—High-magnification view of the region containing myocardium in panel C. Myocardiocytes have undergone degeneration with sarcoplasmic swelling and loss of cross striations. H&E stain; bar = 50 μm. F—Another high-magnification view of the region containing myocardium in panel C. Notice the loss of the myocardiocytes' cross striations (arrow). Phosphotungstic acid–hematoxylin stain; bar = 50 μm.

Citation: Journal of the American Veterinary Medical Association 255, 9; 10.2460/javma.255.9.1023

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Morphologic Diagnosis and Case Summary

Morphologic diagnosis: basilar eccentric hypertrophy of the LV with marked bulbous dilation (ballooning or aneurysm) of the apex and myocardial loss, degeneration, and replacement fibrosis; marked secondary hydrothorax and hydroabdomen; secondary sinusoidal dilation and mild fibrosis (chronic passive congestion) of the liver; and cystadenoma of the left thyroid gland in a cat.

Case summary: left ventricular apical ballooning or aneurysm in a cat.

Comments

The antemortem findings for the cat of the present report were consistent with congestive heart failure (CHF) secondary to end-stage hypertrophic cardiomyopathy (HCM).² Cardiomyopathy is a condition that alters the structure and function of cardiomyocytes. Hypertrophic cardiomyopathy is the most commonly diagnosed form of cardiomyopathy in felids, accounting for 58% to 68% of cardiomyopathies in cats.^3,4 Functional impairment associated with HCM includes dynamic outflow tract obstruction, diastolic dysfunction, arterial thromboembolism, and CHF.⁵ Other forms of cardiomyopathy include restrictive cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, dilated cardiomyopathy, nonspecific cardiomyopathy, and secondary cardiomyopathies such as those attributable to hypertension or hyperthyroidism (or both).⁴ The primary disease process of the cat of the present report was CHF secondary to cardiomyopathy with apical ballooning. There was no echocardiographic or necropsy evidence of valvular disease. The residual hypertrophy of the interventricular septum in diastole could have represented progression to end-stage HCM.

In cats with HCM, progressive thinning of the left ventricular wall (ie, ballooning or aneurysm) and reduction in LV contractile function develop as the disease reaches an end stage.⁶ Gross and histologic changes in cats with HCM or end-stage HCM are similar to those in humans with HCM or end-stage HCM.^6,7 End-stage HCM is defined as dilation of the ventricular chamber, thinning of the ventricular wall, and decreased ventricular systolic function with decreased fractional shortening relative to the patient's previous echocardiographic findings (ie, LV hypertrophy with preserved ejection fraction), typically with left atrial dilation.⁶ In felids and humans, decreased ventricular systolic function is visually evident as global or regional hypokinesis on echocardiograms. Areas of myocardial fibrosis, myocardial fiber disarray,⁶ mature fibrosis of the myocardium and endocardium, and necrosis of surrounding myocytes develop in end-stage HCM. Infarcts are most severe in the LVFW but may also develop in the interventricular septum and RV.⁶

The hallmark feature of end-stage HCM is multifocal myocardial scarring, which is suspected to develop secondary to myocardial infarction. The development of myocardial infarction in cats with HCM has been described secondary to coronary vessel abnormalities (vascular smooth muscle hypertrophy, thromboembolism, and arteriospasm), cardiac muscle hypertrophy that exceeds the ability of the vasculature to provide blood flow with development of ischemia, apoptosis, or genetic mutations.⁶ The coronary vessels appeared normal in the cat of the present report.

The clinical importance of the thyroid cystadenoma in the cat of the present report was unknown. It was plausible that the low serum total thyroxine concentration may have been a result of laboratory error or euthyroid-sick syndrome (wherein true elevation of thyroid hormone concentrations is blunted by a secondary disease process). Alternatively, the cat may truly have had hypothyroidism. To the authors' knowledge, there are no similar reports in the veterinary medical literature documenting left ventricular apical ballooning (or aneurysm) in hypothyroid cats. Excessive circulating concentrations of thyroid hormones can affect the cardiovascular system in several ways, such as causing myocardial hypertrophy, increasing systolic and diastolic function, causing vasodilation, and increasing circulating blood volume, as well as altering heart rate and rhythm. It is possible that the cat previously had hyperthyroidism, which contributed to the development of heart disease⁸; however, we have no definitive evidence of a hyperthyroid state for the cat of the present report.

Among the few reports of myocardial ballooning or aneurysms in veterinary patients, there is a recent description of an LV apical aneurysm with disorganized cardiomyocytes as well as occlusive changes in small arteries in a cat⁹; the findings were consistent with primary cardiomyopathy with differential diagnoses including end-stage HCM, restrictive cardiomyopathy, and nonspecific cardiomyopathy. Additionally, there was atrophy and scarring of the LV adjacent to the aneurysm, suggesting that the lesions resulted from myocardial infarction.⁹

In 2004, Boujon et al¹⁰ described an RV aneurysm and atrial septal defect in a cat. On postmortem examination, the aneurysm was located in the craniolateral free wall of the RV. Histologic examination of sections of the aneurysm revealed loss of endocardial and myocardial cells; myocytes were replaced by fibroblastic cells and fibrocytes and round-cell myocarditis and collagen deposition.¹⁰

Apical aneurysms in the RV in cats with arrhythmogenic RV cardiomyopathy have been reported.¹¹ In 1 study,¹¹ 8 of 12 cats with arrhythmogenic RV cardiomyopathy underwent echocardiography; 4 cats had localized right akinetic or dyskinetic areas with diastolic outward bulging in the apical or subtricuspid areas. On gross postmortem examination, 6 of the 12 cats also had aneurysms in the apical, subtricuspid, and infundibular regions.

In a retrospective review¹² of humans with HCM, 93 of 1,940 (4.8%) persons with LV apical aneurysms were identified. Aneurysms were visualized with echocardiography in 50 of the 93 (54%) patients, with additional identification achieved via cardiac MRI or CT. Humans with HCM and LV apical aneurysms are at high risk for arrhythmic sudden cardiac death and thromboembolic events with 21 of 93 (22.6%) patients experiencing sudden death events or 36 of 93 (38.7%) patients developing adverse complications such as advanced heart failure symptoms, presence of an apical thrombus, or a thromboembolic event.¹²

The presence of a left apical aneurysm should be considered in felids with CHF. When performing an echocardiographic examination of felids with CHF, the sonographer should plan to evaluate the apex of the heart, as this may not be routinely visualized in standard views.⁴ In the cat of the present report, echocardiography revealed a markedly thinned region of the ventricular myocardium at the LV apex with circumferential dilation of the LV cavity. The prognostic importance of LV aneurysm in cats with cardiomyopathy is uncertain, but people with HCM and an LV aneurysm are considered to be at high risk for adverse events.¹² On the basis of information in the human and veterinary medical literature,^9–11 it subjectively appears that cats and humans with HCM and LV apical aneurysms have a poor prognosis. Future studies involving echocardiographic and gross pathological assessments may reveal whether LV apical ballooning or aneurysm is a unique disease process or a variation of end-stage HCM or myocardial infarction.