Uhl’s Anomaly in a Domestic Shorthair Cat

Introduction

Uhl’s anomaly is a rare, congenital heart disease that was originally described in 1952 in an infant.¹ Reports of Uhl’s anomaly in the veterinary literature are isolated. Ishikawa and others (1977) documented a case at autopsy in a mink, and Atwell (1980) reported Uhl’s anomaly in a cat with severe, right-sided cardiac decompensation.^2,3 This report describes a recent case of Uhl’s anomaly in a domestic shorthair cat in Europe.

Case Report

A 2-year-old, 3.0-kg, neutered male, domestic shorthair cat was referred for acute-onset dyspnea. The cat had a 1-month history of weight loss, inappetence, and tachypnea. Episodes of weakness since the cat’s first months of age had been noticed by the owner.

On presentation, the cat was moderately depressed. Respiratory rate was 65 breaths per minute. The cat showed restrictive dyspnea when stressed or when forced to lie down (orthopnea). Mucous membranes were pale with prolonged capillary refill time (3 seconds). Tachycardia (250 beats per minute) and a weak femoral arterial pulse were detected. The jugular veins were distended in the distal half of the jugular furrows, and jugular vein pulsation was observed. Cardiac auscultation revealed muffled heart sounds and a grade 1/6 systolic murmur on the right sternal border. The cat had abdominal distension with palpable ascites.

A standard six-lead electrocardiogram (ECG) showed a normal sinus rhythm (200 to 220 beats per minute) with tall P waves (0.3 to 0.35 mV), consistent with right atrial enlargement. The QRS complexes following the P waves were of low voltage and isoelectric, with an indeterminate mean electrical axis. However, S waves were apparent in leads I, II, and aVF—suggestive of right-ventricular enlargement. Isolated ventricular premature complexes (VPCs) with right bundle branch block (RBBB) morphology were observed [Figure 1A].

The owner of the cat did not consent to a Holter monitoring. Thorax ultrasonography revealed severe pleural effusion. A partial thoracentesis yielded 150 mL of serous fluid consistent with a modified transudate on cytology and biochemistry. Echocardiography^a showed residual pleural and mild pericardial effusions. On M-mode echocardiography, the right ventricle (RV) was severely increased in size (RV end-diastolic dimension was 15.8 mm). The RV free wall was thin, with a depressed systolic thickening. Left cardiac chambers were normal in size and function [Figure 2A]. On B-mode echocardiography, the RV free wall appeared diffusely hypokinetic and thinner than normal, with segments as thin as 1 mm [Figure 1B]. Diastolic paradoxical septal motion was documented by both B-mode and M-mode. The right atrium was severely enlarged. The pulmonary artery was normal in size. No evidence of intracardiac shunts, outflow obstructions, or valvular lesions was seen. Continuous-wave spectral Doppler showed a jet of tricuspid insufficiency (2.23 meters per second) [Figure 2B]. This regurgitant flow was centrally directed and mild (<20% of right atrial chamber involved) at color-flow Doppler mapping. Aortic and pulmonic flows were within normal limits.

Abdominal ultrasonography revealed an enlarged liver with venous congestion. Peritoneal effusion was present. Clinical and ultrasonographic findings were consistent with RV cardiomyopathy and severe right-sided heart failure. After complete drainage of the pleural effusion, the cat was discharged.

Furosemide^b (2 mg/kg per os [PO] q 12 hours) and benazepril^c (0.5 mg/kg PO q 24 hours) were prescribed. Following brief clinical improvement, the cat’s condition progressively worsened, and the cat died naturally from refractory dyspnea related to progressive congestive heart failure 1 month after the initial examination. The owner consented to a postmortem examination.

After gross examination, the whole heart, thyroid gland, and samples of liver, lung, and kidney were fixed in 10% buffered formalin. Transverse sections were prepared of the proximal, medium, and distal portions of the RV and the longitudinal samples of the left ventricle (LV), interventricular septum, and atrial walls. Samples were processed for routine histology, embedded in paraffin wax, sectioned at 5 μm, and stained with hematoxylin and eosin. Myocardial samples were stained additionally with Masson’s trichrome and Van Gieson stain for elastic fibers.

At necropsy, nutritional condition was normal. The abdominal and thoracic cavities contained abundant, pinkish effusion. The liver was enlarged. The visceral pleura showed a multifocal, grayish, irregular thickening. Lungs were enlarged with soft, whitish, rounded margins associated with brownish consolidation of the parenchyma. In the pericardial cavity, a moderate effusion was present. External examination of the heart revealed severe dilatation of the right atrium and RV, which had a parchment-like appearance. Longitudinal sectioning of the heart showed severe thinning of the RV [Figure 3A] and right atrial dilatation. The tricuspid valve apparatus showed a regular appearance; in particular, the diameter and shape of the ring, the origin and morphology of the leaflets, the length and thickness of the chordae tendinea, and position of the papillary muscle were normal. No lesions were present on the interatrial and inter-ventricular septum. The remainder of the heart was normal.

Histopathology of the liver showed diffuse and severe congestion. Diffuse, severe, fibrinous, subacute pleuritis and severe, multifocal atelectasis with alveolar emphysema were present in the lung. No significant lesions were detected in the kidney or thyroid gland. Multiple serial sections of the RV showed diffuse and severe myocardial hypoplasia of the parietal wall associated with a thin connective layer between the epicardial and endocardial surfaces [Figure 3B]. The septal component, the septomarginal trabeculation, and the papillary muscle of the tricuspid valve showed no muscle deficit, and no replacement by fibroadipose tissue or elastic fibers was observed. Histopathology of the LV and interventricular septum showed multifocal and mild interstitial fibrosis. These changes were consistent with Uhl’s anomaly.

Discussion

Uhl’s anomaly is characterized by partial or complete absence of the RV myocardium. In the so-called “parchment heart” is a virtually complete absence of the myocardium of the parietal wall of the RV, which is composed of apposing endocardial and epicardial surfaces with no interposed adipose tissue or evidence of inflammation and necrosis. The parietal myocardium appears paper thin and translucent.^4,5 Fontaine and others (1979) described a condition they called arrhythmogenic right ventricular dysplasia (ARVD); this condition is characterized by local deficiency and fibrofatty replacement of the RV myocardium.⁶ The remaining muscle fibers interspersed with fatty and fibrous tissue provide a substrate for ventricular arrhythmias. The two conditions have been confused for many years.

A more recent study in humans has shown that the two conditions are separate entities, with distinct pathological findings and clinical presentation.⁷ The ARVD manifests especially in adolescence or adulthood with arrhythmias, syncope, and sudden death. Patients affected by Uhl’s anomaly generally present with right-sided failure in infancy or childhood. Arrhythmias and conduction disturbances occur less commonly in Uhl’s anomaly than in ARVD, probably because of the absence of residual foci to initiate or transmit anomalous electrical activity.^5,8 However, studies suggest that the diseases may share a common pathogenesis, incriminating apoptotic anomalies for RV muscle dysplasia/agenesis. In Uhl’s anomaly, the apoptotic process starts earlier and may be incessant with complete destruction of the RV wall, whereas in ARVD an episodic apoptosis may begin at any time, possibly in adolescence.^9,10 The two conditions could then be different manifestations of the same disease process.

The case described herein is of a cat with Uhl’s anomaly and severe, right-sided congestive heart failure. The clinical presentation resembles descriptions of Uhl’s anomaly in humans, and it is also consistent with the previously reported case of Uhl’s anomaly in a cat.^3,11,12 However, one of the most extensive studies of ARVD (also named arrhythmogenic right ventricular cardiomyopathy [ARVC]) in cats reports right-sided congestive heart failure as the most frequent clinical feature of this disease in the domestic cat; this finding is unlike those in human patients, where major findings are ECG abnormalities and sudden death.¹³ In that study, cases were retrospectively selected for death apparently because of congestive heart failure of RV origin, and the authors suggested that the different clinical behavior of feline ARVD could be due to case selection.¹³ However, in a recent report of two cats with ARVC in Europe, both animals presented with clinical signs of right-sided congestive heart failure—similar to signs reported by Fox and others.¹⁴

The major ECG findings in humans with documented Uhl’s anomaly are first-degree atrioventricular block, right axis deviation, low-voltage QRS complexes, and right atrial and ventricular enlargement.^{10,12,15–17} Atrial fibrillation and isolated rare ventricular ectopic beats have been reported in an adult patient with long-standing disease.¹⁸ Cases of ventricular tachyarrhythmias have been reported as well.^19,20 Sinus rhythm and ECG findings suggestive of right atrioventricular enlargement were also reported by Atwell in the cat.³ Conversely, supraventricular tachyarrhythmias (especially atrial fibrillation), complex ventricular ectopy (including ventricular tachycardia), and major conduction disturbances (RBBB, complete atrioventricular block) are frequently encountered ECG abnormalities both in humans and cats with symptomatic ARVD.^13,14 In the case reported here, the ECG documented a normal sinus rhythm with isolated RBBB morphology VPCs, low-voltage QRS, and features of right atrial and RV enlargement. Resting ECG findings were consistent with Uhl’s anomaly as described in humans and cats. Unfortunately, ambulatory ECG monitoring was not performed, and paroxysmal tachyarrhythmias cannot be ruled out.

Echocardiographic findings were similar to those described in human patients with Uhl’s anomaly and included right atrial and RV enlargement, thinning of the RV myocardium with poor systolic function, paradoxical septal motion, and tricuspid regurgitation.^15,19,21,22 Common findings reported in cats with ARVC are abnormal muscular trabecular pattern (particularly in the apical RV cavity) and images consistent with localized RV aneurysm formation in the apical or subtricuspid region.¹³ These findings were not evident in the case reported here.

It could thus be argued that differences in the clinical, ECG, and echocardiographic features between this condition and ARVC in cats are subtle and that definitive diagnosis requires histology. Uhl’s anomaly features partial or complete absence of the myocardium in the RV parietal wall, which is composed only of endocardial and epicardial surfaces separated by fibrous-elastic tissue and eventually by isolated adipocytes.^2–5,7 The septal component, on the other hand, along with the septomarginal trabeculation and the papillary muscles of the tricuspid valve, are normally muscularized.⁸ The ARVC in cats is characterized by fibro-fatty replacement of the RV wall myocardium and trabeculae, with residual myocytes scattered within the areas of fibrosis and fat. Fibrous replacement accompanying ARVC may also be observed in the LV free wall, interventricular septum, and right or left atrium. Patchy inflammatory infiltrates are often present in the RV or LV, interventricular septum, and right or left atrium.¹³ The histopathological findings of the case reported here were thus more consistent with Uhl’s anomaly than ARVC.

Conclusion

Feline Uhl’s anomaly, as described in this case report, is remarkably similar to the condition in human patients and to the previously reported case in the veterinary literature with respect to clinical features and pathological findings. Uhl’s anomaly should be included in the differential list of right congestive heart failure in the cat. Uhl’s anomaly may be misdiagnosed particularly as ARVC because of the similarity of clinical and echocardiographic findings. Uhl’s anomaly should be suspected in young cats with overt signs of right congestive heart failure; marked enlargement of right chambers with thinned, hypokinetic walls; and ECG features of right atrial and/or RV enlargement. However, histopathology is necessary before a definitive diagnosis can be made.