A case of juvenile form of dilated cardiomyopathy in a 6-month-old Shiba Inu dog

Abstract

A 6-month-old Shiba Inu dog was brought to the Veterinary Medical Teaching Hospital because of a cough, exercise intolerance, and pulmonary edema. The dog had a Levine 2/6 systolic murmur. Transthoracic echocardiography revealed left atrial and ventricular dilatation (left atrium to aortic ratio: 2.8), mitral and tricuspid valve regurgitation, and severe left ventricular myocardial hypokinesia (fractional shortening was 11.8%). Bubble contrast echocardiography did not reveal a congenital shunt; therefore, the dog was clinically diagnosed with early onset dilated cardiomyopathy. From the first visit, the dog was treated with pimobendan, taurine, torasemide, and isosorbide dinitrate. After 435 days, echocardiography revealed that systolic function had not improved. On Day 465, atrial fibrillation was confirmed via electrocardiogram, and treatment with diltiazem hydrochloride was initiated. The dog continued to appear clinically stable thereafter, until it died suddenly 1087 days after the initial visit. A postmortem histopathological examination identified severe enlargement of the left atrial and ventricular chambers as well as attenuated wavy fibers in the ventricular myocardium, which confirmed dilated cardiomyopathy in a juvenile. This is the first report of a juvenile form of dilated cardiomyopathy in a Shiba Inu dog. This case report provides evidence that the extended prognosis of this dog differed from that in previously reported cases of dilated cardiomyopathy in young dogs.

Key clinical message:

This is the first reported case of a juvenile form of dilated cardiomyopathy in a Shiba Inu dog. This report provides evidence that the prognosis of this dog differed from that in previously reported cases of dilated cardiomyopathy in young dogs.

Dilated cardiomyopathy (DCM) is a major myocardial disease, characterized by cardiac chamber enlargement and severe systolic dysfunction (1,2). Several reports have shown that DCM mainly affects large-breed dogs, such as the Doberman pinscher, Great Dane, Irish wolfhound, and Scottish deerhound. The common age at diagnosis is 6 to 8 y (1); however, some dogs develop DCM as juveniles and die within a few months. Thus far, the juvenile form of dilated cardiomyopathy has been reported in only 3 breeds: Doberman pinscher, Portuguese water dog, and toy Manchester terrier (3–6). No definitive diagnosis has previously been reported in Shiba Inu dogs, and the clinical course of early-onset DCM has not been described in detail. In the present case, we report clinical findings of DCM, pathologically confirmed by a postmortem examination, in a juvenile Shiba Inu dog.

Case description

A 6-month-old intact, 6.2 kg, female Shiba Inu dog was brought to the Veterinary Medical Teaching Hospital of Nippon Veterinary and Life Science University.

At the referring hospital, the dog exhibited a cough and exercise intolerance. Left-sided heart failure was suspected because of pulmonary edema on thoracic radiography and cardiac dilatation on echography. Therefore, pimobendan (Pimobe Heart; Kyoritsu Seiyaku, Tokyo, Japan), 0.2 mg/kg body weight (BW), PO, q12h and torasemide (Luprac; Mitsubishi Tanabe Pharma., Osaka, Japan), 0.16 mg/kg BW, PO, q12h were administered to treat the left-sided congestive heart failure.

Upon initial visit to our hospital (Day 1), physical examination revealed a heart rate (HR) of 127 bpm and a Levine 2/6 systolic murmur at the left parasternal region. The systolic, diastolic, and mean blood pressure (BP) measured via the oscillometric method (BP 100 DII; Fukuda M-E, Tokyo, Japan) were 136 mmHg [reference range (RR): 121 to 139 mmHg], 57 mmHg (RR: 67 to 71 mmHg), and 81 mmHg (RR: 88 to 92 mmHg), respectively (7). The complete blood (cell) count was within the normal range. Serum biochemical analysis indicated hyperglycemia (162 mg/dL) and hypokalemia (3.1 mmol/L). Other measurements, including thyroxin concentration (3.21 μg/dL), were within reference ranges. Electrocardiography revealed a sinus rhythm with ventricular premature complexes (14 beats/min) and widening of the P wave duration (50 ms) (Figure 1). Thoracic radiography in the dorsoventral and right lateral position showed an enlarged left atrium and ventricle. The vertebral heart size was enlarged (10.5 v) (8). Although cranial pulmonary venous enlargement was shown, pulmonary edema was not observed (Figure 2). A 2-dimensional transthoracic and Doppler echocardiographic study was performed using Vivid 7 echocardiographic equipment (GE Healthcare, Tokyo, Japan). The left atrium was enlarged, and the left atrium-to-aortic root diameter ratio was 2.8 (RR: 0.69 to 1.27) (9). The end diastolic left ventricular dimension (LVDd), end systolic left ventricular dimension (LVDs), end diastolic interventricular septum thickness, and end diastolic left ventricular posterior wall thickness were 42.3 mm (RR: 22.0 to 31.0 mm), 37.3 mm (RR: 12.0 to 22.0 mm), 4.8 mm (RR: 4.0 to 9.0 mm), and 4.1 mm (RR: 4.0 to 9.0 mm), respectively, and fractional shortening (FS) was 11.8% (RR: 25.3 to 49.9%) (Figure 3) (9,10). With body weight normalized, the end diastolic left ventricular interior dimension (LVIDDN) was 2.5 (reference value: < 1.7) (10). The left ventricular end diastolic volume, end systolic volume, and ejection fraction, measured by single plane method of disks using apical 4-chamber view, were 42 mL, 31 mL, and 27% (reference value: 66.5 ± 6.4%), respectively (11). With body surface area normalized, the end diastolic volume and end systolic volume were 124 mL/m² (reference value: 47.6 ± 8.4 mL/m²) and 90 mL/m² (reference value: 15.9 ± 3.9 mL/m²), respectively (11). Sphericity index of the left ventricle at diastole and systole were 1.2 and 1.1 (reference value: > 1.65), respectively (12). E-point to septal separation of the mitral valve leaflet was 14 mm (reference value: < 6.5 mm) (12). Transmitral E and A wave velocities were 0.9 m/s (RR: 0.58 to 1.17 m/s) and 0.4 m/s (RR: 0.39 to 0.86 m/s), respectively (13). The aortic velocity was 1.2 m/s (RR: 0.92 to 1.88 m/s) (13). These examinations confirmed that the systolic function of the left ventricle was decreased. This was accompanied by thinning of the left ventricular wall and dilation of the left ventricle. There was no degeneration or prolapse of the mitral and tricuspid valve leaflets, but color flow Doppler showed a central jet signal of mild mitral and tricuspid valve regurgitation. A contrast-enhanced echocardiogram with a microbubble test was performed to carefully evaluate the presence of congenital shunts. Based on these findings, the dog was clinically diagnosed with DCM.

Figure 1.

Electrocardiography in lead II shows a heart rate of 157 bpm and multifocal ventricular premature complexes (14 bpm) which is a wide QRS wave without a P wave and occur prematurely compared to the underlying rhythm. Also, the P wave is wide. The variation in R-R interval is associated with the breathing movements (respiratory sinus arrhythmia). Therefore, a respiratory sinus arrhythmia with multifocal ventricular premature complexes was diagnosed. Paper speed = 50 mm/s; Gain = 5 mm/mV.

Figure 2.

Dorsoventral (A) and right lateral radiograph (B) taken on Day 1. Although obvious pulmonary edema was not seen, left atrial and left ventricular enlargement as well as cranial pulmonary venous enlargement were shown. The figure also revealed an increased vertebral heart size (10.5 v; standard value: 9.8 ± 0.45 v).

Figure 3.

Right parasternal short-axis view (A — Diastolic phase, B — Systolic phase) on Day 1. Images reveal an end diastolic left ventricular dimension of 42.3 mm, an end diastolic interventricular septum dimension of 4.8 mm, and an end diastolic left ventricular posterior wall thickness of 4.1 mm, as well as fractional shortening of 11.8%.

On Day 1, the dog was treated with oral pimobendan (Pimobe Heart; Kyoritsu Seiyaku, Tokyo, Japan), 0.2 mg/kg BW, PO, q12h; sustained release isosorbide dinitrate (Nitrol R capsule; Eisai, Tokyo, Japan), 1 mg/kg BW, PO, q12h; taurine (Taurine powder 98% “Taisho”; Taisho Pharma., Tokyo, Japan), 500 mg/head, PO, q12h; and torasemide (Luprac; Mitsubishi Tanabe Pharma., Osaka, Japan), 0.15 mg/kg BW, PO, q12h. On Day 34, although echocardiography revealed no improvement in FS (11.9%), LVDd (45.7 mm), LVIDDN (2.55), and LVDs (40.3 mm), the dog showed an improved exercise tolerance; HR was 116 bpm. On Day 74, coughing ceased, and exercise intolerance symptoms were not seen. Radiography revealed no pulmonary edema, pleural effusion, or ascites. The left atrium-to-aortic root diameter ratio decreased to 2.5. However, the ventricular premature complexes increased to 30 bpm. The FS value had slightly decreased, as well as the HR, LVDd, LVIDDN, and LVDs, which were 103 bpm, 44.7 mm, 2.52, and 41.6 mm, respectively.

The prescribed dose of pimobendane, therefore, was increased to 0.36 mg/kg, and carvedilol (Artist; Daiichi Sankyo, Tokyo, Japan), 0.05 mg/kg BW, PO, q12h was added to the treatment regimen. On Day 159, the dog showed no clinical signs, such as dyspnea, cough, syncope, or exercise intolerance, and body weight increased to 7.4 kg, despite the presence of 12% FS. There was no accumulation of ascites or pleural effusion, and the body condition score was 5/9 (14), which was the same as at Day 1. On Day 465, the dog collapsed suddenly while walking. Electrocardiography results revealed atrial fibrillation, and diltiazem hydrochloride (Hemarekeat; Tsuruhara Pharma., Osaka, Japan), 1 mg/kg BW, PO, q8h was prescribed. On Day 502, echocardiography revealed an FS of 14.1%. Although the dog showed no clinical signs, LVDd, LVIDDN, and LVDs were 53.9 mm, 2.95, and 46.3 mm, respectively, and the left ventricular dimensions had worsened. The dog was subsequently followed up by the referring veterinarian. Reportedly, the dog was not brought to the referral animal hospital with clinical signs of heart failure, and cardiac examinations were not performed at the referring practice. The dog was prescribed diltiazem hydrochloride, pimobendan, and torasemide. However, on Day 1087, the dog died suddenly.

Necropsy revealed a heart weight-to-body weight ratio of 13.51 g/kg (RR: 5.8 to 9.4 g/kg) (15). No congenital shunts and congenital aortic and/or mitral dysplasia were identified. The thicknesses of the right ventricular wall, ventricular septum, and left ventricular free wall were 8.0, 8.0, and 6.0 mm, respectively, and dilation of the left ventricle chamber was severe. Histologically, myocardial fibers had an atrophied, attenuated, and wavy appearance. Furthermore, vacuolar degeneration of cardiomyocytes, fatty infiltration, growth of collagen, and mild to moderate edema were also apparent (Figure 4).

Figure 4.

Histological image of the left ventricular myocardium (hematoxylin and eosin staining, 200×) showing attenuated and wavy myocardial fibers with atrophy and thinning. In addition, stromal edema is evident. Bar = 100 μm.

Discussion

Dilated cardiomyopathy is a myocardial disease, characterized by cardiac chamber enlargement, ventricular wall thinning, and decreased contractile function (1,2). Canine DCM mainly affects large-breed dogs and the common age at diagnosis is 6 to 8 y (1). In addition, parvovirus infection, which may cause sudden death or death within a few weeks with gastroenteritis, leukopenia, dehydration, and lethargy, may cause cardiac enlargement in young dogs (16,17).

In this case, the 6-month-old dog was referred to our hospital for evaluation of a cough and exercise intolerance. Echocardiography showed left atrial dilation, left ventricular dilation, and contractile dysfunction. Shunting of blood flow, and hypothyroidism that may cause pathologies similar to DCM were not observed. Parvoviral infection was eliminated as a diagnosis based on the clinical history, clinical presentation, and laboratory findings. The dog was fed a general commercial diet consisting of appropriate calories. Oral taurine administration did not improve left ventricular contraction; therefore, the clinical diagnosis of early-onset idiopathic DCM was established, and the dog was treated medically. In accordance with the histopathological findings at necropsy, the diagnosis was confirmed as a juvenile form of DCM (18).

Dilated cardiomyopathy with early onset of heart failure, reported as juvenile DCM, has only been observed 3 dog breeds: Doberman pinscher, Portuguese water dog, and toy Manchester terrier (3–6). Furthermore, most juvenile dogs with DCM die suddenly without any signs of heart disease or die within a few days due to refractory congestive heart failure (3–6). In a report of Doberman pinschers, 2/6 dogs diagnosed with DCM died of acute pulmonary edema at 10 and 19 d of age, 3 were euthanized at 4 wk of age due to the advanced progression of congestive heart failure, and 1 was euthanized at 11 wk of age due to a decrease in FS (4). A study showed that Portuguese water dogs died suddenly between the ages of 2 and 32 wk after birth or died within 5 d of showing acute left-sided heart failure and no response to medical treatment (5). A report describes that toy Manchester terriers with DCM died suddenly between 10 and 58.3 wk of age (6).

In our case, the clinical course was different from those in previous reports, and the dog survived longer; the treatment included oral pimobendan from Day 1. The dose was increased from 0.2 to 0.36 mg/kg after exercise intolerance recurred. Despite no improvement in echocardiographic findings, clinical signs, such as exercise intolerance, improved and the dog herein survived until the age of 3 y. A previous report suggested that the administration of pimobendan improved the prognosis of a Doberman pinscher with DCM (19).

Genetic predisposition to juvenile DCM has been reported (3,5). Segregation analysis demonstrated that DCM in juvenile Portuguese water dogs is an autosomal recessive disorder (3,5); therefore, a similar gene mutation may exist in Shiba Inu dogs. However, the dog reported in this case could not be followed up for familial information; therefore, we could not ascertain an inherited predisposition. The accumulation of familial and genetic factors and drug responsivity data is necessary to assess the cause and prognosis of a juvenile form of DCM in Shiba Inu dogs. To achieve this, surveys and description of similar cases and their families are required.

This report describes a juvenile case of DCM in a 6-month-old Shiba Inu dog, which had a different clinical course than that previously reported in cases of DCM in young dogs.