RADIOGRAPHIC AND ULTRASONOGRAPHIC FEATURES OF HYPERTROPHIC FELINE MUSCULAR DYSTROPHY IN TWO CATS

Hypertrophic fellne musculer dystrophy has been reported as an X-linked inherited deficiency of a cytoskeletal myofiber protein called dystrophin. This report deserlbes the radiographic and ultrasonographic abnormalities of two male littermate domestic short-hair cats and reviews the previous reported findings assoclated with hypertrophic feline muscular dystrophy. The thoracic radiographic abnormalities included: progressive cardiomegaly, large convex, scalloped irregularities associated with the vetral aspect of the diaphragm, and variable degrees of esophageal dilation (megaesophagus) with associated cranioventral aspiration pneumonia. Echocardiographic features included: concentric left vetricular wall thickening, increased left ventricular and diastolic and systolic dimensions, and an increase in endocardial echogenicity. Abdominal radiographic abnormalities included: hepatosplenomegaly, peritoneal effusion, renomegaly, adrenal gland mineralization, and paralumbar and diaphragmatic musculature enlargement. Abdomlnal ultrasonographic abnormalities included: irregularly thickened muscular portion of the diaphragm; hypoechogenicity of the liver; peritoneal effusion; hepatosplenomegaly; renomegaly with hyperechoic cortex and medulla; and adrenal gland mineralization. The irregular scalloped appearance of the diaphragm (particularly along the ventral/sternal margin) was a consistenl radiographic abnormlity in the two cats with hypertrophic feline muscular dystrophy after the age of 7 months. This finding was confirmed by ultrasound as a thickened irregular, hyperechoic diaphragm. A diagnosis of hypertrophic feline muscular dystrophy should be strongly suspected if this abnormality is identified.     

Tissue Doppler imaging for detection of radial and longitudinal myocardial dysfunction in a family of cats affected by dystrophin-deficient hypertrophic muscular dystrophy

Diagnosis of feline hypertrophic cardiomyopathy currently is based on the presence of myocardial hypertrophy detected using conventional echocardiography. The accuracy of tissue Doppler imaging (TDI) for earlier detection of the disease has never been described. The objective of this sudy was to quantify left ventricular free wall (LVFW) velocities in cats with hypertrophic muscular dystrophy (HFMD) during preclinical cardiomyopathy using TDI. The study animals included 22 healthy controls and 7 cats belonging to a family of cats with HFMD (2 affected adult males, 2 heterozygous adult females, one 2.5-month-old affected male kitten, and 2 phenotypically normal female kittens from the same litter). All cats were examined via conventional echocardiography and 2-dimensional color TDI. No LVFW hypertrophy was detected in the 2 carriers or in the affected kitten when using conventional echocardiography and histologic examination, respectively. The LVFW also was normal for 1 affected male and at the upper limit of normal for the 2nd male. Conversely, LVFW dysfunction was detected in all affected and carrier cats with HFMD when using TDI. TDI consistently detects LVFW dysfunction in cats with HFMD despite the absence of myocardial hypertrophy. Therefore, TDI appears more sensitive than conventional echocardiography in detecting regional myocardial abnormalities.     

Electrodiagnostic evaluation in feline hypertrophic muscular dystrophy

Standard needle electromyography (EMG) of 56 muscles and nerve conduction velocities (NCV) of the ulnar and common peroneal nerves were investigated in each of six cats affected with hypertrophic feline muscular dystrophy, 10 related heterozygote carriers and 10 normal cats. The EMG findings were considered normal in carrier and control cats, and consisted of 33% normal readings, 22% myotonic discharges, 18% fibrillation potentials, 11% prolonged insertional potentials, 10% complex repetitive discharges and 6% positive sharp waves in affected cats. Muscles of the proximal limbs were most frequently affected. No differences in NCV were found between the three cat groups. It was concluded that dystrophin-deficient dystrophic cats have widespread and frequent EMG changes, predominantly myotonic discharges and fibrillation potentials, which are most pronounced in the proximal appendicular muscles.     

Hypertrophic muscular dystrophy in a young dog

Hypertrophic muscular dystrophy was diagnosed in a 10-month-old male Rat Terrier with hypersalivation, dysphagia, gait abnormalities, and generalized weakness. Serum creatine kinase activity was high, and electromyography revealed myotonic discharges. Histologic examination of a muscle biopsy specimen revealed muscle fiber degeneration, clusters of basophilic regenerating fibers, and endomysial fibrosis. Staining for dystrophin, a sarcolemmal protein, was decreased, compared with that in muscle specimens from clinically normal dogs. Treatment with mexilitene hydrochloride and procainimide hydrochloride resulted in temporary improvement in clinical signs, but the disease became refractory to treatment, and the dog was euthanatized. Clinical and histologic characteristics of this dystrophin deficiency-related muscular dystrophy were similar to those of X-linked muscular dystrophy in dogs, hypertrophic muscular dystrophy in cats, and Duchenne muscular dystrophy in humans.     

M-MODE ECHOCARDIOGRAPHY AS A DIAGNOSTIC AID FOR FELINE CARDIOMYOPATHY

Normal cats and cats with congestive cardiomyopathy (CCM) and hypertrophic cardiomyopathy (HCM) were examined using M-mode echocardiography to determine its diagnostic capabilities. Sixteen normal cats were examined to verify previously reported data and to add further echocardiographic inforamtion (left atrial/aortic root ratio, left posterior wall thickness at end systole and end diastole, amplitude of mitral valve excursions, and velocity of valve opening and closure) to aid in differential diagnosis. Significant (p<0.05) changes were detected between the normal cats and those with cardiomyopathy. In each type of cardiomyopathy, alterations in left atrial dimension, left atrial/aortic root ratio, left ventricular dimension, left ventricular wall thickness and percentage of ventricular dimensional change were identified. Altered mitral valve motion was found with HCM. Echocardiography was found to be an accurate technique for definitive diagnosis of feline cardiomyopathy.     

Myocardial collagen deposition and inflammatory cell infiltration in cats with pre-clinical hypertrophic cardiomyopathy

The histological features of feline hypertrophic cardiomyopathy (HCM) have been well documented, but there are no reports describing the histological features in mild pre-clinical disease, since cats are rarely screened for the disease in the early stages before clinical signs are apparent. Histological changes at the early stage of the disease in pre-clinical cats could contribute to an improved understanding of disease aetiology or progression. The aim of this study was to evaluate the histological features of HCM in the left ventricular (LV) myocardium of cats diagnosed with pre-clinical HCM. Clinically healthy cats with normal (n = 11) and pre-clinical HCM (n = 6) were identified on the basis of echocardiography; LV free wall dimensions (LVFWd) and/or interventricular septal wall (IVSd) dimensions during diastole of 6–7 mm were defined as HCM, while equivalent dimensions <5.5 mm were defined as normal. LV myocardial sections were assessed and collagen content and inflammatory cell infiltrates were quantified objectively. Multifocal areas of inflammatory cell infiltration, predominantly lymphocytes, were observed frequently in the left myocardium of cats with pre-clinical HCM. Tissue from cats with pre-clinical HCM also had a higher number of neutrophils and a greater collagen content than the myocardium of normal cats. The myocardium variably demonstrated other features characteristic of HCM, including arteriolar mural hypertrophy and interstitial fibrosis and, to a lesser extent, myocardial fibre disarray and cardiomyocyte hypertrophy. These results suggest that an inflammatory process could contribute to increased collagen content and the myocardial fibrosis known to be associated with HCM.     

Colour M-mode tissue Doppler imaging in healthy cats and cats with hypertrophic cardiomyopathy

OBJECTIVES: To determine whether decreased diastolic and systolic myocardial velocity gradient between the endocardium and the epicardium exist in the left ventricle of cats with hypertrophic cardiomyopathy. METHODS: Myocardial velocity gradient and mean myocardial velocities were measured by colour M-mode tissue Doppler imaging in the left ventricular free wall of 20 normal cats and 17 cats with hypertrophic cardiomyopathy. RESULTS: The peak myocardial velocity gradient (sec(-1)) during the first (E1) (5.71+/-1.75 versus 11.38+/-3.1, P<0.001) and second phase (E2) (3.09+/-1.53 versus 7.02+/-3.1, P=0.005) of early diastole and also the maximum early diastolic myocardial velocity gradient (Emax) (6.12+/-2.1 versus 10.76+/-3.2, P<0.001) were reduced in cats with hypertrophic cardiomyopathy compared with normal cats. Peak myocardial velocity gradient during early systole (Se) was lower in affected cats than in normal cats (6.26+/-2.08 versus 8.67+/-2.83, P=0.006). Affected cats had a lower peak mean myocardial velocities (mm/s) during the two isovolumic periods (IVRb and IVCb) compared with normal cats (2.97+/-6.76 versus 12.74+/-5.5 and 22.28+/-9.96 versus 38.65+/-10.1, P<0.001, respectively). CLINICAL SIGNIFICANCE: This study shows that hypertrophic cardiomyopathy cats have decreased myocardial velocity gradient during both diastole and systole and also altered myocardial motion during the two isovolumic periods. Myocardial velocity gradients recorded by colour M-mode tissue Doppler imaging can discriminate between the healthy and diseased myocardium.     

Hypertrophic feline muscular dystrophy: diagnostic overview and a novel immunohistochemical diagnostic method using formalin-fixed tissue

This paper describes a case of hypertrophic feline muscular dystrophy (HFMD) in the UK. The cat under investigation died unexpectedly following routine vaccination, and postmortem investigation revealed myopathy, particularly affecting the diaphragm as well as multiple skeletal muscles. The right lung lobes were also partially collapsed and this was considered secondary to the effect of the muscular dystrophy. Pathological and immunohistochemical findings are described, macroscopic and microscopic findings are compared with other recorded cases in the literature and a diagnostic overview of HFMD is given. Possible causes of death are also discussed and a novel immunohistochemical method of demonstrating dystrophin deficiency using formalin-fixed tissue is described.     

Excessive moderator bands in the left ventricle of 21 cats

Excessive numbers of moderator bands bridging the left ventricular septum and free wall and entangling papillary muscles were associated with heart failure and death in 21 cats. Clinical findings included dyspnea, anorexia, hypothermia, cardiomegaly, pleural effusion, plumonary edema, heart murmurs, gallop rhythm, electrocardiographic abnormalities (especially conduction disturbances), increased left ventricular end-diastolic pressure, angiocardiographic evidence of left ventricular restriction, and aortic thromboembolism. Pathologic changes included a morphologically distinct network of abnormal numbers of moderator bands in the left ventricle, left ventricular hypertrophy (younger cats--mean age, 4 years) or dilatation (older cats--mean age, 8.7 years), left atrial enlargement and hypertrophy, and pulmonary edema with heart failure cells in the alveoli. Heart weights of affected cats were significantly less than those of cats with congestive, hypertrophic, and restrictive cardiomyopathy (endocardial fibrosis), but were not significantly less than heart weights of clinically normal cats. Pathologic changes were characteristic of the syndrome grossly and histologically, but clinical findings were not clearly definable.     

Naturally Occurring Biventricular Noncompaction in an Adult Domestic Cat

A definitively diagnosed case of left ventricular noncompaction (LVNC) has not been previously reported in a non‐human species. We describe a Maine Coon cross cat with echocardiographically and pathologically documented LVNC. The cat was from a research colony and was heterozygous for the cardiac myosin binding protein C mutation associated with hypertrophic cardiomyopathy (HCM) in Maine Coon cats (A31P). The cat had had echocardiographic examinations performed every 6 months until 6 years of age at which time the cat died of an unrelated cause. Echocardiographic findings consistent with LVNC (moth‐eaten appearance to the inner wall of the mid‐ to apical region of the left ventricle (LV) in cross section and trabeculations of the inner LV wall that communicated with the LV chamber) first were identified at 2 years of age. At necropsy, pathologic findings of LVNC were verified and included the presence of noncompacted myocardium that consisted of endothelial‐lined trabeculations and sinusoids that constituted more than half of the inner part of the LV wall. The right ventricular (RV) wall also was affected. Histopathology identified myofiber disarray, which is characteristic of HCM, although heart weight was normal and LV wall thickness was not increased.     

Morphology and Classification of Right Ventricular Bands in the Domestic Dog (Canis familiaris)

Ventricular bands, also designated as ‘false tendons’, are described as single or multiple strands that cross the ventricles and have no connection to valvular cusps. Previous work indicates these strands are present in the ventricles of humans and some animal hearts and not always associated with cardiac pathologies. Despite these previous studies, the published literature is limited in documenting the morphology of these strands and incidence in animals. In this study, examination of 89 hearts showed six types of ventricular bands in the right ventricle of the domestic dog. These bands were classified according to their prevalence and points of attachment. Type I extended from the interventricular septum to the ventricular free wall, type II connected a musculus papillaris parvus to the ventricular free wall and type III connected trabeculae carneae on the interventricular septum. Type IV connected the trabeculae carneae on the ventricular free wall, type V interconnected papillary muscles and type VI connected the interventricular septum to a papillary muscle. While the study of these ventricular bands provided additional information on the cardiac anatomy of the domestic dog, it also showed their clinical importance. Several studies have proposed that their position in the ventricle may interfere with cardiac catheterization and pacemaker lead placement or be misinterpreted during echocardiography.     

Pulsed tissue Doppler imaging in normal cats and cats with hypertrophic cardiomyopathy

Myocardial motion was quantified in normal cats (n = 25) and cats with hypertrophic cardiomyopathy (HCM) (n = 23) using the pulsed tissue Doppler imaging (TDI) technique. A physiologic nonuniformity was documented in the myocardial motion of normal cats, which was detected as higher early diastolic velocities, acceleration, and deceleration in the interventricular septum compared with the left ventricular free wall (LVFW). HCM cats exhibited lower early diastolic velocities, acceleration, and deceleration and also prolonged isovolumic relaxation time compared with normal cats. These differences were detected mainly along the longitudinal axis of the heart. A cutoff value of E' in the LVFW along the longitudinal axis >7.2 cm/s discriminated normal from HCM cats with a sensitivity of 92% and a specificity of 87%. The physiologic nonuniformity of myocardial motion during diastole was lost in affected cats. Systolic impairment (decreased late-systolic velocities in most segments along the longitudinal axis and decreased early systolic acceleration in both mitral annular sites) was evident in HCM cats irrespective of the presence of left ventricular outflow tract obstruction and congestive heart failure. Postsystolic thickening was recorded in the LVFW along the longitudinal axis only in affected cats (n = 6) and was another finding indicative of systolic impairment in the HCM of this species. This study identified both diastolic and systolic impairment in cats with HCM compared with normal cats. The study also documents the normal physiologic nonhomogeneity in myocardial motion in cats and the subsequent loss of this feature in the HCM diseased state.     

Measurement of M-mode echocardiographic parameters in healthy adult Maine Coon cats

OBJECTIVE: To determine reference values for M-mode echocardiographic parameters in nonsedated healthy adult Maine Coon cats and compare those values with data reported for nonsedated healthy adult domestic cats. DESIGN: Prospective study. ANIMALS: 105 healthy adult Maine Coon cats. PROCEDURE: Over a 3-year period, M-mode echocardiographic examinations (involving a standard right parasternal transthoracic technique) were performed on Maine Coon cats as part of prebreeding evaluations; values of M-mode parameters in healthy individuals were collected, and mean values were calculated for comparison with those reported for healthy adult domestic cats. RESULTS: The mean +/- SD weight of Maine Coon cats was significantly greater than that of domestic cats. Mean values of left ventricular internal dimension at end diastole and end systole (LVIDd and LVIDs, respectively), interventricular septal thickness at end systole (IVSs), left ventricular posterior wall thickness at end systole (LVPWs), left atrial dimension at end systole (LADs), and aortic root dimension (Ao) in Maine Coon cats differed significantly from values in healthy domestic cats. The greatest differences detected between the 2 groups involved values of LVIDd, LADs, and Ao. Linear regression analysis revealed a weak but significant correlation between weight and each of LVIDd, LVPWs, IVSs, Ao, LADs, and left ventricular posterior wall thickness at end diastole. CONCLUSIONS AND CLINICAL RELEVANCE: Values of several M-mode echocardiographic parameters in Maine Coon cats differ from those reported for domestic cats; these differences should be considered during interpretation of echocardiographic findings to distinguish between cardiac health and disease in this breed.     

Effect of amlodipine on echocardiographic variables in cats with systemic hypertension

Left ventricular hypertrophy signals a poor prognosis in hypertensive humans. Cardiac disease is common in cats with systemic hypertension. The aims of this study were to characterize the echocardiographic findings of cats with systemic hypertension and to determine if reducing the degree of hypertension is associated with resolution of cardiac hypertrophy. Echocardiographic examinations were performed on 19 cats with naturally occurring systemic hypertension. Fourteen of these cats were subsequently studied after a minimum of 3 months of treatment with the antihypertensive agent amlodipine. Hypertensive cats had a significantly thicker interventricular septum in both systole and diastole, thicker left ventricular free wall in both systole and diastole, and larger left atrium compared to the published normal values and 74% (14/19) of the cats met criteria for left ventricular hypertrophy (diastolic septal or free-wall thickness > 0.60 cm). Systolic blood pressure was lower after treatment (217 +/- 25 mm Hg, range: 180-275 mm Hg; and 142 +/- 27 mm Hg, range: 90-200 mm Hg). No difference was found in any of the echocardiographic measurements between the untreated and treated cats, although more cats had ventricular hypertrophy before treatment (11/14) than after initiating amlodipine (6/14; P = .006). Ventricular hypertrophy is common in hypertensive cats and may resolve after the initiation of amlodipine.     

Assessment of Left Ventricular Systolic Function by Strain Imaging Echocardiography in Various Stages of Feline Hypertrophic Cardiomyopathy

Background: Diastolic dysfunction occurs in many cats with hypertrophic cardiomyopathy (HCM). Less is known about systolic function in various stages of HCM. Myocardial strain analysis by tissue Doppler imaging (TDI) is a noninvasive echocardiographic method to assess systolic function that has not been reported previously in cats. Objectives: To evaluate systolic function in various stages of feline HCM by measurement of myocardial strain. Animals: Two hundred and sixty‐three cats. Methods: Cats were classified by echocardiography into one of the following groups: clinically healthy (control) group (n = 160), mild HCM (n = 22), moderate HCM (n = 39), and severe HCM (n = 42). Peak myocardial strain, measured by TDI in the basal and midventricular segment of the interventricular septal wall (IVS) and the left ventricular posterior wall (LVPW), was compared among different HCM and control groups. Results: Whereas conventional echocardiography demonstrated an apparently normal or supernormal contractile state based on percentage of fractional shortening, myocardial strain in all HCM groups was significantly decreased compared with the control group (P < .001). There was a significant correlation between strain values and wall thickness (P < .001). Reproducibility of strain analysis was 6.3% in the IVS and 9.7% in the LVPW. Conclusions and Clinical Importance: Myocardial strain analysis is a new, valuable, and reproducible method in cats. This method allows noninvasive detection of abnormal systolic deformation in cats with HCM despite apparently normal left ventricular systolic function as assessed by conventional echocardiography. The abnormal systolic deformation already was present in mild HCM and increased with progressive left ventricular concentric hypertrophy.     

M-MODE ECHOCARDIOGRAPHIC REFERENCE VALUES IN CATS IN THE FIRST THREE MONTHS OF LIFE

Thirty-five young cats were studied by echocardiography from the 2nd to 12th weeks of life to analyze correlation between body weight, body surface area, age and heart rate with fourteen echocardiographic parameters. There was a positive linear correlation (r = 0.49-0.78) between the independent variables (body weight, body surface area, age) and left ventricular wall thickness and diameter, aortic diameter and left atrial diameter, whereas there was a negative correlation (r = -0.39 and r = -0.43) between the heart rate and left ventricular diameter during systole and diastole. No linear dependence of the fractional shortening, ejection fraction, percentage thickening of the interventricular septum and left ventricular posterior wall, LA/AO ratio, and the ratio IVSED/LVWED to the independent variables was observed.     

Papillary muscle measurements in cats with normal echocardiograms and cats with concentric left ventricular hypertrophy

BACKGROUND: Papillary muscle hypertrophy can occur in conjunction with, or as the only indication of, hypertrophic cardiomyopathy or other diseases that result in left ventricular concentric hypertrophy (LVCH). Assessment of papillary muscle size is usually subjective because objective measures have not been reported. HYPOTHESIS: The study hypothesis was that papillary muscle dimensions are different between normal cats and cats with LVCH. ANIMALS: Echocardiograms from 44 normal cats and 40 cats with LVCH were included in the study. METHODS: All measurements were taken from the right parasternal short-axis view at the level of the papillary muscles at end-diastole. Three methods were used to assess papillary muscle size: the area subtraction method, the direct area trace method, and the diameter method. Measurements were compared between cat groups and method comparisons were made among methods for area determination. RESULTS: Cats with LVCH were older and had significantly greater left ventricular septal and free wall thicknesses and larger left atrial measurements than normal cats (P < .0006). Papillary muscle measurements were significantly greater by all measurement methods in cats with LVCH than in cats with normal echocardiograms (P < .0001). The area subtraction method and direct area trace method showed moderate agreement. CONCLUSIONS AND CLINICAL IMPORTANCE: Papillary muscle measurements were larger for LVCH cats than normal cats; however, some overlap was present. The establishment of these objective measures adds to the echocardiographic examination of cats.     

Muscular dystrophy in female dogs

The most common form of muscular dystrophy in dogs and humans is caused by mutations in the dystrophin gene. The dystrophin gene is located on the X chromosome, and, therefore, disease-causing mutations in dystrophin occur most often in males. Therefore, females with dystrophin deficiency or other forms of muscular dystrophy may be undiagnosed or misdiagnosed. Immunohistochemistry was used to analyze dystrophin and a number of other muscle proteins associated with muscular dystrophy in humans, including sarcoglycans and laminin alpha2, in muscle biopsy specimens from 5 female dogs with pathologic changes consistent with muscular dystrophy. The female dogs were presented with a variety of clinical signs including generalized weakness, muscle wasting, tremors, exercise intolerance, gait abnormalities, and limb deformity. Serum creatine kinase activity was variably high. One dog had no detectable dystrophin in the muscle; another was mosaic, with some fibers normal and others partly dystrophin-deficient. A 3rd dog had normal dystrophin but no detectable laminin alpha2. Two dogs could not be classified. This study demonstrates the occurrence of dystrophin- and laminin alpha2-associated muscular dystrophy and the difficulty in clinical diagnosis of these disorders in female dogs.     

Echocardiography, electrocardiography, and radiography of cats with dilatation cardiomyopathy, hypertrophic cardiomyopathy, and hyperthyroidism

The echocardiographic, ECG, and radiographic findings of sequentially examined cats with dilatation cardiomyopathy (DCM, n = 7), hypertrophic cardiomyopathy (HCM, n = 8), and hyperthyroidism (HT, n = 20) were compared with those of healthy control cats (n = 11). Cats with DCM were easily differentiated from healthy cats by echocardiography and from cats with HCM and HT by a dilated left ventricle at end-diastole with a mean +/- SD of 2.20 +/- 0.36 cm, reduced fractional shortening (2.9% +/- 3.7%), reduced aortic amplitude (0.07 +/- 0.05 cm), reduced left ventricular wall amplitude (0.09 +/- 0.09 cm), and increased E-point septal separation (0.83 +/- 0.29 cm). The cats with HCM were most consistently recognized echocardiographically by increased left ventricular wall thickness at end-diastole (0.75 +/- 0.12 cm). Some cats with HT had abnormal echocardiograms with left ventricular wall hypertrophy. These cats could usually be differentiated from the cats with HCM because of normal or increased ventricular wall amplitude, aortic amplitude, or percentage of thickening of the left ventricular wall and interventricular septum. Left atrial enlargement (left atrial diameter greater than 1.57 cm or left atrium/aorta greater than 1.75) was commonly detected by the echocardiogram in cats with DCM, HCM, or HT. The echocardiogram was helpful in differentiating the type of cardiomyopathy (DCM, HCM, or HT) when plain thoracic radiographs indicated that cardiomegaly existed. The ECG may have indicated incorrectly that there was left ventricular enlargement in some cats with HT, and it did not indicate consistently that left ventricular enlargement existed when present in cats with DCM or HCM. The ECG was a poor indicator of left atrial enlargement in all cats.