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(Circulation. 1995;92:2645-2651.)
© 1995 American Heart Association, Inc.
Articles |
Echocardiographic Assessment of Spontaneously Occurring Feline Hypertrophic Cardiomyopathy
An Animal Model of Human Disease
From the Departments of Medicine and Pathology, The Animal Medical Center, Bobst Hospital and Caspary Research Institute for Veterinary Research (P.R.F., S.K.L.), New York, NY; and Minneapolis Heart Institute Foundation (B.J.M.), Minneapolis, Minn.
Correspondence to Philip R. Fox, DVM, Animal Medical Center, Department of Medicine, 510 E 62nd St, New York, NY 10021.
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Abstract |
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Background Necropsy studies in domestic cats have suggested the occurrence of a primary cardiac disease resembling hypertrophic cardiomyopathy (HCM) in humans. We used two-dimensional echocardiography to define morphological and functional features of HCM during life in 46 domestic cats evaluated in a subspecialty veterinary clinic. Cats were 8 months to 14 years old (mean, 6 years).
Methods and Results During the follow-up period of as long as 49 months, 18 cats died (or were euthanatized) due to congestive heart failure, peripheral embolization, or both, and 3 other cats experienced out-of-hospital sudden, unexpected death. Echocardiography showed a small left ventricular cavity, associated with a variety of patterns of hypertrophy. Wall thickening was most often diffuse (involving ventricular septum and free wall) in 31 cats (67%) and segmental in 15 (33%), including 12 with thickening confined to anterior septum; wall thickening was judged to be asymmetrical in 42 and symmetrical (concentric) in 4. In 30 cats (65%), marked mitral valve systolic anterior motion produced dynamic obstruction to left ventricular outflow (Doppler estimated gradients, 25 to 110 mm Hg). Compared with survivors, cats with HCM that died with heart failure had greater left ventricular thickness (8.1±1.5 versus 7.3±0.9 mm; P<.05) and larger left atria (20.1±4.6 versus 16.8±3.4 mm; P=.01) and more often had the nonobstructive form (89% versus 48%; P<.01).
Conclusions A spontaneously occurring disease of domestic cats was identified by echocardiography and was similar in its phenotypic expression to HCM in humans; it was characterized by unexplained left ventricular hypertrophy in a variety of patterns with or without evidence of outflow obstruction. Unfavorable prognosis was associated with greater magnitude of hypertrophy and absence of outflow obstruction. Feline HCM may prove to be a valuable animal model of the human disease.
Key Words: cardiomyopathy • echocardiography
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Introduction |
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TopAbstractIntroductionMethods Results Discussion References |
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A number of spontaneously occurring animal models of human diseases have been described, including a variety of cardiovascular conditions.1 2 3 4 5 6 7 8 9 In particular, forms of hypertrophic cardiomyopathy (HCM), resembling in many morphological respects the human disease entity, have been reported in necropsy studies of cats,8 9 10 11 dogs,8 9 12 and pigs.3 However, the features of HCM in animals during life and their relation to those in patients with this disease have not been completely defined. The recent introduction of echocardiography into clinical veterinary medicine permitted us to define in some detail the morphological and functional features of the feline form of HCM and to assess its applicability as an animal model for the human disease.
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Methods |
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TopAbstractIntroductionMethods Results Discussion References |
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Selection of Animals
Between July 1990 and July 1992, 143 cats were referred to the Hypertrophic Cardiomyopathy Clinic at the Animal Medical Center (Caspary Research Institute and Bobst Hospital) for evaluation. These animals were suspected of having cardiac disease due most often to the presence of a heart murmur, gallop rhythm, arrhythmias, history of a thromboembolic event, dyspnea or tachypnea, or radiographic evidence of pulmonary congestion. Thirty of these 143 cats were excluded because their echocardiograms were of inadequate technical quality to assess the thickness of all left ventricular wall segments; 67 other cats were excluded on the basis of identification of another disease known to increase left ventricular wall thickness in cats, such as hyperthyroidism, severe systemic hypertension with or without renal insufficiency, or other congenital heart malformations.
The remaining 46 cats were judged to have HCM on the basis of the echocardiographic demonstration of a hypertrophied, nondilated left ventricle in the absence of another cardiac or systemic disease,13 and they constitute the present study group. These 46 cats ranged in age from 8 months to 14 years (mean, 6.1±3.6 years), and 34 (74%) were male. Breeds included 41 domestic short hair, 3 Persian, 1 domestic long hair, and 1 Maine coon. Body weights were 2.8 to 7.4 kg (mean, 4.8±1.1 kg).
Thirty-seven other domestic short-hair cats without structural or functional evidence of cardiovascular disease or dysfunction were selected for echocardiographic study as normal control animals. These animals were 7 months to 15 years old (mean, 5.3±3.1 years); 22 (59%) were male. Body weights ranged from 2.1 to 8.0 kg (mean, 4.3±1.6 kg). Control cats did not differ significantly from those with HCM with regard to age, sex distribution, or body weight.
Echocardiographic Methods
Echocardiographic studies were
performed with a
commercially available Vingmed CFM 700 Sonotron instrument and a 5-mHz
transducer. M-mode, two-dimensional M-mode and Doppler
echocardiographic images were recorded
simultaneously at 100 mm/s on 
-in format
videotape with the subjects unsedated and manually restrained by a
technician.
The ultrasound transducer was introduced from below through a hole in a table specially designed for the echocardiographic imaging of veterinary subjects.14 To achieve the parasternal long- and short-axis views, the cat was imaged in the right lateral decubitus position. The probe was placed in the right fourth or fifth intercostal space with the ultrasound beam directed cephalad and to the left. The two- and four-chamber apical views were obtained with the cat in the left lateral decubitus position with the ultrasound beam directed cephalad, dorsal, and to the left, usually in the left fifth to seventh intercostal spaces near the sternum. This examination was performed to achieve, as closely as possible, the standard cross-sectional planes described in humans.15 M-mode echocardiograms were derived from the two-dimensional images under direct anatomic visualization.16 Measurements of chamber dimensions were made from the M-mode echocardiogram (average of measurements from three to five consecutive cycles).17 The presence and magnitude of mitral regurgitation were graded with the use of color flow imaging.18
Assessment of Left Ventricular
Hypertrophy
To assess the distribution of left ventricular
hypertrophy, the left ventricle as viewed in the
parasternal short-axis plane was divided into four relatively equal
segments: anterior and posterior ventricular septa and
anterolateral and posterior left ventricular free
walls.19 End-diastolic thicknesses (ie, at
maximum cavity dimension) of these four left ventricular
wall segments were measured at both the mitral valve and papillary
muscle levels with the use of a television monitor, calipers, and the
calibration scale produced by the instrument, as previously
described.16 19 Anterior ventricular septal
and posterior free wall thicknesses were derived from an integrated
analysis of the two-dimensional and M-mode
echocardiograms.
The maximum wall thickness measurement within each left ventricular segment was considered to be the thickness for that particular region of the ventricle. In addition, the distribution of left ventricular hypertrophy was assessed in the cephalocaudal (longitudinal) plane. For this purpose, the ventricle was divided into two segments: the proximal (basal) portion extending from the cardiac base to the inferior margins of the mitral leaflets and the distal (apical) portion that includes that portion of the left ventricle visualized caudal to the mitral leaflets.16
A segment of left ventricular wall was judged
to be
hypertrophied if 
6 mm in thickness for >50% of its area. This
cutoff value was selected because it clearly exceeded the greatest wall
thickness measurement attained in any cat in the control group or in
normal domestic cats studied by echocardiography as
reported from other institutions.20
It has not been our clinical practice to perform cardiac catheterization in cats with cardiovascular disease, and therefore we used echocardiography in each animal to assess dynamic outflow obstruction. Obstruction to left ventricular outflow was assessed from the presence and extent (magnitude and duration) of systolic anterior motion of the mitral valve21 and by using continuous-wave Doppler when possible.22 23
Statistical Analysis
Data are expressed as mean±SD
values. Differences between
continuous variables were analyzed with the unpaired
Student's t test. Differences between proportions were
assessed with Fisher's exact test.
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Results |
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TopAbstractIntroductionMethods Results Discussion References |
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Extent and Distribution of Left Ventricular Hypertrophy
In the 46 cats with HCM, the maximal ventricular septal thickness ranged from 3.4 to 12.3 mm (mean, 6.5±1.4 mm). For the group, these thicknesses greatly exceeded that in the normal control animals (3.7±0.7 mm; P<.001) (Table
).
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Four patterns of left ventricular
hypertrophy were identified with two-dimensional
echocardiography (Fig 1). Most often
(31 cats; 67%), hypertrophy was diffuse and substantial,
involving portions of ventricular septum as well as the
contiguous anterolateral and posterior free wall (Fig 1A); 15
of these
31 showed hypertrophy involving all segments of left
ventricle, including 4 that were judged to be concentric in
distribution by virtue of differences in thickness between the thickest
and thinnest left ventricular segments of <2 mm, and 16
others had involvement of the anterior portion of the septum as well as
the anterolateral and posterior free wall (but not posterior septum).
The remaining 15 cats (33%) had segmental patterns of
hypertrophy (Fig 1D). In 13 of these, wall thickening was
confined to one left ventricular segment (anterior septum
in 12 and posterior free wall in 1); in 2 other animals (4%), wall
thickening involved noncontiguous segments of left ventricle, ie,
anterior septum and posterior free wall.
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When viewed in the
longitudinal (cephalocaudal) axis, 26 of the 46 cats
(57%) showed substantially greater wall thickening in the proximal
(basal) portion of left ventricle than in the distal (apical) region
(Fig 1D
); 7 of these cats demonstrated a localized and
prominent area
of proximal septal thickening that protruded into the left
ventricular outflow tract. The other 20 cats (43%) had
wall thickening that was similar in magnitude in the proximal and
distal portions of the left ventricle (Fig 1C), and none showed
hypertrophy confined to or predominant in the apical region
of left ventricle.
Other Cardiac Dimensions
Compared with normal control
animals, the 46 cats with HCM showed
similar left ventricular end-diastolic
dimensions but the end-systolic dimensions were
significantly smaller; consequently, percent fractional shortening in
cats with HCM significantly exceeded that of control animals
(P<.001). Fractional shortening was within normal limits
(30% to 60%) in 39 cats with HCM and hyperdynamic (>60%) in the
other 7. In addition, left atrial size was greater in cats with HCM
than in control animals (P<.001).
Clinical Presentation
At the time of echocardiographic study,
22 cats
(48%) had no apparent signs of cardiac dysfunction and at routine
examination had a cardiac murmur, gallop rhythm, or arrhythmia.
The remaining 24 cats (52%) were initially identified by the clinical
profile of heart failure, including dyspnea, radiographic
evidence of pulmonary congestion or pleural or pericardial
effusion, or acute thromboembolism.
Clinical Course
Of the 46 cats, 3 were lost to follow-up and
43 were followed
for as long as 49 months (mean, 20 months). Eighteen of these 43
animals survived, including 13 that have remained
asymptomatic, 3 that have been treated for congestive
heart failure, and 2 that continue to have syncopal episodes. The
remaining 25 cats died (including 10 who were euthanatized); 4 of these
deaths were due to noncardiac causes. Of the remaining 21 cats that
died of cardiac disease (if the clinical state before euthanasia is
considered), the most common cause of death was congestive heart
failure (in 16); in 7 of these 16 cats, clinical deterioration occurred
in the setting of peripheral thromboembolism to the distal
aortic bifurcation or iliac arteries. Two additional cats who died
presented with peripheral thromboembolism but
without clinical or radiographic evidence of congestion.
The 3 remaining cats experienced out-of-hospital sudden and
unexpected death.
The following analysis of natural history was performed after eliminating the 7 cats that were lost to follow-up or that died of noncardiac causes. Of the 17 cats that were asymptomatic at initial presentation, 13 (76%) have survived; in contrast, of the 22 cats that were symptomatic at presentation, only 5 (23%) survived (P<.001).
Drug Treatment
Of the 46 cats, 32 received cardioactive
medications in
standard dosages during the period of follow-up. Twenty-five of
these cats received either a ß-adrenoceptor–blocking agent
(propranolol or atenolol) and/or a calcium channel
blocker (diltiazem), frequently in combination with a diuretic
(usually furosemide); 7 received diuretics alone. In 10 cats
that developed fulminant and refractory heart failure,
angiotensin-converting enzyme inhibitor
(enalapril) was also administered.
Dynamic Obstruction of Left Ventricular
Outflow
Systolic anterior motion of the mitral valve (SAM) was
identified in 31 (67%) of the 46 cats (Figs 2 and
3). In 30 of these 31 animals, the SAM was marked and
the anterior leaflet appeared to make a sharp-angled bend (Fig
2A and 2C) with the distal tip effecting brief
or prolonged
midsystolic contact with the ventricular septum
(Fig 2B and 2D); the other cat showed milder SAM
without septal
contact. Partial midsystolic closure of the aortic valve
(Fig 3A) was demonstrated in 23 of 25 cats with SAM in which
technically acceptable M-mode images of the aortic valve were
obtained.
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Continuous-wave Doppler assessment of left
ventricular outflow tract obstruction was achieved in 25 of
the 31 cats with SAM; velocities ranged from 2.6 to 5.2 m/s, (estimated
subaortic gradients of 25 to 110 mm Hg). Doppler waveforms
typically showed outflow velocities that increased relatively slowly in
early systole but then rose abruptly and peaked in midsystole,
resulting in the concave and asymmetrically shaped waveform (Fig
3B)
previously described as characteristic of patients with obstructive
HCM.22 23 Cats with and without SAM did not differ
with
regard to maximal left ventricular wall thickness (6.8±1.5
versus 6.1±1.2 mm). SAM also occurred with equal frequency in cats
with diffuse or segmental hypertrophy (21 of 31 [68%]
versus 10 of 15 [67%], respectively).
Each of the 31 cats
with SAM had mitral regurgitation
identified by color flow imaging (mild in 9 and moderate in 22).
Regurgitant jets were typically eccentric and directed toward the
posterior aspect of the left atrial wall (Fig 2E and
2F). Of the 15
cats without SAM, mitral regurgitation was absent in 2,
mild in 7, and moderate in 6.
Predictors of Clinical Outcome
The 18 cats surviving at
follow-up and the 21 nonsurvivors
(with HCM-related death) differed with regard to certain clinical and
morphological features. Nonsurvivors showed greater magnitude and
extent of left ventricular hypertrophy with
more marked maximum wall thickness than survivors (8.1±1.5 versus
7.3±0.9 mm; P<.05) and more diffuse and extensive
distribution of hypertrophy (15 of 21 [71%] versus 10 of
18 [55%]), although this latter difference did not achieve
statistical significance. Nonsurvivors also showed a larger left atrial
dimension (20.1±4.6 mm) than survivors (16.8±3.4 mm;
P=.01). In addition, SAM was more common in survivors (16 of
18 [89%]) than in nonsurvivors (10 of 21 [48%];
P<.01), suggesting that the nonobstructive form of feline
HCM without SAM had a more unfavorable prognosis.
Necropsy Findings
The hearts of 13 of the 46 cats were
available for study at
necropsy (Figs 4 and 5). Each had died or
was euthanatized for reasons associated with their cardiac
disease.
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Gross Anatomy
Heart weight normalized for body
weight (6.0±1.4 g/kg)
significantly exceeded that of a group of 36 normal control animals
(4.8±1.2 g/kg; P=.005).11 In 6 of the 13
cats
(each with SAM on echocardiogram), a fibrous mural endocardial plaque
was present on the basal ventricular septum in
apposition to anterior mitral leaflet, and in 5 of the 6, the anterior
leaflet (Fig 4B) showed fibrous thickening.
Left ventricular wall thicknesses assessed by echocardiography (at end diastole) were compared with values obtained at necropsy in the same areas of the ventricle in 8 cats, and, in each, the anatomic location of maximal wall thickness identified by echocardiography was confirmed in the necropsy specimen (anterior septum in 6 and posterior free wall in 2). Values for left ventricular wall thickness, measured from necropsy specimens (10.4±2.2 mm), exceeded those obtained with echocardiography (8.1±2.2 mm; P=.05).
Histology
Disorganized
cardiac muscle cells24 were present
in left ventricular myocardium from 8 of 13
cats studied at necropsy, and the extent was judged to be mild in 2,
moderate in 4, and marked in 2 (Fig 5A). One or more abnormal
intramural coronary arteries25 with thickened
walls and narrowed lumen were present in septal tissue sections
from 9 of the 13 cats and were particularly prominent in 5 of these
(Fig 5B). Areas of substantial interstitial or replacement
fibrosis25 26 were observed in 8 of the 13 cats,
ranging
in severity from mild (in 3), moderate (in 1), and severe (in 4) (Fig
5C).
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Discussion |
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TopAbstractIntroductionMethods Results Discussion References |
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HCM is a diverse disease entity that has intrigued clinicians and generated intense investigation since its initial description in the late 1950s.27 28 Nevertheless, many questions remain regarding the pathophysiology, clinical course, and morphological evolution of HCM that would undoubtedly benefit from access to an animal model of this disease. There have been a few reports, based in large part on necropsy data, of spontaneously occurring cardiac disease entities in animals such as dogs,8 9 12 cats,8 9 10 11 and pigs3 that resemble HCM in humans.16 24 25 26 27 28 29 30 For many years, we9 10 11 12 and others31 32 33 have been interested in the morphological appearance of a cardiomyopathy in the domestic cat, which incorporates several of the anatomic hallmarks of HCM in humans, including asymmetrical left ventricular hypertrophy, cardiac muscle cell disorganization, abnormal intramural coronary arteries, and myocardial fibrosis. We believe, however, that the present study offers the first comprehensive clinical analysis of the feline model of HCM by virtue of documenting in detail the natural history of this disease entity, its full morphological and functional spectra by echocardiographic demonstration of the patterns of left ventricular hypertrophy and dynamic outflow obstruction, and correlations and validation with necropsy data.
In the present study, we used transthoracic echocardiography to better define the morphological and functional features of this disease, which we have come to regard as the clinical equivalent of HCM in humans,16 24 25 26 27 28 29 30 in a sizable group of cats evaluated in an ambulatory outpatient subspecialty clinic of a major New York City veterinary hospital. Approximately one half of the cats were identified clinically because of the development of congestive heart failure or other cardiovascular events, and the remainder were recognized fortuitously. Morphological profiles, including the patterns of left ventricular hypertrophy, were in many respects closely reminiscent of the phenotypic expression of HCM in humans.16 24 25 26 27 28 29 30 34 35 36 37 For example, most cats had a diffuse but asymmetrical distribution of hypertrophy involving substantial portions of septum and free wall, whereas others demonstrated more segmental patterns of hypertrophy, often with abrupt transitions in wall thickness or involvement of noncontiguous segments of the wall.
It should be pointed out that as a clinical model of human disease, the
domestic cat has potential limitations that are in large part related
to its relatively small body size and the dimensions of the heart (in
particular, left ventricular wall thickness). In an effort
to limit uncertainties that could have an impact on the diagnosis of
HCM in the cat, we chose 6.0 mm as the arbitrary cutoff for the upper
normal limits of wall thickness because this value exceeded the range
of our control animals and that of previously reported normal
populations.20
Approximately two thirds of the cats studied showed a pattern of systolic anterior motion of the mitral valve, typical of patients with HCM.30 38 39 40 In this regard, the mitral leaflets made an abrupt and sharp, right-angled bend with only the distal tip of the anterior leaflet effecting localized contact with the ventricular septum, thereby producing increased left ventricular outflow tract velocities reflecting dynamic subaortic obstruction, as well as mitral regurgitation. Also, our morphological data showed no significant differences between the magnitude and pattern of left ventricular hypertrophy and the obstructive and nonobstructive forms (ie, with and without SAM) of feline HCM. This observation supports the proposition that HCM in cats is a primary form of hypertrophy with its morphological phenotype in large part unrelated to the presence or absence of a hemodynamic burden. This circumstance is virtually identical in the human disease entity of HCM, supporting the important similarities between HCM in cats and humans.16 30 41
There also is considerable evidence in the present study and previous reports10 11 31 32 33 that feline HCM has an important impact on the clinical course of the animals. In our series, almost two thirds of the cats ultimately experienced congestive heart failure with or without peripheral thromboembolism (often progressive and leading to death despite medical treatment), syncope, or sudden cardiac death.
Of note, in our study group, unfavorable prognosis was associated with a more-marked morphological expression of HCM and the absence of mitral valve systolic anterior motion and left ventricular outflow tract obstruction. The cats that died of HCM during the period of follow-up proved to have greater left ventricular wall thickening and left atrial enlargement and more frequently had the nonobstructive form of HCM.
Feline HCM, as described in the present report, is remarkably similar to its HCM counterpart in patients with regard to numerous clinical and pathological features. Consequently, HCM occurring spontaneously in cats would appear to have considerable potential value as an animal model of human disease. Specifically, we believe that our feline model of HCM in humans is a potentially important investigative tool for the study of genetic factors and clinical and pathophysiological mechanisms operative in this disease, as well as the molecular mechanisms responsible for its genesis. At present, however, data are in large part lacking with regard to the genetic basis and transmission of feline HCM.42 Future definition of the heritability of HCM in cats and efforts at breeding would be stimulated by more widespread recognition of this disorder. Such investigations will be crucial to the full development of this animal model of human disease and the ultimate judgment of its research potential.
Received February 27, 1995; revision received May 22, 1995; accepted May 30, 1995.
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References |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
1. Andrews EJ, Ward BC, Altman NH, eds. Spontaneous Animal Models of Human Disease. New York, NY: Academic Press; 1979:41-82.
2. O'Brien SJ, Nash WG, Winkler CA, Reeves RH. Genetic analysis in the domestic cat as an animal model for inborn errors, cancer, and evolution. In: Desnick RJ, Patterson DF, Scarpelli DG, eds. Animal Models of Inherited Metabolic Diseases. Prog Clin Biol Res. 1982;94:67-90.
3. Liu SK, Chiu YT, Shyu JJ, Factor SM, Chu R, Lin JH, Hsou HL, Fox PR, Yang PC. Hypertrophic cardiomyopathy in pigs: quantitative pathologic features in 55 cases. Cardiovasc Pathol. 1994;3:261-268.
4. Bajusz E, Maker JR, Nixon CW, Homburger F. Spontaneous, hereditary myocardial degeneration and congestive heart failure in a strain of Syrian hamsters. Ann N Y Acad Sci. 1969;56:105-129.
5. Smucker ML, Kaul S, Woodfield JA, Keith JC, Manning SA, Gascho JA. Naturally occurring cardiomyopathy in the Doberman pinscher: a possible large animal model of human cardiomyopathy? J Am Coll Cardiol. 1990;16:200-206. [Abstract]
6.
Pion PD, Kittleson MD, Rogers QR, Morris JG.
Myocardial failure in cats associated with low plasma taurine: a
reversible cardiomyopathy.
Science. 1987;237:764-768.
7. Moise NS, Meyers-Wallen V, Flahive WJ, Valentine BA, Scarlett JM, Brown CA, Chavkin MJ, Dugger DA, Renaud-Farrell S, Kornreich B, Schoenborn WC, Sparks JR, Gilmour RF. Inherited ventricular arrhythmias and sudden death in German shepherd dogs. J Am Coll Cardiol. 1994;24:233-243. [Abstract]
8. Van Vleet JF, Ferrans VJ. Myocardial diseases of animals. Am J Pathol. 1986;124:98-178. [Abstract]
9. Liu S-K, Roberts WC, Maron BJ. Comparison of morphologic findings in spontaneously occurring human, feline and canine hypertrophic cardiomyopathy. Am J Cardiol. 1993;72:944-951. [Medline] [Order article via Infotrieve]
10. Tilley LP, Liu SK, Gilbertson SR, Wagner BM, Lord PF. Primary myocardial disease in the cat: a model for human cardiomyopathy. Am J Pathol. 1977;86;493-522.
11. Liu S-K, Maron BJ, Tilley LP. Feline hypertrophic cardiomyopathy: gross anatomic and quantitative histologic features. Am J Pathol. 1981;102:388-395. [Abstract]
12. Liu S-K, Maron BJ, Tilley LP. Hypertrophic cardiomyopathy in the dog. Am J Pathol. 1979;84:497-508.
13. Maron BJ, Epstein SE. Hypertrophic cardiomyopathy: a discussion of nomenclature. Am J Cardiol. 1979;43:1242-1244. [Medline] [Order article via Infotrieve]
14. Moise NS. Echocardiography. In: Fox PR, ed. Canine and Feline Cardiology. New York, NY: Churchill Livingstone; 1988:113-156.
15. Tajik AJ, Seward JB, Hagler DS, Mair DD, Lie JT. Two-dimensional real-time ultrasound imaging of the heart and great vessels: technique, image orientation, structure identification and validation. Mayo Clin Proc. 1978;53:271-303. [Medline] [Order article via Infotrieve]
16. Maron BJ, Gottdiener JS, Epstein SE. Patterns and significance of distribution of left ventricular hypertrophy in hypertrophic cardiomyopathy: a wide-angle, two-dimensional echocardiographic study of 125 patients. Am J Cardiol. 1981;48:418-428.[Medline] [Order article via Infotrieve]
17.
Sahn DJ, DeMaria A, Kisslo J, Weyman A.
Recommendation regarding quantitation in M-mode
echocardiography: results of a survey of
echocardiographic measurements.
Circulation. 1978;58:1072-1083.
18.
Helmcke F, Nanda NC, Hsiung MC, Soto B, Adey CK, Goyal
RG, Gatewood RP. Color Doppler assessment of mitral
regurgitation with orthogonal planes.
Circulation. 1987;75:175-183.
19. Spirito P, Maron BJ. Relation between extent of left ventricular hypertrophy and occurrence of sudden cardiac death in hypertrophic cardiomyopathy. J Am Coll Cardiol. 1990;15:1521-1526. [Abstract]
20. Jacobs G, Knight DH. M-mode echocardiographic measurements in nonanesthetized healthy cats: effects of body weight, heart rate, and other variables. Am J Vet Res. 1985;46:1705-1711. [Medline] [Order article via Infotrieve]
21. Gilbert BW, Pollick C, Adelman AG, Wigle SE. Hypertrophic cardiomyopathy: subclassification by M-mode echocardiography. Am J Cardiol. 1980;45:861-872. [Medline] [Order article via Infotrieve]
22. Panza JA, Petrone RK, Fananapazir L, Maron BJ. Utility of continuous wave Doppler in non-invasive assessment of the left ventricular outflow tract pressure gradient in patients with hypertrophic cardiomyopathy. J Am Coll Cardiol. 1992;19:91-99. [Abstract]
23. Sasson Z, Yock PG, Hatle LK, Aldermann EL, Popp RL. Doppler echocardiographic determination of the pressure gradient in hypertrophic cardiomyopathy. J Am Coll Cardiol. 1988;11:752-756. [Abstract]
24.
Maron BJ, Roberts WC. Quantitative
analysis of cardiac muscle cell disorganization in the
ventricular septum of patients with hypertrophic
cardiomyopathy.
Circulation. 1979;59:689-706.
25. Maron BJ, Wolfson JK, Epstein SE, Roberts WC. Intramural (`small vessel') coronary artery disease in hypertrophic cardiomyopathy. J Am Coll Cardiol. 1986;8:545-557. [Abstract]
26. Factor SM, Butany J, Sole MJ, Wigle ED, Williams WC, Rojkind M. Pathologic fibrosis and matrix connective tissue in the subaortic myocardium of patients with hypertrophic cardiomyopathy. J Am Coll Cardiol. 1991;17:1343-1351. [Abstract]
27. Teare RD. Asymmetrical hypertrophy of the heart in young adults. Br Heart J. 1958;20:1-8.
28. Brock R. Functional obstruction of the left ventricle (acquired subvalvular stenosis). Guys Hosp Rep. 1957;106:221-238. [Medline] [Order article via Infotrieve]
29. Maron BJ, Bonow RO, Cannon RO III, Leon MB, Epstein SE. Hypertrophic cardiomyopathy: interrelation of clinical manifestations, pathophysiology and therapy. N Engl J Med. 1987;316:780-789, 844-852. [Medline] [Order article via Infotrieve]
30. Wigle ED, Sasson Z, Henderson MA, Ruddy TD, Fulop J, Rakowski H, Williams SG. Hypertrophic cardiomyopathy: the importance of the site and the extent of hypertrophy: a review. Prog Cardiovasc Dis. 1985;28:1-83. [Medline] [Order article via Infotrieve]
31. Atkins CE, Gallo AM, Kurzman ID, Cowen P. Risk factors, clinical signs and survival in cats with a clinical diagnosis of idiopathic hypertrophic cardiomyopathy: 74 cases (1985-1989). J Am Vet Med Assoc. 1992;201:613-618. [Medline] [Order article via Infotrieve]
32. Peterson EN, Moise NS, Brown CA, Erb HN, Slater MR. Heterogeneity of hypertrophy in feline hypertrophic heart disease. J Vet Intern Med. 1993;7:183-189. [Medline] [Order article via Infotrieve]
33. Bright JM, Golden L, Gompf RE, Walker MA, Toal RL. Evaluation of the calcium channel-blocking agents diltiazem and verapamil for treatment of feline hypertrophic cardiomyopathy. J Vet Intern Med. 1991;5:272-282. [Medline] [Order article via Infotrieve]
34. Shapiro LM, McKenna WJ. Distribution of left ventricular hypertrophy in hypertrophic cardiomyopathy: a two-dimensional echocardiographic study. J Am Coll Cardiol. 1983;2:437-444. [Abstract]
35.
Ciró E, Nichols PF, Maron BJ.
Heterogeneous morphologic expression of genetically
transmitted hypertrophic cardiomyopathy:
two-dimensional echocardiographic
analysis. Circulation. 1983;67:1227-1233.
36. Klues HG, Schiffers A, Maron BJ. Phenotypic spectrum and patterns of left ventricular hypertrophy in hypertrophic cardiomyopathy: morphologic observations and significance as assessed by two-dimensional echocardiography in 600 patients. J Am Coll Cardio. In press.
37. Spirito P, Maron BJ, Bonow RO, Epstein SE. Severe functional limitation in patients with hypertrophic cardiomyopthy and only mild localized left ventricular hypertrophy. J Am Coll Cardiol. 1986;8:537-544. [Abstract]
38.
Klues HG, Roberts WC, Maron BJ. Morphologic
determinants of echocardiographic patterns of mitral
valve systolic anterior motion in obstructive hypertrophic
cardiomyopathy.
Circulation. 1993;87:1570-1579.
39. Spirito P, Maron BJ. Patterns of systolic anterior motion of the mitral valve in hypertrophic cardiomyopathy: assessment by two-dimensional echocardiography. Am J Cardiol. 1984;54:1039-1046. [Medline] [Order article via Infotrieve]
40. Shah PM, Taylor RD, Wong M. Abnormal mitral valve coaptation in hypertrophic obstructive cardiomyopathy: proposed role in systolic anterior motion of mitral valve. Am J Cardiol. 1981;48:258-262. [Medline] [Order article via Infotrieve]
41.
Spirito P, Maron BJ. Significance of left
ventricular outflow tract cross-sectional area in
hypertrophic cardiomyopathy: a two-dimensional
echocardiographic assessment.
Circulation. 1983;67:1100-1108.
42. Kittleson MD, Pion PD, Mekhamer Y. Hypertrophic cardiomyopathy in a group of highly interrelated Maine coon cats. J Vet Intern Med. 1993;7:117A. Abstract.
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