Tissue Doppler Imaging in Maine Coon Cats with a Mutation of Myosin Binding Protein C with or without Hypertrophy
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J Vet Intern Med 2007;21:232–237
Tissue Doppler Imaging in Maine Coon Cats with a Mutation of
Myosin Binding Protein C with or without Hypertrophy
Kristin A. MacDonald, Mark D. Kittleson, Philip H. Kass, and Kathryn M. Meurs
Background: The cardiac myosin binding protein C gene is mutated in Maine Coon (MC) cats with familial hypertrophic
cardiomyopathy.
Hypotheses: Early diastolic mitral annular velocity is incrementally reduced from normal cats to MC cats with only an
abnormal genotype to MC cats with abnormal genotype and hypertrophy.
Animals: Group 1 consisted of 6 normal domestic shorthair cats, group 2 of 6 MC cats with abnormal genotype but no
hypertrophy, and group 3 of 15 MC cats with hypertrophy and abnormal genotype.
Methods: The genotype and echocardiographic phenotype of cats were determined, and the cats were divided into the 3
groups. Tissue Doppler imaging (TDI) of the lateral mitral annulus from the left apical 4-chamber view was performed. Five
nonconsecutive measurements of early diastolic mitral annular velocity (EM) or summated early and late diastolic velocity
(EAsum) and heart rate were averaged.
Results: There was an ordered reduction in Em-EAsum as group number increased (group 1, range 9.7–14.7 cm/s; group 2,
range 7.5–13.2 cm/s; group 3, range 4.5–14.1 cm/s; P 5 .001). Using the lower prediction limit for normal Em-EAsum, the
proportion of cats with normal Em-EAsum decreased as the group number increased (P 5 .001). However, Em-EAsum was
reduced in only 3 of 6 cats in group 2.
Conclusion: The incremental reduction of Em-EAsum as group severity increased indicates that diastolic dysfunction is an
early abnormality that occurs before hypertrophy development. TDI measurement of Em or EAsum of the lateral mitral
annulus is an insensitive screening test for identification of phenotypically normal, genotypically affected cats.
Key words: Diastolic function; Genotype; Phenotype; Hypertrophic cardiomyopathy.
ypertrophic cardiomyopathy (HCM) is the most TDI echocardiography has emerged as one of the
H common heart disease of cats and is inherited as
an autosomal dominant trait in a family of Maine Coon
most sensitive and specific methods for noninvasive
assessment of diastolic function and is relatively un-
cats.1 The causative mutation of HCM in this family of affected by loading conditions.7 Diastolic function is
Maine Coon cats is a missense mutation in the most commonly assessed by measuring the early di-
sarcomeric protein myosin binding protein C gene astolic velocity of the mitral annulus (Em).8–11 Em is
(MYBPC3), that results in a change from the conserved reduced in cats with HCM when compared to normal
amino acid alanine to proline, thus altering protein cats.6,10 Em also correlates with invasive measurements
conformation.2 Myosin binding protein C is located at of diastolic function in cats.12 Potential pathophysiologic
the transverse band within the A band of the sarcomere consequences of severe HCM and diastolic dysfunction
and attaches to titin and B-myosin heavy chain. It is include development of congestive heart failure and
believed to have both structural and regulatory roles.3 systemic thromboembolism.
Mutations in MYBPC3 are the most common cause Population screening and early recognition of HCM
of familial HCM in people, and occur in 14–26% of has become important in human medicine and in certain
familial cases.4 Incomplete penetrance is common with breeds of cats that appear predisposed to HCM. Until
mutations in this gene, often making echocardiographic now, HCM diagnosis in cats was dependent on
diagnosis of HCM difficult in heterozygous individuals.3 identification of left ventricular concentric hypertrophy
Maine Coon cats with HCM develop concentric by echocardiography in the absence of other diseases
hypertrophy, myofiber disarray, interstitial and replace- that cause hypertrophy. The use of a genetic screening
ment fibrosis, and possibly left atrial enlargement.1 test for the mutation of MYBPC3 is useful to identify
Systolic anterior motion of the mitral valve is common. genotypically affected Maine Coon cats within this
Cats with HCM have impaired relaxation and diastolic colony.2 However, there are no genotypic screening tests
dysfunction evident on traditional echocardiography for familial HCM in purebred cats other than Maine
and tissue Doppler imaging (TDI) echocardiography.5,6 Coon cats. Because there are more than 200 mutations
of 10 sarcomeric genes in people, it is likely that each
From the Departments of Medicine and Epidemiology (MacDo- breed will have a different mutation and identifying
nald, Kittleson) and Population Health and Reproduction (Kass), them will be a long and laborious process.13 Therefore,
School of Veterinary Medicine, University of California, Davis, identification of left ventricular concentric hypertrophy
Davis, CA; and the Department of Veterinary Clinical Sciences, by echocardiography will remain the fundamental basis
College of Veterinary Medicine, Washington State University, of diagnosis of HCM in cats for some time. However,
Pullman, WA (Meurs). TDI echocardiography might be a useful earlier
Reprint requests: Kristin MacDonald, Animal Care Center of screening modality to identify diastolic and systolic
Sonoma, 6470 Redwood Dr., Rohnert Park, CA 94928; e-mail:
abnormalities in familial HCM before development of
kamacdonald@ucdavis.edu.
Submitted November 30, 2005; Revised May 4, 2006, September
concentric hypertrophy because it is abnormal in
27, 2006; Accepted November 7, 2006. humans and other animal models before the develop-
Copyright E 2007 by the American College of Veterinary Internal ment of left ventricular wall thickening.14,15
Medicine The hypothesis of the study was that cats with the
0891-6640/07/2102-0005/$3.00/0 identified mutation of MYBPC3 without phenotypicTDI in Cats with cMyBP-C 233
Fig 1. Pulsed-wave tissue Doppler imaging (TDI) in normal cats and cats with hypertrophic cardiomyopathy. Pulsed-wave TDI was
performed at the lateral mitral annulus using a left apical 4-chamber view with the gate placed perpendicular to the motion of the heart (A).
TDI of a normal cat in group 1 shows fusion of the early and late diastolic velocities into a single EAsum wave, and there was a rapid heart
rate of 220 bpm (B). TDI of a Maine Coon cat with severe hypertrophic cardiomyopathy without heart failure in group 3, showing reduced
Em velocity and E : A reversal, which indicate diastolic dysfunction, and there was a slow heart rate of 104 bpm (C). EA, summated early
and late diastolic velocity wave; S, systolic wave; Em, early diastolic mitral annular velocity, A, late diastolic mitral annular velocity.
evidence of hypertrophy have diastolic dysfunction cuts specifically at a GGCC region, and incubated at 37uC for
when assessed by TDI echocardiography. Specific aims 2 hours. The affected cats have a mutation that replaces the second
were to determine if there was an ordered decrease in G and prevents the enzyme from cutting an appropriate sized
diastolic function from normal cats to cats with the fragment compared to normal cats. Sixteen microliters of the
sample was run on a polyacrylamide gel for 45 minutes to 1hour at
mutation but no hypertrophy to cats with the mutation
250 V. The gel was placed into an ethidium bromide solution for
and hypertrophy, and to determine if measurement of
5 minutes, rinsed in distilled water for 5 minutes, and viewed under
early diastolic mitral annular velocity was a useful ultraviolet light to evaluate the fragment sizes. Unaffected cats
means of screening cats without hypertrophy for the were identified by the presence of 50 and 55 base pair sized
mutation. fragments, affected cats were identified by the presence of 50 and
75 base pair fragments.
Materials and Methods Samples from affected cats were subsequently genotyped by
sequencing on an ABI377 sequencer,b and the sequence was
Study Population evaluated to determine if they were heterozygous (G/CCC) or
This study consisted of normal domestic shorthair (DSH) cats homozygous (CCC) for the mutation.2
(group 1), Maine Coon cross cats with the MYBPC3 mutation in the
absence of left ventricular hypertrophy (group 2), and Maine Coon Echocardiography
cats and Maine Coon cross cats with the MYBPC3 mutation and left
ventricular hypertrophy (group 3). Group 1 cats were normal DSH Standard echocardiography was performed on all affected cats
cats residing within another research colony and were unrelated to while sedated with 0.1 mg/kg acepromazine and 0.1 mg/kg hydro-
the Maine Coon and Maine Coon cross cats. Unrelated DSH cats morphone SC.c A left ventricular free wall end diastolic thickness
were chosen for group 1 because Maine coon cats and Maine coon (LVFWd) or an interventricular septal end diastolic thickness
cross cats residing in the HCM colony could not be declared as (IVSd) .6 mm was defined as abnormal. Left atrial and aortic
normal based on a normal genotype for MBYPC3. There is another diameters were measured by 2-dimensional echocardiography of
mutation within the colony that causes HCM, and the mutation has the right parasternal short-axis basilar view, and left atrial dilation
yet to be defined. Therefore, it was necessary to use unrelated DSH was defined as the ratio of left atrium to aortic diameter (LA:Ao)
cats in the control group. Maine Coon cats and Maine Coon cross $1.5. Systolic blood pressure was measured in all cats with
cats in group 2 and group 3 live in a research colony of cats with concentric hypertrophy and had to be within the normal range of
familial hypertrophic cardiomyopathy. This numbering was em- ,160 mmHg for a cat to be included in the study.d The metatarsal
ployed to indicate the ordering of relative severity of clinical disease region of one hind limb of each cat was shaved, and a 3-cm cuff
among groups in this study population. was placed above the tarsus. Serial blood pressure measurements
were made for 5 minutes, and the lowest consistent value obtained
in 3 measurements was chosen.
Mutational Analysis
Two milliliters of blood was collected from Maine Coon cats Tissue Doppler Imaging
residing in a familial HCM research colony. DNA was extracted
from peripheral lymphocytes from all cats as previously de- Pulsed-wave TDI of the lateral mitral annulus from the left-
scribed.16 An oligonucleotide was designed for amplification of apical 4-chamber view was performed using a 12-MHz probe, with
exon 3 of the MYBPC3 gene in cats, using known human the pulsed-wave Doppler gate placed perpendicular to myocardial
sequences (GenBank U91629) and Primer3 software.17 The exon motion (Fig 1).c Specific TDI settings included: Nyquist limit 10–
was amplified at 95uC (5 minutes) followed by 40 cycles of 94uC 15 cm/s; sweep speed 100 cm/s; gate width 0.11 cm; and filter
(20 seconds), 57uC (20 seconds), and 74uC (39 seconds). The 50 Hz. Heart rate (HR) was measured by an electrocardiogram.
polymerase chain reaction product was run on an agarose gel, Five nonconsecutive measurements of Em or summated early and
cut from the gel, and purified with the QiaQuick kit.a Restriction late diastolic velocity (EAsum) of the lateral mitral annulus were
enzyme digests were performed to confirm the identification of the recorded and averaged (Fig 1). The HRs of the 5 nonconsecutive
mutation by running 10 mL of the sample combined with 3-mL measurements were also averaged. Early and late diastolic mitral
HaeIII buffer, 5.5-mL water, and 1.5-mL HaeIII, an enzyme that annular velocity waves fuse when there are high HRs, preventing234 MacDonald et al
Table 1. Echocardiographic measurements of normal domestic shorthair cats (group 1), Maine Coon cats and
Maine Coon cross cats with myosin binding protein C mutation and no left ventricular hypertrophy (group 2), or with
hypertrophy (group 3).
Group 1 (n 5 6) Group 2 (n 5 6) Group 3 (n 5 15)
2Genotype +Genotype +Genotype
Echocardiographic 2Phenotype 2Phenotype +Phenotype
Measurement Median (Range) Median (Range) Median (Range)
LVFWd (mm) 4.8 (4–5.3) 4.7 (4–5.1) 6.6 (4.7–7.8)
IVSd (mm) 5.7 (4–6) 4.5 (3.8–5.3) 6.3 (4.1–7.6)
Em (cm/s) 11.6 (9.7–14.7) 8.4 (7.5–13.2) 7.7 (4.5–14.1)
HR (beats/min) 204 (143–260) 172 (157–244) 175 (101–256)
LVFWd, left ventricular free wall end diastolic thickness; IVSd, interventricular septal end diastolic thickness; Em, early diastolic mitral
annular velocity; HR, heart rate.
the measurement of individual Em waves in many cats (Fig 1B). cats with the MYBPC3 mutation. Median values of wall
The tracings that were chosen had the highest velocities and thickness of group 1 cats were LVFWd 4.8 mm (range
minimal artifact. The operator (KM) obtaining and reading the 4–5.3 mm) and IVSd 5.7 mm (range 4–6 mm) (Table 1).
echocardiogram and TDI was blinded to the group number of the All cats in group 1 had normal left atrial size. There were
cat, with the exception of group 1 cats.
6 Maine Coon cross cats (3 male and 3 female) with
Normal reference values of Em-EAsum were obtained by
a mutation of MYBPC3 but no phenotypic evidence of
another investigator from 20 normal, awake DSH cats.e,6 Sixty-four
measurements of Em-EAsum were made at HRs ranging from 115–
left ventricular hypertrophy (group 2). All cats in group
242 bpm.6 Because Em-EAsum is positively correlated with HR, 2 were heterozygous for the MYBPC3 mutation. No
95% prediction intervals were constructed to determine the upper cats in group 2 had left ventricular hypertrophy,
and lower limits of normal Em-EAsum depending on the HR, papillary hypertrophy, or left atrial enlargement (medi-
using the following formulas: an LVFWd 4.7 mm, range 4–5.1 mm; median IVSd
vffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi 4.5 mm, range 3.8–5.3 mm) (Table 1). Last, there were
u
u 1 ðX { X Þ2 15 Maine Coon cats and Maine Coon cross cats (7 male
SIND ~ SY:Xu t1 z n z P P 2 and 8 female) with MYBPC3 mutation and phenotypic
ð Xi Þ
Xi2 { n evidence of left ventricular hypertrophy (group 3). One
cat in group 3 was homozygous for the MYBPC3
mutation, and the remaining 14 cats were heterozygous
Prediction interval 5 Yc 6 tSIND
Where_ Y is predicted individual value of Em-EAsum; X, heart
for the mutation. All cats in group 3 had mild to severe
rate; X, mean heart rate; n, sample number; SIND, square root of concentric left ventricular hypertrophy (LVFWd median
variance of Y; and t, the t multiple determined for n-2 degrees of 6.6 mm, range 4.7–7.8 mm; IVSd median 6.3 mm, range
freedom. 4.1–7.6 mm), and 3 cats (20%) had mild to severe left
atrial enlargement (LA/Ao 1.6, 1.8, and 2.0, respectively)
Statistical Analysis (Table 1). Median ages and age ranges of cats in group
1, group 2, and group 3 were 3.5 years (3–4 years),
The Jonckheere-Terpstra test was used to assess the presence of 5.5 years (2.8–6.1 years), and 8.4 years (2.4–12.9 years),
a continuous Em-EAsum response according to ordinal group, ie,
respectively. There was no difference in ages among the
that Em-EAsum decreases as group number (severity) increases.
3 groups (P 5 .35).
The Kruskal-Wallis test for singly ordered contingency table data
was used to compare ordinal groups (group 1, then group 2, then
group 3) to a dichotomous grouping of EM-EAsum (normal or Tissue Doppler Imaging
reduced). Em-EAsum was defined as normal or reduced by using
Em-EAsum decreased as group number (ie, severity
95% prediction intervals of Em-EAsum depending on HR.
of disease) increased, meaning that there was an ordered
Kruskal-Wallis 1-way analysis of variance was used to assess
whether HR and age were different among the 3 groups of cats.
response of Em-EAsum depending on the group number
Sensitivity and specificity of Em-EAsum for detecting genotypical- (group 1, median 11.6 cm/s, range 9.7–14.7 cm/s; group
ly affected cats was calculated. A level of significance was defined 2, median 8.4 cm/s, range 7.5–13.2 cm/s; group 3 median
as P , .05. 7.7; range 4.5–14.1; P 5 .001) (Table 1, Fig 2). Using
Em-Easum and HR was obtained 2 separate days within the 95% prediction intervals for the lower limit of
10 days by the same operator in 10 Maine Coon and Maine Coon normal Em depending on HR, no normal cats, 3 cats
cross cats. Time-intraobserver differences were statistically assessed (50%) in group 2, and 12 cats (80%) in group 3 had
by a paired t-test.f abnormally low Em-EAsum relative to HR (Fig 3).
Using the Kruskal-Wallis test for singly ordered
Results contingency table data, there was an ordered difference
in the number of cats with normal Em-EAsum depend-
Study Population
ing on group number, such that the number of cats with
There were 6 normal DSH cats (Group 1) that were normal Em-EAsum decreased as the group number
unrelated to the Maine Coon cats and Maine Coon cross increased (P 5 .001). Using the Kruskal-Wallis test, HRTDI in Cats with cMyBP-C 235
(80%) and specific (100%) for detection of the affected
genotype in cats in group 3.
There was no time-intraobserver difference in Em-
EAsum (P 5 .9) or HR (P 5 .07) in 10 Maine Coon and
Maine Coon cross cats that were examined twice within
a 10-day period by the same (blinded) operator.
Discussion
This study found that there was an ordered decrease
in Em-EAsum that corresponded to the increase in
group number, ie, as the group number increased from
normal to genotype-positive phenotype-negative to
genotype and phenotype positive, Em-EAsum de-
Fig 2. Box and whisker plots of early mitral annular diastolic creased. As has been shown previously, Em-EAsum
velocity in normal domestic shorthair cats (group 1), Maine Coon was also reduced in Maine Coon cats and Maine Coon
cats and Maine Coon cross cats with myosin binding protein C cross cats with the MYBPC3 mutation with concentric
mutation without left ventricular hypertrophy (group 2), or with hypertrophy.18 This study demonstrates that diastolic
hypertrophy (group 3). As group number (X axis) increased, early dysfunction can be an early component of the patho-
mitral annular velocity (Em) decreased (P 5 .001; Group 1, median physiology of HCM rather than merely a consequence
11.6 cm/s, range 9.7–14.7 cm/s; Group 2, median 8.4 cm/s, range
of left ventricular hypertrophy and fibrosis. However,
7.5–13.2 cm/s; Group 3, median 7.7 cm/s, range 4.5–14.1 cm/s).
on an individual basis, Em-EAsum of the lateral mitral
annulus was reduced in only 50% (3/6) of the cats with
was not different among the 3 groups (P 5 .49; group 1, the mutation of MYBPC3 without hypertrophy and is
median 204 bpm, range 143–260 bpm; group 2, median therefore not a sensitive enough screening test (sensitiv-
179 bpm, range 158–244 bpm; group 3, median ity 50%) for detection of genotypically affected cats with
175 bpm, range 101–250 bpm). no hypertrophy. TDI measurement of Em-EAsum is
TDI measurement of Em-EAsum of the lateral mitral a very sensitive test (80%) for detection of genotypically
annulus was insensitive (50%) but specific (100%) for affected cats with hypertrophy.
detection of the affected genotype in group 2 cats. TDI These findings are consistent with a previous report
measurement of Em-EAsum was both highly sensitive that identified impaired systolic and diastolic function
using TDI in a mutant B-myosin heavy chain transgenic
rabbit model of HCM before development of concentric
hypertrophy.15 There are also several small studies
evaluating the use of TDI measurement of diastolic
function as a screening test for identification of
genotypically affected people with familial HCM in the
absence of hypertrophy.19,20 In one study of 13 people
with a mutation for familial HCM but no hypertrophy,
30 people with a mutation and concentric hypertrophy,
and 30 age-matched controls, Em was 100% sensitive
and 90% specific for the diagnosis of people with only
the abnormal genotype.19 Another study using TDI to
predict genotype (B-myosin heavy chain mutation) in
people with preclinical HCM found a substantial over-
Fig 3. Tissue Doppler imaging echocardiography measurement lap of EM velocities between genotypically affected
of early diastolic myocardial velocity at the lateral mitral annulus
people without hypertrophy (n 5 18) and normal people
in normal domestic shorthair cats (group 1), Maine Coon cats and
Maine Coon cross cats with a myosin binding protein C mutation
(n 5 18), with a sensitivity of 75% and a specificity of
without left ventricular hypertrophy (group 2) or with hypertrophy 86% for detection of the affected genotype.20 Another
(group 3). (under fig): As group number increased, early diastolic study revealed that TDI is predictive of HCM de-
mitral annular velocity (Em) decreased (P 5 .001). Maine Coon velopment in genotypically affected people, again
cats and Maine Coon cross cats with a mutation in the myosin without evidence of hypertrophy.14 People with a lower
binding protein C gene without hypertrophy (group 2) had an baseline Ea velocity had a greater increase in left
intermediate reduction in Em compared to the normal domestic ventricular mass across 2 years (R 5 20.86).14 Further
shorthair cats (group 1), and Maine Coon cats and Maine Coon follow-up of the genotypically affected cats without
cross with the MYBPC3 mutation and hypertrophy (group 3) had
hypertrophy in the current study would be useful to
the lowest early diastolic mitral annular velocity (Em). Heart rate
was not significantly different among the 3 groups (P 5 .49). The
identify whether the same relationship exists between
solid line represents the 95% prediction interval for lower limit of baseline Ea and subsequent development of hypertrophy
normal Em depending on heart rate. Based on the lower prediction in cats.
limit for normal Em, the number of cats with normal Em decreased One hypothesis in familial HCM is that the initial
as the group number increased (P 5 .001). phenotype is a functional sarcomeric defect and there236 MacDonald et al
are intermediary pathways that connect the initial defect Maine Coon cats that were genotypically affected but
to the final phenotype of left ventricular hypertrophy, phenotypically normal.
myocardial fibrosis, and myofiber disarray.3 Gene Because of the limited number of normal cats and the
transfer studies in adult rat ventricular cardiomyocytes need to measure Em-EAsum across a wide range of
expressing HCM-associated mutant troponin T protein HRs, it was necessary to measure Em-EAsum several
have demonstrated myocyte dysfunction before devel- times in some cats. Repeated measures of Em-EAsum
opment of myofibrillar disarray.21,22 Impaired cardio- within individual normal cats may falsely narrow
myocyte mechanical function leads to increased myocyte prediction intervals if there are cat-specific effects of
stress and activation of stress-responsive intracellular HR on EM-EAsum. The number of normal DSH cats in
signaling kinases, calcium-sensitive signaling molecules, group 1 was small.
and trophic factors.3 Transcriptional machinery of the Systolic blood pressure was not measured in the
myocyte is activated, which leads to myocyte hypertro- group 1 and group 2 cats that did not have evidence of
phy, collagen synthesis, and myocyte disarray. Left concentric hypertrophy. These cats were young, overtly
ventricular hypertrophy is a compensatory process healthy, and free of any clinical signs.
occurring later in the disease in familial HCM models. In conclusion, this study found that Maine Coon cats
Dysfunctional myosin binding protein C (cMyBP-C) and Maine Coon cross cats with a MYBPC3 mutation
protein may negatively impact the structure and have incrementally reduced Em depending on the
function of the sarcomere.23 The axial alignment of absence or presence of hypertrophy as compared with
cMyBP-C along the B2MHC backbone and the in- normal DSH cats. Cats that were genotypically affected
teraction of cMyBP-C with titin are necessary for with no hypertrophy had intermediate Em values as
ordered, stabilized arrangement of the sarcomere. a group compared to normal DSH cats and cats that
Consequently, the absence of cMyBP-C in transgenic were genotypically affected and had hypertrophy,
cMyBP-C knockout mice resulted in malalignment of suggesting that the pathophysiology of the disease in
the sarcomeric striations.23 cMyBP-C also interacts with Maine Coon cats may be similar to that seen in humans
the beta-myosin heavy chain (b-MHC) head and acts as and genetic models of HCM. However, on an individual
a braking mechanism between the interaction of actin level, TDI is an insensitive screening test to identify
and b2MHC. When cMyBP-C is phosphorylated, it genotypically affected cats before the presence of
undergoes a conformational change in the C0–C1 linker hypertrophy.
region that releases the myosin head to be in a favorable
position to bind with actin.24 The mutation in MYBPC3
in Maine Coon cats was localized to the C0 and C0–C1
linker region involved with binding to myosin, actin, or Footnotes
both.2 In an experimental model of interrupted cMyBP- a
QiaQuick, Qiagen Inc, Spoorstraat 50, KJ Venlo 5911, Nether-
C and myosin interaction in ventricular myocytes, there
lands
was increased calcium sensitivity, force of contraction, b
ABI377 sequencer, Applied Biosystems, Foster City, CA
and time to half-relaxation.25 Similarly, in a knock-in c
HP Sonos 5500, Philips Medical Systems, Andover, MA
mouse familial HCM model missing the linker between d
Parks Medical Electronics, Inc, Aloha, OR
motifs C0–C1, there was an increased calcium sensitivity e
Acuson 128XP/10, upgraded with Acoustic Response Technolo-
to force production.26 These experimental findings may gy, Acuson DTI software, and Regional Expansion Selection,
help identify possible pathophysiologic mechanisms of Acuson Corps, Mountain View, CA
f
familial HCM in Maine Coon cats with mutation of StatXact, Version 6, Cytel Software Corporation, Cambridge,
MYBPC3. MA
There were several limitations of this study. TDI
measurement only included the lateral mitral annulus
early diastolic velocity or summated early and late
diastolic velocities, which is an index of global diastolic References
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