Journal of Veterinary Cardiology (2015) 17, S134eS149

www.elsevier.com/locate/jvc

REVIEW

Screening for hypertrophic

cardiomyopathy in cats
Jens Häggström, DVM, PhD a,*,
Virginia Luis Fuentes, MA, VetMB, PhD, MRCVS b,
Gerhard Wess, DVM, Dr. habil c

a
Department of Clinical Sciences, Faculty of Veterinary Medicine and Animal Science,
Swedish University of Agricultural Sciences, Box 7054, Uppsala, Sweden
b
The Royal Veterinary College, Department of Clinical Science and Services,
Hawkshead Lane, Hatfield AL9 7TA, United Kingdom
c
Clinic of Small Animal Medicine, LMU University, Veterinaerstr. 13, 80539 Munich,
Germany

Received 16 March 2015; received in revised form 27 June 2015; accepted 1 July 2015

KEYWORDS Abstract Hypertrophic cardiomyopathy (HCM) is the most common heart disease
Echocardiography; in cats, and it can lead to increased morbidity and mortality. Cats are often
Breeding programs; screened for HCM because of the presence of a heart murmur, but screening for
Biomarkers; breeding purposes has also become common. These cats are usually purebred cats
Genetic background of breeding age, and generally do not present with severe disease or with any clin-
ical signs. This type of screening is particularly challenging because mild disease
may be difficult to differentiate from a normal phenotype, and the margin for error
is small, with potentially major consequences for the breeder. This article reviews
HCM screening methods, with particular emphasis on echocardiography.
ª 2015 Elsevier B.V. All rights reserved.

Introduction when a heart murmur is detected), this article

focuses on hypertrophic cardiomyopathy (HCM)
Although it is common to investigate cats for the screening of cats for breeding purposes. These cats
possible presence of heart disease (particularly are usually purebred cats of breeding age, and
generally do not present with severe disease or
* Corresponding author. with any clinical signs. Population screening to
E-mail address: Jens.Haggstrom@slu.se (J. Häggström). exclude disease-affected cats from breeding is

http://dx.doi.org/10.1016/j.jvc.2015.07.003
1760-2734/ª 2015 Elsevier B.V. All rights reserved.
Screening for hypertrophic cardiomyopathy in cats S135

with non-sarcomere mutations (such as metabolic

Abbreviations storage diseases and mitochondrial cardiomyo
pathies) should also be considered part of the
FS fractional shortening human HCM spectrum, or should be excluded as
HCM hypertrophic cardiomyopathy ‘secondary’ cardiomyopathies.3 Such causes of LV
IVRT isovolumic relaxation time hypertrophy have not been widely explored in
IVSd interventricular septal wall thick- cats. The ‘hallmark’ feature of HCM in humans is
ness at end-diastole myofiber disarray on myocardial histopathology,
LV left ventricle which appears in the form of bizarre, disorganized
LVFWd left ventricular wall thickness at cellular architecture but which nevertheless may
end-diastole only be present in a proportion of the left ven-
MYBPC3 myosin-binding protein C tricular myocardium.4 Myofiber disarray is also
NT-proBNP N-terminal pro B-type natriuretic reported in cats,5 although in one study, was only
peptide reported to be present in 27% of cats with naturally
PW pulsed wave occurring HCM6 and was inconsistently found in
ROC receiver operating characteristics another recent morphometric study of cats with
SAM systolic anterior motion hypertrophied hearts.7 As myofiber disarray can be
SNP single nucleotide polymorphism missed if sections miss focally affected areas, it is
SR strain rate unclear whether this is a less typical feature of
TDI tissue Doppler imaging cats than humans, but abnormal small intramural
TVI tissue velocity imaging coronary arteries and increased interstitial or
2-D two-dimensional replacement fibrosis are additional common
3-D three-dimensional findings.5e7

only possible when the disease can be defined, the

disease is inherited, and the disease can be ante Inheritance of hypertrophic
mortem diagnosed. To be practical, diagnosis cardiomyopathy
should be cost-effective and minimally invasive.
Echocardiographic-screening cats for HCM meets Hypertrophic cardiomyopathy is the most common
or partially meets most of these criteria, but many familial genetic heart disease in humans, affecting
challenges remain. In particular, there is a prob- one in 500 individuals.8,9 In humans, over 1400 dif-
lem in differentiating mild disease from a normal ferent mutations in at least 11 different sarcomere-
phenotype, and the margin for error is small. For and myofilament-related genes have been found in
the individual cat, this is usually not a problem association with HCM.9e12 Recent studies have also
because mild HCM is associated with a com- linked mutations of Z-disc-associated genes and
paratively good long-term prognosis, but for the calcium handling genes to HCM.13 In 60% of human
breeder the consequences may be serious. This HCM cases, it is inherited as an autosomal dominant
article reviews HCM screening methods, with par- trait while exhibiting an enormous phenotypic and
ticular emphasis on echocardiography. genotypic heterogeneity. Some individuals in affec-
ted human families may have two or even three
concurrent sarcomere mutations,14,15 and de novo
Definition of hypertrophic mutations can also be a sporadic cause of HCM.16e18
cardiomyopathy It is suspected that HCM in cats has a similar genetic
basis, and HCM has been reported to be familial in
On the simplest level, HCM is defined as hyper- some cat breeds such as American Shorthair, Maine
trophy of a non-dilated left ventricle in the Coon, Norwegian Forest, Sphynx and Persian
absence of abnormal loading conditions capable of cats,19e24 as well as in two families of non-purebred
producing the magnitude of wall thickening evi- cats.25,26 Hypertrophic cardiomyopathy is inherited
dent.1,2 In people, HCM is usually (but not always) as an autosomal dominant trait in Maine Coon Cats,
associated with mutations in sarcomere-encoding and this mode of inheritance is also suspected in
genes, with variable age-dependent phenotypic other breeds.21 Mutations in the gene for myosin-
expression, so that left ventricular (LV) wall binding protein C (MYBPC3) have been reported in
thickness may be normal in some mutation- both Maine Coon cats and Ragdoll cats.22,27 Inherited
positive individuals. There is controversy over HCM in pedigree breeds of cats is thought likely to be
whether LV concentric hypertrophy associated associated with a single mutation in each breed, but
S136 J. Häggström et al.

it is also possible that some breeds may have multi- thickness to within fractions of a millimeter. The
ple causal mutations. vast improvements in ultrasound technology over
the years has led to better image quality and res-
olution, but adequate echocardiographic skills and
Ante mortem diagnosis of hypertrophic consistent technique on the part of the operator
cardiomyopathy are also essential. It is now recognized that HCM is
characterized by a broad range of phenotypic
Clinical diagnosis is based on detection of other- patterns of LV hypertrophy ranging from localized
wise unexplained LV hypertrophy, customarily and relatively mild wall segment thickening to
using echocardiography; alternatively, in humans, extreme generalized hypertrophy, and no single
diagnosis can be confirmed with cardiac magnetic pattern can be considered characteristic for the
resonance imaging.1,3,5 In humans, in the absence disease (Fig. 1).33,34 In localized forms, the entire
of systemic hypertension or aortic stenosis, a interventricular septum, or free wall, or a region
maximal end-diastolic wall thickness of 15 mm in of them may be affected; the apex or the papillary
any LV segment is considered to be diagnostic of muscles are primarily affected.33
HCM.3 An end-diastolic wall thickness of 13 mm is
considered sufficient grounds for diagnosis in first- Normal reference intervals for left ven-
degree relatives of HCM patients.3 In cats, in the tricular wall thickness
absence of systemic hypertension or hyper-
thyroidism, diagnosis is usually based on meas- Because of the heterogeneous distribution of
urement of maximal end-diastolic wall thickness hypertrophy, HCM is a diagnosis that is probably best
on 2-D or M-mode echocardiography. established by examining the heart in several echo-
cardiographic views and using all the modalities at
hand. Subjective assessment of the LV (such as pap-
Physical examination illary muscle hypertrophy and/or regional thickening
of the LV wall) should be supported by averaged
Breed screening usually includes comparably young measurements of LV wall thickness at end-diastole
and supposedly healthy cats, so physical findings from the region of thickening. M-mode has the
indicative of congestive heart failure (CHF) are advantage of excellent temporal resolution, owing
unusual. Heart murmurs are common in cats to the high frame rate,35 and many widely-used
(including those used for breeding) although not all feline reference intervals have been measured
cats with heart murmurs have heart disease,28,29 and using M-mode,36e39 but a standard M-mode echo-
auscultatory abnormalities (such as a heart murmur, cardiogram of the left ventricle (taken from imme-
arrhythmia, and gallop sound) are not always present diately below the mitral valve) may underestimate
in affected cats.30 Excluding functional murmurs and wall thickness by missing regional hypertrophy,29,40
congenital heart disease, the most common cause of or may overestimate myocardial thickness as a
a heart murmur in cats is LV outflow tract obstruction result of erroneous positioning of the cursor across
associated with systolic anterior motion (SAM) of the the papillary muscles (which can be very difficult to
anterior mitral valve leaflet, with or without avoid when papillary muscles are prominent).40
dynamic right ventricular outflow tract obstruction Measurement of focal areas of hypertrophy in 2-D is
(DRVOTO).31,32 Both SAM and DRVOTO may be pres- therefore recommended. Measurements should be
ent in cats with HCM. Depending on the definition, an average of measurements over three cardiac
the prevalence of myocardial hypertrophy in cats cycles, and ECG monitoring is preferable (but not
with heart murmurs has been estimated at always possible in cats) for timing of the measure-
18e62%.28,29,31,32 Auscultation alone is not a sensi- ment in the cardiac cycle.
tive or specific screening test to diagnose HCM. The upper limit of normal for LV end-diastolic
thickness has traditionally been set at a maximum
of 5.5 mm and anything >6 mm is widely consid-
Echocardiography ered to be evidence of LV hypertrophy in the
absence of preload depletion.33 This limit may be
In cats, echocardiography is the gold standard for conservative, as recent reports have suggested a
ante mortem diagnosis. However, echocardio- more narrow reference interval in specific
graphic screening for HCM is challenging, and in breeds.41,42 Some male cats have a lean body
order to differentiate normal from affected cats, weight up to twice as great as small female cats,
it is necessary to record differences in LV wall and although body weight is not consistently taken
Screening for hypertrophic cardiomyopathy in cats S137

Figure 1 A. Right parasternal short axis view of a normal cat showing the left and right ventricles (LV and RV,
respectively) in diastole, and from cats with symmetric hypertrophy (B), and asymmetric hypertrophy involving the LV
lateral wall and posterior papillary muscle (C), and septal and bilateral papillary muscle hypertrophy (D).

into account, larger cats are likely to have a Sharply delineated endocardial borders are needed
greater LV wall thickness.41e44 The normal refer- for accurate measurements of both sides of the
ence limit for end-diastolic LV septal or free wall interventricular septum. It is important to optimize
thickness in Maine Coon cats extends up to 5.0 mm near field imaging to identify right ventricular
in those weighing <6 kg,41,42 although values out- structures such as tricuspid valve chordae and right
side this range may not necessarily indicate that ventricular papillary muscles, which if included,
the cat has HCM. Breed-specific reference ranges may cause erroneously high values of interven-
are available for only a few breeds, but few of tricular septal thickness. A ‘leading-edge-to-lead-
them account for body size.23,45,46 Normal refer- ing-edge’ technique is usually employed for M-
ence intervals are unavailable for most breeds, mode measurements,47 but there is less consensus
partly because of difficulties in defining what is on the exact measurement technique with 2-D
‘normal’ and what is ‘HCM’. Most of the con- measurements, with recommendations ranging
troversy concerns cats with LV wall thickness from excluding all endocardial borders,28 to
between 5 and 6 mm. Because of the overlap including all endocardial borders29 or excluding
between normal phenotypes and mild HCM, the only the left ventricular endocardial border of the
diagnosis of HCM may be impossible to determine septum (leading-edge-to-leading-edge), as with M-
with certainty in some cats, particularly with a mode measurements. Including endocardial bor-
single wall thickness measurement using an arbi- ders can increase septal wall measurements by
trary cut-off value. Some screening programs allow 0.5 mm or more (Fig. 2). All three authors currently
a subjective assessment to be incorporated, and use a leading-edge-to-leading-edge technique.
cats with borderline measurements may be clas-
sified as ‘equivocal’, indicating that the cat cannot Dynamic left ventricular outflow tract
be considered with certainty to be either normal obstruction
or HCM-affected. Repeat examinations over time Dynamic obstruction of the LV outflow tract is a
may help to rule out or confirm HCM in these cats. common echocardiographic finding in cats with
There is little guidance available on the appro- HCM (Fig. 3).33 Systolic anterior motion of the
priate measurement technique for wall thickness. mitral valve is characterized by systolic
S138 J. Häggström et al.

Figure 2 Current methods used for measuring interventricular septal thickness. A. ‘Leading-edge-to-trailing-edge’,
including both endocardial borders of the septum. B. ‘Leading-edge-to-leading-edge’, using the same convention as
used for M-mode. C. ‘Trailing-edge-to-leading-edge’, where endocardial borders are excluded.

displacement of the anterior mitral valve leaflet whether SAM is an indicator of HCM, even in the
towards the septum, which in turn, causes a nar- absence of LV hypertrophy.32 In some cats, the site
rowing of the LV outflow tract, turbulence of blood of LV dynamic obstruction is in the mid ventricle.49
flow and mitral valve insufficiency. Dynamic LV It appears that this type of obstruction may occur
outflow tract obstruction is usually associated with if the myocardial hypertrophy is at the level of the
a heart murmur. In some cats, SAM is persistently papillary muscles. The impact of this phenomenon
present, but in many cats, dynamic LV outflow on progression of disease is unknown.
tract obstruction is absent at rest or under seda-
tion, and appears with excitement or as the heart
rate increases.48 Dynamic left ventricular outflow Papillary muscles
tract and SAM can be identified by studying the Papillary muscle hypertrophy is a common feature
motion of the anterior mitral valve leaflet in the M- of HCM (Fig. 1), and it is thought that some cats may
mode echocardiogram, but more commonly, it is present with papillary muscle hypertrophy as the
assessed on the 2-D echocardiogram. Not all cats first or only sign of HCM, as suggested in humans.50
with HCM demonstrate SAM, and some cats have Papillary muscle hypertrophy can lead to end-
SAM without LV hypertrophy. There is controversy systolic obliteration of the LV cavity or mid-
as to whether SAM can be a normal finding, is ventricular obstruction.21,51 Papillary muscle mor-
associated with congenital malformations, or phology and size is generally evaluated subjectively,
Screening for hypertrophic cardiomyopathy in cats S139

Figure 3 A. Right parasternal long axis view of a normal cat showing the left atrium (LA) and ventricle (LV) and the
aorta (Ao) in systole. Systolic anterior motion (SAM) of the mitral valve is a common feature of HCM in cats and is
illustrated by the cat in B and C. The abnormal motion of the mitral valve (B) leads to a dynamic narrowing of the left
ventricular outflow tract and turbulence of blood and mitral valve insufficiency (C).

but measurements can be made of papillary muscle mitral valve dysplasia, or as preclinical HCM.
area or dimensions.51,52 Whichever method is used, Elongated mitral valve leaflets appear to be a
there is overlap between normal cats and cats with common feature of human HCM, and are consid-
HCM. The evaluation of papillary muscles may also ered an important contributor to dynamic LV out-
be difficult because of variation in papillary muscle flow tract obstruction.55 Anterior mitral leaflet
morphology (Fig. 4). Abnormal papillary muscle elongation has been reported in HCM genotype-
position and bifid papillary muscles have been positive but phenotype-negative humans, sug-
implicated in outflow tract obstruction in human gesting a role for mitral leaflet morphology in the
HCM.53 However, ectopic papillary muscles are pathway between a sarcomeric mutation and LV
commonly found in apparently healthy cats, and hypertrophy.56 Elongated mitral valve leaflets have
there is no consensus on how variations in papillary also been reported in cats, in association with LV
muscle morphology should be interpreted in the outflow tract obstruction, and it seems plausible
context of HCM screening in cats. A recent report that mitral leaflet abnormalities also form part of
suggested that the focal thickening (ectopic papil- the feline HCM phenotypic spectrum.52
lary) where false tendons attach (see below), do not
change over time.54 False tendons
Left ventricular ‘false tendons’ are cord-like
Mitral valve abnormalities structures that traverse the LV cavity (Fig. 5).
There is no consensus as to whether cats with LV They attach to the septum, papillary muscles, or
outflow tract obstruction and normal LV wall the free wall of the LV, but not to the mitral valve
thickness should be classified as normal, as having leaflets.57 The clinical significance of false tendons
S140 J. Häggström et al.

Figure 4 Evaluation of papillary muscle morphology is challenging and controversial, largely because prospective
studies of how phenotypes change over time are currently unavailable. Examples of papillary muscle polymorphism,
where an ectopic papillary muscle is located in the left ventricular outflow tract in one cat in a oblique right para-
sternal long axis view (A), and only one papillary muscle is present in the apical portion of the LV in a right parasternal
short axis view (B), and unusual morphology of a papillary muscle (C) in the interventricular septum with false tendons
attaching in a left apical four chamber view.

is unknown, and variously thought to be beneficial echocardiographic abnormality.43,59 Because the

(by stabilizing the LV) or detrimental (by causing tricuspid insufficiency is so mild, it is inaudible
turbulence and obstruction).58 False tendons with a stethoscope.43,59 Mild, trivial, heart valve
appear to be a normal finding, but may cause insufficiency may also be found for the other heart
problems estimating LV wall thickness and evalu- valves, but it is less common and has been
ating presence of regional hypertrophy, not only by described in <10% of screened healthy cats.59
making it difficult to distinguish the false tendon
from the LV endocardium, but also because false Testing for other causes of left ventricular
tendons may insert into ectopic papillary muscles.54 hypertrophy
Some false tendons may produce a focal thickening
at the insertion area of the LV, which could be A diagnosis of HCM is based on the presence of LV
mistaken for focal HCM. To correctly identify false hypertrophy in the absence of abnormal loading
tendons, it is important to use ultrasound equip- conditions or other possible causes of hypertrophy,
ment with a high resolution and frame rate, and to so hyperthyroidism, aortic stenosis, hypertension,
use the cine-loop function at slow speeds or scroll and acromegaly should theoretically be ruled out.
through stored images frame by frame.
Serum thyroxine
Tricuspid valve insufficiency Hyperthyroidism is a condition of older cats,
Mild/trace tricuspid insufficiency has been descri- whereas cats screened for HCM for breeding pur-
bed in 25e65% in screened cats without any other poses are usually comparatively young (<5 years),
Screening for hypertrophic cardiomyopathy in cats S141

Figure 5 Examples of cats in right parasternal short axis view with LV false tendons (arrows) traversing the LV from
the papillary muscle to the interventricular septum (A and C). The false tendons may cause problems of identifying
correct reference points for measurements in the M-mode echocardiogram, as illustrated in B (which was obtained in
the same cat as A). Chordae tendinea (arrow) may sometimes be observed in the left ventricular outflow tract, as
illustrated by the example in D in a right parasternal long axis view.

so serum thyroxine is rarely measured as part of Blood pressure measurement

the screening before breeding. Most hypertensive cats are beyond breeding age. If
blood pressure is measured after echocardiog-
Aortic stenosis raphy, some cats will be too stressed for reliable
Echocardiography is necessary to diagnose aortic blood pressure measurements, making it difficult
stenosis, although fixed subaortic stenosis can to ‘rule out’ systemic hypertension on a single
sometimes be difficult to differentiate from visit.
chronic dynamic LV outflow tract obstruction that
has led to an impact lesion of endocardial fibrosis. Acromegaly
Valvular aortic stenosis is usually evident on 2-D Most cats with hypersomatotropism are diabetic,
echocardiography. The spectral Doppler waveform with poor glycemic control, and they are usually
should also be different between dynamic and older than breeding age. Serum glucose is not
fixed forms of LV outflow tract obstruction. The normally measured as part of HCM screening.
dynamic form is associated with a characteristic
waveform with a characteristic abrupt accel- Pseudohypertrophy
eration in mid-systole, producing a concave, Pseudohypertrophy due to dehydration should also
asymmetrically shaped waveform. The fixed form be considered as a possible cause of increased LV
lacks this appearance, despite high flow velocities. wall thickness,60 although most cats presented for
S142 J. Häggström et al.

screening before breeding are healthy and are severe diastolic dysfunction associated with
unlikely to present with pseudohypertrophy. reduced LV compliance and severely elevated left
atrial pressures, and is evidenced by E:A >2,
Pregnancy and lactation decreased E-wave deceleration time, and short-
Pregnancy and lactation alter maternal hemody- ened IVRT. Tissue velocity is a sensitive and non-
namics, and in mammalian species, a rise in car- invasive tool to assess diastolic and systolic
diac output is associated with increased circulating function.64,65 In cats with HCM, indices of diastolic
blood volume and decreased systemic vascular function measured by TVI are different from those
resistance.61 These changes have the potential to of healthy cats and similar to those values repor-
change heart rate and echocardiographic meas- ted in human beings with HCM and restrictive
urements (i.e. increase LV dimensions and reduce cardiomyopathy.66e74
wall thickness).61 It is therefore inadvisable to Color-coded TDI, which enables the clinician to
screen pregnant or lactating female cats. measure color-coded TVI, strain and SR measure-
ments, was later introduced to evaluate regional
myocardial deformation magnitude and rate,
respectively. The application of TVI in human
Value of newer modalities (tissue Dop- beings with HCM has shown that, in contrast to
pler imaging, speckle tracking, 3-D) traditional echocardiographic techniques, which
consider diastolic dysfunction as the main abnor-
Many cats with HCM have diastolic dysfunction, mality of the disease, systolic impairment is also
and abnormalities in diastolic function have pre- evident, despite the apparently normal or super-
viously been characterized using mitral valve normal contractile state of the LV based on per-
inflow profiles.62,63 Tissue Doppler imaging (TDI) is centage of fractional shortening (FS%) and
a relatively new echocardiographic technique that percentage of ejection fraction calculations.75 In
uses Doppler principles to measure the velocity of cats with HCM, abnormal systolic function has also
myocardial motion. In TDI, the same Doppler been found using both conventional echocardiog-
principles are used to quantify the higher- raphy and TVI measurements,26,30,67,69,71,76 but
amplitude, lower-velocity signals of myocardial even when conventional echocardiographic sys-
tissue motion. Whereas TDI describes the general tolic indices are normal, TVI may reveal systolic
technique, several modalities can be derived from dysfunction.23,70,77 One study evaluated longi-
color-coded tissue Doppler imaging, such as tissue tudinal systolic myocardial deformation (strain)
velocity (TVI), and newer modalities such as strain and found that it reduced in cats with HCM,
and strain rate (SR). The term TDI and TVI are despite normal echocardiographic indices of global
often used interchangeably, but to be more pre- LV systolic function, which suggests the presence
cise, the term TVI is used to measure the velocity of a global subclinical systolic dysfunction.78 Sys-
of the myocardial wall in relation to the transducer tolic myocardial strain can be decreased, even in
and allows the measurement of the peak systolic mild forms of HCM, and deteriorates further in
wave (S-wave), as well as early (E-wave) and late more severe HCM stages.78
diastolic (A-wave) movement of the myocardial Three-dimensional (3-D) echocardiography has
wall; TVI is therefore used for those measurements recently been evaluated in humans with HCM, and
in this article. Diastolic function can be assessed demonstrated superior performance than 2-D
using pulsed-wave (PW) Doppler and/or using TVI. echocardiography for the evaluation of myo-
Pulsed-wave Doppler measurement of mitral cardial hypertrophy, LV volumes, LV ejection
inflow velocity from the left apical four-chamber fraction, and LV mass.79 However, most currently
view often shows a delayed relaxation pattern available 3-D probes have limited use in cats
(early diastolic filling wave (E) to atrial systole (A) because of their resolution, frame rate, and other
wave ratio of <1, prolonged isovolumic relaxation technical issues.
time (IVRT), and prolonged E-wave deceleration Despite the fact that some of the new echo-
time) in cats with preclinical HCM. Delayed relax- cardiographic modalities might be useful in
ation is the first stage of diastolic dysfunction, detecting early systolic and diastolic dysfunction,
when there is impaired early diastolic filling of the there are currently no large-scale studies that
LV and augmented filling with atrial contraction. As have evaluated the role of TVI, strain or strain rate
diastolic dysfunction worsens, left atrial pressure measurements, or 3-D echocardiography for
increases, leading to a pseudonormal filling pat- screening purposes. Furthermore, there are few
tern on mitral inflow velocity measurement. A longitudinal studies of how TDI or 3-D variables
restrictive filling pattern may be seen in cats with change over time in cats as HCM develops.
 Screening for hypertrophic cardiomyopathy in cats
Table 1 Examples of screening program guidelines.
PawPeds ARCH VCS/FAB
Microchip ID required? Yes Yes No
Screener qualifications ACVIM or ECVIM cardiology diplomate, members of ACVIM or ECVIM ACVIM, ECVIM, or RCVS Cardiology
the Collegium Cardiologicum or PawPeds list of cardiology diplomate. Diplomate or on VCS list of accredited
accredited screeners. screeners.
M-mode/2-D Either Either Either
HCM criteria Subjective assessment (such as papillary muscle IVSd or LVFWd 6 mm. IVSd >5 mm
morphology, presence of SAM) supported by regional LVFWd 5.5 mm.
or symmetrical measurement of IVSd or LVFWd
5.5 mm in cats within the normal weight range
2.5e6 kg. Others on case-to-case basis.
Equivocal Subjective assessment (such as papillary muscle IVSd or LVFWd >5.5 to Normal LV wall measurements with
morphology, presence of SAM) with or without <6 mm. papillary muscle hypertrophy or SAM, or
support of measurement (IVSd or LVFWd end systolic cavity obliteration.
>5 mme<5.5 mm) in cats within the normal weight
range 2.5e6 kg. Others on case-to-case basis.
Normal Normal subjective assessment supported by IVSd or IVSd or LVFWd IVSd or LVFWd <5.5 mm.
LVFWd <5 mm. In cats within the normal weight <5.5 mm.
range 2.5e6 kg.
Subjective assessment Yes e papillary muscle hypertrophy or end-systolic No Yes e papillary muscle hypertrophy, SAM,
included? cavity obliteration, or SAM considered equivocal if no end systolic cavity obliteration, LA
LVH. enlargement taken into account.
Need to exclude other No Yes e hypertension, No
causes of LVH? hyperthyroidism,
acromegaly.
Frequency/timing Annually from 1 year. At least one scan at >3 years Annual exam Annual exam recommended.
old. Recommended at 5 and 8 years. recommended.
Excluded from screening Cats with significant organ or systemic disease. <12 months old, pregnant.
Recommendation not to screen pregnant or lactating
females.
Sedation allowed? Yes, but must be noted on screen report. Not specified? Not specified?
Other Necropsy recommended in the event of death.
Mandatory for all results Yes No No
to be made publically
available?
ARCH (ACVIM), ACVIM Registry of Cardiac Health (American College of Veterinary Internal Medicine); VCS/FAB, Veterinary Cardiovascular Society/Feline Advisory Bureau (now
International Cat Care); LVH, left ventricular hypertrophy.

S143
S144 J. Häggström et al.

Electrocardiography N-terminal pro B-type natriuretic peptide

Although NT-proBNP is not the active polypeptide
Although electrocardiography is used in some product, its plasma concentration reflects the
human programs that screen for HCM in young plasma concentration of active BNP;88 therefore, it
athletes, QRS waveform abnormalities and mean has been used as a more stable marker of BNP
electrical axis deviation are relatively insensitive activity. Using a cut-off value of >270 pmol/L, NT-
tests for ventricular hypertrophy.80 Some cats with proBNP is a valuable test in dyspneic cats to differ-
HCM have normal ECG findings,80 although entiate congestive heart failure from respiratory
increased R-wave voltages (>1.0 mV in Lead II) and disease.85,89 One recent study evaluated NT-proBNP
a left shift in the mean electrical axis are sugges- in various stages of HCM. A cut-off value (>49 pmol/
tive of LV hypertrophy. Recent studies have sug- L) had a high sensitivity of 97.8%, but a specificity of
gested that most cats with ventricular 66.7% to differentiate healthy cats from cats with
tachyarrhythmias have underlying structural heart HCM. Using a higher NT-proBNP cut-off value
disease that is echocardiographically identifi- (>100 pmol/L) increased specificity (93.9%), while
able.81,82 Because of the suspicion of cardiomy- retaining high sensitivity (92.4%). Specificity
opathy, any arrhythmia detected in a cat by increased to 100% using a cut-off value of
auscultation should be further evaluated by ECG >150 pmol/L.90 Another multicenter study evaluat-
and echocardiography, but the ECG does not ing the ability of NT-proBNP to discriminate between
appear to be a useful screening test for HCM in cats cats with occult cardiomyopathy and normal cats
for breeding purposes. showed 100% sensitivity and 71% specificity using a
cut-off of 91 pmol/L, with an area under the curve
Thoracic radiography (AUC) of 92% on receiver operating characteristics
(ROC) analysis.91 Cats with NT-proBNP concen-
Thoracic radiography is useful for evaluating the trations in the range of 50e100 pmol/L therefore
presence of congestive signs and abnormal cardiac may have HCM, or may be normal. In these cases, NT-
size. However, radiography is a comparatively proBNP should either be re-measured after a few
insensitive test for myocardial hypertrophy in cats, weeks, or echocardiography should be immediately
as cardiac size may be normal on thoracic radio- performed if there are no financial constraints.90
graphs despite significant myocardial hypertrophy. Despite these promising data, NT-proBNP measure-
Although an abnormal cardiac shape (the so-called ment is probably not sensitive enough to detect the
‘Valentine’ shaped heart) usually indicates sig- mild or early forms of HCM that may be present in
nificant atrial dilatation, echocardiography is a young cats evaluated for breeding screening;
more sensitive test for left atrial enlargement.83,84 therefore, measurement of NT-proBNP is not cur-
Even when cardiac size is increased on radio- rently recommended for this purpose.
graphs, this is not specific for hypertrophic
cardiomyopathy.80,83 Troponin-I
Cardiac troponin-I is used as a biomarker for
Cardiac biomarkers myocyte damage and has been evaluated in cats
with HCM.92e95 Although this biomarker appears to
The concept of blood-based tests to detect car- confer both diagnostic and prognostic information
diomyopathy is attractive for a number of rea- in cats, it is more likely to detect moderate-to-
sons. Assays to measure cardiac biomarkers are severe disease than mild disease and, thus, is
widely available, do not require advanced train- unlikely to be useful as a screening tool for
ing, and biomarker concentrations can be objec- breeding purposes.94,95
tively quantified.85e87 Measurement of
biomarkers is less expensive than some other
screening methods. Myocardial disease is likely to Genetic testing for hypertrophic
result in increased cardiomyocyte release of the cardiomyopathy
N-terminal pro B-type natriuretic peptide (NT-
proBNP), and this has been the most widely Hypertrophic cardiomyopathy in Maine Coon cats is
evaluated biomarker for HCM screening. reportedly caused by a single point mutation in the
Troponin-I also has uses in the evaluation of feline MYBPC3 gene (A31P), and a single point mutation
cardiomyopathy, because it is a marker of myo- in the same gene (R820W) is thought to cause the
cardial injury, and ischemia may cause Troponin-I same disease in Ragdoll cats.22,27 Another study
to leak into the circulation. has suggested that the single nucleotide
Screening for hypertrophic cardiomyopathy in cats S145

polymorphism (SNP) (A74T) of the MYBPC3 causes For the individual cat that is neutered or not
HCM in Maine Coon cats,96 but this causality for intended for breeding, it may be less important to
this mutation has been questioned in subsequent detect subtle LV hypertrophy, as cats with HCM
publications.97,98 Genetic tests for the mutations and normal left atrial size are likely to have a good
in Maine Coon and Ragdolls cats are commercially long-term prognosis.30 However, the consequences
available. A recent publication reported that the of breeding borderline cats (classified as equivocal
A31P mutation is present in about 34% of all Maine or mild HCM) are potentially grave with a disease
Coon cats worldwide,99 although another study that has such variable expression, as offspring may
suggested the value of the current genetic tests for exhibit a more severe phenotype than the parents.
Maine Coon cats was low in a European Maine Coon The impact of excluding cats with HCM from
cat population.97 Of cats with the A31P mutation, breeding may not unduly restrict the gene pool, as
83.3% were healthy on echocardiographic exami- analysis of the PawPeds database suggests that
nation at a mean age of 65 months.97 In the same only 3e5% of screened cats are diagnosed with
study, 75.0% of cats with HCM were genotype- HCM. If this were generally true, the risks of
negative for A31P.97 Therefore, the mutations excessively restricting the gene pool would appear
that have been analyzed appear to have low pen- to be small. The interpretation of variation from
etrance, and even homozygous cats can remain normal morphology remains challenging, and lon-
healthy. The prevalence of the R820W mutation in gitudinal studies are needed to clarify how ven-
Ragdoll cats has been estimated between 17 and tricular phenotype changes over time.
23%.98 Similar studies comparing genotype and To the authors’ knowledge, there are no pub-
phenotype as for the A31P mutation in Maine Coon lished studies available concerning the efficacy of
cats are currently unavailable for Ragdoll cats, breeding measures aimed at reducing the inci-
although a study based on owner questionnaires dence of HCM in cat breeds. Current breeding
reported that R820W homozygous cats had a recommendations are, therefore, general in
shorter life and were more likely to die from heart nature and based on the assumption that HCM is
disease compared with heterozygous and wild- inherited as an autosomal dominant trait with
type cats.100 Echocardiography remains the most variable penetrance in all cat breeds. Recom-
valuable test to establish the diagnosis of HCM. mendations are slightly different in different pro-
grams. In general, it is recommended that cats be
screened for HCM with echocardiography during
the time they are bred, preferably at least until
Overview of screening programs for
the age of 3 years. Follow-up examination is
hypertrophic cardiomyopathy commonly recommended when the cat is older
(i.e. 5e8 years). Cats with echocardiographic evi-
The demand from breeders and veterinarians to dence of HCM should not be bred. Young, close
reduce the incidence of HCM in purebred cats has relatives of a cat with early onset of HCM should be
led to development of screening programs using bred with caution, preferably not until the cat has
echocardiography (Table 1). Breeds currently been proven free from evidence of HCM at a
being screened include: Maine Coon, Norwegian mature age (e.g. 2e3 years), and then only for a
Forest, Siberian, British Shorthair, Ragdoll, Cornish restricted number of matings. Cats with equivocal
and Devon Rex, and Sphynx. In many countries, echocardiographic findings should preferably not
such as Germany, no formal screening examina- be bred until the diagnosis of HCM has been refu-
tions are required by breed clubs, and interested ted. If bred while still being classified as equivocal,
breeders either use the PawPeds program or a it is recommended to wait until the cat has
similar classification system, and publish the reached well into adulthood (e.g. 2e3 years), and
results on their website without having the results to only mate with a cat free from HCM, and only a
entered into a database. The largest program, in restricted number of litters should be considered.
terms of number of screened cats per year, is the When making breeding decisions, caution is
PawPeds program (www.pawpeds.com). The main advised on interpreting the results from genetic
problem for the examiner has been how to classify tests,97 as some of the mutations appear to have
cats with echocardiographic evidence of mild wall low penetrance, and homozygous cats can remain
thickening, or only regional thickening, or slight- healthy.97 Long-term longitudinal studies of the
to-moderate hypertrophied papillary muscles. outcome of cats with the A31P mutation in Maine
Differentiating mild disease from unusual, but Coon cats and the R820W mutation in Ragdoll cats
potentially normal, phenotypes is a major chal- are scarce. Some breeding programs (such as
lenge, even for experienced screeners. PawPeds) advise against using cats that are
S146 J. Häggström et al.

homozygous for the mutation for breeding, and to Mahrholdt H, McKenna WJ, Mogensen J,
mate a heterozygous cat without echocardio- Nihoyannopoulos P, Nistri S, Pieper PG, Pieske B,
Rapezzi C, Rutten FH, Tillmanns C, Watkins H, Watkins H.
graphic evidence of HCM with a healthy cat free 2014 ESC Guidelines on diagnosis and management of
from the mutation. As with all cats used for hypertrophic cardiomyopathy: The Task Force for the
breeding (HCM may develop as a cause of other Diagnosis and Management of Hypertrophic Cardiomyop-
mutation), it is recommended to also examine athy of the European Society of Cardiology (ESC). Eur
these cats at an older age (e.g. 5 and 8 years) to Heart J 2014;35:2733e2779.
4. Maron BJ, Sato N, Roberts WC, Edwards JE, Chandra RS.
detect later onset HCM. The actual benefit that Quantitative analysis of cardiac muscle cell disorganiza-
these recommendations confer in terms of reduc- tion in the ventricular septum. Comparison of fetuses and
tion of HCM in affected breeds remains unknown. infants with and without congenital heart disease and
patients with hypertrophic cardiomyopathy. Circulation
1979;60:685e696.
5. Fox P. Hypertrophic cardiomyopathy. Clinical and patho-
Conclusions logic correlates. J Vet Cardiol 2003;5:39e45.
6. Liu SK, Roberts WC, Maron BJ. Comparison of morphologic
Screening cats for HCM for breeding purposes is findings in spontaneously occurring hypertrophic car-
most effectively performed by echocardiography, diomyopathy in humans, cats and dogs. Am J Cardiol 1993;
as genetic tests are only available in a few breeds 72:944e951.
7. Kershaw O, Heblinski N, Lotz F, Dirsch O, Gruber AD.
and most other tests, including cardiac bio-
Diagnostic value of morphometry in feline hypertrophic
markers, have not been shown to be effective in cardiomyopathy. J Comp Pathol 2012;147:73e83.
identifying mild form of HCM. Echocardiographic 8. Bos JM, Ommen SR, Ackerman MJ. Genetics of hyper-
diagnosis of moderate-to-severe HCM is usually not trophic cardiomyopathy: one, two, or more diseases? Curr
problematic, but milder forms of HCM may be Opin Cardiol 2007;22:193e199.
9. Maron BJ, Maron MS. Hypertrophic cardiomyopathy. Lan-
difficult to distinguish from normal phenotypes.
cet 2013;381:242e255.
There is a need for more specific guidelines on 10. Michels M, Hoedemaekers YM, Kofflard MJ, Frohn-Mulder I,
standardization of echocardiographic measure- Dooijes D, Majoor-Krakauer D, Ten Cate FJ. Familial
ment techniques, and the importance of specific screening and genetic counselling in hypertrophic car-
echocardiographic findings, including new echo- diomyopathy: the Rotterdam experience. Neth Heart J
2007;15:184e190.
cardiographic techniques, needs further longi-
11. Keren A, Syrris P, McKenna WJ. Hypertrophic cardiomy-
tudinal evaluation. opathy: the genetic determinants of clinical disease
expression. Nat Clin Pract Cardiovasc Med 2008;5:
158e168.
Conflicts of Interest 12. Alcalai R, Seidman JG, Seidman CE. Genetic basis of
hypertrophic cardiomyopathy: from bench to the clinics. J
Cardiovasc Electrophysiol 2008;19:104e110.
There are no known conflicts of interest associated 13. Kimura A. Molecular basis of hereditary cardiomyopathy:
with this publication and there has been no sig- abnormalities in calcium sensitivity, stretch response,
nificant financial support for this work that could stress response and beyond. J Hum Genet 2010;55:
have influenced its outcome. 81e90.
14. Maron BJ, Maron MS, Semsarian C. Double or compound
sarcomere mutations in hypertrophic cardiomyopathy: a
potential link to sudden death in the absence of conven-
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