Download diagnosis and treatment of feline hcm

DIAGNOSIS AND TREATMENT OF FELINE HCM
Iolanda Navalón Calvo
Ars Veterinaria
c/.Cardedeu nº3
Barcelona
Spain
INTRODUCTION
Hypertrophic cardiomyopathy (HCM) is characterized by a hypertrophy of the left ventricle due to
problems inherent to the myocardium, in absence of other heart or systemic conditions that can lead to a
concentric hypertrophy of the myocardium, such as aortic stenosis, blood hypertension, infiltrative
myocarditis (neoplastic or infectious), hyperthyroidism or acromegaly.
The incidence of heart disease in the cat is estimated around 8-10% and the HCM is the most frequent
form, representing approximately 2/3 of the feline CM.
Hypertrophy in cats is typically concentric and symmetrical, including the whole left ventricle. However,
there are also regional asymmetrical hypertrophies, involving the upper aspect of the septum, the free
wall of the ventricle, or papillary muscles. Most of apparently normal cats have a LV < 4.5 mm. 1
Most cases of HCM have an unknown cause and, thus, it is called primary HCM (genetic). It is thought
(although this is not completely described) that there may be mutations in the sarcomere of the myocytes
that alter the muscle contraction at a molecular level and the replication of the sarcomere may be
activated causing an increase of the thickness of the myocytes and hypertrophy.
In cats, there is breed prevalence, suggesting a hereditary component of the HCM. It has been described
in Siberia, Sphynx, American shorthair, Cornish Rex, Persian, European and British shorthair, Chartreux,
Bengal and Norway forest cats. Two distinct mutations of the protein "myosin protein C3 bniding"
(MYBPC3) with dominant autosomal traits and incomplete penetrance have been identified in Maine
Coon and Ragdoll Mutation A31P (g-c) in the Main Coon and R820W in the Ragdoll 2, 3. Apart from
inherited cases of HCM, the rest could be caused by "de novo" sarcomere mutations, as in humans,
though there are also cases with unknown cause where the existence of additional mutations are
suspected, or even potential environmental causes or other influences.
Males are predisposed, and the condition is more frequent in young cats (5 months to 6 years of age),
although is has been described in up to 16 years-old cats. In mild to moderate cases, it may be
asymptomatic and the diagnosis may be incidental, but they may develop heart failure when there is
severe thickening. They may present with lethargy, anorexia, tachypnea and dyspnea due to pulmonary
oedema, pleural effusion, or both. It can also cause systemic arterial thromboembolism (SATE) with acute
paralysis or paresis, or even sudden death, which is likely to be caused by a coronary embolism,
ventricular arrhythmia or by a not diagnosed congestive heart failure (CHF) that causes hypoxia.
Auscultation may help: systolic murmur is more frequent (usually on the sternal border) and can be by
mitral regurgitation or by left-sided obstructive flow with systolic anterior movement of mitral valve (SAM Systolic Anterior Motion) or gallop sounds (S3, S4).
DIAGNOSIS
The diagnosis is primarily based on echocardiography:

Increased ventricular thickness (≥ 5.5 mm), symmetrical or asymmetrical. Sometimes,
hypertrophy is only from papillary m. (early sign). Sometimes, M-mode is not sufficient to detect
the asymmetries.
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



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Increased LA (Left Atrium), indicating an increase of the pressure in the LV (left ventricle left) at
the end of the diastole. It has prognostic significance, since it usually relates to the severity of the
diastolic failure or MR and can predict the risk of CHF and SATE.
Decreased intraventricular size.
Normal or increased systolic shortening fraction.
In chronic HCM, LV contractility may decrease, the chamber can be dilated and there may be
evidence of progression of the restrictive disease.
SATE is observed with relative frequency and can be increased with the sympathetic tone. Its
aetiology is controversial, with an initially proposed theory of the Venturi effect (or blood flow),
although it is currently recognized that the presence of secondary morphological alterations due
to the hypertrophy may be the main cause. It can be identified using 2B and M-mode and colour
Doppler, where two turbulent flows originating in the LV outflow are observed, one regurgitating
into de LA and the other into the aorta. Spectral Doppler can be used to determine the pressure
gradient through the dynamic stenosis.
The assessment of the LV diastolic dysfunction is important. The main functional features include
the assessment of the global function, relaxation and "untwist", the elasticity of the chamber,
filling volume and pressures. Filling pressures can be evaluated in a semiquantitative way using
echocardiography, as well as other variable such as the transmitral flow, the LVRT (left
ventricular relaxation time), pulmonary veins flow, Tissue Doppler tissue or filling pressures ratios
E/E' or E/LVRT as most important values allowing us to make a classification of the LV diastolic
dysfunction.4
ECG: it may be abnormal. Abnormalities of ventricular conduction (left bundle branch block, left anterior
fascicular block pattern and preexcitation syndrome) can be seen. Arrhythmias are uncommon.
X-rays may be normal, but may show cardiomegaly (elongation) and dilation of the left atrium in
advanced cases. The assessment of lung patterns, such as prominent vascular patterns that may indicate
secondary pulmonary hypertension, high LV diastolic pressure, or increased lung densities (patched
interstitial and alveolar patterns) that are compatible with pulmonary oedema or signs of pleural effusion,
which are rather frequent in cases of ICC, will also be useful.
Blood tests, as well as the measurement of blood pressure, are used to rule out other systemic diseases
that may cause phenotypical HCM.
Cardiac biomarkers such as NT-ProBNP or inhibitory cardiac troponin (cTnI) have diagnostic and
5,
prognostic value. NT-ProBNP is useful to differentiate patients with respiratory disease vs. heart disease
6
and as screening test for asymptomatic patients. Its increase has also been described in cardiac derived
7
pleural effusion. Troponin has more prognostic value (values > 0.7ng / ml), increasing the value
proportionally to the increase of the risk of death, regardless of the presence of heart failure or left atrial
8
dilatation.
Anatomical pathology
Histopathology reveals:
 Myocyte hypertrophy. (Increased size of cells, enlarged nuclei, rectangular and hyperchromic).
Some show degenerative changes such as myofibrillar lysis, sarcoplasmic vascularization,
agglutination of the Z line material and abundant lipofucsin granules.
 Disorders of the myocardial myofibers, with groups of muscle cells that are aligned at right angles
or obliquely.
 Interstitial fibrosis.
 Abnormalities in the intramyocardial small vessels, with fibromuscular dysplasia of the intramural
coronary artery. 9
TREATMENT
It must be taken into account that here are no extensive and controlled studies indicating benefits with the
treatment in cases of asymptomatic disease, cats with recurrent episodes of CHF or for the evolution of
the heart failure itself. Therefore, treatment is based on recommendations and the experience of different
authors, experimental or retrospective studies in cats, or extrapolated evidences from canine or human
medicine. A persistent problem in HCM is the prevention of the arterial thromboembolism.
In case of asymptomatic patients with SATE with potentially negative effects, it is not clear that the
reduction of the gradient has beneficial effects due to the lack of efficacy assays. However, treatment with
β blockers (atenolol), calcium channel blockers (diltiazem) and sinoatrial node I f current blockers
(Ivabradine)10 are proposed.
In cases of acute HCF, it is important to minimize the stress, so it is advisable to give time to calm down
before performing diagnostic tests. In general, we would start with a sedation (buprenorphine,
butorphanol, midazolam), together with oxygen therapy and furosemide. As the IV administration can be
stressful, we can use the IM route. The starting dose would be 1 - 4 mg/Kg, depending on the degree of
11
HF decompensation, and repeated every 1 or 2 hours.
In the case of large amounts of pleural effusion, diuretics will not be sufficient and a thoracocentesis will
usually be needed. In addition, the analysis of the fluid will be useful to confirm that the nature of it is
compatible with CHF.
Positive inotropes, like pimobendan, are not registered for cats, although compared with what we know in
dogs, they seem to have a longer elimination time and a greater maximum blood concentration, although
the therapeutic dose is still not well defined12. However, there are clinicians who prescribe them in acute
CHF, especially if there is systolic dysfunction, severe pleural effusion, severe lung oedema, renal failure,
13, 14
or in refractory cases.
Pimobendan has also vasodilation effects by inhibiting the action of the
phosphodiesterase 3. Pimobendan (0.625-1.25 mg/cat/12 h IV or PO).
Dobutamine could also be used as inotropic, although with a very strict monitoring of the blood pressure
and the possibility of tachyarrhythmias, as most relevant adverse effects. Other vasodilators like
nitroglycerin, have no clear therapeutic benefit. For nitroprusside, its significant hypotensive effect could
limit its use.
Arrhythmias can contribute to the morbidity and mortality of the HF. Studies in human medicine show that
the treatment with antiarrhythmic drugs has increased the mortality of the population instead of being
beneficial in many cases. For this reason, in the case of low grade arrhythmias, treatment is not
recommended and we only consider it in situations where there is evidence of hemodynamic alterations.
In the case of chronic CHF, diuretics can be used, like the minimum effective dose of furosemide, ideally
once a day, monitoring the respiratory rate at home (Sleep Respiratory Rate SRR). 15 ACE inhibitors could
also be used, based on the fact that diuretics increase the activity of the RAAS and also because they
have a renoprotective effect, which could be interesting in animals that also have kidney disease. 16 (0.25 0.5 mg/Kg/12 - 24 h PO)
There are authors who use β blockers such as atenolol, especially in cats with LVOTO (left ventricular
outflow tract obstruction) with a gradient > 50mmHg and especially at risk of sinus tachycardia and
normal left atrial function. It is recommended to start with low doses (6.25 mg / cat / 12 h PO) once the
clinical congestive signs are corrected, and subsequently increased if necessary. However, there is a
study which shows no benefit in cases of HCM.17
The administration of pimobendan could be recommended in combination with the rest of the
conventional treatment in cases with a history of CHF characterized by systolic dysfunction and without
LVOTO as determined by ultrasound. There is a study where the administration of pimobendan in HCM
increased the survival time. 14 However, there are authors who reserve it as salvage therapy, in very
critical situations where the treatment is not working and as the last resort. 16
Antiplatelet agents are commonly used for the prevention of thrombotic disease
18
. Clopidogrel has shown
to be superior to aspirin in the FAT CAT Study, with a lower recurrence rate of SATE and also a reduced
19
rate of recurrence after one year.
PROGNOSIS
The prognosis can be very variable, with animals remaining asymptomatic lifelong and patients that
progress to CHF, sudden death or SATE. Clinical signs of CHF, with or without the presence of SATE,
the dilatation of the left atrium, senior life stage, predisposed breeds as Ragdoll or Maine Coon and gallop
rhythm or arrhythmias could be considered negative prognostic factors. Negative echocardiographic
prognostic values: severe hypertrophy > 9 mm, diastolic dysfunction with FS < 30%, regional hypokinesis,
decreased atrial function, positive contrast or intracardiac thrombi and advanced diastolic dysfunction,
with restrictive pattern. 20-22
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