Difference between revisions of "Hypertrophic Cardiomyopathy - Feline Cardiomyopathies"

Revision as of 12:09, 3 December 2012

Overview

Hypertrophic cardiomyopathy (HCM) is the most common myocardial disease in cats (75% of cardiomyopathies). It is characterised by a hypertrophied left ventricle, however there is phenotypical variability since hypertrophy can affect different portions of the interventricular septum (IVS), left ventricular free wall (LVFW) or both.

Aetiology

In humans, more than half of HCM cases are due to heritable genetic defects, the remaining cases are a result of spontaneous mutations that arise de-novo. Several hundred genetic mutations have been associated with HCM. These mutations usually affect genes that encode proteins that are encorporated into contractile elements or sarcomeres of the cardiomyocyte. There is familial heritability in some pedigree cats, including the Ragdoll and Maine Coon. Other breeds that may be predisposed include the British Shorthair, Norwegian Forest Cat, Turkish Van, Scottish Fold, Bengal and Rex.

Pathophysiology

An abnormality in the sarcomere, a contractile unit of the cardiac myocyte, is hypothesised to be the initial abnormaility in HCM. Altered sarcomeric function leads to increased signal transduction of kinases, calcium sensitive signalling molecules and trophic factors. This results in activation of transcriptional machinery of the myocyte, leading to myocyte hypertrophy, collagen synthesis and myofibre disarray. The phenotype of LV hypertrophy is a compensatory change which occurs later in disease.

Dynamic Left Ventricular Outflow Obstruction (LVOTO)

This may be caused by systolic anterior motion of the mitral valve (SAM) and mid-systolic contact of the left ventricular free wall (LVFW) with the interventricular septum (IVS) during systole.

Systolic Anterior Motion of the Mitral Valve (SAM)

This is where the anterior mitral valve leaflet moves towards the IVS in systole, therefore creating obstruction in the left ventricular outflow tract which interferes with the LV outflow in mid-systole. As a result of this movement, the mitral valve leaflet does not completely seal the atrioventricular annulus; this causes a secondary mitral regurgitation. The combination of turbulent blood flow in the left ventricular outflow tract and mitral regurgitation causes a systolic murmur which can be identified on auscultation.

Clinical Signs

Diagnosis

Genetic Testing

A causative mutation for HCM has been identified in Maine Coon and Ragdoll cats. This mutation involves the sarcomeric gene for cardiac myosin binding protein C (MYBPC3) in both breeds. However, the mutation in the two breeds appears in different regions of this gene. In Maine Coons it is between domains C0 and C1, in Ragdolls it is in domain 6. There are likely additional mutations that are yet to be identified in Maine Coon cats, as some cats with phenotypic evidence of HCM do not have an identifyable mutation in the MYBPC gene. Conversely, cats may carry the mutation without having phenotypic evidence of HCM.

Differential Diagnoses

Before a diagnosis of HCM can be made, causes of secondary myocardial hypertrophy need to be excluded. These include:

Systemic hypertension
Hyperthyroidism
Hypersomatotropism (Acromegaly)
Hypovolaemia (pseudohypertrophy)
Myocarditis
Methylprednisolone acetate administration
Infiltrative myocardial neoplasia e.g. Lymphoma
Feline muscular dystrophy

Treatment

Prognosis

@@ Line 8: / Line 8: @@
 ===Dynamic Left Ventricular Outflow Obstruction (LVOTO)===
-This may be caused by systolic anterior motion of the mitral valve (SAM) and mid-systolic contact of the left ventricular free wall (LVFW) with the interventricular septum (IVS) during systole - cavity obliteration.
+This may be caused by systolic anterior motion of the mitral valve (SAM) and mid-systolic contact of the left ventricular free wall (LVFW) with the interventricular septum (IVS) during systole.
 ====Systolic Anterior Motion of the Mitral Valve (SAM)====
 This is where the anterior mitral valve leaflet moves towards the IVS in systole, therefore creating obstruction in the left ventricular outflow tract which interferes with the LV outflow in mid-systole.  As a result of this movement, the mitral valve leaflet does not completely seal the atrioventricular annulus; this causes a secondary mitral regurgitation. The combination of turbulent blood flow in the left ventricular outflow tract and mitral regurgitation causes a systolic murmur which can be identified on auscultation.
-The mechanism of SAM is not completely understood. One hypothesis is that deformation of the mitral valve architecture (leaflets, chordae tendinae, papillary muscles) and the hyperdynamic state caused by myocardial hypertrophy cause SAM.
-===Diastolic Dysfunction===
-Myocardial hypertrophy and interstitial fibrosis leads to reduced LV compliance. Tachycardia can exacerbate diastolic dysfunction by reducing diastolic time, and hence the time allowed for ventricular filling.  Since coronary blood flow to supply the myocardium occurs in diastole, tachycardia may accelerate myocardial ischaemia.  Diastolic dysfunction causes increased LV filling pressure. Left atrial (LA) enlargement initially compensates for this until maximal compliance of the atrium is reached. Once this point is reached, atrial pressure rises. This will subsequently result in pulmonary venous hypertension and eventually left-sided congestive heart failure. SAM and mitral regurgitation further contribute to ventricular filling pressure.
-===Systolic Dysfunction===
-Systolic dysfunction can be a feature of any myocardial disease in which there is significant ischaemia and replacement fibrosis of the myocardium.  This results in reduced stroke volume and increased ventricular filling pressure.
 ==Clinical Signs==
-A large proportion of cats with HCM are asymptomatic, and diagnosed as a result of echocardiography for investigation of a murmur or gallop rhythm detected on auscultation. A murmur is present in >50% of cats with HCM, due to dynamic left ventricular outflow tract obstruction and mitral regurgitation caused by SAM of the mitral valve.
 ==Diagnosis==
 ===Genetic Testing===
@@ Line 38: / Line 29: @@
 ==Treatment==
 ==Prognosis==
-[[Category:Cardiology Section]]