Idiopathic hypertrophic cardiomyopathy Flashcards
Give a definition of hypertrophic cardiomyopathy
The vast majority of cats with heart disease will have HCM
HCM is a disease of the myocardium that results in concentric or asymmetric hypertrophy of the left ventricular wall and/or interventricular septum in the absence of identifiable causes such as an increase in afterload (e.g., aortic stenosis, systemic hypertension), hormonal disease (e.g., thytotoxicosis, acromegaly) or infiltrative disease (e.g., lymphoma)
- systemic hypertension and hyperthyroidism do not cause severe LVH, so if a cat has severe LVH (>=7 mm) and systemic hypertension or hyperthyroidism, it can generally be assumed that these systemic disorders are not the sole cause of LVH
- aortic stenosis is rare in cats
- lymphoma is a rare cause of an increase in LV wall thickness
How frequent is HCM
Hypertrophic cardiomyopathy is common in apparently healthy cats, in contrast with other cardiomyopathies
- it affects 1 in 7 cats
The HCM prevalence increases with age
What are the characteristics of HCM
HCM is characterized by a thickened, functionally stiff myocardial wall (due to fibrosis and/or fiber disarray)
- often these cats have a reduced LV chamber size
Normal diastolic filling cannot be achieved because of impaired ventricular relaxation (which is an energy consuming process) and ventricular stiffness
- this results in elevated left atrial and pulmonary venous pressures with subsequent pulmonary edema or pleural effusion formation
What is the mechanism explaining the obstructive form of the HCM
In approximately 67% of cats with HCM, dynamic left ventricular outflow obstruction, and mitral valve regurgitation occurs secondary to abnormal motion of the mitral valve (typically called systolic anterior motion)
What is the main cause for heart murmur in cats with HCM
Systolic anterior motion of the mitral valve is the usual cause of a heart murmur in a cat with HCM
The murmur is often dynamic, which means it becomes louder when the cat is excited/stressed and softer when the cat relaxes
- this occurs because physical or emotional stress increases the severity of SAM and of DLVOTO, in turn increasing the velocity of flow through the dynamic outflow tract obstruction
How is the genetic trait for HCM in Maine coon cats
In the Maine coon, a genetic defect which has an autosomal dominant mode of inheritance with incomplete penetrance has been identified
- the genetic defect consists of a single base pair change (G to a C) within the gene that encodes for feline myosin binding protein C (MYBPC3)
- the mutation is called A31P
What is the mutation in Ragdolls
Ragdolls have a different defect in the same gene as Maine coon (MYBPC3)
- a C to T base pair change
- it is called R820W
Ragdolls are not related to Maine coons, so it is likely that this represents a completely independent mutation
Explain why DNA testing is superior to echocardiographic screening for HCM
Ultrasonography may be affected by operator interpretation and variable age to onset of myocardial hypertrophy in individual animals
- even if not all affected cats will develop HCM, they ideally should be withdrawn from the breeding pool
Despite this being the general rule, cats without a mutation should be screened echocardiographically for HCM, since a small percentage will have unequivocal findings of HCM due to some unknown cause
What would be your recommendation to a Maine coon breeder
The current recommendation is to continue breeding only phenotypically normal heterozygotes (normal echo on annual examination) with mutation-negative cats
Only mutation negative offspring should then be chosen as breeding replacements
How is a diagnosis of idiopathic HCM made
Diagnosis is made by the documentation of an interventricular septal or left ventricular free wall thickness (at any location) of > 6mm during diastole, in the absence of other causes of myocardial thickening
- rule out hypertension, hyperthyroidism, aortic stenosis, acromegaly, …
- remember that myocardial thickening can be asymmetric
Explain how a cardiac condition can manifest as transient neurologic signs
Cats that present for transient neurological abnormalities should also be evaluated for occult heart disease, as these signs may be caused by emboli arising from an intracardiac thrombus secondary to HCM
What are the typical histopathological findings in heart with HCM
Cardiomyocyte hypertrophy
Myofiber disarray
Interstitial fibrosis
Arteriosclerosis of the small coronary arteries
What are the known genetic factors in hypertrophic cardiomyopathy
Two mutations in cardiac myosin binding protein C, a gene within the cardiac sarcomere, have been identified
- A31P mutation in Maine Coons
- R820W mutation in Ragdolls
Other variants of these mutations very likely exist given that Maine Coons and Ragdolls without these mutations also develop HCM
How would you characterize the prevalence and penetrance of HCM in Maine Coons
There is a high prevalence in Maine Coons (34% in one study)
The penetrance (detection of HCM phenotype) is low in Maine Coons with a heterozygotus genotype, and cats with the homozygous genotype can remain healthy
How would you explain the apparition of a congestive state in a cat with HCM
A common functional abnormality seen with HCM is diastolic dysfunction
- this means the LV is stiff and so for any given blood volume that flows into the LV chamber in diastole, the diastolic pressure in the LV chamber is increased
- since the mitral valve is open in diastole, whatever pressure is present in the LV in diastole is also present in the left atrium
- as a result, an increase in LV diastolic pressure causes an increase in LA pressure
An increase in LA pressure results in LA enlargement
- the increased LA pressure also results in increased pulmonary venous pressure, and therefore enlargement of the pulmonary veins, and in increased pulmonary capillary pressure, which causes pulmonary edema
The veins that drain the pleura that lie on the surface of the lungs (visceral pleural veins) drain into pulmonary veins
- so an increase in LA and pulmonary venous pressure is also assumed to cause pleural effusion in cats
Pulmonary hypertension in cats in left heart failure due to a cardiomyopathy is uncommon and, when present, is usually not severe
Which factor worsens SAM: increased heart rate or increased myocardial contractility
Increased heart rate is not a worsening factor
- ivabradine, an agent that decreases heart rate without decreasing contractility, has little to no effect on SAM
SAM worsens when contractility increases with stress (i.e., catecholamine stimulation) and decreases when contractility is lessened with a beta blocker such as atenolol
Explain why a cat in stage D won’t respond adequately to high-dose furosemide PO
A cat that is not responding adequately to high-dose furoosemide PO may not be responding because not enough drug is getting to the nephron due to poor bioavailability (poor absorption from the GI tract)
Such a cat can be treated with parenteral (SC) furosemide (100% bioavailability) or switched to oral torasemide, which is more readily absorbed from the GI tract
- the dose of torasemide is 1/10 to 1/20 that of furosemide
What are the key facts about pimobendan in with HCM
Despite a serum concentration 10 times higher in normal cats than in normal dogs for a comparable dose administration orally, LV myocardial function is only mildly increased for a short time when compared with dogs
Piumobendan is a phosphodiesterase III inhibitor and a calcium sensitizing agent that increases contractility (positive inotrope) by increasing the binding of calcium to troponin C
- pimobendan increases myocardial contractility to a degree comparable to dobutamine but without increasing myocardial oxygen consumption
Pimobendan :
- have the potential ability to improve diastolic function and reduces diastolic filling pressure
- may improve systolic LA function (for a short time)
- typical dose is 0.1-0.25 mg/kg, PO, q12h
