Feline Myocardial Disease Flashcards
1
Q
Describe the phenotypical varioations in the patterns of hypertrophy in feline HCM
A
- Concentric hypertrophy is the primary change, without evidence of a cause for pressure overload or hormonal stimulation
- There is marked variation
- Mild to severe
- Diffuse (2/3) to segmental
- Diffuse hypertrophy can be symmetrical or asymmetrical
- Occasionally only one segment is thickened, most commonly the basal IVS (can cause a fixed LVOTO)
- Marked diffuse hypertrophy including the papilliary muscles can result in end-systolic LV cavity obliteration and endocardial contact plaques
- RV hypertrophy may or may not be present and is much less common than LV changes.
2
Q
Describe the histopathological lesions that lead to the phenotypical expression of HCM
A
- Myocardial fibre disarray - varying degree
- Mild to severe arteriosclerosis of the intramural coronary arteries
- Interstitial myocardial fibrosis and replacement fibrosis
- Disorganized cardiac muscle cells in the IVS of ~ 30%
- This can occur even in regions that are not hypertrophied
- Explains the findings on TDI of myocardial dysfunction in apparently normal segments (normal thickness)
- Fibrous contact plaques can be seen at the site of mitral valve systolic apposition on the IVS in HOCM.
- Neutrophilic and lymphocytic infiltrates have been found together with increased myocardial collagen deposition in pre-clinical HCM - possible inflammatory process early in the disease.
3
Q
Discuss the known genetic contribution to HCM in the Maine Coon breed
A
- A causative mutation int he cardiac Myosin Binding Protein C sarcomeric gene (MyBPC3)
- Autosomal dominant inheritance
- Single base pair change - guanine to cytosine
- Alteration to protein structure - alanine replaced by proline
- This mutation is highly specific to the Maine Coon breed
- High prevalence of the mutation - 31% (Asia and North America) to 46% (Australia)
- HCM phenotype is strongly dependent on the genetic status of this mutation
- relative risk of 9.9 for heterozygotes
- relative risk 35.5 for homozygotes
- Other mutations are likely involved given some homozygous wild type Maine Coon cats may develop HCM.
4
Q
Describe the known genetic basis for HCM in non-Maine Coon cats
A
- A substitution mutation in the MyBPC3 gene has been described in the Ragdoll breed.
- Single base pain change of cytosine to thymine
- Seconday amino acid change of arginine to tryptophan
- In a survey of 236 Ragdoll cats, 34% were positive for the MyBPC3 mutation
- 85% of the affected cats were heterozygous for the mutation
- British Shorthair, Sphynx, Norwegian Forest Cat and non-pedigree breeds have all been demonstrated to have familial forms of HCM.
- Sphynx - autosomal dominant with incomplete penetrance
5
Q
Briefly describe the pathophysiological consequences of HCM in sequence
A
- Diastolic dysfunction is the major mechanism that explains the progression through to CHF
- Diastolic dysfunction primarily from myocyte disorganisation and fibrosis.
- Reduced diastolic function lead to increased end diastolic LV pressures
- This leads to increased LA pressures, eventually leading to eccentric hypertrophy of the LA
- Visceral plueral veins drain into the left atrium - increased LA pressures can lead to pleural effusion due to decreased venous drainage
- Left auricular enlargement leads to decreased blood velocities, predisposing to thrombus formation
- Regional to global systolic dysfunction may develop
- SAM, elongation of the anterior mitral leaflet and false tendons in the LVOT can contribute to:
- LVOTO - decreased cardiac output
- Mitral valve regurgitation
- Further increase in end diastolic volume, contributing to LA dilatation
- LVOTO - increased LV systolic pressures could exacerbate the hypertrophic change
- Ventricular arrhythmias, myocardial dysfunction and dynamic LVOTO all result from the predominantly left ventricular myocardial changes.
6
Q
Describe the clinical signs or clinical findings at the time of diagnosis of feline HCM
A
- Various studies have reported from 33-77% of cats to have no clinical signs at the time of diagnosis.
- Non-clinical cats are typically investigated for the presence of a heart murmur, for breed screening purposes or cardiovascular assessment prior to anaesthesia
- Signs of CHF - 70-80% of clinically affected cats
- tachypnoea or dyspnoea
- pulmonary oedema or pleural effusion
- Anorexia and lethargy are common with CHF and may precede the onset of CHF
- Signs attributable to ATE - second most common clinical sign
- 4-17% of HCM cats at the time of diagnosis
- Syncope and weakness - 1-6% of cats
- Open mouth breathing / dyspnoea in the absence of radiographic signs of CHF - may be due to angina like chest pain.
- Abnormal cardiac auscultation - 78-92% of cats
- systolic murmur (typically left apical) 64-89% - common in asymptomatic cats
- Gallop rhythm up to 33% of cats - rare in asymptomatic cats
- Arryhthmia in 6-10% of cats - most are symptomatic
7
Q
Describe the wide variation in clinical course and prognosis in cats with HCM
A
- Due to widespread screening programs and the variable presence of auscultatory abnormalities on clinical examination, coupled with the lack of overt clinical signs in potentially significantly affected cats, HCM is diagnosed very early or very late and at all stages in between.
- The huge variation in the timing of HCM diagnosis contributes largely to the vast variation in prognosis.
- There is a marked heterogeneity in the progression of the disease also, largely due to underlying complex genetic factors
- Cats without signs of CHF live significantly longer than cats with clinical signs: >3617 d versus 194 days (Payne et al)
- Rush et al. 2002: median survival based on clinical signs
- Occult disease - 1129 days
- Syncope - 654 days
- CHF - 563 days
- ATE - 184 days
- 80% of cats with asymptomatic HCM died of other disease, 80% of cats with symptomatic HCM died of cardiac causes.
8
Q
What are the pathological lesions identified in cats with restrictive cardiomyopathy
A
- Two distinct forms of RCM are described
- Myocardial RCM
- Endomyocardial fibrosis RCM
- Histopathological features of HCM are seen in cats with RCM
- myocyte diarray
- abnormal intramural coronary arterioles
- replacement scarring
- Endomyocardial form - severe endomyocardial scarring - spider web or tubular bands in the mid-portion of the LV
- In both forms, the endocardial thickening is associated with:
- interstitial fibrosis
- variably myocyte hypertrophy and necrosis
- intramural coronal arteriosclerosis
- inflammatory infiltrates
9
Q
Discuss the major clinical findings in cats diagnosed with RCM
A
- The majority of cats diagnosed with RCM have overt clinical signs at the time of diagnosis. Ie. Diagnosis of occult disease is uncommonly detected
- In one study of 112 RCM cats, 94 (84%) were symptomatic.
- 16% were referred for murmur or arrhythmia investigation
- 76% (of the 94) had dyspnoea: 71% of these were due to pleural effusion
- 56% - non specific signs - lethargy, weakness, anorexia
- 17% ascites
- Paresis with ATE - 10%
- A heart murmur is present in ~ 2/3 of cats with RCM
- A gallop rhythm is detected in ~ 1/3 of cats with RCM
10
Q
Discuss the clinical course and prognosis in cats with restrictive cardiomyopathy
A
- In general, the prognosis for cats diagnosed with RCM is poor.
- The majority of cats diagnosed with RCM die from cardiac disease (60-86%).
- Survival times of 132 and 273 days have been reported
- Approximately 1/3 of cats diagnosed with RCM have been euthanised or die spontaneously
- Excluding cats that die within the forst 24 hours of diagnosis, a median survival time of 364 days has been reported.
11
Q
Discuss and define the echo parameters used to diagnose restrictive cardiomyopathy.
Note typical and common echo findings in cats with RCM
A
- Marked left atrial to biatrial enlargement is common
- Spontaneous echo contrast may be present
- Restrictive bands may be seen in the endomyocardial form of the disease
- Restrictive filling patterns
- Altered transmitral flow - peaked and short E wave, reduced A wave
- Reduced ventricular systolic function as measured by reduced tissue Doppler movements
- Reduced peak velocity of pulmonary venous flow
- Normal left ventricular wall measurements - ie. not hypertrophic
- Pleural effusion or small volume pericardial effusion is common with CHF
12
Q
Describe the echo based assessments of diastolic function in cats with cardiomyopathy
A
- LA enlargement: In the absence of significant mitral regurgitation, LA enlargement is largely influenced by LV diastolic dysfunction. As left atrial size mirrors chronic changes in LV diastolic dysfunction, it is a useful and prognostically significant measure
- Transmitral flow (E:A ratio)
- Important “eye ball index” to assess diastolic function
- Measured from optimised left apical 2 or 4 chamber view. Use colour Doppler to ensure accurate orientation
- Use PWD at tip of opened mitral leaflets
- Average of 3 measurements is recommended
- E - early transmitral pressure gradient determined by:
- Relaxation
- Suction
- Recoil
- Chamber capacity
- LV compliance
- LA pressure
- Filling volume
- A wave is determined by atrial contractility, LA preload and LA afterload
- IVRT (Isovolumic relaxation time)
- Time from aortic closure to start of mitral inflow
- Measured in L apical 3 or 5 chamber view using PWD
- Most useful at extremes, as changes reflect a product of LV relaxation and LA pressure changes
- Deceleration time of transmitral flow
- Time for E wave to return to baseline after peak.
- Determined by how fast the maximal capacitance of the LV is reached - ie. how quickly LVP increases
- Pulmonary vein flow velocity
- Strongly influenced by LV diastolic properties
- Mitral Annular velocities
- Assessed by tissue Doppler imaging
13
Q
Document the pathophysiological consequences of dilated cardiomyopathy in cats
A
- Degenerative myocardial lesions predominate
- Myocytolysis
- Fibrosis
- Arteriosclerosis
- Inflammatory infiltrates
- Initial lesions responsible for reduced systolic function
- Decreased systolic function leads to end systolic volume overload and dilatation
- Dilatation of the ventricles leads to dilatation of the annulus and secondary mitral (and tricuspid) valve insufficiency
- Mitral valve insufficiency in ~ 69% of cases
- Both mitral and tricuspid insufficiency in ~ 35% of cases
- The combination of diastolic dysfunction and mitral regurgitation leads to increased LA pressures and LA enlargement
- Left atrial enlargement will lead to spontaneous echo contrast in ~ 10% of cases.
14
Q
List the incidence of cardiac specific clinical signs at the time of diagnosis for feline DCM
A
- Most present with signs of CHF
- Pleural effusion 69%
- Pulmonary oedema 34%
- Ascites in 6/11 in one case series
- Systemic hypotension or weakness described in ~ 55%
- ATE ~ 10%
- Collapse is rare at ~ 3%
- Assymptomatic diagnosis is possible but uncommon
- Auscultation abnormalities are common
- Gallop sounds in 72%
- Systolic murmur in 34%
- Arrhythmia in 28%
- Muffled heart sounds in ~ 3%
15
Q
Describe the expected prognosis with feline DCM
Note the report prognostic indicators in the answer
A
- Prognosis is poor with DCM, one of shortest survivals of all primiary cardiomyopathies
- Occult phase is likely but poorly described - natural history leading up to CHF is therefore not known
- Median survival of 49 days versus 12 days in a cohort of 32 cats who received pimobendan and standard treatment versus standard treatment only (retrospective study - Hambrook and Bennett)
- Hypothermia and FS% < 20% at diagnosis are considered to be negative prognostic indicators
- Euthanasia due to refractory CHF: 42%
- Sudden death: 36%
- Euthanasia due to ATE: 19%
