Canine Myocardial Disease

Question 1

List the known causes or contributing factors to the development of dilated cardiomyopathy in dogs

Answer 1

1. Genetic factors
   
   • Doberman: Autosomal dominant
     
     • Splice mutation in pyruvate dehydrogenase kinase 4 (PDK4)
   • Irish Wolfhounds: Autosomal recessive with sex-specific alleles (males may be over-represented)
   • Great Dane: X-linked inheritance due to over-representation of males
   • Portugese water dog and Manchester toy terrier - early onset disease: Likely autosomal recessive and linked to a region on chromosome 8 (PWD)
2. Nutritional factors - taurine deficiency is the best documented example
3. Viral infection - secondary to myocarditis?
4. Toxic factors - including doxorubicin treatment

Question 2

Describe the clinical presentation and history of dogs with dilated cardiomyopathy

Answer 2

• Typical clinical history could involve lethargy, exercise intolerance, collapse/syncope, tachypnoea, soft cough, or owner identification of an abnormal heart rhythm.
• Soft systolic murmur over the mitral region or a gallop due to audible S3 (increased blood volume in the ventricle)
• Arrhythmia - tachyarrhythmia or intermittent arrhythmia. Ventricular and supraventricular arrhythmias are both common
• Pulse deficits
• Any sign of congestive heart failure - left or right sided.

Question 3

List the typical findings on routine cardiac screening diagnostic tests in a dog with clinically significant DCM

Answer 3

1. ECG:
   
   • Atrial or ventricular enlargement patterns - tall P or R waves
   • VPCs or APCs with atrial fibrillation common.
   • Sinus tachycardia in the face of HCF and sympathetic wind-up
2. Radiography:
   
   • Cardiomegaly may be evident
     
     • With out without clear left or right atrial enlargement
   • Distended pulmonary veins with congestion
   • Pulmonary oedema with CHF
   • Pleural effusion is uncommonly seen
3. Echocardiography:
   
   • Diagnostic test of choice
   • Left ventricular enlargement (increased LVDd and LVDs) and reduced contractility (reduced FS% or ejection fraction)
   • Central mitral jet due to annulus dilatation
4. Biomarkers:
   
   • ANP and Troponin 1: increased in both occult and overt heart failure. Not sensitive enough to be used as a screening marker for occult disease (sensitivity above 85% had a specificity < 50%)
   • BNP: increased in occult and overt disease. Sensitivity of 95.2%, specificity of 61.9% - therefore a dog with increased BNP needs an echo to confirm/monitor for disease presence.
   • BNP not increased in boxer dogs with ARVC (due to lack of chamber enlargements as trigger for release)

Question 4

Describe the various clinical and clinicopathological presentations for doberman dogs with dilated cardiomyopathy.

Answer 4

• Genetic mutations are suspected however the specific mutation has not been identified. The splice mutation in the PDK4 gene identified in American debermans was not associated with the disease in European dobermans
• Adult onset disease
• Generally a long occult or pre-clinical phase.
• Arrhythmias or systolic dysfunction may predominate during the occult phase
  
  • ventricular arrhythmia may occur prior to the development of ventricular dilatation
  • Syncope is most commonly due to ventricular tachycardia, with clinically significant bradycardia only occasionally present.
  • > 50 VPC’s in a 24 hour Holter is suggestive of occult disease
• Early echo parameters include increased LVDd (> 46 mm) and LVDs (>38 mm)

Question 5

Discuss the typical clinical findings at presentation for giant breed dogs with DCM

Answer 5

• Atrial tachyarrhythmias and atrial fibrillation frequently preceed the development of a heart murmur, systolic dysfunction and CHF in the Great Dane and Irish Wolfhound.
• Lone atrial fibrillation is common in the giant breeds but when present, DCM is significantly more likely
  
  • In IW, 26/52 developed cardiac disease.
    
    • 22/49 dogs with AF died from cardiac disease - CHF or sudden cardiac death.
  • In IW without AF, 5/49 progressed to develop and die from cardiac disease.
  • AF preceeds the development of CHF by ~24 months
• Biventricular failure is common in IW, with chylothorax occasionally seen.

Question 6

Discuss the relationship between taurine deficiency in dogs with dilated cardiomyopathy.

Include breed specific information and cited evidence.

Answer 6

• Kittleson et al (1997) described a cohort of 14 American Cocker Spaniel dogs with DCM in which plamsa taurine was found to be < 50 nmol/L.
• Supplementation with taurine and carnitine resulted in significant improvement in LVDd, IVDs and EPSS echo parameters within 3-6 months
• All taurine and carnitine supplemented dogs were successfully weaned from other cardiovascular drugs
• Echo parameters did not return to normal
• Dogs < 10 years lived ~4 years, Dogs > 10 years lived ~14 months
• Taurine deficiency and DCM has also been documented in a family of Golden retriever dogs and a group of 12 dogs fed a commercial lamb based diet (likely taurine deficient) - Fascetti et al. 2003

Question 7

Note the evidence supporting the various treatment options for Doberman dogs with occult dilated cardiomyopathy

Answer 7

• PROTECT study (Summerfield): 76 dogs - placebo controlled, randomized and blinded study.
  
  • median time to end-point (CHF or SD) was 718 days in the pimobendan group and 441 days in the placebo group.
  • Median survival was 623 d versus 466 d
• ACEI:
  
  • Benazepril has been assessed in a few studies of occult DCM and in numerous studies for dogs with overt CHF due to DCM or valvular disease
  • One retrospective study suggested a benefit for using benazepril in the occult phase - 425-454 days versus 339-356 days
• Beta-blockers
  
  • Good evidence of improvement in QOL and mortality in humans
  • One study has demonstrated no difference in cardiac parameters or QOL measures with 3 months of Carvedilol (Oyama 2007).
  • Risk documented due to the known reduction in systolic function that may be augmented by beta blocker use

Question 8

Describe the genetics of ARVC in boxer dogs

Answer 8

• Autosomal dominant trait with variable penetrance
• A genetic deletion mutation in the gene striatin
  
  • Striatin protein was localised to the intercalated disc region of the caridac myocyte and co-localised with 3 desmosomal proteins
  • The human variant also has genetic mutations that result in abnormal encoding of desmosomal proteins - which are essential for intercellular junctions
• Most affected dogs are heterozygous for the genetic mutation
• Homozygous dogs develop a more severe form of the disease - significantly more VPCs and more likely to develop overt DCM

Question 9

Describe the typical historical and clinical findings in boxer dogs with ARVC.

How is a definitive diagnosis achieved?

Answer 9

• The majority of boxer dogs present with a history of syncope or collapse, often after exercise.
• Exercise intolerance or lethargy is common
• Sudden death prior to exhibiting symptoms may occur
• ~10% of dogs present with signs of left or biventricular heart failure
• Clinial examination is typically normal apart from the presence of a tachyarrhythmia
• A systolic murmur or gallop (S3 sound) may be evident
• Definitive diagnosis is best achieved with the use of a Holter monitor. However, a short 2-5 minute ECG may be sufficient to identify a ventricular arrhythmia
• Ventricular premature complexes typically have a left nbundle branch morphology (positive in lead II)

Question 10

Discuss when treatment is indicated for ARVC

Answer 10

• Treatment is typically commenced if there are clinical signs attribuatable to the arrhythmia, namely syncope.
• Treatment is also recommended if there is evidence of a pre-malignant arrhythmia such as RonT phenomenon on the 24 hour Holter (or a short ECG)
• Treatment is recommended for the assymptomatic dog if there are > 1000 VPCs in 24 hours based on Holter recording
• Treatment for systolic dysfunction or congestive heart failure is as described for DCM and other causes of CHF

Question 11

What are the treatment options and considerations?

Answer 11

• Sotolol is the first drug of choice
  
  • Typical starting dose is 1-2 mg/kg PO q 12 hours
  • Sotolol is a combined non-selective beta blocker and potassium channel inhibitor
    
    • Slows heart rate
    • Prolongs repolarisation and refractoriness
• Mexiletine
  
  • Typically used at 5-8 (or 5-6 when combined with sotolol) mg/kg PO q 8 hours.
  • Indicated for dogs with systolic dysfunction who may not tolerate a beta blocker
  • Indicated if sotolol is not providing sufficient arrhythmia contrtol
  • Class Ib anti-arrhythmic - inhibits inward sodium channel, slows the rate of rise of the AP (phase 0). Effective refractory period is also reduced
• Serial ECG or Holter recording can be utilised to assess the effectiveness of arrhythmia control.

Question 12

List the major known causes of myocarditis in the dog

Answer 12

1. Trypanosoma Cruzi
   
   • Cause of Chagas Disease
2. Leishmania
   
   • ​​Protozoan parasite endemic in regions around the Mediterranean basin
3. Other Protozoan organisms
   
   • Toxoplasma gondii
   • Neospora Caninum
4. Parvovirus
5. West Nile Virus
6. Fungal Myocarditis
   
   • Blastomyces has rarely been report to cause myocarditis.