Canine Myocardial Diseases - PDF

CANINE MYOCARDIAL DISEASES Eduardo J Benjamin, DVM, MS, Diplomate ACVIM (Cardiology) December 10, 2024  PollEv.com/eduardobenjamin856  Text EDUARDOBENJAMIN856 to 37607 to join  Questions: [email protected] Objectives  Describe common causes of myocardial disease in dogs  D...

CANINE MYOCARDIAL DISEASES Eduardo J Benjamin, DVM, MS, Diplomate ACVIM (Cardiology) December 10, 2024  PollEv.com/eduardobenjamin856  Text EDUARDOBENJAMIN856 to 37607 to join  Questions: [email protected] Objectives  Describe common causes of myocardial disease in dogs  Describe possible cardiac complications secondary to myocardial disease in dogs  Familiarize with common physical examination findings in dogs with myocardial disease  Familiarize with diagnostic tools and medical management for dogs with myocardial disease Myocardial disease  Affect the heart muscle  Not secondary to valve, endocardial or pericardial problem LV  Decreased contractility  Arrhythmias Canine Cardiomyopathies Dilated Cardiomyopathy (primary DCM) Secondary Causes Nutritional cardiomyopathy (L-carnitine, taurine, ‘grain-free’, ‘BEG’ diets) Myocarditis, infiltrative disease Tachycardia-induced cardiomyopathy Hypothyroidism Drug-induced cardiomyopathy (e.g. doxorubicin)  Canine Cardiomyopathies  Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)  Hypertrophic Cardiomyopathy (HCM)  Atrial Standstill (atrial cardiomyopathy) Functions of the Cardiovascular system  Blood pressure = Cardiac output * SVR  Cardiac output = Stroke volume * HR (L/min) (volume/beat) (beats/minute)  Stroke volume = Preload, Afterload, Contractility  As many other diseases: myocarditis, Dilated Cardiomyopathy (Primary) nutritional Ruled out cardiomyopathy, tachycardia induced, ect  Characterized by dilation and systolic dysfunction  Primary/idiopathic  Diagnosis of exclusion  Genetic mutation  Altered protein structure and function  Genetics of Dilated Cardiomyopathy In humans 30 – 50% of the cases are familial – Over 50 mutations identified to date In dogs, prevalence is high in certain breeds – Several important mutations have been identified Doberman: PDK4 (‘DCM1’) & Titin (‘DCM 2’), “DCM 3 and 4” identified in European Dobbermans – Several modes of inheritance have been identified Irish Wolfhound: autosomal recessive  What breeds get DCM?  Large breed, male, middle aged dogs  Doberman  Boxer  IrishWolfhound  Great Dane  Portuguese Water Dog  English Cocker Spaniel  American Cocker Spaniel Incidence & Prevalence of MVD vs DCM in the Dog da · big dog % of DCM dog de esmall dogs Mitral Valve degeneration 1kg 20kg 35kg 60kg+ Weight (kg) Pathogenesis of DCM Poor contraction (systolic dysfunction) Less volume ejected Poor cardiac output Compensatory mechanisms (Renin-Angiotensin-Aldosterone System) Main goal of RAAS: water retention; increase preload – regulate BP Stretch receptors/remodeling pathway; Eccentric hypertrophy  Decreased Stroke Volume in DCM Normal DCM 70 mls 25 mls 100 mls 100 mls Normal contractility EF% of 70 Decreased contractility EF% of 25 Renin-Angiotensin-Aldosterone System Soupvector  Advanced Dilated Cardiomyopathy Normal DCM 100 mls 50 mls 70 mls 70 mls 100 mls 100 mls 100 mls 280 mls Normal contractility EF% of 70% Severe DCM phenotype EF% of 25% Pathogenesis of DCM Neurohormonal activation (RAAS) Sodium and water retention Cardiac Remodeling: Eccentric hypertrophy Increased preload Increased Sphericity Fibrosis Abnormal systolic function Abnormal diastolic function Arrhythmias Progression of heart disease Clinical Consequences of DCM – Congestive Heart Failure PA Edema PV  Clinical Consequences of DCM - Arrhythmias Normal Sinus Rhythm Ventricular Tachyarrhythmias Arrhythmias – Atrial fibrillation  No p waves  Irregularly irregular rhythm  Clinical DCM – Weakness, Syncope Decreased CO; cerebral hypoperfusion How do arrhythmias decrease CO?  Heart fills during diastole  With severe tachycardias, diastolic time shortens  Preload is reduced; Reduced SV, CO Diastole Diastole  Clinical Course – 3 phases Genetic predisposition Clinical (overt) phase (Stage A) (Stage C) - CHF - Syncope - Sudden cardiac death - Weakness - Exercise intolerance Preclinical (occult) phase - Weight loss (Stage B) - Arrhythmias - Systolic dysfunction - Sudden cardiac death “Occult” DCM – No clinical signs Normal Early DCM LV LV History and Clinical signs - DCM  None in occult DCM  Respiratory signs  Coughing  Increased respiratory rate/effort  Abdominal distension (common in Irish Wolfhounds, Newfoundlands)  Syncope  Exercise intolerance/Weakness  Weight loss/anorexia  Physical exam findings  Soft (1-3/6) systolic murmur at the left apex  However, the absence of a murmur does not rule out DCM!  Gallop sound (S3) S3  Arrhythmia Phono  Weak peripheral ECG pulses/Pulse deficits  Jugular venous distention/pulsation Physical exam findings - CHF  Pale/cyanotic mucous membranes  Pulmonary crackles  Tachypnea/Dyspnea  Tachycardia  Hypothermia  Fluid wave Diagnosis - Echocardiogram  Diagnosis - Echocardiogram  Fractional shortening %  Dimension in diastole (LVIDd) – in systole (LVIDs)/Dimension in diastole *100  ~25-45% = normal Fractional Shortening = (7.1 – 6.2) x 100% =  45% = normal Wess, et all, 2017 Diagnosis - Echocardiogram Right parasternal short axis (La/Ao view) La:Ao < 1.6 (Normal) La:Ao > 2 (Abnormal)  Diagnosis - Echocardiogram Murmur: Mitral regurgitation secondary to LV dilation (annular stretch)  Diagnosis - Electrocardiogram ❑ 5 min ECG ❑ 24 hr Holter >300 VPCs in 24 h considered diagnostic for DCM Diagnosis – Thoracic radiographs ***A normal cardiac silhouette does not rule out systolic dysfunction Diagnosis - Biomarkers  NTproBNP – useful to detect cardiac enlargement  >550 pmol/L (sensitivity 78.6% and specificity 90.4% in Dobbermans) Wess, et all, 2011  Cardiac Troponin I – Myocardial cellular damage  >0.22 ng/mL (sensitivity 79.5% and specificity 84.4% in Dobbermans) Wess, et all, 2010 **Do not replace echocardiogram or Holter monitor Genetic testing (PDK4, Titin genes)  **Should not be used in place of standard screening  Useful when taken into consideration when selecting breeding pairs  **The absence of a mutation does not ensure the patient will never develop DCM  Incomplete genetic penetrance  tool echocardiogram- key diagnostic ECGor 24 hour holt monitor moracic vadiographs Biomarkers - NTproBNP - cardian proponin e genetic festing Screening for DCM – Review papers Goal: Identify disease early in the occult phase PIMOBENDAN RANDOMIZED OCCULT DCM TRIAL TO EVALUATE CLINICAL SYMPTOMS AND TIME TO HEART FAILURE: The PROTECT study - A randomized clinical trial RESULTS  Median time to primary end point (CHF or Protect Investigators: JVIM. 2012 Nov-Dec;26(6):1337 sudden death) for dogs receiving Median pimobendan was 718 days compared to Pimobendan 718 d (24 mn) 441 days for dogs in the placebo group Placebo 441 d (15 mn) Log-rank p = 0.0088 (P value of 0.0088).  Dogs in the pimobendan group had an average time before reaching primary end point that was 63% longer (9 months) longer than those onIncrease placebo.of 277 days = 9 months!!! Ace inhibitors during preclinical DCM Median time to onset of CHF or sudden cardiac death: Benazepril group: 425 days Placebo 339 days Treatment for Dogs with Overt DCM  Inotropic Support  Afterload Reduction  Pimobendan (0.25-0.3 mg/kg  Pimobendan PO BID)  ACE inhibitors  Dobutamine  Amlodipine (0.1-0.4 mg/kg PO BID)  Digoxin  Ventricular Arrhythmia control  Neurohormal Blockade  Lidocaine/Mexiletine  ACE inhibitor (0.25-0.5 mg/kg  Sotalol PO BID)  Amiodarone  Spironolactone (1-2 mg/kg PO  Supraventricular Arrhythmias - heart SID-BID) rate control  Preload Reduction (for CHF)  Diltiazem  Furosemide (2 mg/kg PO BID)  Digoxin  Low Na+ diet  Amiodarone  Treatment for Dogs with Ventricular Arrhythmias  Class I drugs (Na+ channel blockers) Nonsustained Monomorphic VT  Lidocaine ◼ IV only, bolus (2 mg/kg), then CRI (50-100 mcg/kg/min)  Mexiletine ◼ Oral 5-8 mg/kg q 8 hours ◼ Nausea/Diarrhea Nonsustained Polymorphic VT  Procainamide ◼ IV 2-4 mg/kg IV, then CRI (20-50 mcg/kg/min)  Class III drugs (K+ channel blockers)  Sotalol ◼ K+/β-blocker, oral 1-3 mg/kg q 12 hours Sustained Monomorphic VT  Amiodarone ◼ 10 mg/kg PO BID loading dose then 5 mg/kg q 24 hours. ◼ Neutropenia, liver dysfunction, thyroid dysfunction  Summary/Staging of DCM ❑ Stage A ❑ Genetic testing for DCM 1 & DCM 2(Dobbermans) through NC State genetics lab; Avoid breeding any homozygotes ❑ Breed heterozygotes to negatives ❑ Start echo and holter/ECG screening at age 3 ❑ Stage B1 (presence of arrhythmias) ❑ Yearly (or bi-yearly if homozygous) echo and holter/ECG ❑ +/- Antiarrhythmics ❑ Stage B2 (presence of systolic dysfunction +/- arrhythmias) ❑ Pimobendan, ACE inhibitor, +/- Antiarrhythmics ❑ Monitor resting respiratory rate ❑ Stage C (clinical signs of heart failure), Stage D (refractory) ❑ Stage B2 treatments plus Lasix, spironolactone and in end stages higher doses of all of the above or switch to torsemide. Prognosis (Stage C) DCM  < 1 year (typically 6 months)  Negative predictors for survival  Ascites (from concurrent RCHF)  Atrial fibrillation  Really decreased function (%FS = single digits) MONITORING FOR RECURRENT CHF Resting Home Respiratory Rate – excellent home monitoring tool for owners in conjunction with scheduled recheck points Schober et al. JAVMA 2011:239(4)  Taken daily when sleeping or resting quietly over 30 sec  >30 (sleep) to 35 (rest) per min = abnormal or increased Secondary Causes – Systolic dysfunction Secondary cardiomyopathies Nutritional Volume or Pressure Toxic Overload Decreased Systolic Function Infiltrative Metabolic Myocarditis Tachycardia Ischemic  Nutritional cardiomyopathy  2018 – Cases of DCM in uncommon breeds increased  “Non-traditional” or “BEG” diets  Boutique/Exotic-novel proteins and carbohydrates  Grain-free  Some home-made diets “I have no business in getting DCM!!”  BEG diets and DCM  In July 2018, the FDA started an investigation https://www.fda.gov/animal-veterinary/news-events/fda-investigation-potential-link-between- certain-diets-and-canine-dilated-cardiomyopathy#taurine BEG Diets and DCM No specific cause determined Hypothesis: – Absolute deficiencies of nutrients – Altered bioavailability of certain nutrients Smith, et all, 2021 – Inadvertent inclusion of toxic ingredients (pesticides, mycotoxins, additives) Diagnosis – Nutritional Cardiomyopathy  Echocardiogram  Diet history  Taurine levels (https://www.vetmed.ucdavis.edu/labs/reference-data-dogs) ***Many dogs with diet associated DCM have normal Taurine levels  Plasma: 60-120 nmol/ml  Whole blood: 200-350 nmol/ml  Response to therapy/diet change Treatment for Diet-associated DCM  As for primary DCM  Additionally:  Switch to standard diet (consider prescription if allergies)  Check taurine levels in suspected patients  Report to FDA suspected cases (collect brand, formulation, duration of diet, other supplements, etc.) Outcome  Reverse remodeling is possible in cases of diet-associated DCM!  Nutritional cardiomyopathy  Taurine – Amino acid with many functions (myocardium, retina)  Golden Retrievers and American Cocker Spaniels  L-carnitine - transporting fatty acids into the mitochondria  Cocker Spaniels and Boxers  MYOCARDITIS  The presence of myocardial necrosis or inflammation  Variety of infectious agents, physical (trauma)  Chamber enlargement and myocardial dysfunction, phenotypically similar to DCM  Tachy and bradyarrhythmias common  Diagnostics: Cardiac troponin I (cTnI) often elevated MYOCARDITIS – INFECTIOUS ETIOLOGY  Protozoal: Trypanosoma cruzi (Chagas), Leishmania, Neospora, Toxoplasmosis gondii  Viral: Parvovirus, Distemper, COVID  Fungal: Blastomycosis  Bacterial: Lyme disease, Bartonella  Travel history? CHAGAS DISEASE MYOCARDITIS  Incidence is low but increasing; infected dogs are usually from Texas  Parasite enters myocardium and multiplies rapidly, RV > LV  Acute Stage  Dogs develop severe fulminant CHF  Both brady & tachyarrhythmias are reported  Sudden death is common  Chronic Stage Kissing Bug  Dogs who survive acute stage  Progressive myocardial damage - systolic dysfunction and myocardial dilation (indistinguishable from idiopathic DCM)  Patients may present for symptomatic bradyarrhythmias CHAGAS DISEASE MYOCARDITIS  Diagnosis  Antibody titers (IFA)  Identification of trypomastigotes in peripheral blood  Identification of amastigotes on myocardial biopsy/necropsy  Treatment  Supportive care for arrhythmias and CHF  No known effective treatment in dogs  Benznidazole currently under investigation  Tachycardia induced cardiomyopathy ~300 bpm! Treatment: Stop the tachycardia! Medical (antiarrhythmics) Ablation Prognosis: Good with adequate tx response  Metabolic - Hypothyroidism  Reduced adrenergic receptor number, reduced Na/K ATPase activity among other molecular changes  Diagnostics: Thyroid panel  Treatment: Levothyroxine  Prognosis: Good with therapy Drug related - Doxorubicin  Chemotherapeutic agent  Cardiotoxic  Dose dependent  Arrhythmias and/or systolic dysfunction  Treatment: No direct treatment  Dexrazoxane (Zinecard) may help  Prognosis: Poor Secondary cardiomyopathies Nutritional Volume or Pressure Toxic Overload Decreased Systolic Function Infiltrative Metabolic Myocarditis Tachycardia Ischemic ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY (ARVC) Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)  Previously known as “ Boxer Cardiomyopathy”  Boxers are an animal model of the human form  Characterized by ventricular arrhythmias, syncope and sudden death  Ventricular systolic dysfunction and dilation can also be seen ARVC - Pathology  Fibrous fatty infiltrate of the right ventricular free wall +/- left  Familial disease in Boxers  Autosomal dominant trait  Deletion of gene encoding for striatin  Homozygous; more severe disease  Variable penetrance  Other genetic defects are involved but not yet identified ARVC  3 Types Originally Described (Harpster 1983)  Class I: asymptomatic  Class II: collapse/syncope  Class III: Arrhythmia and LV systolic dysfunction + CHF (left or biventricular)  All classes are characterized by RV arrhythmias Physical exam and Diagnosis of ARVC  Most affected Boxers have a completely normal examination  Arrhythmia may be auscultated  Electrocardiogram  Holter monitor (>100 VPCs, couplets, triplets, Vtach)  Echocardiography  Majority of dogs have normal structure and function  Not good for screening, helpful for dogs with overt signs of CHF  Biomarkers  cTnI – correlated with both VPC number and complexity, may provide supportive information  Brain natriuretic peptide – did not identify a difference Diagnosis of ARVC  Electrocardiogram Positive VPCs (“wide and bizarre” complexes) in lead 2 Severe ventricular arrhythmias - ARVC  Ventricular tachycardia, R on T phenomenon QRS complex R on T phenomenon T wave Diagnosis of ARVC – Holter monitor Treatment of ARVC  Treatment generally started  > 1000 VPCs/day  Runs of Ventricular tachycardia or evidence of R-on-T phenomenon  Clinical signs of syncope or weakness  Treatment  Sotalol, Mexilitine (often combination of both), Amiodarone  Exercise restriction  Pimobendan, ACE inhibitors, diuretics (for systolic dysfunction and CHF) Prognosis for ARVC  Sudden cardiac death is always a risk  Many dogs live for years on antiarrhythmic drugs without symptoms  Dogs with evidence of CHF typically have a survival time similar to DCM  Hypertrophic cardiomyopathy  Differential diagnosis for LV concentric hypertrophy  Shih Tzu, Terrier breeds  Mostly subclinical  3/68 dogs developed CHF  6/68 dogs died suddenly  Prognosis:  Survival time range: 8 months – 14 years after diagnosis Atrial myopathy/Persistent atrial standstill  English Springer Spaniels, Labrador Retrievers  Selective destruction of atrial myocardium resulting in James Buchanan Cardiology atrial standstill and bradycardia Library  Exercise intolerance, weakness, syncope, R CHF  Treatment: Pacemaker Prognosis: Guarded Questions?  [email protected]