Cardiovascular Flashcards
Functions of AT2 receptor?
Vasodilation, natriuresis, antigrowth factor, anti fibrosis, tissue regeneration
Functions of AT1 receptor?
Vasoconstriction, increased PVR, increased Na resorption, increased aldosterone and increased Na resorption in collecting ducts, increased vascular growth factors, atherogenesis, increased ADH, thirst, CO, decrease GFR, cardiac hypertrophy, fibrosis, ROS, inflamm cytokines
Sex bias in dogs for hypertension?
Males
Cats age and hypertension?
Increases with increasing age and with increasing HR
CKD and hypertension in cats?
20 - 60 %, 65 - 100 % of hypertensive cats with TOD have evidence renal dysfunction.
No corr with severity
Pathophys hypertension renal dz?
RAAS Symp tone Na retention Excess free water Structural arterial changes and endothelial dysfunction,. lack of local NO, increased ET Ox stress/ROS
SDMA and BP?
? assoc with NO?
ADMA no corr with hypertension or TOD
What types of CKD more likely have hypertension dogs?
Glomerular
60 % of glomerular dz secondary to leishmania
T/F: cats with polycystic kidney disease have high BP?
False, not common
Evidence for antihypertensives in cats?
60 % cats with SHT reached 15 % decrease or less than 150 BP using amlodipine, cf 18 % placebo
Decreased clin manifestations too but no imp survival
May decrease aldosterone secretion
T/F: amlodipine is really excreted?
No - hepatic metab, no need to drop dose in renal disease
What glomerular arteriole does amlodipine preferentially dilate?
Afferent
Amlodipine and antifungals?
Azoles might decrease metabolism
When to use emergent BP management?
TOD and > 180
> 200
MAP calculation?
Diastolic + (systolic - diastolic)/3
Neural control of vascular tone?
Vasomotor centre, medulla oblongata, constrict tissue bed dilate muscle with sympathetic stim
Baroreceptors in carotid body and aortic arch lack of stretch
Atria and pulm artery lack of distension (stretch receptors)
Also hypoxaemia/hypercarbia via chemoreceptors carotid body and aortic arch
Also effects macula densa to decrease GFR and conserve sodium
Mechanism of hypotension in sepsis/SIRS?
NO production
Depletion vasopressin
Disrupted smooth muscle calcium
Downregulation catecholamine receptors
How much hypovolaemia to cause hypotension?
20 - 25 %
Cardiac effects of SNS activation?
Increased SA node firing
Beta adrenergic receptor activation - increase slow inward calcium current so increase SA node firing
Shift activation curve inward pacemaker current (If), more pos voltage, Gs adenyl cyclase
Adrenergic activity increases contractility - beta - SERCA2, ryanodine, L type calcium channels, phospholamban
Augmented calcium induced calcium release and reuptake into SR
PKA force and contraction myofilaments
Effect of cardiac disease on CO at increased HR?
CO drops off at lower HR than healthy
NB downreg/uncoupling (beta arrestin, beta receptor kinase) beta1 receptors in heart failure, diminished contractility
Depletion cardiac norepinephrine stores, reply on systemic
Decreased response to adrenergic stim
Why can’t peripheral nerves produce epinephrine?
No phenylethanolamine N methyltransferase
Catecholamines in heart failure?
NE and epi higher than controls for both DCM and valve dz, NE maybe higher in DCM, corr with severity
Cats - both increased in cardiac dz also cong and noncong
Heart disease SNS or RAAS 1st?
SNS
Stim for renin?
SNS beta 1 activation juxtaglomerular cells
Decreased renal perfusion
Decreased sodium absorption PCT
ATII inhibits renin release
ATII remodelling?
MAPK
NB activation chymase myocardium
ATIII less potent
ROS (ATII and aldosterone) myocardial hypertrophy
Where do the natriuretic peptides come from? Effects?
BNP ANP atria
CNP endothelium
More BNP in chronic cardiac as ventricles start to make
Counteract RAAS. A type natriuretic peptide receptor. Induce natriuresis/diuresis. Inhibit tubular sodium transit inner medullary collecting duct.
Vasorelaxation
Inhibit renin and aldosterone release
NPRB does vasodilation from CNP (local)
NPRC clears the natriuretic peptides from circulation (ANP > BNP)
N terminal fragments of pro forms renal excretion so longer
Use of BNP in diagnostics?
Cats - marked increase BNP in myocardial dz
More useful than ET1
What is conivaptan?
V1A/V2 blocker
Normalise sodium and help congestion
Tolavaptan = V2 specific
AVP increased in heart failure
What factors cause vasoconstriction when CO falls?
Norepi, vasopressin, ET, ATII - calcium mediated vasoconstriction (muscle hypertrophy when chronic)
What causes endothelin release?
Hypoxaemia, stretch, ATII AVP NE bradykinin
Growth factors cytokines tGFbeta
ET1 and NO?
ET 1 increases NO which then decreases ET1
When is ET1 increased?
Cardiac dz pulm hypertension renal disease not systemic hypertension
Cardiac remodelling?
Physiological reversible pathologic not.
Hypertrophy from increased wall stress, wall stress normalised by hypertrophy (compensation), exhaustion and death of cardiomyocytes, fibrosis, ventricular dilation, decreased CO
Fibroblast proliferation AT11 aldosterone
Law of Laplace?
Wall stress = pressure x radius/2x wall thickness
Pressure overload - compensate with increased wall thickness, still increased energy requiremenet
Volume overload - modest wall thickness inc with chamber enlargement - appropriate workload redistribution, less increase in total work
Concentric hypertrophy - parallel sarcomere replication
Most common cause of death aortic stenosis?
Sudden death vent arrhyth (hypoxia?)
Terminal concentric hypertrophy?
Initial decrease collagen breakdown (metalloproteinase inhibitor decrease MMP 1 and 9(
Then collagen breakdown increases and hypertrophied ventricle dilates and fails
When is pleural effusion in heart failure most likely?
Biventricular due to overload of lymphatic drainage
What nitrate vasodilators effect pre and afterload?
Nitroglycerin preload - venodilator, nb tachyphylaxis
Nitroprusside balanced vasodilator
ACEi in CHF?
No prospective evidence preclinical MVD, retrospective DCM though benazepril improved outcome
Use in chronic diuretic
Dobutamine mechanism of action?
Beta1 antagonist - inotrope and lusitrope
Beta blockers in feline myocardial disease?
Detrimental heart failure, neutral preclinical
Dog - detrimental heart failure
What is atropine used to predict?
Medical management for sick sinus syndrome, doesn’t predict well with AV block
What factors determine the impact of arrhythmia on animal?
Rate Length sustained for Atrial ventricular temporal assoc Sequence of ventricular activation Myocardial/valvular function Cycle length irregularity Drug therapy Extra cardiac influences
What causes wide QRS?
Macro reentry
BBB
Ventricular premature complex
Eg asynchronous ventricular depolarisation
T wave should also be abnormal
What does vagal predominance do to ECG?
Wandering pacemaker - increased P w/ increased HR on insp
Sinus arrhythmia
What is ventriculophasic sinus arrhythmia?
P-P interval longer during AV block cf surrounding - P-P interval flanking QRS (2nd or 3rd degree)
Differentiate wandering pacemaker or sinus arrhyth from atrial arrythmia?
HR < 150
P’s taller not narrower
Degree of prematurity
Criteria for APC?
Premature timing Normal QRS (v occasionally wide/absent if timing dose to repol of ventricle) Non compensatory pause Diff amplitude P Diff P-R interval
Often structural. Also HT4 digitalis atrial tumour.
Atrial tachycardia = three or more APC > sinus rate (160/220)
Criteria for atrial flutter?
Flutter waves (rhythmic monomorphic)
Lack fo return to baseline
Normal QRS
Variable R-R
Macroreentrant
Treat if many passing AV node (tachycardia mediated cardiomyopathy > 240 > 3w)
Atrial fibrillation?
15 % canine arrhythmias, present in 50 % DCM
Electrical disorganisation at atrial level
Chaotic fibrillation waves
Irregular R-R
No P waves
Normal QRS
Afib prognostic importance?
Cause impacts rate - lone then subclin then CHF
Lone better px
Afib worsen prognosis large dogs with MMVD and CHF
How to treat AFib?
Digoxin and diltiazem, change dose of latter, aim 130 - 145, ECG assessment
Better HR control together cf alone
Beta blockers inferior
Treatment improves survival time in CHF large breed MMVD dogs if add digoxin cf diltiazem alone
Conversion - defib, amiodarone, lidocaine
Atrial dissociation?
Larger P wave passes AV other one stays in atrium - no significance
VPC criteria?
Most common pathological rhythm disturbance
Wide QRS, different with different T and no P
Narrow R-R interval
Diagnostic of VT: Fusion beat (normal and premature collide) Capture beat (normal PQRST after VPCs)
Usually compensatory pause or interpolation
> 3 in a row vtach
Must differentiate from: Escape complexes Potassium disturbance Cardiomegaly Bundle branch block Motion
More commonly cardiac in cats than dogs
NB inherited sudden cardiac death GSD - myocardial depolarisation defect
Cut offs for ventricular arrhythmias?
< 70 idioventricular, < 160 accelerated idioventricular, > 160 vtach
What should accompany ventricular fibrillation?
Unconscious, no pulses
What is Torsades de Pointes?
Ventricular arrythmia, arises from Q-T interval prolongation
Rotation of peaks due to changing geometry of reentrant circuit
Diagnosis:
Slow rhythm with prolonged QT before
R on T extrasystole (R occurs during vulnerable T wave)
Rapid ventricular rhythm with QRS complexes more regular than VF but with changing amplitude and polarity
Causes:
Hypokalaemia and hypocalcaemia
Congenital long QT syndrome of dalmatians
Class 1A antiarrthythmics eg quinidine
Tx - magnesium
Describe AV blocks
1st degree: long PR interval - high vagal tone/digitalis/alpha2
2nd degree: complete transient AV conduction interruption.
Mobitz I - progressive lengthening, Wenckeback phenomenon. High AV node good prognosis. Rare clin signs.
II - sudden, more guarded/poor px (?). Essentially if high grade same as 3rd degree and need pacing.
3rd degree: complete sustained with escape rhythm.
Can be incidental 110 - 140 bpm cats, can be subclin, but most likely of the 3 to cause clin signs
Sometimes caused by atrial dilation
2/3 can be functional alpha 2 hyperkalaemia digitalis but more common structural age inflamm or degen
Low number 3rd degree resolve or convert to second degree spontaneously
Treatment of AV block?
Pacing high degree 2nd II/3rd degree, increase survival cf no pacing
Feline AV block?
More than half have cardiomyopathy, in general have long survival times with no pacing as incidental
What are bundle branch blocks?
Altered bundle of his conduction - not arrhythmias in and of themselves
Wide QRS due to ventricular desynchronisation
Duration QRS > 0.07 dog or > 0.04 cat
Lead II - polarity pos left neg right
Hypertrophy, dilation, inflammation
Right - no issue
Left - indicative of left ventricular enlargement
What block do cats with heart disease get?
Left anterior fascicle block- degeneration/fibrosis/osseous metaplasia of left bundles more common than right
Tall R wave lead 1
Deep S wave II and III
Left axis deviation
What causes atrial standstill?
Hyperkalaemia
Atrial myopathy eg marked stretch
ECG artifact
Cardiac effects of hypokalaemia?
Cardiomyocytes more negative and AP longer (prolonged repolarisation) therefore near threshold longer - proarrhythmic
Latter effect clinically dominates < 3.5
Prolonged QT, atrial dissoc
Class I antiarrhythmics eg lidocaine act on sodium channels which require K to function, so hypokal can cause refractoriness to antiarrhythmics
Cardiac effects of hyperkalaemia?
Increased membrane potassium permeability during depolarisation when mild - rhythm stabilising, this predominates over depolarising effects (makes cell more pos overall)
Mild - short Q-T, narrow tall T wave (only 15 % for latter)
Decrease activity normal pacemaker tissue/decrease slope phase 4 depolarisation - sinus bradycardia, however HR unreliable
Wide QRS and decreased R wave amplitude - interfere cell-cell transmission velocity in ventricles
P-R prolongation, absence of P waves
Atria more sensitive than ventricles, myocardium most in atria, - sinoventricular rhythm (don’t see P but SA is firing)
Cardiac effects of hypocalcaemia?
Alter myocyte AP threshold, not resting potential. Low decrease threshold and facilitate depol. This is most in skeletal muscle minimal in cardiac.
Prolongs initial ventricular depolarisation - prolong QT
Why is calcium cardio protective?
Potassium raise resting membrane potential, calcium raise depolarisation threshold - so more normal gradient
What should be monitored during calcium infusion?
Shortened QT, ventricular complexes, decrease HR
Calcium raises depol threshold and shortens ventricular repol
What is an orthodromic AV reentrant tachycardia?
Normograde transmission AV node retrograde through accessory - macroreentrant loop - WolffParkinsonWhite
Diagnosis of sick sinus syndrome?
Prolonged sinus pauses, 1st/2nd degree AV block, bursts of supra ventricular tachycardia/ventricular asystoles - get ECG during episode of syncope/stumbling etc - episodes occur during bradycardia
Atropine response predict response to medical management - eg theophylline controls 50 %
Sometimes only sinus bradycardia
Criteria to institute pacing?
High degree second or any third degree AV block
SSS/SND with clin signs HR < 50, sinus pauses >3s when awake
What congenital cardiac defect do Chartreux cats get?
ASD and TVD
Siamese?
Supravalvular mitral stenosis, endocardial fibroelastosis
Most common congenital cardiac dz cat/dog?
Dog - PDA, AS, PS
Cat - VSD, PDA, TVD, MVD
What congenital conditions can severity be predicted from murmur duration and intensity?
SAS, PS
Lesions in Eisenmenger’s syndrome?
R to L shunt
Pulmonary arterial intimal thickening, medial hypertrophy, plexiform lesions
+/- pulm vasoconstriction
Embryology of PDA?
Embryonic left sixth aortic arch
Should close 7 - 10 d
Only elastic no muscular fibres in ductal media
Tapering most common, non tapering more severe and uncommon (the latter assoc with pulm hypertension and r-l or bidirectional shunting
Name 3 breeds common PDA?
GSD, Lab, cocker
also poodle, bichon
female!
Ddx for continuous murmur?
PDA, aortopulm shunt, coronary AV fistula
ECG with right ventricular hypertrophy?
Right axis deviation, deep S wave
Difference cat PDA?
More common pulm hypertension development
What PDAs not amenable to amplatz?
Non tapering - type III
Genetic VSD?
Keeshond
Breeds ASD?
Boxer, Samoyed, Doberman
Chartreux, Persian
Breeds VSD?
English bulldog, WHWT, ESS
Maine coone
ECG VSD?
Notched/wide Q
TVD breeds?
Labrador - autosomal dominant mutation with incomplete penetrance
Gret, Gt Dane, GSD
male!
Mitral valve stenosis?
Bull terrier
Mitral valve dysplasia?
GSD, Get, Gt Dane
ECG TVD?
Splintered QRS
Pulmonic stenosis breeds?
Beagle, cocker, Lab
Supravalvular - giant schnauzer
Subvalvular - boxer and English bulldog, anomalous corony artery development - circles RVOT below pulmonic valve
Cause of pulmonic stenosis?
Subvalvular/valvular obstruction or valve dysplasia
Thickening, leaflet fusion, annular hypoplasia, tethered valves
Overproduction normal valve collagen
Pulmonic stenosis severity?
Mild < 50
Severe > 80
Mild/mod probably normal life
Severe > 125 frequent major consequences
Criteria for pulmonic stenosis intervention?
Severe > 100
Symptomatic
Tricuspid regurgitation
Balloon - decrease pressure 50 % + in 80 %
50 % reduction mortality
Breeds for SAS?
Boxer, rottie,
Bull terrier valvular
Newfie - autosomal dominant, PICALM gene
Dogue de Bordeaux auto recessive
GRet
Normal boxer aortic annulus is smaller cf other breeds
What other abnormality assoc with SAS?
Mitral valve lesions
SAS severity?
80 - 100 = mod
can overest if CO high
Mild around 2.3 - 2.4 m/s
< 50 normal life
> 125 severe consequence
SAS management?
Prophylactic ABs (though evidence?) Balloon - decrease severity 50 % but improvement attenuated over time, no sig diff survival cf atenolol
Beta blockers to decrease myocardial ischaemia, decrease HR, decrease myocardial o2 consumption, increase diastolic time
However again no sig survival benefit atenolol
Breed for ToF?
Keeshond, English bulldog
Abnormalities ToF?
Transposed aorta, right ventricular hypertrophy, VSD, RV outflow obstruction
MMVD signalment?
CKCS, dachshund, mini poodle, yorkie
Male > female
Males develop younger than female
What happens if breed two MMVD early onset dogs?
Earlier onset dz in pups, and vice versa
Gene loci 13 and 14 assoc with age of onset in CKCS
MMVD histopath?
Weakened/disturbed connective tissue, prominent spongiosa, disorganised collagen fibres iin fibrosa layer, increased mucopolysacharide/glycosaminoglycan, endothelial cells damaged esp edge
Pathophys MMVD?
Endothelial damage > ET1 > valvular interstitial cells become myofibroblast/smooth muscle cells (serotonin driven - increased in CKCS), MMPs
Which leaflet more likely to prolapse MMVD?
Anterior - more mobile, jet lesions laterally directed
MMVD heart chamber enlargement?
Initially slow, fast in 6-12 months before CHF
MMVD XR changes?
Elevation caudal trachea and left mainstream bronchus, bulge/straightening caudal border heart, bulge 2-3oclock
XR pulm oedema - dorsocaudal, perihilar, often RHS worse - cranial can be first in acute
XR right heart enlargement?
Increased sternal contact, elevation trachea, straight cranial border, vena cava enlargement, bulge 9 - 12 - reverse D shape
How to measure LA?
Right parasternal short axis view
MMVD - why would regurgitant jet velocity be low?
Hypotension, myocardial failure, increased LA pressure, impending CHF
Risk factors MMVD progression?
Large breed, older, male, severity of valve lesion, severity MR/LA/LV dilation, HR, NTproBNP, troponin, arrythmia, syncope
Ddx for MMVD?
Endocarditis, DCM, congenital cardiac dz
Endocarditis lesions more isolated and echogenic
Evidence for stage B MMVD tx?
ACEi mono therapy: no difference survival placebo control - SVEP/VETPROOF
Beta blocker: experimental? prospective placebo control trial terminated due to lack of efficacy
Amlodipine: ? imp echo?
Pimobendan: decrease cardiac size. EPIC delays onset CHF (doubles time) in B2 (LVIDD > 1.7, LA:Ao > 1.6, VHS > 10.5)
Goals in management of stage C MMVD?
Reduce venous pressure
Maintain CO
reduce regurg and cardiac workload
Protect heart from negative neurohormonal effects
Benefit of torasemide?
Longer duration of action, potency less affected by diuretic resistance, aldosterone antagonist properties
Evidence for stage C MMVD?
Pimobendan: VETSCOPE/QUEST - adjunct to diuretic, less severe CHF and longer survival cf ACEi + diuretic. Decrease HR, decrease free water retention, decrease heart size, decrease regurg.
ACEi: less severe clin signs less exercise intolerance live longer. Counteract reflex RAAS stim when diuretics admin.
Spironolactone: decrease cardiac death/euthanasia/worsening CHF when add to other tx
Digoxin: weak pos inotrope, decrease baroreceptor reflex tachycardia/decrease central symp activity no evidence
Prognostic factors after onset CHF?
Pos: pimo, ACEi,
Neg: higher furosemide dose, worsening exercise tolerance, cardiomegaly, worse MR, LVIDD, E wave velocity, worsening systolic function, decreasing creatinine (cachexia), complication development
What drugs might reduce MR/LA size?
Pimobendan, afterload reducers (amlodipine hydralazine ACEi), diuretic
Pulmonary hypertension in MMVD?
Pressure gradient > 55 neg prog factor
Endocarditis signalment?
Male middle age medium to large purebreed
Pathophys endocarditis?
Either direct bacterial contact or haematogenous (capillaries in valves) - bacteria usually req predisposing factors to colonise eg immune supp, endothelial damage/platelet-fibrin complex deposition - adhere to valve
Extracellular matrix protein, thromboplastin and tissue factor trigger coagulation, coagulum forms, inflamm starts
Inflamm and bacterial enzymes cause valve tissue degradation
Endocarditis bacteria?
Staph (aureus, pseudintermedius, coagulation pos and neg)/Strepp (canis, bovis, beta haemolytic). Ability to adhere to valves.
Also - E coli, P aeruginosa, Corynebacterium
Staph aureus and Bartonella (henselae, clarridgeiae, washoensis) internalise in endothelium, evade immune system and antibacterials
Some no detectable infection elsewhere
Consequences of endocarditis - what factors?
Bacteria - virulence/production of endocrine or exotoxins (gram neg paracute/acute, chronic subacute/chronic)
Site of infection and impact on valve function - necrosis/destruction of valve stroma/chordae tendinae peracute/acute with CHF
Sequelae eg immune complex deposition, vegetative thrombi/metastatic infection - thromboembolic 30 - 40 %, lungs then kidneys most common, then distal aorta
Most common valves endocarditis?
Left heart, mitral > aorta, aortic more common Barttonella
Might involve wall (mural endocarditis) but rarely RHS
What is an intracardiac vegetation made of?
Platelets, WBC, fibrin, bacteria, RBC - often covered by intact endothelium
When to raise suspicion for endocarditis?
Immunosuppression Non-oral surgery within 3m Trauma to or infections of oral or genital mucosa Indwelling catheters Infected wounds Abscess Pyoderma
Most common clin sign endocarditis?
Lameness 34 %, new heart murmur (diastolic with bounding pulses = aorta - aortic insufficiency)
Heart murmur 75 %
Ventricular arrythmia 60 % aortic, arrthymia 50 - 75 % overall
Fever 50 - 90 % (absence more common in aortic or Bartonella)
Endocarditis echo?
Hyperechoic, independent movement, irregular outline
Erosive more difficult to identify - severe aortic regurg raise suspicion
However congenital SAS/systemic hypertension could also cause this/myxomatous valve/quadricuspid aortic valve
Arrhythmias in endocarditis?
Ventricular most common
ST segment deviation (?myocardial hypoxia/embolism/ischaemia)
CHF in endocarditis?
50 % - perihilar/caudodorsal pulm oedema - no diff with valve affected
LA enlargement not common (acute)
Blood culture endocarditis?
Negative in up to 60 - 70 % of cases - ABs, encapsulated infection, non-infectious endocarditis, Bartonella/slow growing organisms
In positive cultures, 90 % pos in 72 h
Bartonella in endocarditis?
28 % of cases in Cali, 50 % of those with neg culture
Also cause in cats
Concurrent pos serology for tick borne dz common (tick/flea vector)
Criteria for canine endocarditis diagnosis?
Definitive: histopath of valve, 2 major, 1 major and 2 minor
Possible - 1 major 1 minor, 3 minor
Rejected - other disease, resolution valve abnormalities in 4d, no PM evidence
Major - pos echo (vegetative/erosive/abscess), new valvular insufficiency (> mild aortic, no SAS/annuloaortic ectasia), pos culture (>1 pos or > 2 if common skin contaminant)
Minor - fever, > 15 kg, thromboembolic or immune mediated disease, pos culture (other), pos bartonella serology > 1:1024
What should you not use alongside aminoglycosides?
Diuretic - potentiate nephrotoxicity
ABs for endocarditis?
Beta lactam and aminoglycoside (or enro but resistance poss)
Depends on organ involvement
Also seek source
IV AB 1-2w, 6w overall, apt blood culture after 1-2w AB and 1-2w after. stop
Repeat echo during and after too
Monitor Bartonella with serology 1m after start AB - increased = ineffective, decreased = effective
Neg px endocarditis?
Late dx/late start tx
Aortic
Valvular vegetation
Bartonella
Gram neg
Heart/renal complications not responding to tx
Septic embolisation or metastatic infection
Throbocytopenia, increased ALP or hypoalb (70 % mort with latter)
Concurrent steroids
Bacteriostatic AB/premature AB termination
Pos px endocarditis?
Mitral valve (MST > 400 d) G pos from skin/abscess/cellulitis/wound
When to use prophylactic AB to prevent endocarditis?
SAS PDA VSD - also make sure treat any infection aggressively
Amoxi-clav/clindamycin
NOT MMVD even if doing dental
Juvenile onset DCM?
Portuguese water dog (autosomal recessive chromosome 8, sudden death or CHF), toy Manchester terrier (sudden death) - < 1y
Forms of DCM?
Occult/overt (former murmur/echo/arrhythmia, latter coughing weakness etc)
DCM echo findings?
Decreased FS, ejection fraction, end. systolic diameter/volume
Many also diastolic dysfunction
No valve thickening
Systolic dysfunction or ventricular dilation can occur first
NB EPSS, sphericity index
Biomarkers for DCM?
ANP in dobermann’s sig increased in occult and overt - other breeds not found sens/spec
Troponin - increased doberman overt/occult, not sens/spec
NTproBNP - increased in occult, quite sens, up to 1.5y pre-overt
Structural changes DCM?
Eccentric hypertrophy
L > R
Attenuated. waxy myofibrils, vacuolated myocytes, collagen fibres replace myocytes, fibrosis, necrosis, fatty infiltration
Specifics of cocker spaniel DCM?
ACS and ECS
Taurine ACS - supp taurine/l-carnitine and increase FS/decrease LVIDD in 4m (not completely normal) - blood better than plasma. cont supp for life. often can discont cardio meds 3-4m when FS > 20 %
ECS - familial? nutritional not identified. Marked LV enlargement. Variable dz course.
Dalmatian DCM?
Males
Only left sided
Arrhythmias uncommon
Survival 1.5 - 30 m, no sudden death, refractory CHF
Low protein diet? No evidence carnitind/taurine def.
NB Dals occ get AV valve dz
Doberman DCM?
Left/bivent (left > right), Afib/sudden death
Overt - Afb/VPC/CHF
If syncope do holter - Brady and tachyarrhythmias
Annual echo/holter = best predictors - increased LV end diastolic or systolic diameter; > 50 vpc/24h, couplets or triplets
Genetic mutations in DCM?
Doberman - autosomal dominant. PDK4 splice site mutation. Incomplete penetrance. Genetic test avail. not sole cause and this is only US NOT European.
Great Dane - Xlinked
Irish wolfhound - autosomal recessive, sex specific male dogs overrep
Standard schnauzer - RNA binding motif protein 20 gene (RBM20), auto recessive, genetic test available
Great Dane DCM?
Weight loss/coughing. Ascites. Afib. Occ VPC.
Afib before echo changes.
Irish wolfhound DCM?
Males.
Afib before structural. Precede CHF 24m.
Sometimes VPC/LAFB
Occ sudden death. More CHF (bivent, sometimes chylothorax)
Low taurine?
Newfie DCM?
No gender predip.
CHF, cough, bivent.
V few have heart murmur.
Afib most common.
Taurine in DCM?
Less likely in dog than cat as cats can’t synthesise taurine dogs can.
ACS taurine/carnitine
Lamb meal/rice diet (rice bran/whole rice?)
GRet - familial taurine deficiency
Taurine blood < 150 plasma < 40
Supp might fix - reecho
Evidence for DCM meds?
ACEi: delay onset of CHF in doberman with ventricular dilation (retrospective)
Beta blockers: 3m carvedilol no diff on anything
Pimobendan: PROTECT study placebo control, support use in doberman in occult phase - survival benefit and delay CHF/sudden death. Also increase survival symptomatic.
Risk factor for cardiac death DCM?
Arrhythmias - rapid VT, complex ventricular, combination of vent arrhythmia, systolic dysfunction and chamber dilation - risk sudden death
But sudden death occurs without these factors
These are factors poss to treat arrhythmias - sotalol (beta blocker/potassium channel blocker) - dose cautiously if systolic dysfunction
Mexilitene
Amiodarone (cf neutropenia hepatic enzymes)
Negative prognostic indicators DCM?
Age of onset, pleural effusion, pulm oedema, ascites, AFib, end systolic vol index, ejection fraction, restrictive transmittal flow pattern
ARVC histopath?
Fibrous fatty infiltration RV wall, myocyte vacuolation and loss
Features of ARVC?
Boxer
Vent arrhythmia/collapse/syncope/sudden death, some CHF (10 %, either left or bivent), some asymptomatic
Small number systolic dysfunction and ventricular dilation
Autosomal dominant inheritance with variable penetrance
Genetic cause ARVC?
Striatin gene mutation - genetic test available
Homozygous severe - type III ARVC, structural heart disease variety and higher numbers of arrhythmias
HOWEVER can have without the mutation
Type III ARVC?
Homozygous
Systolic murmur/gallop, ventricular dilation/systolic dysfunction
What physiological murmurs do Boxers get?
Left basilar systolic (can also be aortic stenosis…)
NOT indication of ARVC
Biomarkers for ARVC?
Troponin: increased, corr with VPC number and grade and arrythmia complexity BUT sensitivity lacking
BNP not useful
ECG ARVC?
VPC single/pairs/paroxysmal runs
Left bundle branch block morphology to VPC due to right ventricle affected
> 100 VPC/24h or periods of couplets, triplets, runs VTach on holter considered suggestive, may have APC in vent dilation/systolic dysfunction
Echo ARVC?
Usually normal - might find right vent enlargement
When to treat ARVC?
> 1000 VPC/24h, vtach runs, RonT
Early if homozygous for striatin mutation?
Treatment:
Decreases vpc and syncopal episodes
Sotalol or mexiletene, sometimes need combo
Therapeutic effect = 85 % reduction VPC number (due to daily variation)
Fish oils decrease VPC? Not > variation…
Lcarnitine might imp systolic function/prognosis
Also standard cardiac
ARVC px?
If no vent dilation or systolic dysfunction, comparable to non-ARVC - live to around 11y
What is myocarditis?
Necrosis, degeneration, inflammation
Physical/chemical/infectious
May cause chamber dilation, arrhythmia, systolic dysfunction
Protozoal/viral most common in dog
Troponin often increased
Possible infectious causes of myocarditis?
Trypanosoma cruzi (serology, circulating trypomastigotes - tx with cysteine protease inhibitor? for heart effects, arrhythmia and RCHF)
Leishmania (parasite in myocardium and assoc inflammation, AV block)
Toxo/Neo
Parvo (peracute, 3-8w puppies or < 1y DCM)
West Nile (RTPCR, IHA, serology, virus isolation)
Blastomyces (uncommon presentation and poor px)
Borrelia burgdorferi
HCM in dogs?
HOCM in pointers, heritable
T/F: doberman DCM is caused by hypoT4?
False, no link
Difference between primary and secondary cardiomyopathies in cats?
Primary - confined to myocardium, genetic/non genetic/mixed
Secondary - myocardial involvement of systemic/multiorgan disorder
Prevalence of the different cardiomyopathies?
HCM 58 % RCM 21 % DCM 10 % UCM 10 % ARVC uncommon
Left ventricular moderator bands?
Might be incidental
If dense network may have cardiac consequences - poss role in HOCM? More commonly in the outflow tract in HOCM than healthy or non obst HCM
Types of HCM?
Either diffuse concentric left vent hypertrophy (2/3) - which can be asymmetric IVS/LVFS or one segment (basal IVS or apex)
OHCM - obstruction of LVOT often by protruding thickened basal IVS
Papillary hypertrophy can cause systolic mid ventricular cavity obstruction and endocardial contact plaques
Can get infarction LVFW
Right ventricle can also be thickened.
NB dilated stage with thin walls
Breeds and HCM types?
OHCM Persian/Chartreux (44 % cf 18 % other breeds)
50 % Maine coone diffuse symmetric LVH
HCM histopath?
Myocardial fibre disarray, fibrosis, arteriosclerosis
Inflammatory infiltrates in preclin
Signalment HCM?
Male
DSH, DLH, BSH, Himalayan, sphinx
5-7y
Maine coone/sphynx/ragdoll younger?
Genetic HCM?
Maine coone - myosin binding protein C sarcomeric gene (MyBPC3) auto dom but higher risk of HCM for homozygotes, incomplete penetrance hetero at middle age
Ragdoll - MyBP3 (diff mutation). homozygotes worse px.
Sphynx - auto dom incomplete penetrance
Cats pleural effusion?
Can be caused by LHS dz as visceral pleural veins drain to LA
What cardiac auscultation abnormalities are more common in symptomatic HCM cats?
Gallop and arrhythmia
Clinical predictors of cardiac death in HCM?
Arrhythmia, gallop, CHF, ATE, syncope.
LA enlargement, severe LVH, decreased systolic function, decreased LA function, RV enlargement, regional wall hypokinesia, spontaneous contrast, restrictive diastolic filling pattern
Ragdolls (homozygote) and Maine coone more poor px
Types of RCM?
Fibrosis in walls, fibrosis on walls, fibrosis between walls - myocardial/endomyocardial
Same histopath cf HCM (sarcomere mutation?)
RCM signalment?
10y - older cf HCM
Conflicting studies on sex
DSH, Burmese, siamese, Persian, birman, maine coone
Clin signs RCM?
Almost all clinical at presentation, cf HCM
Px RCM?
Poor 200 d cf 1000 HCM
DCM histopath?
Myocytolysis, fibrosis, coronary arteriosclerosis, inflamm infiltrates
DCM signalment?
9y
Conflicting sex predilection
Clin signs DCM?
Usually symptomatic, often hypotensive
Px DCM?
Days, sl better (month) if add pimobendan tx to standard (taurine, furosemide, acei)
Negative - hypothermia, FS < 20 %
What is striatin?
Located at intercalated disc cardiomyocytes, co localised with other desmosomal proteins involved in human ARVC
ARVC in cats?
< 5 %
No genetic
Histopath - diffuse/segmental RV wall thinning, aneurysm, RA enlargement
Myocardial atrophy and fatty or fibrous tissue replacement
Usually CHF at presentation but can be asymptomatic
Poor px if overt - days/weeks survival
ARVC signalment cats?
7Y
No breed/sex predilection
Familial?
Taurine and feline myocardial disease?
Cats have low cysteine sulfinic acid decarboxylase so can’t synthesise much taurine from cysteine
Exclusively use taurine for bile acid conjugation (cf glycine)
25 % taurine deficient cats get myocardial failure (also retinal central degeneration, CNS, immune, repro)
DCM - check taurine and retina (1/3 and may be sign of past taurine def) and diet hx (whole blood taurine better but affected by fasting)
Diet - heat processing in canning, potassium depletion, acidification, rice brain/whole rice
Difficult to diagnose so supplement if DCM (rapid improvement if taurine deficient, some persistent signs but better and aymptomatic)
UCM echo changes?
Segmental LVH, regional hypokinessia, marked LAE
Could be form of HCM or RCM
Signalment UCM?
Female
8y
Px UCM?
Better (900d, cf HCM 500, RCM 100, DCM 11)
What should be ruled out when considering primary cardiomyopathy in cats?
HT4, lymphoma in wall, myocarditis, muscular dystrophy, hypersomatotropism, aortic stenosis, hypertension, taunt, doxorubicin, sustained tachyarrhythmia
VHS in cats?
> 8 specific not sensitive, esp left dz
Acute dyspnoea - > 9 highly specific
Significance of valentine heart?
Not spec for HCM or even cardiac disease, doesn’t predict biatrial enlargement
What interferes with echo in cats?
Dehydration - increase wall thickness and decrease LV diameter
Volume - increase LV diameter, fractional shortening and LA:Ao, with appearance of a murmur
Less skilled echo overest wall thickness
Breed - sphinx 5 or 5.5 in < or > 5kg, > 6 others
LA size in cats?
Prognostic and marker of chronicity
1.3 end diastole, 1.5 end systole
Biomarkers feline myocardial disease?
Troponin: cTNI and TNT predictor of death in HCM but low sens/spec, TNI more sens. No corr echo.
TNI higher in cardiac dyspnoea cf non cardiac but overlap
NTproBNP: 90 % accurate to distinguish cardiac resp signs
70 % sens/100 % sens to identify occult dz cf healthy if > 99. Corr LV thickness and LA:Ao.
Echo marker of decreased diastolic function?
Inversed E:A = relaxation pattern (<1 HCM), restrictive pattern (E:A increase > 2 with increased E decreased A)
How to classify evidence levels?
Level 1 - at least 1 PRCT
Level 2 - at least one well designed clinical trial without randomisation, cohort/case controlled studies lab models, dramatic uncontrolled
Level 3 - opinion , pathophys justification
Medication evidence in feline cardiac disease?
Beta blockers: atenolol - decrease HR/ increase diastole, decrease LVOTO, negative inotrope, decrease myocardial O2 demand which is antiarrhythmic
Ivabradine - inhibit If current in SA node so negative chronotrope - level 1 evidence for imp diastolic function in HEALTHY cats
Calcium channel blockers - negative chrono/inotrope, imp LV relaxation, coronary vasodilation, antiarrhythmic. Level 3 evidence to avoid dihydropyridine (amlodipine) because of excess vasodilation. Diltiazem (less potent negative inotrope/vasodilator cf verapamil) more commonly used.
ACEi\aldosterone blocker - stop myocardial hypertrophy, reverse lesions, vasodilatory and imp diastolic in LVH animal models
Stage B feline cardiac dz management evidence?
80 % asymptomatic HCM die non cardiac dz
Atenolol: no survival benefit (level 1 evidence), no decrease in biomarker Maine coone (level 2), may be deleterious as decreases LA function and flow velocity in left auricle of healthy cats (risk factors for ATE) 0 ? deleterious? Use in LVOTO or vent arrhythmia?
Benazepril: level 1 for increase mitral E:A ratio cf diltiazem, but not sig
Ramipril/spironolactone: no imp diastolic function Maine coone
Spironolactone: facial dermatitis 1/3 @ 2.5m reversible when stop, dose 2mg/kg BID (level 1)
Clopidogrel: no evidence
Stage C feline cardiac dz management evidence?
Furosemide, sedation, thoracocentesis, cage rest (level 3)
Diltiazem: imp clin signs and imaging with 94 % survival at 6m (level 2)
Benazepril: added to diltiazem, imp clin signs and LV (level 2)
Enalapril: with furosemide, survival longer cf diltiazem or placebo or atenolol (920, 227, 235, 72d) - level 1 with no stat sig
Stage D feline cardiac dz management evidence?
Spironolactone (level 3) Hydrochlorthiazide added (level 3) Pimobendan - LV systolic dysfunction (level 2), not OHCM due to worsening/hypotension (level 3)
Other feline cardiac dz management evidence?
Taurine for DCM (level 1)
Pimobendan DCM (level 2 as increased MST)
ARVC - similar DCM, level 3 evidence
Breed for PPDH?
Weimeraner
DLH, Main coone
ECG in PPDH?
Low voltage complexes
Shift electrical axis
What is cardiac tamponade?
Impairment of ventricular filling due to fluid accumulation in pericardial space, reducing SV and CO
Diastolic collapse of right heart
What volume of pericardial fluid is required for cardiac tamponade?
Acute - 50 - 150 ml for 20 kg dog
Chronic - stretch allows for more fluid - can accommodate several hundred more litres
Clinical presentation of cardiac tamponade?
Acute - arterial hypotension due to decreased diastolic filling of left heart due to decreased right heart output
Chronic - RCHF
Increase in diastolic pressure req to cause leaking of systemic capillaries is lower than that required for pulmonary - so pulm oedema not common
Difference in neurohormonal activation pericardial effusion cf heart failure?
No ANP increase, limits natriuresis and contributes to volume overload - this is why chronic causes effusion
Changes in stroke volume during inspiration?
Neg intrathoracic pressure causes pooling in RHS - compliant - and decreased LV preload, RV output higher LV lower (hence increased HR on inspiration)
Pericardial effusion on inspiration?
Ventricular interdependence, increased right heart at expensive of left, so decreased LV output (pulsus paradoxus)
How many dogs with cardiac HSA have concurrent splenic?
30 %
Most common site of mesothelioma metastasis?
Intrathoracic LNs
Metastasis heart base thyroid gland carcinoma?
Pericardium
Idiopathic pericarditis aetiology?
Viral/immune mediated.
Mononuclear inflamm/fibrosis target pericardial blood vessels ad lymphatics.
Damaged blood vessels > bleeding.
Chronic. 50 % don’t recur. 50 % do days - years
Sequel = restrictive
Infectious agents causing pericarditis?
Actinomyces, strep. bacteroides, pasteurella, coccidoises
XR for pericardial eff?
Not sens or spec
ECG pericardial effusion?
Electrical alternans
Decreased QRS voltage - also fat pleural eff etc
Ventricular arrhythmias
pH of pericardial fluid for aetiology?
Not reliable
Treatment of choice for recurrent idiopathic pericarditis?
Thoracotomy - 100 % survival MST not reached 3y
Thoracocoscopic window - disease free interval 11.6m, MST 13m
Mesothelioma pericardial eff tx?
No sig diff surg vs window, approx 10m MST both
Chemo might imp survival
Heart base mass and pericardial eff?
Partial pericardectomy MST 700d vs 42d w/out
Chemo didn’t help survival
This is for aortic body tumours
Cardiac HSA?
Pericardectomy doesn’t prolong survival.
Resection and doxo prolongs survival. Doxo alone also.
Neg px mass size and decreased platelet but NOT mets
What pericardial disease doesn’t have pulsus paradoxus?
Constrictive pericarditis
D. immitis lifecycle in the dog?
Female worms produce L1, microfilariae, which circulate in the blood.
Female mosquito feeds, L1 molts to L3 over 8 - 17 d - temp and Wolbachia pipientis dependent
L3 infective, transmitted when mosquito feeds again
L3 > L4 in subq/muscle/adipose 1 - 12 d
L4 > S5 2 - 3 months post-infection
Juvenile adult migrates to right pulmonary vessels, matures (females bigger than males) and mates. Life cycle completes in 180 - 210 days. Live mostly in caudal pulmonary vascular tree.
Microfilaremia 6-7m post infection.
Microfilaria persist 30m, adults 5 - 7 y
What determines severity of consequences of heart worm infection?
Burden of worms, duration of infection, interaction with immune system.
Worm toxic substance/physical trauma/immune stim
Dead worms severe inflamm reaction
exercise increases pulm hypertension?
Occult heartworm disease?
Microfilaria immune mediated destruction in pulmonary circulation, amicrofilaraemia and eosinophilic pneumonitis
Cytological difference between D immitus and its imitator?
D. immitus - many, stationary, larger, straight body and tail with tapered head
Dipetalonema reconditum - few, progressive motion, curved body blunt head curved tail, smaller
Test for D. immitus in dogs?
Mod. Knott more sens than direct smear.
10 - 20 % amicrofilaraemic, macrocyclic lactones do this
Antigen test - only female adult - low worm burden false neg
Macrocyclic lactones and heartworm?
Milbemycins and avermectins
Terminate L3/L4 larval development in 1st 2m infection
Minimal adverse reaction microfilaraemic dogs. Some adulticidal. Many microfilariacidal
Resistance reported
Moxidectin imidacloprid heartworm/microfilaria, render females sterile, kill adults
Ivermectin 3m reach back
doxycycline synergistic
Adulticide therapy for heartworm?
Melarsomine, 90 % worm kill 70 % dogs cleared
Split dose safer - 50 % worm kill 1st then 100 % 1 month later
Pro/con single dose/split dose protocol D. immitus?
Single - cheaper, don’t have to exercise restrict so long, less melarsomine exposure (better if hepatorenal dz)
Split - safer and more efficacious, better resolution proteinuria
Doxycycline also reduces severity of lung lesions on worm kill
When to recheck antigen after adulticide tx in heartworm?
8m
What dogs are most likely to get heartworm naval syndrome?
Males
Differences in feline heartworm?
More resistant, often worms don’t mature, longer prepatent period, get pulmonary dz even if worms don’t mature.
50 % exposed get heartworm assoc resp dz
Pulmonary arterial response more marked (pulmonary interstitial macrophages) even though worm burden lower
Embolisation more significant as cats less pulm collaterals
Wollbachia might mediate bronchoconstriction
Cytokines in feline heartworm dz?
PGE2 HARD, TXB2/LTB4 mature HW
Differences between HARD and mature heartworm infection in cats?
HARD - clin signs 3m, due to immature heart worms in pulm arteries, resp signs, antigen neg AB pos filaria neg, bronchointerstitial with normal echo
Mature - > 7m, pulm and cardiac, neuro, emesis, more severe resp, Ag pos/neg, AB pos, microfilaria sometimes, variable XR with vessel changes, echo sometimes abnormal
Difference between arterial thrombosis and. thromboembolism?
AT: made at site, shear stress and narrowed vessel
ATE: vessel normal, from diff site, due to stagnant flow
ATE common AT not
Venous > arterial uncommon (unless ASD) - exception is pulm venous emboli eg d/t neoplasia
Coag changes in canine thrombosis
Low - AT, protein C
High - I, II, V, VII - X, XII
Platelet hypersensitivity
Pathophys ATE?
In aorta, acute and release vasoactive substances from activates platelets causes vasoconstriction which inhibits development of collateral supply and get ischaemic neuromyopathy
NB serotonin
Second most common vascular obstruction in feline cardiac dz?
Right subclavian
Mechanism of heparin?
AT mediated II, X-XII, and thrombin catalysed V and VIII, inhibit thrombin platelet aggregation and vWF
Reperfusion injury?
Metabolic acidosis and hyperkalaemia
40 - 70 % cats undergoing thrombolytic tx
Thrombolytics most dangerous aortic, less so cerebral/splanchnic/renal?
Thrombolytic tx?
Streptokinase - activate plasminogen
- one study all cats died
- another 50 % return femoral pulses 24h, motor function 30 %, single limb better (80 % motor function), bleeding 1/4 and severe, 50 % reperf
- dogs good response small number cases
Urokinase - more fibrin specific eg just fibrin bound plasminogen
- LMW molecules bind greater affinity to lysine-plasminogen form which accumulate in thrombi
- cats 50 % motor function 27 % pulse no bleeding, 1/4 reperf
- dogs all dead
tPA: case reports, works in some
How to improve collateral flow thromboembolism?
Aspirin (TXA2 inh, vasodilation)
Clopidogrel inh serotonin release
Negative px indicator cat ATE?
Hypothermia two limbs bradycardia absent motor function
Around 30 % survival.
MST 50 - 350d.
Feline thrombosis prevention?
Suggested if LA:Ao > 2 or spontaneous contrast
If have antithrombotic added on initial event, 17 - 75 % happen again, 25 - 50 % in a year
FAT CAT - clopidogrel decreases recurrence and increases time to recurrence versus aspirin - 443 vs 192 and reduced likelihood of recurrence/cardiac death = 346/128 d
Aspirin mechanism of action?
Inhibits secondary platelet aggregation, reduce TXA2 and prostacyclin production (latter endothelium compensates for in vivo)
Lower dose no sig diff thromboembolic recurrence but less GI
Survival increased in IMHA dogs
Clopidogrel mechanism of action?
ADP2Y12 blocker
Primary and secondary platelet aggregation
Inhibit ADP induced GPIIb/IIIa conformational change so no vWF/fibrinogen binding
Impairs platelet release reaction - decrease vasoconstriction/proaggregate serotonin/ADP
Hepatic biotransformation p450
No bleeding complications reported.
LMW heparin?
Less II inhibition so aPTT normal
Similar recurrence/MST in cats cf warfarin with ATE - warfarin study 42 - 53 % and MST 471 d (vs 210d) - lots of bleeding
Infrequent bleeding LMW hep
Lymphatic ducts?
Thoracic duct drains everything apart from that drained by the right lymphatic duct which drains the right heart/neck and right forelimb
