Cardiovascular System Disorders Flashcards
5 clinical signs of left sided congestive heart failure
- Pulmonary Venous Congestion
- Pulmonary Oedema (increased RR/RE, cough, orthopnea, pulmonary crackles, tiring, cyanosis, hemoptysis)
- Postcapillary pulmonary hypertension
- Secondary right-sided heart failure
- Cardiac arrhythmias
7 CS of right sided congestive heart failure
- Systemic venous congestion (increased ventral venous pressure, jugular vein distension)
- Hepatic +/- splenic congestion
- Pleural effusion (increased RE, orthopnea, cyanosis)
- Ascites
- Small pericardial effusion
- Subcutaneous oedema
- Cardiac arrhythmias
CS of low cardiac output
Tiring
Exertional Weakness
Syncope
Prerenal azotaemia
Cyanosis (from poor peripheral circulation)
Cardiac arrhythmias
Cardiovascular causes of syncope/intermittent weakness
- Bradyarrhythmias (2-3rd degree AV Block, Sinus Arrest, Sinus sick syndrome, atrial standstill)
- Tachyarrhythmias (paroxysmal atrial or ventricular tachycardia, reentrant supraventricular tachycardia, atrial fibrillation)
- Congenital ventricular outflow obstruction (pulmonic or subaortic stenosis)
- Acquired ventricular outflow obstruction (heartworm and other causes of pulmonary hypertension, hypertrophic obstructive cardiomyopathy, intracardiac tumour, thrombus)
- Cyanotic heart disease (tetralogy of Fallot, pulmonary hypertension, and ‘reversed’ shunt)
- Impaired forward cardiac output (severe valvular insufficiency, dilated cardiomyopathy, myocardial infarction or inflammation)
- Impaired cardiac filling (eg. cardiac tamponade, constrictive pericarditis, hypertrophic or restrictive cardiomyopathy, intracardiac tumour, thrombus)
- Cardiovascular drugs (diuretics, vasodilators)
- Neurocardiogenic reflexes (vasovagal, cough-syncope, other situational syncope)
3 pulmonary causes of syncope/intermittent weakness
- Disease causing hypoxaemia
- Pulmonary hypertension
- Pulmonary thromboembolism
Metabolic and haematologic causes of syncope/intermittent weakness
- Hypoglycaemia
- Hypoadrenocorticism
- Electrolyte imbalance (esp. potassium and calcium)
- Anaemia
- Sudden haemorrhage
Neurological causes of syncope
- CVA
- Brain tumour
- Seizures
Neuromuscular diseases that cause syncope
Narcolepsy, cataplexy
Define syncope
Syncope is characterised by transient unconsciousness, with loss of postural tone (collapse) from insufficient oxygen or glucose delivery to the brain.
Causes of pale omm
Anaemia or poor cardiac output/high sympathetic tone
Causes of injected/brick-red omm
- Polycythemia (erythrocytosis)
- Sepsis
- Excitement
- Other causes of peripheral vasodilation
Causes of cyanotic omm
- Pulmonary parenchymal disease
- Airway obstruction
- Pleural space disease
- Pulmonary oedema
- Right-to-left shunting congenital cardiac defect
- Hypoventilation
- Shock
- Cold exposure
- Methemoglobinaemia
Causes of icteric omm
- Hemolysis
- Hepatobiliary Disease
- Biliary Obstruction
Causes of differential cyanosis
Reversed patent ductus arteriosus (head and forelimbs receive normally oxygenated blood, but caudal part of the body receives desaturated blood via the ductus, which arises from the descending aorta)
Causes of jugular venous distention (alone)
- Pericardial effusion/tamponade
- Right atrial mass/inflow obstruction
- Dilated cardiomyopathy
- Cranial mediastinal mass
- Jugular vein/cranial vena cava thrombosis
Causes of jugular venous pulsation +/- distention
- Tricuspid regurgitation of any cause (degenerative, cardiomyopathy, congenital, secondary to diseases causing right ventricular pressure overload)
- Pulmonic stenosis
- Heartworm disease
- Pulmonary hypertension
- Ventricular premature contractions
- Complete (3rd-degree) heart block
- Constrictive pericarditis
- Hypervolaemia
Causes for weak arterial pulses
- Dilated cardiomyopathy
- (Sub)aortic or pulmonic stenosis
- Shock
- Dehydration
Causes for bounding arterial pulses
- Patent ductus arteriosus
- Fever/sepsis
- Severe aortic regurgitation
Describe the grading of heart murmurs
1 = very soft murmur, heard only over its site of origin, after prolonged listening in quiet surroundings
2 = soft murmur but easily heard over its site of origin (usually a particular valve area)
3 = moderate-intensity murmur; usually radiates to other precordial/valve areas too
4 = Loud murmur without a precordial thrill; radiates widely and usually can be heard over most precordial regions
5 = Loud murmur with a palpable precordial thrill; radiates widely and usually can be heard over all precordial regions
6 = Very loud murmur with a precordial thrill; radiates widely, generally is heard clearly over all precordial areas, and can be heard with the stethoscope chest piece lifted slightly (~1cm) from the chest wall (at the murmur PMI))
Common murmurs with left sided PMI
- PDA - patent ductus arteriosus (top)
- PS - pulmonic stenosis (most cranial)
- SAS - subaortic stenosis (mid)
- MR - mitral regurgitation/insufficiency (most caudal)
Common murmurs with right sided PMI
- SAS - subaortic stenosis (mid-cranial)
- TR - tricuspid regurgitation (mid -most caudal)
- VSD - ventricular septal defect (ventral cranial)
Demonstrate how to do a VHS
using a lateral thoracic radiograph add the dimensions of the long-axis and the short-axis of the heart together; recorded as the number of vertebrae beginning with the cranial edge of T4
What non-cardiac abnormalities can elevate NT-proBNP?
renal dysfunction
pulmonary hypertension
hyperthyroidism (in cats)
how are cardiac troponins useful indicators of cardiac dysfunction?
Cardiac troponins are regulatory proteins attached to the cardiac actin (thin) contractile filaments. Circulating concentrations of cardiac troponin proteins are normally very low; however, myocyte injury allows their leakage into the cytoplasm and extracellular fluid. Cardiac troponin I is the protein usually measured; it is more sensitive for detecting myocardial injury than other biochemical markers of muscle damage (ie. cardiac-specific creatine kinase).
Common DDx for generalised enlargement of the cardiac shadow
- Dilated cardiomyopathy
- Chronic mitral and triscupid insufficiency
- Pericardial effusion
- Peritoneopericardial diaphragmatic hernia
- Tricuspid dysplasia
- Ventricular or atrial septal defect
- Patent ductus arteriosus
Common DDx. for left atrial enlargement alone
- Early mitral insufficiency
- Hypertrophic cardiomyopathy
- Early dilated cardiomyopathy (esp. in doberman pinschers)
- (Sub)aortic stenosis
Common DDx. for left atrial and ventricular enlargement
- Dilated cardiomyopathy
- Hypertrophic cardiomyopathy
- Mitral insufficiency
- Aortic insufficiency
- Ventricular septal defect
- Patent ductus arteriosus
- (sub)aortic stenosis
- Systemic hypertension
- Hyperthyroidism
Common Ddx. for right atrial and ventricular enlargement
- Advanced heartworm disease
- Chronic, severe pulmonary disease
- Tricuspid insufficiency
- Pulmonic stenosis
- Tetralogy of Fallot
- Atrial septal defect
- Pulmonary hypertension
- Mass lesion within the right heart
What is M-mode echocardiography?
This modality provides a one-dimensional (depth) view into the heart. M-mode images represent echoes from various tissue interfaces along the axis of the beam (displayed vertically on the screen). These echoes, which move during the cardiac cycle, are displayed against time (on the horizontal axis). Thus the ‘wavy’ lines seen on these recordings correspond to the positions of specific structures in relation to the transducer, as well as to each point in time. Measurements of cardiac dimensions and motion throughout the cardiac cycle often are more accurately obtained from the M-mode tracings, especially when coupled with a simultaneously recorded ECG (or phonocardiogram).
Standard M-mode views are obtained from what position?
the right parasternal transducer position
Explain how to perform an La:Ao and what is normal
La:Ao is best measured in 2-D echocardiography (rather than M-mode which tends to underestimate). The “Scandinavian” method employs the right parasternal short-axis view and compares the LA dimension in diastole to the aortic diameter. The 2-D image is optimised to include the LA and the auricle, as well as the aortic valve. The internal LA dimension is measured in early diastole, along a line extending from and parallel to the commissure formed by the closed left and noncoronary aortic valve cusps. The aortic dimension measurement also aligns with the same valve commissure in the same frozen 2-D frame.
Normal in dogs is between 1.3-1.4.
what types of doppler echocardiography are used clinically?
- Pulsed wave; uses short bursts of ultrasound to analyze echoes from a specific area along the doppler cursor line. The advantage of PW doppler is that blood flow velocity, direction and spectral characteristics can be calculated from a specific location within the heart or blood vessel. Main disadvantage is that the maximum measurable velocity is limited.
- Continuous wave; employs continuous and simultaneous ultrasound transmission and reception along the line of interrogation. No maximum velocity limit with CW doppler, so high-velocity flows can be measured. Disadvantage - range ambiguity.
- Colour Flow Mapping: a form of PW Doppler that combines the M-mode or 2-D modality with blood flow imaging. Instead of one sample volume along one scan line, many sample volumes are analyzed along multiple scan lines. The mean frequency shifts obtained from multiple sample volumes are colour coded for direction (in relation to the transducer) and velocity. (most red = toward, blue = away)
What are important clinical applications of doppler echocardiography?
- Abnormal flow direction, turbulence and increased flow velocity
– detection and quantification of valvular insufficiency, obstructive lesions and cardiac shunts
what is the ‘Nyquist limit’ in relation to PW doppler?
the maximum measureable velocity - defined as two times the pulse repetition frequency, lower frequency transducers and closer sample volume placement increase the nyquist limit.
How is pressure gradient estimation used in echocardiography?
Doppler estimation of pressure gradients is used to assess the severity of congenital or acquired flow obstructions. In addition, the peak velocity of a valvular insufficiency jet can be used to estimate the pressure gradient across a regurgitant valve. The instantaneous pressure gradient across a stenotic or regurgitant valve is estimated using a maximum measured velocity of the flow jet. A modified Bernoulli equation is used to estimate pressure gradient.
Pressure gradient = 4x(maximum velocity)^2
Pulmonary hypertension is associated with maximal tricuspid regurgitation jet velocity (TRmax) of what value?
TRmax value > 2.8m/sec
- Mild = TRmax 2.9-3.5m/sec (~35-50mmHg systolic pulmonary artery pressure)
- Moderate = 3.6-4.3m/sec (50-75mmHg)
- Severe = >4.3m/sec (>75mmHg)
What event is related to a P-wave?
depolarisation (activation) of atrial muscle
PR-interval event (also called PQ interval)
time from onset of atrial muscle activation, through conduction over the AV node, bundle of His, and Purkinje fibres
QRS complex event
Depolarisation of ventricular muscle, by definition, Q is the first negative deflection (if present), R first positive, and S is the negative deflection after the R wave
J point event
End of the QRS complex (and ventricular muscle activation), junction of QRS and ST segment
ST segment event
Represents the period between ventricular depolarisation and repolarisation (correlates with phase 2 of the AP)
T wave event
Ventricular muscle repolarisation
QT interval event
Total time of ventricular depolarisation and repolarisation
Causes of sinus bradycardia
hypothermia
hypothyroidism
drugs (eg, some tranquilisers, anaesthetics, B-blockers, calcium entry blockers, digoxin)
increased intracranial pressure
brainstem lesions
ocular pressure
carotid sinus pressure
other causes of high vagal tone (ie. airway obstruction)
sinus node disease
severe metabolic disease (Hyperkalaemia, uremia)
normal variation (athletic dog)
cardiac arrest
Causes of sinus tachycardia
fever/hyperthermia
hyperthyroidism
anaemia/hypoxia
heart failure
hypotension
shock
sepsis
anxiety/fear/excitement
pain
exercise
drugs (sympathomimetics, anticholinergics)
toxicities (chocolate, amphetamines, theophylline)
electric shock
Other causes of high sympathetic tone
define ectopic rhythms
impulses originating from outside the sinus nose (known as ectopic impulses) are abnormal and create an arrhythmia (dysrhythmia)
described based on general site of origin (atrial, junctional, supraventricular, ventricular)
timing; premature or late/escape
define supraventricular premature complexes
impulses that originate above the AV node (atria or AV junctional area)
define supraventricular tachycardias
tachycardias of supraventricular origin often involve a reentrant pathway using the AV node (either within the AV node or using an accessory pathway); a premature supraventricular or ventricular impulse can initiate reentrant supraventricular tachycardia (SVT)
define atrial flutter
produced by rapid (>400 impulses/min) waves of electrical activation regularly cycling through the atria. The ventricular response rate may be regular/irregular depending on the pattern of AV conduction.
Atrial flutter is not a stable rhythm and often degenerates into atrial fibrillation.
define atrial fibrillation
characterised by rapid and chaotic electrical activity within the atria. No P waves because there is no uniform atrial depolarisation wave. The ventricular heart rate is determined by the AV conduction velocity and recovery time. (influenced by prevailing autonomic tone).
what are VPCs?
VPCs (ventricular premature complexes) originate below the AV node. Ventricular ectopic complexes usually are wider than sinus-origin complexes because of the slower intramuscular conduction. Because VPCs usually are not conducted backward through the AV node into the atria, the sinus rate continues undisturbed and the VPC is followed by a so called compensatory pause in the sinus rhythm.
VPCs can be monomorphic/uniform or polymorphic/multiform.
define ventricular tachycardia
ventricular tachycardia consists of a series of VPCs (at a rate >100bpm). The QRS to QRS (RR) interval is most often regular. Non-conducted sinus P waves may be superimposed on or between the ventricular complexes, although unrelated to the VPCs because the AV node and/or ventricles are in the refractory period (physiologic AV dissociation).
define torsades de pointes
a specific form of polymorphic ventricular tachycardia associated with Q-T interval prolongation
define accelerated idioventricular rhythm
accelerated ventricular rhythm/idioventricular tachycardia, originates within the ventricles and has a rate of about 60-100bpm in the dog. The rate is slower than a true ventricular tachycardia thus usually less serious disturbance. Common rhythm in dogs recovering from MVA.
Can progress to ventricular tachycardia.
describe ventricular fibrillation
a lethal rhythm characterised by multiple reentrant circuits causing chaotic electrical activity within the ventricles.
The ECG shows an irregularly undulating baseline with no recognisable waveforms.
NO effective ventricular pumping function.
“Coarse” and “Fine” VF (depending on size of oscillations)
describe ‘escape complexes’
originate from automatic (subsidiary pacemaker) cells within the atria, the AV junction, or the ventricles, and constitute a protective mechanism.
an escape complex only occurs after a pause in the dominant (usually sinus) rhythm. If the dominant rhythm does not resume, the escape focus continues to discharge at its own intrinsic rate, producing an escape rhythm.
describe escape rhythms
usually regular
ventricular escape rhythms (idioventricular rhythms) have an intrinsic rate of less than 40-50bpm in dogs, 100bpm in cats.
junctional escape rhythms usually range 40-60bpm in dogs, faster in cats.
Escape activity should never be suppressed
what is the mean electrical axis
The MEA describes the average direction of the ventricular depolarisation process in the frontal plane. It represents the summation of the various instantaneous vectors that occur from beginning until completion of ventricular muscle depolarisation.
By convention, only the 6 frontal plane leads are used to determine MEA.
ECG changes associated with hyperkalaemia
- Peaked (tented) T waves (can be large or small)
- Short QT interval
- Flat or absent P waves
- Widened QRS
- ST segment depression
ECG changes associated with hypokalaemia
- Prolonged QT interval
- ST segment depression
- Small, biphasic T-waves
- Tachyarrhythmias
ECG changes associated with hypercalcaemia
- Few effects
- Short QT interval
- Prolonged conduction
- Tachyarrhythmias
ECG changes associated with hypocalcaemia
- Prolonged QT intervals
- Tachyarrhythmias
ECG changes associated with digoxin toxicity
- PR prolongation
- 2nd or 3rd degree AV block
- Sinus bradycardia or arrest
- Accelerated junctional rhythm
- Ventricular premature complexes
- Ventricular tachycardia
- Paroxysmal atrial tachycardia with block
- Atrial fibrillation with slow ventricular rate
ECG changes associated with lidocaine toxicity
AV block
Ventricular tachycardia
Sinus Arrest
ECG changes associated with B-blocker toxicity
Sinus bradycardia
AV Block
Prolonged PR interval
ECG changes associated with quinidine/procainamide
Atropine-like effects
Prolonged QT interval
AV block
Ventricular tachyarrhythmias
Widened QRS complex
Sinus Arrest
ECG changes associated with medetomidine/xylazine
Sinus bradycardia
Sinus arrest/sinoatrial block
AV Block
Ventricular tachyarrhythmias (esp. halothane, epinephrine)
ECG changes associated with barbituates/thiobarbiturates
Ventricular bigeminy
ECG changes associated with halothane/methoxyflurane
Sinus bradycardia
Ventricular arrhythmias (increased sensitivity to catecholamines, esp. halothane)
explain the use of central venous pressure measurement
CVP if the fluid pressure within the RA and by extension the intrathoracic cranial vena cava. Influenced by intravascular volume, venous compliance, and cardiac function. CVP measurement helps in differentiating high right heart-filling pressure (as from right heart failure or pericardial disease) from other causes of pleural or peritoneal effusion.
Important to note that pleural effusion itself can raise CVP in absence of cardiac disease thus measure CVP post thoracocentesis.
The CVP in normal dogs and cats ranges from 0-8 (up to 10)cm H2O
explain how CVP is measured
CVP is measured via a large-bore jugular catheter that extends into or close to the RA. The catheter is placed aseptically and connected by extension tubing and a three-way stopcock to a fluid administration set and container of crystalloid fluid. A water manometer is attached to the stopcock and positioned vertically with the stopcock (representing 0cm H2O) placed at the same horizontal level as the patient’s RA. Usually the patient is in lateral or sternal recumbency for CVP measurement. The stopcock is turned off to the animal, allowing the manometer to fill with fluid, then the stopcock is turned off to the fluid reservoir so that the fluid column in the manometer equilibriates with the patient’s CVP.
Small fluctuations in the manometer’s fluid meniscus can occur with the heartbeat, slightly larger movements associated with respiration. Marked changes in height associated with the heartbeat represent severe tricuspid insufficiency or the catheter tip is in the RV.
when is cardiac catheterisation used
necessary for balloon valvuloplasty, ductal occlusion and other interventional procedures
define cardiac remodeling
refers to the changes in myocardial size, shape and stiffness that occur in response to various mechanical, biochemical and molecular signals induced by the underlying injury or stress.
what is the Frank-Starling mechanism?
acute increases in ventricular filling (preload) induce greater contraction force and blood ejection. Allows beat-to-beat adjustments that balance the output of the two ventricles and increase overall cardiac output in response to acute increases in haemodynamic load. in the short term, the Frank-Starling effect helps normalise cardiac output under conditions of increased volume or pressure loading, but these conditions also increase ventricular wall stress and oxygen consumption.
what is Laplace’s law?
Ventricular wall stress is directly related to ventricular pressure and internal dimensions, and inversely related to wall thickness.
what is concentric hypertrophy?
myocardial fibres and ventricular walls thicken as contractile units (sarcomeres) are added in parallel. (induced by increased ventricular systolic pressure load)
what is eccentric hypertrophy?
myocardial fibre elongation and chamber dilation occur as new sarcomeres are laid down in series.
what are the major neurohormonal mechanism changes in heart failure?
- Increased sympathetic nervous tone
- Attenuated vagal tone
- Renin-angiotensin-aldosterone system activation
- Increased release of Vasopressin (ADH) and endothelin
how do the NH systems work to enhance cardiac output?
- Increased vascular volume (by enhancing sodium and water retention and thirst) as well as vascular tone
- Expanded vascular volume increases ventricular filling (preload) which then enhances cardiac output
how is baroreceptor function affected by chronic heart failure?
baroreceptor responsiveness becomes attenuated in chronic heart failure –> sustained sympathetic and hormonal activation and reduced inhibitory vagal effects.
explains the roles of renin in heart failure
- renin is released from the renal juxtaglomerular apparatus (occurs secondary to low renal artery perfusion pressure, renal B-adrenergic receptor stimulation, and reduced Na+ delivery to the macula densa of the distal renal tubule)
- renin facilitates conversion of angiotensinogen to angiotensin I ++ ACE –> angiotensin II
explain the role of angiotensin II in chronic heart failure
- potent vasoconstriction
- stimulation of aldosterone release from the adrenal cortex
- increased thirst and salt appetite
- facilitation of neuronal norepinephrine synthesis and release
- blockade of neuronal norepinephrine reuptake
- stimulation of Vasopressin release
- increased adrenal epinephrine secretion
roles of aldosterone
- promotes sodium and chloride reabsorption
- promotes potassium and hydrogen ion secretion in the renal collecting tubules
** increased aldosterone promotes hypokalaemia, hypomagnesemia and impairs baroreception function - blocks NE reuptake (potentiating catecholamine effects)
role of ADH
released from posterior pituitary gland
- causes vasoconstriction and promotes free water reabsorption in the distal nephrons
** continued release of ADH contributes to the dilutional hyponatremia sometimes found in patients with heart failure
what is endothelin?
- a potent vasoconstrictor whose precursos peptide is produced by vascular endothelium - stimulated by hypoxia, vascular mechanical factors and angiotensin II, ADH, NE, cytokines ++
what endogenous mechanisms oppose vasoconstrictor responses
- natriuretic peptides
- adrenomedullin
- nitric oxide (NO)
- vasodilator prostaglandins
what is ANP?
Atrial natriuretic peptide
- synthesized by atrial myocytes as a prohormone, which is then cleaved to the active peptide after its release
- mechanical stretch of the atrial wall stimulates ANP release
what is BNP?
Brain natriuretic peptide
- synthesized by the heat (mainly ventricles) in response to myocardial dysfunction or ischemia
what is Adrenomedullin?
- a natriuretic and vasodilatory peptide produced in the adrenal medulla, heart, lung and other tissues
what is NOS?
endothelin-nitric oxide synthetase (stimulates production of NO by the vascular endothelium)
NO is a functional antagonist of endothelin and angiotensin II
what are the major pathophysiological groups of CHF?
- Myocardial failure
- Volume-Flow Overload
- Pressure overload
- Impaired ventricular filling
common causes of myocardial failure?
- idiopathic dilated cardiomyopathy
- infective myocarditis
- drug toxicities (e.g doxorubicin)
- myocardial ischemia/infarction (rare)
common causes of volume-flow overload?
- mitral valve regurgitation (degenerative, congenital, infective)
- aortic regurgitation (infective endocarditis, congenital)
- ventricular septal defect
- patent ductus arteriosus
- tricuspid valve regurgitation (degenerative, congenital, infective)
- tricuspid endocarditis (rare)
- chronic anaemia
- thyrotoxicosis
Common causes of pressure overload?
- (sub)aortic stenosis
- systemic hypertension
- pulmonic stenosis
- heartworm disease
- pulmonary hypertension
common causes of impaired ventricular filling?
- hypertrophic cardiomyopathy
- restrictive cardiomyopathy
- cardiac tamponade
- constrictive pericardial disease
outline the Modified AHA/ACC heart failure staging system
A - no apparent structural disease, yet considered ‘at risk’ for developing heart disease (for example, breed-associated risk for DCM in doberman Pinschers, and CMVD in Cavies)
B - structural cardiac abnormality is evident (such as a murmur) but no clinical signs of heart failure have occurred
B1 - asymptomatic disease, with no/minimal radiographic or echo evidence of cardiac chamber enlargement/remodeling
B2 - asymptomatic disease, but cardiac chamber enlargement is evident
C - structural cardiac abnormality evident, with clinical signs of heart failure either in the past (resolved with therapy) or currently present. (C1-3 based on CHF signs - 1= no signs, 3= severe/overt)
D - persistent or end-stage heart failure signs, refractory to standard therapy (ie. require >8-12mg/kg/day of Furosemide)
name two other grading systems of heart failure severity other than the ACC/AHA system
- Modified NYHA (New York Heart Association) Functional Classification (I - IV)
- International Small Animal Cardiac Health Council Functional Classification (I - III)
outline the goals of acute treatment of decompensated CHF
- Minimize patient stress and excitement
- Improve oxygenation
- Diuresis; furosemide
- Support cardiac pump function (inodilator); pimobendan
- Reduce Anxiety (Butorphanol/buprenorphine)
- +/- Additional vasodilators; nitroglycerin ointment, sodium nitroprusside, hydralazine
- +/- Additional Inotropic Support if myocardial failure or persistent hypotension; dobutamine, amrinone, digoxin
- +/- reduce bronchoconstriction; aminophylline
explain how to improve oxygenation in CHF treatment
- O2 supplementation via face mask, hood, nasal catheter, ETT, oxygen cage
- oxygen cage with temperature control (65F), flow 6-10L/minute.
- Oxygen concentrations of 50-100% may be necessary initially but this should be reduced within a few hours to 40% to avoid lung injury
- nasal tube; humidified O2 delivered at a rate of 50 to 100ml/kg/min
- extremely severe pulmonary oedema with respiratory failure may require ETT/tracheotomy tube, airway suctioning and mechanical ventilation. Positive end-expiratory pressure helps clear small airways and expands alveoli.
explain the use of diuretics in the treatment of CHF
- rapid diuresis with IV furosemide; effects begin within 5 minutes, peak at 30, DOA 2 hours. Can be given as CRI which may provide greater diuresis than IV boluses.
- Furosemide 50mg/ml can be diluted to 10mg/ml with 5% Dextrose, LRS or sterile water.
A. DOGS; 2-5mg/kg IV/IM/SQ bolus then 1-4mg/kg q1-4hrs until resp. rate decreases, then 1-4mg/kg q6-12hrs OR use 0.6-1mg/kg/hr CRI over next 6 hours if inadequate response to boluses
B: CATS; 1-4mg/kg initial bolus then 1-2mg/kg q1-4h until resp rate decreases, then 1-2mg/kg q6-12h - once diuresis has begun and respiration improves the dosage is reduced to prevent excessive volume contraction or electrolyte depletion
how do vasodilators treat patients in CHF?
- can reduce pulmonary oedema by increasing systemic venous capacitance, lowering pulmonary venous pressure and reducing systemic arterial resistance.
arteriolar vasodilation is not recommended for heart failure caused by diastolic dysfunction or ventricular outflow obstruction
explain the MOA and use of nitroprusside in CHF treatment
- sodium nitroprusside is a potent arteriolar and venous dilator with direct action on vascular smooth muscle
- route: IV CRI due to short DOA. Dose titration to maintain MAP 80mmHg (at least >70mmHg) or SAP 90-110mmHg. CRI used for 12-24hours; dose adjustments necessary as drug tolerance develops rapidly. Should not be mixed with other drugs + is light sensitive.
explain the use of hydralazine in the treatment of CHF
- an alternative to nitroprusside
- a pure arteriolar dilator
- useful for refractory pulmonary oedema caused by mitral regurgitation (MR) because it can reduce regurgitant flow and lower left atrial pressure
- oral dose of 0.5-1mg/kg can be repeated every 2-3hours until the SAP btwn 90-110mmHg (or 0.05-0.1mg/kg IV or IM)
explain the mechanism of nitroglycerin
- oral or transcutaneously administered nitrate acts mainly on venous smooth muscle to increase venous capacitance and reduce cardiac filling pressure
list 5 diuretics used to treat chronic heart failure
- Furosemide
- Torsemide
- Spironolactone
- Chlorothiazide
- Hydrochlorothiazide
list 6 ACE inhibitors used to treat chronic heart failure
- Enalapril
- Benazepril
- Captopril
- Lisinopril
- Ramipril
- Imidapril
list 6 other vasodilators (not ACE inhibitors) used to treat chronic heart failure
- Hydralazine
- Amlodipine
- Prazosin
- Nitroglycerin 2% Ointment
- Isosorbide dinitrate
- Isosorbide mononitrate
name two positive inotropes used to treat chronic heart failure
- Pimobendan
- Digoixn
describe the use of catecholamines in acute CHF
may be indicated in acute CHF caused by poor myocardial contractility or with persistent hypotension
- 1-3 days with an IV sympathomimetic (catecholamine) or phosphodiesterase (PDE) inhibitor drug can help support arterial pressure, forward cardiac output and organ perfusion when myocardial failure or hypotension is severe
outline the goals of therapy in treatment of CHF caused by diastolic dysfunction
CHF caused by hypertrophic or restrictive cardiomyopathy;
- thoracocentesis (if needed)
- diuretics
- oxygen therapy
- B-blockers; atenolol or esmolol can reduced the frequency of ectopic beats, control heart rate and reduce the LV outflow pressure gradient esp. in cats with rapid tachyarrhythmias or marked LV outflow obstruction
with is pimobendan theoretically contraindicated in cats with HOCM
because increased contractility and arterial vasodilation can worsen dynamic LV outflow obstruction and potentially cause hypotension
outline exercise restriction in the management of chronic heart failure
- if active CHF; no exercise should be allowed until signs well controlled
- patients with no CS of congestion; mild to moderate activity (as tolerated) is thought to be beneficial for patients with no clinical signs of congestion
- chronic heart failure is associated with skeletal muscle changes that lead to fatigue and dyspnoea - physical training is known to improve cardiopulmonary function and quality of life in human patients
- Regular mild to moderate activity is encouraged, as long as excessive respiratory effort or fatigue is not induced.
outline the general considerations to manage chronic heart failure
- medications; furosemide, pimobendan, ACI (enalapril/benazepril) +/- spironolactone
- a diet moderately reduced in salt
- exercise (regularly or restriction)
- draining of effusions (ascites, pleural or pericardial) as required
MOA and administration of furosemide
- interferes with ION TRANSPORT in the LOH and has the ability to promote both SALT AND WATER LOSS
- acts of the ASCENDING LIMB in the LOH to inhibit active Cl-, K+, Na+ cotransport, thereby promoting excretion of these electrolytes and H+, Ca2+, Mg2+ are also lost in the urine
- can also INCREASE SYSTEMIC VENOUS CAPACITANCE; possibly by mediating RENAL PROSTAGLANDIN RELEASE
- may PROMOTE SALT LOSS by increasing total renal blood flow and preferentially ENHANCING RENAL CORTICAL FLOW
- PO - diuresis occurs w/in 1 hr, peaks 1-2hrs, DOA 6hrs
when is torsemide indicated in CHF treatment
in dogs with refractory CHF and diuretic resistance - it promotes greater Na+ excretion, has a LONGER HALF LIFE, and some ANTI-ALDOSTERONE effects
- dosed at 1/10 of the patient’s prior frusemide dose
MOA of spironolactone
COMPETETIVE ANTAGONIST OF ALDOSTERONE
- in the kidney; PROMOTES Na+ LOSS and K+ RENTENTION in the DISTAL RENAL TUBULE (reduces potassium wasting of other diuretics)
- in the heart; thought to mitigate aldosterone-induced cardiovascular REMODELING and BARORECEPTOR DYSFUNCTION
- slow onset of action; peak within 2-3days, give WITH FOOD
- contraindicated in hyperkaelamic patients
- adverse effects; excess K+ retention, GI, ulcerative facial dermatitis in cats
MOA of thiazide diuretics
- decrease Na+ and Cl- and increase Ca2+ absorption in the DISTAL CONVOLUTED TUBULES
- mild to moderate diuresis with excretion of Na+, Cl-, Mg2+, and alkalosis can occur
- thiazides DECREASE RENAL BLOOD FLOW and SHOULD NOT be used in AZOTAEMIC animals
- adverse effects; severe azotaemia, hypokalaemia or other lyte disturbances, hyperglycaemia in diabetic/pre-diabetic animals by inhibiting conversion of proinsulin to insulin
- typically diuresis within 1-2hrs, peak at 4hrs, DOA 12hrs
MOA of Angiotensin-Converting Enzyme Inhibitors in treatment of chronic heart failure
- blocking the formation of angiotensin II - allows arteriolar and venous vasodilation
- inhibition of aldosterone release helps reduce Na+ and water retention and therefore oedemas/effusions + the direct effects of aldosterone on the heart (remodelling etc)
- reduce ventricular arrhythmias and rate of sudden death (due to inhibition of angiotensin II-induced facilitation of norepinephrine and epinephrine)
- directly modest vasodilatory and diuretic effects
adverse effects of ACE-inhibitors
- vomiting, diarrhoea, deterioration of renal function, hypotension, hyperkalaemia
- measurement of creatinine and electrolytes within 1 week of initiating therapy and periodically thereafter
- other AE reported in people; rash, pruritus, impairment of taste, proteinuria, cough and neutropaenia
DOA of benazepril
- PO – peak ACE inhibition occurs within 2 hours, effects can last 24hours.
- benazepril is the preferred ACEI for animals with renal disease + may slow progression in cats with kidney disease
- drug is eliminated equally in urine and bile in dogs
- in cats; 86% excreted in faeces and 15% in urine
DOA of enalapril
- PO - peak ACEI activity occurs within 4-6hours in dogs, DOA is 12-24hours. Often initially SID by becomes BID in CHF dogs.
- cats peak activity 2-4hours, and persists for 2-3days.
- enalapril and metabolites excreted in the urine; renal failure and severe CHF prolong its half-life - so reduced doses OR use benazepril instead
what are ARBs?
angiotensin receptor blockers - drugs that directly block type I angiotensin II receptors rather than reduce the production of angiotensin II
- ‘sartans’ (telmisartan, losartan, valsartan)
- in experimental models of myocardial ischaemia and heart failure, ARB treatment has reduced ventricular remodeling, fibrosis and dysfunction
MOA of pimobendan
- inodilator; increased contractility whilst causing systemic and pulmonary vasodilation
- calcium-sensitizing effect on the contractile proteins by increasing the affinity of the regulatory protein troponin C for Ca2+ —> promotes increased contractility without an increase in free cellular Ca2+ and thus myocardial O2 requirement.
- as a benzimidazole-derivative phosphodiesterase III inhibitor, pimobendan also slows cAMP breakdown and enhances adrenergic effects on Ca2+ fluxes and myocardial contractility.
administration and DOA of pimobendan
- give without food
- highly protein bound, elimination mainly hepatic metabolism and biliary excretion
- peak plasma conc. occur w/in 1 hr of dosing
- adverse effects; anorexia, vomiting or diarrhoea
MOA of digoxin
- oral positive inotropic drug; ability to sensitize baroreceptors and modulate NH activation
- most often used for heart rate control in dogs with AF; it is moderately effective for slowing AV conduction
- increases contractility by competitively binding and inhibiting the Na+, K+-ATPase pump at the myocardial cell membrane. Intracellular Na+ accumulation then promotes Ca2+ entry via the sodium-calcium exchange.
- anti-arrhythmic effects mediated by increased parasympathetic tone to the sinus and AV nodes and atria. Some direct effects prolong conduction time and refractory period of the AV node.
administration of digoxin and ongoing monitoring
- PO without food/antacids/kaolin-pectin compounds
- takes 2-3 days to reach therapeutic levels with BID dosing, cats longer
- risk of toxicity increases with renal failure, animals with reduced muscle mass/cachexia
- serum conc. should be measured at 7 days, 10days for cats, samples taken 8-10hrs post dose
Cs of digoxin toxicity
- anorexia, depression, vomiting, borborygmi, diarrhoea
- ventricular or supraventricular tachyarrhythmias, sinus arrest ,Mobitz type 1 second-degree AV block, junctional rhythms
treatment of digoxin toxicity
- lidocaine is used to treat digoxin-induced tachyarrhythmias because it can suppress arrhythmias caused by re-entry or late after depolarisations with little effect on sinus rate and AV conduction
- GI signs; respond to drug withdrawal and correction of fluids/lytes
MOA of hydralazine
directly relaxes arteriolar smooth muscle when the vascular endothelium is intact but has little effect on the venous system
- reduces arterial blood pressure
- improves pulmonary oedema
- increased jugular venous oxygen tension
- peaks within 3 hours, lats 12 hours
MOA of amlodipine
dihydropyridine L-type Ca2+ channel blocker causes peripheral vasodilation as its major action, has little effect on AV conduction
- peaks in 3-8hours, DOA 24hours, maximal effect develops over 4 to 7 days
- slow up-titration of dose recommended with weekly BP monitoring
- chronic administration associated with gingival hyperplasia in a small number of dogs
MOA of nitrates
act as ventilators - metabolized in vascular smooth muscle to produce NO, which indirectly mediates vasodilation.
outline dietary considerations in management of patients with chronic heart failure
A good-quality diet with adequate calories and protein, as well as moderate salt restriction, is recommended for most patients with chronic heart failure.
* heart failure can interfere with the kidney’s ability to excrete sodium and water loads, thus moderate dietary salt and restriction is recommended to help control fluid accumulation (however very low salt intake (<7mg/kg/day) can increase RAAS activation)
aim for 30mg/kg/day of sodium
explain the pathogenesis of cardiac cachexia
involves multiple factors, esp. pro-inflammatory cytokines, TNFa and interleukin-1
- these substances suppress appetite and promote hypercatabolism
what are the benefits of omega-3 fatty acids in the management of chronic heart failure?
- EPA (eicosapentaenoic) + DHA (docosahexaenoic acids)
- reduce cytokine production
- improve endothelial function
- appear to have antiarrhythmic effects
Oral doses of 40mg/kg/day EPA + 25mg/kg/day DHA have been suggested
what breeds with DCM have been associated with L-carnitine deficiency?
Boxers
Doberman Pinschers
Strategies for refractory (Stage D) CHF
- Furosemide 8-12mg/kg/day OR use torsemide instead
- additional after load reduction in dogs with MR or DCM (Amlodipine or hydralazine)
- Increase Pimobendan dosing from BID to TID
- for dogs with severe pulmonary hypertension and collapse episodes or Right sided CHF signs – additional of Sildenafil 1-2mg/kg PO BID
- cough suppressant (marked LA enlargement or bronchomalacia)
what is a realistic goal when managing arrhythmias?
significant reduction in frequency (>70-80%) or repetitive rate of ectopic beats to eliminate clinical signs
outline the major steps in ECG interpretation
- Rate?
- Rhythm? (regular/irregular)
- P-QRS-T relationships? (present/absent)
- Are all P waves followed by a QRS and all QRS complexes preceded by a P wave?
- Are QRS complexes normal or wide/different configuration than sinus complexes (implying a ventricular origin)?
- Are premature QRS complexes preceded by an abnormal P wave (suggesting atrial origin)?
- Are there baseline undulations instead of clear and consistent P waves, with a rapid, irregular QRS occurrence (compatible with atrial fibrillation)?
- Are there long pauses in the underlying rhythm before an abnormal complex occurs? (escape beats)?
- Is an intermittent AV conduction disturbance present?
- Is there a lack of consistent temporal relationship between P waves and QRS complexes, with a slow and regular QRS occurrence (implying complete AV block with escape rhythm)?
- For sinus and supraventricular complexes, is the mean electrical axis normal?
- Are all measurements and waveform durations within normal limits?
Outline the approach to arrhythmia management?
- Record and interpret an ECG
- Patient evaluation; evidence of haemodynamic impairment? other signs of cardiac disease? + any other abnormalities
- Decide whether to use antiarrhythmic drug therapy
- Define goals of therapy for the patient
- Initiate treatment and determine drug effectiveness
- Monitor patient status - rpt ECG, AEs
List extra-cardiac factors that predispose to atrial arrhythmias
- catecholamines
- electrolytes
- digoxin toxicity/other drugs
- thyrotoxicosis
- severe anaemia
- hypoxia
- thoracic surgery
- acidosis/alkolosis
List extra-cardiac factors that predispose to ventricular arrhythmias
- electrolytes (K+)
- hypoxia
- hypothermia or fever
- sepsis or toxaemia
- GD/GDV
- splenic mass or splenectomy
- haemangiosarcoma
- trauma
- pulmonary disease
- uremia
- pancreatitis
- phaechromocytoma
- thyrotoxicosis
- DM, Addisons, hypoT
- high sympathetic tone (pain, anxiety, fever)
- CNS disease
- drugs
common arrhythmias that are fast and irregular
- atrial or supraventricular premature contractions
- paroxysmal atrial or supraventricular tachycardia
- atrial flutter or fibrillation
- ventricular premature contractions
- paroxysmal ventricular tachycardia
common arrhythmias that are fast and regular
- sinus tachycardia (<300bpm usually)
- sustained supraventricular tachycardia (possibly >300bpm, but rare)
- sustained ventricular tachycardia
common arrhythmias that are slow and irregular
- sinus bradyarrythmia
- sinus arrest
- sick sinus syndrome
- high-grade second-degree AV block
common arrhythmias that are slow and regular
- sinus bradycardia
- complete (third degree) AV block with ventricular escape rhythm
- atrial standstill with ventricular escape rhythm
what is a vagal maneuver?
- performed by firmly massaging the area over the carotid sinuses (below the mandible in the jugular furrows) or by applying firm bilateral ocular pressure for 15 to 20 seconds.
- can help differentiate among tachycardias caused by an ectopic automatic focus, those dependent on a reentrant circuit involving the AV node, or excessively rapid sinus node activation. The vagal maneuver may transiently slow or intermittently block AV conduction, exposing abnormal P’ waves, and thus allow an ectopic atrial focus to be identified.
- the maneuver can terminate reentrant SVTs involving the AV node by interrupting the reentrant circuit
outline acute therapy for ventricular tachycardia in cats vs. dogs
Cats - initially b-blockers, then IV lidocaine low-dose (sensitive to neurotoxicity)
Dogs - IV lidocaine (to max dose if necessary) .. to CRI
IF these steps do not work; then ensure serum K+, Mg2+ normal then try other drugs; procainamide +/- b-blocker or amiodarone, or sotolol, or mexiletine, or quinidine
what is the favoured long-term oral therapy of patients with ventricular tachyarrhythmias
- sotalol
- mexiletine with atenolol
- mexiletine with sotalol
- amiodarone
outline treatment of atrial fibrillation
- Digoxin PO +/- Diltiazem/ B-blocker
typically the combination of diltiazem and digoxin PO are used because they control rate better than either agent alone
*Digoxin is NOT used in cats with HCM and AF
how does ventricular preexcitation affect treatment of AF?
do not use AV nodal blocking drugs in these patients (Ca2+blockers, digoxin, possibly B-blockers) — they can paradoxically increase the ventricular response rate
- Amiodarone is recommended in these cases, sotalol or procainamide also can be used
define ‘lone atrial fibrillation’
AF sometimes develops in large or giant-breed dogs without cardiomegaly or other evidence of structural heart disease = “lone AF”
- can occur transiently in association with trauma/surgery - may convert to sinus rhythm spontaneously or in response to drugs (amiodarone, diltiazem (PO ~ 3 days) or possibly sotalol)
when should sinus bradycardia be treated?
if associated with signs of weakness, exercise intolerance, syncope or worsening underlying disease, an anticholinergic (or adrenergic) agent is given
what is sick sinus syndrome?
- a condition of erratic SA function characterised by episodic weakness, syncope, and, sometimes, convulsive syncope (Stokes-Adams seizures) triggered by cerebral hypoxia.
- older female Mini Schnauzers and Westies are most commonly affected, also in daxies, pugs, cocker spaniels
- affected dogs have episodes of marked sinus bradycardia with sinus arrest (or SA block)
- sick sinus syndrome is extremely rare in cats
what does bradycardia-tachycardia syndrome refer too?
dogs with sinus sick syndrome with prolonged periods of asystole followed by paroxysmal SVTs
how is atropine used to diagnose sick sinus syndrome?
an atropine challenge test is done in dogs with persistent bradycardia, the normal response is an increased in the heart rate of 150% or to more than 130 to 150bpm, dogs with sick sinus syndrome generally have a subnormal response
what is atrial standstill?
a rhythm disturbance that is characterised by loss of effective atrial electrical activity (with no P waves and a flat baseline); a junctional or ventricular escape rhythm controls the heart
- most cases have occurred in english springer spaniels with muscular dystrophy, although infiltrative and inflammatory disease of the atrial myocardium also can result in atrial standstill
- extremely rare in cats
explain the CS associated with AV blocks
high grade 2nd degree AV blocks (many blocked P waves) and complete (3rd degree) heart blocks usually cause lethargy, exercise intolerance, weakness, syncope and other signs of low cardiac output. These signs become severe at HR <40bpms.
1st and 2nd degree blocks are usually asymptomatic and abolished with exercise or anticholinergics.
mechanism and ECF effects of Class I antiarrhythmic drugs
decreases fast inward Na+ current; membrane stabilising effects (decreased conductivity, excitability, automaticity)
IA: moderately decreases conductivity, increases AP duration, can prolong QRS complex and Q-T interval (quinidine, procainamide)
IB: little change in conductivity, decrease AP duration, QRS complex and Q-T interval unchanged (lidocaine, mexiletine, phenytoin)
IC: markedly decreases conductivity without change in AP duration (propafenone, flecainide)
mechanism and ECF effects of Class II antiarrhythmic drugs
B-adrenergic blockade - reduces effects of sympathetic stimulation (no direct myocardial effects at clinical doses)
atenolol, propranolol, esmolol, metoprolol, carvedilol
mechanism and ECF effects of Class IV antiarrhythmic drugs
decreases slow inward Ca2+ current (greatest effect on SA and AV nodes)
verapamil, dilitazem
outline of class I antiarrhythmic drugs
- block membrane Na+ channels and depress the AP upstroke (phase 0) which slows conduction velocity along the cardiac cells
- subclasses
- most depend on extracellular K+ concentration for their effects, and they lose effectiveness in patients with hypokalaemia
mechanism and ECF effects of Class III antiarrhythmic drugs
selectively prolongs AP duration and refractory period; antiadrenergic effects; Q-T interval prolonged
sotalol, amiodarone, ibutilide, dofetilide
outline of class II antiarrhythmic drugs (B-adrenergic blockers)
- act by blocking catecholamine effects; slow HR, reduce myocardial O2 demand and increase AV conduction time and refractoriness
- antiarrhythmic effects related to B1-receptor blockade
- used in animal with supraventricular and ventricular tachyarrhythmias (especially those induced by enhanced sympathetic tone)
- classed on selectivity for B1/B2/B3 receptors (B1 located mainly in the myocardium and mediate increases in contractility, HR, AV conduction velocity, the automaticity in specialized fibres) (B2 mediate bronchodilation and vasodilation, + insulin and renin release)
outline of class III antiarrhythmic drugs
- prolongation of cardiac AP and effective refractory period without a decrease in conduction velocity
- effects are mediated by inhibition of potassium channels responsible for repolarisation (delayed rectifier current)
- useful against ventricular arrhythmias, especially those caused by reentry
- antifibrillatory effects
describe ‘innocent murmurs’
- physiologic cause is incompletely understood but may involve mismatch in growth rate between the heart and great vessels, relative anaemia, or high sympathetic tone compared to adult animals
- usually soft systolic ejection-type murmurs heard best at the left heart base
- tend to get softer and usually disappear by about 4 months of age
what are the three most common congenital cardiovascular abnormalities in dogs
- patent ductus arteriosus (PDA)
- pulmonic stenosis (PS)
- subaortic stenosis (SAS)
what is the most common congenital malformation in cats
ventricular septal defect (VSD)
breed predisposition for PDA
maltese, poms, shelties, english springer spaniels, bichons, toy and mini poodles, yorkies, collies, chihuahuas, GSD, cocker spaniel, labs, newfoundlands, welsh corgies
females > males
breed predispositions for subaortic stenosis
newfies, goldens, rotties, boxers, GSD, great danes, GSP, samoyed
breed predispositions for ventricular septal defect
english bulldog, springer spaniel, keeshond, westies
Cats!
breed predisposition for atrial septal defect
samoyed, boxer, doberman pinscher
breed predisposition for tricuspid dysplasia
labds, GSD, boxers, weimaraner, great dane, english sheepdog, goldens
cats
breed predisposition for mitral dysplasia
bull terrier, GSD, golden retriver, newfies, mastiff, dalmation, rottie
cats
breed predisposition for tetralogy of fallot
keeshond, english bulldog
breed predisposition of persistent right aortic arch
GSD, great dane, irish setter
explain the etiology and pathophysiology of PDA
- ductus fails to close, blood shunts through it from the descending aorta into the pulmonary artery
- shunting occurs continuously during systole and diastole; left-right shunt (dt higher aortic pressure) causes a volume overload of the pulmonary circulation, LA and LV
- hyperkinetic arterial pulses are characteristic of PDA
clinical features of PDA
- usually asymptomatic when diagnosed but can have CS consistent with LSCHF (exercise intolerance, cough, tachypnoea)
- continuous murmur heard best at the left base often with precordial thrill
- hyperkinetic arterial pulses
- 2x greater prevalence in female dogs
- mini poodles!
treatment and prognosis of PDA
- closure via surgical ligation (left lateral thoracotomy) with periop mortality of 5%
- if PDA not corrected prognosis depends on size and level or pulmonary vascular resistance; LSCHF is the eventual outcome, more than 50% of affected dogs die within the first year of life
explain the pathophysiology of a ventricular outflow obstruction
- SAS and PS are the most common
- stenotic lesions impose a pressure overload on the affected ventricle requiring higher systolic pressure and a slightly longer time to eject blood across the narrowed outlet
- concentric myocardial hypertrophy typically develops in response to a systolic pressure overload, some dilation can also occur
- ventricular hypertrophy can impede diastolic filling (by increasing ventricular stiffness) or lead to secondary AV valve regurgitation
explain the etiology and pathophysiology of subaortic stenosis
- subvalvular narrowing caused by a fibrous or fibromuscular ring is the most common type of LV outflow stenosis in dogs; large breed dogs are predisposed (Newfies, goldens, Rotties)
- unlike many other congenital heart defects, the lesion itself is not present at birth; rather, patients are born with abnormal tissue in the subvalvular region of the conotruncal septum that retains the ability to proliferate and undergo chondrogenic differentiation - obstructive lesion usually develops postnatally during the first several months of light and may continue to worsen until the dog is fully grown (1-2yo)
- graded from I (mild) to III (severe); severity of the stenosis determines the degree of LV pressure overload and resulting concentric hypertrophy; coronary perfusion is compromises, myocardial capillary density is inadequate, high systolic wall tension lead to intermittent myocardial ischaemia and secondary fibrosis
clinical features of subaortic stenosis
- most patients are asymptomatic, CS of exercise intolerance, syncope, sudden death occur in 1/3 of dogs
- characteristic murmur; harsh, systolic ejection murmur heard near the aortic valve area at the left heart base, with or without a precordial thrill; murmur often radiates to right heart base
- weak or late-rising femoral pulses (pulsus parvus et tardus)
prognosis of subaortic stenosis
- median survival time is 4.5yrs
- sudden death is more common in dogs younger than 3 years of age (approximately 20% of dogs with SAS die suddenly)
- infective endocarditis and CHF are more likely to develop in older surviving dogs
etiology and pathophysiology of pulmonic stenosis
- more common in small breeds of dogs
- dysplastic valve leaflets are variably thickened, asymmetric and partially fused, with or without a hypoplastic valve annulus
- RV pressure overload leads to concentric hypertrophy as well as secondary dilation of the RV
- severe ventricular hypertrophy promotes myocardial ischaemia and its sequelae
- turbulence caused by high-velocity flow across the stenotic orifice leads to post-stenotic dilation in the main pulmonary trunk
- right atrial dilation from secondary tricuspid insufficiency and high RV filling pressure predisposes to atrial tachyarrhythmias and right-sided CHF
clinical features of PS
- many dogs are asymptomatic; some develop RSCHF
- CS may not develop until the animal is several years old, even with severe stenosis
- a systolic ejection murmur heard best high at the left heart base, with or without precordial thrill, murmur can radiate cranioventrally and to the right in some cases
- early systolic click sometimes heard
treatment and prognosis of PS
- balloon valvuloplasty (> surgical intervention) with severe cases
- B-blockers
- prognosis in patients with PS is variable and depends on the severity of the lesion and any complicating factors
- animals with severe PS often die within 3 years of diagnosis, normal lifespan with mild PS
explain the etiology and pathophysiology of VSDs
- most VSDs located in the membranous part of the septum, just below the aortic valve and beneath the septal tricuspid leaflet (perimembranous VSD)
- usually VSDs cause volume overloading of the pulmonary circulation, LA, LV and RV outflow tract
- small defects may be clinically unimportant, but large defects tend to cause left heart dilation and can lead to LSCHF, pulmonary hypertension secondary to overcirculation with large shunts
what are the clinical features of VSDs?
- mostly asymptomatic, or exercise intolerance and LSCHF
- holosystolic murmur, heard loudest at the cranial right sternal border, a split S2 sound may be audible due to delayed closure of the pulmonic valve, concurrent diastolic decrescendo murmur at left base if aortic regurgitation present
treatment and prognosis of VSDs
- small restrictive VSDs have excellent prognosis with a normal lifespan typically
- possible spontaneous closure within the first two years of life
- large nonrestrictive VSDs (greater than 60% of aortic diameter, shunt velocity less than 4.0m/s) have a guarded prognosis with LSCHF the common outcome
- treatment; medical management of CHF vs. open-heart surgery (patch grafting) or transcatheter delivery of an occlusion device
- surgery should not be attempted in the presence of pulmonary hypertension and shunt reversal
what is a small restrictive VSD
a VSD less than 40% of aortic diameter, shunt velocity greater than 4.5m/s
what are the two most common locations of atrial septal defects?
- fossa ovalis (ostium secundum defects) - common in dogs
- lower interatrial septum (ostium primum defect) is likely to be part of the AV septal (endocardial cushion or common AV canal) defect complex - common in cats
explain the pathophysiology of ASDs
- in most cases blood shunts from the LA to the RA resulting in volume overload to both the right heart and pulmonary circulation
- IF PULMONARY HYPERTENSION is present; right to left shunting and cyanosis can occur
clinical features of animals with ASD
- because the pressure difference between the right and left atria is minimal, no murmur is expected, although large left to right shunts can cause a murmur of relative PS
- FIXED SPLITTING of the second heart sound is the classic finding caused by delayed pulmonic and early aortic valve closures
- large ASDs can lead to signs of RS or biventricular CHF
treatment of ASDs
- large shunts can be treated with open-heart surgery and patch-grafting under cardiopulmonary bypass
- ostium secundum defects can sometimes be treated with transcatheter device occlusion
- otherwise medical management of CGF
what factors effect the prognosis of ASDs
- shunt size
- concurrent defects
- level of pulmonary vascular resistance
list possible congenital malformations of the mitral valve apparatus
- shortened, fused or overly elongated chordae tendinae
- direct attachment of the valve cusp to a papillary muscle
- thickened, cleft, or shortened valve cusps
- prolapse of valve leaflets
- abnormally positioned or malformed papillary muscles
- excessive dilation of the valve annulus
what are the clinical features of mitral dysplasia?
- similar to MMVD except in younger patients; LSCHF
- atrial arrhythmias (especially AFIB)
- holosystolic murmur at the left apex
what does ‘an Ebstein-like anomaly’ refer to in reference to tricuspid dysplasia
the tricuspid valve is displaced ventrally into the ventricle
what animals are commonly associated with tricuspid dysplasia?
- large breed dogs; esp. Labs, and males
explain the pathophysiology of TD
- severe cases result in marked enlargement of the right heart chambers
- resultant RSCHF
what is the characteristic murmur of TD
right sided holosystolic murmur
- however not all cases have a murmur because the dysplastic leaflets may gape so widely in systole that there is little resistance to backflow and thus minimal turbulence
prognosis of TD
- depends on severity
- dogs with severe TR and marked cardiomegaly have a guarded to poor prognosis, but some dogs survive for many years
when does visible cyanosis occur?
when the desaturated hemoglobin concentration is greater than 5g/dL
what can result from severe erythrocytosis (PCV >65%)
hyperviscosity
- microvascular sludging
- poor tissue oxygenation
- intravascular thrombosis
- haemorrhage
- cardiac arrhythmias
what cardiac malformations cause cyanosis?
Right to left shunting requires;
- the presence of an anomalous connection between the systemic and pulmonary circulations
- suprasystemic right heart pressures, usually due to pulmonary hypertension or PS
how does exercise result in syncope in animals with cyanotic heart disease?
exercise stimulates systemic vasodilation to increase blood flow to skeletal muscles; the resulting decrease in systemic vascular resistance transiently increases right to left shunt volume
what anomalies most commonly cause cyanosis in dogs and cats
- tetralogy of fallot
- PS with an intracardiac shunt (VSD, ASD)
- pulmonary arterial hypertension in conjunction with an intra/extracardiac shunt (PDA, VSD, ASD)
what 4 components make up tetralogy of fallot?
- VSD
- PS
- Dextropositioned aorta
- RV hypertrophy
what causes T of F?
a single embryonic defect; incomplete rotation and faulty partitioning of the conotruncus during separation of the great vessels
- the malalignment of the aorta and pulmonary artery with respect to the interventricular septum causes a large nonrestrictive VSD, obstruction of the RV outflow tract (PS) and an aortic root that extends over the right side of the interventricular septum
- all these components facilitate RV-to-aortic shunting
what breeds are predisposed to T of F
- Keeshond
- terrier breeds
- cats
what is the characteristic murmur associated with T of F
- a holosystolic murmur at the right sternal border consistent with a VSD
- a systolic ejection murmur at the left base compatible with PS
- some animals have no murmur because hyperviscosity associated with erythrocytosis diminishes blood turbulence
treatment of T of F
- definitive repair via open-heart surgery
- palliative surgical procedures to increase pulmonary blood flow by creating a left to right shunts (a modified Blalock-Taussig shunt)
- severe erythrocytosis and CS associated with hyperviscosity; periodic phlebotomy or hydroxyurea (goal to maintain PCV at 62-65% - further reduced can exacerbate hypoxia)
median survival time following diagnosis of T of F
approx. 2 years
what does ‘Eisenmenger physiology’ refer to?
severe pulmonary hypertension with shunt reversal
what histologic changes have been identified in pulmonary arterioles leading to pulmonary hypertension with shunt reversal?
causes increased vascular resistance
- intimal thickening
- medical hypertrophy
- characteristic plexiform lesions
what are possible causes of pulmonary hypertension with shunt reversal?
- high fetal pulmonary resistance may not regret normally
- pulmonary vasculature may react abnormally to an initially large left-to-right shunt flow
what is the major difference between the pathophysiologic sequelae from right-to-left shunts resulting from pulmonary hypertension vs. T of F
the impediment to pulmonary flow occurs at the level of the pulmonary arterioles rather than the pulmonic valve
how does Sildenafil citrate treat pulmonary hypertension?
it is a selective phosphodiesterase-5 inhibitor that reduces pulmonary resistance via Nitric oxide-dependent pulmonary vasodilation
- it can reduce the degree of right-to-left shunting in dogs with pulmonary hypertension
what are possible adverse effects of sildenafil?
- hypotension
- cutaneous flushing
- nasal congestion
- sexual adverse effects in intact animals
outline the method of therapeutic phlebotomy in the treatment of erythrocytosis
- remove 5-10ml blood/kg of body weight vs.
Phlebotomy volume = body weight (kg) x 0.08 (percent blood volume) x 1000ml/kg x (actual hematocrit - desired hematocrit)/(actual hematocrit) - Replace volume with isotonic fluids
is surgical correction of right to left shunts due to pulmonary hypertension recommended?
generally no, as the acute increase in PA pressure causes RV myocardial failure and death
- some rare cases where the shunt is corrected post sildenafil therapy is pressures return to Left to right shunt
what is a persistent right aortic arch?
the most common vascular ring anomaly in dogs
- developmental malformations surrounding the esophagus dorsally and to the right with the aortic arch, to the left with the ligamentum arteriosum, and ventrally with the base of the heart
explain the pathophysiology of a persistent right aortic arch
- vascular ring prevents solid food from passing normally through the esophagus; regurgitation and stunted growth commonly develop within 6 months of weaning
- oesophageal dilation occurs cranial to the ring
- secondary aspiration pneumonia
- sometimes tracheal stenosis; stridor +
what is cor triatriatum
- an uncommon malformations caused by an abnormal membrane that divides either the right (Dexter) or the left (sinister) atrium into two chambers
- occurs sporadically in dogs; large to medium breeds
- cor triatriatum Dexter results from failure of the embryonic right sinus venosus valve to regress. The caudal vena cava and coronary sinus empty into the RA caudal to the intra-atrial membrane; the tricuspid orifice is within the cranial RA ‘chamber’. Obstruction to venous flow through the opening in the abnormal membrane elevates vascular pressure in the caudal vena cava and the structures that drain into it.
what is endocardial fibroelastosis
- diffuse fibroelastic thickening of the LV and the LA endocardium, wih dilation of the affected chambers
- seen in Burmese and Siamese cats
what breeds are predisposed to CMVD?
- Cavalier King Charles Spaniels
- Toy and Mini Poodles
- Mini Schnauzers + Mini Pinschers
- Chihuahuas
- Pomeranians
- Fox + Boston Terriers
- Cocker Spaniels
- Dachshunds
- Whippets
how can CMVD result in syncope?
- tachyarrhythmias, acute vasovagal response
- pulmonary hypertension
- atrial tear
- coughing spells/exercise/excitement
typical murmur associated with CMVD?
- holosystolic murmur in left apex (L4th-6th ICS), radiates in any direction
- S3 gallop may be audible in advanced disease/myocardial failure
how dose NT-proBNP help predict prognosis in dogs with CMVD?
- high levels eg. NT-proBNP >1500pmol/L are more likely to have CHF or develop it sooner
outline treatment guidelines for CMVD in Stage B1
- client education
- routine health maintenance; BP, baseline CXR +/- echo/NT-proBNP, maintain BCS, regular exercise, HW testing and prophylaxis
- manage other medical problems
- avoid high-salt foods
- being RRR monitoring to establish normal baseline
outline treatment guidelines for CMVD in Stage B2
- client education
- routine health maintenance + avoid excessively strenuous exercise
- manage other problems, if arterial BP elevated institute ACEI therapy
- avoid high-salt foods; consider introducing moderately salt-restricted diet now
- institute pimobendan therapy (0.2-0.3mg/kg q12h)
- monitor RRR
outline treatment guidelines for CMVD in Stage C - chronic outpatient
- previous stage considerations
- furosemide as needed
- pimobendan
- ACEI
- spironolactone
- antiarrhythmic therapy
- if CHF signs; complete exercise restriction until after signs fully resolve
- if no current CHF signs; regular mild (to moderate) activity
- moderate dietary salt restriction
- monitor RRR
outline treatment guidelines for CMVD in Stage C - acute, hospitalised care
- supplemental O2
- cage rest + minimal patient handling
- furosemide, more aggressive
- pimobendan, IV if available
- vasodilator therapy (consider IV nitroprusside, or IV/PO hydralazine +/- topical nitroglycerin)
- sedation PRN
- antiarrhythmic therapy
- thoracocentesis PRN
outline treatment guidelines for CMVD in Stage D
- optimise Stage C therapies and drug doses ( increase pimo q8h (0.4-0.5mg/dose, switch from furosemide to torsemide @ 1/10-1/12 of total furosemide dose, if not using torsemide can add thiazide diuretic, can add digoxin)
- rule out systemic arterial hypertension, arrhythmias, anaemia, other complications
- increase furosemide dose/frequency as needed (check renal function and electrolyte status)
- enforced rest
- additional afterload reduction (amlodipine)
- if pulmonary hypertension with signs of RCHF or collapse - add sildenafil 1-3mg/kg q8-12h PO
- bronchodilator or cough suppressant
explain the development of PH with CMVD
usually related to chronic pulmonary venous hypertension
- increased precapillary vascular resistance from hypoxia-induced pulmonary arteriolar vasoconstriction occurring with pulmonary oedema/concurrent pulmonary disease
- reactive pulmonary vascular remodelling can contribute to PH, esp. w/ severe disease
outline the treatment of PH with sildenafil
Sildenafil 1-3mg/kg q8h - start at lower doses q8-12h and then titrate up over several days to a week.
- concurrent admin of L-arginine supplement 100mg/kg q8h PO is thought to enhance sildenafil’s efficacy, because this amino acid is a substrate for nitric oxide production
- occasionally dogs with severe PH and advanced CMVD can develop worsened pulmonary oedema after initial sildenafil treatment
what dogs have a higher prevalence of LA tearing?
Older, male mini poodles, cocker + king charles spaniels, daxies, shelties
prognosis of CMVD
- median survival time of advanced (b2) is slightly more than 2years
- advanced CHF ~ 6-9months
list factors that are associated with worse prognosis of CMVD
- older age
- male
- severe valve lesions, degree of valve leaflet prolapse/MR
- ruptured chordae
- severe LA or LV enlargement
- reduced LV systolic function
- elevated natriuretic peptide levels
what are 3 independent risk factors for first onset of CHF in stage B dogs with CMVD
- NT-proBNP concentrations >1500pmol/L
- End-diastolic LV dimension indexed to aortic root diameter >3
- VHS > 12
CHF likely to occur within 3-6 months
explain the etiology of infective endocarditis
- endothelial damage
- disturbed blood flow
- bacteraemia + bacterial virulence
aortic and mitral valves are most often affected.
- endocardial surface of the valve is infected directly from the blood flowing past it
- endothelial damage with platelet and fibrin aggregation serves as a nidus for circulating bacterial colonization
- highly virulent organisms or a heavy bacterial load increase risk of cardiac infection
- previously damaged valves are at great risk (damage dt mechanical trauma ie. jet lesions from turbulent blood flow or catheter-induced endocardial injury)
what are the most common organisms identified in dogs with endocarditis
- Staphylococcus spp.
- Streptococcus spp.
- Escheria coli
- Bartonella spp.
outline the pathophysiology of infective endocarditis
- endothelial disruption stimulates plt activation and local coagulation response
- circulating bacteria adhere to and colonize the sterile clot
- some colonizing bacteria secrete damaging/ulcerating enzymes –> further stimulate platelet aggregation and coag. cascade —> leading to vegetative lesions
- additional fibrin is deposited over the lesions/bacterial colonies protecting them from normal host defenses and antibiotics
- vegetations cause valve deformity; perforation, tearing of leaflets, insufficiency, rarely stenosis
- eventual CHF, emboli or metastatic infection, myocardial injury resulting from coronary arterial embolization causing myocardial infarction and abscess formation, or from direct extension of the infection into the myocardium, tachyarrythmias, AV blocks
- septic arthritis, discospondylitis, UTIs, renal/splenic infarctions
what is the prevalence of bacterial endocarditis in dogs
0.05-6%
males more commonly than females
list possible cardiac sequelae of infective endocarditis
- valve insufficiency/stenosis; murmur, CHF
- coronary embolization (aortic valve); myocardial infarction, abscess, myocarditis, decreased contractility, arrhythmias
- myocarditis (direct invasion); arrhythmias, AV conduction abnormalities, decreased contractility
- pericarditis (direct invasion); pericardial effusion, cardiac tamponade
list possible renal sequelae of infective endocarditis
- infarction; reducec renal function
- abscess formation and pyelonephritis; reduced renal function, UTI, renal pain
- glomerulonephritis (immune-mediated); proteinuria, reduced renal function
list possible musculoskeletal sequelae of infective endocarditis
- septic arthritis; joint swelling and pain, lameness
- immune-mediated polyarthritis; shifting-leg lameness, joint swelling and pain
- septic osteomyelitis; bone pain, lameness
- myositis; muscle pain
- hypertrophic pulmonary osteopathy
list possible brain and meninges sequelae of infective endocarditis
- abscess; associated neurologic signs
- encephalitis and meningitis
list possible vascular system sequelae of infective endocarditis
- vasculitis; thrombosis, petechiation and small haemorrhages
- obstruction; ischaemia of tissues
list possible lune sequelae of infective endocarditis
- pulmonary emboli
- pneumonia
explain the diagnosis of infective endocarditis
- presumptive diagnosis of infective endocarditis is made based off;
2+ positive blood cultures (or positive Bartonella testing)
and echocardiographic evidence of vegetations or valve destruction
how to perform a blood culture
- 3-4 samples of at least 10ml collected asceptically over 24 hours for bacterial culture with more than 1 hour elapsing between collections
- different venipuncture sites should be used for each sample
- aerobic culture more valuable than anaerobic, both ideally
- prolonged incubation of 3-4wks recommended
why is Bartonella spp an important cause of culture-negative endocarditis in some regions?
- requires specialized conditions and an enriched insect cell culture medium (Bartonella a Proteobacteria growth medium) or heart infusion agar
- low circulating bacterial levels or intermittent bacteremia with bacterial sequestration within endothelial cells and vegetative lesions
treatment of infective endocarditis
- Initially, empiric broad-spectrum;
- B-lactam antibiotic; ampicillin, ticarcillin/clav or a cephalosporin (gram-positive spectrum)
- with Aminoglycoside or fluoroquinolone (gram-negative spectrum)
- Clindamycin or metronidazole provides added anaerobic coverage
ABs administered IV for first 1-2 weeks, then oral afterwards for 6-8 weeks. Adjusted based on culture.
- in patients with positive cultures rpt cultures 1-2weeks after commencement of ABs, and 1-2 weeks after completion of AB therapy recommended
outline the treatment recommendations for a dog with Bartonella endocarditis
- initial amikacin for 7-10 days, combined with doxycycline
- if starting with oral (not IV) in clinically stable patients, recommended to start on drug (doxycycline) followed by additional drug (enro/Prado) in 5 - 7 days to avoid a Jarisch-Herxheimer-like reaction (lethargy, fever, vomiting lasting a few days)
- in patients with positive cultures rpt cultures 1-2weeks after commencement of ABs, and 1-2 weeks after completion of AB therapy recommended
prognosis of infective endocarditis
guarded to poor
- some dogs die within days to weeks, other survive to later die from progressive CHF
when should prophylactic antimicrobial therapy by considered to prevent infective endocarditis?
- patients with certain cardiovascular malformations (SAS) prior to ‘dirty’ procedures
what is DCM?
dilated cardiomyopathy - characterized by poor myocardial contractility, with or without arrhythmias
- thought to have a genetic basis in many cases
- also various biochemical defects, nutritional deficiencies, toxins, immunologic mechanisms and infectious agents many be involved in the pathogenesis of DCM in different cases
explain the pathogenesis of DCM?
- decreased ventricular contractility (systolic dysfunction) is the major functional defect in dogs with DCM
- progressive cardiac chamber dilation (eccentric hypertrophy and remodeling) develops as systolic pump function and cardiac output worsen
- increased diastolic stiffness contributes to development of high end-diastolic pressures, venous congestion and CHF
- cardiac enlargement and papillary muscle dysfunction often cause poor systolic apposition of mitral and tricuspid leaflets, leading to mild to moderate valve insufficiency
what breeds are most commonly affected by DCM?
LARGE and GIANT Breeds (rarely seen in <12kg)
- doberman pinschers
- great danes
- st bernards
- Scottish deerhounds
- Irish wolfhounds
- Labrador retrievers
- newfoundlands
- afghan hounds
- dalmations
what is the prevalence of Afib in dogs with DCM?
approx 30% of doberman pinschers and more than 80% of giant breed dogs with DCM have concurrent AFIB
outline the gross cardiac changes in DCM
- dilation of all cardiac chambers is typical, LA and LV predominate
- ventricular wall thickness may appear decreased relative to lumen size
- flattened, atrophic papillary muscles and endocardial thickening
- concurrent degenerative changes of the AV valve (absent - moderate)
typical signalment of patients with DCM
- prevalence increases with age, 4-10yrs old
- Doberman Pinschers, prevalence approaches 50% in dogs >8yrs, males shown signs earlier then females
CS associated with DCM
- DCM appears to develop slowly and sudden death before CHF signs are relatively common
- CS; exercise intolerance, cough etc.
what are common first-line ventricular antiarrhythmic medications used in DCM
- sotalol
- mexiletine
- in refractory cases; amiodarone, procainamide
prognosis of dogs with DCM
- Doberman Pinschers, occult disease tends to develop at 3-6yo, sudden death occurs in about 20-40% of affected Doberman pinschers (even without evidence of CHF)
- onset of CHF generally occurs within 2 -3 years of disease diagnosis
- following episode of CHF; median survival time is 4-6months
what are some negative prognostic indicators of DCM?
- pleural effusion
- severity of LV systolic dysfunction
- presence of ventricular tachycardia or atrial fibrillation
- higher cardiac biomarker values
treatment outline for dogs with DCM Stage B (occult)
- pimobendan
- ACEI
- +/- B-blocker titration; atenolol, metoprolol
- antiarrhythmic therapy if indicated (sotalol or mexiletine for ventricular tachyarrhythmias, digoxin and diltiazem combination for Afib)
- moderately salt-restricted diet
treatment outline for dogs with Stage C (DCM chronic/outpatient)
- furosemide
- pimobendan
- ACEI
- spironolactone
- antiarrhythmic tx. if needed (sotalol/mexiletine for ventricular, digoxin and diltiazem for AFIB)
- diet; moderate salt restriction, +/- supplement (fish oil +/- taurine/carnitine if indicated)
- exercise restriction until no signs of CHF
treatment outline for dogs with Stage C acute CHF DCM
- supplemental 02, cage rest, minimal patient handling, sedation
- furosemide, pimobendan, dobutamine (esp. if persistent hypotension)
- antiarrhythmic (lidocaine for ventricular tachycardia, diltiazem for uncontrolled AFIB)
- vasodilator (nitroprusside, hydralazine, Amlodipine) for adjuct after load reduction, if necessary
- thoracocentesis if required
treatment outline for dogs with DCM Stage D
- optimise Stage C therapies
- consider adding digoxin for additional inotropic support
- consider additional after load reduction (Amlodipine, hydralazine)
- strictly curtail exercise
what is the goal for heart rate control of AFIB?
140bpm in hospital is the recommended target
100bpm or less at home at expected
explain the genetic links to arrhythmogenic right ventricular cardiomyopathy in boxers
- ARVC in Boxers is familial with an autosomal dominant inheritance pattern
- a mutation in the striatin gene on chromosome 17, which encodes for a protein involved in cell-to-cell adhesions, has been associated with Boxer ARVC. Boxers with at least one copy of the striatin mutation are 40 times more likely to develop ARVC than homozygous negative dogs.
- overall genetic penetrance of this mutation is ~80%, with nearly 100% of homozygous positive dogs affected.
- however the mutation is not present in all Boxers with ARVC, and present in some without ARVC suggest it may collocate with rather than being causative
what is ARVC?
Arrhythmogenic right ventricular cardiomyopathy
- inherited primary myocardial disease of Boxer Dogs
what are the histologic changes in the myocardium with ARVC?
- characterised by fatty or fibrofatty infiltration, usually most severe in the right ventricle free wall
- atrophy of myofibers and myocardial fibrosis are also common
- focal areas of myocytolysis, necrosis, haemorrhage, and mononuclear cell infiltration may be seen.
what are the three clinical manifestations of ARVC?
- occult form; ventricular arrhythmias without CS
- overt ARVC; syncope/weakness associated with paroxysmal or sustained ventricular tachycardia, usually despite normal heart size and LV function
- ARVC + DCM phenotype (10%); ventricular tachyarrhythmias + DCM phenotype with poor myocardial function that progresses to CHF, unless sudden death occurs first.
clinical findings associated with ARVC
- median age at diagnosis is 6yo
- syncope most common complaint
what are the two potential causes for syncope in young adult boxers?
- ventricular tachyarrhythmias with ARVC
- neurocardiogenic (reflex-mediated) syncope; sudden surge in sympathetic activity triggers reflex vagal stimulation and inappropriate bradycardia and hypotension. Neurocardiogenic syncope can occur in normal boxers and boxers with ARVC, can be exacerbated by the use of sotalol/other B-blockers
is genetic testing available for ARVC in Boxer dogs?
Genetic testing for the striatin mutation is available and recommended for animals considered for breeding and may also provide prognostic information about an individual dog (esp. likelihood of developing the DCM phenotype).
- homozygous dogs should not be bred, heterozygous positive dogs should be bred only to dogs negative for the striatin mutation
when is antiarrhythmic therapy for Boxers with ARVC indicated?
- with clinical signs (ie. syncope)
- asymptomatic dogs with holter findings of greater than 1000 single VPCs/24 hours, ventricular tachycardia or close coupling of VPCs to the preceding QRS
what is the prognosis for Boxers with ARVC vs. ARVC DCM phenotype
- ARVC with normal systolic function and good antiarrhythmic treatment = normal median lifespan (10-11yo)
- sudden death is the most common cause of death with ARVC
- DCM phenotype - guarded prognosis - progresses to CHF, survival <6months after CHF onset
explain the pathophysiology of doxorubicin cardiotoxicity
- release of histamine with secondary catecholamine release appears to underlie acute toxicity, which is idiosyncratic and leads to transient ventricular and supraventricular arrhythmias during administration
- chronic cardiotoxicity appears to be mediated by DNA intercalation, inhibition of topoisomerase II, and free-radical production
- chronically cellular toxicity leads to LV dilation and decreased LV systolic function, mimicking idiopathic DCM
what doxorubicin doses are associated with cardiotoxicity?
- Echo changes and CHF seen at cumulative doses >150mg/m2
- ECG changes seen at doses as low as 90mg/m2
- cardiotoxicity becomes particularly likely when cumulative dose of doxorubicin exceeds 240mg/m2
why is ethyl alcohol given at <20% dilution?
- used to treat ethylene glycol intoxication - can cause severe myocardial depression and death
explain the function of L-carnitine in relation to the heart
L-carnitine is an essential component of mitochondrial membrane transport system for fatty acids, which are the hearts most important energy source.
It also transports potentially toxic metabolites out of the mitochondria in the form of carnitine esters
how is L-carnitine related to DCM?
- L-carnitine-linked defects in myocardial metabolism have been found in some dogs with DCM; likely 1+ underlying genetic or acquired metabolic defect
- seen in Boxers, Doberman Pinschers, Great Danes, Irish Wolfhounds, Newfoundlands, Cocker Spaniels
- dogs that respond to supplementation do so within the first month of supplementation
how is taurine used in the treatment of DCM?
- low taurine, and sometimes carnitine, concentrations occur in Cocker Spaniels with DCM
- oral supplementation of these amino acids can improve LV size and function, as well as reduce the need for heart failure medications in this breed
what is brain-heart syndrome?
excessive sympathetic stimulation stemming from brain or spinal cord injury results in myocardial hemorrhage, necrosis and arrhythmias
in what breed is muscular dystrophy of the fasciohumoral type that can result in atrial standstill and heart failure reported in?
english springer spaniels
what cardiac changes can be seen in Golden Retrievers with Canine X-linked muscular dystrophy?
- myocardial fibrosis and mineralisation with subsequent LV systolic dysfunction and CHF
explain ‘tachycardia-induced cardiomyopathy’
TICM refers to the progressive myocardial dysfunction, activation or neurohormonal compensatory mechanisms and CHF that result from rapid, incessant tachycardias.
what dog breed is predisposed to TICM?
Labrador Retrievers; predisposed to accessory pathway-mediated supraventricular tachycardias, often in associated with tricuspid dysplasia
what viruses have been reported to cause viral infective myocarditis in dogs?
- parvoviral myocarditis; peracute necrotizing myocarditis and sudden death
- canine distemper virus
- west nile virus (uncommon); severe lymphocytic and neutrophilic myocarditis and vasculitis, with areas of myocardial haemorrhage and necrosis
explain the etiology and pathophysiology of HCM in dogs
- uncommon in dogs; genetic bases in Pointers
- abnormal, excessive myocardial hypertrophy increases ventricular stiffness and leads to diastolic dysfunction
- LV hypertrophy usually symmetric, but regional variation in wall/septal thickness can occur
- compromised coronary perfusion with severe ventricular hypertrophy –> myocardial ischaemia –> arrhythmias, delayed ventricular relxation, impairs filling
- high LV filling pressure predisposes to pulmonary venous congestion and oedema
clinical features of HCM in dogs
- most commonly diagnosed in young to middle-aged large-breed dogs, often les than 3 years of age
- males more commonly affected
what are the general goals in treatment of HCM in dogs
ENHANCE
- myocardial relaxation
- ventricular filling
CONROL
- pulmonary oedema
SUPPRESS
- arrhythmias
outline treatment of HCM in dogs
- B-blocker (atenolol) used to lower heart rate, prolong ventricular filling time, reduce ventricular contractility and minimize myocardial oxygen requirements. Also reduce dynamic LV outflow obstruction and may suppress arrhythmias induced by heightened sympathetic activity
- Ca2+ channel blocker (diltiazem) could be considered to decrease heart rate and facilitate myocardial relaxation (not commonly chosen dt vasodilatory effect)
prognosis for canine HCM
variable
normal lifespan to sudden death
what organisms are associated with bacterial myocarditis?
- Staphylococcus
- Streptococcus
- Citrobacter
- Bacillus
- Morazella
- Bartonella visonii
what is the organism that cause lyme disease and how is it transmitted?
Borrelia burgdorferi; transmitted to dogs by ticks (esp. Ixodes genus)
what is a characteristic ECG change in lyme carditis?
High-grade AV block
what protozoal organisms are found to cause myocarditis?
- Trypanosoma cruzi
- Toxoplasma gondii
- Neosporum caninum
- Babesia canis
- Hepatozoon americanum
- Leishmania spp.
what is Chagas disease?
- Trypanosomiasis - an important zoonosis in ventral and south america (chagas myocarditis if the most common cause of human cardiomyopathy in the world)
- acute and chronic phases described
- acute stage can involve lethargy, depression, other systemic signs and tachyarrhythmias
- chronic disease is characterised by progressive right-sided or generalised cardiomegaly and various arrhythmias (ventricular tachyarrhythmias are the most common)
- end stage disease is indistinguishable from idiopathic DCM
how does the treatment of acute vs chronic chagas disease differ?
- acute; aims at eliminating the organism and minimizing myocardial inflammation (benznidazole)
- chronic: antiparasitics do not effect outcome; tx. aimed at supporting myocardial function, controlling CHF, suppressing arrhythmias
which organisms can form cysts in the heart?
- Toxoplasmosis
- Neosporosis
- Hepatozoon americanum
what clinical findings are associated with non-infective myocarditis?
- high-grade AV block, sinus arrest, sudden death
- often unexplained onset of arrhythmias or CHF after a recent exposure of infective disease or drug exposure
how do you diagnose non-infective myocarditis?
endomyocardial biopsy specimens are the only means of obtaining a definitive antemortem diagnosis
sepis-induced myocardial dysfunction describes a syndrome….
of reversible myocardial depression that occurs in the setting of sepsis of other critical illness.
sepsis-induced myocardial dysfunction syndrome is characterized by…
- ventricular dilation and systolic dysfunction (a DCM phenotype)
- can involve both LV and RV
- normal or high cardiac output
- low systemic vascular resistance
how do you treat sepsis-induced myocardial dysfunction
- inotropic support; dobutamine or pimobendan
- sepsis treatment
- ventricular size and function completely normalize within 7-10days if treatment successful
list possible mechanisms of myocardial trauma causing traumatic myocarditis
- impact against the chest wall
- compression
- acceleration-deceleration forces
- autonomic imbalance
- ischaemia
- reperfusion injury
- electrolyte/acid-base disturbances
what arrhythmias are commonly associated with traumatic myocarditis
- VPCs
- ventricular tachycardia
- accelerated idioventricular rhythm (60-100bpm)
usually appears within 24-48hours after trauma
list the common classifications of myocardial disease in cats
- hypertrophic
- dilated
- restrictive
OR
‘unclassified’
what is the cause of primary/idiopathic hypertrophic cardiomyopathy in cats?
It is unknown, but heritable abnormality is likely in many cases.
- autosomal dominant inheritance has been identified in Maine Coon, Ragdoll, Sphynx, American Shorthair breeds
in what cat breeds does HCM commonly occur?
- Maine Coon
- Ragdoll
- Sphynx
- American Shorthair Breeds
- British Shorthairs
- Norwegian Forest Cats
- Scottish Folds
- Bengals
- Siberians
- Rex
what breeds of cats have a mutation in the cardiac myosin binding protein C gene associated with HCM?
Maine Coons and Ragdolls
list possible causes of HCM in cats
- mutations of genes that encode for myocardial contractile or regulatory proteins
- increased myocardial sensitivity to or excessive production of catecholamines
- an abnormal hypertrophic response to myocardial ischemia, fibrosis or trophic factors
- a primary collagen abnormality
- abnormalities of the myocardial calcium-handling process
explain the pathophysiology of HCM in cats>
- abnormal sarcomere function is thought to activate abnormal cell signaling processes that eventually produce myocyte hypertrophy and disarray, as well as increased collagen synthesis
- results in thickening of LV wall +/- IVseptum
- many cats have symmetric hypertrophy but some are asymmetric
- myocardial hypertrophy increases ventricular wall stiffness (impairs LV filling and increases diastolic pressure)
- early activation of myocardial relaxation many be slow and incomplete, esp. in the presence of myocardial ischemia or abnormal Ca++ kinetics –> further reduces ventricular distensibility and promotes diastolic dysfunction
- reduced ventricular volume results in a lower stroke volume, which may contribute to neurohormonal activation – higher HRs further interfere with LV filling, promote myocardial ischaemia, contribute to pulmonary venous congestion and oedema by shortening the diastolic filling period
- higher LV filling pressures leads to increased LA and pulmonary venous pressures –> progressive LA dilation + pulmonary congestion + oedema
- Intracardiac thrombi (within the L.auricle or LA/LV) –> arterial thromboembolism
what several factors probably contribute to the development of myocardial ischaemia in cats with HCM?
- narrowing of intramural coronary arteries
- increased LV filling pressure
- decreased coronary artery perfusion pressure
- insufficient myocardial capillary density for the degree of hypertrophy
- tachycardia; increased myocardial O2 requirements + reduced diastolic coronary perfusion time
typical feline HCM signalment
- ave. age of diagnosis is 6yo
- male sex predilection
- heritability
- overall prevalence of HCM is 15%, increasing with age
heart murmur prevalence in apparently healthy cats?
20-40%
prognosis of feline HCM
- overall median survival time for cats diagnosed with asymptomatic HCM is ~5yrs
- 20-40% of cats diagnosed with HCM will develop CHF
- 5-10% suffer an arterial thromboembolism
- 20% experience sudden cardiac death
what VHS is suggestive of significant feline heart disease?
VHS >9.3v (normal is 7.5v)
what NT-proBNP levels are diagnostic for feline myocardial disease?
212-258pmol/L resulting in sensitivity and specificity of approximately 90% (in cats with respiratory distress)
cutoff >46pmol/L had a sensitivity 86% and specificity of 91% for detecting occult HCM
goals of feline HCM therapy
- enhance ventricular filling
- relieve congestion
- control arrhythmias
- minimize ischaemia
- prevent thromboembolism
why are Enalapril and benazepril used to treat feline HCM?
- to reduce neurohormonal activation and abnormal cardiac remodeling
what factors influence the prognosis of cats with HCM?
- speed of disease progression
- occurrence of thromboembolic events +/- arrhythmias
- response to therapy
treatment outline for cats with HCM with severe, acute signs of CHF
- supplemental O2
- minimize patient handling
- furosemide
- sedation
- thoracocentesis
- pimobendan (caution if LV outflow obstruction)
- antiarrhythmic therapy if required
+/- nitroglycerin
+/- dobutamine (if needed for cardiogenic shock)
treatment outline for cats with HCM with mild to moderate signs of CHF
- furosemide
- ACEI
- pimobendan (caution if LV outflow obstruction)
- antithrombotic prophylaxis (clopidogrel +/- anticoagulant)
- exercise restriction
- reduced-salt diet (if the cat will eat it)
+/- B-blocker (atenolol) or diltiazem
treatment outline for cats with HCM with refractory CHF
- furosemide (optimised dose/frequency)
- ACEI
- Pimobendan (caution is severe LV outflow tract obstruction)
- thoracocentesis PRN
- antithrombotic prophylaxis (clopidogrel +/- anticoagulant)
+/- spironolactone
+/- B-blocker or diltiazem
+/- additional antiarrhythmic drug if needed
+/- hydrochlorothiazide (closely monitor lytes/renal function) - home monitoring of RRR and RE
- dietary salt restriction, if accepted
- monitor renal function, lutes etc
- manage other medical problems (hypertension, HyperT)
what are causes of secondary myocardial hypertrophy in cats?
- hyperthyroidism
- acromegaly
- systemic hypertension
- infiltrative myocardial diseases (lymphoma)
how does hyperthyroidism alter cardiovascular function
- direct effects on the myocardium and through the interaction of heightened sympathetic nervous system activity and excess thyroid hormone on the heart and peripheral circulation
- cardiac effects of thyroid hormone include; myocardial hypertrophy and increased heart rate and contractility
- hyperdynamic circulatory state (dt metabolic acceleration) characterised by increased CO, oxygen demand, blood volume and HR
- systemic hypertension further stimulates myocardial hypertrophy
outline the manifestations of hyperthyroid heart disease
- systolic murmur
- hyperdynamic arterial pulses
- strong precordial impulse
- sinus tachycardia
- various arrhythmias
what is the expected cardiac response to systemic arterial hypertension?
- LV concentric hypertrophy
- systemic arterial hypertension increases afterload because of high arterial pressureand resistance
what is RCM?
a myocardial disease phenotype associated with extensive endocardial, subendocardial or myocardial fibrosis of unclear, but probably multifactorial etiology.
Can be a consequence of endomyocarditis, infiltrative neoplasia or idiopathic, no specific familial or genetic mutations identified
what are characteristic features of RCM?
- diastolic dysfunction (restrictive filling physiology)
- severe LA enlargement in the absence of myocardial hypertrophy
histopathologic findings in cats with RCM
- marked perivascular and interstitial fibrosis
- intramural coronary artery narrowing
- myocyte hypertrophy
- areas of degeneration and necrosis
clinical features of RCM
- middle-aged and older cats
- similar to HCM
- systolic murmur of mitral/tricuspid regurgitation, and S4 gallop +/- arrhythmia
prognosis of RCM
generally guarded to poor for cats with RCM and CHF, but some cats survive more than a year after diagnosis
why is feline DCM less common now than in the 1980s?
- taurine deficiency was identified as a major cause and pet foods increased their taurine content
does doxorubicin cause myocardial lesions in cats?
clinically relevant doxorubicin-induced cardiomyopathy is not an issue in the cat (doses of 600mg/mg2 have been given without evidence of cardiotoxicity)
clinical features of feline DCM?
- any age, but generally late-middle to geriatric cats
- no breed or sex predilection
prognosis of feline DCM (taurine related vs. not)
- taurine-deficient cats that survive 1month after initial diagnosis have a 50% chance for 1 year survival
- not taurine deficient DCM in guarded to poor, with median survival time of 49 days with medical treatment
what are characteristics of feline ARVC?
- moderate to severe RV chamber dilation, with focal/diffuse RV wall thickening
- RV wall aneurysm can occur
- dilation of RA > LA
- myocardial atrophy with fatty +/- fibrous replacement tissue, focal myocarditis, evidence of apoptosis
how much dietary taurine is required to maintain normal plasma taurine concentrations in adult cats?
- dry diets with 1200mg taurine/kg dry weight
- canned diets with 2500mg taurine/kg dry weight
prognosis of feline ARVC?
guarded once signs of heart failure appear
what is UCM?
‘Unclassified cardiomyopathy’ - term used in people to describe cases of myocardial disease that do not fit within other defined categories (HCM, RCM, DCM, ARVC)
- in cats most often applied to cases with severe LA or biatrial dilation despite normal LV size, wall thickness, systolic function, and without obvious evidence of endomyocardial fibrosis (which would = RCM)
- comprises~ 10% of feline cardiomyopathy cases
MOA of corticosteroid-associated heart failure
- proposed mechanism if the diabetogenic effect of glucocorticoids causing a transient hyperglycaemia and subsequent intravascular fluid shift, precipitating volume overload and acute CHF
- occurs ~3-7 days after receiving long-acting corticosteroid (Depo-medrol)
what infections have been associated with feline myocarditis?
- coronavirus
- panleukopenia
- Toxoplasma gondii
outline the anatomy of the pericardium
- the normal pericardium forms a closed, double layered sac around the heart and is attached to the great vessels at the heart base
- directly adhered to the heart is the visceral pericardium (epicardium), which is composed of a thin layer of mesothelial cells - this layer reflects back over itself at the base of the heart to line the outer, fibrous layer (parietal pericardium)
- a small volume of fluid (~0.25ml/kg) if between these layers (lubricant)
functions of the pericardium
- anchors the heart in place
- provides a barrier to infection or inflammation from adjacent tissues
- helps balance the output of the right and left ventricles
- limits acute distention of the heart
what is a PPDH?
Peritoneopericardial diaphragmatic hernia (PPDH) is the most common congenital malformation of the pericardium in dogs and cats. It occurs when abnormal embryonic development allows persistent communication between the pericardial and peritoneal cavities at the ventral midline. Abdominal contents herniate into the pericardial space to a variable degree and cause associated clinical signs.
clinical features of PPDH
- majority are diagnosed during the first 4 years of life, usually w/in 1 yr
- males more frequently than females
- Weimaraners, Persians, Himalayan and DLH cats
radiographic features of PPDH
- enlargement of the cardiac silhouette
- dorsal tracheal displacement
- overlap of the diaphragmatic and caudal heart borders
- abnormal fat +/- gas densities within the cardiac silhouette
treatment of PPDH
surgical closure can be done after viable organs are returned to their normal location
perioperative complications are common, usually mild
what is the most common cause of pericardial effusion in dogs vs. cats?
- cats; CHF (» neoplasia, FIP)
- dogs: neoplastic or idiopathic
features of hemorrhagic effusions
- dark red, PCV >7%
- specific gravity of 1.015
- protein conc. >3g/dL
common causes of hemorrhagic pericardial effusions in dogs
- HSA is the most common neoplasm
- Various heart base tumours; Chemodectoma (arises from chemoreceptor cells at the base of the aorta), HSAs (arise from the right heart, esp. right auricle), pericardial mesothelioma, malignant histiocytosis, lymphoma
what breeds may be predisposed to idiopathic pericardial effusion in dogs?
Golden retrievers, Labs, St Bernards
- median age 6-7yo, Males > Females
ddx. of intrapericardial haemorrhage
- HSA, heart base tumours
- LA rupture secondary to severe mitral insufficiency
- coagulopathy (DIC, rodenticide)
- penetrating trauma (iatrogenic laceration of a coronary artery during pericardiocentesis)
- uremic pericarditis
characteristics of transudate
- clear
- low cell count («1000cells/uL)
- specific gravity <1.012
- protein content <2.5g/dL
characteristics of modified transudates
- slightly cloudy or pink tinged
- cellularity 1000-8000cells/uL
- TP 2.5-5g/dL
- specific gravity 1.015-1.030
causes of transudative pericardial effusion in cats and dogs
- CHF
- hypoalbuminaemia
- PPDH
- pericardial cysts
- toxaemias that increase vascular permeability (including uremia)
characteristics of exudates
- cloudy to opaque, serofibrinous to serosangeuinous
- high nucleated cell count >3000cells/uL
- protein 3g/dL
- specific gravity >1.015
what is the most common cause of exudative pericardial effusions?
FIP in cats
other causes; Leptospirosis, Canine Distemper, Idiopathic in dogs
Toxoplasmosis in cats
Penetrating/migrating FBs, extension of pleural/mediastinal infection
cardiac tamponade develops when…
pericardial fluid accumulation raises intrapericardial pressure to or above the normal cardiac diastolic pressure –> external compression of heart limits filling of the more compliant right heart, then the left –> CO falls
explain how pericardial effusion can cause pulsus paradoxus
- term used to described the exaggerated variation in arterial BP that occurs during the respiratory cycle dt cardiac tamponade
- Inspiration: intrapericardial and RA pressure falls, facilitates right heart filling and pulmonary blood flow. Left heart filling is reduced as more blood is held in the pulmonary vasculature and the interventricular septum bulges leftward from the inspiratory increase in the RV
- consequently left heart output and systemic arterial pressure DECREASE during INSPIRATION
how can circulating cardiac troponin concentration be used in the work-up of pericardial effusion?
- cTnI conc. can increase as a result of ischemia or myocardial invasion
- an elevated cTnI helps differentiate pericardial effusion caused by HSA from other causes - HSA does not increased the cTnI concentration if it does not affect the heart
what ECG abnormalities are suggestive of pericardial effusion?
- small amplitude QRS complexes (<1mV in dogs)
- electrical alternans (electrical alternans is a recurring alteration in the size of the QRS complex (or sometimes T wave) with every other beat)
- ST segment elevation (epicardial injury current)
why is differentiating hemorrhagic neoplastic effusions from benign hemorrhagic pericarditis usually not possible based on cytology alone
- reactive mesothelial cells within the effusion can closely resemble neoplastic cells
- chemodectomas and HSAs may not shed cells into the effusion
which neoplastic pericardial effusion is more easily identified?
- lymphoma; typically have a modified transudate with easily identified neoplastic cells
treatment of idiopathic pericardial effusion in dogs
- pericardiocentesis
- glucocorticoids (pred 1mg/kg/day PO tapering over 2-4wks) after ruling out infectious causes
vs. pericardiotomy or subtotal pericardiectomy
prognosis of canine idiopathic pericardial effusion
- apparent recovery occurs after 1-3 pericardial taps in about 50% of cases
treatment of heart base tumours
- surgical resection is usually not possible dt tumour invasiveness
- most cardiac tumours are fairly resistant to chemotherapy
- radiation may be palliative
- consider therapy with antifibrolytic agents
prognosis of canine RA HSA
poor; median survival 2-3wks
- multiagent chemotherapy has allowed survival times of 4-8months in some dogs
prognosis of chemodectomas
- slow growing and locally invasive
- pericardiotomy/partial pericardiectomy may prolong survival for years
treatment of infectious pericarditis
- appropriate antimicrobial drugs based on C&S
- +/- infusion of ABs directly into pericardium after pericardiocentesis
prognosis of infectious pericarditis
- guarded; even with successful elimination of infection, epicardial and pericardial fibrin deposition may lead to constrictive pericardial disease
how much blood should be removed when intrapericardial haemorrhage occurs?
only enough volume to control signs of tamponade, the remaining blood is usually resorbed through the pericardium
outline the steps taken when performing a pericardiocentesis
- Prep region; right precordium from 3rd-7th ICS from sternum to well above the costochondral junction
- Local block with 2% lidocaine (0.5-1ml) into skin and underlying intercostal muscles to the pleura at the puncture site (usually btwn 4th-6th rib at the point of strongest precordial impulse)
- Butterfly needle/catheter (12-16 gauge in large dogs, 18-20G in small dogs) - aim the needle tip towards the point of the patient’s opposite shoulder as chest is entered - assistant should apply gentle negative pressure once under the skin
- Contact the pericardium (increased resistance, subtle scratching sensation) and slowly advance through the pericardium - a loss of resistance may be felt and pericardial fluid (usually dark red) will appear in the tubing connected.
how can you verify the catheter is in the pericardium and not the heart?
- fluid should not clot (unless very recent hemorrhage)
- US ‘bubble’ study
- improving ECG, CDV parameters
list complications of pericardiocentesis
- cardiac injury or puncture causing arrhythmias
- lung laceration (pneumothorax +/ hemorrhage)
- coronary artery laceration with myocardial infarction or further bleeding into pericardial space
- dissemination of infection/neoplastic cells into pleural space
- death
etiology of constrictive pericardial disease
- unknown; acute inflammation with fibrin deposition and varying degrees of pericardial effusion are thought to precede its development
- a sequelae to other conditions of the pericardium (idiopathic hemorrhagic effusion, infectious pericarditis (coccidiomycosis, actinomycosis, mycobacteriosis, blastomycosis, bacteria), penetrating FBs, tumours, prior PPDH sx
pathophysiology of constrictive pericardial disease
- thickening and scarring of the visceral, parietal or both pericardial layers restricting ventricular diastolic expansion and preventing normal cardiac filling
typical signalment of dogs with constrictive pericardial disease
- medium-large breeds
- males
- GSD
treatment and prognosis
- pericardiectomy is required - more successful if only the parietal pericardium is involved
- it is a progressive disease and without successful surgical intervention ultimately fatal
features of HSA
- most common canine cardiac tumour
- right auricle, RA, frequent site of origin, some also infiltrate the ventricular wall extensively
- likely to met to lung and spleen
breeds with higher risk for RA HSA
- goldens/labs
- GSD
- afghan hounds
- cocker spaniel
- english setters
what is another name for a chemodectoma?
nonchromaffin paragangliomas
what are the two most common types of cardiac tumours in dogs?
- HSA
- chemodectomas
what is a chemodectoma?
- masses involving the heart base and ascending aortic region - aortic body tumours
- neoplasms of the chemoreceptor aortic bodies
what breeds have a higher risk of chemodectomas?
brachycephalics; Boxers, Boston Terriers, Bulldogs
what breed may be predisposed to mesothelioma?
golden retrievers; chronic inflammation associated with prior idiopathic pericardial disease is a postulated predisposing factor
what breeds are most affected with malignant histiocytosis
- goldens
- labs
- rottweilers
- greyhounds
clinical features of cardiac tumours
DOGS; middle-older, more than 85% of affected dogs are btwn 7-15yo, speyed females 4-5x more likely than intact females
CATS; any age, about 28% are <7yo
what echocardiography position is best to identify heart base masses
left cranial parasternal transducer position is useful for evaluating the ascending aorta, right auricle and surrounding structures
what chemos have been used in HSA?
- doxorubicin
- carboplatin
offer temporary palliation
prognosis of heart base tumours
- poor
- surgical resection is difficult
- poorly responsive to chemos (ex. lymphoma)
what are normal pulmonary arterial pressures?
20-25/10 (15)
define pulmonary arterial hypertension
systolic pressures >35mmHg or mean pulmonary arterial pressures <25mmHg
what mmHg values correlate mild - severe PAH
mild 35-55mmHg
mod 55-80mmHg
severe >80mmHg
systolic arterial pressures
what are common histopathologic changes in affected pulmonary arteries/arterioles with PAH
- medial hypertrophy
- intimal proliferation and fibrosis
- luminal thrombosis
- arterial necrosis
Define Groups I-V of PAH using the WHO classifications
Group I: idiopathic (primary) pulmonary hypertension, congenital retention of fetal pulmonary vascular resistance, and pulmonary overcirculation from congenital left-to-right shunts causing vascular injury and pulmonary arterial remodeling
Group II: PAH occurring secondary to pressure buildup across the pulmonary capillary bed due to chronically elevated pulmonary venous pressures, as seen in mitral regurgitation and other left-sided cardiac diseases
Group III: PAH includes hypoxic pulmonary disease (eg. pulmonary fibrosis or other chronic bronchopulmonary disease) leading to reactive vasoconstriction, reduced vascular area and vascular remodeling.
Group IV: refers to pulmonary thromboembolic disease. Thrombotic vascular obstruction reduces total cross-sectional pulmonary vascular area by mechanically obstructing vessels and provoking local hypoxic pulmonary vasoconstriction, as well as other reactive changes.
Group V: miscellaneous
what are the most common causes of canine PAH
- pulmonary venous hypertension from left-sided heart disease (Group II)
- hypoxic pulmonary disease (Group III)
*note incidence of HWD in study influential
define precapillary PAH
primarily affecting pulmonary arteries and arterioles, before blood reaches the pulmonary capillary bed
define postcapillary PAH
primarily affecting pulmonary veins, with secondary buildup of pressure across the capillary bed back to the pulmonary arterial tree
clinical signs of PAH
- reduced exercise tolerance
- fatigue
- persistent respiratory difficulty
- cough
- syncope
radiographic findings consistent with PAH
can include
- RV enlargement
- main pulmonary artery dilation (‘bulge’ of pulmonary trunk)
- enlargement, tortuosity and blunting of lobar pulmonary arteries
echocardiographic findings consistent with PAH
- RV and RA dilation
- RV hypertrophy
- flattening of the interventricular septum with paradoxical septal motion
- a small left heart
- pulmonary artery dilation (larger than the aorta)
treatment of precapillary PAH
phosphodiesterase-5 inhibitors (sildenafil and tadalafil)
- decrease the activation of cyclic guanosine monophosphate (GMP), a second messenger of the nitric oxide pathway, leading to vasodilation.
- phosphodiesterase-5 inhibitors are relatively specific for the pulmonary vasculature and thus act as selective pulmonary vasodilators
treatment of postcapillary PAH
focuses on decreasing LA (+ thus pulmonary venous) pressures
- pimobendan + ACEI (systemic vasodilation)
- furosemide (preload reduction)
+/- amlodipine (further systemic arterial vasodilation - afterload reduction)
prognosis for canine PAH
- other than HWD most causes of PAH are advanced and incurable, pulmonary vascular remodeling is irreversible
- prognosis for dogs with severe PAH is poor with median survival times 3-6months, tx. w/ sildenafil improves survival ~75% alive 1yr post diagnosis
how does heartworm disease differ in prevalence between cats and dogs in the USA?
Dogs 5-15%
Cats 0.4% in the same geographic area
summarise the lifecycle of heartworm
D.immitis is transmitted by mosquitoes (obligate intermediate host).
Mosquito ingests microfilariae (L1) from infected animal –> L1-L3 in mosquito in about 2-2.5wks w/ symbiotic Wolbachia bacteria –> L3 enter new host, migrate through SC molting into L4 within 9 - 12 days –> L5 2-3 months after infection –> L5 (juvenile worm) enters vasculature (d100) and migrates to peripheral pulmonary arteries of the Cd.lung lobes –> mature adults after 5-9months –> mated and release microfilariea (L1)
are microfilariae passed via blood transfusion or across the placental barrier infective?
no - require mosquito host to complete L1-L3 maturation
pathogenesis of HWD
- provokes reactive vascular lesions that reduce vascular compliance and lumen size
- pathogenesis is modulate by Wolbachia –> bacterial endotoxins, host immune response to Wolbachia surface protein (WSP) = pulmonary and renal inflammation
- increased pulmonary blood flow exacerbates pulmonary vascular pathology
histopathologic changes associated with HWD
- villous myointimal proliferation of the pulmonary arteries containing HWs
- HW-induced changes begin with endothelial swelling –> endothelial sloughing –> villous proliferations (occur about 3-4 wks after adult worms arrive) –> cause luminal narrowing, promotes thrombosis and perivascular tissue reaction and periarterial oedema
- hypersensitivity (oesinophilic) pneumonitis may contribute to parenchymal lung lesions (oesinophilic granulomas)
major pathogenesis of HWD
- villous myointimal proliferation of the pulmonary arteries
- hypersensitivity pneumonitis
- hypoxia dt PTE or pulmonary infiltrates
- RV dilation and concentric hypertrophy
- circulating immune complexes/microfilarial antigens resulting in glomerulonephritis
- chronic hepatic congestion –> cirrhosis
- caval syndrome; DIC, SIRS
- aberrant systemic arterial worm migration; multifocal embolization
what is the HWD diagnostic test of choice?
Adult HW antigen (AG) tests + microfilariae identification
what can cause false-negatives of Adult HW Ag tests?
- low worm burden
- immature female worms only
- male unisex infection
- inaccurate adherence to test instructions
- Ag-Ab complex formation in blood
what causes a positive HW Ag test?
- at least four female worms 7-8 months old
clinical features of HWD?
males are affected 2-4x more than females, any age but typically 4-8yo
of all dogs diganosed, 70% asymptomatic, 25% exercise intolerance/resp. signs, <5% RSCHF/caval syndrome
Day 0 HWD Management Protocol
- positive AG test verified with microfilaria (MF) test
- if no microfilariae are detected confirm with 2nd Ag test from different manufacturer
- exercise restriction
- pred tapering 4wk course
Day 1 HWD Management Protocol
- if microfilariae present, pretreat with antihistamine and glucocorticoid to reduce risk of anaphylaxis
- administer HW preventative - observe for 8 hours for signs of reaction
Day 1-28 HWD Management Protocol
Doxycycline 10mg/kg/ PO q12h for 4 weeks
- reduced pathology associated with dead HWs and disrupts HW transmission
Day 30 HWD Management Protocol
administer HW preventative
Day 60 HWD Management Protocol
- HW preventative
- Melarsomine Injection 2.5mg/kg IM
- Pred tapering 4 wk course
- cage restriction/leash when using yard
Day 90 HWD Management Protocol
- HW preventative
- 2nd Melarsomine IM
Day 91 HWD Management Protocol
- 3rd Melarsomine IM
- Pred tapering 4 wk course
- continue exercise restriction for 6-8 wks post
Day 120 HWD Management Protocol
test for presence of microfilariae
- if positive treat with additional 30d Doxy course and retest in 4 weeks
- establish yr round HW prevention
Day 271 HWD Management Protocol
- antigen test 6 months after completion, screen for microfilariae
AEs of melarsomine
- local reaction at site (oedema, tenderness) resolve within 4-12 weeks
- behavioural; tremoring, lethargy, ataxia, unsteadiness
- respiratory; panting, crackles, shallow/laboured breathing
when is PTE most likely to occur during HWD Tx?
7-10 days after adulticide therapy, but can occur up to 4 weeks later
Treatment of PTE post HWD tx
- ex. restriction
- pred
- O2
- sildenafil
- clopidogrel/aspirin
- bronchodilator
- cough suppressant
list pulmonary complications of HWD?
- allergic or eosinophilic pneumonitis
- pulmonary eosinophilic granulomatosis
- severe pulmonary arterial disease; including PAH and PTE
list complications of HWD
- pulmonary complications
- RSCHF
- Caval syndrome
prognosis for caval syndrome
- without aggressive tx. most dogs die within 24-72hours dt cardiogenic shock, metbaolic acidosis, DIC, anaemia
- survival rates for surgical removal of worms is 50-80%
list HW preventatives and route of administration
- macrocyclic lactones PO monthyl; ivermectin (heartgard, Iverhart, Tri-heart) and milbemycin oxime (Sentinel, Interceptor, Trifexis)
- monthly topical administration; selamectin (revolution) and moxidectin/imidacloprid (advantage multi) - no bathing 2 hours post appication
- slow-release SQ injection (proheart) moxidectin
what type of HWD is more common in cats?
HW ‘exposure’ with early parasite destruction - ‘pulmonary larval dirofilariasis’ or ‘heartworm-associated respiratory disease’ (HARD)
explain the two stages of pathophysiologic changes in feline HWD?
- Initial HARD Phase; 3-4 months after infection immature worms arrive in the pulmonary arteries and most die from acute host inflammatory reaction involving specialized phagocytic cells located in the pulmonary capillary beds of cats but not dogs. CS mimic feline allergic airway disease and can lead to resp. distress 3-9 months after infection.
- Maturation phase; vascular injury leads to myointimal proliferation, muscular hypertrophy, luminal narrowing, tortuosity and thrombosis in affected pulmonary arteries. Usually only involves a few worms and worm life span is relatively short.
clinical features of feline HWD
- 3-6yo
- shorthaired cats > longhaired cats
- 25% occur in indoors only
- CS: vomiting, resp signs mimicking feline asthma
outline differences between canine and feline HWD diagnosis
- in cats HW Ag tests are regularly negative dt low worm burden in cats, and more frequently unisex infections
- HW antibody tests can be more sensitive in cats to detect exposure
- microfilaraemia is rare in cats
- caval syndrome and RSCHF is very rare in cats
list HW prophylaxis and route of administration in cats
- oral monthly Ivermectin (Heartgard for cats) + Milbemycin oxime (Interceptor Tabs for Cats)
- topical monthly selamectin (Revolution) + moxidectin/imidacloprid combination (advantage multi for cats)
all safe for kittens >6wks
treatment of HWD in cats
- adulticide therapy is not recommended dt severe complications and spontaneous cure can occur
- initiate monthly HW preventative
- use prednisolone for resp signs/pulmonary infiltrates
- Doxycycline 10mg/kg PO 4wks
HW Ab and Ag tests every 6-12months to monitor infection status
what is “French Heartworm”?
Angiostrongylus vasorum in dogs - can cause pulmonary vascular disease similar to D.immitis
briefly outline the lifecycle of A.vasorum
- natural definitive host is the wild fox
- intermediate host; gastropod (slug/snail); L1 larvae ingested –> L3
- dogs eat the intermediate host: L3 penetrate through intestinal mucosa and migrate to abdo LNs –> immature worms travel via portal circulation to pulmonary arteries (d30-35 post infection) –> mature, mate and produce eggs
- eggs lodge and develop in pulmonary capillaries –> L1 hatch into airspace –> coughed up and swallowed –> L1 in faeces
- prepatent period 5-8weeks
treatment for A.vasorum
- fenbendazole 25-50mg/kg PO q24h for 7-21d
- Milbemycin oxime 0.5mg/kg PO q1wk for 4 weeks
- Moxidectin - single topical dose of 2.5mg/kg
+ exercise restriction, glucocorticoids, other supportive meds
outline the diagnosis of A.vasorum
- L1 larvae in faeces of infected dog (intermittent shedding)
- ELISA for Ag produced by adult female worms (positive at 5-9wks post infection)
what are normal systolic BP values in dogs and cats
Cats 120mmHg
Dogs 130mmHg
what is classification of abnormal BPs in dogs and cats based off
risk of damage to ‘target organs’
Systemic arterial hypertension Risk Category I
BP less than 150/95 mmHg have minimal risk to target organs
Systemic arterial hypertension Risk Category II
BP 150-159/95-99mmHg have mild risk to target organs
Systemic arterial hypertension Risk Category III
BP 160-179/100-119mmHg
Systemic arterial hypertension Risk Category IV
BP >180/120mmHg = severe hypertension with severe risk for target organ damage
diseases associated with hypertension in dogs and cats
- renal disease (esp. glomerular)
- hyperadrenocorticism
- hyperthyroidism
- pheochromocytoma
- diabetes mellitus
- hyperaldosteronism (Conn’s syndrome)
- intracranial lesions (increased intracranial pressure)
- high-salt diet
- obesity
what is the reported prevalence of hypertension in feline CKD and hyperT?
25-75%
what is the prevalence of hypertension in dogs with renal disease and hyperadrenocorticism respectively?
30%
80%
explain the pathophysiology of hypertension
BP is the product of CO and systemic vascular resistance. BP is increased by conditions that raise CO (inc. HR, SV +/- blood volume) or by those that increase peripheral vascular resistance. Arterial BP is normally maintained within narrow bounds by the actions of the autonomic nervous system, various hormonal systems, blood volume regulation by the kidneys and other factors. Modulation of these systems can lead to chronic elevation of arterial BP.
High perfusion pressure can damage capillary begs causing vascular remodeling and vascular resistance –> hypoxia, tissue damage, hemorrhage and infarction leading to organ dysfunction.
ocular complications of hypertension
- retinopathy (oedema, vascular tortuosity, haemorrhage, focal ischaemia, atrophy)
- choroidopathy (oedema, vascular tortuosity, hemorrhage, focal ischaemia)
- retinal detachment (bullous or total)
- hemorrhage (retinal, vitreal, hyphema)
- papilloedema
- blindness
- glaucoma
- secondary corneal ulcers
neurologic complications of hypertension
- cerebral oedema, increased ICP
- hypertensive encephalopathy (lethargy, behavioural changes
- cerebrovascular accident (focal ischaemia, haemorrhage)
- seizures
- other acute neuro deficits
renal complications of hypertension
- glomerulosclerosis/proliferative glomerulitis
- renal tubular degeneration and fibrosis
- progression of CKD
- worsening proteinuria
- PU/PD
cardiac complications of hypertension
- LV hypertrophy
- murmur/gallop sound
- aortic dilation
- aortic aneurysm or dissection (rare)
- LSCHF (rare)
list the ‘target organs’?
- eye
- kidney
- heart
- brain
outline the diagnosis of hypertension
- systemic hypertension should be confirmed by measuring BP multiple times and ideally on different days
- systemic BP could be estimated during an echocardiographic exam in animals with mitral valve insufficiency by measuring the peak velocity of the mitral regurgitant jet + the modified Bernoulli equation
BP measurements are indicated in which 3 patient populations
(1) patients with suspected TOD
(2) patients diagnosed with a disease known to be associated with systemic hypertension (hyperT, protein losing nephropathy, CKD)
(3) as a screening test in older cats and dogs beginning at 8yrs
outline the correct method used to when using NIBP measurement
- patient in sternal/lateral recumbency
- limited restraint
- owner present, if useful
- allow 5-10 minutes for acclimatization to environment
- non-dependent limb or tail base
- width of cuff should be about 40% circumference of the limb
- 5-7 readings; discard the lowest and highest, average the rest, should be less than 20% variability btwn readings
approach to hypertension treatment
- manage underlying disease(s)
- avoid drugs that increase BP
- mild-moderate reduction in salt diet
- weight-reduction if obese
- being antihypertensive drug therapy; Dogs - ACEI, Cats w/ proteinuric renal disease - ACEI, cats with hyperT - atenolol +/- amlodipine, other cats - amlodipine
- emergent therapy if needed
- provide client education
re-evaluate in 7-10 days for clinically stable patients;
- try combo therapy (add ACEI or amlodipine), or de-escalate therapy
- re-check q3-4months
list drugs used in a hypertensive crisis
- amlodipine
- hydralazine
- nitroprusside
- esmolol
- propranolol
- acepromazine
- phentolamine
list drugs used to treat hypertension
ACEIs; enalapril, benazepril, ramipril, captopril
Calcium channel blocker; Amlodipine
B-adrenergic blockers; Atenolol, Propranolol
A1-adrenergic blockers: Phenoxybenzamine, Prazosin
what is the goal BP for antihypertensive treatment?
150/95mmHg
potential AEs of antihypertensives
- hypotension; lethargy, ataxia
- hyporexia
what mechanisms does intact endothelium use to exert anticoagulant properties
- Endothelium represents a physical barrier that is negatively charged, discouraging and repelling platelet adhesion.
- The arrangement of phospholipids in healthy cell membranes inhibits coagulation. The outer membrane of the lipid bilayer contains neutral phospholipids, the more reactive phospholipids (PTS -phosphatidylserine, PEA - phosphatidylethanolamine) are localize to the inner membranes.
- Healthy endothelium actively produces substrates that inhibit both platelet adhesion and coagulation. (NO, prostacyclin, ADPase, thrombomodulin, protein S, HSPGs, TFPI)
what antiplatelet substances are produced by vascular endothelium
- nitric oxide
- prostacyclin
- adenosine diphosphatase (ADPase)
what anticoagulant substances are synthesized by intact endothelium
- thrombomodulin
- protein S
- heparin sulfated proteoglycans (HSPGs)
- tissue factor pathway inhibitor (TFPI)
how does the phospholipid arrangement of vascular endothelium change when injured
- normally the outer membrane contains neutral phospholipids and the inner layer contains more reactive phospholipids (PTS, PEA)
- the asymmetry is maintained by active transport of phospholipids by the ATP-dependent enzymes flippase and floppase
- after cell injury the enzymes scramblase shuffles phospholipids btwn the inner and outer membrane, resulting in PTS and PEA expression on the outer membrane.
- membranes with exposed PTS provide a substrate that supports and catalyzes coagulation reactions
how does endothelial damage contribute to thrombus formation
- Injured endothelial cells release endothelin; promotes vasoconstriction and slows local blood flow
- Presence of PTS on the outer lipid membrane of damaged cells dramatically increases speed of coagulation reactions.
- Damaged endothelium exposes cells expressing tissue factor (TF or thromboplastin) which is the key step to initiate thrombus formation
what does primary hemostasis refer to
formation of the primary platelet plug
what does secondary hemostasis refer to
coagulation proteins creating cross-linked fibrin -modelled as a cascade of coagulation proteins involving sequential cleavage of proenzymes, each step activating the next coagulation factor in the series.
- extrinsic and intrinsic parts
what does ‘intrinsic’ and ‘extrinsic’ refer to in secondary hemostasis
intrinsic - within the blood, contact-dependent
extrinsic - outside the blood, TF-dependent
what factor activates the ‘common pathway’
Factor Xa (FXa)
how is the cell-based model of hemostasis divided
- initiation
- amplification
- propagation
explain the initiation phase of the cell-based model of hemostasis
vascular injury
- exposes subendothelial cells expressing TF, which binds to factor VIIa in circulating blood
- TF-VIIa activates Fxa to produce small amounts of thrombin (FIIa)
- FIIa attracts and activates nearby platelets
explain the amplification phase of the cell-based model of hemostasis
- platelet activation by thrombin results in platelet shape change, degranulation and expression of platelet surface receptors
- platelet granules release substances that attract and activate other platelets (thromboxane A2, serotonin, adenosine diphosphate (ADP), calcium, fibrinogen)
- the recruitment and aggregation creates a ‘plug’ of fibrinogen-linked platelets
- the platelet plug (with exposed PTS) create a substrate for ‘propagation phase’
explain the propagation phase of the cell-based model of hemostasis
- activated coagulation factors react on the platelet plug in a series of steps to generate more FXa which along with its cofactor (FVa) cleaves prothrombin into thrombin (FIIa)
- formation of large amounts of thrombin is the ‘final step’ of the cell based model
what does thrombin do?
thrombin converts fibrinogen into fibrin monomers, which polymerize to soluble fibrin, which is then cross-linked by the action of thrombin-activated FXIII (of fibrin-stabilizing factor)
- this insoluble fibrin stabilizes the clot
explain the process of thrombolysis
- plasminogen is converted to plasmin by tissue plasminogen activator (t-PA) when fibrin is present
- endothelial cells also release t-PA
- several other substances also activate plasminogen into plasmin
- plasmin degrades fibrinogen and soluble (noncross-linked) fibrin to yield fibrinogen/fibrin degradation products (FDPs)
what are D-dimers?
byproducts of cleaved cross-link fibrin (by plasmin)
list negative feedback constraints on fibrinolysis
- plasminogen activator inhibitors (PAI)
- a2-antiplasmin
- thrombin-activated fibrinolytic factor
what is Virchow’s triad
3 general situations that promote pathologic thrombosis
1 - abnormal endothelial structure or function
2 - slowed or static blood flow
3 - hypercoagulable state (from either increased procoagulant substances or decreased anticoagulant or fibrinolytic substances)
diseases associated with endothelial disruption
- sepsis
- systemic inflammatory disease
- HWD
- neoplasia
- shock
- massive trauma
- IV catheterisation
- injection of irritating substance
- atherosclerosis
- arteriosclerosis
- hyperhomocysteinemia
diseases associated with abnormal blood flow
- vascular obstruction (ie. mass lesion, adult heartworms, catheter or device)
- heart disease (esp. feline cardiomyopathy)
- CDV neoplasia
- endocarditis
- shock
- hypovolaemia/dehydration
- prolonged recumbency
- hyperviscosity (eg. polycythemia, leukemia, hyperglobulinaemia)
- hypoviscosity (anemia)
- anatomic abnormality ( aneurysm, AV fistula)
diseases associated with increased coagulability
- glomerular disease/protein-losing nephropathy
- hyper adrenocorticism
- IMHA +/- IMTP
- pancreatitis
- PLE
- sepsis/infection
- neoplasia
- DIC
- heart disease
how does stagnant blood flow promote thrombosis
- impeding the dilution and clearance of coagulation factors
- increased time for blood components to contact vessel walls
what is the most common cause of TE in cats?
myocardial disease
what mechanisms of feline myocardial disease cause TE
- poor intracardiac blood flow and blood stasis, esp. w/ large LA
- HCM - increased platelet expression of P-selectin and platelet-endothelial cell adhesion molecules, as well as increased plasma concentrations of fibrinogen, thrombin-antithrombin-complex and D-dimers
- abnormal turbulence from MR or dynamic outflow obstruction
which 3 common systemic diseases are associated with TE diseases in dogs?
- PLN
- IMHA
- hyperadrenocorticism
how does PLN results in TE?
- marked AT deficiency - lost through damaged glomeruli dt its small size
how does hyperadrenocorticism cause TE?
- associated with decreased fibrinolysis
- high levels of several coagulation factors
how is DM thought to cause TE
- platelet hyperaggregability
- hypofibrinolysis
outline the pathophysiology of ATE in cats
- commonly associated with HCM (also associated with HyperT and pulmonary carcinoma)
- thrombi initially form in the LA/auricle
- emboli usually lodge in the aortic trifurcation (saddle-embolus); besides obstructing flow in the affected artery, TE release vasoactive substances that induce vasoconstriction and compromise collateral blood flow around the obstructed vessel
- tissue ischaemia results and causes further damage and inflammation, including ischemia-reperfusion injury after blood flow is restored
clinical features of ATE TE in cats
- acute, dramatic CS
- males cats (dt HCM gender bias)
- 5 Ps;
Pain, Pallor, Paresis, Pulselessness, Poikilothermia
diagnosis of feline ATE
- 5 Ps
- echocardiography
- differential glucose/lactate levels (limb vs. systemic)
outline the tx. of feline ATE
- supportive care
- inhibit extension of existing clot and new TE events
1. antiplatelet; clopidogrel»_space; aspirin
2. anticoagulant; sodium heparin, enoxaparin, dalteparin
MOA of clopidogrel
a second-generation thienopyridine
- inhibits ADP-binding at platelet receptors and subsequent ADP-mediated platelet aggregation
- irreversibly antagonizes platelet membrane ADP2y12 receptores which inhibit a conformation change of the GPaIIbB3 complex resulting in reduced binding to fibrinogen or vWF
- also impairs platelet release of serotonin, ADP and other vasoconstrictive and platelet-aggregating substances
- maximal antiplatelet effects occur within 72 hours, disappear about 7 days after drug discontinuation
MOA of aspirin
irreversibly inhibits cyclooxygenase which reduces prostaglandin and thromboxane A2 synthesis and thus could reduce subsequent platelet aggregation, serotonin release and vasoconstriction
what is heparin’s main anticoagulant effect
occurs through AT activation which in turn inhibits FIXa, FXa, FXIa, FXIIa and FIIa (thrombin)
explain the use of rt-PA
recombinant tissue plasminogen activator
- a single-chain polypeptide serine protease with a higher specificity for fibrin within thrombi and a low affinity for circulating plasminogen
- promotes clot lysis by increasing conversion of plasminogen to plasmin –> facilitating fibrinolysis
- associated with AEs; serious bleeding, reperfusion injury (hyperK, azotaemia) and neurologic signs
what is the prognosis for feline ATE
- poor, about 30-60% euthanised on presentation
- barring complications limb function should begin to return in days to a week; some will be clinically normal within 1-2 months
- rpt ATE events are common, and CHF
- median long-term survival is 6-9months post ATE event
long-term ATE prophylactic drugs for cats
- Platelet inhibitors (clopidogrel > aspirin)
- Factor Xa inhibitors, LMWH
clinical features of canine ATE disease
- males > females
- Greyhounds, KCCS, Labs
- chronic signs associated with in situ embolization (neoplasia)
- associated with PLN, hyperA, IMHA, DM»_space; cardiomyopathies
what neoplasms are associated with canine ATE
- haemangiosarcoma
- pulmonary carcinoma
- osteosarcoma
- intravascular lymphoma
- adrenal tumours
prognosis of canine ATE
- guarded to poor, 50-60% survive to discharge
- rear limb function improves within days - 2 weeks of tx
- poorer prognosis for acute, non-ambulatory
CS associated with venous throbosis
- ascites, oedema, pleural effusion
cranial vena caval thrombosis in dogs has been associted with what disease processes
- IMHA, IMTP
- Sepsis
- PLN
- Neoplasia
- Glucocorticoid therapy
- Cardiac disease
MOA of warfarin
warfarin inhibits enzyme (vit,K epoxide reductase) responsible for activating Vit,K dependent clotting factors (II, VII, IX and X), and protein C and S
