ONLINE VETERINARY CONFERENCE 2009

A Case Based Approach to Cardio-Respiratory Medicine Dr Richard Woolley BVetMed Dip. ECVIM/CA (Cardiology) MRCVS Introduction A cardiac murmur is a common finding on routine physical examination in general practice. However, it may be difficult to assess the clinical relevance of the murmur by auscultation alone. It can also be difficult to decide on the extent of the workup needed in some cases. In symptomatic patients the decision is often easy, as the need for a diagnosis and alleviation of clinical signs is obvious. In asymptomatic patients with abnormal cardiac sounds the decision is not as easy. In these cases the reason for pursuing a cardiac workup is the need to know the underlying cause of the murmur. This information can be important for future decision-making processes. Without the information that a cardiac workup provides, it is not possible to make informed recommendations to the client regarding present and future management of the patient. A diagnosis of cardiac disease is based upon history, physical examination, ancillary tests (electrocardiography, radiography, echocardiography including Doppler, and, in some cases, cardiac catheterization), and response to therapy. History A complete history in conjunction with the physical examination is vital to pursue a diagnosis of cardiac disease in a patient. Signalment This includes the age, breed and gender. Many congenital and some acquired diseases have particular predilections (Appendix 1) Past History Congenital heart disorders may be implied if siblings, dam or sire have been affected. Diet, time spent abroad, frequency of worming and anthelmintic used. R Woolley 2009 www.veteducation.com.au Online Veterinary Conference 2009 Page 1

Cardiopulmonary History Dyspnoea, exercise intolerance, syncope, coughing and cyanosis are common to both cardiac and respiratory disease. Dyspnoea Dyspnoea can be acute or chronic, inspiratory or expiratory and occur at exercise, rest or paroxysmal. Causes of dyspnoea: Acute Chronic Inspiratory Expiratory Exertional Rest Paroxysmal Pulmonary oedema Right-sided heart failure Upper airway obstruction Lower airway obstruction Myocardial failure Pneumothorax Bradyarrhythmia Severe pneumonia Airway obstruction Pneumothorax Pulmonary thromboembolism Non-cardiogenic pulmonary oedema Pericardial disease Bronchial disease Pleural effusions Progressive anaemia Pulmonary neoplasia Tracheal collapse Laryngeal paralysis Chronic obstructive lung disease Pulmonary thromboembolism Pneumonia Severe congestive heart failure Non-cardiogenic pulmonary oedema Tachyarrhythmia Cough Dogs with heart disease frequently present with a cough. However respiratory disease (upper or lower airway) can also be present and make it difficult to determine which is contributing to the cough. Chronic pulmonary congestion may cause mild intermittent coughing or a nocturnal cough. Enlargement of the left atrium due to chronic mitral regurgitation can result in impingement of the left main stem bronchus, which can contribute to chronic coughing. Cardiogenic pulmonary oedema in dogs most frequently results from left-heart volume overload (mitral regurgitation due to endocardiosis) or dilated cardiomyopathy. Coughing is relatively soft, can progresses rapidly in severity and is often accompanied by exertional dyspnoea (in contrast to large airway disease). With fulminant oedema the cough may yield small quantities of frothy pink-tinged foam from the mouth or nares. Large airway disease causes chronic paroxysmal coughing that is harsh in nature. This cough is paroxysmal and usually elicited by excitement. Dogs with large airway disease usually have normal exercise capacity between coughing episodes. R Woolley 2009 www.veteducation.com.au Online Veterinary Conference 2009 Page 2

Collapse Reports of collapse must be carefully evaluated to differentiate between seizures and syncope. Syncopal episodes usually appear to the owner as if the animal has "fainted" and then was "normal" soon after the episode occurred (normally less than a minute). Syncope is a transient loss of consciousness from inadequate cerebral blood flow defines syncope. Seizures are usually associated with pre- and post-ictal periods, and commonly have tonic and/or clonic components that last for several minutes. Conditions associated with cardiac syncope in dogs and cats. - Heart block (high 2 nd or 3 rd degree) - Sick sinus syndrome - Fixed obstructive lesions (aortic or pulmonic stenosis) - Rapid ventricular or supraventricular tachycardia - Pulmonary hypertension - Mitral regurgitation - Vasovagal Causes of weakness and exercise intolerance - Decompensated cardiac failure - Obstruction to ventricular outflow - Cardiac tamponade - Arrhythmias - Anaemia - Systemic and metabolic diseases (e.g., hypoadrenocorticism) - Hypotension - Respiratory disease - Neuromyopathies - Orthopaedic conditions R Woolley 2009 www.veteducation.com.au Online Veterinary Conference 2009 Page 3

Cyanosis Cyanosis is occasionally noted by owners. In the absence of respiratory distress or toxicosis, this should lead to the suspicion of a lesion that results in shunting of blood from the venous to the systemic arterial circulation by a route other than the normal pulmonary circulation. This is diagnosed more frequently in young animals but can be seen in the older patient with an abnormal connection between atria, ventricles, or great vessels that begins to shunt right-to-left when pulmonary vascular resistance rises as a result of primary lung disease or pulmonary thromboemboli. Cardiac defects resulting in right to left shunting and cyanosis. - Right Left patent ductus arteriosus (differential cyanosis normal cranial mucous membranes and cyanotic caudal mucous membranes) - Pulmonic stenosis or pulmonary hypertension with an atrial or ventricular septal defect (e.g. Tetralogy of Fallot) - Other complex defects Response to Previous Therapy Evaluation of the patient's response to therapy can provide useful information regarding the accuracy of a specific diagnosis. Response to medication should guide further adjustments to the therapeutic protocol. Physical Examination Assessment of respiratory effort (at rest) Mucus membrance colour and capillary refill time External jugular vein examination for abnormal distension or pulsations Precordial palpation for the cardiac apex beat (location, strength, point of maximal impulse) and thrills (vibratory sensations which are the palpable results of loud, harsh, low frequency murmurs) Femoral arterial pulse evaluation for strength, regularity and character (normal, hypokinetic, hyperkinetic) Cardiac and lung auscultation Thoracic percussion Abdominal palpation for hepatomegaly or ascites (fluid thrill) R Woolley 2009 www.veteducation.com.au Online Veterinary Conference 2009 Page 4

Auscultation It is important to find a quiet room when auscultating, as barking, talking or even soft humming sounds of equipment in the room can affect your ability to hear heart or lung sounds. The patient should be in a natural standing position with the nose parallel to the floor or table. Animals that are sitting or lying will have displacement of the heart within the thoracic cavity, which will affect your ability to localize the sound or lesion. Panting dogs should be restrained from panting by the owner or nurse. Cats can be refrained from purring by running water in a nearby sink or some practices have installed aquariums to distract cats. If all fails on a first attempt at auscultation, always be willing to repeat your exam after the animal has had time to acclimatize to the environment. R Woolley 2009 www.veteducation.com.au Online Veterinary Conference 2009 Page 5

Heart Sounds In general, heart sounds are created by turbulent blood flow (high velocity flow, incompetent valves, shunts) and by vibrations of the heart and vessels (normal sounds, gallop sounds). Transient Sound S1 S2 Etiology The first heart sound is a normal sound caused by closure of the atrioventricular valves and vibrations of the cardiac walls with abrupt deceleration of blood flow. S1 is typically longer and lower pitched than the second heart sound. It is heard best at the left apex. The second heart sound is produced by closure of the semilunar valves. It is heard loudest over the aortic area. It is a shorter and higher pitched sound than S1. S3 The third heart sound is due to vibrations in the heart walls associated with rapid early ventricular filling. It is a normal sound in large animals, i.e., horses. S4 The fourth heart sound is caused by atrial contraction acutely forcing blood to quickly move into the ventricular cavity (at the very end of diastole). It is Systolic Click also normal in large animals. A transient click can sometimes be heard in mid to late systole over the mitral valve. This is usually the result of delayed closure or prolapsing of a portion of the valve. Pathologic Condition A split S1 can be heard with conduction alterations (right bundle branch, ventricular premature contractions) or can be normal in resting large dogs. A split S2 can occur due to delayed closure of the pulmonic valve (pulmonary hypertension, right bundle branch block, ventricular premature beats, pulmonic stenosis, etc.) or due to paradoxical delayed closure or the aortic valve (left bundle branch block, ventricular premature contractions, subaortic stenosis, systemic hypertension). In dogs an S3 is usually associated with myocardial failure i.e. dilated cardiomyopathy or severe mitral regurgitation and is referred to as an S3 gallop. An S4 can be ausculted in dogs and cats when the atria dilate in response to ventricular stiffness (high filling pressures) such as in hypertrophic cardiomyopathy (S4 gallop). Systolic clicks typically related to mitral valve abnormalities (i.e. early endocardiosis). They can occasionally be found over the tricuspid valve. R Woolley 2009 www.veteducation.com.au Online Veterinary Conference 2009 Page 6

Cardiac Murmurs Cardiac murmurs are longer sounds occurring during normally quiet periods, i.e., between S1 and S2, or between S2 and S1. Cardiac murmurs are described based on: Timing Systolic murmurs can occur at any point between S1 and S2. Holosystolic murmurs occur throughout systole but with both S1 and S2 still audible. Pansystolic murmurs occur throughout systole but S1 and S2 are not discernable. Diastolic murmurs are usually heard early in diastole (just after S2) or throughout diastole. Continuous murmurs occur throughout systole and diastole. To and fro murmurs occur when there are separate systolic and diastolic components. Intensity The intensity of a murmur is graded on a scale of I to VI. This system is used to characterize the murmur; it is not used to assess severity of disease. Grade I: A very soft, focal murmur detected after several minutes listening. Grade II: A soft murmur, readily localized, but quieter than the S1 and S2 heart sounds. Grade III: A moderate intensity murmur, similar audibility to S1 and S2 heart sounds. Grade IV: A loud murmur, louder than S1 and S2 heart sounds, no palpable thrill. Grade V: A very loud murmur, radiates well, accompanied by palpable precordial thrill. Grade VI: Grade V plus audible when the stethoscope is removed from the chest wall. Point of Maximal Intensity (PMI) The PMI is usually described by the hemithorax, valve area or base/apex location where the murmur is the loudest. For example, left apical region or left hemithorax over the 4 th intercostal space at the costrochondral junction is a typical PMI description for mitral regurgitation. R Woolley 2009 www.veteducation.com.au Online Veterinary Conference 2009 Page 7

Radiation over the chest wall A murmur may radiate from the PMI to other cardiac regions and even non-cardiac regions such as the thoracic inlet and calvarium (i.e., sub-aortic stenosis). Radiation is taken into consideration when assessing the murmur intensity. In general, a score is ascribed depending upon the number of heart regions over which the sound is ausculted. The heart can be divided into 4 regions on the thoracic wall 1) left heart base 2) left heart apex 3) right heart base and 4) right heart apex. For example, if a murmur can be heard (PMI + radiation) in 3 of the 4 regions, it would be described as having a grade III/VI intensity. Quality or character Murmurs can also be described according to their quality, frequency and characteristic shape (change in intensity throughout the cycle) recorded by a phonocardiogram. High frequency sounds may be described as musical, whereas, mixed frequency sounds are often described as harsh. The terms flat or plateau, ejection, and blowing are commonly used terms to describe quality of murmurs. For example, systolic flat or plateau murmurs begin and end abruptly, but do not change in frequency or tones throughout systole. These murmurs are most consistent with mitral or tricuspid valvular regurgitation. Systolic ejection murmurs may begin and end abruptly but classically the frequency changes during the cycle. The frequency may increase (crescendo) or decrease (decrescendo) or do both during the cycle. Systolic ejection murmurs are most typically heard with subaortic stenosis, pulmonic stenosis, small ventricular septal defects and physiologic outflow sounds. R Woolley 2009 www.veteducation.com.au Online Veterinary Conference 2009 Page 8

PMI Character Differentials Left Apex Left Base Right Apex Systolic ejection Systolic plateau Continuous Systolic ejection Diastolic, blowing Systolic ejection Systolic plateau Early mitral regurgitation may sometimes manifest a harsher sound; SAS is sometimes best heard over the costochondral junction which reflects the lesion location (SUB-aortic) Mitral regurgitation, classic character and location; Consider endocardiosis if small breed; Consider endocarditis if larger breed with 'new' murmur or if fever; Consider DCM in large/giant breeds with softer murmurs PDA, typically heard very high at the left base; Small breeds of dogs and herding breeds are typical signalment SAS or PS or possibly physiologic murmur (softer); Check location > PS typically more cranial than SAS; Check signalment > PS: small breeds, brachycephalics, terriers, SAS: larger breeds Aortic regurgitation, typically heard best over aortic valve area, sometimes heard with murmur of SAS or VSD; rarely may hear high velocity pulmonic regurgitation VSD, heard best at the right sternal border (most common congenital heart defect in the cat, horse and cow); occasionally high velocity tricuspid regurgitation may have an ejection quality, but PMI should be higher at the right apex Tricuspid regurgitation, classic character and location; Consider endocardiosis, or TR secondary to pressure overload i.e., pulmonary hypertension or PS, or congenital valve dysplasia (Labradors, Great Dane, Boxer, other large breeds) Arterial Pulse Palpation of the arterial pulse simultaneous with cardiac auscultation allows detection of pulse deficits associated with arrhythmias. The pulse "strength" detected by palpation is a function of the difference between the systolic and diastolic arterial pressures (pulse pressure) and the ability of the examiner to place the correct amount of pressure over the artery. A blood pressure of 220/180 cannot be differentiated from a pressure of 120/80 by palpation alone. Bounding pulses are associated with a rapid and exaggerated increase and decay of arterial pressure. The most common clinical correlates are patent ductus arteriosus (left to right shunt) and aortic insufficiency (e.g. associated with aortic stenosis or bacterial endocarditis). Weak pulses may be associated with shock like conditions or conditions that impede ejection of blood from the left ventricle. Clinical correlates include shock (cardiogenic and others), pericardial tamponade and aortic stenosis. R Woolley 2009 www.veteducation.com.au Online Veterinary Conference 2009 Page 9

Systemic Veins Examination of the systemic veins is also an important portion of the physical examination. Distension of systemic veins is associated with elevated systemic venous pressures, often as a result of right heart failure. Important differential diagnoses include venous thrombosis, intra- or extravascular masses, and congenital cor triatriatum dexter, causing obstruction to venous return. The presence of jugular pulses may indicate right heart disease (usually tricuspid insufficiency), but may also be associated with arrhythmias that result in atrioventricular dissociation in which the atria contract when the tricuspid valve is closed resulting in retrograde flow and fluid wave transmission (cannon a-wave). Pericardial tamponade should also be considered when jugular distension or pulsation is detected. Innocent/Physiological murmurs It is unusual to hear significant murmurs in adult dogs that do not have cardiac disease. "Innocent" or "physiologic" murmurs can be heard in young animals. Clues that a murmur falls within this category are that it is a soft (I-II out of VI) murmur, short in duration (cannot be heard throughout systole, usually early systolic), and often found to disappear before maturity is reached (usually at <16 weeks). To decide if a murmur that does not resolve is an indication of significant cardiac disease or not, a chest radiograph and echocardiogram are indicated to definitively rule out significant cardiac disease in any young animal with a persistent cardiac murmur. Any systolic murmur that is loud, or is heard throughout systole and any diastolic murmur should be considered significant. R Woolley 2009 www.veteducation.com.au Online Veterinary Conference 2009 Page 10

Clinical Diagnosis The results of a general and cardiovascular physical examination will, in most cases, provide sufficient information for the clinician to generate a brief list of differential diagnoses. Common ancillary tests available for confirming or ruling out diagnoses include electrocardiography, radiography, and echocardiography. Cardiac catheterization and angiography are rarely used now due to the advances in echocardiography. Electrocardiography Where normal complexes are visible, i.e. those that appear to have arisen in the normal sequence from sinoatrial node to atrioventricular node to the ventricle, then measurement of the amplitude of the constituents of the complexes may be useful in providing information regarding the presence of chamber enlargement. R Woolley 2009 www.veteducation.com.au Online Veterinary Conference 2009 Page 11

Dog Cat Rate 60-160 /min (adults) 120-240/min Up to 220 /min (puppies) Rhythm sinus rhythm, sinus arrhythmia sinus rhythm P duration <0.04 sec <0.04 sec P amplitude <0.4 mv <0.2mV PR interval 0.06-0.13 sec 0.05-0.09 sec R amplitude 3.0 mv in large breeds 0.9mV (max) 2.5 mv in small breeds S amplitude < 0.35mV <0.5mV QRS duration 0.06 sec in large breeds (max) 0.04 sec (max) 0.05 sec in small breeds (max) QT interval 0.15-0.25 sec (depending on heart rate) 0.12-0.18 sec T amplitude 0.0-1.0 mv (or <¼ R wave height), positive, positive, negative or biphasic negative or biphasic ST segment < 0.2 mv depression < 0.15 mv elevation no depression no elevation Mean Electrical Axis +40 to +100 +0 to +160 0 Some changes that may be noticed in P-waves and QRS complexes: Wide P-wave : left atrial enlargement (P-mitrale) Tall P-wave: right atrial enlargement (P-pulmonale) Wide QRS : left ventricular enlargement or left bundle branch block Tall R : left ventricular enlargement (dilation or hypertrophy) Small R: pericardial/pleural effusion, obesity, hypothyroidism Alternate R waves different height: Deep S-wave: Wide S-wave: pericardial effusion right ventricular enlargement ( usually hypertrophy) right bundle branch block Long Q-T: hypocalcemia, hypokalaemia, hypothermia. S-T segment elevation hypoxia, infarcts /depression: S-T segment coving: left ventricular enlargement If signs of chamber enlargement are present on the electrocardiogram, they should still be confirmed by other ancillary tests. The major utility of electrocardiography to the veterinarian is for evaluating rhythm disturbances. In this regard, appropriate therapy, if deemed necessary, can usually be chosen after assessing whether the dysrhythmia represents a bradycardia or tachycardia and whether, in the case of tachyarrhythmias, the rhythm is supraventricular or ventricular in origin. R Woolley 2009 www.veteducation.com.au Online Veterinary Conference 2009 Page 12

Radiography Radiography is useful for detecting left atrial enlargement and can provide an assessment of overall cardiac size. The use of radiography to differentiate between right and left ventricular enlargement can be difficult. Cardiac size evaluation, if performed subjectively, is usually done by comparing heart size to chest cavity size and configuration. It must be remembered that if even if a heart looks large it may be the chest cavity surrounding it that is small. Small chest cavities are common in small and chondrodystrophic breeds, on radiographs not taken at full inspiration (a large % of all chest radiographs) and in obese dogs. It is not unusual to have a heart that appears enlarged when it is not. The opposite may also be true. In large, deep-chested dogs the heart often appears small because of the large chest cavity size surrounding it. Doberman Pinchers with dilated cardiomyopathy often do not have hearts that appear grossly enlarged on chest radiographs. An objective method for measuring cardiac size on radiographs is the vertebral heart scale. This is performed as shown below. T4 VHS = 10.5v (range 8.5 10.5V) R Woolley 2009 www.veteducation.com.au Online Veterinary Conference 2009 Page 13

Radiography is most useful for detecting sequelae to cardiac dysfunction (e.g., pulmonary venous congestion, pulmonary edema, enlarged great veins, pleural effusion, etc.). Care must be taken not to over-interpret pulmonary vascular and parenchymal patterns in radiographs of obese animals or radiographs exposed in an expiratory phase. Radiography is an excellent tool for detecting moderate to severe pulmonary edema, pleural effusions, and ascites. It is relatively poor at detecting mild edema in many dogs. Echocardiography A large number of practices now have access to ultrasound machines and even with basic ultrasound equipment important information can be gleaned from echocardiography. There is a long slow learning curve with echocardiography, the best way to learn is on an echocardiographic course, but with practice a number of standard views can be obtained. R Woolley 2009 www.veteducation.com.au Online Veterinary Conference 2009 Page 14

Right Para-sternal 4 chamber long axis view LA = left atrium LV = left ventricle RV = right ventricle MV = mitral valve MV TV = tricuspid valve View enabling visualization of the mitral valve and subjective assessment of the LA, LV and systolic function. LA Thickened mitral valve leaflet and grossly enlarged left arium. LV LA Grossly enlarged, rounded, thin walled left ventricle with subjectively poor systolic function, consistent with myocardial failure. R Woolley 2009 www.veteducation.com.au Online Veterinary Conference 2009 Page 15

Right Para-sternal cranial short axis view at level of aortic valves LA = left atrium Ao = aorta Aur = left auricle RA = right atrium View allowing objective measurement of LA (compared to Ao). Measurements performed in diastole as shown in diagram. LA:Ao normally < 1.5:1. Gross left atrial enlargement. Left ventricular M-mode (chordae tendineae level) View enabling objective measurement of systolic function of the left ventricle Poor systolic function due to myocardial failure e.g. (DCM) R Woolley 2009 www.veteducation.com.au Online Veterinary Conference 2009 Page 16

Classifying Heart Failure Heart failure is a clinical syndrome resulting from a cardiac disease, which compromises ventricular systolic or diastolic function or both. Heart failure results when the heart is unable to generate a cardiac output sufficient to meet the demands of the body without unduly increasing diastolic pressure. Heart failure may be manifested by symptoms of backwards failure resulting in congestion of vascular beds (WET), or by symptoms of forward failure resulting in poor tissue perfusion (COLD), or both. Backward Heart Failure or Congestive Heart Failure (CHF) This results in increased venous hydrostatic pressures as a result of the failing heart. The increase in hydrostatic pressures results in extravasation of fluid and can be considered WET heart failure. Congestive heart failure can also be subdivided into left (causing pulmonary oedema), right (causing ascites and or pleural effusion) or biventricular heart failure. Forward heart failure This refers to the failure of the heart to maintain normal systemic blood flow resulting in poor peripheral perfusion leading to COLD extremities. Animals with cardiac disease but not in CHF are considered DRY and those without decreased peripheral perfusion WARM. R Woolley 2009 www.veteducation.com.au Online Veterinary Conference 2009 Page 17

Diagnosis Clinical Presentations Suggestive of Heart Failure & Diagnostic Tests Congestive Heart Failure = WET Left Ventricular = Right Ventricular = Cardiogenic Ascites Pleural Pulmonary Oedema Effusion History Tachypnea (>30breaths/min when sleeping) Physical Examination Diagnostic Test(s) Cough Dyspnea Orthopnea Acute <30days Depressed Anorexia Weight loss Tachycardiac (usually >140bpm) Normal lung sounds Increased bronchovesicular sounds Crackles Wheezes 1. Thoracic radiographs (examine for pulmonary oedema and venous congestion) 2. Echocardiography Abdominal distension Tachypnea Orthopnea Dyspnoea Diarrhoea Weight loss Ascites Jugular distention at rest Positive hepatojugular reflex Pleural Effusion Muffled heart sounds Absent lung sounds Ascites 1. Diagnostic abdominocentesis 2. Echocardiography 3. Abdominal ultrasound Pleural Effusion 1. Pleurocentesis 2. Thoracic radiographs 3. Echocardiography Forward Heart Failure = Cold Lethargy Depressed Weakness Exercise intolerance Collapse Syncope Tachycardia Weak pulses Cool extremities Prolonges capillary refill time Subnormal temperature Cyanosis 1. Systemic blood pressure 2. Pre-renal azotaemia 3. Venous O 2 <24mmHg 4. Increased blood lactate 5. Low urine production R Woolley 2009 www.veteducation.com.au Online Veterinary Conference 2009 Page 18

Differentiating between cardiac and respiratory disease In some cases is can be difficult to determine if a dog is showing clinical signs due to cardiac or respiratory disease. Differences in Clinical History, Physical Examination and Radiographs CARDIOGENIC VS RESPIRATORY Pulmonary oedema Small airway disease chronic bronchitis Left mainstem bronchus compression (MVD) Soft cough Tachypnoea & Dyspnoea Occurs whilst resting Acute (less than 30 days) Depressed Decreased appetite Occasional weight loss Murmur Tachycardia (>140bpm) Large airway disease collapsing trachea History Physical Exam Hacking cough often fits Often normal breathing between coughing fits Occurs with activity Often chronic Normal attitude Normal appetite Often obese Murmur Sinus arrhythmia Soft crackles & increased bronchovesicular sounds Loud crackles and wheezes or normal lung sounds Radiographs Cardiomegaly Increased VHS Compression of the main stem bronchus Alveolar pattern Mixed interstitial pattern with a symmetrical perihilar/caudal dorsal distribution Cardiomegaly Diffuse bronchial pattern R Woolley 2009 www.veteducation.com.au Online Veterinary Conference 2009 Page 19

Treatment Common Causes of Canine Heart Failure Chronic Degenerative Valvular Disease Dilated Cardiomyopathy Congenital Canine Heart Disease o Sub-aortic stenosis o Patent ductus arteriosus o Pulmonic stenosis o Mitral valve malformation o Tricuspid valve malformation o Ventricular septal defect o Tetralogy of Fallot Compensatory Mechanisms Initiated in Heart Failure In order to maintain adequate blood pressure the body automatically initiates these compensatory mechanisms: 1. Up regulate adrenergic nervous system - increases heart rate and strength of contraction - selective increase in vascular resistance 2. Activates Rennin Angiotensin Aldosterone System (RAAS) - increases plasma volume Initially the compensatory mechanisms are adaptive with only mild clinical signs of heart failure evident. Overtime these mechanisms become maladaptive contributing to the development of clinical signs of both forward and backward heart failure and disease progression In addition to these compensatory mechanisms, during the process of heart failure, the myocardium undergoes progressive remodeling. Local proinflammatory cytokines, such as tumor necrosis factor-, exacerbate the process by promoting chronic inflammation in the heart, contributing to the development and progression of CHF. R Woolley 2009 www.veteducation.com.au Online Veterinary Conference 2009 Page 20

These neuro-endocrine mechanisms and cytokines represent therapeutic target in the treatment of heart failure. Therapeutic Approach to Heart Failure Dry Wet Warm Warm & Dry 1. Prolong preclinical stage 2. Do no harm Warm & Wet 1. Relieve congestion 2. Preserve perfusion 3. Decrease mortality Cold Dry & Cold 1. Increase peripheral perfusion 2. Decrease mortality Cold & Wet 1. Relieve congestion 2. Increase peripheral perfusion 3. Decrease mortality Relieve Clinical Signs of Congestion 1. Abdominocentesis, if causing dyspnoea by pressure on the diaphragm and pleurocentesis if required 2. Preload reduction - Plasma volume reduction diuretics such as frusemide, hydrochlorothiazide, spironolactone - Venodilation nitroglycerin, pimobendan 3. Inhibition of the rennin angiotensin aldosterone system (RAAS) - Angiotensin converting enzyme inhibitors (ACEi) such as enalapril or benazepril - Aldosterone antagonists such as spironolactone 4. Improve diastolic dysfunction if present - calcium channel blockers - pimobendan positive luciotrope R Woolley 2009 www.veteducation.com.au Online Veterinary Conference 2009 Page 21

Improve or Preserve Peripheral Perfusion 1. Enhance systolic function in diseases characterised by systolic dysfunction - pimobendan calcium sensitiser phosphodiesterase III inhibition - dobutamine (i.v.) - digoxin (weak inotrope) 2. Arteriodilation (afterload reduction) - Pimobendan - Hydralazine - ACEi (very mild effect) 3. Treat haemodynamically significant arrhythmias - Ventricular lignocaine (i.v.), mexiletine, sotalol, amiodarone - Supraventricular digoxin, beta-blocker, calcium channel blocker, amiodarone 4. Treat pulmonary artery hypertension if present and contributing to clinical signs - Phosphodiesterase V inhibition sildenifil, pimobendan Neuroendocrine & Cytokine Modulation 1. Inhibition of RAAS - ACEi enalapril, benazepril 2. Aldosterone antagonism - Spironolactone 3. Inhibition of sympathetic nervous system - Beta-blockers atenolol (selective), propranolol (non-selective) - Adrenergic blockers (alpha & beta blockade) & free radical scavenger - carvedilol 4. Modulation of cytokines - Pimobendan inhibits the activation of transcription factor NF- B, a mechanism which explains its inhibition of cytokine production R Woolley 2009 www.veteducation.com.au Online Veterinary Conference 2009 Page 22

Therapy Prior to the Onset of Heart Failure Aims 1. Prolong the preclinical stage (delay the onset of clinical signs) - Two randomized clinical trials have examining whether treatment with an angiotensin converting enzyme inhibitor delays the onset of clinical signs of heart failure in dogs with chronic valvular heart disease have produced potentially conflicting results. The results of these two trials have failed to produce a consensus among experts. The increase in time to onset of heart failure after pre-chf treatment with an ACEi is perhaps a 3 month delay over what is on average a 3 year period of asymptomatic valve regurgitation prior to the onset of heart failure, ACEi treatment appears to be generally safe. Clearly some individuals may benefit more (or less) than average. No completed clinical trials have addressed the efficacy of combinations of enalapril with other medications that are sometimes recommended in asymptomatic mitral regurgitation (e.g., beta blockers) that might potentially provide a greater benefit. 2. Prolong survival - Neither of the aforementioned studies demonstrated any prolongation of survival when ACEi were used prior to the onset of CHF. 3. Do no harm - A recent study has examined the effects of benazepril and pimobendan when administered to a small (12 dogs) cohort of experimental animals with chronic degenerative mitral valve disease prior to the onset of CHF (off-licence). The study showed an increase in the murmur grade in the pimobendan group, increased mitral regurgitation (measured by an echocardiographic method prone to inaccuracy) and fewer and milder histopathological lesions with benazepril (but there was no sham treated group to monitor the natural change in valve pathology in this population over time). These findings cannot be viewed as increased morbidity or mortality caused by pimobendan and is no reflection on the use of pimobendan in dogs with CHF. I am confident that pimobendan is a R Woolley 2009 www.veteducation.com.au Online Veterinary Conference 2009 Page 23

valuable drug in the treatment of left sided congestive heart failure associated with idiopathic dilated cardiomyopathy and myxomatous mitral valve disease and there is published data in support of this assertion, which was only partially acknowledged by this study. The study also demonstrates no benefits for the use of benazepril prior to the onset of CHF References 1. Fox, PR. The history. In: Fox, PR; Sisson, DD; Moise, NS. eds. Textbook of Canine and Feline Cardiology Principles and Clinical Practice (second edition). Philadelphia: WB Saunders, 1999; 41-45. 2. Sisson, D; Ettinger, SJ. The physical examination. In: Fox, PR; Sisson, DD; Moise, NS. eds. Textbook of Canine and Feline Cardiology Principles and Clinical Practice (second edition). Philadelphia: WB Saunders, 1999; 46-64. R Woolley 2009 www.veteducation.com.au Online Veterinary Conference 2009 Page 24

Appendix 1 Breed predispositions to cardiac disease * Breed Cardiac Disease Abbreviations Beagle PS AVVD AV valve dysplasia Border Collie PDA, VSD DCM Dilated cardiomyopathy Boston Terrier MVD, VSD PAS Persistent atrial standstill Boxer SAS, PS, DCM, PE PDA Patent ductus arteriosus Cavalier King Charles Spaniel MVD, PDA, PAS, PS PE Pericardial effusion Cairn Terrier SSS PS Pulmonic stenosis Chihuahua PS, MVD SAS Subaortic stenosis Chow Chow PS SSS Sick sinus syndrome Cocker Spaniel DCM, MVD, PDA, PS ToF Tetralogy of Fallot Doberman DCM MVD Mitral valve disease English Bulldog SAS, PS, ToF, VSD VSD Ventricular septal defect English Bull Terrier AVVD, SAS English Springer Spaniel PAS Fox Terrier PS, MVD German Shepherd Dog PDA, SAS, DCM, PE, AVVD Golden Retriever DCM, SAS, PE Gordon Setter MVD, DCM Great Dane AVVD, DCM, PE Irish Setter MVD, DCM, PDA Irish Wolfhound DCM Keeshound ToF, VSD Labrador DCM, PS, AVVD Mastiff PS Miniature Poodle PDA, MVD Miniature Schnauzer SSS, MVD, PS Newfoundland SAS, DCM Old English Sheepdog DCM, AVVD, PAS Pekinese MVD Pomeranian PDA Rottweiller SAS Samoyed SAS, PS St Bernard DCM, PE Schnauzer MVD, PS Shih Tzu PS Shetland Sheepdog PDA Springer Spaniel DCM, PAS, VSD West Highland White Terrier PS, SSS, VSD Yorkshire Terrier MVD, PS * Martin, M & Corcoran, B. Appendix 1. In Cardiorespiratory diseases of the dog and cat (second edition). Blackwell Science Ltd., 2006; 185-186. R Woolley 2009 www.veteducation.com.au Online Veterinary Conference 2009 Page 25