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TREATMENT OF CONGESTIVE HEART FAILURE MVB, DVC, MRCVS. Specialist in Vet Cardiology Veterinary Cardiorespiratory Centre, Thera House, Kenilworth, Warwickshire. Understanding Treatment
TREATMENT OF CONGESTIVE HEART FAILURE MVB, DVC, MRCVS. Specialist in Vet Cardiology Veterinary Cardiorespiratory Centre, Thera House, Kenilworth, Warwickshire. Understanding Treatment The aims of therapy, which applies to most causes of congestive heart failure (except pericardial effusion) are as follows: Control volume load (congestive signs) Diuretics should be used at the minimum effect dose - Furosemide the most potent and commonly used diuretic - Spironolactone a weak diuretic but more importantly has anti-aldosterone effects - Co-amilozide (hydrochlorothiazide + amiloride) normally used in addition to furosemide when there is refractory ascites. This combination of diuretics act at different sites within the nephron: the concept of 'sequential nephron blockade'. ACE inhibitors - Have mild diuretic properties in addition to its anti-neurohormonal effects Low sodium diet - Excessive salt intake may exacerbate the 'fluid retention' that occurs in heart failure and therefore it is generally agreed that high salt diets and 'salty-treats' should be avoided. Remove fluids - Drainage of pleural and/or ascitic fluid is unusually only performed when causing dyspnoea, but removal also removes proteins and potentially reduces oncotic forces which could exacerbate oedema fluid Restriction of water intake - This is not advised and water should be provided ad lib. Reduce cardiac work Rest - Caged rest is important, especially in fulminant congestive failure cases - If oxygen administration causes stress, it should be avoided. Consider handsfree methods, eg. oxygen cage, anaesthetic chamber - Once congestive failure signs are controlled, exercise (within the limits of the animal s ability) is considered beneficial, but prevent excessive exercise. Reduce arterial pressure (afterload) - Arterial vasodilators Pimobendan or levosimendan: useful in acute fulminant cases and it is also a positive inotrope ACE inhibitor drugs vasodilator benefits are mild and more long term Reduce the filling pressure (preload) - Venodilators Diuretics furosemide reduces preload, but is also reported to have venodilator properties when given i/v Glyceryl trinitrate Pimobendan, levosimendan ACE inhibitors (mild) Weight reduction in obese animals - Obesity is a recognised cause of increased cardiac workload, especially during exercise. Improve cardiac efficiency when myocardial failure is present Enhance contractility with positive inotropic drugs: - Pimobendan, levosimendan - Digoxin - Dobutamine Improve diastolic function - Improve ventricular relaxation Beta blockers and calcium channel blockers may be useful in hypertrophic cardiomyopathy - Control arrhythmias such as: Atrial fibrillation digoxin would be the most commonly preferred drug Frequent supraventricular premature complexes or ventricular premature complexes Improve myocardial or vascular remodelling - Counter the neurohormonal effects ACE inhibitors Angiotensin receptor antagonists Beta blockers Aldosterone antagonists, eg. spironolactone Basic fundamentals of treatment As a general rule, all dogs with congestive heart failure due left sided congestive heart failure (ie. MVD or DCM) will require the following: 1. The anti-neurohormonal drugs: ACE inhibitor + spironolactone 2. Inodilator drug: pimobendan 3. Diuretic for congestion (and proportional to severity): furosemide +/- co-amilozide Note: There is some interest in the use spironolactone at sub-diuretic doses (one quarter normal dose) as part of the treatment medications to minimise/reduce myocardial fibrosis. Cough This is a common problem and often poorly managed. As a general rule, coughing in dogs with chronic MVD is most commonly due to compression of the airways by the huge left atrium. Thus is is a physical stimulus. Oedema can also cause coughing, but dyspnoea is also a more common symptoms in these cases. Treament Oral medication with codeine linctus at 1-2mg/kg tid/qid (or a similar anti-tussive) given for a week and then reduced to the minimum effective dose or as required. TREATMENT STRATEGIES Acute fulminant congestive failure (pulmonary oedema) Can occur in any dog or cat with rapidly progressing or uncontrolled congestive failure, but some common causes of acute failure are: - Ruptured chordae tendineae secondary to mitral valve disease - Acute onset dilated cardiomyopathy, particularly Dobermanns and Cocker Spaniels - Cardiomyopathies in cats can present acutely, which may be associated with recent steroid administration or a salt load Strict rest and stress-free handling cannot be over emphasised Gentle sedation results in: - Reduction in anxiety - Slower deeper respiration - Dogs: morphine at mg/kg i/m - Cats: butorphanol at 0.1mg/kg i/m Oxygen supplementation without stressing the animal, using hands free methods Furosemide : 3 (- 4) mg/kg in dogs and 2mg/kg in cats - administered i/v if it is not stressful to the animal, otherwise i/m - given every 1-2 hours until there is evidence of : diuresis (urination) improvement in respiration (reduction in pulmonary oedema) at which time the frequency of administration is reduced to every 6 hours Note: Excessive dosing can potentially be counterproductive and may result in Dehydration Reduced cardiac output Circulatory collapse Electrolyte depletion Renal failure Venodilators Essentially redistribute blood volume away from the lungs to the large capacitance veins, thereby reducing pulmonary oedema - Glyceryl trinitrate ¼ to 1 in dogs tid, ¼ in cats tid/qid Simpler to use than sodium nitroprusside, although may be less effective Applied to a hairless part of the body: inner ear or inside thigh (not rubbed in) Caution: Need to use gloves when using or handling dog Positive inotropes / inodilators Beneficial in dogs with dilated cardiomyopathy, but also useful in dogs in acute failure due to mitral valve disease. Generally not used in cats in acute failure. - Pimobendan at 1 3 mg/kg bid, per os. (on an empty stomach) Simpler to use than dobutamine Additionally provides arterial & venous vasodilation Absorbed rapidly from gut - Digoxin not normally used as an emergency drug It is a weak positive inotrope Steady state levels take 5-7 days to achieve, which is not appropriate in emergency cases The intravenous preparation is difficult to use and has a narrow margin of safety Summary: Treatment strategies for the management of acute fulminant congestive heart failure in dogs Option 1 - Intensive therapy Rest Gentle sedation Oxygen supplementation Furosemide Sodium nitroprusside CRI Dobutamine CRI Option 2 Less intensive (more likely to be an option in general practice) Rest Gentle sedation Oxygen supplementation Furosemide i/v or i/m Glyceryl trinitrate percutaneous Pimobendan orally Chronic congestive failure (out-patient treatment) The majority of heart failure patients will fall into this category. The general rule is that treatment should not be initiated until there are clinical signs. Exercise considered important, but should be well within the capabilities of the patient ACE inhibitors indicated in all dogs with heart failure (due to mitral valve disease or dilated cardiomyopathy) due to the importance of inhibiting the adverse neuroendocrine responses that are induced by CHF. Being increasingly used in cats. - There are a large number of ACE inhibitors available, none has a particular advantage or benefit compared to others - Start at standard manufacturer recommended dose - Dose can be doubled to bid in long standing or advanced cases Diuretics dose should be adjusted and optimised in each case - Furosemide dose range is ½ 3 mg/kg bid in dogs, 1 2mg/kg sid/bid in cats Initial dose is proportional to severity Oral furosemide solution is often a more convenient medication for cats and more accurately titrated when the dose is small. Following a response the dose should be reduced to the minimum effective dose In many cats (without concurrent pleural effusion) the furosemide can often be weaned off, being maintained on an ACE inhibitor. Note: Diuretic over dosage can lead to: subclinical dehydration, inappetance, lethargy, pre-renal azotaemia, depletion of electrolytes, polydipsia/polyuria. Management of Atrial fibrillation (AF) - Important when the ventricular response rate exceeds 150/min - May not be necessary in giant breed dog with lone AF - Digoxin would be the most commonly used drug Primarily used in dogs, indications for use in cat are rare and not discussed Dose = 0.22mg/m 2 every 12 hours, however the boxed text below provides a simple guideline for a starting dose Digoxin starting dose in dogs Body weight Tablet size Tablet dose 1 5 kg 62.5µg (PG) ½ q12 hours 6 13 kg 62.5µg (PG) 1 q12 hours kg 125µg 1 q12 hours kg 125µg 1 ½ q12 hours 37 kg 250µg 1 q12 hours Note: Dobermann dose is 125µg tablet 1 q12 hours Steady state levels are achieved in 5-7 days Serum digoxin levels should be measured (approximately 6 hours post pill, day 5-7) to confirm the dose is correct, as it varies between individual patients. Therapeutic serum levels are between ng/ml; between 1 2 ng/mg is a reasonable target Therapeutic aims are to reduce the resting heart rate to less than /min, however judging the heart rate in-clinic may result in falsely high heart rates, so clinical judgement needs to be made, but Holter monitoring is recommended. Causes of a persistent high heart rate listed in the boxed text below Causes of a persistently high heart rate in dogs with atrial fibrillation receiving digoxin Elevation of the heart rate in-clinic due to nervousness at the time of examination may require 24 hour Holter to determine average heart rate at home Inadequate control of the congestive failure signs - sympathetic drive is still high Dehydration / hypotension due to over diuresis / vasodilation Inadequate serum therapeutic levels of digoxin Concurrent medical disease, e.g. renal failure Advanced myocardial failure and end stage heart disease Heart rate poorly responsive to digoxin - needs additional antiarrhythmic drugs Bioaccumulation of digoxin may occur with azotaemia, low serum albumin, cachexia Signs of over dosage are: depression, anorexia, vomiting/diarrhoea, arrhythmias, in which case the drug should be stopped and re-introduced at a lower dose when signs have completely resolved. Positive inotropic drugs Pimobendan. - Indications: dogs with dilated cardiomyopathy or mitral valve disease may be of benefit in cats with cardiomyopathy where there is reduced wall motion - Pimobendan at mg/kg bid, on a empty stomach Also has arterial vasodilator properties Positive lusitropic properties Additional effects are: improvement in the animals demeanour, alertness and activity, and sometimes an improvement in appetite Inhibits platelet aggregation Note: Calcium channel antagonists may reduce the efficacy of pimobendan Summary: Treatment strategy for treatment of chronic congestive heart failure (out-patient treatment) in dogs Exercise yes, but within animals capability ACE inhibitor (ACE I) Pimobendan Furosemide to minimum effective dose Digoxin primarily in cases with atrial fibrillation Refractory chronic heart failure in dogs (often with ascites) This occurs primarily in dogs with dilated cardiomyopathy, but eventually is seen in dogs with mitral and tricuspid valve disease. Ascites (+/- pleural effusion) becomes refractory to the above treatment, including top-doses of furosemide (3mg/kg bid). In these cases the dose of ACE inhibitors should be doubled to bid and the dose of pimobendan maximised. If ascites remains refractory then additional diuresis is required: - Co-amilozide (hydrochlorothiazide + amiloride) at 1-3mg/kg (combined dose rate) a potent and useful diuretic amiloride is a potassium sparing diuretic. Monitoring of acquired heart failure in dogs and cats Once heart disease and congestive failure has been diagnosed it is imperative that there is ongoing, life-long, monitoring of the heart failure with constant adjusting of drug doses to ensure these are optimised for each individual animal. This is a guideline that may be of benefit, but needs to be adapted to each patient s circumstances. Physical examination By the owner at home: Monitor the resting respiratory rate - this increases when there is pulmonary oedema or pleural effusion. Monitoring the heart rate is sometimes useful - but this can be difficult especially when there is an arrhythmia such as atrial fibrillation (AF) and thus less reliable. Keep rechecking response for example - is the quality of life satisfactory? In particular is there an improvement, or not, in coughing, respiratory character, appetite, thirst, etc. By the vet: Check general demeanour and attitude, respiratory effort, mucosal colour, heart and pulse rates (particularly when there is an arrhythmia such as AF), presence of ascites, body weight. Blood tests 1. As a baseline a full blood profile should be performed before administering therapy in virtually all cases. 2. The first follow-up profile should ideally be performed within 1 to 2 weeks of instituting cardiac therapy, with the aims of monitoring renal and hepatic parameters, protein levels, electrolytes and haematology. For example dehydration or electrolyte imbalance may occur and may dictate reduction in diuretic dosage. Mild elevations in urea and creatinine are acceptable in most cases when on therapy. 3. Further follow-up profiles should be considered within 4 weeks and then at 3-4 month intervals to monitor long term, depending upon each individual case and the type of underlying heart disease. Serum Digoxin Measure initially within 7 to 10 days of introducing digoxin, ideally 8-10 hours post morning pill (or mid-way between tablets). Ongoing digoxin levels should be assessed every 6 months. Serum levels may increase due to chronic renal failure or weight loss for example. Thoracic Radiography The purpose of follow-up chest radiographs is to check if any pulmonary oedema or pleural effusion is adequately controlled - this cannot be reliably performed by clinical examination alone. Thus ensuring that the dose of diuretics used is not too much (or too little). If there is uncertainty as to the cause of any change in symptoms, such as deterioration in coughing, then chest radiographs can help to decide if the cough is due to progressing cardiomegaly or not. If heart disease has been detected before the onset of symptoms, such as a murmur due to mitral valve disease, then monitoring for the development of cardiomegaly can help to decide when treatment should be instituted. Echocardiography In dogs the main value is monitoring for the progression or development of myocardial failure (reduced ventricular contractility). For example occult dilated cardiomyopathy will progress and lead to signs of heart failure, or long standing mitral valve disease may lead to secondary myocardial failure. Suspected acute rupture of a chordae tendineae is another indication for a repeat echocardiographic examination. In cats, repeat echocardiography after 4 to 6 months of therapy is useful, particularly with hypertrophic cardiomyopathy to document the response to therapy, degree of left ventricular hypertrophy or outflow tract obstruction. Alterations in therapy may be required according to findings. Recommended Reading Notes on Cardiorespiratory Diseases of the Dog and Cat, 2 nd edition. Martin & Corcoran (2006) Blackwell Science. ISBN Small Animal ECGs: An Introductory Guide, 2 nd edition. (2007), Blackwell. ISBN DRUG GLOSSARY For detailed information regarding uses, contra-indications and side-effects the reader should consult appropriate formularies and the product data sheets. Amlodipine Aspirin Atenolol. Atropine Benazepril. Bromohexine. Butorphanol (anti-tussive) Co-amilozide (amiloride + hydrochlorothiazide) Codeine. Clenbuterol Dalteparin (low-molecular weight heparin) Dextromethorphan. Digoxin Diltiazem. Dobutamine Cat: mg per cat q24hr (to q12hr) Dog: Starting dose of 0.5mg/kg q12hr increasing to effect to a maximum of 2mg/kg q12hr Dogs: 5mg/kg daily Cats: 5 20mg per cat twice a week Dog mg/kg q12hr orally. Cat 1-2mg/kg q12-24hr orally. Dog/cat: 20-60µg/kg q6-8hr orally Dog/cat: 40µg/kg s/c Dog 0.25mg/kg q24hr orally. Cat 0.5mg/kg q12-24hr orally. Dog 2mg/kg q12hr orally. Cat 1mg/kg q24hr orally. Dogs: mg/kg q6-12hrs orally. Dogs/cats: 1-3mg/kg q12hr Dogs: 0.5-2mg/kg q8-12/hr orally. Dog: 1-5µg/kg q8-12hr Cat: 1µg/kg q12-24hr iu/kg s/c q12hr Dogs 0.1-5mg q8-12hr orally. Dog: (0.22mg/m 2 q12 hrs) for recommended starting dose see above Cat: 4kg mg tablet 1/2 q48 hours & 4kg mg tablet 1/2 q24 hours Dog 1-3mg/kg q8hr orally, start low and titrate up Cat mg/kg q8hr orally. Slow release (Dilacor XR) 30mg per cat q24 hr Dog: µg/kg/min i/v Enalapril. Enoxaparin (low-molecular weight heparin) Esmolol Fenbendazole Treatment of lungworm Fish oils Furosemide (frusemide) Glyceryl Trinitrate (2% ointment). Heparin Imidapril. L-carnitine Lidocaine (Lignocaine) Magnesium amino chelate (200mg tablets) Mexilitine. Morphine Pimobendan. Propantheline bromide. Dog 0.5mg/kg q12hr orally. 100iu/kg s/c q12hr Dog/cat: mg/kg slow i/v Mild infection: 100mg/kg daily for 5 7 days Moderate infection: 50mg/kg daily for 7-10 days Severe infection: 20mg/kg daily for days Eicosapentaenoeic acid (EPA) = 40mg/kg per day Docosahexaenoeic acid (DHA) = 25mg/kg per day Starting dose: Dog: 0.5-2mg/kg q12hr (up to 4mg/kg q8hr) Cat: 0.5-1mg/kg q12-24hr (up to 2mg/kg q12hr) Acute failure: Dog: 3-4mg/kg q2hr i/v or i/m Cat: 1-2mg/kg q2 hr i/v or i/m Dog cm (small-large breed) q6-8hr for 3d topically. Cat 0.5cm q8hr for 3d topically. 250iu/kg q8hours Dog 0.25mg/kg q24hr orally. Dogs: 50mg/kg q8hr Dog 2-3mg/kg slowly iv, every few minutes to a max. of 9mg/kg in minutes. Dog 25-75µg/kg/min iv infusion. Cat: mg/kg, can repeat after 20 minutes Dog: 10mg/kg daily with food Dog 5-8mg/kg q8hr orally. Dogs: mg/kg q4-6hr Cats: 0.1mg/kg q6-8hr Dog mg/kg q12hr orally, on empty stomach Dog 0.5-2mg/kg q8hr orally. Cat: 7.5mg q8-12hr Propranolol. Ramapril. Sodium nitroprusside Sotalol. Spironolactone. Streptokinase Taurine Terbutaline. Theophylline. Dog 0.2-2mg/kg q8hr orally, start low an titrate up. Cat 2.5mg q8hr orally, up to 5mg q8hr. Dog/cat: mg/kg i/v, start low and titrate up Dog 0.125mg/kg q24hr orally, increasing to 0.25mg/kg. Dog: µg/kg/min i/v Dog: 0.5-2mg/kg q12hr orally. Dog: Diuretic dose: 1-2mg/kg q12-24hr Cat: Diuretic dose: 1-2mg/kg q12-24hr Cat: 90000iu over 30 minutes; then 45000iu per hour for 3-6 hours Dogs: 500mg q12hr Cats: 250mg q12hr Dog mg per dog q8-12hr orally. Cat: mg per cat q8-12hr orally. Dog 10-20mg/kg q12hr orally. Cat: 20mg/kg q12-24hr SUMMARY Bloods Antitussives BP Monitor Cough COPD?? Digoxin AF HF Congestion Diuretics Co-amilozide or spironlactone Refractory ascites Spiron ACEi Advanced HF ACEi to bid Pimo
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