March 2006 Cardiology John E. Rush, DVM, MS, DACVIM (Cardiology), DACVECC Tufts University School of Veterinary Medicine Congenital Heart Disease Congenital heart disease is defined as a cardiovascular malformation present at birth. Genetic and hereditary factors can play a role in development of congenital defects. A polygenic mode of inheritance has been proposed for many canine defects, however several defects in humans are proved to result from a single genetic abnormality. Exposure to environmental factors in fetal life such as drugs, toxins, infectious diseases, or poorly defined "stressors" may cause cardiac malformation, but in the vast majority of cases a genetic cause is thought to be present. Congenital heart disease incidence is reported in dogs is 5-10 cases per 1000 births, and the estimated incidence in cats is 2-10/1000 births, although the true incidence unknown. In most dogs and cats, the earliest indication of cardiac malformation is auscultation of a cardiac murmur. Many young animals have soft murmurs due to flow through the great vessels, mild anemia, and reduced muscle and adipose tissue deposition around the heart and thorax. These innocent murmurs are usually soft (grade I-III/VI), systolic, they may be of short duration (less than the entire duration of systole), and may have a musical character over the heart base. Innocent murmur can change character with changes in body position, and they typically disappear by 6 to 12 months of age. Loud murmurs of long duration and those associated with stunted growth, altered pulse quality, or other evidence of cardiac limitation are often the result of cardiac malformation. The cardiovascular work up for congenital heart disease typically includes thoracic radiographs and an electrocardiogram, although some animals with significant disease (e.g., aortic stenosis) will have normal findings on these tests. Echocardiography (with Doppler studies) is currently the diagnostic technique of choice to diagnose congenital heart defects. Selective cardiac catheterization is indicated in cases where catheter-directed therapies are possible, when cardiac surgery is anticipated, or when the diagnosis remains in question after routine testing. Patent Ductus Arteriosus (PDA) in dogs and cats is usually a left to right shunting defect. The lesion is a persistent patency of the ductus arteriosus which connects the aorta to pulmonary artery. Blood flows from the high pressure aorta to the lower pressure pulmonary artery throughout the cardiac cycle, leading to a continuous cardiac murmur. Female dogs are predisposed to PDA and pure breeds including Pomeranian, poodle (proved heritable cause), Keeshond, Bichon frise, Chihuahua, Maltese, Shetland sheepdog, Yorkshire terrier, English springer spaniel, Dachshund, miniature schnauzer, German shepherd, cocker spaniels, and Irish setters, and +/- Siamese cats are predisposed. PDA is common in dogs and much less common in cats. The physical examination findings include a continuous murmur found high in the left heart base, many dogs also have a systolic murmur over the mitral valve, and bounding arterial pulses. Some cats with PDA may only have a systolic murmur. Between 10-25% of affected animals have signs of CHF at the time of diagnosis. The ECG is often abnormal with a left ventricular enlargement pattern and some cases also have a left atrial enlargement pattern. Cardiac arrhythmias of atrial fibrillation and ventricular premature depolarizations are uncommon. Thoracic radiography often identified generalized cardiomegaly with left ventricular and left atrial enlargement and pulmonary overcirculation. The VD radiographic view may have 3 distinct bumps at the 1:00 (aorta or ductus bump), 2:00 (main pulmonary artery) and 3:00 (left auricular enlargement) positions. While the above information usually is sufficient to establish the diagnosis in many cases, echocardiography is useful to confirm the diagnosis and search for other concurrent cardiac defects. Echocardiographic findings include a volume overload to the left ventricle and left atrium with continuous turbulent flow in an enlarged main pulmonary artery. The ductus can typically be visualized with color-flow Doppler, and mitral regurgitation is present in some cases due to annular dilation. Treatment: Uncorrected PDA is reportedly associated with a 40 to 70% mortality rate in the first year of life. If CHF is found then stabilization with standard medical therapy (diuretics, ACE inhibitors) is recommended prior to surgery. It is desirable to correct the defect before 4-5 months of age as this allows remodeling as the animal can "grow into" the enlarged heart. The 2 main methods of correction are: 1) Surgical ligation of the ductus and 2) Coil occlusion via catheter delivery. Surgery requires a thoracotomy, is associated with significant post-operative pain, and has a higher risk for mortality. Coil occlusion requires a small inguinal incision, has little post-operative pain and a quicker recovery, and has a lower mortality rate; however the ductal morphology can preclude coil occlusion in up to 10% of dogs. Animals with a short ductus that fails to taper often cannot be occluded with a coil; the German shepherd is more likely to have this morphology than other breeds. Pulmonic Stenosis is one of the most common congenital cardiac defects in the dog, however isolated pulmonic stenosis is rare in cats. The stenotic lesion results from narrowing of the pulmonary outflow tract due to either: 1) valvular dysplasia with valvular stenosis, 2) Subvalvular stenosis with fibrosis, 3) supravalvular stenosis, 4) Pulmonary outflow narrowing due to anomalous coronary vessel or some combination of the above lesions. Secondary infundibular (muscular) hypertrophy may complicate the stenosis. Several canine breeds are predisposed including English bulldog, Schnauzer, Beagle, Chihuahua, Terriers (Scottish, wire haired fox, west highland white, Yorkshire), Cocker spaniel, and Samoyed. The English bulldog and Boxer are predisposed to coronary artery anomaly. Classic findings on physical examination include a loud, harsh ejection quality systolic murmur with PMI at the left cardiac base (2nd or 3rd intercostal space). A second right-sided murmur of tricuspid regurgitation may be present, the cardiac apex beat may be strongest on the right hemithorax, and animals with critical stenosis may have pallor and weak arterial pulse quality. Signs of right ventricular failure include hepatomegaly, ascites, pleural effusion, and jugular venous distention and/or pulsation. Many animals are asymptomatic at the time of diagnosis, but when clinical signs develop they usually reflect either low output (syncope) or right-sided CHF (ascites). The ECG may be normal in dogs with mild or moderate pulmonic stenosis. A right ventricular enlargement pattern is common in dogs with more severe pulmonic stenosis, and P pulmonale may develop if right atrial enlargement or concurrent tricuspid valve dysplasia is present. Ventricular arrhythmias possible but supraventricular arrhythmias are more common in dogs with RA enlargement. Findings from thoracic radiography include evidence of right ventricular enlargement with a post stenotic dilation of the main pulmonary artery on the VD view at the 2:00 position. Right atrial enlargement is variably noted, the caudal vena cava may be enlarged, and pulmonary vasculature may appear attenuated. The echocardiographic findings include concentric hypertrophy of the right ventricle with prominent papillary muscles, a post stenotic dilation of the pulmonary artery, +/- RA enlargement or tricuspid regurgitation. The pulmonary outflow tract may appear narrowed and hyperechoic (sub-valvular), the valve leaflets may be thickened and/or have abnormal valve excursion (valvular dysplasia). The interventricular septum is hypertrophied and may move toward the RV during systole (paradoxical septal motion). An anomalous coronary vessel can be seen in some affected dogs. Supravalvular pulmonic stenosis is the main cause of obstruction in some cases. Doppler echocardiography can be used to document turbulent systolic blood flow in the main pulmonary artery and provides an accurate estimate the pressure gradient across the pulmonic valve. Pulmonic insufficiency is common. The pressure gradient across the pulmonic valve is used to grade the severity of disease. Mild PS in dogs is defined as a gradient of 10 to 50 mmHg, moderate gradients are between 50 and 100 mmHg, and severe gradients are those in excess of 100 mmHg. Treatment: Dogs with mild PS usually remain asymptomatic and do not require therapy. Untreated dogs with severe stenosis and clinical signs rarely live beyond 4 years of age. The decision on whether to perform balloon valvuloplasty, surgery, or no therapy is made based on the gradient, the degree of RV hypertrophy, the nature of the stenosis (valvular or sub-valvular; abnormal coronary anatomy), the degree of tricuspid regurgitation and right atrial enlargement, and the presence of clinical signs. Balloon valvuloplasty has been used to successfully relieve the stenosis in many dogs with valvular pulmonic stenosis, however the results are less impressive in many dogs with sub-valvular PS. Medical therapy is limited to antiarrhythmic drugs and judicious use of diuretics and low-salt diet to control signs of congestive heart failure. Several surgical procedures have been described, including bistoury, valvotomy, and patch graft techniques to enlarge the pulmonic outflow region. Effective surgery results in a significant decrease in the gradient across the pulmonic valve, although some institutions report a 20% mortality rate with surgical correction of pulmonic stenosis. Aortic Stenosis results from narrowing of the aortic outflow tract due to 1) Subvalvular stenosis with fibrosis (90% of dogs) 2) valvular dysplasia, 3) supravalvular stenosis (more common in cats). Several canine breeds are predisposed including the Newfoundland, German shepherd dog, boxer, golden retriever, rottweiler, bloodhound, and German shorthair pointer. Aortic stenosis has been proven to be transmitted genetically in the Newfoundland breed. Physical examination findings include a loud, harsh systolic, ejection quality (crescendo decrescendo) murmur with a PMI at the left heart base, usually at the 3rd or 4th intercostal space. The murmur may be equally loud at right heart base, and radiate to the thoracic inlet and up the carotid arteries. Often there is a prominent left apical impulse, and femoral pulses often are weak and slow rising. Cardiac arrhythmia, especially ventricular arrhythmia, is possible. The ECG can be normal in mild cases or abnormal findings can include a left ventricular enlargement pattern, ST segment depression and/or T wave abnormalities may be noted. Significant ST segment depression at rest (>0.2 mV in lead II) is suggestive of myocardial ischemia/fibrosis, and this finding can be found in some dogs if an ECG is obtained after exercise. Left ventricular enlargement may be present on thoracic radiographs, but the concentric hypertrophy is difficult to detect radiographically. A post stenotic dilation of the aorta, cranial to the heart on both lateral and ventrodorsal projections, is often found in dogs > 1 year but is less commonly evident on radiographs in young dogs. The echocardiographic findings in subvalvular aortic stenosis include a thickened, subvalvular hyperechoic rim of tissue +/- valvular dysplasia, concentric hypertrophy of the left ventricle, and the endocardium and papillary muscles are often hyperechoic in cases with myocardial fibrosis. The post-stenotic dilation of the aorta is usually evident on echocardiography, and mild aortic regurgitation is present in most cases. Turbulent systolic flow is noted in the aorta and Doppler echo is used to estimate the gradient across the aortic valve. Mild stenosis is defined by a gradient of 10 to 40 mmHg; moderate stenosis by a 40 to 80 mmHg gradient; and severe stenosis by a gradient in excess of 80 mmHg. Treatment: Dogs with mild aortic stenosis (gradient < 40 mmHg) usually remain asymptomatic and do not require therapy. Many dogs with SAS develop syncope or sudden death before congestive heart failure. Marked LV hypertrophy and compromised myocardial (coronary) perfusion lead to ventricular arrhythmias, which can cause sudden death, especially during physical exertion. Surgical techniques have not been clearly documented to result in improved survival, and surgical correction of subaortic stenosis is infrequently attempted due to the requirement for cardiopulmonary bypass. Some institutions have had reasonable success with balloon valvuloplasty, although the balloon appears to be incapable of consistently stretching the subvalvular fibrous tissue ring. This technique is perhaps most useful in animals with a component of valvular aortic stenosis. Propranolol, atenolol or other beta adrenergic blocking drugs have been used to reduce the myocardial oxygen demand and diminish the risk of arrhythmic death. One recent study failed to find a benefit of valvuloplasty when this procedure was compared to dogs treated with atenolol alone. Aortic stenosis predisposes dogs to aortic valve endocarditis, therefore prophylactic antibiotics (i.e., penicillin for dental procedures, ampicillin and gentamicin for genitourinary or gastrointestinal surgery) are indicated for procedures associated with bacteremia. Ventricular Septal Defect is a common cardiac malformation in the cat. The lesion is a defect in the interventricular septum that allows communication between the left and right ventricles. The VSD may occur anywhere in the interventricular septum, although the most common site is high, in the membranous portion of the septum below the aortic valve, under the septal tricuspid leaflet. Blood flow is from left to right ventricle in most cases. In some cases with a large muscular VSD, pulmonary hypertension will develop and right to left shunting with cyanosis will develop. The VSD is one of the most common congenital defects in the cat. Lakeland terrier, West Highland white terrier, English Springer spaniel, Basset hound, Keeshonds, Akitas, Shi Tzu, and English bulldogs are likely predisposed as well. Physical examination findings include a harsh, holosystolic murmur auscultated loudest at the right cranial sternal border. The character of the murmur is highly variable but it may be a plateau, crescendo, or crescendo decrescendo murmur. An accompanying murmur of relative pulmonic stenosis (left heart base) or other murmurs may be noted. The ECG findings are highly variable but can include atrial or ventricular enlargement, arrhythmias or a conduction disturbance. Abnormalities on thoracic radiography include generalized cardiomegaly, often with left atrial and ventricular enlargement, pulmonary overcirculation, and variable RV enlargement. If CHF develops then signs of pulmonary edema and/or pleural effusion (esp. cats) will be noted. A volume overload (eccentric hypertrophy) develops in the left atrium and ventricle in the classic left to right shunting VSD, and this is easily appreciated on echocardiography. Medium to large VSD's can often be visualized as an echolucent region at the top of the IV septum. Doppler studies confirm the location and direction of the blood flow, with left-to-right shunts having a high velocity jet traveling from the LV to the RV. Treatment: The size of the shunt is usually expressed as a ratio of the blood flowing through the pulmonary and systemic circulations, and this is best measured by cardiac catheterization however some estimation can be made based on echocardiography. If the flow through the pulmonary circuit is greater than or equal to 2.5 times the systemic circulation, the animal is at risk of developing pulmonary vascular disease (hypertension) or heart failure, and surgical therapy is recommended. Pulmonary artery banding can be done to reduce the volume of blood shunting through the VSD. Definitive repair of the VSD requires cardiopulmonary bypass. There have been a few reports of closure of an ASD or VSD using a catheter-delivered coil or patch device. This technique can be technically challenging, and the patch can easily trap open either the AV or aortic valve leaflets, so further studies of these devices are needed before they can be routinely performed. Those animals that have clinical signs of failure may respond well for several months to standard medical therapy with diuretics and ACE inhibitors. Atrioventricular Valve Malformations may be the most common congenital malformation in the cat. Congenital mitral and tricuspid malformations may result in valvular insufficiency, stenosis, or both. Atrioventricular valvular insufficiency is the most common sequela to malformation. Valve leaflets may be thickened or fused and abnormal (short and thick or long and thin) chordae tendineae may be observed. In addition the papillary muscles may be malpositioned, incompletely developed, or absent, and malpositioning of the papillary muscles on the ventricular wall has been frequently described. Atrioventricular valvular insufficiency places a volume overload (with resulting eccentric hypertrophy) on the affected ventricle. This results in enlargement to the affected atrium and ventricle, and eventually heart failure. Mitral and tricuspid valve dysplasia were reported in one survey as the most common congenital cardiac defect in the cat. Large breed dogs, especially the Great Dane, German shepherd, Labrador retriever (esp. tricuspid valve dysplasia) and Weimerianer may be predisposed to atrioventricular valve dysplasia. Dogs with atrioventricular valve dysplasia often develop clinical signs at an early age, including weight loss, exercise intolerance, dyspnea, ascites or pleural effusion. Episodic weakness or syncope may result from cardiac arrhythmias. While some cats are severely affected at a young age, other cats live for many years with no overt evidence of cardiac dysfunction. Cats with mitral valve malformation may develop pulmonary edema or bi ventricular failure as well as systemic arterial embolism. Physical examination usually reveals a pansystolic murmur over the affected valve. Animals with mitral insufficiency have radiographic evidence of left atrial and ventricular enlargement, and when heart failure occurs pulmonary venous distention and pulmonary edema is present in dogs. Cats with mitral valve dysplasia are more likely to develop biventricular congestive failure. Tricuspid valve dysplasia leads to right heart enlargement and signs of right heart failure. ECG findings may include evidence of atrial or ventricular enlargement and supraventricular arrhythmias. The abnormal morphology of the AV valve leaflets, chordae tendineae, papillary muscles, or left atrial and ventricular enlargement may be appreciated with echocardiography. Cardiac angiography or Doppler studies are employed to document AV valvular regurgitation. Surgical repair of these lesions requires cardiopulmonary bypass, and valve replacement (rather than valve repair) is usually required. Tetralogy of Fallot is defined as a cardiac defect with four pathologic findings: 1) pulmonic stenosis, 2) a high ventricular septal defect, 3) dextroposition of the aorta such that it overrides the interventricular septum, and 4) secondary right ventricular hypertrophy. Hypoxemia leads to secondary polycythemia. A genetic predisposition for a spectrum of conotruncal abnormalities, including Tetralogy of Fallot, has been documented in the keeshond breed. The English bulldog is also predisposed. Tetralogy of Fallot is also a relatively common defect in the cat. Clinical signs usually result from arrhythmias, systemic hypoxemia, and/or complications of polycythemia. Exercise intolerance, dyspnea, syncope, cyanosis and stunting can be seen. Polycythemia can produce hyperviscosity and red blood cell sludging in small vessels and may lead to cerebrovascular accident. An additional sequela of Tetralogy of Fallot is systemic embolism because thrombi, normally filtered by the lungs, freely cross the VSD to the systemic circulation. Congestive heart failure is uncommon. The murmur of pulmonic stenosis is heard best at the left base, and a second murmur (ventricular septal defect), is loudest at the right cranial sternal border. The murmurs may be attenuated in animals with polycythemia, severe pulmonic stenosis, or minimal blood flow through the VSD. Thoracic radiographs may demonstrate right ventricular hypertrophy. Pulmonary undercirculation, evident by decreased vascular marking and a post stenotic dilatation of main pulmonary artery may be observed. Most cyanotic animals with TF have ECG evidence of right ventricular enlargement. Polycythemia is common and blood gas analysis documents hypoxemia. The echocardiogram documents the ventricular septal defect, evident high on the interventricular septum, just below the aortic valve. Right ventricular hypertrophy and abnormalities in the pulmonic valve or pulmonary outflow tract are also readily appreciated on echocardiography. Contrast echocardiography will demonstrate right to left blood flow across the VSD with the appearance of microbubbles in the ascending aorta. Animals who are not cyanotic and who have mild pulmonic stenosis may be managed conservatively with low dose aspirin therapy to reduce the likelihood of venous to arterial thromboembolism. Periodic phlebotomy is indicated in polycythemic animals to maintain a hematocrit near 60%. Hydroxyurea produces reversible bone marrow suppression and can be also used to control polycythemia. Non-selective beta blocking drugs (i.e., propranolol) are advocated to decrease heart rate and myocardial contractility. The latter may diminish additional pulmonary outflow obstruction posed by infundibular hypertrophy. These drugs also increase systemic vascular resistance which decreases right to left shunting. Surgical correction has been described and requires cardiopulmonary bypass. Several palliative surgical procedures appear to be useful, and involve anastomosis of a systemic artery to the pulmonary artery thereby increasing pulmonary blood flow. Cardiac Arhymtha Managing Difficult to Control Cardiac Arrhythmias Case 1 - 6 year old Boxer with 1 episode of collapse and cardiac arrhythmias noted on examination. The echocardiographic findings include normal LV contractile function and mild concentric hypertrophy of the left ventricle. Aortic outflow tract velocity is normal. Case 2 - 5 year old CM DSH with I/VI systolic murmur and echocardiographic evidence of mild left ventricular hypertrophy with a normal left atrial size. The murmur was noted on examination but the cat is otherwise asymptomatic. Case 3 - 6 month old German shepherd dog with arrhythmias noted during examination. The dog is asymptomatic and the echocardiogram is WNL. Case 4 - 1 year old Weimaraner with exercise intolerance 2 weeks after PDA occlusion. Case 5 - 6 year old German Shepherd dog with episodic collapse. Moderate cardiomegaly was noted on echocardiography, with good LV contractile function. Thoracic radiographs show cardiomegaly but no evidence of CHF. Case 6 - Boxer presented for tachypnea and "pounding heart". Pre and Post-Rx Case 11 - 2.5 year old mixed breed dog, 50#, with multiple episodes of collapse and one episode of CPA that was treated (with CPR) by the owner, who is a veterinary technician. Prior treatment with sotalol was ineffective. Procainamide plus a beta-blocker was also ineffective. The dog has been marginally controlled (no collapse for 1 month) on amiodarone, although the episode of CPA was yesterday. Case 12 - 8 year old dog hospitalized after intestinal surgery. Case 13 - 8 year old Golden retriever with dilated cardiomyopathy and mild to moderate pulmonary edema. Case 14 - 12 year old miniature schnauzer with weakness and seizures. Management of Canine Heart Failure Management of chronic congestive heart failure (CHF) has undergone some significant changes in the last few years. Traditionally, animals with heart disease have been treated, at least in part, based on the morphologic appearance and function of their ventricle. This approach belies the fact that the neurohumoral stimulation, which is a critically important factor in the development of congestive signs, is activated mostly at sites that are distant from the heart. Therefore, to control congestive heart failure, it might be argued that therapies that act to blunt this neurohumoral activation should be the same in all patients, regardless of the underlying appearance and function of the ventricle. The role that the neurohumoral responses play in the development and maintenance of heart failure is highlighted by recent human clinical trials. The therapies documented to improve survival in humans act by interfering with these neurohumoral mechanisms (e.g., angiotensin-converting enzyme inhibitors, beta-blockers, and spironolactone). There has been progressive support for use of therapies that interrupt these compensatory responses. Studies into the effects of neurohumoral activation at the cellular (myocardial) level have identified that progressive myocardial hypertrophy, cardiac remodeling, myocardial fibrosis, and progressive cardiac enlargement all are directly impacted by these seemingly exuberant compensatory reactions. In summary, therapies that interrupt these neurohumoral responses, in both human heart failure patients and in a variety of animal models, have been documented to prevent progressive cardiac remodeling, slow the progression of CHF, and improve survival. Drug therapy for heart failure Angiotensin-Converting Enzyme Inhibitors - Angiotensin-converting enzyme (ACE) inhibitors are commonly used in the management of CHF. Their use is predicated on the knowledge that interfering with the activation of the renin angiotensin system leads to diminished plasma levels of angiotensin II and reduced stimulation of aldosterone. As a result, fluid retention and vasoconstriction are blunted. Newer information documents the benefit of ACE inhibition with respect to altering the progressive cardiac enlargement and remodeling known to attend most forms of heart failure. This effect on cardiac remodeling seems to be mediated (at least in part) via an increase in bradykinin, another substance affected by ACE inhibitors. The beneficial effects of ACE inhibition likely result from both the vasodilation and the drug's effects to reduce cardiac remodeling. If the progressive ventricular enlargement and progressive replacement of myocytes with non-distensible fibrous tissue can be avoided, survival might be prolonged, and symptoms of heart failure can be reduced. Underutilization of ACE inhibitors has been documented in a number of retrospective human studies. Underutilization can take the form of failure to use the drug or use of doses that have not been documented to result in and improved survival. The veterinary doses recommended are close to the higher end of the dose, but veterinarians should be attempting to use at least the minimum recommended doses. Angiotensin-converting enzyme inhibitors have proved to be useful in a variety of settings. In a large number of human heart failure trials, ACE inhibitors have been proven to prolong survival. In addition, these drugs have been documented to slow the progressive cardiac enlargement, and delay the onset of CHF in humans with left ventricular dysfunction. In well designed canine heart failure trials, ACE inhibitors resulted in improved clinical signs and a prolonged the time until an animal dropped out of the study (equivalent to improved survival). Which animals should be treated with ACE inhibitors? There is very good experimental evidence to support the use of ACE inhibitors in dogs with congestive heart failure due to either dilated cardiomyopathy or chronic valvular disease (endocardiosis). Most veterinary cardiologists would agree that ACE inhibitors are probably effective in dogs with congestive heart failure due to endocarditis, congenital heart diseases associated with volume overload, and other forms of left-sided congestive heart failure in dogs. There is also general agreement that ACE inhibitors are useful in cats with congestive heart failure due to dilated cardiomyopathy and certain unclassified forms of cardiomyopathy. There is also consensus that ACE inhibitors are useful in the management of systemic hypertension seen in dogs and cats due to renal disease, especially glomerular disease, and hypertension that is idiopathic in origin. Unfortunately, in many clinicians experience, ACE inhibitors are only modestly successful in reducing blood pressure to the normal range and other medications (i.e., amlodipine) are often more successful as single agents to control systemic hypertension. There is less agreement about the use of ACE inhibitors in cats with hypertrophic cardiomyopathy and in animals with asymptomatic heart disease. Furosemide (Lasix) - It has been documented that asymptomatic heart disease is usually not associated with measurable activation of certain neuroendocrine systems, however, these neuroendocrine responses are stimulated following therapy with a diuretic. This stimulation of the neuroendocrine system is counterproductive, especially if one is to believe the prevailing attitudes regarding the progression of heart failure. Many cardiologists would now not recommend single agent use of furosemide for treatment of CHF. This does not mean that appropriate diuretics should not be used when congestion develops! Still, it is quite difficult to define the exact dose of diuretic required by any individual dog or cat with CHF. The dose required to clear significant edema accumulations and cause the animal to be minimally symptomatic (the desired dose) is often close to a dose that might result in electrolyte disturbance, dehydration and the development of pre-renal azotemia. The combined use of ACE inhibitors and diuretics compromises one of the kidneys' normal compensatory mechanisms (vasoconstriction of the efferent arteriole) and can lead to elevation of BUN and creatinine when 1) excessive diuretic dose is initiated or 2) significant pre-existing renal disease is present. Since most cardiologists now concurrently use ACE inhibitors and diuretics for animals with CHF, the risk of pre-renal azotemia with excessive doses of furosemide is quite real. For this reason, I currently advocate use of the "Lowest possible dose of Lasix" in animals with CHF. This often means a degree of experimentation must be performed to best evaluate an individual animal's needs. Giving an owner upper and lower limits for acceptable furosemide dose, and carefully explaining to them that they should "give more for difficulty breathing or rapid respirations, and give less if the animal seems weak, lethargic, anorexic, or depressed" has worked successfully for the author. In most instances, canine patients are given less than 2 mg/kg q 12 h, and in most cats I initially try to use 6.25 mg/cat/day for chronic therapy. Some cats require higher doses of furosemide, but many can be treated with 6.25 mg/cat every other day. When a dose of 2.2 mg/kg twice a day is exceeded during chronic therapy, the author usually thinks that diuretic resistance has been reached and adds in a combination hydrochlorothiazide with spironolactone instead or going to higher and higher doses of furosemide. Digoxin - The debate over when to use digitalis glycosides will likely continue for many years. There is good experimental evidence to support either side of the argument, and it does not seem that a definitive answer to the question "should I use digoxin?" will be convincingly answered in the near future. The arguments for using digoxin include the potential benefits from its positive inotropic effect, the recognition that digitalis can restore blunted baroreceptor responses towards normal, and that digitalis might restore excessive sympathetic tone towards a more normal level. In a large human clinical trial, digitalis did not impact mortality; however, it did appear to reduce the need for hospitalization in humans with CHF. Those who are not enthusiastic users of digoxin would point out that the drug has significant potential for toxicity, that it can be difficult to dose in veterinary patients, and that it has not been documented to improve survival. Since the proposed neurohumoral benefits can only be evaluated under closely monitored experimental settings, and since they did not apparently yield any long-term survival benefit, arguments to use the drug based on these purported benefits are somewhat "hollow". Finally, mild to moderate toxicity in human patients is unlikely to be life-threatening; however similar toxicity in veterinary patients has the very real potential to contribute to a decision for euthanasia. In the study quoted above, serum digoxin levels in people were maintained in the 0.8-0.9 ng/ml range, which is towards the lower end of the therapeutic range for most laboratories. While many cardiologists advocate "standard triple therapy" for management of all dogs with congestive heart failure, the author is often happy to employ ACE inhibitors and diuretics for the early stages of congestive heart failure, and add in digoxin when significant supraventricular arrhythmias or advancing CHF requires additional therapies. Beta-Blockers - Beta blockade has gained favor recently as a therapeutic modality for treatment of CHF. Several early studies on the use of metoprolol, and more recent studies on the use of carvedilol have documented benefits that accrue from chronic treatment with beta-blockers. These effects are often not seen for several months after initiation of beta blockade. Such benefits include up regulation of previously down regulated beta-receptors, improved cardiac performance (improved stroke volume), and improved survival. These clinical benefits appear to have sound theoretical basis, and are currently being evaluated in veterinary patients with naturally occurring CHF. It is true that beta-blockers are negative inotropes, and this may be the most demonstrable effect when these drugs are used in animals with active CHF. The negative inotropic and negative chronotropic effects of the drugs will likely contribute to worsening of CHF in animals with active failure or those that are on the edge of compensation. Beta-blockers are best employed in animals that are minimally symptomatic with early/mild heart failure, or in animals in later stages of CHF that are already well controlled on a stable cardiac drug regimen. Metoprolol has been used at 0.2 mg/kg BID, with slow titration upwards q 2-3 weeks up to 0.4-6.6 mg/kg BID. Carvedilol has been used by some cardiologists with doses of 0.2 mg/kg BID and slow titration upwards towards a dose of 0.8 mg/kg BID, however many dogs with CHF will not tolerate this upward titration. Side effects can include the development of congestive heart failure, bradycardia or AV block, hypotension, syncope, and GI side effects. Spironolactone - Spironolactone, classified as a potassium sparing diuretic, is a weak diuretic agent and is uncommonly used for as a single agent diuretic. This drug acts through antagonism of aldosterone recptors by competitively binding to the set of plasmic receptor in aldosterone-responsive cells in the distal tubule and early collecting duct. By blocking potassium-sodium exchange they conserve potassium and promote sodium excretion. Through this action, they result in a mild diuresis. Perhaps more importantly, they conserve potassium which is typically lost with administration of other diuretic agents. Spironolactone may also have important aldosterone antagonist effects away from the heart, i.e., at the baroreceptors and in the myocardium of the heart itself. Spironolactone is usually used in combination with furosemide, thiazides or another more potent diuretics. It is often used after hypokalemia has proven to be a problem. Newer information from human patients with congestive heart failure suggests that aldosterone receptor blockade can improve survival when it is added to a background therapy of ACE inhibitors, beta-blockers and other standard therapies for CHF. The dose used to achieve an improved survival was relatively low compared to the dose needed to achieve additional diuresis. As a result of these studies, some cardiologists are using spironolactone earlier in the management of congestive heart failure. Alternatively, they may be used to provide an additional mild diuresis after high doses of other diuretics have been achieved and congestive heart failure is refractory. Potassium sparing diuretics are usually contraindicated in animals with hyperkalemia. They are not recommended to be used in combination with oral potassium supplements or renal insufficiency. Spironolactone is available as an oral tablet formulation either alone or as a combination drug with hydrochlorothiazide (Aldactazide). Side effects can include GI side effects (vomiting) and it is recommended that spironolactone be given with food. The dose in dogs is 1-4 mg/kg administered once or twice a day. Pimobendan - Pimobendan is a calcium sensitizing drug that is useful as a positive inotrope in addition to having properties as a phosphodiesterase inhibitor with vasodilating effects. It has been studied in dogs with chronic valvular disease and in dogs with dilated cardiomyopathy. In dogs with dilated cardiomyopathy many authors indicate that there is a profound clinical benefit to addition of pimobendan to background therapies for heart failure. There are ongoing studies in the US, but the drug has been approved in Canada and in many European countries for use in dogs with heart failure. A preliminary trial in human CHF patients lead to concerns regarding increased mortality compared to placebo, however this was a non-significant finding and similar findings have not been reported in the veterinary literature to date. There is a good chance that the drug will be approved in the US, and it is the author's opinion that the drug should be used as an "add on" drug to other CHF therapies rather than as an alternative to current drugs. Dietary Modifications Sodium restricted diets have been part of the therapy of animals with congestive heart failure for many years. Certainly owners that have fed table scraps and treats should be counseled to avoid this behavior and/or feed treats that are low in sodium (Pasta, potatoes, rice, low-salt bread or low-salt cheese, cooked lean meat (chicken, turkey, beef), cooked egg, fruits and vegetables). Food items to be avoided include fatty foods like meat trimmings and ice cream, sandwich meats, most cheeses, processed foods and treats (chips), pizza and most breads. The prescription low sodium diets have not always been well accepted by CHF patients, in part due to appetite alterations seen with CHF, cardiac cachexia, drug side effects, and rapid introduction of the diets. Some diets have been advocated based on their degree of sodium restriction are probably too restricted in protein for most dogs with congestive heart failure (e.g., k/d diet). Severe sodium restriction might not be required in dogs with milder CHF. In addition to the prescription low sodium and cardiac diets, other canine diets that have moderate sodium content can be used for mild congestive heart failure. There is ongoing debate as to whether sodium restriction is useful before CHF has developed and there is now a diet that has been specifically formulated for dogs before the onset of congestive heart failure or for use once mild heart failure has occurred. When should I recheck him (or her), and want should I do? The author routinely recommends re-evaluation of the patient with a chemistry profile to check renal function and electrolytes 7 to 10 days after initiation or alteration of cardiac medications. Serum digoxin levels should be obtained, ideally 8 hours post-pill, an examination 7 to 10 days after initiation of the medication. In almost all cases, some adjustment to cardiac medications will be required within the 7 to 10 day period - rarely is the clinician both lucky and intelligent enough to pick the right doses and types of medications after the initial evaluation for CHF. Physical examination, packed cell volume, total proteins, blood pressure, follow-up thoracic radiographs, follow-up electrocardiography, and historical reports from the owner are all useful in trying to assess response to therapies. The author has made it a point to talk to owners about the anticipated need for alteration of the types of medications in an attempt to prevent clients from getting discouraged about how their animal is responding to medications. In many instances, the doses or types of medications need to be adjusted at the time of this initial recheck and a subsequent visit 7 to 10 days later should be scheduled. The next recheck visit should be scheduled for 2 to 3 months and at that time a physical examination with chemistry profile should be performed. Finally, 6 months after initial diagnosis the author recommends a follow up examination with echocardiogram to search for changes in the appearance of the heart or other alterations which might dictate a need for change in therapy. Feline Heart Disease Cardiac disease, common in cats, often leads to congestive heart failure (CHF), arterial thromboembolism (ATE), syncope, or sudden death. Many affected cats show no outward evidence of cardiac disease until one of these major crises has developed. The physical examination can play a vital role in asymptomatic cats as the first evidence of heart disease is often a soft cardiac murmur or a transient gallop. Given the severe clinical consequences of cardiac disease in cats, the author is an advocate of pursuing diagnostic testing for all cats with auscultatory abnormalities, cardiac arrhythmias, or a history of open mouth breathing / prior unexplained respiratory distress. Congenital heart disease, uncommon in the elderly cat, can still result in clinical signs later in life. For example, some cats with mitral valve malformation will live for many years before becoming symptomatic. Cardiac diseases that are more common in the geriatric cat include hypertrophy, restrictive, and dilated cardiomyopathy, systemic hypertension, myocarditis, and arterial thromboembolism. Cats with dyspnea following administration of fluids and those with dyspnea following anesthesia should be considered as prime candidates to have cardiac disease as a cause of the respiratory distress. Myocarditis has been reported in cats, however this is a difficult diagnosis to confirm antemortem, and it is unclear whether specific anti-inflammatory therapy improves the outcome in affected cats. In some areas of the country, heartworm disease is a common cause of cardiopulmonary signs in cats. Hypertrophic Cardiomyopathy Hypertrophic cardiomyopathy is the most common form of feline heart disease. Affected cats have concentric or asymmetric left ventricular hypertrophy without identifiable cause. While the cause of HCM in the cat has not been conclusively identified, there is good evidence to suggest that an abnormality in the genes encoding for sacromeric proteins is the cause in at least some cats. Molecular studies have determined that the genetic alterations that cause hypertrophic cardiomyopathy in humans include mutations in the genes that encode for several proteins in the sarcomere. These include mutations for ß-myosin heavy-chain, cardiac troponin T, -tropomyosin, myosin binding protein C and myosin light chains. The formation of these abnormal myocardial proteins leads to the inappropriate ventricular hypertrophy in affected individuals. A genetic cause is suspected based on breeding studies on a colony of Maine coon cats and on other work done with American shorthair cats and Persian cats. Asymmetric hypertrophy involving either the interventricular septum or the left ventricular free wall is identified in some cases, although the former is more common and problematic due to the development of systolic anterior motion of the mitral valve and secondary mitral regurgitation. Left atrial enlargement is usually evident, and variable right heart enlargement or hypertrophy may develop over time. In cases with profound hypertrophy of the interventricular septum and narrowing of the left ventricular outflow tract, the anterior mitral valve leaflet may become thickened. Hypertrophic cardiomyopathy can negatively impact cardiac performance through a number of mechanisms. Classically, the hypertrophy of the left ventricle leads to a small left ventricular internal dimension, and this impedes diastolic filling. The hypertrophied muscle can become stiff, and the fibrous tissue replacement seen in some cats can contribute to the impediment to diastolic filling. Tachycardia further compromises diastolic function by limiting the time available for coronary blood flow and myocardial perfusion. Catecholamine stimulation causes tachycardia and can further impede diastolic filling. The resulting compromise in diastolic filling results in elevations of left ventricular diastolic pressure, leading to a rise in left atrial filling pressures and eventually the development of left-sided congestive heart failure with pulmonary edema. In some cats, chronic elevation of left atrial pressure can be transmitted back through the pulmonary vascular circuit and can lead to pulmonary hypertension with eventual biventricular heart failure, manifest as pleural effusion with left atrial enlargement and milder pulmonary edema. Intravenous or subcutaneous fluids, long acting corticosteroids, and megestrol acetate can precipitate congestive heart failure in previously asymptomatic cats. Historical and Physical Examination Findings - Clinical signs in cats with congestive heart failure often include lethargy, hiding, reluctance to interact with the owner, and anorexia. Many owners do not recognize tachypnea, dyspnea or respiratory distress until it is at an advanced stage. Coughing occurs in some cats with pleural effusion but is an uncommon sign of CHF in the cat. Syncope occasionally occurs; many cats with CHF have anorexia and/or an episode of vomiting just prior to presentation. Weight loss in infrequently documented in cats with CHF. The physical examination can be normal in up to 30% of cats with HCM. During the course of routine examination a cardiac murmur (esp. near the sternal border) and/or cardiac gallops are often identified in 60-70% of affected cats. Physical exam findings can include increased respiratory rate and effort, loud pulmonary crackles (pulmonary edema), lung sounds may be muffled ventrally (pleural effusion), and jugular vein distension or hepatomegaly (esp. in cats with pleural effusion). Arterial pulses may be normal or weak, mucous membrane color may be normal or somewhat cyanotic, and capillary refill time may be delayed. A prominent cardiac apex beat is often noted on the left side of the chest. Hypothermia is common in cats with CHF and the heart rate in these cats may seem inappropriately low. Arterial thromboembolism to the rear legs results in the acute onset of posterior paresis or paralysis. Most cats cannot use their rear limbs and vocalize, presumably as a result of pain. The pulses are usually absent to both rear legs, although there may be reduced flow or weak pulses in only one limb. The nail beds of the affected limb(s) are cyanotic when compared to the nail beds of the normal limbs. The affected limbs are usually colder than the normal limbs. The gastrocnemius muscles are usually firm in the affected rear limb(s). Most cats retain the ability to move their tail and retain anal tone, and many retain some ability to flex their hip. Diagnostic Testing in Cats with HCM - The electrocardiogram can be normal. Sinus tachycardia is common; however sinus bradycardia is often seen in hypothermic cats with CHF. Deep S waves in lead II signal the presence of an axis shift, which is usually a left axis shift or a left anterior fascicular block. Many arrhythmias can be seen including ventricular arrhythmias, supraventricular tachycardia, atrial fibrillation and atrioventricular block. Cardiomegaly is identified on the thoracic radiographs of most cats with moderate to severe hypertrophic cardiomyopathy and left atrial enlargement, however this finding is not consistent in cats with milder forms of the disease. The classic finding of biatrial enlargement, or a valentine-shaped heart on the dorsoventral (DV) or ventrodorsal (VD) view, is present in some affected cats, but can also be seen in cats with other forms of cardiomyopathy. Most cats with significant left atrial enlargement will also have enlargement of both pulmonary artery and vein on the DV view. On the lateral view, a bulge is often noted on the caudodorsal aspect of the cardiac silhouette and cats with chronic left atrial enlargement often have a tortuous pulmonary vein returning to the left atrium from the caudal lung lobes. Pulmonary edema can be initially manifested as an increased interstitial pattern in the lungs that coalesces into in alveolar pattern as CHF worsens. In many cats this radiographic pattern develops ventrally or is distributed into multifocal, patchy areas of edema rather than in the classic perihilar regions. Pleural effusion can be seen in association with hepatomegaly and enlargement of the caudal vena cava. Classic echocardiographic findings seen in cats with HCM include hypertrophy of the interventricular septum and left ventricular wall (<0.55 to 0.6 cm in diastole in normal cats). Additionally, the systolic dimensions of the interventricular septum and left ventricular free wall are typically greater than 0.9 cm in affected cats. The earliest indicator of hypertrophic cardiomyopathy may be hypertrophy of the papillary muscles. Left ventricular outflow obstruction often occurs due to septal hypertrophy. The thickened septal tissue protrudes into the outflow tract, and turbulent blood flow can be identified in the left ventricular outflow tract or proximal aorta. Doppler studies often identify increased aortic flow velocity indicating a significant transvalvular pressure gradient resulting from the outflow tract obstruction. Systolic anterior motion of the mitral valve results from the previously described motion of the septum into the outflow tract during systole. In many of these cases, when color flow Doppler is performed, there is a distinct jet of mitral regurgitation which travels above the surface of the posterior mitral valve leaflet towards the distal wall of the left atrium. Significant left atrial enlargement is often present. In cats with long standing left atrial enlargement and secondary pulmonary hypertension, the pulmonary artery is often enlarged and bigger than the aorta and these cats often have accompanying right-sided heart failure. Pericardial effusion resulting from congestive heart failure may be identified in some cats; however, pericardial effusion infrequently results in cardiac tamponade. Thrombus formation can be identified echocardiographically in some cats (esp. in the left auricular appendage) and swirling, spontaneous echo contrast or "smoke" in the left atrium is also judged to be a marker of a cat at increased risk for arterial thromboembolism. Clinical pathology and ancillary testing can be helpful to exclude other disease which can mimic hypertrophic cardiomyopathy such as systemic hypertension and hyperthyroidism. Thyroid testing should be performed on all cats with heart disease that are six years of age or older. Systemic arterial hypertension results in secondary concentric left ventricular hypertrophy so a normal arterial blood pressure reading should be obtained to exclude a diagnosis of systemic hypertension. A complete blood count is rarely helpful. The serum biochemistry profile is usually normal in the asymptomatic cat. Stress hyperglycemia, mild hepatic enzyme elevations due to chronic passive congestion, and prerenal azotemia may occur. Prerenal azotemia is more common in cats that have been treated with diuretics. Prerenal azotemia, metabolic alkalosis, hyponatremia, hypokalemia, hypochloremia, and hypomagnesemia can all result from high dose furosemide therapy. Treatment of Cats with HCM - Treatment is directed toward heart rate reduction, management of congestive heart failure, and interventions to prevent or treat arterial thromboembolism. Drugs that can help to reduce heart rate and thereby improve diastolic cardiac function include diltiazem and beta-blockers like atenolol. Congestive heart failure is often managed with a combination of diuretics such as furosemide and an Angiotensin-converting enzyme inhibitor. Advanced heart failure sometimes responds well to the addition of spironolactone with or without hydrochlorothiazide. Thoracocentesis should be performed on any cat with a moderate or large volume of pleural effusion. Dietary sodium restriction is recommended to the owner. Once heart failure develops, feeding a moderate to severely restricted sodium diet is more important. Finally, aspirin, clopidogrel, dalteparin or warfarin can be used in selected cases to try to prevent arterial thromboembolism. Dilated Cardiomyopathy Dilated cardiomyopathy (DCM) is now one of the least common forms of heart disease in the cat. Virtually all cats with dilated cardiomyopathy have developed clinical signs of heart disease by the time of presentation such as CHF or ATE. The history should be checked to determine whether the cat has been eating a diet that might be considered either vegetarian or otherwise unbalanced and subject to reduced dietary taurine intake. A key distinguishing feature of most cats with myocardial failure, especially those with DCM, is the presence of a very loud S3 gallop. Many cats also have either a soft murmur or a cardiac arrhythmia. Cats with DCM and CHF often have developed appreciable pleural effusion on thoracic radiographs. The characteristic echo findings of dilation of all 4 cardiac chambers with reduced left ventricular systolic function and thinning of the walls of the ventricles help to establish the definitive diagnosis. Unfortunately, the majority of cats with DCM have myocardial failure that is not a result of dietary taurine deficiency. Nonetheless, plasma and whole blood measurement of taurine is indicated as the expected result from taurine supplementation should be known as soon as possible. It can be difficult to administer medications, and if taurine levels are perfectly normal then the owner can be advised to stop taurine administration, especially if administration of taurine proves problematic. The outcome is often related to the presence or absence of taurine deficiency. Cats with low plasma and whole blood taurine levels often respond well, if they can be made to survive for the first 2 weeks. Cats with normal taurine concentrations often respond poorly to medical therapy and may only live for a short time (days to months). Restrictive Cardiomyopathy and Intergrade Forms of Cardiomyopathy There is a lack of uniform use of the terms restrictive cardiomyopathy, intergrade cardiomyopathy, and intermediate forms of cardiomyopathy. Some authors feel that most of the cats that do not fulfill the classic criteria for HCM or DCM should be classified as restrictive cardiomyopathy, while others reserve this title for cases with known restrictive physiology (via Doppler studies) or those with restrictive physiology and documented endomyocardial fibrosis. From an etiologic, scientific and classification perspective the distinction might be critical, however there are limited studies to document whether cats with one set of echocardiographic or physiologic patterns either respond better to certain interventions or have different prognostic criteria. It is the author's opinion that the clinical response in most of these cases is not determined most tightly by the name applied but by the clinical manifestations of the disease such as the presence or absence of CHF, serious arrhythmia or ATE and the size of the left atrium. It is also the author's opinion that many cats originally documented to have HCM with progress to having left ventricular dilation with reduced contractile function and thinning of the walls, findings normally diagnosed as restrictive of intermediate cardiomyopathy by most echocardiographers. For these reasons, these disorders will be considered as a single entity termed RCM/ICM. History and Physical Examination Findings The majority of cats with RCM/ICM live for many years before clinical signs are manifest. Some cats that are asymptomatic at rest will have a history of reduced exercise capacity or open mouth breathing following exertion. In cats with congestive heart failure, the clinical signs of increased respiratory rate and effort are often missed by the owners until they are severe, so the initial manifestations of cardiac disease can be lethargy, weakness, reduced interaction with people or housemates, infrequent vomiting and reduced appetite. Overt respiratory distress often follows, usually within 1-3 days, and increased respiratory rate and effort are often magnified on exam due to the stress of transportation to the hospital and the new environment. Abrupt onset of posterior paresis, vocalization and open mouth breathing are typical in cats with ATE. Physical examination findings that are common to cats with RCM/ICM include a cardiac murmur, cardiac gallop, or cardiac arrhythmia, although up to 1/3 of cats with significant heart disease lack a murmur or gallop. Murmurs in cats are often loudest at the left or right sternal border, and in many cats the murmur will be missed if this area is not examined closely. Cardiac gallops are heard best in most cats at the left cardiac apex with the bell of the stethoscope. A very loud cardiac gallop is often associated with reduced myocardial function on echo. Cats with isolated left heart failure and pulmonary edema usually develop loud pulmonary crackles, often with severe respiratory distress. In cats with biventricular heart failure (usually the result of longstanding left heart failure) respiratory distress is often accompanied by jugular vein distention, hepatomegaly, and muffled lung sounds ventrally due to pleural and/or pericardial effusion. A small volume ascites may be present in cats with biventricular heart failure; however marked cardiogenic ascites in the cat is usually due to isolated right heart disease. Cats with CHF are often hypothermic, mucous membrane color may be cyanotic, capillary refill time may be delayed. They often appear to be dehydrated based on skin turgor despite the fact that they clearly have excessive circulating intravascular volume based on the presence of pulmonary edema, pleural effusion, and jugular vein distention. Weak arterial pulses are common once congestive signs develop, and cats with low-output left heart failure often have very weak arterial pulses. In cats with ATE, arterial pulses are usually absent to the affected limb(s), the nail beds are cyanotic, the limb is cool, and there is overt limb dysfunction. Pain is usually evident in the first 12 to 48 hours after the onset of ATE. The gastrocnemius muscles often are firm in cats with acute ATE to the rear limbs. CHF develops in a significant proportion of cats within 72 hours of the onset of ATE. Diagnostic Testing in Cats with RCM/ICM The ECG rarely provides a specific diagnosis, yet electrocardiography is still useful to identify arrhythmias and to provide supportive evidence for heart disease. Cardiac arrhythmias are common in cats with heart disease and sometimes are the cause or a major contributing factor to the development of CHF, syncope, or sudden death. Thoracic radiographs are indicated to search for evidence of CHF, to differentiate heart disease from respiratory or heartworm disease, and to provide supportive evidence of cardiomegaly in cats with murmurs, gallops, or arrhythmias. Generalized cardiomegaly is usually the rule, and some cats with RCM/ICM have the classic valentine shaped heart on the dorsoventral view. Pleural effusion, pulmonary edema, enlargement of the caudal vena cava and hepatomegaly can be seen in cats with CHF. Cats with RCM/ICM sometimes develop pericardial effusion and this can result in severe enlargement and rounding of the cardiac silhouette. Blood pressure should be routinely measured in cats with heart disease. Use of the Doppler measuring device is probably the most accurate in awake cats. Abnormalities on a biochemistry profile can include mild increased in liver enzymes, especially AST or ALT, resulting from chronic passive congestion of the liver, stress hyperglycemia, and azotemia. Azotemia is often pre renal in origin. Plasma taurine levels should be assessed in cats with evidence of myocardial failure or thinned LV walls. Cats over 6 years of age with concentric LV hypertrophy should be tested for hyperthyroidism, but one should keep in mind that cats with advanced heart disease can have low T4 levels (below the normal range) due to euthyroid sick syndrome. Echocardiography is the best tool to distinguish RCM/ICM from other forms of feline heart disease. In addition, echocardiography is a useful adjunct to other clinical parameters in estimating the severity of disease. Thrombus formation can be identified echocardiographically in some cats (esp. in the left auricular appendage) and swirling, spontaneous echo contrast or "smoke" in the left atrium is also judged to be a marker of a cat at increased risk for arterial thromboembolism. In some cats, a more specific diagnosis or description can be made based on the echocardiographic findings. In the case of endocardial restrictive cardiomyopathy, left ventricular endocardial or subendocardial fibrosis is present, sometimes with concurrent inflammation and necrosis in the underlying myocardial tissue. The LV endocardial fibrosis can be identified as hyperechoic tissue, the papillary muscle appear abnormal, and marked left atrial enlargement results from the impaired diastolic filling of the LV. Contractility can also be impaired. Cats with myocardial restrictive cardiomyopathy have restrictive physiology on Doppler studies of mitral and pulmonary venous inflow, despite the fact that they lack clear endocardial restrictive disease. Finally, some cats develop excessive left ventricular moderator bands and this has been reported to be a distinct form of cardiomyopathy. In the author's experience, many cats with a variety of forms of heart disease have increased numbers of moderator bands and therefore the role that these bands of tissue play in restrictive disease is uncertain. The clinical signs can be difficult to distinguish from other forms of feline cardiomyopathy, but the bands of endocardial tissue are often apparent on echocardiographic examination. Cardiac Medications for Cats Drugs to Slow the Heart Rate Diltiazem Mechanism of action: Calcium channel blocker Main clinical uses in cats: Hypertrophic cardiomyopathy to slow heart rate and thereby improve diastolic filling, systemic hypertension, supraventricular arrhythmias. Coronary artery dilation may be another beneficial effect of the drug in cats with HCM. Dosing information: Diltiazem has a very short half-life and duration of action. In order to be present in the blood stream for enough time to be useful it must be given 3 times a day or in a sustained release formulation. The proposed dose (0.5 to 1.5 mg/kg q 8 hr) usually translates into a starting dose of one quarter of a 30 mg tablet three times per day, and this dose can be increased up to 15 mg PO q 8 hr. To limit non-compliance, an extended-release formulation of diltiazem (Dilacor or generic) is often preferred. Dilacor is available in 240 mg capsules, and inside each 240 mg capsule there are four 60 mg tablets. These 60 mg tablets can be cut in half for a dose of 30 mg. This 30 mg/cat dose is administered either q 12 hr or q 24 hr. Cardizem CD can also be formulated by a compounding pharmacy and then administered at a dose of 10 mg/kg q 24 H. Side effects: The most common side effects result from excessive blockade of calcium channels. These side effects include systemic hypotension, myocardial depression due to the negative inotropic effects of the drug, and bradycardia that can be either sinus bradycardia or AV block. These are often manifest in the clinical signs of weakness, lethargy, inability to rise, syncope, or anorexia and may be most profound 1 to 4 hours after administration of the drug. Side effects are more commonly seen in older cats when multiple cardiac medications with overlapping hypotensive actions are used. Diltiazem is relatively contraindicated in geriatric cats with AV block. Atenolol and Propranolol Mechanism of action: Atenolol and propranolol are beta-receptor blocking (ß blockers) drugs and act to blunt the effects of adrenergic stimulation. Atenolol is a hydrophilic, relatively ß-1 selective, meaning that it blocks the beta receptors on the heart. Propranolol is a non-selective beta-blocker, meaning that both ß-1 and ß-2 receptors are blocked. Main clinical uses in cats: Beta-blockers can be used for management of hypertrophic cardiomyopathy, systemic hypertension, and various cardiac arrhythmias including supraventricular and ventricular tachycardias. These drugs reduce heart rate and myocardial oxygen demand. By decreasing inotropic state, ß blockers may reduce the left ventricular outflow gradient in some cats with systolic anterior motion of the mitral valve. While beta-blockers have been used in humans to help manage congestive heart failure, the drugs found to be effective in prolonging survival (carvedilol, metoprolol) have not been well studied in cats. In general, beta-blocker use in cats is intended to slow heart rate, before the onset of CHF, and in fact one study (unpublished except as an abstract) suggested that atenolol use might be associated with a reduced survival in cats once CHF has developed. Dosing information: In general, when using ß blockers, the initial low dose is selected and the dose is titrated upward until the desired effect of heart rate reduction or arrhythmia control is achieved. Due to the short half-life of propranolol in cats (T ½ = 0.49 hours), this drug should usually be given at least three times per day. A low starting dose is initiated (2.5 mg q 8 h) and the dose is titrated upward to as high as 10 mg three times a day. Atenolol has been used successfully by some authors using a once a day dosing schedule, however pharmacologic studies and heart rate monitoring indicate that twice a day dosing is preferable. Pharmacologic testing in normal cats defined the half-life of atenolol as approximately 3.5 hours and the duration of heart rate reduction as at least 12 hours. Based on this information, it appears that twice a day dosing of atenolol is preferable in cats. In most cats, an initial dose of 6.25 mg per cat q 24 hours is titrated up to as high as 12.5 mg per cat q 12 hours if adequate therapeutic response is not achieved at the lower dose. Some pharmacies are now formulating transcutaneous methods for drug delivery, however these have not been well studied and the efficacy and drug absorption properties of the various formulations remains to be established - preliminary work suggests that these formulations are not absorbed well enough to be effective. Side effects: Side effects usually are a result of excessive beta-blockade and include hypotension, bradycardia or AV block, and the development of CHF due to negative inotropic effects. These signs are often manifest as weakness, lethargy, reduced energy, or anorexia. The drug should not be used in geriatric cats with advanced AV block. Propranolol is usually not recommended for cats with active or recent ATE due to loss of beta-2 receptor vasodilatative effects. Drugs for CHF Angiotensin-converting enzyme inhibitors (enalapril, lisinopril, benazapril, etc.) Mechanism of action: Inhibition of angiotensin-converting enzyme, blocking the formation of angiotensin II. This leads to reduced vasoconstriction so less afterload, reduced myocardial fibrosis and hypertrophy (in some animal models), and reduced release of spironolactone thereby limiting fluid retention by the kidney. Main clinical uses in cats: Angiotensin converting enzyme (ACE) inhibition is indicated in cats with congestive heart failure, including cats with HCM and CHF. The author also uses these drugs in cats with moderate to severe left atrial enlargement. The author has had mixed results in cats with isolated right heart failure and marked ascites. Dosing information: Enalapril is often used at doses between 0.5 and 0.75 mg/kg once or twice a day - 2.5 mg q 24 hours is usually a good starting dose for the average sized cat with CHF. Lisinopril can be dosed at 0.5 mg/kg once a day. Benazapril can be dosed at 0.25 to 0.5 mg/kg q 12-24 hours. The dose may need to be reduced in cats with azotemia, and it is often a good idea to delay initiation of an ACE inhibitor until hypotension has resolved (usually this means waiting for 1-3 days after using high doses of furosemide to treat severe pulmonary edema). Side effects: Side effects of ACE inhibitors can include dehydration, azotemia, weakness, hypotension, and anorexia. Azotemia is more likely to occur in cats that are dehydrated, those that have received high doses of diuretics, and those with pre-existing renal dysfunction. In most cases, a reduction in diuretic dose will improve renal function and restore blood pressure to normal. Reassessment of renal function and electrolytes in indicated 7 to 10 days after starting an ACE inhibitor and every 3-6 months thereafter. Furosemide Mechanism of action: Loop diuretic which blocks chloride absorption in the ascending limb of the loop of Henle to create a profound diuresis, especially at high doses. Main clinical uses in cats: Furosemide is the diuretic that forms the backbone of therapy of congestive heart failure in cats. Dosing information: In cases of acute and severe congestive heart failure with pulmonary edema, high doses of furosemide are needed (4 mg/kg IV q 1 hour). For chronic management of heart failure, a much lower dose of furosemide is used. In many cats, furosemide administration at 6.25 mg per cat every other day is sufficient to control signs of congestion, and the vast majority of cats can be effectively treated with 6.25 mg per cat twice a day or less. Cats with pleural effusion seem more likely to require high furosemide doses during chronic therapy. When combined with an angiotensin-converting enzyme inhibitor, a low dose of furosemide is essential to avoid side effects. Very old cats that have lost muscle mass and are azotemic are particularly likely to have side effects and a lower starting dose is recommended for these cases. Side effects: Common side effects result from overzealous use of furosemide, often in the setting of severe heart failure. Side effects can include hypotension, azotemia, hypochloremia, hyponatremia, hypokalemia, hypomagnesemia, metabolic alkalosis, vomiting and pancreatitis. Spironolactone Mechanism of action: Aldosterone receptor blockade leads to reduced renal retention of sodium and water. Main clinical uses in cats: Used as an "add on" diuretic to furosemide in cats with refractory heart failure. This is a particularly useful drug in cats with recurrent pleural effusion. The author often combines spironolactone and hydrochorothiazide (the combined product is called aldactazide) in this setting, the dose of furosemide is continued, although in some cats a reduced dose of furosemide is possible in 3 to 10 days after starting spironolactone. There is renewed enthusiasm for the drug due to the improved survival in human CHF treated with aldosterone receptor blockers and the greater recognition that the drug might favorably alter the remodeling process and lead to reduced myocardial fibrosis. Dosing information: 1-2 mg/kg q 24 hours initially; increase to 2 mg/kg q 12 hours of pleural effusion or ascites require additional centesis. Side effects: Anorexia and lethargy are the most common side effects, especially when the dose rises toward 4 mg/kg q 12 hrs. The drug can cause vomiting and therefore it has been advised to be given with food. Hyperkalemia is one of the more severe side effects, and so serial electrolyte measurement is strongly recommended. Nitroglycerine Mechanism of action: Acts as a nitric oxide (NO) donor to create vasodilatation. The venous vasodilatation is thought to account for at least some of the beneficial effect that might occur in acute CHF. Arterial vasodilatation and coronary artery dilation might also contribute to either clinical benefit or side effects. Main clinical uses in cats: Most often used in the setting of acute severe pulmonary edema, for 1-3 days, until other medications can be initiated. Dosing information: 1/8 to 1/4" applied topically, using gloves, q 6 to 8 hours. Side effects: The most common side effects are hypotension, weakness, lethargy, and presumably hypotension (a common complication in humans with CHF). Digoxin Mechanism of action: Digoxin blocks the sodium-potassium-ATPase pump and via this mechanism the drug is a modest positive inotrope. The drug also has vagomimietic effects to slow heart rate and slow AV conduction. Main clinical uses in cats: Digoxin can be used in cats with rapid supraventricular arrhythmias and atrial fibrillation. It can also be used as a drug to help manage congestive heart failure. Dosing information: The author rarely sees geriatric cats with clear clinical indication for digoxin administration. When used, the dose should be reduced for cats with reduced muscle mass. A starting dose of ¼ or a 0.125 mg tablet every other day is a reasonably starting dose for most elderly cats, although a lower dose might be appropriate for cats with reduced skeletal muscle mass. Side effects: The most common side effects are a result of digitalis intoxication leading to clinical signs of anorexia, vomiting, depression, and cardiac arrhythmias. Toxicity is more common in cats with azotemia as this leads to reduced renal elimination of digoxin. The initial dose should be reduced in geriatric cats for any number of reasons including concurrent renal failure, loss of skeletal muscle mass, large volume effusion, and anorexia. A post-pill digoxin blood sample, obtained 8 to 12 hours after dosing, can be used to help guide dose adjustments. The author recommends a post-pill blood sample in the 0.8 to 1.2 ng/ml range. Drugs for Arterial Thromboembolism ATE is a common complication of cardiomyopathy, occurring in 20-40% of cats. The thrombus may develop in either the left ventricle or the left atrium, however, a left atrial origin is most common. Unfractionated heparin Mechanism of action: Combines with antithrombin to inactivate certain activated clotting factors (IIa, IXa, Xa, XIa, and XIIa). Main clinical uses in cats: Short term administration to cats with recent arterial thromboembolism or in cats where thrombus is seen in a cardiac chamber on echocardiography. Heparin is the drug most commonly used to prevent further enlargement of the thrombus once ATE has developed. Dosing information: While several doses of heparin have been proposed, it is the author's opinion that if heparin is to be used without thrombolytic drugs, high doses should be used (200-300 IU/kg q 6-8 hours). Heparin can be administered subcutaneously or intravenously. An initial intravenous bolus of heparin can be followed by a continuous rate infusion of heparin (10 to 25 u/kg/hr) or subcutaneous administration. Ideally, a baseline partial thromboplastin time is obtained and serial partial thromboplastin times obtained q 24 hours. Heparin is usually continued until the time of hospital discharge or until coumadin therapy has been initiated for at least 48 hours. Side effects: Side effects are usually limited to bleeding with excessive dosing or in cases with pre-existing coagulopathy. Low Molecular Weight Heparins (Dalteparin and Enoxaparin) Mechanism of action: Major action is to inactivate clotting factor Xa. Main clinical uses in cats: As a preventative for ATE or PTE. Dosing information: Low molecular weight heparin has been recently used as another drug to prevent thrombus formation. We have used dalteparin (Fragmin; 100U/kg) subcutaneously once or twice a day, but the drug can be expensive to use on a long term basis. Side effects: Bleeding is an uncommon side effect, injection site pain is uncommon. Clopidigrel Mechanism of action: Antiplatelet drug from the thienopyridine family. Main clinical uses in cats: May be useful as an antithrombotic drug to prevent ATE Dosing information: 18.75 mg/cat SID Side effects: Insufficient experience to advocate routine use; bleeding complications are possible Warfarin Mechanism of action: Coumadin, or warfarin, works by blocking the formation of vitamin K dependent clotting factors II, VII, IX and X. Main clinical uses in cats: By titrating the dose of warfarin, a degree of anticoagulation can be achieved in an attempt to reduce thrombus formation. Coumadin use has been advocated for cats with severe left atrial enlargement and in those with prior thromboembolic disease. Frequent serial testing of the prothrombin time is a requirement for used of the drug, usually every 3 to 5 days for the first 3 to 6 weeks of therapy. Dosing information: 0.05 to 0.1 mg/kg/day as initial starting dose. Give with heparin for the first 2-3 days. Side effects: Bleeding complications are the most frequent side effect. Bleeding is usually internal, rather than external; signs of intoxication include lethargy, anorexia, reduced interactions with owners, and toxic clinical signs are usually present for only a short period of time (hours to 1-2 days) before life-threatening hemorrhage occurs. Aspirin Mechanism of action: Aspirin inhibits the cyclo-oxygenase pathway for thromboxane synthesis, thereby reducing platelet aggregation irreversibly for the life of the platelet. Main clinical uses in cats: Aspirin may be used in an attempt to reduce the occurrence of thromboembolism; however it will certainly not prevent this complication in all cats. If aspirin is effective it probably results in a modest reduction (5-10% decrease) in the incidence of ATE. The author recommends aspirin therapy for cats judged to have at least moderate left atrial enlargement, if they tolerate the drug. The drug is usually not used in cats with renal dysfunction, and history of frequent intermittent vomiting, and the drug is usually stopped by the author in geriatric cats who develop azotemia while taking the drug. Dosing information: (70-81 mg/cat) q 48-72 hours; some authors advocate a lower dose than this. Side effects: Aspirin must be used in low dose as hepatic metabolism is limited. Vomiting on the day of administration is the most common side effect. Chronic use could conceivably contribute to renal insufficiency. Thrombolytic drugs Mechanism of action: Streptokinase, urokinase and tissue plasminogen activator are thrombolytic drug that activate plasminogen, leading to the formation of plasmin, which degrades fibrin into fibrin split products. This action can lead to dissolution of the thrombus and restoration of arterial pulses and blood flow to affected tissues Main clinical uses in cats: ATE in cats; if given should be administered within the first 6 hours of clinical signs as it is suspected that the earlier use is the best. Dosing information: Streptokinase at 90,000 U/cat as a CRI over 30 minutes, then 45,000 U/cat/hr for 3 to 24 hours. Side effects: The reported incidence of side effects is high and includes sudden death, bleeding complications, and severe hyperkalemia with metabolic acidosis which follow limb reperfusion. Drugs for Cardiac Arrhythmias Ventricular arrhythmias are common in cats with advanced heart disease, however therapy is only usually required for cats with sustained ventricular tachycardia (> 30 seconds) and in cats with frequent ventricular ectopy and syncope or other clinical signs resulting from arrhythmia. Atrial fibrillation is usually seen in cats with marked to severe left atrial enlargement. Depending upon the heart rate and the underlying form of cardiac disease, atrial fibrillation may benefit from treatment with digoxin, diltiazem, or a beta-blocker. Diltiazem and Atenolol - See Above Procainamide Mechanism of action: Class IA antiarrhythmic drug, sodium entry blocker Main clinical uses in cats: Ventricular tachycardia Dosing information: 60 mg/cat q 8 hrs. Side effects: Side effects can include vomiting, anorexia, proarrhythmic effect (arrhythmia gets worse), and a variety if hematological or immune complications (other species). Experience in cats is somewhat limited. Sotalol Mechanism of action: Main actions are as a class III antiarrhythmic drug (prolongs action potential duration) and as a class II antiarrhythmic (beta-blocker properties). Main clinical uses in cats: Used as an antiarrhythmic for either ventricular or supraventricular arrhythmias. Dosing information: 10-20 mg/cat q 12 hours; start at lower dose Side effects: Most common side effects include weakness and lethargy, possibly due to hypotension or bradycardia. There is somewhat limited clinical experience with this drug in cats. Canine Dilated Cardiomyopathy Cardiomyopathy can be defined as diseases of myocardial structure or function that are independent of valvular disease, congenital heart disease, pericardial disease, and pulmonary or systemic hypertensive disorders. In common usage, the term cardiomyopathy suggests that the underlying cause for the myocardial disease is unknown. If the etiology is unknown, the cardiomyopathy is classified as primary (e.g., idiopathic dilated cardiomyopathy). If the cause can be determined (i.e., toxic as in doxorubicin, inflammatory as post viral myocarditis, nutritional, or ischemic) then the disease is classified as secondary cardiomyopathy (doxorubicin cardiomyopathy = doxorubicin-induced cardiotoxicity). Dilated cardiomyopathy (DCM) is the second most common cause of congestive heart failure in the dog. Although congestive heart failure is the most commonly recognized complication of DCM on cardiac performance, cardiac arrhythmias, episodic weakness, syncope, thromboembolism and sudden death are other recognized clinical manifestations. Pathology - Dilated cardiomyopathy results in severe left and right ventricular and atrial enlargement (dilation of all 4 chambers) with modest thinning of the ventricular free walls and septum. The papillary muscles appear flattened, and the AV valve circumference increases due to cardiac dilation. Microscopic findings include mild endocardial fibrosis, mild interstitial fibrosis and edema, and focal areas of myocytolysis with a mild mononuclear infiltrate. Attenuated wavy fibers (i.e., myocardial cells < 6 um in diameter with a wavy appearance) have been described in dogs with DCM. Boxers with cardiomyopathy often develop fibrofatty replacement of the myocardium in the right ventricle and outflow tract and to a lesser degree the left ventricle. Pathophysiology - DCM results in myocardial systolic dysfunction, although most cases also have significant diastolic dysfunction as well. Systolic pump failure leads to reduced cardiac output and results in activation of the neuroendocrine compensatory responses (sympathetic nervous system, renin-angiotensin system, etc.). Dilated cardiomyopathy leads to progressive cardiac dilation and AV valve dilation can lead to mitral or tricuspid valve incompetence. Congestive heart failure eventually results, although there seem to be differences in whether the predominant clinical manifestation will be cardiac arrhythmias, left or right heart failure. Etiology - The disease is almost certainly a highly heterogenous condition. Clinical findings typical of DCM can be seen in a variety of other known causes of heart diseases in their advanced or late stages. Thus, the failure of systolic contraction can be viewed as the end result of any number of causes of myocardial cell damage or dysfunction. The anatomic and/or biochemical basis for this functional failure has not been clearly defined in dogs, although many hypotheses exist. In people, genetic causes have been identified for many people with DCM. Abnormalities in various cytoskeletal proteins appear to be the causes of the disease. Examples of these proteins include dystrophin, metavinculin, vinculin, desmin, and other proteins that form the myocardial "skeleton" for the sarcomeric proteins. In Boxer dogs with arrhythmogenic right ventricular cardiomyopathy (ARVC) the defect is suspected to involve a genetic mutation of the ryanodine receptor. Alterations in energy metabolism also have been documented to cause DCM (i.e., abnormalities in Acyl-CoA dehydrogenase and mitochondrial transport and/or proteins). Taurine deficiency is a proven cause of DCM in the cat, and carnitine and taurine deficiency have been study as potential causes or contributors to the development of DCM in dogs. Myocardial (+/- plasma) carnitine deficiency has been described in some dogs (esp. Boxer, English bulldog, Cocker spaniel, +/- Doberman) with dilated cardiomyopathy. As some humans develop myocardial carnitine deficiency with severe CHF, it is unclear whether this finding represents a significant deficiency or is simply an end result of CHF with myocardial failure. In affected dogs, myocardial carnitine levels were increased following oral L-carnitine supplementation. In general, dogs with DCM and myocardial carnitine deficiency do not revert back to normal systolic function after supplementation with carnitine. Some affected dogs appear to demonstrate clinical improvement, but not cure, with oral carnitine supplementation. Taurine supplementation has also been documented, although there have been conflicting reports regarding the clear association of taurine deficiency and reversible DCM in dogs. Some dogs with DCM (esp. Cocker Spaniels) have been documented to have low plasma and whole blood taurine concentrations. It has been proposed that certain breeds of dogs, especially if fed certain lamb-based foods or high fiber foods, may develop plasma or whole blood taurine deficiency. Post-viral inflammation and myocarditis-induced DCM have also been proposed as etiologies for the syndrome. Signalment - Giant breed dogs such as Irish Wolfhound, Great Dane, St Bernard, Newfoundland, and German Shepherd Dogs are at risk. Doberman pinschers and Boxer are predisposed, and Cocker spaniels and Portuguese water dogs also have forms of the disease. Males predominate in many clinical surveys, although testing within a specific breed to search for frequency of DCM has sometimes failed to find a male predisposition. An age range from 0.2 14 years has been reported, although onset of clinical signs between 4 8 years of age is typical for most breeds. History - Common historical complaints include dyspnea, cough, syncope, weight loss, lethargy, exercise intolerance, abdominal distention, and anorexia. Clinical signs may appear acutely, although in retrospect many owner notice that the dog has been "slowing down" for several weeks. In the author's practice, cough in a mature large breed dog with a bronchial and interstitial pattern is rarely due to bronchitis and is often due to dilated cardiomyopathy with early heart failure. Physical examination - Physical examination can be normal in the early (occult) stage of the disease. Common auscultatory findings include a soft (II-III/VI) systolic murmur of mitral or tricuspid valve regurgitation and/or a cardiac gallop, typically an S3 gallop. When CHF is present findings can include dyspnea, pulmonary crackles, jugular vein distention, hepatosplenomegaly, ascites, weight loss, and diminished heart and/or lung sounds if pericardial and/or pleural effusion is present. Mucous membrane pallor or cyanosis may be noted and arterial pulses are often weak. Cardiac arrhythmias with pulse deficits are often noted on physical examination. Electrocardiography - The electrocardiogram can be normal, but some ECG abnormality is present in most animals. Common findings include evidence for left ventricular enlargement or biventricular enlargement, left atrial enlargement pattern (P mitrale), and conduction disturbances like left bundle branch block. Common arrhythmias include atrial fibrillation, supraventricular depolarizations and ventricular depolarizations. A left ventricular enlargement pattern is uncommon in Boxer cardiomyopathy. Thoracic radiographs - Generalized cardiomegaly is often present. Congestive heart failure can cause pulmonary venous distention and interstitial or alveolar pulmonary infiltrates (pulmonary edema). In some dogs, right heart failure or biventricular failure predominate and enlargement of the caudal vena cava, hepatomegaly, ascites, and/or pleural effusion are present. Echocardiography -Classic echocardiographic findings include left ventricular dilation with thinned walls and atrophied papillary muscles and markedly diminished LV contractility (reduce fractional shortening to less than 28%). There is reduced thickening of the IV septum and the LV free wall, left atrial enlargement, increased E point to septal separation on M mode, reduced aortic root motion, RV and RA dilation. Clinical pathology - Elevated BUN or creatinine (prerenal azotemia due to inadequate cardiac output, possibly diuretic/ACE inhibitor induced following initiation of therapy), elevated liver enzymes (chronic passive congestion), mild hypoproteinemia, and hypokalemia, hypochloremia, and metabolic alkalosis can be seen after high dose diuretic therapy. Treatment - The classic therapies include digoxin, diuretics (furosemide), ACE inhibitors (lisinopril, benazapril, enalapril), a reduced sodium diet, and exercise restriction. Anti arrhythmic medications are used as needed. Dogs with severe congestive heart failure and evidence of low cardiac output or cardiogenic shock may benefit from a constant rate infusion of dobutamine ± sodium nitroprusside for 2-3 days. Recent interest in successful use of beta-blockers in people with CHF and systolic dysfunction has lead some to initiate their use in dogs with DCM - CHF should be well controlled before any attempts are made to start beta-blockers in dogs with DCM. There has also been renewed interest in spironolactone. Taurine and/or carnitine therapy has been used in some cases, and there has also been great interest in used of other supplemental therapies such as coenzyme Q10. Canine Cardiomyopathy Syndromes - While all dogs with cardiomyopathy share some clinical findings, it appear that some breeds have specific clinical syndromes. The descriptions below will summarize how the various breeds might differ with respect to the clinical presentation and/or manifestation of DCM. Giant breed dilated cardiomyopathy - Giant breed dogs commonly have left or biventricular heart failure and one of the most common rhythm diagnoses is atrial fibrillation. Sudden death may also occur. Prognosis usually 6 months or less if CHF, possible 1-2 years if discovered early or if arrhythmia is the primary presenting problem. >Dilated cardiomyopathy in Irish Wolfhounds - Pleural effusion (often chylothorax) is usually the predominant clinical manifestation of CHF in this breed. Some cardiovascular abnormality was present in 50% of 632 dogs screened in one study. Fractional shortening was reduced to 20.7% in the largest study to date of dogs with CHF, and this value is somewhat higher than is seen in many dogs with advanced DCM and CHF. Atrial fibrillation was present in 55/66 (83.3%) of dogs. Abnormal QRS morphology also appears to be common in the breed. The disease can be slowly progressive. There is controversy as to whether Irish wolfhounds with atrial fibrillation and modest reductions in fractional shortening have DCM or "lone" atrial fibrillation - research by Vollmar indicates that most of these dogs will eventually progress to overt DCM. Dilated cardiomyopathy in Newfoundland dogs - Most dogs are middle age to older, although the disease has been reported in dogs as young as 3.5 months. Normal male dogs had a LVIDd <5.5cm and normal female dogs were < 5.0cm. It appears that some apparently normal Newfoundland dogs have a fractional shortening between 20 and 28%. Atrial fibrillation can develop, however sudden death might not be as common in this breed as other dogs with DCM. Refractory CHF was the most common cause for death or euthanasia in affected dogs. Doberman pinscher cardiomyopathy: For many years, it has been recognized that dilated cardiomyopathy is a common problem in Doberman Pinschers. While it was assumed that the disease progressed over some period of time, it was generally thought that, given the very short duration of clinical signs before development of congestive heart failure, in most dogs the disease progressed rather rapidly. Information from researchers at Guelph and the University of Georgia indicates that the disease is usually present for a significant period of time before any clinical signs are manifest, and this syndrome has been termed "occult cardiomyopathy." Many Doberman Pinschers have echocardiographic criteria indicative of early cardiomyopathy at a time when they are completely asymptomatic. Over a period of years, many of dogs with early evidence of DCM will develop overt disease. Criterion proposed to identify dogs with occult DCM included presence of ventricular arrhythmia or echocardiographic findings of a left ventricular internal dimension in diastole of greater than 4.6 cm or a left ventricular internal dimension in systole greater than 3.8 cm. It has been estimated that 45-63% of Doberman pinschers have occult DCM. The exact role each of these criteria (echocardiographic parameters and ventricular arrhythmias) should be used in making breeding recommendations to owners is unclear. At this point in time, the author recommends that any Doberman pinscher with ventricular arrhythmias, and those with LVIDD greater than 4.6 cm and LVIDS greater than 3.8 cm (esp. if concurrent low fractional shortening) be restrained from breeding. Some preliminary work has also indicated that early use of angiotensin-converting enzyme inhibitors in these dogs may slow the progression of cardiac disease and might prolong survival. It has been estimated that 40-50% of Doberman pinschers with DCM die suddenly. While bradyarrhythmias can cause sudden death, it is felt that sudden death in most Doberman pinschers results from ventricular arrhythmias/ventricular fibrillation. The age of presentation for clinical signs ranges from 2 15 years (6.5 years average). Thoracic radiographs may have primarily left atrial and left ventricular enlargement (vertebral heart size is helpful to establish cardiomegaly), pulmonary edema, and pleural effusion is less commonly present. Atrial fibrillation is common less frequently than other breeds with DCM, and when present this arrhythmia often is associated with a worse prognosis. Sinus rhythm with a left axis shift, wide QRS complex, or biventricular enlargement pattern is common. Ventricular arrhythmias often have a RBBB pattern (negative QRS in Lead II). Doberman Pinschers affected with DCM presented for syncope are at high risk for sudden death. Severe congestive heart failure can develop with pulmonary edema and concurrent signs of low-output CHF (hypothermia, cold limbs, pre-renal azotemia, mucous membrane pallor and slow CRT). Intravenous dobutamine (2.5 to 10 mg/kg/min CRI), with sodium nitroprusside (2 to 8 mcg/kg/min), administered for 24 to 72 hours, is helpful in some cases. Caution is advised to avoid excessive doses of furosemide, as this may result in hypovolemia, hypotension and azotemia. Caution is also advised with respect to use ACE inhibitors in animals with dehydration and/or azotemia. In selected dogs, we have had successes in long-term management using lisinopril (0.5 mg/kg q 12-24 hrs), low dose digoxin (0.125 mg/Doberman q 12 hr), metoprolol (12 to 25 mg/Doberman q 12 hr), and the lowest dose of furosemide necessary to control signs of congestive heart failure (ideally, 50 mg PO q 12 hr or less). Pimobendan, when readily available, should be a valuable adjunctive therapy for management of CHF in this breed. Nevertheless, the short-term outlook is very guarded, and survival beyond six months is generally considered exceptional once CHF is already present. Boxer cardiomyopathy - Age of onset is 0.5 to 15 years (mean = 8 years). The male to female ratio is nearly equal, and there seems to be an autosomal dominant mode of inheritance. Ventricular arrhythmias common and can be refractory to antiarrhythmic therapy. Boxers often get rapid, sustained ventricular tachycardia at rates of 350-400/minute or faster, and the VPC morphology often has a LBBB pattern (positive QRS in Lead II). Sudden death due to ventricular arrhythmias/ventricular fibrillation is common. Radiographs and echocardiograms may be normal in early disease. This disease has been noted to be associated with fibrofatty replacement of the right ventricular wall and to a lesser extent inflammation and fibrofatty changes in the left ventricle. This syndrome closely mimics a disease called Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) in man and this term is currently the preferred term to describe this disorder in Boxer dogs. Boxers are more likely to have ventricular arrhythmias that lead to syncope than other breeds. Syncope is common in Boxers, and in very young boxers, Cardiomyopathy must be differentiated from vasovagal syncope, a more benign cause of syncope. Holter monitor recording to search for ventricular arrhythmias has been proposed as a method to identify affected dogs and might be useful as a screening tool. It has been proposed that unaffected Boxers should have less than 50 to 100 VPC in a 24-hour ECG recording. Histologic lesions in Boxers with DCM may include myocarditis with myocyte loss and fatty tissue replacement, especially in the right ventricle. Boxers with cardiomyopathy can eventually develop typical signs of cardiac dilation with reduced fractional shortening (e.g., classic DCM). Many clinicians have found use of the drug Sotalol to be beneficial in controlling ventricular arrhythmias in these dogs, and another study has identified that the combination of mexiletine and atenolol was also successful in many dogs. Carnitine may also be supplemented as carnitine deficiency was described in a family of Boxers with cardiomyopathy, although the majority of Boxer dogs do not derive dramatic clinical benefit from this supplement. English and American Cocker Spaniel Cardiomyopathy - The typical age at the time of diagnosis in 10 months to 13 years (average 6-10 years), and there is no obvious sex predisposition in most reports. Electrocardiographic findings often include evidence for LV enlargement (R wave > 3.0 mV) and APC's are commonly observed. Radiographic findings include generalized cardiomegaly with pulmonary edema. Like other forms of DCM, the echocardiographic findings can progress slowly in selected dogs. Endocardiosis may accompany myocardial disease, although these are presumably separate disease processes. Many affected Cocker spaniels have been documented to have low plasma or whole blood taurine concentrations. Following supplementation with taurine +/- carnitine, taurine concentrations have risen. Some individuals have been documented to have appreciable echo improvements and have been able to be tapered from some, or rarely all, cardiac medications. Dilated cardiomyopathy in the Dalmatian - The median age of reported dogs was 6.8 years, and there seems to be a male predisposition. Most dogs (8/9) were fed a low-protein diet formulated to prevent urate uroliths. Remarkable findings included predominant left-sided CHF with pulmonary edema, marked LV dilation, and a relative lack of arrhythmias. Median survival was 10 months. Taurine levels, measured in 4 dogs, were not low. Two dogs live a long time and both were treated with coenzyme Q10. Dilated Cardiomyopathy in Young Portuguese Water Dogs - A syndrome of sudden death and peracute congestive heart failure has been described in young Portuguese water dogs. Affected dogs can be as young as 5 weeks of age. With very little warning, otherwise healthy puppies are found dead or develop respiratory distress and die shortly afterward. With this form of DCM, many puppies die or develop congestive heart failure at 2-3 months of age. The necropsy findings include the characteristic gross changes of severely enlarged and rounded hearts with dilatation of the left atrium and ventricle. A specific etiology was not identified and the histologic findings were consistent with a form of dilated cardiomyopathy. There are conflicting reports regarding the role of dietary taurine with associated plasma taurine deficiency in the development of DCM. Affected puppies often show few clinical signs indicative of cardiomyopathy or impending congestive heart failure. Pulmonary edema is often present prior to death/euthanasia or at necropsy. Hepatomegaly has also been noted both clinically and at necropsy, although it is usually not evident until overt CHF develops. Infrequent atrial or ventricular premature depolarizations may be noted. Clinical findings in affected dogs often include a cardiac gallop or a soft murmur (I-II/VI), although these auscultatory findings can be difficult to appreciate in active, young puppies. Echocardiography identifies the characteristic echocardiographic findings of cardiac dilation, enlargement of all 4 cardiac chambers. Dilation of the left ventricle with depressed LV fractional shortening are typically seen. However, some affected puppies can have a normal echo at the time of the initial echo study and develop a rapidly progressive, severe myocardial failure in just a few weeks. Emerging Cardiac Drugs Carvedilol and Metoprolol As evidence accumulates showing improved survival with these beta-blocking drugs in human patients with congestive heart failure, one must wonder whether beta-blockers should be used in dogs and cats with heart failure. One feline study, presented in abstract form by Dr. Fox and colleagues, identified that atenolol use in cats with cardiomyopathy and congestive heart failure resulted in an inferior outcome compared to other therapies. This is keeping with the observation and clinical experience from many veterinary cardiologists who have experienced a lack of tolerance of atenolol, at recommended dose, once congestive heart failure has developed in dogs. Many human heart failure trials have documented benefit in cardiac function and survival following implementation of beta-blocking drugs, although not all beta-blockers are associated with an improved survival benefit. There is increasing interest in drugs like metoprolol and carvedilol as these drugs have been shown to be associated with an improved survival benefit. Carvedilol is a beta-blocker that also has alpha1 adrenergic receptor blocking action. The drug is also a potent scavenger of free radicals of oxygen. Bioavailability may be as low as 10% in dogs. At 0.625 mg/kg orally carvedilol starts to block the increase in heart rate caused by isoproterenol (Hamlin) and doses of 1.25 mg/kg BID causes a 50% suppression of isoproterenol's tachycardic response. A carvedilol study is undertaken at Texas A&M University identified that carvedilol doses below 0.3 mg/kg q 12 hours failed to result in significant beta-blockade, and that if the drug could be titrated to 0.5 mg/kg q 12 hours that beta-blocking effect could be demonstrated, however ideal beta-blockade probably requires doses of 0.8 mg/kg q 12 hours. A published retrospective study examined the clinical response to metoprolol in 87 dogs with heart disease. Side effects were noted in 16% of dogs. The survival time on metoprolol was 329 days for dogs with DCM and 192 days for dogs with chronic valvular disease (Rush). The initial dose of 0.2 mg/kg BID was titrated to 0.43 mg/kg BID. The exact role that carvedilol, metoprolol or any beta-blocker will play in the management of dogs with naturally occurring heart disease is yet to be determined. It is reasonably prudent to suggest that, if these drugs are used, they should be started at low doses and the drug dose should be titrated upward over a several week period. The other clinical finding to keep in mind is that these drugs are being used based on the presumption that they can improve survival in dogs, not based on an expected improvement in clinical signs, so owners and clinicians should probably not expect to see an improvement in CHF signs right after starting the medication. Pimobendan Pimobendan is a new cardiac medication with acts as a calcium sensitizing agent to increase inotropic state. Because the drug increases the sensitivity of the contractile elements to the existing calcium there seems to be fewer deleterious effects than the drugs that act by increasing calcium flux into the myocardium. Inhibition of phosphodiesterase may also account for some of the beneficial effects of pimobendan, however these effects are pronounced only at higher drug doses. Veterinary clinical trials have demonstrated the improvement in clinical signs which results from pimobendan administration to dogs with congestive heart failure. While human clinical trials also showed improved clinical signs and exercise tolerance, the drug was suspected of having an increased risk of mortality, although this finding was not statistically significant. There has been no documentation of an increased mortality in dogs treated with pimobendan, and indeed improvements in survival could be attributable to resolution of clinical signs which might have otherwise resulted in euthanasia due to poor quality of life. The dose of pimobendan in the cat has been proposed to be 1.25 mg/cat q 12 hours, however there is very limited experience with this drug in the cat. The canine dose is 0.25 mg/kg q 12 hours. Antiarrhythmics for Boxers with Arrhythmogenic Right Ventricular Cardiomyopathy Dr. Meurs and coworkers at the Ohio State University have extensively studied the use of Holter monitor recordings in Boxers with cardiomyopathy and ventricular arrhythmias. Ventricular arrhythmias are common in Boxers that are otherwise healthy, and they may represent an early stage of the disease. Longitudinal studies will be required to develop endpoints for screening for dogs > 2 years of age, but as few as 50 VPCs per 24 hour recording maybe abnormal. Asymptomatic Boxers that are judged to be affected with cardiomyopathy usually have normal physical examinations (except possible arrhythmia) and most have normal LV systolic function on an echocardiogram. Holter recordings can be used to assess the efficacy of treatments, and the criteria for "successful" antiarrhythmic therapy is likely an 80-85% reduction in arrhythmia frequency with resolution of sustained (>30 seconds) ventricular tachycardia and resolution of clinical signs. With respect to therapy of dogs with severe arrhythmias, Sotalol and a combination of mexiletine and atenolol were identified to result in clinical improvement in a large proportion of Boxers, whereas procainamide did not routinely cause an 85% reduction in arrhythmia frequency. Amiodarone In Boxers who have not responded to either sotalol or the combination of mexiletine and atenolol, we have had some success using amiodarone. Amiodarone is a Class III antiarrhythmic drug with effects to prolong the action potential duration. Amiodarone also has mild beta-blocking effects and is also noted to have some Class I and Class III effects. The drug has a very long half-life and a loading dose is often required at the beginning of therapy. Amiodarone also is available in an injectable formulation which can be used for management of severe ventricular arrhythmias such as sustained ventricular tachycardia. There is limited experience with the injectable formulation; however growing experience is developing with use of amiodarone in dogs for chronic management of severe arrhythmias. Amiodarone has many side effects, and the side effects can limit the clinical utility of the drug. The most commonly reported side effect in dogs is a hepatopathy that seems to be reversible with discontinuation of the drug. Blood dyscrasia can also develop, and thyroid abnormalities are also possible. Due to the variable half-life and the challenges of dosing this particular drug, serum blood levels are recommended for dogs on chronic therapy. Serum concentrations between 1 and 2.5 ug/ml are thought to represent therapeutic blood levels, while blood concentrations above 3 ug/ml are often associated with toxicity and do not result in improved therapeutic outcome. An initial dose of 10-15 mg/kg BID for 7 to 10 days is then reduced to 8 to 10 mg/kg once a day for chronic therapy. We have had some good success in Boxers and other dogs that developed severe, life threatening ventricular arrhythmias. However, due to the high side effect profile, amiodarone should not be considered a first line therapy for management of ventricular arrhythmias in dogs. Furosemide as a Bolus or as a CRI for Severe Congestive Heart Failure? Recent studies have indicated that a continuous rate infusion of furosemide may result in a greater diuresis and natriuresis, reduced side effects, and fewer electrolyte changes than when equivalent doses of furosemide are administered as repeated bolus injections. In other manuscripts, several authors have advocated that it is probably better to give lower doses of furosemide and use sodium nitroprusside instead as this may result in improved control of severe CHF with less residual volume contraction and electrolyte disturbance. Avoidance of high doses of furosemide has been associated with improved clinical outcome and shorter hospitalizations in human patients with CHF. In addition, inotropes have been associated with equivalent or worse outcomes compared to vasodilators for management of emergent or severe congestive heart failure. For these reasons, plus the development of recombinant human BNP which is also useful in management of severe CHF, the current trend in human emergency settings is to avoid inotropes and use more vasodilators with lower doses of diuretics. A continuous rate infusion of furosemide can be titrated to between 0.1 and 1 mg/kg/hour. Furosemide is available as 50 mg/ml, and it can be diluted in 5% dextrose in water to a concentration of either 5 mg/ml or 10 mg/ml without precipitation. Low Molecular Weight Heparin Several new options are being evaluated for prevention or management of cats with arterial thromboembolism. The first is low dose aspirin, which has been proposed as a preventative in cats. The debate as to whether blocking prostaglandins leads to loss of beneficial vasodilator substances has lead some clinicians to avoid use of aspirin at the traditional dose of 80 mg/cat q 2-3 days. The low dose proposed is 5 mg/cat q 72 hours. Further studies are required before the effectiveness of this approach can be evaluated. Other investigators are looking into use of low molecular weight heparin as a long-term therapy to prevent arterial thromboembolism. We have been using Fragmin (dalteparin) at a dose of 100u/kg sub-Q either once or twice a day. Twice a day administration is desirable based on pharmacokinetic studies, but not all owners can afford this drug twice a day. Dalteparin requires that the owner be comfortable with twice a day subcutaneous injections for use of the drug. We have not noted overt side effects and a retrospective review of treated cases indicated that the drug is likely safe at this dose. It is less clear whether this dose, or a different dose or formulation of low molecular weight heparin, will be useful in preventing arterial thromboembolism in cats. Experiences are also growing with enoxaparin, another low molecular weight heparin which is useful in prevention of venous thromboembolism in human patients. Finally, there have been preliminary investigations into the use of clopidogrel, and antiplatelet drug, for prevention of arterial thromboembolism in cats. ACE inhibitors: Appropriate in dogs with asymptomatic heart disease? Two studies have examined whether ACE inhibitors are useful before signs of heart failure develop in dogs with mitral regurgitation due to chronic valvular disease. The first study, evaluating Cavalier King Charles Spaniels exclusively, failed to show a clinical benefit of early ACE inhibitor use. The second study (preliminary results reported) also failed to show a statistically significant improvement, although there was a trend for delayed onset of CHF. While controversy exists regarding the optimal time to initiate ACE inhibitors in dogs with mitral regurgitation, any benefit in the asymptomatic dog is likely quite modest. There is greater enthusiasm regarding the use of ACE inhibitors in dogs with asymptomatic left ventricular systolic dysfunction, but studies documenting effectiveness in this setting have not been published in dogs with naturally occurring heart disease.

© 2006 - John E. Rush, DVM, MS, DACVIM (Cardiology), DACVECC - All rights reserved