Cardiovascular Diseases in the Ageing Dog Diagnostic and Therapeutic Problems

Veterinary Research Communications, 27 Suppl. 1 (2003) 555–560 © 2003 Kluwer Academic Publishers. Printed in the Netherlands

Cardiovascular Diseases in the Ageing Dog: Diagnostic and Therapeutic Problems C. Guglielmini Department of Veterinary Clinical Sciences, School of Veterinary Medicine, University of T eramo, V iale Crispi 212, I-64020 Cartecchio (T E), Italy E-mail: guglielmini@vet.unite.it Keywords: age, cardiac diseases, dog, echocardiography, electrocardiography

THE AGEING CARDIOVASCULAR SYSTEM Increased life expectancy is a common scenario for dogs living in the third millennium, since many advances in canine medicine and surgery, as well as in nutrition and preventive health care, have taken place over the last few decades. According to a study conducted on a population of 9248 subjects, cardiac diseases are the second most prevalent cause of death in the dog, accounting for a percentage of 16.3% (Eichelberg and Seine, 1996). A complete understanding of the pathophysiological mechanisms of cardiovascular diseases in the geriatric dog should include the complete knowledge of diseases primarily involving the cardiovascular system, as well as those affecting other systems with a known influence on cardiovascular function, in addition to a clear understanding of the modifications of the cardiovascular structure and function associated with advanced age. Age-related changes of canine cardiovascular function include decreased blood flow, blood velocity, and arterial compliance and distensibility (Miller et al., 1976; Haidet et al., 1996), as well as increased ventricular systolic and diastolic stiffness associated with prolonged duration of myocardial contractility (Templeton et al., 1976, 1979). A decline in cardiovascular responsiveness to beta-adrenergic stimulation has also been demonstrated in aged dogs (Yin et al., 1979; Haidet 1993). Progressive loss of organ reserve and adaptability, probably due to functional changes in the catecholaminergic system, was proposed as an inciting mechanism for cardiovascular diseases in older dogs by Strasser and colleagues (1997). However, unlike human beings, primary systemic hypertension (i.e. occurring in the absence of any underlying endocrine or renal disease) does not appear to be a common clinical problem in healthy geriatric dogs (Meurs et al., 2000). Furthermore, arteriosclerosis and related ischaemic heart disease are uncommon in the dog, but their real incidence may be underestimated (Falk and Jo¨nsson, 2000). The precise relationship between the above-mentioned negative modifications of cardiovascular function and the development of specific cardiovascular diseases is difficult to ascertain. A recent study reported the overall prevalence of cardiac pathological alterations observed in beagle dogs employed as control subjects in four life-span studies at 555

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different research centres in the U.S.A. (Van Vleet, 2001). Valvular endocardiosis was the most frequently observed cardiac lesion, followed by different alterations occurring at a lower frequency including endocarditis, myocardial degeneration, myocardial hypertrophy, chamber dilatation, myocardial calcification, myocardial fibrosis, myocardial necrosis, and primary and secondary neoplasms. Cardiovascular diseases with a known increased prevalence in aged dogs include chronic degenerative valvular disease (CDVD) or valvular endocardiosis, secondary myocardial hypertrophy, dilated cardiomyopathy (DCM), cardiac neoplasia, amyloidosis, valvular endocarditis, lipofuscinosis, sick sinus syndrome, and other myocardial and vascular lesions.

CARDIOVASCULAR DISEASES IN THE GERIATRIC DOG Chronic degenerative valvular disease Valvular endocardiosis is the most common canine-acquired cardiovascular disease (Buchanan, 1992). The mitral valve is most frequently involved, followed by the tricuspid valve that may be affected in about 30% of dogs with mitral endocardiosis.

Many small-sized canine breeds can be affected with Cavalier King Charles Spaniel and Dachshund having a particular predisposition, for which a genetic base has strongly been suspected (Swenson et al., 1996; Olsen et al., 1999). Male subjects are more frequently affected than females and usually develop congestive heart failure (CHF) more rapidly. The prevalence of CDVD is age-dependent, reaching about 75% for dogs over 16 years old (Kwart and Haggstrom 2000). Mitral valve degeneration leads to mitral regurgitation that then results in chronic left-sided cardiac volume overload. Compensatory mechanisms secondary to mitral insufficiency include peripheral arterial vasoconstriction, in order to compensate for the reduced stroke volume, and increased preload. The disease progresses slowly, since the compliant left atrium can accommodate a large volume of regurgitant blood, resulting in left atrial dilatation, with slightly increased internal pressure. The main consequences of left atrial enlargement include compression of the left main stem bronchus, development of supraventricular arrhythmias, and increased pressure in the pulmonary bed leading to pulmonary oedema. Cough, exercise intolerance, dyspnoea and syncope are the main symptoms in dogs affected by mitral endocardiosis. On physical examination, a systolic murmur best heard over the mitral area is always appreciable. In addition, an irregular cardiac rhythm and adventitious respiratory sounds may be appreciated in advanced cases. Jugular pulsation, abdominal distension and ascites may also be found when the tricuspid valve is involved. The diagnosis of mitral CDVD is not difficult based on the above clinical signs and results of radiographic and echocardiographic examinations. Thoracic radiographs are particularly helpful in evaluating the haemodynamic impact of mitral endocardiosis on the pulmonary vascular bed.

Enlarged left atrium and ventricle, dorsal displacement of the carena and of the left mainstem bronchus, dilated pulmonary veins, eventually associated with interstitial

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and/or alveolar patterns indicating pulmonary oedema, are the main radiographic signs observed on survey thoracic radiography. Hyperechogenic and thickened mitral valve leaflets and chordae tendinae, abnormal mitral valve motion, enlarged left atrium, eccentric hypertrophy of the left ventricle, and hyperdynamic interventricular septum and left ventricular free wall can be appreciated on echocardiographic examination of dogs with mitral endocardiosis. In aged small-breed dogs, CDVD and concurrent chronic respiratory disorders (e.g. lower airway collapse or chronic bronchitis) can often be found. Therefore, some difficulties may arise in exactly identification of the origin of the cough in such patients. Careful examination of thoracic radiographs helps to rule out or confirm the presence of primary respiratory diseases associated with valvular endocardiosis, thus suggesting more appropriate therapeutic protocol in each patient. Preload and afterload reducers are the most useful drugs employed in the treatment of mitral endocardiosis. Diuretics, such as frusemide, are particularly helpful to alleviate pulmonary congestion and/or oedema in advanced cases. Mixed vasodilators (i.e. the ACE-inhibitors enalapril, benazepril, and ramipril) may counteract the negative effect of chronic activation of the renin–angiotensin– aldosterone system, which promotes excessive fluid retention in cardiopathic dogs, in addition to their positive effect on cardiac workload mediated by arteriolar dilatation.

Nevertheless, the use of ACE-inhibitors in the early stages of CDVD (i.e. before the onset of CHF) does not positively modify the clinical course of the disease in affected subjects, as was recently demonstrated in a large, multicentric, double-blind, placebocontrolled study (Kwart et al., 2002). Digoxin or antiarrhythmic drugs (i.e. betablockers or calcium-channel antagonists) are usually recommended when supraventricular tachyarrhythmias are present.

Dilated cardiomyopathy Dilated cardiomyopathy is the most common canine myocardial disease. The prevalence of DCM increases in middle-aged or older dogs, especially in males. Giant breed dogs, Doberman pinschers, Boxers, and English and American cocker spaniels are mainly affected. The disease is characterized by a progressive deterioration of the myocardial pump function leading to progressive dilatation of the ventricles, mainly the left ventricle, according to the Frank-Starling mechanism. The decline in systolic ventricular function progresses slowly and, therefore, a pre-symptomatic form, so-called occult DCM, has been described (Calvert, 2000). The clinical signs of DCM in symptomatic subjects include weakness, exercise intolerance, anorexia, and coughing. On cardiac auscultation, an early diastolic gallop (S ) associated with rapid 3 ventricular filling of dilated ventricular chambers, and a soft systolic murmur of atrioventricular valve regurgitation may be heard. Other signs include pale mucous membranes and augmented capillary refill time, cardiac arrhythmias associated with pulse deficits, and hypokinetic pulse. Ventricular arrhythmias may be found in Doberman pinschers and Boxers, whereas giant breed dogs more commonly exhibit

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atrial fibrillation. In advanced cases, signs of left-sided (i.e. dyspnoea and respiratory crackles) and/or right-sided (i.e. ascites, jugular distension, and pleural effusion) CHF may develop. Electrocardiography allows precise diagnosis of cardiac dysrhythmias.

Generalized cardiomegaly, eventually associated with signs of CHF (i.e. enlarged pulmonary vessels, interstitial and/or alveolar pattern, and enlarged vena cava) is the main radiographic feature of DCM. The echocardiographic examination allows formulation of definitive diagnosis when dilated ventricular chambers, enlarged left atrium, reduced systolic function, and increased E-point to septal separation are found. Specific echocardiographic parameters have been proposed to distinguish normal Doberman pinscher dogs from subjects of the same breed suffering from occult DCM (Calvert, 2000). The use of a Doppler-derived index was recently proposed to evaluate the combined systolic and diastolic myocardial performance in Newfoundland dogs with familial prevalence of DCM (Lee et al., 2002). Amelioration of ventricular contractility, preload and afterload reduction, heart rate and rhythm control are the main therapeutic goals in dogs with overt DCM. Thus, positive inotropes, ACE-inhibitors, diuretics, and antiarrhythmics are the cornerstones of the therapeutic protocol. Digoxin is used either for its weak positive inotropic effect or for its sensitizing effect on b-adrenoreceptors. It also may have a positive action in treatment of supraventricular tachyarrhythmias. The use of Pimobendan, a benzimidazole compound with a phosphodiesterase inhibiting action, has recently been proposed to ameliorate the myocardial contractility in dogs with DCM and CHF (LuisFuentes et al., 2002).

Myocardial hypertrophy Myocardial concentric hypertrophy is the result of an augmented load to the heart secondary to primary non-cardiac disorders. Therefore, it usually represents the functional response of the ventricles to increased peripheral resistances. Right ventricular hypertrophy can be observed with chronic obstructive pulmonary disease, dirofilariasis, and pulmonary thromboembolism. Left ventricular hypertrophy may be the consequence of systemic arterial hypertension, usually secondary to chronic renal failure and hyperadrenocorticism. The clinical signs are mainly related to the primary disorder. Jugular distension, hepatomegaly, and ascites can be observed when the right ventricle is involved, since both eccentric and concentric hypertrophy develops in response to right-sided pressure overload leading to tricuspid regurgitation.

Thoracic radiography is useful for evidencing signs of right ventricular enlargement.

Echocardiography gives evidence of both left-sided and right-sided cardiac hypertrophy. Therapy is aimed at treating the primary disorder.

Cardiac neoplasia Cardiac neoplasms, either primary or metastatic, are uncommon in the dog and they may occur in intracavitary, intramural, pericardial locations, or at the heart base.

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Primary and metastatic haemangiosarcoma and heart base tumours (i.e. chemodectoma and ectopic thyroid or parathyroid gland tumours) are the most frequently observed canine cardiac neoplasia (Ware and Hopper, 1999). Many cardiac neoplasms occur in aged dogs of different breeds, with a known predisposition towards haemangiosarcoma and heart base tumours for German shepherd and brachicefalic dogs, respectively (Carlton, 2001). The clinical signs of patients with cardiac neoplasms are variable depending on the type, location, and size of the tumour.

Pericardial effusion and cardiac tamponade are frequently associated with cardiac tumours, but cardiac arrhythmias and CHF due to impaired ventricular filling or ventricular ejection may also be found. Cardiac ultrasonography is the most useful non-invasive tool for diagnosis of a cardiac neoplasm. Biopsy of the identified mass is necessary for a definitive diagnosis. The long-term prognosis of dogs with cardiac tumours is usually poor and therapy is aimed at reducing physical discomfort.

Pericardiectomy at the time of surgical biopsy of the mass is associated with a significantly longer survival time for dogs with aortic body tumours (Ehrhart et al., 2002).

Sick sinus syndrome This syndrome, also called bradycardia–tachycardia syndrome, is the resultant of a dysfunction of the sino-atrial node leading to impaired function of the natural pacemaker. Aged dogs, particularly female miniature schnauzers, Pomeranians, and terriers are affected. Episodic weakness and syncopal episodes due to cerebral ischemia are the main clinical signs (Moneva-Jordan et al., 2001). On physical examination, cardiac arrhythmia with alternating phases of bradycardia and tachyarrhythmia are evident. Electrocardiography confirms the suspected diagnosis. Pacemaker implantation is the only method of treatment for affected subjects.

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