HEART disease is a common condition that the general practitioner has to deal with fairly frequently. It can be defined as a structural abnormality of the heart valves, cardiac chambers, myocardium or the main vessels, and it may or may not lead to heart failure.
Asymptomatic or compensated heart disease is usually diagnosed during routine checks, commonly by auscultation of a murmur. However, not all cardiac conditions are presented with a murmur [e.g. some patients with dilated cardiomyopathy (DCM), cyanotic heart disease, etc.] and they may remain occult until overt heart failure is diagnosed.
In addition, murmurs might be caused by an underlying non-cardiac disease (such as anaemia) or may be present in healthy animals (such as puppy and flow murmurs, or cats with trivial atrioventricular valve regurgitation or right ventricular outflow tract obstruction).
Heart failure, in contrast, is a syndrome characterised by the inability of the heart to fulfill the tissue metabolic needs at normal filling pressures. In other words, the heart can only keep up maintaining enough tissue perfusion at the expense of activation of compensatory mechanisms that will cause an increase in heart rate and high filling pressures and fluid effusions.
Some heart diseases can be managed before they lead to heart failure.Agood example are congenital heart conditions such as patent ductus arteriosus (PDA) or pulmonic stenosis (PS), which can be managed by conventional surgery (ligation of the PDA) or by interventional techniques (PDA occlusion by keyhole techniques via the femoral vessels, or balloon valvuloplasty for PS via femoral or jugular vein).
However, we cannot currently offer such management for other conditions such as myxomatous mitral valve disease (MMVD) or DCM and many of these patients will eventually develop life-threatening congestive heart failure (CHF), low-output failure or sudden death.
Compensatory mechanisms in CHF: the Renin-AngiotensinAldosterone-System and the Sympathetic System
We should by now be all familiar with the concept of the neuroendocrine dysfunction that occurs as a result of the primary biomechanical dysfunction in CHF.
In other words, when the heart is unable to maintain the cardiac output (either because of a leaky valve, a narrow valve, an abnormal communication, or a weak or stiff myocardium), the arterial baroreceptors will sense it and will send signals to the central autonomic control centres, which will activate the vasomotor and cardiostimulatory centres.
These centres will mediate the release of catecholamines (adrenaline, noradrenaline), which will act at the cardiac level (increasing the heart rate) and at the vascular level (causing peripheral vasoconstriction). In addition, the decrease in cardiac output will also be sensed by the kidneys, leading to the release of renin.
This enzyme will act on the circulating angiotensinogen and will produce angiotensin I, which will be further transformed to angiotensin II by the angiotensin converting enzyme (ACE), mainly in the pulmonary vascular bed.
Angiotensin II will act at different levels, but is involved in aldosterone release by the adrenal glands, vasopressin release by the neurohypophysis and further stimulation of the sympathetic system (creating a “vicious circle” of stimulation). The aim of this complex activation is the retention of fluid (via increased thirst and pure water retention and sodium retention in the kidney), vasoconstriction in non-vital organs and the remodelling of the myocardium, so it can “grow” and adapt to the new situation (either by eccentric hypertrophy in situations of volume overload or by concentric hypertrophy in pressure overload).
This is the same system that will activate in case of haemorrhage, and if the primary insult can be controlled it can give a chance to the body to overcome it. However, in heart disease, the primary biomechanical dysfunction continues and eventually the compensatory mechanisms will fail to maintain the cardiac output.
Hence, once the heart failure is present, these mechanisms become harmful for the already deteriorated cardiac function, and contribute to effusions, myocardial hypoxia, fibrosis and arrhythmias.
Two relatively new concepts which should be considered in the pathophysiology of CHF are the presence of tissue angiotensin II production at the myocardial level and the phenomenon called aldosterone escape. This is one of the reasons the treatment of CHF relies on polypharmacy, which refers to the use of different drugs that treat the pathological process at different levels, complementing each other.
Diuretics and the sequential nephrone blockade
Decreasing the preload is one of the mainstay treatments in congestive heart failure, and particularly life-saving in cases of acute pulmonary oedema. Furosemide is a potent loop diuretic and is widely used in general practice. The dosage and route will depend on the severity of the presenting signs. For stable patients with mild signs or compensated pulmonary oedema, oral administration is usually adequate, with dosages of approximately 2mg/kg two or three times a day.
The lowest effective dose should be used, and dosages higher than 12mg/kg/day usually necessitate the addition of other diuretics, as the nephrone can hypertrophy in distal segments to compensate for chronic furosemide administration.
For severely affected patients, parenteral furosemide (ideally intravenously) should be used, with oxygen supplementation and minimising stress. Recent data favour the use of constant rate infusion of furosemide, instead of repeated bolus injections.
With progression of congestive heart failure, diuretics that act at more distal segments of the kidney can be combined with furosemide, such as hydrochlorthiazide. Frequently, these diuretics are used in combination with potassium sparing diuretics, such as amiloride. Spironolactone is a weak potassium sparing diuretic that acts to inhibit aldosterone (different mechanism than amiloride) and will be discussed in the next section.
As the CHF progresses, and especially if ascitis is present, drug absorption might be compromised. Alternating subcutaneous furosemide injections and periodic abdominocentesis could be used in these cases. Torasemide is a potent loop diuretic that can inhibit aldosterone release and is being studied as a “rescue” treatment in patients that become refractory to furosemide. It is 10 times more potent than furosemide and is available in the UK as a tablet.
It is vital to stress the importance of monitoring of renal function and electrolyte levels in patients with CHF, as severe alterations can be induced by the use of combinations of diuretics.
ACE inhibitors and others
A second basic part of treatment in CHF is based on ACE inhibitors (ACEi), as demonstrated in several clinical trials in dogs. It is important to remember that ACEi should be started as soon as the patient is stable, as diuretics will further stimulate the RAAS. However, as previously mentioned, tissue angiotensin II and aldosterone can “escape” from ACEi, contributing to the progression of the disease.
The addition of aldosterone inhibitors (spironolactone) has been proven to be beneficial in humans, and a study in dogs (due to be published) found similar results. In cats this drug should be used with care, as dermatological side effects have been reported in asymptomatic cats with heart disease.
Newer drugs used in human medicine include angiotensin II receptor antagonists (such as losartan) and endothelin antagonists (such as bosentan), but they need further study in dogs and cats.
Positive inotropes: pimobendan
Recent clinical trials have demonstrated the importance of using positive inotropes such as pimobendan for the treatment of CHF caused by MMVD and DCM.
Although most of these trials compared the benefits of ACEi versus pimobendan, both drugs work at different levels and it is common sense to assume that the beneficial effects of both drugs will be maintained when used in combination.
Pimobendan belongs to the calcium sensitiser family (hence the positive inotropic effect) and offers additional vasodilatory effects mediated by phosphodiesterase inhibition. Newer drugs such as levosimendan offer similar drug effects without the phosphodiesterase action and might become available for the use in dogs and cats in the near future.
Nutraceuticals and diets: fish oils, L-carnitine, taurine
Omega-3 fatty acid supplements offer beneficial effects in CHF, especially in patients with cardiac cachexia. Recent studies have also suggested antiarrhythmic properties in Boxers with arrhythmogenic cardiomyopathy. Eicosapentaenoic and docosahexaenoic acid are commonly used in dogs with CHF and dosages of 25mg/kg/day and 40mg/kg/day have been recommended in CHF, respectively.
Taurine supplementation should be considered in cats presenting with DCM, although only a small percentage will respond to it (250-500mg orally once or twice daily). Taurine levels should be checked in dogs of unusual breeds or with abnormal diets presenting with DCM, and supplementation should be started if low taurine is found (500-1,000mg orally once or twice daily).
Cardiomyopathy responsive to taurine and L-carnitine has been described in American Cocker Spaniels and other Spaniel breeds and in these cases a 2-3 month treatment trial could be performed. The dosage for L-carnitine supplementation in dogs is 50-100mg orally three times a day.
Early dietary sodium restriction, prior to onset of CHF, is generally not recommended, as it can activate RAAS and contribute to progression of heart disease.
Avoidance of high salt treats or snacks is probably a forgotten but very important step in early CHF. Sodium restricted diets are usually indicated in overt CHF, as they might spare the use of diuretics. However, protein restriction should be avoided, as these patients are prone to cardiac cachexia.
Recent studies of dietary patterns in dogs and cats with heart disease have shown that anorexia is a common feature in dogs and cats with CHF. These studies also revealed that approximately 25% of the total sodium intake was received from treats in dogs, which overall had a higher than recommended sodium intake.
A high percentage of owners were using food or treats to medicate their pets. As sodium restricted diets are usually less palatable, they might not be accepted by patients with decreased appetite and this might further complicate administration of drugs by the owner.
Ensuring appropriate caloric intake and ability to medicate becomes a priority in these patients.
■ References available on request.
