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Principles of Therapy of Cardiovascular Disease


Also see Systemic Pharmacotherapeutics of the Cardiovascular System.

Although therapy is disease-specific, there are some general goals of therapy for heart disease: 1) Chronic stretch on myocardial fibers should be minimized, because chronic stretch injures and irritates fibers, causes them to consume excess quantities of oxygen, and leads to their death and replacement by fibrous connective tissue (remodeling). 2) Edema fluid should be removed because it makes the lungs wet, heavy, and stiff, and causes ventilation-perfusion inequalities and fatigues muscles of ventilation. 3) The circulation should be improved, and the amount of regurgitation (most often mitral regurgitation) decreased. Improved circulation enhances blood flow to important organs, and reducing mitral regurgitation decreases stretch on the left atrium and pulmonary veins, pulmonary capillary pressure, and edema formation. 4) Heart rate and rhythm should be regulated. A heart beating too slowly fails to eject enough blood, while a heart beating too rapidly does not have time to fill adequately and consumes too much oxygen at a time when there is too little coronary blood flow. A heart beating too irregularly may deteriorate into ventricular fibrillation and sudden death. 5) Oxygenation of the blood should be improved. Inadequate oxygenation leads to inadequate energy to fuel both contraction and relaxation of the myocardium. Inadequate oxygenation of the myocardium may also lead to arrhythmia. 6) β1-adrenergic receptors should be up-regulated; down-regulation of β1-adrenergic receptors interferes with the ability to fight diseases of other organ systems. 7) The likelihood of thromboembolism should be minimized. Cats with hypertrophic cardiomyopathy may shed emboli from the enlarged left atrium, which may block major arterial branches and lead to ischemia and death. 8) Mature heartworms and microfilariae should be killed. Mature heartworms may initiate severe changes in the pulmonary arteries that ultimately impede blood flow through the lungs.

The ultimate goals of therapy for cardiovascular disease are achieved when the animal can be classified as functional Class I after treatment, the respiratory and heart rates are not increased at rest, and there is a respiratory sinus arrhythmia.

Common Therapeutic Agents

Furosemide is a loop diuretic that decreases resorption of sodium, chloride, and potassium in the ascending loop of Henle. It is also a venodilator when used IV. It is the most important and effective means for removing edema fluid from animals with heart failure, and frequently is life saving over the short run. Diuresis with furosemide may be augmented by using thiazide diuretics (eg, hydrochlorothiazide). Thiazides suppress resorption of sodium and water at the distal renal tubules. When using a loop diuretic and a diuretic that works at the distal tubules, the ability of the kidneys to conserve water is reduced dramatically, so dehydration and hypokalemia may develop. This may be signaled by worsening azotemia.

Spironolactone is a potassium-sparing diuretic that blocks aldosterone. Like thiazides, it exerts its effect principally at the distal convoluted tubule. While spironolactone effectively maintains potassium levels, recent data suggest that it does not induce a significant diuretic effect. Spironolactone minimizes remodeling of both blood vessels and the heart, and like angiotensin-converting enzyme (ACE) inhibitors and β-blockers, has been shown to decrease symptoms and to prolong the lives of people with heart failure. Amiloride and triamterine are also potassium-sparing diuretics.

Digitalis glycosides exert their effects by inhibiting membrane Na+/K+-ATPase. This increases intracellular sodium, which activates the sodium-calcium pump that increases intracellular calcium. Digoxin increases the force of myocardial contraction, slows the heart rate, and improves baroreceptor function.

Enalapril, benazepril, and ramipril are ACE inhibitors commonly used in heart failure management in dogs. They are all equally effective at blocking the conversion of angiotensin I to angiotensin II. They minimize remodeling of both blood vessels and myocardium.

Amrinone and milrinone, analogs of theophylline that deactivate other forms of phosphodiesterase, are potent IV inodilators. That is, they are both positive inotropes and vasodilators. Piomendan, which is a calcium-sensitizing agent and phosphodiesterase inhibitor, is also an inodilator that has been shown to improve the quality of life and improve survival in dogs with CHF.

Both procainamide and quinidine, class IA antiarrhythmics used formerly to manage ventricular arrhythmias, have been superceded by the β-blocker sotalol and the class IB antiarrhythmic mexiletine. They are used most often for ventricular arrhythmias that are not life threatening. Lidocaine, a class IB antiarrhythmic, is used only IV for emergency ventricular arrhythmias.

Atenolol, propranolol, and metoprolol are oral β-blockers, and esmolol is an IV β-blocker, that slow the heart rate, suppress arrhythmias, and up-regulate adrenergic receptors. Carvedilol is a β- and α-adrenergic blocker that scavenges oxygen-free radicals. Like ACE inhibitors and spironolactone, carvedilol has been shown to both prolong life and decrease symptoms in people with heart failure.

Diltiazem is a calcium-channel blocker that is useful for slowing ventricular rate in animals with atrial fibrillation. It is also used to decrease myocardial stiffness in cats with hypertrophic cardiomyopathy. Amiodarone is useful for managing all forms of arrhythmias, but there is relatively little clinical experience with it. However, dogs commonly develop increased liver enzymes while on therapy.

Atropine and glycopyrrolate block the effects of the vagus nerve on the SA node. Because the vagus nerve slows discharge of the SA node and heart rate, these compounds speed heart rate and may be useful when the heart beats too slowly. Nitroglycerine is a venodilator that is usually applied in a paste form to the skin inside the earflap or thigh; blood pools in the dilated peripheral veins, decreasing left ventricular preload and pulmonary edema. Aspirin, clopidogrel, dalteparin, enoxaparin, and coumadin are antithrombotics that may prevent thromboembolism in cats with cardiomyopathy. Taurine and l-carnitine are amino acids useful in preventing dilated cardiomyopathy in cats and in a limited number of dogs, respectively. Melarsomine is used to kill mature heartworms; ivermectin, milbemycin, and selamectin are used to kill microfilariae.

Pimobendan and ACE inhibitors have been proved to be safe and effective to treat dogs with heart failure or arrhythmias. Furosemide and digoxin are approved, but without data proving either safety or efficacy. Use of other agents to manage heart failure or rhythm disturbances is based on anecdotal evidence or unblinded, uncontrolled reports.

Last full review/revision March 2012 by Daniel F. Hogan, DVM, DACVIM (Cardiology)

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