Getting to the Heart of New Cardiac Drugs
By Dr. Brad Hines, DVM, Diplomate, ACVIM
Originally published at Use It On Monday, 11/9/2008
Updated February 2019
The more things change, the more they stay the same. We continue to see many pets with heart disease and both our diagnostic and treatment capabilities have evolved and continue to improve. The diagnosis of heart disease is generally straightforward and can be based on a complete clinical history, thorough physical examination, and basic diagnostic testing such as evaluation of an ECG, blood pressure, and thoracic radiographs. With the increased availability of cardiac ultrasound examination, we are able to better define the problems in these pets.
Recent Diagnostic Advances:
Many times we are presented with the pet who has respiratory distress and is on a combination of medications including antibiotics, steroids, and furosemide. It can be difficult to determine if a patient has primary heart disease and congestive heart failure, primary lung disease related to pneumonia or an allergic or immune-mediated response.
Ultrasound examination remains the gold standard in evaluating pets with suspected heart disease. With the addition of color flow Doppler and evaluation of pulse wave and continuous Doppler, even more information can be gained into the severity of heart conditions and better assist in directing the treatment options.
In the last two years, advances have been made in helping to determine whether a pet in respiratory distress has primary cardiac disease or primary lung disease. N-terminal probrain natriuretic peptide and N-terminal atrial natriuretic peptide are chemicals released from stretched myocardial cells in the atria and ventricles that can help to differentiate primary pulmonary disease from primary cardiac disease. This test is readily available through commercial laboratories.
Old and New Testament Options:
The arrival of newer medications such as pimobendan and sildenafil citrate have improved our ability to treat patients with congestive heart failure due to advanced mitral valve disease, dilated cardiomyopathy, and pulmonary hypertension. Ongoing studies in veterinary cardiology have re-examined some of the older medications and recently there has been a recommendation for earlier use of pimobendan. Traditionally there have been four basic principles of veterinary medicine when treating patients with cardiac disease. These include the four Ds: Diet, Diuretics, Dilators, and Digoxin.
There are multiple diuretic choices available for the management of heart failure in animals and the loop diuretic; furosemide remains the most common. However, there are also indications for the use of thiazide diuretics and potassium sparing diuretics such as spironolactone, along with some risks. The most common side effect of diuretics in general is azotemia. This effect may be increased when these medications are combined with angiotensin coverting enzyme inhibitors. Torsemide is a loop diuretic that we now use when other diuretics fail.
Angiotensin converting enzyme (ACE) inhibitors reduce the conversion of Angiotensin I to Angiotensin II, a potent vasoconstrictor. By reducing the circulating levels of Angiotensin II, systemic arterioles and veins are allowed to relax. In addition, Angiotensin II stimulates sodium and water retention by increasing release of aldosterone from the adrenal gland. By inhibiting the release of aldosterone, there is also a mild diuretic effect of ACE inhibitors. This effect is not as pronounced as that seen with diuretics and ACE inhibitors should not be used for the management of acute heart failure. Enalapril and Benazepril are the most commonly used ACE inhibitors in veterinary patients. Because of more rapid metabolism, Enalapril must be administered twice daily compared to once daily administration with Benazepril. In addition, Benazepril may have fewer adverse side effects. Many studies in veterinary medicine have demonstrated the benefits of ACE inhibition in the management of heart disease in veterinary patients. Possible side effects of these medications include hypotension, hyperkalemia, and azotemia.
Perhaps the most beneficial advance in veterinary cardiology in the last several years is the introduction of pimobendan for the management of congestive heart failure in dogs with advanced valvular disease and in dogs with dilated cardiomyopathy. Pimobendan is classified as an inodilator. This medication enjoys both positive inotropic properties as well as dilator properties. It can be used safely with other cardiac medications, but should not be used indiscriminately in animals with heart murmurs. Recent studies have shown that if the LA: AO ratio is greater than 1.7 (on a short axis 2 D echocardiogram image) that the early use of Pimobendan may delay the onset of CHF by up to 2 years.
In our practice, we see an increased number of patients experiencing cough, syncope, and lethargy with or without a heart murmur. Radiographs may reveal primary lung disease along with right sided cardiomegaly. Ultrasound examination can be useful in identification of pulmonary hypertension. The causes of pulmonary hypertension may include pulmonary fibrosis, pneumonia, chronic obstructive pulmonary disease, heartworm disease, and primary cardiac conditions such as tricuspid dysplasia, tricuspid regurgitation, reverse PDA, etc. Dogs with pulmonary hypertension may have a dilated right ventricular chamber with flattening the intraventricular wall, tricuspid valve regurgitation, or pulmonic valve regurgitation. Indirect measurement of peak tricuspid valve regurgitation flow velocity or peak pulmonic insufficiency flow velocity may aid in the diagnosis of pulmonary hypertension.
Sildenafil citrate (Viagra) has been shown to improve the clinical condition of veterinary patients with pulmonary hypertension, even in the absence of demonstrable improvement of peak velocities of the regurgitant jets. Sildenafil is now available as a generic medication and is more cost effective. Keep in mind that the use of sildenafil in pets with significant mitral valve disease can increase blood flow from the lungs to the left atrium and exacerbate or induce heart failure.
Cardiac arrhythmias may be associated with many different systemic conditions as well as primary cardiac disease. There are many treatment options for the management of arrhythmias in veterinary patients. Lidocaine is a class I anti-arrhythmic that is probably the most commonly used, but additional anti-arrhythmic agents such as procainamide, mexilitine, and amiodarone may be useful considerations for your practice. Some drugs with anti-arrhythmic properties may also be useful in treating other cardiac conditions. An example is diltiazem or atenolol for use in the management of hypertrophic cardiomyopathy in cats.
Nutraceuticals have a proven role in the management of cardiac disease in veterinary patients. Taurine deficiency in cats was responsible for an increase in the number of dilated cardiomyopathies in the years past. Today, taurine deficiency is recognized as a contributing factor in the role of dilated cardiomyopathy in both American and English Cocker Spaniels. L-carnitine supplementation has been reported to be of benefits in Doberman pinschers and Boxers as well as other breeds with dilated cardiomyopathy. Recent studies have suggested that certain grain free diets are taurine deficient and may contribute to DCM in non-traditional needs.