Mitral regurgitation (Proceedings)

Mitral regurgitation (MR) is the most common heart disease in dogs (seen in approximately 85% of dogs with heart disease); dilated cardiomyopathy (dCMy) is next most common (seen in approximately 5% of dogs with heart disease). If the dog has heart disease and you can pick it up with one hand, it's probably MR; if it takes 2 hands, it's probably dCMy. MR occurs with increasing frequency in dogs over 6 years old, except in Cavalier King Charles Spaniels in which it may occur at 2 to 3 years of age. It is no doubt a familial (hereditary disease), but the genetic transmission is not clear.

Most heart disease of importance affects the left side of the heart: left atrium, left ventricle, aorta, and reduces forward flow (cardiac outpt=CO) and/or cause blood to dam-up in the lungs. Two general formas of heart disease occur: one in which the ventricle lacks enough power, or in the presence of MR or aortic stenosis (narrowing) to pump blood into the aorta—so-called systolic failure; the other in which the ventricle fails to fill properly because it is too stiff—so-called diastolic failure. Symptoms/signs and mortality arise equally from diastolic and systolic failure and it is very hard to tell them apart.

We intend to focus on treatment of disease, so here are a few rules about ordering tests to find out what is wrong and prescribing drugs to improve the quality of life or lengthening it:

1. Don't do something just because you can.

2. Don't do something because others do.

3. Don't do something because it's always been done.

4. Do something because there is a reasonable expectation that it will change, favorably, the outcome of the case, or because it will answer a question the owner has.

What do you (the DVM, nurse, assistant) want top know?

1. Diseases you can exclude from consideration.

2. Goals to achieve for therapy.

3. Methods to achieve those goals.

4. Risk—and how you might minimize them—to achieving goals.

5. How do you know when goals are achieved?

6. What do you do if goals are not achieved?

Goals of therapy are:

1. Never to treat a name or a murmur.

2. Generally to prolong life and decrease symptoms/signs.

3. Adjust fluid balance.

4. Improve force of contraction and rate of relaxation of the ventricles.

5. Decrease hindrance to ejection.

6. Regulate rhythm.

7. Improve oxygenation—remember that most animals that die fro heart or ling disease do so from asphyxia resulting from fatigue of muscles of respiration.

8. Diminish remodeling. Remodeling is a change in structure or electrophysiological properties.

9. "Up-regulate" beta receptors

10. Return baroreceptors to normal.

11. "Build a bridge from diagnosis to when the animal has enough beta blockers on board."

Remember that the the sympathetic nervious system may save your life for short spurts, but it is your mortal enemy the rest of the time. Pay attention to it.

The following is an outline of precisely when to use each drug in your pharmacopoeia:

1. left atrial enlarge met—ACE inhibitor

2. left ventriculae enlargement—digoxin, spironolactone, carvedilol, pimobendan

3. wheezes—theophylline

4. edema—furosemide

5. refractory edema—add a ....thiazide

6. atrial fibrillation—diltiazem

7. ventricular arrhythmia—sotalolo/procainamide-mexiletine

Afterload—the hindrance to the flow of blood from the left ventricle into and through the aorta. It is due to:

1. the stiffness of the aorta (how constricted the smooth muscle is in the wall)

2. how much blood is in the ventricle just before it contracts—the preload (see below)

3. how thin the ventricular wall is just before it contracts

Preload—the volume of blood in the ventricle just before it contracts—is determined by:

1. the weight of blood pushing in from the lungs—termed the end-diastolic pressure, which is determined by:

a. total blood volume—a balance between water drunk and urine made

b. how well the ventricle sucks blood out of the lungs and pumps it into and through the arteries

c. how stiff or compliant the ventricle is

d. the height of the pleural pressure

2. how forcefully the left atrium contracts—the atrial "kick"

Another very important issue you must address is the amount of oxygen in the heart muscle [O2], because this oxygen is necessary produce ATP, the fuel for everything done in the body. The amount of oxygen present is a balance between how much is delivered (by the lung, the hemoglobin in the blood, and coronary blood flow), and how much is removed by how fast beats, hoe vigorously it contracts (vmax), and the peak tension—afterload—it develops.

Finally it is important to understand the relationship between heart rate (HR) and blood p[ressure (BP)—the Marey reflex. When BP changes, HR usually changes in a direcvtion to minimize the change in BP. This is mediated via the high pressure baroreceptor reflex (HPBR). This reflex originates with receptors in the aortic arch and carotid sinus which monitor the level of BP, send the information to the medulla oblongata, which then changes HR appropriately. With heart disease, these receptors become blunted, so that they always "believe" the BP is too low when it is not. Therefore the medulla, "thinking" the BP is too low, increases HR (causing the heart to consume excess oxygen and to have less time for filling or coronary blood flow) and constricts arterioles (hindering blood flow). Disease of the HPBR arises from their becoming loaded with a chemical called Na-K ATPase, the loading arsies from aldosterone, and aldosterone comes from the adrenal gland having been stimulated by angiotensin-II. Thus you may reset the HPBR by either blocking Na-K ATPase with digoxin, blocking aldosterone with spironolactone, or blocking angiotensin-II with an angiotensin converting enzyme inhibitor.

MR occurs because the leaflets of the mitral valve become thickened and gnarled due to deposits of abnormal proteins Thus they do not close completely, and blood leaks from the left ventricle (LV) into the left atrium (LA) instead of all going into the aorta. As it leaks, it produces a murmur, usually heard best at the left 5th intercostal space near the left sternal border, but the intensity of the murmur does not tell you how much blood is leaking, only the velocity with which it leaks.

Precisely what drugs should be given, and when, can usually be determined by thoracic radiographs and an electrocardiogram. Therefore it is essential to know what structure(s) if enlarged contribute what shadow(s) to the cardiac silhouette. Examining the silhouette from the ventral view, the heart may be observed as the hands of a cock, where the most cranial portion is 12 o'clock. The left border of the shadow is usually straight, and a bulge from 1 to 2 o'clock indicates left atrial enlargement. A broad, notched P wave of the ECG also indicates left atrial enlargement, and it is not unusual for the stretched left atrium to discharge premature beats which break the normal rhythm and may lead to bursts (paroxysms) of atrial tachycardia. With greater and persistent left atrial enlargement, it is not uncommon to evolve into atrial fibrillation, a state in which the atria wiggle like a bag of worms and contribute nothing to ventricular filling. A bulge from 3 to 7 o'clock indicates left ventricular enlargement, which in the ECG may produce a tall and often broad R wave of the QRS complex in the ECG. Chronic stretch and other irritation of the left ventricle may lead to ventricular fibrillation in which the ventricles wiggle like a bag of worms and eject no blood.

Arrhythmias

Normally the atria are stimulated and contract just before the ventricles, and both beat at a rate dependent upon physiological needs, i.e., slowly (30 to 60/minute) during rest and sleep, fast (up to 240/minute) during exercise and excitement. Interestingly, large dogs do not have heart rates different from small dogs! Heart rate is best studied by electrocardiography (ECG), which displays P waves every time the atria are stimulated and QRS complexes when the ventricles are stimulated. The heart rate is highly irregular in the dog, but it is termed regularly-irregular, because it speeds during inspiration and slows during expiration. If the rate is too slow, it must be accelerated (usually with atropine or glycopyrrolate); if it is too fast, it must be slowed (usually with a beta blocker like atenolol, a calcium channel blocker like diltiazem, or with digitalis).

The normal pacemaker for the heart is the SA node in the right atrium. It sends out a shock wave which travels first through the atria (producing the P wave), then after traveling very slowly over the AV node, it travels through the ventricles (producing the QRS complex). The interval between opnsety opf P and onset of QRS is termed the PQ or PR interval, and most of the duration is attributable to very slow conduction through the head of the AV node. Whatever changes heart rate changes AV conduction similarly. With disease or in response to certain drugs, other regions (in the atria, in the AV junction, in the ventricles) may become irritated and discharge without waiting for the SA node. This leads to premature beats which occur singly, for short bursts (termed paroxysms), or continuously (termed tachycardias). Atrial tachycardias may evolve into atrial fibrillation in which the heart beats rapidly and irregularly-irregular; ventricular tachycardias may evolve into ventricular fibrillation in which the heart ceases to beat and the patient dies. Sudden death occurs commonly in Boxers and Doberman Pinschers, and may be presaged by less severe arrhythmias. Some believe that less severe arrhythmias should not be treated, because the very drugs used to treat them may actually make arrhythmias worse; the proponants of this believe that arrhythmias should not be treated unless they make the patient faint or weak. However frequently the first symptom indicating need for therapy is sudden death.

It is usually quite easy to determine where the irritated focus for an arrhythmia is. First there is a premature beat. Second, make certain it is not merely an exaggeration of the respiratory sinus arrhythmia. Thirdly determine if the QRS and T waves of the premature beats are normal-appearing or are screwy-looking. If normal the beat arose from the atrtia or AV junction; if screwy it arose from within the ventricles. Furthermore, if the QRS of a ventricular premature beat is of the same sign as the QRS of the sinus beats, it arose frobm the right vedntricle. If the sign is different, it arose from the left v entricle. Atrial premature beats are seldom life-threatening, and may be extinguished or reduced in number with diltiazem, atenolol or amiodarone; ventricular premature beats may lead to sudden death and may be extinguished or reduced in number with sotalol, procainamide/mexiletine, or amiodarone. Life-threatening ventricular arrhythmias are almost always treatable with IV lidocaine, but the patients is almost immediately switched to an oral drug, so most cardiologsts omit the lidocaine since oral sotalol usually terminates the arrhythmia within 2 hours of dosing.

Nasty ventricular arrhythmias occur ubiquitously in Boxer cardiomyopathy. The disease may be inferred by single, seemingly unimportant ventricular premature beats, but even these dogs are at significant risk for sudden death. For that reason many cardiologsts recommend treating these Boxers with either sotalol or procainamide/mexiletine. There is no good ev idence that this treatment is successful, but most cardiologists sleep better thinking that some protection against sudden death has been used.

Atrial fibrillation is probably the most common arrhythmia of clinical importance. Although it may occur rarely as a benigh arrthythmia in Newfoundlands, most often it occurs due to left atrial enlargement in dogs with mitral regurgitation or dilated cardiomyopathy, and is a harbinger of terrible clinical outcome. It is presumed to occur whenever the heart rate is rapid and irregularly-irregular, there is a pulse deficit (i.e., fewer femoral pulses than heart beats), the 2nd heart sound is highly variable in intensity, and the ECG shows no P waves but rather coarse, low amplitude undulations in the baseline. The treatment is directed at slowing the ventricular rate of retarding conduction through the AV node with diltiazem>>atenolol>>>digitalis.