As many as three-fourths of all dogs with signs of congestive heart failure suffer from mitral regurgitation caused by myxomatous degeneration (MXD) of the valve leaflets or chordae tendineae. The prevalence of MXD increases with advancing age so that approximately 10% of dogs 5 to 8 years old, 20 to 25% of dogs 9 to 12 years old, and 30 to 35% of dogs over 13 years old exhibit murmurs. A higher than average prevalence of myxomatous valvular degeneration has been reported for cavalier King Charles spaniels, poodles, miniature schnauzers, Chihuahuas, Doberman Pinschers, fox terriers, Boston terriers, and cocker Spaniels. Male dogs are affected more frequently than female dogs.
The volume of mitral regurgitant flow depends on the size of the regurgitant orifice, and the pressure gradient between the left ventricle and the left atrium. The size of the regurgitant orifice, in turn, depends on the severity of myxomatous changes in the valve and the degree of dilation and distortion of the annulus resulting from left atrial and ventricular enlargement. A vicious cycle is established whereby mitral regurgitation results in ventricular dilatation, which subsequently leads to greater mitral regurgitation. When left atrial pressure rises sufficiently, pulmonary congestion develops accompanied by the usual signs of left-sided congestive heart failure. Mean left atrial pressure is dependent on: (1) the volume of regurgitant flow; (2) the output of the right heart; (3) left ventricular diastolic pressure; and (4) the compliance of the left atrium. Severe pulmonary congestion is most likely to develop when left atrial compliance is low and the regurgitant orifice is large, as happens when a previously compensated patient suffers sudden rupture of a chordae tendineae.
When severe mitral regurgitation develops over a long period of time, the dilated left atrial chamber becomes more compliant, buffering the pressure rise in the atrium as it compensates to provide an adequate ventricular filling volume. As a result, left atrial pressure may be only slightly elevated even in the face of massive regurgitant volumes. Left atrial pressure is also dependent on myocardial contractility and the compliance of the left ventricle. When contractility declines in patients with CDVD, signs of pulmonary congestion are usually already evident. Cardiac performance in dogs with mitral regurgitation is extremely dependent on the optimized preload provided by an appropriately timed "atrial kick." During chronic mitral regurgitation, the left atrium enlarges in size and mass as it develops a more powerful booster action. Loss of this augmented booster pump action can be catastrophic in dogs with severe mitral regurgitation. Atrial fibrillation in dogs with severe mitral regurgitation is usually heralded by sudden cardiac decompensation and the development of pulmonary congestion and signs of low cardiac output. Maintenance of sinus rhythm is a high priority in the treatment of dogs with mitral regurgitation.
Moderate to severe heart failure in dogs with experimentally created or naturally occurring mitral regurgitation is accompanied by increased sympathetic nervous system activity and activation of the renin-angiotensin-aldosterone (R-A-A) system.Diuretic treatment further intensifies the activity of the R-A-A system. The precise sequence and extent of neurohormonal activation in the early stages of degenerative valvular disease has not yet been clearly elucidated, but appears to be less than in dogs with dilated cardiomyopathy. Current research will determine the extent and clinical relevance of neurohormonal activation in dogs with mitral insufficiency, but it appears RAAS activation is not pronounced until late in the course of the disease.
History and clinical signs
Most of the early signs of mitral regurgitation result from pulmonary congestion, and most owners seek treatment for their dog after noticing some degree of respiratory distress. Coughing is a common but nonspecific sign of developing heart failure in dogs. Many older, small breed dogs cough because of chronic bronchitis or from a collapsing trachea. When due to heart failure, coughing is usually accompanied by an elevated respiration rate (tachypnea) and increased respiratory effort (dyspnea). However, cough without dyspnea can occur with compression of the left mainstem bronchus by an enlarged left atrium. Some dogs with CDVD develop signs of right heart failure due to MXD of the tricuspid valve, as a consequence of pulmonary hypertension, or a combination of these disorders. Severe pulmonary hypertension occurs in a small minority of patients with chronic mitral regurgitation and most of these dogs have evidence of serious, underlying pulmonary disease. On rare occasion, signs of right heart failure develop from cardiac tamponade caused by a left atrial tear. Regardless of the underlying cause, the development of abdominal distension and ascites is usually accompanied by signs of low output heart failure and a decline in the severity of pulmonary congestion. Generalized muscle weakness and progressive exercise intolerance become evident when forward output is impaired by severe valvular regurgitation, pulmonary hypertension, and/or declining myocardial contractility. Syncope tends to occur primarily when cardiac output declines precipitously. It is an uncommon sign in dogs with CDVD and is usually associated with a serious cardiac arrhythmia or paroxysms of coughing.
Cardiac auscultation by a skilled examiner is the most practical and economical diagnostic method for detecting mitral regurgitation. The classic murmur of mitral regurgitation is holosystolic, constant in intensity, of mixed frequency, and loudest at the left apex. A soft, grade 1/6, systolic murmur over the mitral area is the first clinical sign of CDVD. A mid or late systolic click or a click-murmur can sometimes be auscultated prior to the development of a holosystolic murmur. Presumably, the mechanism of the click-murmur in dogs is similar to what occurs in human patients with mitral valve prolapse. There is a strong relationship between murmur intensity, heart size, the severity of regurgitation, and NYHA class of heart failure. Dogs with a murmur of grade 3/6 or less and a clearly audible second heart sound are likely to have mild disease. With the development of more severe disease, the murmur becomes louder, the second heart sound becomes softer or inaudible, and a gallop heart sound may be auscultated. An S3 heart sound is often mistaken for the second heart sound when S2 is obscured by the holosystolic murmur. With experience, gallop sounds can be readily identified as they are lower pitched than S2 sounds and they are loudest at the cardiac apex.
Electrocardiograms are frequently normal in dogs with mitral regurgitation even when cardiomegaly can be demonstrated on radiographs or an echocardiogram. Sinus rhythm (cats), sinus arrhythmia (dogs), or sinus tachycardia predominates in animals with mitral regurgitation. Premature ventricular and supraventricular beats are the most common rhythm disturbances recorded in dogs with mitral regurgitation. Atrial fibrillation develops in a small but substantial number of dogs with severe CDVD. It is observed most often in male dogs with severe regurgitation and marked left atrial enlargement. The onset of atrial fibrillation is usually accompanied by marked clinical deterioration. Paroxysmal or sustained supraventricular tachycardia, ventricular tachycardia, and other arrhythmia occur less frequently.
Left atrial enlargement is the earliest and most consistent radiographic feature of mitral regurgitation. Thoracic radiographs are the most sensitive clinical indicator of pulmonary hemodynamics available to the veterinary practitioner. As left-sided congestive heart failure develops, the evaluation of good quality radiographs permits the visualization of early changes in the pulmonary veins and the interstitium of the lung. As pulmonary venous pressures rise, the pulmonary veins distend and become more evident centrally and in the peripheral lung fields. The dilated veins become more dense and larger than the pulmonary arteries that accompany them. At this stage, there is an increased rate of transfer of fluid from the pulmonary capillaries to the interstitium. Further elevations of venous pressure result in the development of radiographically detectable interstitial edema. Fluid accumulation in perivascular lymphatics and the interstitium causes the margins of pulmonary vessels to loose their crisp definition. Fluid accumulates in a similar fashion in the walls of the bronchi and bronchioles causing peribronchiolar cuffing. The overall increase in pulmonary fluid content results in decreased radiolucency of the lung and a loss of contrast between the parenchyma and bronchovascular structures. These changes are often most apparent in the hilar regions of the lungs or in the right caudal lung lobes.
Abnormalities detected by M-mode and 2-dimensional echocardiography reflect changes caused by volume overload of the left heart and are not specific for mitral regurgitation. These changes include an enlarged left atrial dimension, increased left atrial to aortic ratio, an increased ventricular diastolic dimension, exaggerated septal motion and left ventricular wall motion, excessive mitral valve amplitudes of motion and a steep E to F slope. Structural abnormalities of the degenerative mitral valve identifiable by two-dimensional echocardiography include thickened valve leaflets, mitral valve prolapse (inclusive of tip protrusion into the left atrium), and flail leaflets caused by chordal rupture. Mitral regurgitation produces a high velocity, turbulent jet of disturbed blood flow in the left atrium that can usually be detected by pulsed, continuous wave, or color flow Doppler echocardiography. In most cases, mitral regurgitant flow continues throughout systole at a velocity of 5 to 6 meters per second. Flow velocity is a function of the pressure difference between the left ventricle and left atrium. Depending on the color flow display format of the echocardiograph, mitral regurgitant flow appears as a mosaic of yellow and blue pixels or as a bright green spray of color. The sensitivity and specificity of Doppler techniques for the detection of mitral regurgitation are over 90%.
Diuretics, vasodilators, angiotensin converting-enzyme inhibitors, and positive inotropic drugs all have the demonstrated capacity to lessen the severity of mitral regurgitation under certain conditions. The relative merits of specific agents vary with the clinical circumstances of each patient. In general, patients with acute congestive heart failure respond best to diuretics and rapidly acting vasodilators. The current standard of therapy for dogs with chronic congestive heart failure due to mitral regurgitation is combination therapy using furosemide, an ACE inhibitor, and digoxin. Such therapy is sometimes referred to as "triple-drug" therapy. The value of newer agents, such as the inodilator pimobendan, has not been sufficiently evaluated either as sole therapy or in combination with other drugs. Dogs requiring medical therapy to control the signs of heart failure should avoid strenuous exercise. Increasingly severe exercise restriction should be enforced as the disease progresses. The prognosis varies with the stage of the disease and it is currently impossible to predict the rate of progression for an individual patient.
Complications and sequelae
Rupture of the first-order chordae tendineae, particularly of the septal leaflet, results in eversion of the valve leaflet into the atrium, severe mitral insufficiency, and the likelihood of rapid decompensation and acute, severe pulmonary edema. The signs are those of acute left heart failure and massive pulmonary edema. Treatment is often difficult and unsuccessful allowing for postmortem documentation. Vigorous therapy with an intravenous vasodilator, such as nitroprusside, diuretics, and oxygen should be included in the therapeutic plan. Endocardial splitting of the left atrial wall may complicate chronic mitral insufficiency particularly in aged (8 to 15 years), male (86%) Dachshunds and Cocker Spaniels. Perforating myocardial splits most often produce hemopericardium or more rarely atrial septal defects. The sudden development of cardiac tamponade or signs of right heart failure in a previously compensated patient should alert the astute clinician to this possibility. Atrial fibrillation occurs uncommonly but is hemodynamically one of the most serious rhythm disturbances observed. As a result of the loss of the atrial transport, clinical signs usually dramatically worsen with the onset of this rhythm disturbance. Death usually follows within 6 months.