Figure 6-1 A specimen that demonstrates the gross features of severe mitral valve degeneration. The mitral valve leaflets are abnormally thick and nodular.

(The author acknowledges the Department of Veterinary Pathology, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, Canada S7N 5B4, for providing this photograph.)

Etiopathogenesis

• The cause of MVD is unknown.

• MVD is often observed in chondrodysplastic dog breeds. Because MVD has been associated with concurrent disorders such as bronchomalacia and intervertebral disc disease, it has been suggested that MVD is but one expression of a systemic connective tissue disease.

• Recent evidence suggests a possible role for the vasoactive peptide endothelin in the pathogenesis of MVD. Relative to mitral valve tissue obtained from healthy young dogs, degenerative mitral leaflets had a greater density of endothelin receptors. Furthermore, the density of endothelin receptors was related to the severity of MVD.

• Because distinct breed predispositions are recognized, it is likely that there is a genetic predisposition for the development of MVD. Available evidence suggests that the tendency to develop MVD is not subject to simple Mendelian inheritance but rather is a polygenic trait.

• In Cavalier King Charles Spaniels, parental status with respect to age and murmur intensity is an important determinant of the prevalence of murmurs in 5-year-old offspring. Based on this, it appears that the age at which MVD develops is inherited.

Key Point

The cause of MVD is not known but genetic factors are likely important.

Pathophysiology

• The mitral valve apparatus consists of the mitral valve leaflets, the fibrous valve annulus, the chordae tendineae, and the left ventricular papillary muscles.

• The two mitral leaflets are known as the septal (anterior) and the caudal (posterior) leaflets. In health, the mitral leaflets are thin, translucent structures that are tethered to the left ventricular papillary muscles by the chordae tendineae. The two left ventricular papillary muscles arise from the caudal (free) wall of the left ventricle. The basilar attachment of the mitral leaflets is to the fibrous left atrioventricular valve ring, known as the mitral annulus.

• The initiation of valve closure is a passive process; in early systole, when left ventricular pressure exceeds left atrial pressure, the mitral valve leaflets are forced into apposition. In normal individuals, the tethering effect of the chordae tendineae prevents prolapse, or bowing, of the leaflets into the left atrium.

• Coaptation of the normal mitral leaflets is complete, and there is little or no regurgitation through the valve orifice. The normal mitral valve ensures that the entirety of the left ventricular stroke volume is ejected through the aorta. When the mitral valve is incompetent, a fraction of the left ventricular stroke volume is ejected through the mitral valve regurgitant orifice into the left atrium.

• Mitral valve regurgitation (MR) may be mild and have minimal consequences, or it can be severe. The severity of MR is determined principally by the size of the regurgitant orifice and the relationship between left atrial and left ventricular systolic pressure. Potentially, both of these determinants can be pharmacologically manipulated by administration of vasodilators.

• MR increases left atrial pressure which potentially results in left atrial dilation. When the mitral valve leaks, the pulmonary venous return is augmented by the regurgitant volume; in consequence, the ventricle is filled in diastole not only by blood that has returned from the lungs, but also by blood that has been regurgitated into the atrium. Therefore, MR imposes a volume load on the left ventricle and the left atrium.

• High end-diastolic pressures and volumes result in ventricular dilation and hypertrophy. Hypertrophy of this type, in which the ratio of wall thickness and chamber size remains roughly unchanged, is known as eccentric hypertrophy.

• Severe MR may increase left ventricular filling pressures. High filling pressures are reflected backward, raising pulmonary vein pressure and potentially initiating the development of pulmonary edema.

• The syndrome of clinical signs and neuroendocrine activation that results from cardiac dysfunction is known as heart failure. Because veterinary patients cannot offer subjective observations—the perception of breathlessness during exertion for example—the presence of congestive signs is generally used as an objective criterion for the diagnosis.

• CHF is the syndrome of clinical signs caused by venous pressure elevations that result from cardiac dysfunction. Left-sided CHF is defined by the presence of cardiogenic pulmonary edema. Right-sided CHF refers to clinical signs that result from systemic congestion; in dogs, ascites is the most common manifestation of right-sided CHF.

• Due to maladaptive neuroendocrine responses associated with heart failure, cardiac dysfunction tends to be progressive. Because of this, the elimination of congestive signs does not signify resolution of the heart failure state. When the disorder responsible cannot be definitively corrected, heart failure is a terminal syndrome.

• The imposition of a chronic volume load on the heart can result in deterioration of systolic myocardial function, a state sometimes known as cardiomyopathy of overload. In general, MR is relatively well tolerated by the myocardium because the left atrium represents a low-pressure reservoir into which the ventricle can eject blood. In fact, dogs that develop CHF due to MR often do so at a time when systolic myocardial function (contractility) is, based on echocardiographic indices, normal or only mildly diminished.

• MR may remain clinically silent until it is advanced. When CHF results from MR, clinical signs may include weakness, syncope, cough, and dyspnea.

• Cough is a centrally mediated reflex, and most cough receptors are located in the large airways. The etiology of cough associated with MR in small-breed dogs is probably multifactorial and may result from any of the following:

• Pulmonary edema when fluid floods the alveoli

• Compression of the mainstem bronchi by an enlarged left atrium

• Reflexes mediated through stimulation of the juxtapulmonary (J) receptors; these receptors are associated with the pulmonary capillaries and are sensitive to increases in pulmonary venous pressure.

Key Point

It is important to recognize that cough can be associated with MVD in the absence of pulmonary edema. When this is the case, the cough is a sign of heart disease but not a sign of heart failure; this distinction is important because a diagnosis of CHF carries important prognostic and therapeutic implications.

Clinical Presentation

History

• MVD exhibits a broad spectrum of severity. In most affected dogs, MVD does not cause clinical signs, and the disease is detected when a cardiac murmur is incidentally identified in patients presented for routine health care or for management of noncardiac disease.

• In cases in which MVD does become clinically apparent, cough is usually the clinical sign that is first observed by the dog owner. Coughing due to bronchial compression is often dry and harsh. When coughing is due to pulmonary edema or congestion, other signs, such as exercise intolerance and tachypnea, are usually present. The cough associated with pulmonary edema may be moist and productive. The expectoration of pink froth is sometimes observed in patients with fulminant pulmonary edema.

• Occasionally, syncope is the clinical sign that is seen first in dogs with MVD. Syncope is a transient loss of consciousness that is usually related to a sudden and precipitous decline in cerebral perfusion. MVD can be responsible for syncope when cardiac enlargement predisposes to arrhythmias. Additionally, exertional syncope may result when MR limits stroke volume so that cardiac output does not adequately increase to meet the physiologic demands of exercise. Alternatively, syncope on exercise or excitement or associated with paroxysmal cough can result from sudden onset of reflex-mediated bradycardia.

• Other clinical signs related to reduced cardiac performance, including tachypnea, exercise intolerance, and abdominal distention caused by ascites, occasionally prompt owners of affected dogs to seek veterinary attention.

Physical Findings

• The most notable feature of the physical examination is a systolic murmur that is usually heard best over the left cardiac apex. The murmur of MVD is indistinguishable from the murmur caused by other disorders, such as IE or dilated cardiomyopathy (DCM), which also can result in MR. Importantly, however, an acquired, left apical, systolic murmur in an older, small-breed dog is almost always due to MVD. The intensity of the murmur depends on a number of factors, but severe MR usually causes a loud murmur. Severe MR associated with a nonrestrictive regurgitant orifice can result in a soft murmur but this is extremely uncommon in MVD. Phonocardiographically, the murmur of MR typically has a plateau-shaped configuration meaning that the murmur has a similar intensity throughout systole; when the murmur is loud, the second heart sound may be obscured (Figure 6-2).

• An exaggerated apical impulse is often evident on precordial palpation of patients with moderate or severe MR. By definition, a precordial thrill is present when the murmur intensity is grade V/VI or greater.

• A high-frequency, mid-systolic click (Figure 6-3) is sometimes heard in older, small-breed dogs. These clicks may be associated with prolapse of the mitral valve. In many dogs, clicks are a precursor of MR. Often, a soft systolic murmur of MR can also be heard in patients that have systolic clicks.

• When MR is severe, the third heart sound sometimes is audible and results in an S3 gallop. Care must be taken to distinguish a mid-systolic click from a gallop. In general, a systolic click is louder than is the third heart sound, and in patients with MVD, a click typically is heard in association with findings that suggest mild MR. In contrast, an S3 gallop usually reflects severe MR and generally is heard in patients with loud murmurs. Note that S3 is sometimes audible in patients with DCM. However, DCM is typically a disorder of large and giant breed dogs.

• The femoral arterial pulse is usually of normal strength when MR is present, but the pulse may have a rapid rise. Very severe MR can be associated with diminished pulse strength.

• Crackles may be heard in patients with pulmonary edema. It should be recognized that the prevalence of primary respiratory diseases such as chronic bronchitis in the patients most often affected by MVD is relatively high. Primary respiratory tract diseases can explain adventitious pulmonary sounds, such as crackles, in the absence of pulmonary edema.

• Abdominal palpation is usually normal in patients with MVD, but hepatic enlargement or even ascites may be present when there is severe tricuspid valve disease, or when pulmonary hypertension complicates the presentation of MVD.

Key Point

Patients with clinically evident MVD have cardiac murmurs. The intensity of the murmur roughly parallels disease severity so that severe MR usually results in a loud murmur.

Figure 6-2 A phonocardiogram recorded from a 13-year-old female spayed mixed-breed dog with a grade 4/6 systolic murmur. The systolic murmur (SM) begins at the first heart sound (S1), is evident throughout systole and obscures the second heart sound.

Figure 6-3 A phonocardiogram recorded from an 11-year-old male castrated Shih-Tzu. A mid-systolic click (click) is shown.

Patients with Mitral Regurgitation and Concurrent Respiratory Tract Disease

• Primary diseases of the respiratory tract, such as collapsing trachea and chronic bronchitis, are common in the patient group that is affected by MVD. In an individual patient, it can be difficult to determine whether cardiac disease or respiratory disease bears the greatest responsibility for the development of clinical signs.

• In general, patients that have severe MR are more likely than patients with respiratory disease to have poor body condition.

• Although loud murmurs of MR are sometimes clinically inconsequential, it is extremely uncommon for soft murmurs to indicate severe MR with cardiac enlargement.

• The presence of respiratory sinus arrhythmia (RSA) can also be of diagnostic value. Much of the moment-to-moment heart rate variability observed in healthy dogs is due to the effect of vagal discharge. In patients with severe cardiac disease, there is little vagal influence on heart rate and rhythm and as a result, RSA is not prominent. In contrast, sinus arrhythmia is often preserved or even accentuated when primary respiratory tract disease is responsible for clinical signs. The physical finding of RSA is virtually incompatible with a diagnosis of CHF.

• Although exceptions occur, clinical signs are usually related to respiratory tract disease in patients that are overweight, have sinus arrhythmia and a soft cardiac murmur.

• In contrast, the clinical signs of thin patients with loud murmurs and tachycardia are more likely to result from cardiac disease or CHF.

• Coughing in elderly, small-breed dogs that do not have cardiac murmurs is almost always due to primary respiratory tract disease (Table 6-1).

Key Point

Primary respiratory tract disease is relatively common in the patient group affected by MVD. The patient history and physical findings are helpful in distinguishing clinical signs caused by cardiac disease from signs caused by respiratory disease.

Table 6-1 Guidelines for Clinical Assessment of Elderly Small-Breed Dogs With Cough and Cardiac Murmur ^*

	Cardiac Disease	Respiratory Disease
Body condition	Thin	Obese
Cardiac murmur	Loud	Often soft, occasionally loud
Heart rate	Rapid	Normal or slow
Rhythm	Regular, unless pathologic arrhythmias are present	Exaggerated respiratory arrhythmia may be present

* It is important to recognize that exceptions to these generalities certainly occur. However, when a patient exhibits all of the findings in the left-hand column, it is likely that cardiac disease or, perhaps, congestive heart failure, is responsible for the cough. It must be recognized that some patients have both respiratory tract disease and cardiac disease. Ultimately, the distinction between respiratory tract disease and cardiac is made through diagnostic imaging; thoracic radiographs are indispensable, and echocardiography often provides useful, complementary data.

Large-Breed Dogs with Mitral Valve Disease

• A syndrome of severe MR and concurrent myocardial dysfunction is recognized in medium- and large-breed dogs. The fact that this observation was made relatively recently is probably explained by the increasing availability of echocardiography and not by a change in the epidemiology of MVD. Before widespread availability of this technology, large-breed dogs with heart failure generally were assumed to have primary myocardial disease.

• For reasons that are not known but may relate to the geometry or pattern of contraction of inherently larger ventricles, large-breed dogs with MR are more apt to develop echocardiographically evident myocardial dysfunction than are small-breed dogs.

• The gross appearance of the valvular lesions in large dogs tends to be less impressive than it is in small breed dogs.

• Perhaps because myocardial dysfunction complicates MVD in large dogs more often than it does in small dogs, the prognosis may be worse than in smaller dogs.

Diagnostic Findings

Thoracic Radiography

In most cases, thoracic radiography is the most important element of the diagnostic approach to MVD. MVD is extremely common but progresses at a rate that varies greatly among individuals. Many patients with MVD are subclinical (“asymptomatic”) and never develop clinical signs related to MR. Early in the course of MVD, the cardiac silhouette is normal. If clinically consequential MR develops, then there is enlargement of the cardiac silhouette. It should be recognized that the ability of thoracic radiographs to delineate specific cardiac chambers is limited. In general, the left atrium can be assessed with the greatest certainty. This is fortunate because, in the overwhelming majority of cases, left atrial enlargement precedes the development of CHF. A diagnosis of left-sided CHF secondary to MVD rarely can be supported in the absence of radiographic left atrial enlargement.

Radiographic Appearance of Left Atrial Enlargement

• The left atrium is left of, and caudal to, the right atrium. Radiographically, it occupies the caudodorsal area of the cardiac silhouette in the lateral projection.

• In the absence of left atrial enlargement, the caudal portion of the trachea curves ventrally over the caudal aspect of the cardiac silhouette.

• When the left atrium is enlarged, the caudal border of the cardiac silhouette straightens, and the trachea is forced dorsally to varying degrees. With marked left atrial enlargement, the left mainstem bronchus is narrowed, and the trachea adopts a path that is parallel to the thoracic vertebrae. Occasionally, severe left atrial enlargement has the appearance of a mass that splits the mainstem bronchi.

• In the ventrodorsal projection, the left atrium is located near the center of the cardiac silhouette. When enlarged, the left atrium splits the mainstem bronchi to varying degrees. This is apparent in well-penetrated radiographs and results in an appearance that is sometimes known as the “crab sign” or the “bowlegged cowboy” (Figures 6-4 and 6-5).

• Additionally, in the ventrodorsal view, enlargement of the left atrium may cause a bulge which represents the atrial appendage at the 3 o’clock position.

Figure 6-4 Lateral (A) and ventrodorsal (B) thoracic radiographs obtained from a 10-year-old mixed-breed dog with degenerative mitral valve disease. There is relatively mild but distinct left atrial enlargement, as evidenced by elevation of the trachea and loss of the caudal waist in the lateral film.

Figure 6-5 A lateral thoracic radiograph obtained from a 14-year-old female spayed mixed-breed dog with severe mitral valve incompetence due to degenerative disease. The left atrium is markedly enlarged, and the left mainstem bronchus is compressed.

Radiographic Findings of Pulmonary Congestion and Edema

• The radiographic finding of pulmonary venous distention reflects increases in pulmonary venous pressure. Pulmonary venous distention suggests pulmonary congestion and may precede the development of pulmonary edema.

• A central, or perihilar, distribution often characterizes cardiogenic pulmonary edema in dogs.

• The development of interstitial pulmonary edema precedes the appearance of alveolar edema.

• Blurring of vascular detail in the presence of left atrial enlargement and, sometimes, concurrent pulmonary venous distention characterizes the radiographic appearance of interstitial pulmonary edema.

• When tissue fluid weeps into the pulmonary alveoli, it provides contrast with air-filled structures such as the bronchi, resulting in air bronchograms. Alveolar pulmonary opacities together with radiographic evidence of left atrial enlargement are diagnostic of left-sided CHF (Figure 6-6). The presence of alveolar pulmonary edema indicates severe CHF that is almost invariably associated with noticeable respiratory distress.

Key Point

In most cases, thoracic radiography is the most important aspect of the diagnostic approach to MVD.

Figure 6-6 Lateral (A) and ventrodorsal (B) thoracic radiographs obtained from an 11-year-old female spayed Miniature Poodle with degenerative mitral valve disease. The cardiac silhouette is markedly enlarged, and there is evidence of left atrial enlargement. Pulmonary opacities compatible with edema are distributed throughout the lung; the edema is most noticeable in the caudodorsal lung field.