INTRODUCTION

Acquired degenerative valvular disease is the most common cardiovascular disorder identified in small animals, accounting for approximately 75% of cardiovascular disease seen in dogs.¹ The condition may also be referred to as myxomatous valvular degeneration (MVD), mitral valve prolapse, or valvular endocardiosis. Because the mitral valve is most frequently affected, the condition is often referred to as mitral valve disease. This latter designation is technically incorrect, and the condition may affect all four cardiac valves.² For the purpose of this discussion, myxomatous valvular degeneration will be used to describe the condition.

MVD most frequently affects canine patients, although it may occur in any mammalian species. Feline patients rarely are affected. In the dog, small breeds are over-represented. Breeds commonly associated with the disease include the Poodle, Miniature Schnauzer, Chihuahua, Cocker Spaniel, Dachshund, Cavalier King Charles Spaniel, Lhasa Apso, Shih Tzu, and terrier breeds.^2,3 However, the differential should not be excluded in large-breed dogs with a heart murmur in the left apical position. The disease typically is seen in elderly patients, but some breeds are known to develop MVD relatively early in life (Cavalier King Charles Spaniel).⁴ A male predisposition has been suggested.⁷

PATHOLOGY

The exact cellular and hormonal mechanisms that result in MVD are unknown. One attractive theory suggests that collagen degeneration and collagen synthesis are imbalanced. This is supported by the observation that chondrodystrophic breeds with other connective tissue disorders (collapsing trachea, intervertebral disk disease) frequently develop MVD.² Neurohormonal factors have been implicated, including serotonin and nitric oxide, but the exact role of these hormonal messengers in the development and progression of the disease is unknown.^11-13 A common misconception is that previous or chronic vegetative endocarditis from periodontal disease contributes to MVD, but evidence to support this hypothesis is lacking.

Detailed descriptions of the histologic changes that accompany MVD are beyond the scope of this discussion, and the readers are referred to other sources for this information.^3,5,6 Grossly, the changes are evident as valve thickening and elongation, which subsequently alter the normal coaptation of valve leaflets and may result in valve prolapse. The myxomatous changes have been characterized into classes of severity that are useful in a research setting, but these designations rarely are used clinically.⁵

If the degenerative changes or valve prolapse are significant, they result in a valve regurgitation that increases atrial pressure and decreases forward cardiac output (in the case of atrioventricular valve regurgitation). The degree of valvular insufficiency is dependent on the regurgitant orifice area, the pressure gradient across the valve, and the duration of systole (for the atrioventricular valves) or diastole (for the semilunar valves). In response to the decreased forward cardiac output and increased atrial pressure, several compensatory mechanisms are activated (see Pathophysiology) that result in eccentric hypertrophy (dilation) of the cardiac chambers on either side of the insufficient valve. The valve annulus then enlarges, causing further displacement of the leaflets and more regurgitation. In contrast to diseases with primary myocardial failure (i.e., dilated cardiomyopathy), ventricular function usually is maintained until late in the course of MVD, and patients frequently are symptomatic before severe myocardial failure develops. Large breed dogs may develop myocardial failure sooner during the course of the disease for reasons that are not completely understood, although increased wall stress due to a larger ventricular diameter may be a factor.³ Many patients with MVD have a long preclinical phase before the onset of clinical signs. In these patients the murmur of valvular regurgitation frequently is identified during routine physical examination or when the patient is seen for an unrelated problem. The factors that result in progression from the asymptomatic stage to overt signs of heart failure in some dogs but not others are not completely understood.

PATHOPHYSIOLOGY

A detailed description of the pathophysiology of heart failure is presented elsewhere in this text (see Chapter 36, Left Ventricular Failure), but a brief description is presented here. Decreased forward stroke volume and decreased mean arterial pressure results in neurohormonal activation: increased sympathetic tone, activation of the renin-angiotensin-aldosterone system, and a change in the concentration of numerous other neurohormones (endothelin 1, tumor necrosis factor-α, nitric oxide).^9,10 The net result of these changes is vasoconstriction, sodium and water retention, and an increased forward cardiac output and blood pressure. This is accomplished though increased contractility (sympathetic stimulation), volume expansion, and eccentric hypertrophy. Other neurohormonal mechanisms may be activated to modulate this response (i.e., natriuretic peptide production secondary to increased atrial pressure and stretch), but these measures frequently are overwhelmed or downregulated with chronically altered cardiac output. Chronic activation of the renin-angiotensin-aldosterone system and sympathetic nervous system occurs at the expense of circulating volume and atrial pressure, which is ultimately transmitted to the pulmonary or systemic venous system. Capillary hydrostatic pressure eventually overcomes other forces in Starling’s law (interstitial hydrostatic pressure and capillary oncotic pressure) that help to maintain a balance in movement of fluid across the capillary membrane, and fluid transudation results. Initially the pulmonary and systemic lymphatic systems accommodate the extra fluid transudation, but these systems eventually become overwhelmed, and overt pulmonary edema or third-space fluid accumulation result (congestive heart failure). Additional complications particular to MVD such as rupture of chordae tendineae may also occur. This may be well tolerated with a minor chord but may result in a large increase in regurgitant orifice area and left atrial pressure with acute pulmonary edema. Rarely, left atrial rupture occurs secondary to endothelial tearing at the site of impact of a high-velocity regurgitant jet. This complication results in acute tamponade (see Chapter 43, Cardiac Tamponade and Pericardiocentesis). collapse, and frequently death.

HISTORY AND PHYSICAL EXAMINATION

Patients with MVD frequently have a history of a cardiac murmur that was identified during a routine physical examination. The murmur is often chronic, although it may be a new finding in the case of chordal rupture. The intensity of the murmur has been correlated with the severity of regurgitation.⁸ The patient may be brought in for evaluation of a cough, dyspnea, exercise intolerance, syncope, or collapse. Physical examination findings with left-sided heart failure are attributable to pulmonary edema: dyspnea, orthopnea, cyanosis, and abnormal lung sounds. It should be noted that all patients with pulmonary crackles do not have cardiogenic pulmonary edema, although soft crackles may be present. Tachyarrhythmias (sinus tachycardia, atrial premature contractions, or atrial fibrillation) may also be noted. Right-sided heart failure may result in the accumulation of pleural effusion or ascites, with decreased ventral lung sounds or abdominal distention, respectively. Jugular distention or pulsation should be visible in patients with right heart failure. An S₃ gallop sound may be detected with careful auscultation at the left sternal border in a patient with severe valvular disease.⁸ Femoral pulses usually are strong until late in the course of the disease unless acute chordal or left atrial rupture occurs. With left atrial rupture, patients demonstrate symptoms of cardiac tamponade (see Chapter 43, Cardiac Tamponade and Pericardiocentesis).

LABORATORY EVALUATION

Laboratory findings for patients with MVD often are nonspecific. The complete blood count may be normal or may demonstrate a normochromic, normocytic nonregenerative anemia. A stress leukogram (neutrophilia, monocytosis, lymphopenia, eosinopenia) frequently is present in patients with congestive heart failure. The biochemical profile may be normal or may demonstrate abnormalities consistent with other diseases of aged patients (e.g., chronic renal failure, hepatopathies). Blood gas analysis may reveal varying degrees of hypoxemia with metabolic acidosis secondary to peripheral vasoconstriction and poor perfusion (lactic acidosis).

Research has identified several biochemical markers that may aid in the assessment of the patient with heart failure. The concentration of natriuretic peptides (ANP, BNP) is known to increase in congestive heart failure (CHF), and several studies have demonstrated that these hormones are sensitive and specific in differentiating patients with cardiogenic edema from those with dyspnea of other causes.¹⁴ Human “bedside” analyzers for B-type natriuretic peptide are available and may eventually be included in the veterinary emergency hospital laboratory. Cardiac troponins (particularly cardiac troponin I, or cTnI) have also been investigated as blood-based biomarkers for heart disease in dogs and may be clinically applicable in the future for patients with MVD.^15,16