Page 148 - Small Animal Internal Medicine, 6th Edition

120 PART I Cardiovascular System Disorders

and other components increases. In addition, the normal than angiotensin-converting enzyme (ACE), is the enzyme
layered arrangement of collagen within the valve fibrosa responsible for interstitial production of angiotensin II in the
VetBooks.ir layer becomes altered and attenuated, as GAG infiltration myocardium, which contributes to continued ventricular
remodeling. The interstitial collagen loss allows myocardial
disrupts collagen bundles. Altered collagen fiber orientation
within the valve leaflets affects mechanical strain forces
hypertrophy, and changes in LV geometry, produces the
during the cardiac cycle, and, in turn, influences various fiber slippage and, along with myocardial cell elongation,
cellular functions. The altered collagen fibril organization typical progressive eccentric (dilation) hypertrophy pattern
results in mechanically weaker and less flexible valves. Myx- of chronic volume overloading. Stretching of the valve
omatous changes are most severe in the free edge to distal annulus as the ventricle dilates contributes to further valve
third of the valve leaflets. The leaflets thicken and lengthen regurgitation and volume overload.
as CMVD progresses. Myxomatous degeneration of the The compensatory changes in heart size and blood volume
chordae reduces their tensile strength and can predispose to allow most dogs to remain asymptomatic for a prolonged
rupture. period. Left atrial (LA) enlargement may become massive
Gross pathologic valve changes develop gradually with before any signs of decompensation appear, and some dogs
age. Early lesions consist of small nodules on the free margins never show clinical signs of heart failure. The rate at which
of the valve. Over time these become larger, coalescing the regurgitation worsens, as well as the degree of atrial
plaques that thicken and distort the valve. This myxomatous distensibility and ventricular contractility, influences how
interstitial degeneration causes valvular nodular thickening well the disease is tolerated. A gradual increase in atrial,
and deformity, weakening the valve and its chordae tendin- pulmonary venous, and capillary hydrostatic pressures stim-
eae. Redundant tissue between chordal attachments often ulates compensatory increases in pulmonary lymphatic flow.
bulges (prolapses) like a parachute toward the atrium. Mitral Overt pulmonary edema develops when the capacity of the
valve prolapse may be important in the pathogenesis of the pulmonary lymphatic system is exceeded. Pulmonary hyper-
disease, at least in some breeds. In severely affected regions, tension (PH) secondary to chronically increased LA and
the valve surface also becomes damaged, and endothelial pulmonary venous pressure, and worsening tricuspid regur-
cells are lost in some areas. Despite loss of valvular endothe- gitation (TR) can lead to right-sided CHF signs. In addition
lial integrity, however, thrombosis and endocarditis are rare to pulmonary venous hypertension, other factors contribut-
complications. ing to increased pulmonary vascular resistance can include
Affected valves gradually begin to leak because their hypoxic pulmonary arteriolar vasoconstriction, impaired
edges do not coapt properly. Regurgitation usually develops endothelium-dependent vasodilation, and chronic neurohu-
slowly over months to years. Pathophysiologic changes relate moral activation.
to volume overload on the affected side of the heart after the Ventricular pump function usually is maintained fairly
valve or valves become incompetent, with progressive atrial well until late in the disease, even in the face of severe con-
and ventricular chamber enlargement. Mean atrial pressure gestive signs. Nevertheless, studies of isolated myocardial
usually remains fairly low during this time, unless a sudden cells from dogs with subclinical MR show reduced contrac-
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increase in regurgitant volume (e.g., ruptured chordae) tility, abnormal Ca kinetics, and evidence of oxidative
occurs. Secondary atrial jet lesions and endocardial fibrosis stress. Progressive myocardial dysfunction exacerbates ven-
then develop. In patients with advanced disease, partial- or tricular dilation and valve regurgitation and therefore can
even full-thickness atrial tears can form. As valve degenera- worsen CHF. Assessment of LV contractility in animals with
tion worsens, a progressively larger volume of blood moves MR is complicated by the fact that the commonly used clini-
ineffectually back and forth between the ventricle and cal indices (echocardiographic fractional shortening or ejec-
atrium, diminishing the forward flow to the aorta. Compen- tion fraction) overestimate contractility because they are
satory neurohormonal mechanisms are activated and obtained during ejection and are therefore affected by the
augment blood volume to meet the circulatory needs of the reduced ventricular afterload caused by MR. Estimation of
body (see Chapter 3); these include increased sympathetic the end-systolic volume index (ESVI) and some other echo/
activity and renin-angiotensin-aldosterone system (RAAS) Doppler indices also can be helpful in assessing LV systolic
activation. Natriuretic peptide production also increases in and diastolic function (see p. 25).
advanced disease. Chronic valvular disease also is associated with intramu-
Dilation and remodeling of the affected ventricle (and ral coronary arteriosclerosis, microscopic intramural myo-
atrium) gradually occurs in response to growing end- cardial infarctions, and focal myocardial fibrosis. The extent
diastolic wall stress. A multitude of changes in left ventricu- to which these changes cause clinical myocardial dysfunc-
lar (LV) gene expression have been shown, many related to tion is not clear because senior dogs without valvular disease
upregulated proinflammatory responses, collagen degrada- also have similar vascular lesions.
tion, and reduced interstitial matrix production. The LV
remodeling process is characterized by degradation and loss COMPLICATING FACTORS
of the normal collagen weave between the cardiomyocytes, Although CMVD usually progresses slowly, certain compli-
thought largely due to increased production of matrix metal- cating events can precipitate acute clinical signs in dogs with
loproteinases and chymase from mast cells. Chymase, rather previously compensated disease (Box 6.1). For example,