**2. Pathogenesis and clinical signs**

Pathological features of canine CMVI are degenerative changes on mitral valve, mitral valve thickening and opacity, several degrees of leaflet retraction, node of valve's end, and length‐ ened chordae tendineae (**Figure 1**) [17, 18] and are similar to human MVP [19, 20]. Disruption of collagen and deposition of glycosaminoglycans in mitral valve are also common micro‐ scopic feature in this disease [11, 19, 21]. Long‐standing mitral valvular insufficiency can

**Figure 1.** Pathological features of canine chronic mitral valvular insufficiency are degenerative changes on mitral valve, mitral valve thickening and opacity, several degrees of leaflet retraction, node of valve's end and lengthened chordae tendineae. (A) Diagram of normal mitral valve (top) and mitral regurgitation (bottom), (B) diagram of mitral valve insufficiency from chronic degenerative changes on mitral valve leaflets (box).

cause volume overload of both the LA and the LV. Furthermore, the increased end‐diastolic volume in LV can cause pressure overload on the LA. Subsequently, the increased pressure in the LA inhibits drainage of blood from the lungs via the pulmonary veins and thus causes pulmonary congestion. If this condition is untreated, it will eventually develop LV dysfunc‐ tion and CHF [22].

Coughing, especially nocturnal cough, may be the first clinical signs in CMVI. However, in dogs with advanced stage of heart failure (HF), dyspnea such as shortness of breath, difficulty breathing, and orthopnea may be the major signs. Depending on the severity of CMVI, the dog maybe had certain degree of exercise intolerance, lethargy, reduced appetite, and weight loss [23].
