**5.3. Impaired function of digestive system**

Right‐sided heart failure is common, especially in dogs with long‐standing history of CMVI. Right‐sided heart failure can be occurred by either/both concurrent chronic tricuspid insuf‐ ficiency from myxomatous degeneration and/or the PHT from LA volume and pressure overload. Dogs with marked PHT generally show marked exercise intolerance with signs of weakness or collapse. Signs related to right‐sided heart failure (e.g., ascites, pleural effusion, hepatic and splenic congestion, and distention of the jugular veins with abnormal pulsations) can be noticed in physical examination. The presence and degree of PHT can be accurately assessed by Doppler echocardiography. Oxygen supplementation and pulmonary arterial

Tachyarrhythmias are more commonly occurred in dogs having an enlarged LA. Common tachyarrhythmias in dogs with CMVI are supraventricular premature beats, atrial fibrillation, and supraventricular tachycardia. If the tachyarrhythmia has ventricular rate >180 bpm, it can cause hemodynamically significant change in dogs with CMVI and cause an acute onset of pulmonary edema. This condition is more often seen in dogs with long‐standing CMVI. Therapeutic goals for these dogs are directed to relieve the pulmonary edema along with the

Left atrial rupture and cardiac tamponade can be occurred by marked dilation of LA in dogs with CMVI, because the LA becomes thin walled and more vulnerable to increase in pressure. One study found that endocardial splitting is more common in dogs with long‐standing CMVI [133]. Long‐standing and marked LA volume and pressure overload can progress to rupture of the LA, subsequently with the acute onset of hemopericardium, cardiac tamponade, and sudden death. Acute development of ascites, collapse, or marked exercise intolerance can be signs for sudden development of LA rupture and cardiac tamponade. Echocardiography is necessary for confirming the presence of significant pericardial effusion. Although immedi‐ ate pericardiocentesis may be helpful to alleviate clinical signs, the prognosis is usually poor.

Cardio‐renal syndrome (CRS) is a clinical syndrome broadly in which dysfunctional hearts and dysfunctional kidneys can "initiate and perpetuate disease in the other organ though common hemodynamic, neurohormonal, and immunological/biochemical feedback path‐ ways" [134]. General definition of CRS is a pathophysiologic disorder of the heart and kidneys, whereby acute or chronic dysfunction in one organ may induce acute or chronic dys‐ function in the other organ. According to human medical literature [134], the CRS is largely divided into five types: (1) Type I (acute CRS) is acute kidney injury induced by acute heart failure (e.g., acute cardiogenic shock or acutely decompensated CHF), (2) Type II (chronic CRS) is permanent and progressive chronic kidney disease induced by chronic heart failure (e.g., chronic abnormalities in cardiac function), (3) Type III (acute reno‐cardiac syndrome, RCS) is acute heart failure induced by acute kidney diseases (e.g., acute kidney ischemia or glomerulonephritis), (4) Type IV (chronic RCS) is chronic heart failure induced by chronic kidney disease (e.g., chronic glomerular or interstitial disease), and (5) Type V (secondary CRS) is heart and renal failure induced by systemic diseases (e.g., diabetes mellitus, sepsis). Major mechanisms of CRS include renal hypoperfusion directly resulting from a decreased

vasodilator (e.g., sildenafil) are helpful to lessen clinical signs in dogs [131, 132].

reduction in heart rate to an acceptable rate for improving cardiac output.

**5.2. Cardio‐renal syndrome**

110 Canine Medicine - Recent Topics and Advanced Research

Impaired function of digestive system is associated with malassimilation (i.e., maldigestion and malabsorption) induced weight loss [136]. The weight loss is a major clinical finding in certain degenerative diseases including CMVI [23], hepatobiliary disease [137], and pancre‐ atitis [138]. Aging is involved in the pathogenesis of CMVI in dogs [6–8, 139] and can induce several anatomical changes and involve in progressive deterioration of the vital physiological functions. The organ congestion and poor body perfusion can be occurred by heart failure [25], and these can lead to organ damage (i.e., pancreas, liver, intestine) and dysfunction (i.e., maldigestion and malabsorption, hepatomegaly, ascites) [23, 140–144]. Therefore, pancreatic dysfunction associated with heart failure can be occurred in dogs with advanced stage of heart diseases. Ischemia can induce acute/chronic pancreatitis and is one of the important etiologies of acute pancreatitis in human. Several mechanisms are involved in pathogenesis of pancreatitis, such as hemorrhage or hypotension, mesenteric macro‐vessel occlusion, post‐ transplantation pancreatitis, cardiopulmonary bypass. Different causes of ischemia can lead to a hypoperfusion of the pancreas with a consecutive induction of an inflammatory response. Diagnosis of pancreatitis is straightforward with in‐house diagnostic test kit (SNAP® cPLI™), which has 95% correlation on sensitivity to the reference laboratory. One recent study found that CMVI is associated with pancreatic injury in congestive heart failure caused by CMVI. Therefore, periodic monitoring on cPLI could be useful in monitoring dogs in heart failure [27].

Oral cavity is one of the blood‐rich organs. Hypoxia can induce many dental problems includ‐ ing dental tartar and periodontitis, which is requiring general anesthesia for treatment. We developed anesthetic protocol for dogs with cardiac diseases [145]. Our study was designed to evaluate the effects on cardiovascular system in dogs using anesthetic combination of alfaxalone, butorphanol, and midazolam. Compared to the baseline value (before anesthesia), all cardiac indices were decreased, although only heat rate and aortic blood pressure were statistically significantly decreased (*p* < 0.05). However, the cardiac depression was minimal and transient by this combination of anesthetic agents [145].

Cardiac cachexia is generally seen in dogs with history of long‐standing CMVI [23, 99]. Once heart failure develops, an important indicator of a worsening condition is the occurrence of cardiac cachexia, which is unintentional rapid weight loss (a loss of at least 7.5% of normal weight within 6 months).

#### **5.4. Prognosis**

Many dogs with CMVI may live for years before developing any symptoms. Prognosis for dogs with CMVI is greatly depending on the severity of heart failure and duration and qual‐ ity of medical therapy and patient monitoring. Generally, the average survival time of dogs with CMVI is ~3 years in dogs with ISACHC I stage heart failure, while 1–3 years in dogs with ISACHC II stage heart failure and ~6–12 months in dogs with ISACHC III stage of heart fail‐ ure, respectively [13]. There are several prognostic indicators for dogs with CMVI. The degree of exercise intolerance [146], degree of cardiomegaly [53], degree of LA/LV enlargement [7, 147], and certain ECG indices (e.g., the degree of tachycardia or vagus tone index) [51] were closely related to the prognosis. Furthermore, certain echocardiographic indices (e.g., LA/Ao ratio, E/A wave ratio, EDVI) were found to be a good prognostic indicator in dogs with CMVI [84, 148]. Weight loss (e.g., cachexia) and degree of azotemia by reduced glomerular filtration rate (GFR) are indicators for worsening clinical signs.
