**5. Complications and prognosis**

heart rate increases by 10% or rises over 180 bpm. It is also recommended to supply oxygen by tent, cage, mask, and neck collar or even mechanical ventilation. Clinicians should relieve dyspnea/discomfort via appropriate humidity, environmental temperature, and body posi‐

Several studies have evaluated what cardiac medications can retard the progression of heart failure and can be more effective in asymptomatic HF dogs [18, 104], although most mono‐ therapy was not able to achieve these goals, to date. One recent study has evaluated the out‐ come of dogs with preclinical cardiomyopathy with atrial fibrillation after either pimobendan monotherapy or benazepril monotherapy, and has found that pimobendan monotherapy provided significantly better outcome (i.e., prolonged time to onset of HF or reduced inci‐ dence of sudden death [105]). Unfortunately, several studies failed to find beneficial effects on survival and onset of HF in asymptomatic dogs with various heart diseases after the long‐ term administration of ACEI including enalapril [99, 105]. One recent small pilot study in dogs with asymptomatic HF found modest evidence of beneficial effect on retarding the onset of clinical HF after pimobendan and enalapril dual therapy [106]. One other recent study in asymptomatic dogs with CMVI has also found echocardiographic evidences on improvement of cardiac performance (i.e., increased %LVEF and decreased ESVI) for the first few months after pimobendan monotherapy [107], although this effect did not last to the end of test period (6 months). One recent study on preclinical CMVI dogs after long‐term treatment of enalapril has found long‐term administration of enalapril could significantly delay onset of HF and the endpoint of HF‐all‐cause death [104], although the other study in asymptomatic Cavalier

King Charles Spaniels with CMVI has failed to find this beneficial effect [99].

**Isosorbide dinitrate (ISDN)** is a moderate‐ to long‐acting organic nitrate, and its venodilatory effects may help reduce preload and hence pulmonary edema. In humans, ISDN is used for treating or preventing angina, treating esophageal spasm and achalasia [108, 109]. In addition, it is widely used for CHF outpatients as an adjunctive treatment in CHF [110, 111]. In dogs, it occasionally used to adjuvant agent for management of chronic heart failure or in combina‐ tion with an arteriolar dilator for patients unable to tolerate an ACEI [112]. However, there is limited experience in using this drug in veterinary medicine, and adverse effect is not well known. In humans, the most common adverse effects are headache and postural hypotension. Tachycardia, restlessness, or gastrointestinal effects are not uncommon. There have been rare cases of patients who are hypersensitive to organic nitrates. One recent study has evaluated the efficacy of ISDN for treating advanced stage CHF due to CMVI [113]. Twenty dogs with CMVI were enrolled in this study. All dogs were administered sustained‐release ISDN (1 mg/ kg, q12hr, PO) along with conventional cardiac medication. Changes in systolic blood pres‐ sure (SAP), heart rate (HR), and echocardiographic indices indicating the progression of CHF were evaluated at 7, 15, 30, and 60 days after the administration of ISDN. Significant improve‐ ments in echocardiographic indices were found at 7, 15, 30, and 60 days after the administra‐ tion of ISDN, although the Systolic arterial pressure (SAP) was slightly decreased and the HR

tioning during oxygen supplementation.

108 Canine Medicine - Recent Topics and Advanced Research

**4.3. Guideline for asymptomatic dogs with CMVI**

**4.4. New therapeutic agents in dogs with CMVI**

There are some complications due to heart failure from CMVI such as ruptured chordae ten‐ dineae (RCT), pulmonary hypertension (PHT), acute exacerbation of pulmonary congestion, LA rupture, and cardio‐renal syndrome (CRS) caused by forward heart failure from CMVI [23, 129].
