**4. Treatment**

strain rate imaging are TDI‐based measurement and represent regional myocardial deforma‐ tion and deformation rate, respectively [85, 86]. The two‐dimensional STE is recently available and can be used to assess regional myocardial function. The STE is created by irregularities in reflected ultrasound from neighboring structures [87]. Very few data are available regard‐ ing advanced echocardiographic techniques data associated with canine heart diseases. TDI provides myocardial and annular velocity. Unlike Doppler patterns of mitral inflow, TDI assessment of diastolic function is relatively load‐independent. The early mitral inflow veloc‐ ity to early mitral annular tissue velocity (E:Ea) can be used to assess LV diastolic function (**Figure 6D**). The E:Ea ratio is significantly correlated with left ventricular filling pressures

Because most dogs affected by CMVI are older, progression of CMVI can lead to diastolic dysfunction, with time. Diastolic dysfunction is characterized by increased resistance to fill‐ ing and increased left ventricular filling pressure secondary to decreased compliance and impaired relaxation [90, 91]. The assessment of left ventricular diastolic function is difficult to undertake in the dogs with CMVI. Diastolic function can be assessed using several param‐ eters, including isovolumetric relaxation time (IVRT), transmitral flow velocities, and myo‐

Elevated LA pressure caused by MR and volume overload was found in dogs with moder‐ ate‐to‐severe CMVI [92, 93]. For the noninvasive assessment of LA pressure, the IVRT can be used in volume overload model [93]. IVRT is the time that elapses from aortic valve closure to mitral valve opening. In recent studies, the duration of IVRT and the ratio of E to IVRT were used in the diagnosis of elevated LA pressure [94, 95]. Decrease in IVRT is indicative for

The left ventricular diastolic function can be assessed by Doppler patterns of mitral inflow. The transmitral flow profile consists of E and A and is affected by the pressure gradient between the LA and LV. Elevated E represents increased LA pressure and a worsening of heart failure (**Figure 6A**) [5]. If diastolic function is normal, E is greater than A. In early diastolic dysfunc‐ tion, a reversal of E and A can be occurred, as left ventricular compliance decreases. Further worsening of diastolic function leads to pseudonormalization associated with increased LA pressure. Because mitral inflow velocities are load‐dependent, the use of transmitral flow

One recent study has evaluated the diagnostic value of left atrial volume index (LAVi) and the ratio of early filling to early diastolic mitral annular velocity (E/Ea) on the progression of heart failure in 51 dogs with CMVI and body weight matched 18 healthy control dogs, along with other known echocardiographic markers [96]. The LAVi and E/Ea were well correlated with the severity of heart failure in this study group. Based on the receiver‐operating characteristic analysis on echocardiographic variables, the echocardiographic indications for advanced heart failure in this study were left atrium to aorta ratio (LA:Ao) >2.0, left ventricular diastolic dimen‐

, transmi‐

, E‐peak

, while indications for healthy or dogs with

sion to aorta ratio (LVIDd:Ao) >2.4, end‐diastolic volume index (EDVI) >100 ml/m<sup>2</sup>

no signs of cardiac enlargement were LA:Ao <1.3, LVIDd:Ao <1.7, EDVI <45 ml/m<sup>2</sup>

in dogs with CMVI.

[88, 89].

cardial velocities.

104 Canine Medicine - Recent Topics and Advanced Research

increase in LA pressure.

profile to assess diastolic function remains limited.

tral E‐peak >1.2 m/s, E/Ea >9.0 and LAVi 49 ml/m<sup>2</sup>

<0.65 m/s, E/Ea <6.0 and LAVi <15 ml/m<sup>2</sup>

Before initiating treatment for dogs with CMVI, proper staging of heart failure in each affected dogs is required. Two classification systems can be applied in dogs: International Small Animal Cardiac Health Council System (ISACHC) and American College of Veterinary Internal Medicine (ACVIM) classification (**Table 1**).

Basic strategies for treating CMVI are (1) to lessen cardiac workload, (2) to improve clinical conditions from CHF, (3) to retard cardiac remodeling from neurohormonal response from heart failure, and (4) to reduce complications from heart failure. Several therapeutic strate‐ gies have been recommended in the veterinary literatures [18, 97–101]. In 2009, the ACVIM released an expert consensus statement and provided therapeutic guideline for dogs with


**Table 1.** International Small Animal Cardiac Health Council System (ISACHC) and American College of Veterinary Internal Medicine (ACVIM) classification in dogs with heart failure.

CMVI [3]. In practice, the first‐line medications for heart failure in dogs with CMVI should include furosemide, pimobendan, and angiotensin‐converting enzyme (ACE) inhibitor. The route and dose of furosemide administration should be adjusted based on the degree of respi‐ ratory distress and disability. Monitoring renal function is necessary for every dogs, espe‐ cially before and 3–5 days after initiation and adjustment of furosemide and an ACE inhibitor (ACEI). Either surgical replacement or valvuloplasty of damaged mitral valve has been suc‐ cessfully applied in dogs. Furthermore, experimental prosthetic devices for treating CMVI in dogs are under development and evaluation [102, 103].

#### **4.1. Guidelines for long‐term management of CMVI**

**Stage A (risk for heart failure):** Certain breeds of dogs with genetic etiologies, family history of heart disease, a breed predisposition, or concurrent systemic disease with cardiovascular implications (e.g., Cavalier King Charles Spaniels) may have high risk of heart diseases. In these dogs, periodical monitoring for heart diseases is necessary, although no specific therapy is required before the evidence of heart diseases is detectible, according to recent guideline from ACVIM [3]. Dogs used for breeding should be removed from the breeding program if CMVI is present in earlier life. It should be recommended to the dog's owner for periodic cardiac examinations. It is also recommended to manage predisposing condition and to man‐ age systemic hypertension, if present. No dietary sodium modifications are necessary in this stage.

**Stage B1 (heart disease is present: no symptoms, no obvious chamber enlargement):** It is better to inform the owner clinical signs related to CHF (tachypnea, dyspnea, coughing) as early as possible. Periodic reevaluation for signs of disease progression and complications is necessary. For patients with CMVI, there is no evidence indicating that there is any beneficial effect of using an ACE inhibitor (ACEI) or pimobendan at this stage.

**Stage B2 (heart disease is present: no symptoms, cardiomegaly present):** It is generally rec‐ ommended the use of ACEI (enalapril 0.5 mg/kg PO sid to bid; benazepril 0.5 mg/kg PO sid) and highly palatable mildly sodium‐restricted diet. Some cardiologists suggested the use of spironolactone 1 mg/kg PO bid for possible aldactone escape. More detailed guideline can be found in the section "Guideline for asymptomatic dogs with CMVI."

**Stage C1 (stabilized CHF):** If dogs had historical signs of congestive heart failure (CHF), but had no symptoms currently, it is important to keep clinical signs stabilized. Drugs for routine use are furosemide (mandatory) along with ACEI, and/or pimobendan. Drugs for selected patients are spironolactone, digoxin, thiazide, amlodipine/hydralazine, or other vasodilator. In this stage of dogs, excessive sodium intake, beta‐blockers, corticosteroid, and intravenous (IV) fluid should be avoided, if possible (unless required for concurrent disease). If IV fluid is given to this dog, it requires careful monitoring of the respiratory rate trend.

**Stage C2 (mild‐to‐moderate CHF):** Therapeutic goals are to eliminate pulmonary edema or effusions, to improve hemodynamics, and to modulate neurohormonal activation. In dogs with CMVI, drugs include furosemide (1–2 mg/kg PO bid), ACEI (enalapril 0.5 mg/kg PO bid), and pimobendan (0.25 mg/kg PO bid). Digoxin may be beneficial, if atrial fibrillation is present. Beta‐blockers should not be introduced firstly, unless the dog is being medicated. In this stage of dogs, excessive sodium intake, beta‐blockers, corticosteroid, and intravenous (IV) fluid should be avoided, if possible (unless required for concurrent disease). If IV fluid is given to this dog, it requires careful monitoring of the respiratory rate trend.

CMVI [3]. In practice, the first‐line medications for heart failure in dogs with CMVI should include furosemide, pimobendan, and angiotensin‐converting enzyme (ACE) inhibitor. The route and dose of furosemide administration should be adjusted based on the degree of respi‐ ratory distress and disability. Monitoring renal function is necessary for every dogs, espe‐ cially before and 3–5 days after initiation and adjustment of furosemide and an ACE inhibitor (ACEI). Either surgical replacement or valvuloplasty of damaged mitral valve has been suc‐ cessfully applied in dogs. Furthermore, experimental prosthetic devices for treating CMVI in

**Stage A (risk for heart failure):** Certain breeds of dogs with genetic etiologies, family history of heart disease, a breed predisposition, or concurrent systemic disease with cardiovascular implications (e.g., Cavalier King Charles Spaniels) may have high risk of heart diseases. In these dogs, periodical monitoring for heart diseases is necessary, although no specific therapy is required before the evidence of heart diseases is detectible, according to recent guideline from ACVIM [3]. Dogs used for breeding should be removed from the breeding program if CMVI is present in earlier life. It should be recommended to the dog's owner for periodic cardiac examinations. It is also recommended to manage predisposing condition and to man‐ age systemic hypertension, if present. No dietary sodium modifications are necessary in this

**Stage B1 (heart disease is present: no symptoms, no obvious chamber enlargement):** It is better to inform the owner clinical signs related to CHF (tachypnea, dyspnea, coughing) as early as possible. Periodic reevaluation for signs of disease progression and complications is necessary. For patients with CMVI, there is no evidence indicating that there is any beneficial

**Stage B2 (heart disease is present: no symptoms, cardiomegaly present):** It is generally rec‐ ommended the use of ACEI (enalapril 0.5 mg/kg PO sid to bid; benazepril 0.5 mg/kg PO sid) and highly palatable mildly sodium‐restricted diet. Some cardiologists suggested the use of spironolactone 1 mg/kg PO bid for possible aldactone escape. More detailed guideline can be

**Stage C1 (stabilized CHF):** If dogs had historical signs of congestive heart failure (CHF), but had no symptoms currently, it is important to keep clinical signs stabilized. Drugs for routine use are furosemide (mandatory) along with ACEI, and/or pimobendan. Drugs for selected patients are spironolactone, digoxin, thiazide, amlodipine/hydralazine, or other vasodilator. In this stage of dogs, excessive sodium intake, beta‐blockers, corticosteroid, and intravenous (IV) fluid should be avoided, if possible (unless required for concurrent disease). If IV fluid is

**Stage C2 (mild‐to‐moderate CHF):** Therapeutic goals are to eliminate pulmonary edema or effusions, to improve hemodynamics, and to modulate neurohormonal activation. In dogs with CMVI, drugs include furosemide (1–2 mg/kg PO bid), ACEI (enalapril 0.5 mg/kg PO bid), and pimobendan (0.25 mg/kg PO bid). Digoxin may be beneficial, if atrial fibrillation is

effect of using an ACE inhibitor (ACEI) or pimobendan at this stage.

found in the section "Guideline for asymptomatic dogs with CMVI."

given to this dog, it requires careful monitoring of the respiratory rate trend.

dogs are under development and evaluation [102, 103].

106 Canine Medicine - Recent Topics and Advanced Research

**4.1. Guidelines for long‐term management of CMVI**

stage.

**Stage C3 (severe and/or life threatening CHF):** Therapeutic goals are to treat hypoxemia, to increase cardiac output, and to stabilize the patient in hospital with intravenous drugs. Drugs for routine use in stage C2 are needed with oxygen supplementation (depending on dog's condition) and high dose of furosemide (2–8 mg/kg IV; repeat injections every 1–2 h if there is no improvement in respiratory rate) with nitrate therapy (e.g., nitroglycerin patch/cream, sodium nitroprusside, isosorbide dinitrate). As the respiratory rate decreases, the dosage and frequency of administration are reduced to the lowest dose effective in controlling the pulmo‐ nary edema. Renal function should be kept monitoring.

**Stage D (refractory, chronic CHF):** Drugs for routine use in stage C3 are needed with increased dose/frequency of pimobendan (up to 0.7 mg/kg, PO, tid), supplementation of spironolactone (1–2 mg/kg PO, bid) and hydrochlorothiazide (1–2 mg/kg, PO, bid), subcutaneous furose‐ mide, repeated centesis for effusions, digoxin or other antiarrhythmic drugs if needed, and very low sodium intake. Triple diuretics (furosemide, spironolactone, hydrochlorothiazide) can reduce the dose of furosemide required to control the patient's congestive signs. In CMVI, it can be considered for additional amlodipine (0.05 mg/kg PO, sid, then 0.1 mg/kg PO, with blood pressure monitoring) if blood pressure is normally preserved.
