J. Häggström, Professor, DVM, PhD, DECVIM-CA (Cardiology)
Department of Clinical Sciences, Faculty of Veterinary Medicine and Animal Science, Swedish University of Agricultural Sciences, Uppsala, Sweden
Myxomatous mitral valve disease (MMVD) and dilated cardiomyopathy (DCM) in dogs may lead to signs of congestive heart failure (CHF). During the last 20 years, an important paradigm shift has occurred in the demand for data to support our clinical decisions in dogs with heart disease. Today, several drugs have in clinical trials been shown to improve outcome in small animal CHF patients, as evidenced by improved quality of life and increased survival times. This presentation reviews current treatment alternatives from asymptomatic to progressed stages, associated with severe clinical signs of CHF, in dogs with MMVD or DCM.
Treatment by Disease Stage
Dogs with heart disease may progress into CHF at different rates. The American College of Veterinary Internal Medicine (ACVIM) has proposed a new scheme of classification of heart failure, with classes ranging from A to D. Although this scheme was intended for dogs with MMVD, it may, to some extent, be applicable to dogs with DCM.
Risk Populations (Class A)
No therapy is indicated at this stage, but screening for heart disease is typically conducted in this category of dogs.
Asymptomatic Heart Disease (Class B)
Because of important clinical implications for prognosis and treatment, Stage B is subdivided into Class B1 and B2. Class B1 refers to asymptomatic dogs with no signs of cardiomegaly. Class B2 refers to asymptomatic dogs that have signs of cardiomegaly.
Myxomatous Mitral Valve Disease
The ACE inhibitors were the first studied pharmacological modality in class B MMVD dogs. The SVEP and the VetProof studies investigated the effects of enalapril compared to placebo in delaying the onset of CHF in dogs with MMVD. The two trials showed a similar outcome with a non-significant difference in the time from initiation of therapy until diagnosed CHF. Recently, the results of a trial called the EPIC trial were published. The trial included 360 dogs with cardiomegaly secondary to MMVD, but no signs of CHF, that were randomly allocated to pimobendan or placebo. The primary endpoint was diagnosed CHF or cardiac-related death/euthanasia. The main result was that the median time to the primary endpoint was 1228 days (95% Cl 856–NA) in the pimobendan group and 766 days (95% Cl 667–875) in the placebo group (p=0.0038). Adverse events were not different between treatment groups. Dogs in the pimobendan group lived longer (p=0.012). The EPIC trial is a landmark trial in small animal cardiovascular medicine.
The PROTECT Study was published in 2012 and comprised Doberman pinscher dogs with asymptomatic (stage B) DCM. Pimobendan prolonged the time to the onset of CHF or sudden death (Median 718 days versus the placebo group 441 days, p=0.0088), and increased survival time (Median 623 days versus the placebo group 466 days, p=0.034). Although the PROTECT study was restricted to Doberman Pinscher dogs, the results speak in favor of treating dogs of other breeds with DCM in class B with pimobendan. Finally, there is evidence that some cocker spaniels develop a form of DCM responsive to taurine and carnitine supplementation.
Symptomatic Heart Disease (Class C)
Class C of the ACVIM classification, denotes dogs which have developed signs of CHF. Dogs with severe signs of CHF require hospitalization for stabilization with the goal of chronic management at home. Treatment of dogs with DCM in acute CHF is comparably similar to strategies outlined for MMVD dogs, with a few exceptions. Dogs with DCM in acute CHF are more likely to benefit more from inotropic support and more likely in need of antiarrhythmics. Very few studies are available on efficacy of medical treatments for acute CHF and treatment modalities are often based on clinical experience. Acute treatment of CHF in dogs with MMVD or DCM include furosemide (IV/IM/SC), pimobendan, oxygen supplementation, and centesis if needed. The following drugs may be considered: ACE inhibitors, nitroglycerin ointment, dobutamine, hydralazine.
Dogs with CHF may present with clinical signs mild enough to allow home therapy, or they may have been previously stabilized during hospitalization for acute CHF. Again, DCM dogs are more likely to present with an arrhythmia that might need controlling. Most clinical studies in veterinary cardiovascular medicine are aimed at investigating pharmacological effects and outcomes in this disease category.
MMVD and DCM
The ACVIM panelists recommended the following agents for home therapy (so-called "triple therapy") for class C dogs by consensus:
- Furosemide (1–2 mg/kg PO q12h to 4–6 mg/kg PO q8h)
- Pimobendan (0.25–0.3 mg/kg q12h)
- ACE-inhibitor therapy (e.g., enalapril 0.5 mg/kg, PO q12h)
Other drugs that may be considered:
- Spironolactone (0.25–2.0 mg/kg PO q12–24h)
- Beta-adrenergic receptor antagonists
- Cough suppressants
Clinical Trials in MMVD Class C Dogs
To study the effect of pimobendan on survival in dogs with CHF secondary to MMVD, the QUEST study was undertaken. The aim of the study was to compare the time taken to reach the primary endpoint for dogs receiving either pimobendan or benazepril in conjunction with other therapy. The primary endpoint was a composite of spontaneous cardiac death/euthanasia or treatment failure. 260 dogs were recruited and dogs were included if they had demonstrated evidence of CHF. Dogs receiving pimobendan had a longer survival time compared to those receiving benazepril (pimobendan 267 days versus benazepril 140 days, p=0.0099), a difference in survival time that is of genuine clinical importance.
The introduction of the ACE inhibitors to the veterinary market in the early 1990s and the clinical trials, upon which market approval was based, represented a landmark in the advancement of evidence-based veterinary medicine. These studies show that ACE inhibitors are indicated in advanced MMVD with CHF, as adjunct therapy to diuretics, because dogs receiving an ACE inhibitor benefitted in terms of time until death, euthanasia or treatment failure.
Spironolactone is approved for use within the European Union in dogs with CHF, secondary to MMVD, as adjunctive therapy at a dosage of 2 mg/kg q 24h. This approval was based on improved survival in double-blind, placebo-controlled trials in dogs receiving spironolactone and standard therapy as compared to the placebo group.
Clinical Trials in DCM Class C
Chronic home therapy of dogs with DCM is similar to that of dogs with MMVD. In comparison to placebo, pimobendan has been shown to prolong survival times in Doberman pinschers with DCM, and ACE inhibitors have been shown to improve quality of life variables in two large clinical studies.
Refractory Heart Failure (Class D)
Class D denotes dogs which have developed signs of CHF and/or low output signs (e.g., exercise intolerance, weakness, syncope) and which have been treated and relapsed or failed to respond to standard CHF therapy consisting of recommended drugs and dosages. Dogs in class D are more likely in need of body cavity centesis than in other classes. Very limited numbers of clinical studies are available for dogs in refractory heart failure. This stage represents advanced stages of the disease, and measures instituted may only serve to buy limited extra time. Accordingly, owners should be educated of the prognosis.
While there are many unanswered questions in the management of CHF in dogs, clearly progress has been made in our understanding as to which pharmacological agents may be useful; how we might use them; and in which particular circumstances they will be most valuable. Perhaps even more importantly, we have observed a shift in the demand for data to support our clinical decisions, by both academic and private practitioners and by the public as well. There are, however, areas that need further studies, particularly optimal management of acute CHF.
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