Effects of afterload reduction with amlodipine in mitral regurgitation severity and Renin Angiotensin Aldosterone System in dogs with Myxomatous Mitral Valve Degeneration

The University of Florida College of Veterinary Medicine is currently recruiting dogs with Myxomatous Mitral Valve Disease (MMVD) ACVIM stage B2 for a clinical trial evaluating the effect of decreasing systemic blood pressure (afterload) with an anti-hypertensive (high blood pressure) medication (amlodipine) on the amount of mitral regurgitation (backwards blood flow) present and activation of the Renin-Angiotensin-Aldosterone-System (RAAS).

Enrollment Status: Enrolling

Inclusion Criteria: Dogs that have been diagnosed with MMVD ACVIM stage B2 (cardiac remodeling based on EPIC criteria with no history of congestive heart failure), are receiving only pimobendan, and have a blood pressure between 120-170 mmHg will be considered for study enrollment. 

Exclusion Criteria: Dogs that are receiving any medications other than pimobendan and preventatives (flea/tick/heartworm), presence of additional congenital or acquired heart disease other than MMVD, presence of concurrent diseases known to be associated with RAAS activation (high blood pressure, protein in the urine), and dogs that have underlying disease found on screening tests performed (complete blood count, chemistry panel, urinalysis) are not eligible for enrollment in the study.

Study design: This study is a double-blinded, randomized, placebo-controlled crossover study where dogs will receive one treatment for two weeks (either amlodipine or placebo), have one week of no treatment (washout period), then receive two weeks of the other treatment (either amlodipine or placebo, whichever was not given in the first treatment period). The order in which dogs receive the treatment (amlodipine first vs. placebo first) is randomized and the clinicians and owners will not be informed of the order until after the study is concluded (blinded study). 3 visits to UF Cardiology at the Veterinary Teaching Hospital in Gainesville are required, with one visit at the start of the study, one visit after the first treatment period (day 15), and one visit after the second treatment period (day 46). At each visit, the patient will receive a full physical exam, blood pressure measurement, blood chemistry panel and RAAS blood profile, and echocardiogram. After conclusion of the second treatment period, the dog has completed the study and no long term follow up is required for study purposes.

Costs: The study will cover the cost of screening tests (complete blood count, serum chemistry panel, RAAS profile, urinalysis, urine protein/creatinine ratio (if required), and blood pressure measurement); two recheck visits and associated testing at each visit (echocardiogram, RAAS profile, serum chemistry, blood pressure); and medications associated with the study (two weeks of amlodipine and two weeks of placebo). The study will not cover the initial echocardiogram for diagnosis of acquired heart disease and will not cover any other costs associated with diagnosis or treatment of your dog.

Contact: Dr. Eduardo J Benjamin or Dr. Meriel LeSueur Cardiology Service (352) 392-2235. If you have further questions or want to see if your dog qualifies, please complete the Cardiology Study Interest Form.

Principal Investigator: Dr. Eduardo Benjamin, DACVIM (Cardiology)

Background: Myxomatous mitral valve degeneration (MMVD) is the most common acquired heart disease in dogs. Over time, significant heart enlargement can occur, and some dogs may develop complications, including left-sided congestive heart failure (LCHF) and arrhythmias. Most dogs with MMVD are treated medically. Common medications used in management include pimobendan in order to promote forward blood flow as well as ACE-inhibitors (e.g. enalapril) and mineralocorticoid receptor blockers (e.g. spironolactone) in order to manage the renin-angiotensin-aldosterone system (RAAS). The RAAS system is used in the body to regulate sodium and water retention, as well as plays a role in remodeling the heart during the disease process. Among other complementary medications, amlodipine, an anti-hypertensive (blood pressure) medication, is used to reduce afterload, which is the force the left heart has to pump against as blood is sent to the body. We hypothesize that therapy with standard doses of amlodipine will increase forward blood flow in the left heart, decrease mitral regurgitation volume and not lead to further RAAS upregulation.

Goal: The goal of this study is to evaluate dogs that have MMVD but don’t have symptoms of heart disease (ACVIM Stage B2) by:

1.) Comparing mitral regurgitation severity before and after amlodipine.

2.) Comparing RAAS activation, blood pressure, blood kidney values and electrolytes before and after amlodipine.

Funding for this research is provided by the American College of Veterinary Internal Medicine (ACVIM).