Cardiology

An Everyday Approach to Canine Degenerative Mitral Valve Disease

An Everyday Approach to Canine Degenerative Mitral Valve Disease
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Mark A. Oyama, DVM, Diplomate ACVIM (Cardiology)

Degenerative mitral valve disease (DMVD) is a common canine cardiac disease; approximately 30% of dogs over age 10 possess the characteristic left-sided systolic murmur of DMVD and resulting mitral regurgitation (MR).1 DMVD is most common in small breeds, with some breeds being highly predisposed. For example, virtually all Cavalier King Charles spaniels will develop DMVD during the course of their lifetimes.

Developing a standardized approach to patients with DMVD can help the clinician concentrate on the most important diagnostic aspects of disease as well as provide useful information about monitoring and prognosis. This overview will focus on the role of the physical examination and thoracic radiographs and how information from these tests can aid in the everyday diagnosis and management of DMVD.

Diagnosis of DMVD

Diagnosis of DMVD is one of the easiest clinical aspects of the disease. A presumptive diagnosis can be made on the basis of patient signalment and physical examination, wherein the hallmark finding is an adult small-breed dog with a left-sided systolic murmur. In these instances, it is reasonable to assume that the source of the murmur is MR and hence, DMVD is present. Once a diagnosis has been made, the next question is: what is the severity of DMVD?

Assessing Severity of DMVD

Pathophysiology

As DMVD worsens, the valve leaflets degenerate, resulting in worsening MR. The reduction in forward cardiac output triggers activation of several neurohormonal pathways, including the renin–angiotensin–aldosterone system and sympathetic nervous system. For instance, reduction in renal perfusion results in renin release from the macula densa, which results in downstream production of angiotensin II via angiotensin-converting enzyme (ACE).

Angiotensin II and its related molecule aldosterone act to conserve sodium and water and expand plasma volume. In this way, cardiac output is maintained and there is an increase in cardiac stroke volume and, over time, ventricular size. Thus, the degree of volume retention and subsequent eccentric cardiac hypertrophy is a marker of MR severity.

Thoracic Radiography

Measuring heart size is extremely useful in assessing severity of DMVD (Figure). Thoracic radiography is a relatively simple and cost-efficient tool for assessing heart size and identifying the presence of pulmonary venous distention or edema.

Screen Shot 2015-04-29 at 3.01.12 PM

Measurement systems, such as the vertebral heart size (VHS) system, are useful in reducing inter-observer variability and tracking longitudinal changes in a patient’s heart size. The VHS technique has been well-described.2 Normal VHS size in dogs is < 10.7; severe heart enlargement and hence, severe DMVD, is usually considered to be > 12.

I recommend performing baseline thoracic radiographs to assess heart size on every dog with a newly discovered murmur. Baseline radiographs establish the initial degree of disease severity and assess rate of disease progression during subsequent follow-up (recheck radiographs should be performed 6–12 months after initial detection and are often repeated every 3–12 months depending on rate of progression).

Electrocardiography & Echocardiography

The value of electrocardiography (ECG) and echocardiography (echo) in the diagnosis and monitoring of DMVD varies from case to case. Clearly, ECG is the gold standard for assessment of arrhythmias, but ECG criteria for heart enlargement (eg, increased R wave amplitude indicating left ventricular enlargement) are relatively insensitive.

Echo is the gold standard for assessment of cardiac structure and function, but in most cases of DMVD, especially those that are relatively mild, the information obtained by echo rarely adds to what was already known from the physical examination and thoracic radiographs. While echo is helpful in some cases to detect concurrent cardiac disease, such as tricuspid regurgitation or pulmonary hypertension, lack of echo should not affect the ability to make an initial assessment of disease severity based on radiographic heart size.

In most cases of DMVD, appropriate diagnostic, monitoring, and therapeutic decisions can be made without echo provided that radiographs are performed.

Monitoring Progression of DMVD

It is reassuring to remember that most dogs with DMVD will not develop enough MR to cause congestive heart failure or clinical signs.3 The preclinical course of disease can be many years and only a minority of dogs will progress to the point of heart failure.

Classifying Patients

By performing longitudinal examinations of heart size, clinicians can gradually stratify dogs into (1) those that have slowly progressive disease and are unlikely to develop signs versus (2) those with more rapidly progressing disease that are at risk for future heart failure. In general, it is very uncommon for dogs to develop congestive heart failure with VHS < 11.5.

High-Risk Patients

Once VHS > 11.5, both absolute VHS and rate of increase in VHS are linked to risk of heart failure. In these patients, more frequent rechecks and increased owner vigilance for subtle signs of early heart failure, such as mild increase in respiratory rate or effort while at rest, decreased activity tolerance, or lethargy, is recommended. Previous studies4 have shown that a rate of VHS increase > 0.25 vertebra over a 3-month period suggests that risk for heart failure is high.

Slowing Progression of DMVD

Unfortunately, there are no proven interventions that slow the rate of DMVD progression or significantly delay the onset of heart failure in preclinical DMVD.

Role of Ace Inhibitors

While 2 large studies5,6 failed to demonstrate that ACE inhibitors significantly affected the primary endpoint of first-onset heart failure, the majority of cardiologists and members of the consensus panel on DMVD recommend ACE inhibitors prior to onset of heart failure, after cardiac enlargement is detected.7 In contrast, most cardiologists do not advocate use of furosemide prior to onset of congestive heart failure.

Monitoring & Prompt Therapy

Other medications are being assessed in ongoing clinical trials, but until these trials are completed, I recommend that dogs at high risk for heart failure are simply monitored more closely, both by the clinician and owner. Detection of subtle signs of heart failure as previously mentioned followed by prompt initiation of conventional therapy can prevent development of severe and life-threatening heart failure that requires emergency visits, intravenous treatment, and prolonged hospitalization.

Treatment of DMVD

Clinical Signs

In dogs with severe DMVD, progressive MR and chronic neurohormonal activation ultimately leads to congestion in the form of pulmonary edema. Dogs often present for respiratory signs, ranging from:

  • Mild increase in respiratory rate
  • Increased effort with abdominal component
  • Fulminant respiratory distress.

Coughing is often considered a sign of heart failure, yet most dogs with the isolated complaint of cough suffer from primary airway or respiratory disease as opposed to heart failure. Etiology of the cough can be differentiated by paying close attention to:

  • Radiographic heart and pulmonary vein size
  • Type and distribution of pulmonary pattern
  • Evidence of upper airway collapse.

Medical Therapy

Once a diagnosis of heart failure is made, 4 medications comprise the cornerstones of treatment for heart failure secondary to DMVD.

1. Diuretics: The most commonly prescribed diuretic is furosemide, which is typically administered at 2 to 3 mg/kg/day PO in dogs with mild heart failure and up to 4 to 6 mg/kg/day PO in dogs with more severe signs. Boluses of intravenous furosemide, 2 to 4 mg/kg IV Q 2 to 4 H, are used for rapid diuresis in dogs with life-threatening failure.

2. ACE Inhibitors: ACE inhibitors directly address activity of the renin–angiotensin–aldosterone system and work in tandem with diuretics to control congestion. Enalapril, 0.5 mg/kg PO Q 12 H, is the most commonly prescribed ACE inhibitor and is generally well-tolerated. Renal biochemistry values and electrolytes are usually checked before and 3 to 5 days after starting diuretics and ACE inhibitors or changing doses.

3. Inodilators: The inodilator agent pimobendan counteracts DMVD and MR through 2 different mechanisms: the first through calcium sensitization and increased myocardial contractility; the second through vasodilation. Pimobendan improves survival in dogs with heart failure secondary to DMVD and when compared directly against benazepril, extends longevity by almost 2-fold (median survival, 4 months longer in pimobendan group) over ACE inhibitors.8

These 3 medications—furosemide, pimobendan, and enalapril—comprise what cardiologists refer to as triple therapy and are considered standard of care for heart failure secondary to DMVD. In my practice, if owners are constrained to administering less than 3 medications, such as instances in which the dog is difficult to pill, the priority of administration is furosemide, pimobendan, and then enalapril.

4. Aldosterone Antagonists: The aldosterone antagonist, spironolactone, is the fourth agent commonly used for treatment of heart failure. It provides additional blockade of the renin–angiotensin–aldosterone system and produces modest diuresis. In a European study, spironolactone, 2 mg/kg PO Q 24 H, was shown to significantly increase survival in dogs with heart failure due to DMVD9; it is currently approved for use in dogs in the European Union. Cardiologists have been slower to adopt spironolactone as standard therapy, primarily due to the somewhat atypical nature of the study cohort. Additional studies to better clarify the utility of spironolactone are currently ongoing.

In Summary

  • The diagnosis of DMVD is relatively simple and based on auscultation and signalment.
  • Thoracic radiography is an excellent modality to ascertain baseline and progressive heart size, which directly correlates to severity of disease. In addition, in dogs with clinical signs, radiographs help distinguish cardiac from respiratory causes.
  • Dogs with large hearts and rapidly increasing heart size are at high risk for heart failure; increased owner and veterinary monitoring is warranted.
  • There are no drugs that have been unequivocally proven to slow progression of disease in the pre-clinical stage.
  • If and when heart failure develops, therapy with furosemide, pimobendan, and an ACE-inhibitor (+/-spironolactone) should be instituted with attention paid to renal blood analysis, patient respiratory effort and rate, and activity level.

Disclosure Statement

Dr. Oyama has received funding for clinical studies and speaking honoraria from Boehringer Ingelheim Vetmedica (makers of pimobendan) and consults for and has received speaking honoraria from CEVA Pharmaceuticals (makers of spironolactone).

ACE = angiotensin-converting enzyme;
DMVD = degenerative mitral valve disease;
ECG = electrocardiography; echo = echocardiography;
MR = mitral regurgitation; VHS = vertebral heart size

References

  1. Buchanan JW. Chronic valvular disease (endocardiosis) in dogs. Adv Vet Sci 1977; 21:57-106.
  2. Buchanan JW, Bucheler J. Vertebral scale system to measure canine heart size in radiographs. JAVMA 1995; 206:194-199.
  3. Borgarelli M, Savarino P, Crosara S, et al. Survival characteristics and prognostic variables of dogs with mitral regurgitation attributable to myxomatous valve disease. J Vet Intern Med 2008; 22:120-128.
  4. Lord PF, Hansson K, Carnabuci C, et al. Radiograhic heart size and its rate of increase as tests for onset of congestive heart failure in Cavalier King Charles spaniels with mitral valve regurgitation. J Vet Intern Med 2011; 25:1312-1319.
  5. Kvart C, Haggstrom J, Pedersen HD, et al. Efficacy of enalapril for prevention of congestive heart failure in dogs with myxomatous valve disease and asymptomatic mitral regurgitation. J Vet Intern Med 2002; 16:80-88.
  6. Atkins CE, Keene BW, Brown WA, et al. Results of the veterinary enalapril trial to prove reduction in onset of heart failure in dogs chronically treated with enalapril alone for compensated, naturally occurring mitral valve insufficiency. JAVMA 2007; 231:1061-1069.
  7. Atkins CE, Bonagura J, Ettinger S, et al. Guidelines for the diagnosis and treatment of canine chronic valvular heart disease. J Vet Intern Med 2009; 23:1142-1150.
  8. Haggstrom J, Boswood A, O’Grady M, et al. Effect of pimobendan or benazepril hydrochloride on survival times in dogs with congestive heart failure caused by naturally occurring myxomatous mitral valve disease: The QUEST study. J Vet Intern Med 2008; 22:1124-1135.
  9. Bernay F, Bland JM, Haggstrom J, et al. Efficacy of spironolactone on survival in dogs with naturally occurring mitral regurgitation caused by myxomatous mitral valve disease. J Vet Intern Med 2010; 24:331-341.

f02_authorMark Oyama, DVM, Diplomate ACVIM (Cardiology), is a professor in the Department of Clinical Studies at University of Pennsylvania School of Veterinary Medicine. His interests lie in the pathophysiology of mitral valve disease and cardiomyopathy and in new blood-based tests for detection of heart disease. He is a past president of the ACVIM Specialty of Cardiology and an Editorial Peer Review Board member for Today’s Veterinary Practice. Dr. Oyama received his DVM degree from University of Illinois and completed an internship at The Animal Medical Center in New York City and residency at University of California–Davis.

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value='Lebanon' >Lebanon</option><option value='Lesotho' >Lesotho</option><option value='Liberia' >Liberia</option><option value='Libya' >Libya</option><option value='Liechtenstein' >Liechtenstein</option><option value='Lithuania' >Lithuania</option><option value='Luxembourg' >Luxembourg</option><option value='Macau' >Macau</option><option value='Macedonia' >Macedonia</option><option value='Madagascar' >Madagascar</option><option value='Malawi' >Malawi</option><option value='Malaysia' >Malaysia</option><option value='Maldives' >Maldives</option><option value='Mali' >Mali</option><option value='Malta' >Malta</option><option value='Marshall Islands' >Marshall Islands</option><option value='Martinique' >Martinique</option><option value='Mauritania' >Mauritania</option><option value='Mauritius' >Mauritius</option><option value='Mayotte' >Mayotte</option><option value='Mexico' >Mexico</option><option value='Micronesia' >Micronesia</option><option value='Moldova' >Moldova</option><option value='Monaco' >Monaco</option><option value='Mongolia' >Mongolia</option><option value='Montenegro' >Montenegro</option><option value='Montserrat' >Montserrat</option><option value='Morocco' >Morocco</option><option value='Mozambique' >Mozambique</option><option value='Myanmar' >Myanmar</option><option value='Namibia' >Namibia</option><option value='Nauru' >Nauru</option><option value='Nepal' >Nepal</option><option value='Netherlands' >Netherlands</option><option value='New Caledonia' >New Caledonia</option><option value='New Zealand' >New Zealand</option><option value='Nicaragua' >Nicaragua</option><option value='Niger' >Niger</option><option value='Nigeria' >Nigeria</option><option value='Niue' >Niue</option><option value='Norfolk Island' >Norfolk Island</option><option value='North Korea' >North Korea</option><option value='Northern Mariana Islands' >Northern Mariana Islands</option><option value='Norway' >Norway</option><option value='Oman' >Oman</option><option value='Pakistan' >Pakistan</option><option value='Palau' >Palau</option><option value='Palestine, State of' >Palestine, State of</option><option value='Panama' >Panama</option><option value='Papua New Guinea' >Papua New Guinea</option><option value='Paraguay' >Paraguay</option><option value='Peru' >Peru</option><option value='Philippines' >Philippines</option><option value='Pitcairn' >Pitcairn</option><option value='Poland' >Poland</option><option value='Portugal' >Portugal</option><option value='Puerto Rico' >Puerto Rico</option><option value='Qatar' >Qatar</option><option value='Réunion' >Réunion</option><option value='Romania' >Romania</option><option value='Russia' >Russia</option><option value='Rwanda' >Rwanda</option><option value='Saint Barthélemy' >Saint Barthélemy</option><option value='Saint Helena' >Saint Helena</option><option value='Saint Kitts and Nevis' >Saint Kitts and Nevis</option><option value='Saint Lucia' >Saint Lucia</option><option value='Saint Martin' >Saint Martin</option><option value='Saint Pierre and Miquelon' >Saint Pierre and Miquelon</option><option value='Saint Vincent and the Grenadines' >Saint Vincent and the Grenadines</option><option value='Samoa' >Samoa</option><option value='San Marino' >San Marino</option><option value='Sao Tome and Principe' >Sao Tome and Principe</option><option value='Saudi Arabia' >Saudi Arabia</option><option value='Senegal' >Senegal</option><option value='Serbia' >Serbia</option><option value='Seychelles' >Seychelles</option><option value='Sierra Leone' >Sierra Leone</option><option value='Singapore' >Singapore</option><option value='Sint Maarten' >Sint Maarten</option><option value='Slovakia' >Slovakia</option><option value='Slovenia' >Slovenia</option><option value='Solomon Islands' >Solomon Islands</option><option value='Somalia' >Somalia</option><option value='South Africa' >South Africa</option><option value='South Georgia' >South Georgia</option><option value='South Korea' >South Korea</option><option value='South Sudan' >South Sudan</option><option value='Spain' >Spain</option><option value='Sri Lanka' >Sri Lanka</option><option value='Sudan' >Sudan</option><option value='Suriname' >Suriname</option><option value='Svalbard and Jan Mayen Islands' >Svalbard and Jan Mayen Islands</option><option value='Sweden' >Sweden</option><option value='Switzerland' >Switzerland</option><option value='Syria' >Syria</option><option value='Taiwan' >Taiwan</option><option value='Tajikistan' >Tajikistan</option><option value='Tanzania' >Tanzania</option><option value='Thailand' >Thailand</option><option value='Timor-Leste' >Timor-Leste</option><option value='Togo' >Togo</option><option value='Tokelau' >Tokelau</option><option value='Tonga' >Tonga</option><option value='Trinidad and Tobago' >Trinidad and Tobago</option><option value='Tunisia' >Tunisia</option><option value='Turkey' >Turkey</option><option value='Turkmenistan' >Turkmenistan</option><option value='Turks and Caicos Islands' >Turks and Caicos Islands</option><option value='Tuvalu' >Tuvalu</option><option value='Uganda' >Uganda</option><option value='Ukraine' >Ukraine</option><option value='United Arab Emirates' >United Arab Emirates</option><option value='United Kingdom' >United Kingdom</option><option value='United States' >United States</option><option value='Uruguay' >Uruguay</option><option value='US Minor Outlying Islands' >US Minor Outlying Islands</option><option value='Uzbekistan' >Uzbekistan</option><option value='Vanuatu' >Vanuatu</option><option value='Venezuela' >Venezuela</option><option value='Vietnam' >Vietnam</option><option value='Virgin Islands, British' >Virgin Islands, British</option><option value='Virgin Islands, U.S.' >Virgin Islands, U.S.</option><option value='Wallis and Futuna' >Wallis and Futuna</option><option value='Western Sahara' >Western Sahara</option><option value='Yemen' >Yemen</option><option value='Zambia' >Zambia</option><option value='Zimbabwe' 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