Chronic Degenerative Valve Disease in Dogs

Epidemiology
Chronic Degenerative Valvular Disease (CDVD) is the most common cardiac disease of dogs.  It is the most common cause of a heart murmur in an adult dog.  It estimated to account for approximately three-quarters of all cases of cardiac disease seen in veterinary practices.  Small breed dogs (<20 kg, <44 lb) are approximately twice as likely to have CDVD than medium and large breed dogs (>20 kg, 44 lb), with a particularly high prevalence in certain breeds (Table 1).  Males dog are about 50% more likely to be affected than females.  CDVD develops more frequently with age.  In one study, 100% of Cavalier King Charles Spaniels over 10 years of age had some degree of CDVD.  While the exact cause for CDVD is not known, the knowledge of dog size, dog breed, gender, and age predispositions indicate that the most important factors are genetics and time.  This is supported by studies that have identified genetic associations with CDVD in dogs.  There is no convincing evidence of an association with dental disease, infections, obesity or diet.

Table 1
Dog breeds reported to be most commonly affected by CDVD

Cavalier King Charles Spaniels
King Charles Spaniels
Dachshunds
Poodles
Small Terrier breeds
Shih Tzus
Miniature Schnauzers
Maltese
Chihuahuas
Pomeranians
Sighthounds of small or medium size (e.g. Greyhounds, Whippets)
Border Collies


Terminology
CDVD does not have a single accepted name.  Various names for the condition are used interchangeably in veterinary cardiology (Table 2).  There is a logic for these names.  The descriptors “chronic”, “degenerative” and “acquired” that are often used refer to the role of age in the disease.  The words “myxomatous”, “prolapse” and “endocardiosis” are terms for the structural abnormalities of the valve tissue that occur in CDVD.  The terms “atrioventricular” and “mitral” refer to the observation that, of the 4 valves in the heart, the left “atrioventricular” or “mitral” valve is most affected by CDVD.  The right atrioventricular or tricuspid valve is the second most affected, followed by the aortic valve and finally the pulmonic valve.

Table 2
Other names for CDVD that are used in veterinary cardiology

Chronic Valvular Disease
Degenerative Valvular Disease
Chronic Acquired Valvular Disease
Acquired Atrioventricular Valve Disease
Mitral Valve Disease
Myxomatous Mitral Valve Disease
Degenerative Mitral Valve Disease
Mitral Valve Prolapse
Endocardiosis


Pathophysiology
When the heart beats, a normal mitral valve allows blood to flow from the lungs, via the left atrium (LA), to the body, via the left ventricle (LV).  In a dog with CDVD of the mitral valve, thickening and weakening of the valve leaflets ultimately result with blood leaking backward from the LV to the LA (mitral regurgitation).  This is seen in Figures 1A & 1B.  Mitral regurgitation (MR) causes the heart murmur that is the most common first sign of the disease.  For most dogs, the murmur is not accompanied by any symptoms and they live normal lives.  For some dogs, a large leak develops, resulting in heart enlargement, signs of coughing, fainting, decreased activity and breathing difficulties.  Heart failure is typically diagnosed when one or more these signs occur in association with fluid on the lung (pulmonary edema).

Figure 1

Echocardiographic images
A: Top picture shows dilated LA and LV, with arrows pointing to thickened MV leaflets.
B: Bottom picture shows severe MR (green color) with color flow mapping Doppler.

CARDIO1

Diagnosis
Diagnosis of CDVD requires echocardiography (ultrasound scan of the heart) (Figures 1A & 1B).  Echocardiography is also the most accurate method to determine whether heart enlargement has occurred, to assess heart function, and to measure pressure in the heart and lung circulation.  Chest x-rays are a less accurate test for determining whether there is heart enlargement, but it is a good test for the presence of fluid on the lung (pulmonary edema) (Figures 2A & 2B).  NT-proBNP is a cheap and useful blood test to screen for heart failure.  If proBNP is elevated in a dog with a typical heart murmur and symptoms of coughing or breathing difficulties, further testing with chest x-rays and echocardiography are recommended.  Electrocardiography (ECG or EKG) has limited use for diagnosing CDVD or heart failure.  It is most useful for diagnosing abnormal heart rhythms (arrhythmias), such as atrial fibrillation  (AFib), which may occur as a result of severe CDVD.

Figure 2

Chest x-rays
A: Top picture shows an enlarged heart with enlarged LA (arrows) and normal lung (black area).
B: Bottom picture shows more severe heart enlargement and pulmonary edema (grey-white areas in the lung).

CARDIO2

Treatment
Dogs with CDVD and no heart enlargement do not require treatment.  The disease does not cause any signs, it may not progress or may only progress over several years, and just as importantly, there are no treatments that have been shown to be effective in delaying progression.  Serial monitoring with echocardiography or chest x-rays is typically recommended every 6-12 months.

Dogs with CDVD and heart enlargement, with or without symptoms, benefit from starting the medication, pimobendan.  A recently published, large clinical trial that evaluated the possible benefit for pimobendan in dogs with CDVD and heart enlargement (EPIC study).  The study compared 180 dogs that received pimobendan with 180 dogs that received a placebo tablet of identical appearance.  The study found that the dogs that received pimobendan took 60 % more time to develop heart failure or die suddenly.  The average prolongation in time was 15 months.  Furthermore, pimobendan was shown to be safe and well tolerated; the frequency of adverse events in the pimobendan group was no different to the frequency in the placebo group.  Since the study is the largest clinical trial that has been undertaken in veterinary cardiology and involved dogs from 36 hospitals across 15 countries, which were followed up over a period of 6 years, it can be considered a very reliable study.  Prior to this result, many dogs with CDVD and heart enlargement were prescribed the ACE inhibitor, enalapril.  This is despite a lack of evidence that enalapril has any benefit.  This includes two large clinical trials that compared enalapril to a placebo, both of which found that administering enalapril to dogs with CDVD and heart enlargement did not result in any delay in the time to develop heart failure.

When heart failure develops, multiple drugs are required to improve symptoms and prevent the otherwise inevitable rapid progression to death.  The diuretic, furosemide (Lasix) is the most effective therapy.  Giving an ACE inhibitor (enalapril, benazepril) in addition to furosemide is more effective than furosemide alone.  Furthermore, the combination of pimobendan and furosemide is even more effective than ACE inhibitor and furosemide.  Consequently, dogs with heart failure from CDVD will receive at least furosemide and pimobendan.  Most will also receive an ACE inhibitor, such as enalapril.  Some will require additional diuretics, such as spironolactone, hydrochlorothiazide, or other drugs to dilate blood vessels, such as amlodipine or sildenafil.  Dogs receiving diuretics are at increased risk of developing kidney dysfunction.  Consequently, it is recommended to monitor kidney function with blood tests on a regular basis.

Prognosis
The average life expectancy for dogs with heart failure from CDVD is 8-12 months.  However, the actual prognosis in individual dogs is notoriously difficult to predict, with a minority dogs living for only a few days after starting treatment, and at the other end of the spectrum, occasional dogs that live for over 2 years after their first episode of heart failure.

Emerging therapies for CDVD
The ideal therapy for CDVD is one that eliminates or decreases the severity of valve regurgitation.  In humans, surgical repair of the mitral valve is the most effective treatment and is indicated in patients with severe disease.  This requires open-heart surgery and cardiopulmonary bypass.  Despite being an effective treatment, it carries a high surgical risk and is very expensive.  Consequently, it has not been adopted as a routine treatment for dogs with CDVD.  Nevertheless, a group in Japan has been undertaking surgical mitral valve repair in dogs with CDVD for over 10 years with high success rate.  Unfortunately, this surgery is not carried out in the US.

Consequently, transcatheter techniques for repairing or replacing the mitral valve have been developed, such as the MitraClip (Abbott Vascular, USA).  All transcatheter mitral valve therapies involve the delivery of a device via an artery into the heart, without the need for open chest surgery or by-pass.  However, none have been shown to be as effective as surgical mitral valve repair.

Consequently, there is growing interest in developing transcatheter mitral valve therapies for dogs. These therapies involve the delivery of a device via an artery into the heart, without the need for open chest surgery or by-pass.  A number have been developed for humans with MR.  The development of a transcatheter therapy that is both safe and affordable for canine patients would be one of the biggest advances in veterinary cardiology, as it could impact the lives of thousands of dogs.  The cardiologists at Hope Veterinary Specialists are involved in developing one such pioneering device.  Hopefully, this or another technique will be a viable treatment for canine CDVD in the future.

Submitted by: Simon Dennis BVetMed, MVM, MRCVS, DECVIM (Cardiology)

References

  • Atkins CE, Keene BW, Brown WA, et al. Results of the veterinary enalapriltrial to prove reduction in onset of heart failure in dogs chronically treated with enalapril alone for compensated, naturally occurring mitral valve insufficiency. J Am Vet Med Assoc. 2007; 231(7): 1061-9. http://avmajournals.avma.org/doi/abs/10.2460/javma.231.7.1061
  • Oyama MA, Rush JE, Rozanski EA, et al. Assessment of serum N-terminal pro-B-type natriuretic peptide concentration for differentiation of congestive heart failure from primary respiratory tract disease as the cause of respiratory signs in dogs. J Am Vet Med Assoc. 2009; 235(11) :1319-25. http://onlinelibrary.wiley.com/doi/10.1111/jvim.12591/full

 

 

 

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