Vet Times The website for the veterinary profession https://www.vettimes.co.uk Advances in canine cardiology Author : PEDRO OLIVEIRA, ANTONIA MAVROPOULOU Categories : Vets Date : June 16, 2014 PEDRO OLIVEIRA DVM, DipECVIM-CA(Cardiology), MRCVS ANTONIA MAVROPOULOU DVM, MSc, PhD, Resident ECVIM-CA(Cardiology), MRCVS explain recent developments in two of the most researched areas in the field of dog heart studies, including approaches to diagnosis and treatment Summary The field of veterinary cardiology is continually expanding. Every year, numerous scientific articles are published as a result of the work of international study groups. The literature increases our knowledge and has a direct impact on the quality of the services we provide for our patients, although it makes it very difficult to keep up to date with this plethora of information. This discussion will focus on advances in two of the most researched areas in canine cardiology the study of chronic valvular heart disease (CVHD) and dilated cardiomyopathy (DCM). The most relevant aspects in the diagnosis and treatment of these diseases will be discussed in light of recent publications. Key words cardiology, dog, mitral valve disease, dilated cardiomyopathy EVERY year, numerous articles are published in scientific journals on several topics related 1 / 15
to veterinary medicine. This wealth of knowledge is very important to ensure our patients continue receiving the best care possible, at all times but it is, however, virtually impossible to keep up with every single new publication. The following discussion will focus on canine cardiology and highlight some of the most relevant advances published in regards to two of the most researched areas in this field. These are chronic valvular heart disease and dilated cardiomyopathy. Chronic valvular heart disease Chronic valvular heart disease (CVHD) also known as myxomatous mitral valve disease, or simply, mitral valve disease is the most common acquired heart disease in dogs1,2. This is a degenerative disease of the cardiac valves affecting particularly the mitral and to a lesser extent tricuspid valves. The valvular apparatus (for example, leaflets and chordae tendineae) becomes deformed and this results in several degrees of insufficiency (Figure 1). Clinical signs are not observed until heart failure develops. Symptoms include a reduction in exercise tolerance, which can be very difficult to appreciate; tachypnoea and dyspnoea secondary to pulmonary oedema; and, in later stages, syncope secondary to tachyarrhythmias or acute vasodilation. A cough is typically attributed to heart disease and is described in many textbooks as a sign of cardiogenic pulmonary oedema. However, a study showed congestive heart failure (CHF) was not significantly associated with a cough in CVHD. Dyspnoea and tachypnoea were consistent with pulmonary oedema, while a cough in the absence of other respiratory signs was an unlikely sign of CHF. The same study suggested the presence of airway disease and left atrial enlargement represented risk factors for coughing in dogs with CVHD3, although a previous smaller study had failed to show an association between left atrial enlargement and airway collapse in dogs with CVHD4. This suggests the cough observed in these dogs may be due to concomitant airway disease and is not a direct sign of heart disease or failure. It would explain why some dogs in heart failure do not cough at all, while others with well controlled CHF cough very frequently. This is very relevant since management of these cases should take this into account and we should think twice before starting treatment for heart failure merely based on whether a dog coughs. Diagnosis Diagnosis of CVHD is not particularly challenging. Identification of a characteristic murmur in a particular breed of a certain age is usually sufficient to raise suspicion. If every practitioner was 2 / 15
fortunate enough to have access to echocardiography, this disease could be diagnosed by anyone with a few basic echocardiography skills (Figure 1). The real challenge in these cases is often knowing when and how to treat. To help us with these decisions, a group of opinion leaders in veterinary cardiology proposed guidelines for classification and treatment5,6. The following disease stages were proposed: Stage A Dogs at high risk for developing CVHD (for example, cavalier King Charles spaniels) that at the present time do not have identifiable signs of the disease. Stage B Dogs with evidence of CVHD that have never developed clinical signs. Stage B dogs are further subdivided into two subclasses: Class B1 asymptomatic dogs without radiographic or echocardiographic evidence of cardiac remodelling (that is, dilation). Class B2 asymptomatic dogs with left-sided heart enlargement (Figures 1 and 2). Stage C Dogs with current or past clinical signs of left-sided heart failure (for example, dyspnoea) and/or low output symptoms (for example, exercise intolerance, syncope) secondary to CVHD. Stage D Dogs with clinical signs of CHF or low-output that are refractory to standard therapy (maximal recommended or tolerated furosemide dose associated with an angiotensin-converting enzyme [ACE] inhibitor and pimobendan). The course of CVHD is variable. Some dogs rapidly progress to the symptomatic stage, while others remain free of symptoms for several years. Treatment is only recommended when Stage C of the disease is reached and, therefore, much interest is put on timely recognition of the onset of clinical signs. For this purpose, several studies have focused on the use of biomarkers for the prediction of heart failure. The natriuretic peptides for example, the N-terminal pro-brain natriuretic peptide (NTproBNP) showed the most promise. Several studies have shown they increase in patients with heart disease, their concentration increases as the disease progresses, and they are predictive of 3 / 15
the onset of CHF and of mortality7,8,9. They may help to discriminate dogs with dyspnoea caused by CHF from dogs with primary respiratory disease10. However, it is important to remember they do not provide a definitive diagnosis and other diseases may lead to increased levels of natriuretic peptides (for example, kidney disease or pulmonary hypertension). Further investigation is always indicated, although a decision may be made on whether this should focus on heart disease or respiratory disease. Medical treatment We do not possess any drug capable of slowing valve degeneration. It is accepted that dogs in Stage A or Stage B Class B1 do not need treatment, but this is controversial for Stage B Class B2. Treatment is recommended for all dogs in Stage C and has to be tailored for each patient. Chronic treatment should always include furosemide, an ACE inhibitor and pimobendan5,6. Spironolactone may also be beneficial11. As disease progresses, the furosemide dosage is increased to effect although, in some patients, even dosages as high as 6mg/kg every eight hours are not enough to control CHF this is Stage D. Use of parenteral (subcutaneous) rather than oral furosemide is usually helpful in these cases. Spironolactone is used, if not already started, and the highest recommended dosages of ACE inhibitors and pimobendan are used. Torsemide a long-acting loop diuretic that is 10 times as potent as furosemide is another option in these cases12. Sildenafil may be used in cases with evidence of pulmonary hypertension. Cough suppressants and bronchodilators can also be used in both Stage C and Stage D5,6. Surgical repair of mitral valves Perhaps the most exciting news in recent times is reports of success with surgical mitral repair from a Japanese group. A few publications described the technique and results available so far13,14,15. In human medicine, mitral valve repair or replacement is common for treatment of degenerative valve disease. This is very challenging and requires a great deal of experience with cardiopulmonary bypass, full awareness and understanding of how the mitral valve apparatus works and, of course, outstanding surgical skills. Under cardiopulmonary bypass, an incision is made in the left atrial wall to access the mitral valve. A suture or a soft prosthetic ring is placed around the mitral annulus to reduce annular size and the chordae tendineae are replaced with expanded polytetrafluoroethylene as necessary14. 4 / 15
The results of this technique in 48 cases have been reported13. The survival rate at discharge was 94 per cent (45 out of 48) with significant reductions in mitral regurgitation and cardiac size. These dogs were alive and well at least five months after surgery. Of the three dogs that did not survive, one died as a result of bleeding during recovery from anaesthesia and the other two died of thrombosis within eight days of the surgery13. Long-term outcome has been reported in three cases15. One died after two years due to partial circumferential suture detachment, resulting in severe mitral regurgitation and CHF. The other two cases survived for more than five years, although mitral valve stenosis was present in one. The replaced chordae did not rupture in any dog. Hopefully, with time, these procedures will become more available and bring new hope for our patients. Dilated cardiomyopathy Dilated cardiomyopathy (DCM) is a disease of the cardiac muscle characterised by a progressive loss of contractile strength and consequent dilation of the ventricular chambers. The disease is almost certainly genetic in origin in most dogs and is more prevalent in some breeds such as the Dobermann pinscher, which is the typical example. The prevalence of the disease differs between countries and depends on the gene pool in a particular region16. A scientific paper reported how the prevalence of DCM in great Danes in the UK is higher than previously reported17. Other affected breeds include boxers, Labradors and golden retrievers, Newfoundlands, St Bernards, and English and American cocker spaniels16. The disease progresses through an occult to an overt stage. Three distinct phases have been described in the Dobermann pinscher. Dogs in Stage I are asymptomatic and evidence of morphological or electrical abnormalities is not detectable. Dogs in Stage II (occult phase) are also asymptomatic, but electrical abnormalities, morphological changes or both are present. Most of these dogs eventually progress to Stage III (overt stage) in which clinical signs such as syncope or CHF occur. Long-term survival is poor at this stage and it is not uncommon for sudden death to be the first and only clinical sign of the disease. For this reason, great effort is made to identify these dogs while still in the occult stage. Diagnosis of occult DCM Diagnosis of DCM in the occult stage is very challenging. It involves either detection of ventricular arrhythmias on an electrocardiogram (ECG; usually a 24-hour ambulatory ECG Holter), detection of left ventricular enlargement due to systolic dysfunction on echocardiography, or both (Figures 3 and 5 / 15
4 ). This requires referral to a trained individual with access to the necessary facilities. Additionally, dogs can remain in this stage for a few years and the incidence increases with age. For this reason, yearly screening is recommended from an age as low as two years in the case of Dobermann pinschers. This translates into significant cost and owner commitment throughout the dog s life. A study involving 155 Dobermann pinschers suggested the use of NT-proBNP could be useful for detection of occult DCM, particularly if combined with information from a Holter monitor18. According to the results, an NT-proBNP value of more than 457pmol/L would only allow identification of 69.9 per cent of the affected dogs. However, if combined with the presence of greater than 50 ventricular premature complexes (VPCs) in 24 hours during Holter monitoring, 94.6 per cent of these dogs would be identified. A previous report involving 328 Dobermann pinschers indicated that asymptomatic dogs with Holter evidence of arrhythmias (greater than 100 VPCs over 24h) and no abnormalities on echocardiography had increased NT-proBNP levels, while apparently healthy dogs that subsequently developed DCM within 1.5 years had higher NT-proBNP values than control dogs19. Based on this information it would not be wrong to assume that in this breed, performing these two tests once yearly might be a good way to start, followed by echocardiography in all suspected cases. Further studies are required to determine the value of these diagnostic tests in the preclinical phase of the disease in other affected breeds. Treatment in overt stage Treatment of DCM aims to reduce clinical signs and increase survival and quality of life. This includes use of diuretics, ACE inhibitors, inotropic agents (for example, pimobendan) and antiarrhythmic drugs. Treatment in occult stage A very important question when managing any disease is whether starting treatment with a certain drug during the asymptomatic stage will result in a delay of onset of clinical signs and better survival. A study provided some insight into the use of pimobendan in these cases20. Pimobendan was given to 39 Dobermann pinschers with occult DCM, while another 37 received a placebo. The median time to either sudden death or development of CHF was significantly longer (nine months) for dogs receiving pimobendan than for dogs receiving placebo. Additionally, no evidence of increased risk of proarrhythmia or sudden death was noticed with pimobendan. 6 / 15
Based on the results of this study, pimobendan appears to be safe and effective in prolonging time to onset of CHF and sudden death in Dobermanns with preclinical DCM20. It is important to point out all these dogs had signs of left ventricular enlargement identified on echocardiography and that, before starting this drug in a dog with suspicion of DCM, a full investigation is recommended, including Holter monitoring and echocardiography. The results of this study only indicate pimobendan might prolong time to CHF or sudden death, but do not suggest it prevents their occurrence. Additionally, this study only included Dobermann pinschers and therefore extrapolation to other breeds is not possible. Please note some drugs mentioned in this article are not licensed in dogs and are used under the cascade. References 1. Buchanan J (1992). Causes and prevalence of cardiovascular disease. In Kirk R and Bonagura J (eds), Kirk s Current Veterinary Therapy XI, W B Saunders, Philadelphia: 647-655. 2. Borgarelli M and Buchanan J (2012). Historical review, epidemiology and natural history of degenerative mitral valve disease, Journal of Veterinary Cardiology 14(1): 93-101. 3. Ferasin L, Crews L, Biller D S, Lamb K E and Borgarelli M (2013). Risk factors for coughing in dogs with naturally acquired myxomatous mitral valve disease, Journal of Veterinary Internal Medicine 27(2): 286-292. 4. Singh M K, Johnson L R, Kittleson M D and Pollard R E (2012). Bronchomalacia in dogs with myxomatous mitral valve degeneration, Journal of Veterinary Internal Medicine 26(2): 312-319. 5. Atkins C, Bonagura J, Ettinger S, Fox P, Gordon S, Häggström J, Hamlin R, Keene B, Luis-Fuentes V and Stepien R (2009). Guidelines for the diagnosis and treatment of canine chronic valvular heart disease, Journal of Veterinary Internal Medicine 23(6): 1,142-1,150. 6. Atkins C E and Häggström J (2012). Pharmacologic management of myxomatous mitral valve disease in dogs, Journal of Veterinary Cardiology 14(1): 165-184. 7. Takemura N, Toda N, Miyagawa Y, Asano K, Tejima K, Kanno N, Arisawa K, Kurita T, Nunokawa K, Hirakawa A, Tanaka S and Hirose H (2009). Evaluation of plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) concentrations in dogs with mitral valve insufficiency, The Journal of Veterinary Medical Science 71(1): 925-929. 8. Moonarmart W, Boswood A, Luis Fuentes V, Brodbelt D, Souttar K and Elliott J (2010). N-terminal pro B-type natriuretic peptide and left ventricular diameter independently predict mortality in dogs with mitral valve disease, Journal of Small Animal Practice 51(2): 84-96. 9. Chetboul V, Serres F, Tissier R, Lefebvre H P, Sampedrano C C, Gouni V, Poujol L, Hawa G and Pouchelon J (2009). Association of plasma N-terminal pro-b-type natriuretic peptide concentration with mitral regurgitation severity and outcome in dogs with 7 / 15
asymptomatic degenerative mitral valve disease, Journal of Veterinary Internal Medicine 23(5): 984-994. 10. Fine D M, DeClue A E and Reinero C R (2008). Evaluation of circulating amino terminalpro-b-type natriuretic peptide concentration in dogs with respiratory distress attributable to congestive heart failure or primary pulmonary disease, Journal of the American Veterinary Medical Association 232(11): 1,674-1,679. 11. Bernay F, Bland J M, Häggström J, Baduel L, Combes B, Lopez A and Kaltsatos V (2010). Efficacy of spironolactone on survival in dogs with naturally occurring mitral regurgitation caused by myxomatous mitral valve disease, Journal of Veterinary Internal Medicine 24(2): 331 341. 12. Oyama M A, Peddle G D, Reynolds C A and Singletary G E (2011). Use of the loop diuretic torsemide in three dogs with advanced heart failure, Journal of Veterinary Cardiology 13(4): 287-292. 13. Uechi M, Mizukoshi T, Mizuno T, Mizuno M, Harada K, Ebisawa T, Takeuchi J, Sawada T, Uchida S, Shinoda A, Kasuya A, Endo M, Nishida M, Kono S, Fujiwara M and Nakamura T (2012). Mitral valve repair under cardiopulmonary bypass in small-breed dogs: 48 cases (2006 2009), Journal of the American Veterinary Medical Association 240(10): 1,194-1,201. 14. Uechi M (2012). Mitral valve repair in dogs, Journal of Veterinary Cardiology 14(1): 185-192. 15. Mizuno T, Mizukoshi T and Uechi M (2013). Long-term outcome in dogs undergoing mitral valve repair with suture annuloplasty and chordae tendinae replacement, Journal of Small Animal Practice 54(2): 104-107. 16. Kittleson M and Kienle R (1998). Primary myocardial disease. In Kittleson M and Kienle R (eds), Small Animal Cardiovascular Medicine, Mosby. 17. Stephenson H M, Fonfara S, Lopez-Alvarez J, Cripps P and Dukes-McEwan J (2012). Screening for dilated cardiomyopathy in great Danes in the United Kingdom, Journal of Veterinary Internal Medicine 26(5): 1,140-1,147. 18. Singletary G E, Morris N A, Lynne O Sullivan M, Gordon S G and Oyama M A (2012). Prospective evaluation of NT-proBNP assay to detect occult dilated cardiomyopathy and predict survival in Dobermann pinschers, Journal of Veterinary Internal Medicine 26(6): 1,330-1,336. 19. Wess G, Butz V, Mahling M and Hartmann K (2011). Evaluation of N-terminal pro-btype natriuretic peptide as a diagnostic marker of various stages of cardiomyopathy in Dobermann pinschers, American Journal of Veterinary Research 72(5): 642-649. 20. Summerfield N J, Boswood A, O Grady M R, Gordon S G, Dukes- McEwan J, Oyama M A, Smith S, Patteson M, French A T, Culshaw G J, Braz-Ruivo L, Estrada A, O Sullivan M L, Loureiro J, Willis R and Watson P (2012). Efficacy of pimobendan in the prevention of congestive heart failure or sudden death in Dobermann pinschers with preclinical dilated cardiomyopathy (the PROTECT study), Journal of Veterinary Internal Medicine 26(6): 1,337-1,349. 8 / 15
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Figure 1. Chronic valvular disease echocardiographic images illustrating mitral valve thickening and prolapse (1a and 1b) causing regurgitation evidence on colour flow Doppler (1c). Figure 2. Chronic valvular disease chest radiographs illustrating cardiomegaly. 11 / 15
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Figure 3. Dilated cardiomyopathy echocardiographic images illustrating marked left ventricular enlargement (3a and 3b) and poor contractility evidence on M-mode (3c). Figure 4. Dilated cardiomyopathy electrocardiogram showing frequent ventricular premature complexes (4a) and ventricular tachycardia (4b). 14 / 15
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