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Addition in clinical signs, diagnostics and treatment
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In cases where DMVD becomes clinically significant, a '''cough''' is usually the first clinical sign noticed by the owner. The coughing is likely of multifactorial aetiology and may be related to pulmonary oedema, stimulation of the juxtapulmonary (J) receptors that are associated with pulmonary capillaries and detect increases in pulmonary venous pressure, compression of a mainstem bronchi by an enlarged left atrium and concurrent airway disease.  Occasionally, '''syncope''' is the first sign of clinically significant DMVD. This may occur due to arrhythmias or on exertion where mitral regurgitation limits stroke volume and therefore cardiac output.
 
In cases where DMVD becomes clinically significant, a '''cough''' is usually the first clinical sign noticed by the owner. The coughing is likely of multifactorial aetiology and may be related to pulmonary oedema, stimulation of the juxtapulmonary (J) receptors that are associated with pulmonary capillaries and detect increases in pulmonary venous pressure, compression of a mainstem bronchi by an enlarged left atrium and concurrent airway disease.  Occasionally, '''syncope''' is the first sign of clinically significant DMVD. This may occur due to arrhythmias or on exertion where mitral regurgitation limits stroke volume and therefore cardiac output.
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Other symptoms that may occur include increased exercise intolerance and efficiency, tachypnea or dyspnea during exercise, ascites, weight loss, anorexia and thromboembolisms.
    
== Diagnosis==
 
== Diagnosis==
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Fractional shortening may be increased (hyperynamic left ventricle). This is because, in the setting of mitral regurgitation, impedance to ventricular emptying is reduced (blood can be ejected into the low pressure left atrium)and end-diastolic ventricular stretch is increased by the addition of the regurgitant fraction, increasing the force of contraction.  
 
Fractional shortening may be increased (hyperynamic left ventricle). This is because, in the setting of mitral regurgitation, impedance to ventricular emptying is reduced (blood can be ejected into the low pressure left atrium)and end-diastolic ventricular stretch is increased by the addition of the regurgitant fraction, increasing the force of contraction.  
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A serious complication of DMVD is chordae tendinae rupture, resulting in a 'flail leaflet' and acute worsening of mitral regurgitation. A leaflet segment typically 'flails' back into the left atrium during systole.
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A serious complication of DMVD is '''chordae tendinae rupture''', resulting in a 'flail leaflet' and acute worsening of mitral regurgitation. A leaflet segment typically 'flails' back into the left atrium during systole.
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'''Left atrial rupture''' is a major complication of DMVD. Left atrial endocardial and endomyocardial splits are usually multiple and may heal or perforate the atrial wall, causing haemopericardium or an acquired atrial septal defect depending on their depth and location.
    
===Electrocardiogram (ECG)===
 
===Electrocardiogram (ECG)===
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* P-mitrale: wide P waves in leads II, III and aVF, indicates left atrial enlargement
 
* P-mitrale: wide P waves in leads II, III and aVF, indicates left atrial enlargement
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* high R-wave
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* Stage C2-D:  (supra-) ventricular extrasystoles
    
===Laboratory Tests===
 
===Laboratory Tests===
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== Treatment ==
 
== Treatment ==
 
===Stage B===
 
===Stage B===
There is no evidence that any therapy slows the progression of asymptomatic disease.  
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There is no therapy demonstrated to be beneficial in dogs with stage B1 disease. Nevertheless the cardiac function should be controlled after 12 months or earlier if the general condition gets worse.
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The results of the EPIC study demonstrated that administration of '''Pimobendan''' to dogs with stage B2 disease resulted in prolongation of the asymptomatic phase of disease by approximately 15 months. Dogs receiving Pimobendan were around 33% less likely to go into congestive heart failure or suffer a cardiac death than those not receiving the drug. Pimobendan appears safe and well-tolerated. The cardiac function should be controlled after 6-12 months.
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Based on findings of the EPIC study, dogs with typical mitral valve murmurs of grade III/VI or higher should be investigated to look for evidence of cardiomegaly. If cardiomegaly is apparent, then the dog may benefit from starting Pimobendan, as opposed to the 'watch and wait' approach that was previously recommended.
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===Stage C===
 
===Stage C===
 
Medical management is intended to alleviate clinical signs and prolong life.  
 
Medical management is intended to alleviate clinical signs and prolong life.  
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The addition of an '''ACE inhibitor''' is considered standard therapy.  The benefits of ACE inhibitors are related to their vasodilator action and also protecting the heart from the detrimental effects of RAAS activation.  
 
The addition of an '''ACE inhibitor''' is considered standard therapy.  The benefits of ACE inhibitors are related to their vasodilator action and also protecting the heart from the detrimental effects of RAAS activation.  
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'''Pimobendan''' is phosphodiesterase inhibitor that is both a ''positive inotrope'' and ''vasodilator'' (inodilator). A randomized clinical trial (QUEST) demonstrated a survival benefit associated with Pimobendan administration, relative to Benazepril. Use of triple therapy with furosemide, an ACE inhibitor and Pimobendan is recommended. When financial or compliance concerns limit the therapeutic choices, evidence suggests that Pimobendan is superior to an ACE inhibitor.  
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'''Pimobendan''' is phosphodiesterase inhibitor and calcium sensitiser that is both a ''positive inotrope'' and ''vasodilator'' (inodilator). A randomized clinical trial (QUEST) demonstrated a survival benefit associated with Pimobendan administration, when evaluated relative to treatment which was considered at that time to be the gold standard; benazepril. Use of triple therapy with furosemide, an ACE inhibitor and Pimobendan is recommended. When financial or compliance concerns limit the therapeutic choices, evidence suggests that Pimobendan is superior to an ACE inhibitor.  
    
Aldosterone may contribute to the development of myocardial fibrosis. Complete suppression of RAAS is generally not achieved by ACE inhibition alone. Therefore the addition of '''Spironolactone''' may be beneficial.
 
Aldosterone may contribute to the development of myocardial fibrosis. Complete suppression of RAAS is generally not achieved by ACE inhibition alone. Therefore the addition of '''Spironolactone''' may be beneficial.
    
Surgical mitral valve repair in dogs is currently being performed. However, availability is limited by the expense, required expertise and cardiopulmonary bypass facilities.
 
Surgical mitral valve repair in dogs is currently being performed. However, availability is limited by the expense, required expertise and cardiopulmonary bypass facilities.
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If the patient shows supraventricular tachycardia '''Digoxin''' can be prescribed. If that does not work effectively '''calcium canal blockers''' can be added.
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Relevant ventricular extrasystoles can be treated with '''sodium canal blockers.'''
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Syncopes or acsites can be treated with '''Sildenafil.'''
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'''Amlodipin''' can be used to treat systemic hypertension that occurs as a result to the valvular degeneration.
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''<u>Clinical Example:</u>''
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A patient is presented in an acute cardiac crisis. He is staged as C3-D. The therapy goal is to get him to C1.
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# inpatient admission
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# '''Furosemide'''
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#* depending on the degree of severity: 2-4 mg/kg body weight, parenteral, every 2-6 hours
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#* better is an intravenous drip that covers half of the conservation needs (1 mg/kg body weight per hour), can be reduced by half when the breathing rate has normalized
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# '''Pimobendan'''
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#* 0,15 mg/kg body weight once i.v.;
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#* when the symptoms persist the injection can be repeated after 12 hours
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# Oxygen
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# thoracocentesis if there is a liquidothorax
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# punction of the ascites if there is a right heart failure
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# '''Dobutamin''': 5–10µg/kg body weight/min (Stadium D)
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# '''Nitroglycerin''' with an atomizer: 1–2 pumps in the mouth (cave: do not breath in, wear gloves!)
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# '''ACE inhibitors''' and '''Spironolactone''' should be added as soon as oral treatment is possible
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'''''When the patient is stabilized:'''''
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# treatment can be continued at home
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# '''Sildenafil''' for the pulmonary hypertension
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===Stage D===
 
===Stage D===
 
If congestive heart failure signs are not controlled by high doses of Furosemide, addition of a thiazide and Spironolactone should be considered. Together these drugs have a synergistic action, by providing sequential nephron blockade, allowing lower doses of the individual agents.
 
If congestive heart failure signs are not controlled by high doses of Furosemide, addition of a thiazide and Spironolactone should be considered. Together these drugs have a synergistic action, by providing sequential nephron blockade, allowing lower doses of the individual agents.
    
==Monitoring and Follow Up==
 
==Monitoring and Follow Up==
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For dogs in stage B, owners should be made aware of signs of congestive heart failure. In dogs with Stage B2 disease where congestive heart failure is imminent, it is useful to give the owner Furosemide to administer if the dog develops signs of respiratory distress. Owners of Stage B2 and Stage C dogs should be educated on how to measure sleeping respiratory rate and should begin recording this regularly.
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The frequency of follow-up examinations is dependent on the severity of disease and owner compliance. For dogs with preclinical disease, rechecks can be recommended every 6-12 months depending on the severity of mitral regurgitation and cardiac remodeling. Following hospitalization for control of acute congestive heart failure, dogs should receive a follow up examination within 2 weeks to check for resolution of clinical signs, hydration status, electrolytes and renal function. For dogs in stage C with stable disease, re-checks can be every 3-6 months.
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== Prognosis ==
 
== Prognosis ==
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Asymptomatic patients may live for many years. Once heart failure occurs, life expectancy is usually around 6-12 months, although some patients remain stable for years. Risk factors for progression include severity of valvular lesions, increased age and male gender. Risk factors for onset of congestive heart failure include severity of mitral regurgitation, left atrial enlargement and elevated NT-proBNP. Development of complications such as atrial fibrillation or chordae tendinae rupture are associated with a poor prognosis.  
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Asymptomatic patients may live for many years. Dogs with stage B2 disease have a median of 27 months before developing congestive heart failure. Once heart failure occurs, life expectancy is usually around 6-12 months, although some patients remain stable for longer. Risk factors for progression include severity of valvular lesions, increased age and male gender. Risk factors for onset of congestive heart failure include severity of mitral regurgitation, left atrial enlargement and elevated NT-proBNP. Development of complications such as atrial fibrillation or chordae tendinae rupture are associated with a poor prognosis.  
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==References==
 
==References==
* Ettinger, S.J. and Feldman, E. C. (2000) Textbook of Veterinary Internal Medicine Diseases of the Dog and Cat Volume 2 (Fifth Edition), W.B. Saunders Company
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* Tilley,L.P., Smith, F.W.K, Oyama, M., Sleeper, M. (2016) '''Manual of Canine and Feline Cardiology (Fifth Edition)''' ''Saunders''.
* Ettinger, S.J, Feldman, E.C. (2005) Textbook of Veterinary Internal Medicine (6th edition, volume 2), W.B. Saunders Company
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* Luis Fuentes, V, Johnson, L.R, Dennis, S. (2010) '''BSAVA Manual of Canine and Feline Cardiorespiratory Medicine (Second Edition)'''
* Fossum, T. W. et. al. (2007) Small Animal Surgery (Third Edition), Mosby Elsevier * Merck & Co (2008) '''The Merck Veterinary Manual (Eighth Edition)''' ''Merial''
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* Boswood, A. et al. Effect of Pimobendan in Dogs with Preclinical Myxomatous Mitral Valve Disease and Cardiomegaly: The EPIC Study - A Randomized Clinical Trial. JVIM, September 2016. DOI: 10.1111/jvim.14586
* Nelson, R.W. and Couto, C.G. (2009) '''Small Animal Internal Medicine (Fourth Edition)''' ''Mosby Elsevier''.
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* Tilley, L.P. and Smith, F.W.K.(2004) '''The 5-minute Veterinary Consult (Third edition)''' ''Lippincott, Williams & Wilkins''.
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* Tilley,L.P., Smith, F.W.K, Oyama, M., Sleeper, M. (2007) '''Manual of Canine and Feline Cardiology''' ''Saunders''.
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