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Degenerative Mitral Valve Disease (view source)
Revision as of 14:16, 11 May 2021
, 14:16, 11 May 2021Addition in clinical signs, diagnostics and treatment
The '''mitral apparatus''' consists of the mitral '''valve leaflets''', valve '''annulus''', '''chordae tendinae''' and '''papillary muscles'''. The mitral valve leaflets are known as '''anterior''' and '''posterior''' leaflets. In the normal dog, these are thin, translucent structures that are anchored to the papillary muscles by chordae tendinae. Both papillary muscles (anterior and posterior) arise from the left ventricular free wall. The mitral valve prevents the backflow of blood from the left ventricle to the left atrium during systole. In early systole, when left ventricular pressure exceeds left atrial pressure, the mitral valve leaflets close. In normal dogs, the chordae tendinae tether the leaflets to prevent them prolapsing into the left atrium. When the mitral valve is incompetent, there is ''regurgitation'' of blood from the left ventricle to the left atrium. Mitral regurgitation may be mild, with no clinical consequence, or may be severe. The severity of mitral regurgitation is determined primarily by the size of the orifice, that results from incomplete apposition of the mitral valve leaflets, and the relationship between left ventricular and left atrial systolic pressures. Mitral regurgitation causes an increase in left atrial pressure, which over time can lead to left atrial dilation. In diastole, the left ventricle is filled by both pulmonary venous return and blood that has been regurgitated into the left atrium. Therefore, both the left atrium and left ventricle become volume overloaded. This may result in ''ventricular dilation and eccentric hypertrophy''. In severe cases, increased left ventricular and left atrial filling pressures may result. This leads to an increase in pulmonary venous pressure and may result in [[Heart Failure, Left-Sided|left-sided congestive heart failure]].
The '''mitral apparatus''' consists of the mitral '''valve leaflets''', valve '''annulus''', '''chordae tendinae''' and '''papillary muscles'''. The mitral valve leaflets are known as '''anterior''' and '''posterior''' leaflets. In the normal dog, these are thin, translucent structures that are anchored to the papillary muscles by chordae tendinae. Both papillary muscles (anterior and posterior) arise from the left ventricular free wall. The mitral valve prevents the backflow of blood from the left ventricle to the left atrium during systole. In early systole, when left ventricular pressure exceeds left atrial pressure, the mitral valve leaflets close. In normal dogs, the chordae tendinae tether the leaflets to prevent them prolapsing into the left atrium. When the mitral valve is incompetent, there is ''regurgitation'' of blood from the left ventricle to the left atrium. Mitral regurgitation may be mild, with no clinical consequence, or may be severe. The severity of mitral regurgitation is determined primarily by the size of the orifice, that results from incomplete apposition of the mitral valve leaflets, and the relationship between left ventricular and left atrial systolic pressures. Mitral regurgitation causes an increase in left atrial pressure, which over time can lead to left atrial dilation. In diastole, the left ventricle is filled by both pulmonary venous return and blood that has been regurgitated into the left atrium. Therefore, both the left atrium and left ventricle become volume overloaded. This may result in '''ventricular dilation and eccentric hypertrophy'''. In severe cases, increased left ventricular and left atrial filling pressures may result. This leads to an increase in pulmonary venous pressure and may result in [[Heart Failure, Left-Sided|left-sided congestive heart failure]].
==Signalment==
==Signalment==
Degenerative mitral valve disease tends to affect middle-aged and older dogs, with males being predisposed. The disease more commonly affects small breed dogs, with Cavalier King Charles Spaniels, Chihuahuas, Boston Terriers, Poodles, Pomeranians and Bull Terriers being predisposed. The disease is also recognized in large breed dogs.
Degenerative mitral valve disease tends to affect middle-aged and older dogs, particularly males. The disease more commonly affects small breed dogs, with Cavalier King Charles Spaniels, Chihuahuas, Boston Terriers, Poodles, Pomeranians and Bull Terriers being predisposed. The disease is also recognized in large breed dogs.
==History==
==History and Clinical Signs==
Animals may remain asymptomatic for years, the disease is usually clinically silent until it is advanced.
Animals may remain asymptomatic for years, the disease is usually clinically silent until it is advanced.
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.
Other symptoms that may occur include increased exercise intolerance and efficiency, tachypnea or dyspnea during exercise, ascites, weight loss, anorexia and thromboembolisms.
== Diagnosis==
===Physical Examination===
* Systolic murmur with point of maximal intensity over the left apex. Murmur grade is usually correlated with severity of mitral regurgitation, severe regurgitation causes a loud murmur.
* Mid-systolic click, associated with mitral prolapse. In many dogs, clicks are a precursor to mitral regurgitation.
Other findings will depend on the stage of disease. Crackles may be detected on thoracic auscultation in patients with pulmonary oedema, resulting from [[Heart Failure, Left-Sided|left-sided congestive heart failure]]. Abdominal palpation is usually normal, but ascites and hepatomegaly may be present when there is concurrent [[Heart Failure, Right-Sided|right-sided congestive heart failure]].
Primary respiratory disease, such as chronic bronchitis, is also common in older small breed dogs. It is important to distinguish between the patient with clinically significant respiratory disease and incidental DMVD from the patient with clinically significant DMVD. Respiratory sinus arrhythmia, indicating vagal influence on heart rate and rhythm, is usually not present in severe cardiac disease. In contrast, sinus arrhythmia is usually preserved or accentuated when respiratory disease is the cause of clinical signs.
===Diagnostic Imaging===
===Diagnostic Imaging===
====Radiography====
====Radiography====
Early in the course of DMVD, thoracic radiographs will be normal. As the disease progresses, cardiomegaly will become apparent. There may be evidence of left atrial enlargement, with or without dorsal displacement of the trachea and narrowing of the mainstem bronchus. Pulmonary venous distension may be observed if there is increased pulmonary venous pressure. Interstitial pulmonary oedema may precede alveolar pulmonary oedema. Evidence of [[Heart Failure, Right-Sided|right-sided congestive heart failure]] may be present in severe cases, radiographic findings include distension of the caudal vena cava, hepatomegaly, ascites and pleural effusion.
====Echocardiography====
* Thickened mitral valve leaflets
* Prolapse of mitral valve leaflets into the left atrium during systole
* Tricuspid leaflets may also be affected, though usually not as severely as the mitral valve
* Increased diastolic left ventricular diameter
* Hyperdynamic left ventricle
* Colour Doppler jet of mitral regurgitation
*(Flail leaflet)
Thickening of the mitral valve leaflets is usually diffuse, but most pronounced at the leaflet edges. With myxomatous degeneration, the mitral valve becomes stiffer and distorted. The conformation of the valve remains constant throughout the cardiac cycle. Normally, the mitral valve leaflets do not extend beyond a line across the mitral annulus in systole. In dogs with DMVD, the mitral leaflets prolapse towards the left atrium during systole. Colour Doppler can be used to demonstrate the jet of mitral regurgitation. The size of the jet is related to the severity of mitral regurgitation. Most mitral regurgitation jets in DMVD are eccentric.
The more severe the DMVD, the greater the degree of left ventricular and left atrial dilation.
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.
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.
'''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)===
Electrocardiography is primarily used to diagnose arrhythmias, but can provide evidence of chamber enlargement. Most arrhythmias in DMVD are supraventricular in origin and occur secondary to left atrial stretch. Ventricular arrhythmias may develop in association with left ventricular dilation and fibrosis.
* P-mitrale: wide P waves in leads II, III and aVF, indicates left atrial enlargement
* high R-wave
* Stage C2-D: (supra-) ventricular extrasystoles
===Laboratory Tests===
===Laboratory Tests===
Pro-brain natriuretic peptide (N-BNP) is a newly described cardiac hormone considered to be an effective marker of severity and prognosis of acute coronary syndromes and congestive heart failure. Circulating levels of the hormone increase in peripheral blood with increased myocardial stress. Commercial assays are not currently available.
Pro-brain natriuretic peptide ('''NT-proBNP''') concentration is associated with severity of DMVD. Elevated NT-proBNP levels are useful in discriminating patients with respiratory distress caused by heart failure from those with primary respiratory tract disease.
==Staging==
Staging according to American College of Veterinary Internal Medicine (ACVIM) is as follows:
* '''Stage A''': Dog predisposed to the development of DMVD
* '''Stage B''': Subclinical disease
** ''B1'': Without cardiac remodeling
** ''B2'': With cardiac remodeling
* '''Stage C''': Current or prior clinical signs
* '''Stage D''': Refractory heart failure
== Treatment ==
== Treatment ==
===Stage B===
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.
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.
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.
===Stage C===
Medical management is intended to alleviate clinical signs and prolong life.
'''Furosemide''' is a potent first-line diuretic that can be administered orally or parenterally, depending on the clinical status of the patient. Most patients with congestive heart failure secondary to DMVD require lifelong diuretic therapy.
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.
'''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.
Surgical mitral valve repair in dogs is currently being performed. However, availability is limited by the expense, required expertise and cardiopulmonary bypass facilities.
If the patient shows supraventricular tachycardia '''Digoxin''' can be prescribed. If that does not work effectively '''calcium canal blockers''' can be added.
Relevant ventricular extrasystoles can be treated with '''sodium canal blockers.'''
Syncopes or acsites can be treated with '''Sildenafil.'''
'''Amlodipin''' can be used to treat systemic hypertension that occurs as a result to the valvular degeneration.
''<u>Clinical Example:</u>''
A patient is presented in an acute cardiac crisis. He is staged as C3-D. The therapy goal is to get him to C1.
# inpatient admission
# '''Furosemide'''
#* depending on the degree of severity: 2-4 mg/kg body weight, parenteral, every 2-6 hours
#* 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
# '''Pimobendan'''
#* 0,15 mg/kg body weight once i.v.;
#* when the symptoms persist the injection can be repeated after 12 hours
# Oxygen
# thoracocentesis if there is a liquidothorax
# punction of the ascites if there is a right heart failure
# '''Dobutamin''': 5–10µg/kg body weight/min (Stadium D)
# '''Nitroglycerin''' with an atomizer: 1–2 pumps in the mouth (cave: do not breath in, wear gloves!)
# '''ACE inhibitors''' and '''Spironolactone''' should be added as soon as oral treatment is possible
'''''When the patient is stabilized:'''''
# treatment can be continued at home
# '''Sildenafil''' for the pulmonary hypertension
===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.
==Monitoring and Follow Up==
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.
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.
== Prognosis ==
== Prognosis ==
Asymptomatic patients may live for many years. Once heart failure occurs, life expectancy is usually around one year although some patients remain stable for years on heart failure medications.
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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{{Learning
==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
* Tilley,L.P., Smith, F.W.K, Oyama, M., Sleeper, M. (2016) '''Manual of Canine and Feline Cardiology (Fifth Edition)''' ''Saunders''.
* Luis Fuentes, V, Johnson, L.R, Dennis, S. (2010) '''BSAVA Manual of Canine and Feline Cardiorespiratory Medicine (Second Edition)'''
* 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''.
* Tilley, L.P. and Smith, F.W.K.(2004) '''The 5-minute Veterinary Consult (Third edition)''' ''Lippincott, Williams & Wilkins''.
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