Doença Valvular Degenerativa: Diagnóstico e Tratamento

Chronic degenerative valvular disease is the most common cardiovascular disease in small animals, and is also known as endocardiosis or myxomatous valve degeneration.

It is seen more commonly in older small-breed dogs, and males appear to be predisposed and develop more severe disease.

Anatomy

 Mitral valve (dog) - large anterior leaflet, smaller posterior leaflet and small commissural cusps between the two leaflets. Both leaflets are semicircular and are attached to the mitral valve annulus (fibrous ring) and to the papillary muscles (through chordae tendineae).

 Tricuspid valve - two primary leaflets and multiple commissural cusps. The mural leaflet is significantly larger than the septal leaflet.

 Aortic valve - three semi-lunar cusps.

Pathology

 Mitral valve lesions are the most common, but the tricuspid valve and rarely the aortic valve can also be affected.

 Gross inspection reveals thickened and redundant valve leaflets. The free margins of the leaflets are the most commonly affected areas, which have nodules and are opaque.

 Mitral valve prolapse - a portion of the body of the leaflet protrudes into the left atrium.

Structures involved: leaflets and chordae tendineae

Lesions:

 Redundancy of the leaflets

 Lengthening of the chordae tendineae

 Thickened and/or fenestrated leaflets

Histopathology

The atrioventricular valves have four layers:

 Atrialis (endocardial)

 Spongiosa (collagen, fibroblasts, elastic fibers, and mucopolysaccharides)

 Fibrosa (collagen bundles)

 Ventricularis (endocardial)

In myxomatous AV degeneration the spongiosa increases in size and the fibrosa degenerates. A significant increase in extracellular matrix is observed and fibroblasts proliferate forming nodules.

Etiology

 Likely hereditary. Evidence suggests that degenerative valvular disease is inherited as a polygenic threshold trait in Cavalier King Charles spaniels.

Pathophysiology

 Valvular regurgitation → increased atrial volume → atrial dilatation

 Eccentric hypertrophy → annular dilation → worsening regurgitation

 Increased atrial pressure → congestive heart failure

 Severe regurgitation → decreased forward flow

 -Decreased forward flow → renin-angiotensin-aldosterone system (RAAS) stimulation

 Pulmonary hypertension can develop secondary to chronic pulmonary venous hypertension.

 Myocardial failure usually occurs in the latter stages of the disease and is more commonly identified in large-breed dogs.

 Atrial tears/rupture can cause cardiac tamponade secondary to acute hemopericardium.

History/Clinical Signs

Coughing, labored breathing, syncope, distended abdomen

Physical Exam

Mucous membrane color and CRT, jugular veins, thoracic auscultation and peripheral pulses.

Common PE findings:

 Heart murmur, increased intensity of the first heart sound, systolic click, third heart sound, arrhythmias, tachypnea/tachycardia, crackles and wheezes, distended jugular veins, brisk femoral pulses.

Diagnostic Tests

 Thoracic radiographs, ECG, echocardiogram, blood pressure, laboratory tests.

Laboratory tests

 B-type natriuretic factor/peptide (BNP) and cardiac troponin-I (TnI)

Real-time 3D echocardiography

Real time three-dimensional echocardiography is a new ultrasound modality that provides comprehensive views of cardiac valves. This technique potentially provides a more accurate echocardiographic means of evaluating cardiac chamber volumes and a more precise postoperative tool.

Asymptomatic Disease

 ACE inhibitors

 Pimobendan?

 β-blockers?

Heart Failure

 Congestive heart failure is the end result of severe heart disease

 Clinical syndrome of congestion and edema

 Poor peripheral perfusion +/- systemic hypotension

Acute Treatment

 Oxygen, diuretics, vasodilators and positive inotropes

Loop diuretics

 Potent diuretics

 Block Na⁺/K⁺/2Cl^- co-transport

 Increase K⁺, Mg⁺⁺, and Ca⁺⁺ excretion

 Intermittent IV boluses or continuous rate infusion (CRI)

 IV boluses: furosemide 2–4 mg/kg q4–8 h

Vasodilators

Sodium nitroprusside

 Produces nitric oxide in vascular smooth muscle

 Intravenous

 Peripheral vasodilation: arteriolar and venodilator

Hydralazine

 0.5–3 mg/kg PO BID

 Alters Ca⁺⁺ metabolism

 Acts on vascular smooth muscle (arterioles)

 Increases aortic compliance and decreases peripheral vascular resistance and BP

Nitroglycerine

 Relaxes vascular smooth muscle

 Veins

 Dose-dependent effect on arterioles

 Decrease myocardial oxygen demand

 Improve coronary artery circulation

 Metabolites vasodilator activity

Positive inotropes

Dobutamine

 Synthetic catecholamine

 Beta 1 agonist; some beta 2 and alpha 1 effects

 Increases contractility

 Mild chronotropic, arrhythmogenic, and vasodilatory effects

Chronic Treatment

Diuretics

Loop diuretics

 Thick ascending loop of Henle

 Furosemide: 2–4 mg/kg PO BID–TID (dogs); 1–4 mg/kg PO BID–TID (cats)

 Torsemide (0.2–0.4 mg/kg PO BID)

Thiazides

 Hydrochlorothiazide (1–4 mg/kg EOD–BID)

 Na⁺/Cl^- channel in the distal convoluted tubule

K⁺ sparing diuretics/aldosterone blockers

 Spironolactone: 1–4 mg/kg PO BID–TID

 Distal tubule

 Inhibits aldosterone

 Decreases myocardial fibrosis?

 Restore baroreceptor function CHF

Vasodilators

ACE inhibitors

 Enalapril: 0.5 mg/kg PO BID

 Benazepril: 0.5 mg/kg PO SID–BID)

 Decrease efferent arteriole pressure and the glomerular filtration rate (GFR)

Calcium channel blockers

 Amlodipine: 0.1–0.5 mg/kg PO SID

 Inhibits calcium flux across cell membranes (vascular smooth muscle > cardiac)

 Depresses automaticity and conduction velocity (cardiac muscle)

Phosphodiesterase-5 inhibitors

 Sildenafil: 1 mg/kg PO TID

 Tadalafil: 1 mg/kg PO SID–BID

 Prevent enzymatic hydrolysis of cGMP

 Smooth muscle relaxation

Positive Inotropes

Pimobendan:

 0.2–0.3 mg/kg PO BID–TID

 Inodilator

 Phosphodiesterase-3 inhibitor

 Ca⁺⁺ sensitizer

 Quest study: improves median survival time and quality of life

Digitalis glycosides (Digoxin)

 Inhibit Na⁺/K⁺ ATPase

 Positive inotrope

 Decreased AVN conduction

 Caution with renal disease

 Toxicity - GI signs, arrhythmias

Recent clinical trials concerning the use of ACE inhibitors, β-blockers, spironolactone, and pimobendan in asymptomatic disease and heart failure will be reviewed.

QUEST - Pimobendan vs. benazepril trial in patients with congestive heart failure secondary to degenerative mitral valve disease.

VETPROOF (follow-up) - Enalapril trial in asymptomatic patients with degenerative mitral valve disease.

Benazepril study - University of Alfort - Benazepril trial in asymptomatic patients with degenerative mitral valve disease.

Spironolactone studies - spironolactone reduces the risk of cardiac death and is safe to use in dogs in congestive heart failure secondary to degenerative valve disease.

EPIC study - multicenter study evaluating the use of pimobendan in asymptomatic patients with degenerative mitral valve disease.

References

1.  Kittleson MD, Kienle R. Small Animal Cardiovascular Medicine. St. Louis, MO: Mosby; 1998.

2.  Plumbs Veterinary Drugs, online edition.

3.  Lefebvre HP, Ollivier E, et al. Safety of spironolactone in dogs with chronic heart failure because of degenerative valvular disease: a population-based, longitudinal study. J Vet Intern Med. 2013;27(5):1083–91.

4.  Bernay F, Bland JM, 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(2):331–41.

5.  Häggström J, Boswood A, et al. Longitudinal analysis of quality of life, clinical, radiographic, echocardiographic, and laboratory variables in dogs with myxomatous mitral valve disease receiving pimobendan or benazepril: the QUEST study. J Vet Intern Med. 2013;27(6):1441–51.

6.  Atkins CE, Keene BW, 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. J Am Vet Med Assoc. 2007;231(7):1061–9.

7.  Pouchelon JL, Chetboul V, et al. Effect of benazepril on survival and cardiac events in dogs with asymptomatic mitral valve disease: a retrospective study of 141 cases. J Vet Intern Med. 2008;22(4):905–14.