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eMedicine Specialties > Cardiology > Valvular Heart Disease

Mitral Regurgitation

Author: Ivan Hanson, MD,, Fellow, Department of Cardiovascular Disease, William Beaumont Hospital
Coauthor(s): Luis C Afonso, MD, Assistant Professor, Department of Internal Medicine-Cardiology, Program Director of Cardiology Fellowship Program, Wayne State University; Director of Echocardiography Laboratory, Harper University Hospital
Contributor Information and Disclosures

Updated: Jan 8, 2010

Introduction

Background

Mitral regurgitation (MR) is defined as an abnormal reversal of blood flow from the left ventricle to the left atrium. It is caused by disruption in any part of the mitral valve apparatus, which comprises the mitral annulus, the leaflets (a large anterior [aortic] leaflet and a small posterior [mural] leaflet), the chordae tendineae, and the papillary muscles (anteromedial and posterolateral). The most common etiologies of MR include mitral valve prolapse (MVP), rheumatic heart disease, infective endocarditis, annular calcification, cardiomyopathy and ischemic heart disease. The pathophysiology, clinical manifestations and management of MR differ with the chronicity of the disease and the etiology. 

Pathophysiology

MR can be caused by organic disease (eg, rheumatic fever, ruptured chordae tendineae, myxomatous degeneration, leaflet perforation) or a functional abnormality (ie, a normal valve may regurgitate [leak] because of mitral annular dilatation, focal myocardial dysfunction, or both). Congenital MR is rare but is commonly associated with myxomatous mitral valve disease. Alternatively, it can be associated with cleft of the mitral valve, as occurs in persons with Down syndrome, or a ostium primum atrial septal defect.

Acute mitral regurgitation

Acute MR is characterized by an increase in preload and a decrease in afterload causing an increase in end-diastolic volume (EDV) and a decrease in end-systolic volume (ESV). This leads to an increase in total stroke volume (TSV) to supranormal levels. However, forward stroke volume (FSV) is diminished because much of the TSV regurgitates as the regurgitant stroke volume (RSV). This, in turn, results in an increase in left atrial pressure (LAP). According to the Laplace principle, which states that ventricular wall stress is proportional to both ventricular pressure and radius, LV wall stress in the acute phase is markedly decreased since both of these parameters are reduced.

Chronic compensated mitral regurgitation

In chronic compensated MR, the left atrium (LA) and ventricle have sufficient time to dilate and accommodate the regurgitant volume. Thus LA pressure is often normal or only minimally elevated. Because of the left ventricular dilatation via the process of eccentric hypertrophy, TSV and FSV are maintained. Wall stress may be normal to slightly increased as the radius of the LV cavity increases but the end-diastolic LV pressure remains normal. As the LV progressively enlarges, the mitral annulus may stretch and prevent the mitral valve leaflets from coapting properly during systole, thus worsening the MR and LV dilatation.

Chronic decompensated mitral regurgitation

In the chronic decompensated phase, muscle dysfunction has developed, impairing both TSV and FSV (although ejection fraction still may be normal). This results in a higher ESV and EDV, which in turn causes a elevation of LV and LA pressure, ultimately leading to pulmonary edema and, if left untreated, cardiogenic shock.

Frequency

United States

Acute and chronic MR affect approximately 5 in 10,000 people. Mitral valve disease is the second most common valvular lesion, preceded only by aortic stenosis. Myxomatous degeneration has replaced rheumatic heart disease as the leading cause of mitral valvular abnormalities. Mitral valve prolapse has been estimated to be present in 4% of the normal population. With the aid of color Doppler echocardiography, mild MR can be detected in as many as 20% of middle-aged and older adults. MR is independently associated with female sex, lower body mass index, advanced age, renal dysfunction, prior myocardial infarction, prior mitral stenosis, and prior mitral valve prolapse. It is not related to dyslipidemia or diabetes.

International

In areas other than the Western world, rheumatic heart disease is the leading cause of MR.

Clinical

History

Acute mitral regurgitation

When associated with coronary artery disease and acute myocardial infarction (typically, inferior myocardial infarction, which may lead to papillary muscle dysfunction), significant acute mitral regurgitation (MR) is accompanied by symptoms of impaired LV function, such as dyspnea, fatigue, and orthopnea. In these cases, pulmonary edema is often the initial manifestation because of rapid volume overload on the left atrium and the pulmonary venous system.

Chronic mitral regurgitation

• Often results from a primary defect of the mitral valve apparatus with subsequent progressive enlargement of the left atrium and ventricle. In this state, patients may remain asymptomatic for years.
• Patients may have normal exercise tolerance until systolic dysfunction of the LV develops, at which point they may experience symptoms of a reduced forward cardiac output (ie, fatigue, dyspnea on exertion, or shortness of breath).
• With time, patients may feel chest palpitations if atrial fibrillation develops as a result of chronic atrial dilatation. For related information, see Medscape's Atrial Fibrillation Resource Center.
• Patients with LV enlargement and more severe disease eventually progress to symptomatic congestive heart failure with pulmonary congestion and edema. At this stage of LV dilatation, the myocardial dysfunction often becomes irreversible. For related information, see Medscape's Heart Failure Resource Center.

Physical

Palpation

• Brisk carotid upstroke and hyperdynamic cardiac impulse
• Prominent LV filling wave may be present

Auscultation

• S ₁ may be diminished in acute MR and chronic severe MR with defective valve leaflets.
• Wide splitting of S ₂ may occur due to early closure of the aortic valve.
• S ₃ may be present due to LV dysfunction or as a result of increased blood flow across the mitral valve.
• P ₂ may be accentuated if pulmonary hypertension is present.
• Murmur
• Quality
• Usually high-pitched, blowing
• Location
• Usually best heard over the apex
• Usually radiates to the left axilla or subscapular region
• Posterior leaflet dysfunction causes murmur to radiate to the sternum or aortic area
• Anterior leaflet dysfunction causes murmur to radiate to the back or top of the head
• Duration
• Usually holosystolic
• May be confined to early systole in acute MR
• May be confined to late systole in MVP or papillary muscle dysfunction
• S ₁ will probably be normal in these cases since initial closure of mitral valve cusps is unimpeded.
• A midsystolic click preceding murmur is suggestive of MVP.
• Intensity
• Little correlation exists between intensity of murmur and severity of MR.
• Intensity may be diminished in severe MR caused by LV dysfunction, acute myocardial infarction, or periprosthetic valve regurgitation. 

Causes

Acute mitral regurgitation

• Coronary artery disease (ischemia or acute myocardial infarction)
• Papillary muscle dysfunction
• The posteromedial papillary muscle is supplied by the terminal branch of the posterior descending artery and is more vulnerable to ischemic insult than the anterolateral papillary muscle, which is usually supplied by both the left anterior descending and circumflex arteries.
• Transient ischemia may result in transient MR associated with angina.
• Myocardial infarction or severe prolonged ischemia produces irreversible papillary muscle dysfunction and scarring.
• Chordae tendineae dysfunction or rupture
•  
• Infectious endocarditis
• Abscess formation
• Vegetations
• Rupture of chordae tendineae
• Leaflet perforation
• Status post valvular surgery
• Trauma
• Percutaneous valvuloplasty
• Suture interruption
• Tumors (most commonly atrial myxoma)
• Myxomatous degeneration
• Mitral valve prolapse
• Ehlers-Danlos syndrome
• Marfan syndrome
• Systemic lupus erythematosus (Libman-Sacks lesion)
• Acute rheumatic fever (Carey Coombs murmur)
• Acute global left ventricular dysfunction
• Prosthetic mitral valve dysfunction

Chronic mitral regurgitation

• Rheumatic heart disease
• Systemic lupus erythematosus
• Scleroderma
• Myxomatous degeneration
• Mitral valve prolapse
• Ehlers-Danlos syndrome
• Marfan syndrome
• Calcification of mitral valve annulus
• Infective endocarditis (can affect normal, abnormal, or prosthetic mitral valves)
• Ruptured chordae tendineae
• Trauma
• Mitral valve prolapse
• Endocarditis
• Spontaneous
• Rupture or dysfunction of papillary muscles
• Coronary artery disease (see causes for acute MR)
• Dilation of mitral valve annulus and/or left ventricular cavity (functional MR)
• Dilated cardiomyopathies
• Aneurysmal dilation of the left ventricle
• Hypertrophic cardiomyopathy
• Perivalvular prosthetic leak
• Congenital
• Mitral valve clefts
• Mitral valve fenestrations
• Parachute mitral valve abnormality
• Drug-related
• Ergotamine, methysergide, pergolide, anorexiant medications

Differential Diagnoses

Aortic Regurgitation	Mitral Valve Prolapse
Aortic Stenosis	Pulmonic Regurgitation
Complications of Myocardial Infarction	Pulmonic Stenosis
Mitral Stenosis	Ventricular Septal Defect

Other Problems to Be Considered

Calcified aortic stenosis also produces a prominent murmur at the apex (Gallavardin phenomenon) and may be confused with mitral valve regurgitation.

Tricuspid regurgitation also causes a holosystolic murmur. However, it is located at the left lower sternal border rather than the apex, it does not radiate to the axilla, and it increases in intensity with inspiration, whereas MR does not.

A ventricular septal defect produces a harsh holosystolic murmur at the lower left sternal border, but it generally radiates to the right of the sternum rather than the axilla and typically has a thrill.

Workup

Imaging Studies

Chest radiography

• Evidence of LV enlargement due to volume overload may be observed (particularly in chronic MR), although pulmonary congestion (eg, increased pulmonary markings) may not be observed until heart failure has developed.
• Left atrial enlargement may also be observed in the AP view as a double shadow in the right cardiac silhouette and/or straightening of the left cardiac border due to the large left atrial appendage.

Echocardiography

ACC/AHA Class I indications¹ for performing transthoracic echocardiography

• Baseline eval‎uation for LV size and function, RV and LA size, pulmonary artery pressure, and severity of MR
• Parameters of severity of MR
• Color flow jet width and area
• Intensity of continuous-wave Doppler signal
• Pulmonary venous flow contour
• Peak early mitral inflow velocity
• Regurgitant orifice area
• Regurgitation volume
• Left ventricular and left atrial size
• Determining the etiology of MR
• With acute MR, a ruptured chordae tendineae or papillary muscle, a flail valve leaflet, or infective endocarditis may be identified as the etiology.
• A central color flow jet of MR with a structurally normal mitral valve suggests functional MR.
• Annual or semiannual surveillance of LV ejection fraction and end-systolic dimension in asymptomatic patients with moderate-to-severe MR
• Eval‎uation of the mitral valve apparatus and LV function after a change in signs or symptoms
• Eval‎uation of LV size and function and mitral valve hemodynamics in the initial eval‎uation after MV replacement or repair.

 [ CLOSE WINDOW ]

Transthoracic echocardiogram demonstrating bioprosthetic mitral valve dehiscence with paravalvular regurgitation.

ACC/AHA Class I indications¹ for performing serial transthoracic echocardiography

• Asymptomatic patients with mild MR and no evidence of LV enlargement, LV dysfunction, or pulmonary hypertension can be observed on a yearly basis; serial echocardiography is not indicated.
• Patients with moderate MR should have an echocardiogram performed yearly.
• In asymptomatic patients with severe MR, echocardiography and clinical eval‎uation should be done every 6-12 months to assess symptoms and development of LV dysfunction.

ACC/AHA Class I indications¹ for performing transesophageal echocardiography

• Assessment of etiology of severe MR in patients for whom surgery is recommended to determine the feasibility of valve repair
• Eval‎uation of mitral valve and associated structures in patients for whom transthoracic echocardiography provides nondiagnostic information

 [ CLOSE WINDOW ]

Transesophageal echocardiogram demonstrating prolapse of both mitral valve leaflets during systole.

Other Tests

Electrocardiography

• Ischemia or infarction in the inferior or posterior leads is present when acute MR is due to papillary muscle rupture. 
• In chronic mitral valve regurgitation, LV dilatation and hypertrophy are observed with increased QRS voltage and ST-T wave changes in the lateral precordial leads. 
• Left atrial enlargement in chronic mitral valve regurgitation produces a negative P wave in lead V₁, and/or a wide notched P wave in leads II, III, or aVF. Atrial fibrillation may be observed in the late stages.

BNP assessment

Pizarro et al found that in patients with severe asymptomatic mitral regurgitation and normal left ventricular function, levels of brain natriuretic peptide (BNP) have an independent and additive prognostic value. In a prospective study of 269 consecutive patients with severe asymptomatic organic mitral regurgitation and left ventricular ejection fraction above 60%, the receiver-operating characteristics curve yielded an optimal cutoff point of 105 pg/mL of BNP that was able to discriminate patients at higher risk. Pizarro et al recommend considering BNP assessment in the routine clinical workup for risk stratification, which may aid in the selection of patients for early surgery.²

Procedures

ACC/AHA Class I indications¹ for performing cardiac catheterization

• Left ventriculography and hemodynamic measurements are indicated when noninvasive tests are inconclusive regarding severity of MR, LV function, or the need for surgery.
• Hemodynamic measurements are indicated when pulmonary artery pressure is out of proportion to the severity of MR as assessed by noninvasive testing.
• Left ventriculography and hemodynamic measurements are indicated when the clinical and noninvasive findings are conflicting regarding severity of MR.
• Coronary angiography is indicated before MV repair or MV replacement in patients at risk for coronary artery disease or when the MR is suspected to be ischemic in origin.

Treatment

Medical Care

Prehospital care 

For the patient with acute MR, the electrocardiogram should be examined closely for evidence of acute myocardial infarction (MI). 

• If present, treatment with supplemental oxygen, analgesics for anginal chest pain, and sublingual nitrates for acute MI are the components of prehospital care.
• In the absence of acute MI, endocarditis should be excluded with blood cultures. 
• Transthoracic echocardiography should be performed.

Emergency department care

• Any patient with acute or chronic mitral valve regurgitation with hemodynamic compromise should be eval‎uated for acute myocardial infarction.
• Consultations with specialists in cardiology and cardiothoracic surgery should be obtained early during patient stabilization.
• Diuretic therapy is administered to individuals with pulmonary congestion, and an echocardiogram must be performed immediately. Patients with hemodynamic compromise should be expeditiously transferred to a cardiac critical care unit for central and pulmonary arterial pressure monitoring. 

Medical therapy

• Afterload-reducing agents (such as nitrates and antihypertensive drugs) and diuretics are helpful for maintaining the forward cardiac output in persons with MR with symptoms and/or LV dysfunction.
• Beta-blockers and biventricular pacing are used for primary treatment of LV dysfunction in functional MR.
• Intra-aortic balloon counterpulsation should be considered in the patient with acute MR and hemodynamic compromise.
• If atrial fibrillation is encountered, maintenance of a normal ventricular response with beta-blockers, calcium channel blockers, and/or digitalis therapy is considered.
• Anticoagulation is considered for patients who develop atrial fibrillation or have had mitral valve replacement surgery.
• Guidelines for the use of prophylactic antibiotics prior to periodontal procedures have recently changed.³ In addition to maintaining good oral hygiene, antibiotics are recommended prior to any dental procedure that involves manipulation of gingival tissue, the periapical region of a tooth, or perforation of oral mucosa in patients with any of the following conditions:
• Prosthetic heart valve
• Previous infectious endocarditis
• Some forms of congenital heart disease
• Valvulopathy in a cardiac transplant recipient
• Inotropic agents should be considered in chronic severely symptomatic MR, and consultation with a specialist in cardiothoracic surgery should be obtained.

Surgical Care

The risks and benefits of surgery should be assessed based on the age and comorbidity of each individual patient, with the decision to proceed or not to proceed being grounded in uniformly accepted guidelines.

• Operative mortality is higher in the patients older than 75 years.
• Coronary artery disease and other valvular diseases are preval‎ent in older patients who often require concomitant coronary artery bypass surgery, further increasing operative risk.

ACC/AHA indications¹ for mitral valve surgery

• Repair of mitral valve is recommended over replacement in most patients with severe chronic MR who require surgery, and patients should be referred to experienced surgical centers (Class I).
• Surgery is indicated for symptomatic patients with acute severe MR (Class I).
• Chronic severe MR
• Symptomatic
• New York Heart Association (NYHA) functional Class II-IV symptoms without severe LV dysfunction (EF ≥ 0.30 and/or end-systolic dimension ≤ 55 mm) (Class I).
• Chronic severe MR due to a primary abnormality of the mitral valve apparatus and NYHA functional Class III-IV symptoms and mild-to-moderate LV dysfunction (EF <0.30 and/or end-systolic dimension >55 mm) in whom MV repair is highly likely (Class IIa).
• Asymptomatic
• Asymptomatic patients with chronic, severe MR and mild-to-moderate LV dysfunction (EF 0.65 and/or end-systolic dimension ≥ 45 mm) (Class I).
• Mitral valve repair is reasonable in experienced centers for asymptomatic patients with chronic severe MR with preserved LV function (EF >0.65 and end-systolic dimension <45 mm) in whom the likelihood of successful repair without residual MR is greater than 90% (Class IIa).
• Surgery is reasonable for asymptomatic patients with chronic severe MR, preserved LV function, new onset atrial fibrillation, or pulmonary artery hypertension (pulmonary artery systolic pressure >50 mm Hg at rest or >60 mm Hg with exercise) (Class IIa).

Consultations

Consult specialists in cardiology and cardiothoracic surgery early during the patient eval‎uation in the emergency department.

Diet

A diet low in sodium is indicated for patients with symptomatic chronic MR or those with LV dysfunction.

Activity

Asymptomatic patients with MR of any severity can exercise without restriction if all of the following criteria are met:

• Sinus rhythm
• Normal LV and left atrial dimensions
• Normal pulmonary artery pressure 

Medication

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Diuretics

Help decrease pulmonary congestion.

Furosemide (Lasix)

Increases excretion of water by interfering with chloride-binding cotransport system, which, in turn, inhibits sodium and chloride reabsorption in the ascending loop of Henle and distal renal tubule. Dose must be individualized to patient.

Adult

20-80 mg/d PO as single dose; second dose can be administered 6-8 h later depending on response; increments of 20-40 mg can be given, but no sooner than within 6-8 h of the previous dose until desired diuresis achieved; if dose is >80 mg/d, can be given qd or bid; perform clinical and laboratory tests
Alternatively, administer 20-40 mg IM/IV; IV injection should be given slowly (over 1-2 min); if response not satisfactory within 1 h, dose can be increased to 80 mg IV (over 1-2 min)

Pediatric

2 mg/kg PO; increase by 1-2 mg/kg no sooner than 6-8 h after previous dose; doses > 6 mg/kg not recommended
Alternatively, 1 mg/kg IV/IM can be given slowly under close supervision; in case of unsatisfactory response, dose can be increased by 1 mg/kg no sooner than 2 h after previous dose until desired effects are seen; doses > 6 mg/kg not recommended

· 

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Perform frequent serum electrolyte, carbon dioxide, glucose, creatinine, uric acid, calcium, and BUN determinations during first few months of therapy and periodically thereafter

Angiotensin-converting enzyme inhibitors

Used in the presence of MR for afterload reduction.

Captopril (Capoten)

Competitive inhibitor of ACE. Reduces angiotensin II levels, decreasing aldosterone secretion. Goal is to decrease afterload to left ventricle (by reducing systemic blood pressure and by peripheral vasodilatation), which decreases amount of blood pumped by left ventricle and pressure at which blood is being ejected. This reduces amount of blood regurgitated by mitral valve from the left ventricle into the left atrium during systole. Elimination of drug is primarily by renal excretion. Impaired renal function requires dosage reduction. Absorbed well PO. Give at least 1 h before meals. If added to water, use within 15 min.

Adult

25 mg PO tid 1 h pc; most patients improve with 50-100 mg PO tid; allow up to 2 wk to determine satisfactory response; not to exceed 450 mg/d

Pediatric

Neonates: 0.1-0.4 mg/kg/d, PO divided q6-8h
Infants (<2 mo): 0.05-0.1 mg/kg/dose, PO q6h or q8h
Children: 0.15 mg/kg/dose PO q8h initially

· 

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in patients with renal impairment, valvular stenosis, or severe congestive heart failure; adjust dose in patients with acute renal failure; pruritic rash, photosensitivity, proteinuria (1:100 patients), neutropenia/agranulocytosis, anemia, thrombocytopenia, pancytopenia, cough (0.5-2% of patients), bronchospasm, hypotension, diminution of taste perception (ie, dysgeusia), angioedema, asthenia, gynecomastia, blurred vision, and impotence have been reported

Enalapril (Vasotec)

Competitive inhibitor of ACE. Reduces angiotensin II levels, decreasing aldosterone secretion. Goal is to decrease afterload to left ventricle (by reducing systemic blood pressure and by peripheral vasodilatation), which decreases amount of blood being pumped by left ventricle and pressure at which blood is being ejected. This reduces amount of blood regurgitated by the mitral valve from left ventricle into left atrium during systole.

Adult

2.5 mg PO bid initially; therapeutic range approximately 2.5-20 mg/d in 2 divided doses; not to exceed 40 mg/d

Pediatric

0.1 mg/kg PO bid/qid, not to exceed 40 mg/d
5-10 mcg/kg (micro) slow IV over 5 min qid, not to exceed 1.25 mg

· 

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in patients with renal impairment, valvular stenosis, or severe congestive heart failure; reduce dose in renal failure

Lisinopril (Zestril, Prinivil)

Prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in lower aldosterone secretion.

Adult

5 mg/d PO with diuretics and digitalis; usual effective dosage range is 5-20 mg qd; in hyponatremic patients (s-sodium <130 mEq/L), initiate dose at 2.5 mg qd

Pediatric

Not established

· 

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in patients with renal impairment, valvular stenosis, or severe congestive heart failure

Nitrates

Used for decreasing blood pressure and increasing coronary blood flow.

Nitroglycerin (Deponit, Nitro-Bid, Nitrostat, Nitrol)

Causes relaxation of vascular smooth muscle by stimulating intracellular cyclic guanosine monophosphate production. Result is decrease in blood pressure.

Adult

SL: Dissolve 1 tab under tongue or in buccal pouch at first sign of acute anginal attack; repeat q5min until relief obtained; do not use > 3 tab in 15 min; can also be used prophylactically 5-10 min prior to activities that may precipitate angina
SR tab: 2.5-2.6 mg tid/qid with possible increase in increments of 2.5-2.6 mg bid/qid depending on response; caps must be swallowed and are not for chewing or SL use
Transdermal patch: Apply qd to skin site free of hair and not subject to excessive movement; 0.2-0.4 mg/h initially; patch-on period of 12-14 h and patch-off period of 10-12 h is appropriate; doses 0.4-0.8 mg/h have shown continued effectiveness for 10-12 h qd for at least 1 mo of intermittent administration; nitrate-free interval of 10-12 h is sufficient; tolerance is major factor in limiting efficacy when system is used continuously for >12 h
Topical: Usual therapeutic dose is 1-2 in q8h, not to exceed 4-5 in q4h; begin with 0.5 in q8h and increase by 0.5 in with each application to achieve desired effects; 1 in of ointment contains 15 mg of nitroglycerin

Pediatric

Not established

· 

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in coronary artery disease and low systolic blood pressure

Inotropic agents

Because of its antiarrhythmic properties, digoxin is used if atrial fibrillation is encountered; however, it is not expected to improve overall cardiac function.

Digoxin (Lanoxin)

Cardiac glycoside with direct inotropic effects in addition to indirect effects on cardiovascular system. Acts directly on cardiac muscle, increasing myocardial systolic contractions. Indirect actions result in increased carotid sinus nerve activity and enhanced sympathetic withdrawal for any given increase in mean arterial pressure.
Digitalizing dose is approximately 20% less than PO dose. IM injection offers no advantage and can cause severe pain at injection site. IV is preferred. IV digoxin begins to have effect after 15-30 min and peaks in 1.5-3 h.

Adult

0.5 mg slow IV over 10-20 min; additional 0.25 or 0.125 mg may be administered after 3 h; total dose of 1-1.25 mg is usually required to achieve full digitalis effect, but smaller doses might be adequate in older patients and those with small, lean body mass
If a full effect is desired rapidly, administer 1-1.25 mg in divided doses over initial 24-h period; an additional 0.5 mg is added during the second 24-h period; 0.5 mg PO qd for 3 d can achieve maximal effects, which can follow usual maintenance dose; PO maintenance dose ranges from 0.125-0.5 mg qd; smaller doses are necessary in presence of renal insufficiency

Pediatric

Loading dose: 10 mcg/kg PO; not to exceed 375 mcg
Maintenance dose: 5 mcg/kg PO, not to exceed 125 mcg
Premature infants: Half loading and maintenance dose q6h X 4
If given IV, administer 75% of PO dose bid

· 

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Hypokalemia may reduce positive inotropic effect; hypercalcemia predisposes patients to digitalis toxicity, and hypocalcemia can make digoxin ineffective until serum calcium levels are within reference range; magnesium replacement therapy must be instituted in patients with hypomagnesemia to prevent digitalis toxicity; patients diagnosed with incomplete AV block may progress to complete block when treated with digoxin; exercise caution in patients with hypothyroidism, hypoxia, and acute myocarditis; adjust dose in patients with renal impairment; highly toxic (overdoses can be fatal)

Antibiotics, prophylactic

Provide subacute bacterial endocarditis prophylaxis. Use prior to any interventional therapy to protect the diseased valves.

· 

Pregnancy

B - Usually safe but benefits must outweigh the risks.

Precautions

Adjust dose in patients with renal failure; eval‎uate rash and differentiate from hypersensitivity reaction

Follow-up

Complications

• Medical complications
• Pulmonary edema
• Congestive heart failure
• Irreversible LV systolic dysfunction
• Thromboembolism resulting from atrial fibrillation 
• Surgical complications
• Operative risks include infection, bleeding, intraoperative myocardial infarction, and stroke.
• In young patients, bioprosthetic valves (ie, porcine valves) have a propensity for early degeneration due to calcification.
• Mechanical valve complications include prosthetic valve dysfunction and valve thrombosis with or without embolism, particularly in the patient who is not adequately anticoagulated. 
• Hemolysis may occur in the patient with a ball and cage mechanical valve because of mechanical valve destruction of circulating red blood cells. Hemolysis in the patient with a tilting disk valve usually indicates the presence of a perivalvular leak.
• Thromboembolism in patients with mechanical valves who are on anticoagulation therapy occurs at a rate of 1-3% per year. 
• In the absence of anticoagulation, thromboembolism occurs at a rate of approximately 1.5% per year with a porcine valve.
• Prosthetic valve infection may occur in bioprosthetic or mechanical valves.

Prognosis

• Asymptomatic chronic severe degenerative MR
• Mortality ranges from 50-73% at 5 years.
• Mortality in patients with preserved LV function ranges from 27-45%.
• Sudden death may be as common as 1-8% per year in patients with a flail leaflet.
• Mitral valve surgery operative mortality
• Isolated mitral valve repair surgery carries a 2% mortality.
• Mitral valve replacement surgery
• 4% mortality for patients younger than 50 years.
• 17% mortality for patients older than 80 years.
• Tribouilloy et al found that, in patients with organic mitral regurgitation (MR) due to flail leaflets, left ventricular end-systolic diameter (LVESD) is independently associated with increased mortality. Analysis of results in 739 patients showed that LVESD ≥ 40 mm independently predicted overall mortality (hazard ratio [HR] 1.95; 95% confidence interval [CI], 1.01-3.83) and cardiac mortality (HR 3.09; 95% CI, 1.35-7.09) under conservative management. Mortality risk increased linearly with LVESD >40 mm (HR 1.15; 95% CI, 1.04-1.27 per 1-mm increment). Tribouilloy et al conclude that these findings support prompt surgical rescue in patients with LVESD ≥40 mm but also suggest that operating on patients before LVESD reaches 40 mm will best preserve survival.⁴

Patient Education

For excellent patient education resources, visit eMedicine's Heart Center. Also, see eMedicine's patient education article Mitral Valve Prolapse.

Miscellaneous

Medicolegal Pitfalls

• Failure to institute appropriate echocardiographic testing before irreversible damage occurs
• Failure to obtain consultations with specialists in cardiology and cardiothoracic surgery early during patient stabilization
• Failure to institute proper antibiotic prophylaxis before an interventional treatment
• Failure to exclude myocardial infarction in patients experiencing an exacerbation of chronic mitral valve regurgitation with hemodynamic compromise

Acknowledgments

The authors and editors of eMedicine gratefully acknowledge the contributions of previous authors Shivkumar H Jha, MD; Jatin Dave, MD, MPH; Kishorkumar Desai, MD; and Abraham G Kocheril, MD, FACC, FACP to the development and writing of this article.