There are multiple conditions that can cause acute or chronic mitral regurgitation (MR) involving the mitral valve leaflets, mitral annulus, chordae tendineae, or papillary muscles (Table 29-4). Involvement of the leaflets is usually due to rheumatic disease leading to shortening or retraction of one or both leaflets. Infective endocarditis, trauma, or systemic lupus erythematosus with Libman-Sacks endocarditis can lead to significant MR (Fig. 29-9). Finally, mitral valve prolapse can present with severe MR due to myxomatous change of the valve leaflets.
Table 29–4. Causes of Mitral Regurgitation |Favorite Table|Download (.pdf)
Table 29–4. Causes of Mitral Regurgitation
- Disorders of the mitral leaflets
- Rheumatic heart disease
- Infective endocarditis
- Systemic lupus erythematosus
- Myxomatous mitral valve prolapse
- Congenital mitral valve clefts/fenestrations
- Parachute mitral valve
- Disorders of the mitral annulus
- Left ventricular dilation
- Mitral annular calcification
- Disorders of the chordae tendineae
- Myxomatous involvement in mitral valve prolapse
- Infective endocarditis
- Spontaneous rupture
- Disorders of the papillary muscles
- Dysfunction (myocardial ischemia/infarction/infiltrative diseases)
- Rupture (infarction/trauma)
Mitral regurgitation secondary to endocarditis and a flail posterior mitral valve leaflet. Transesophageal echocardiogram showing thickened mitral valve leaflets with vegetations (arrows). The posterior leaflet has prolapsed from the left ventricle (LV) into the left atrium (LA). The second panel depicts severe mitral regurgitation by Doppler echocardiography (arrows). AV, aortic valve; RV, right ventricle.
Abnormalities of the mitral annulus involve dilation and calcification. Severe dilation of the left ventricle, as seen in dilated cardiomyopathies, is associated with mitral regurgitation, although the amount of leakage tends to be less than that seen in primary valvular disorders. Calcification of the mitral annulus is a common degenerative change that when severe, may cause significant MR.
The chordae tendineae and papillary muscles may be involved in patients with ischemic heart disease. Myocardial ischemia or infarction may lead to papillary muscle dysfunction or frank rupture of the muscle head, causing acute severe MR. Ischemia of the papillary muscles may be transient, with improvement in the MR occurring after relief of the ischemia or revascularization therapy. On the other hand, patients with moderately severe to severe MR complicating an acute myocardial infarction have a high risk of mortality.58 Chordae tendineae may rupture in patients with infective endocarditis and in patients with myxomatous mitral valve prolapse. Mitral valve prolapse is becoming the most common etiology for patients requiring valvular surgery for mitral regurgitation.
In patients who develop acute MR, the left ventricle is initially unloaded, with the regurgitant volume ejected into the left atrium. The left ventricular wall tension is reduced, since acute MR reduces systolic ventricular pressure and volume. Early diastolic filling of the left ventricle is enhanced, causing small elevations in myocardial contractility and ejection fraction. Following initial compensation, the left ventricle dilates rapidly. The increase in left ventricular end-diastolic volume increases wall tension. Ejection indices will eventually decline to normal, reflecting impairment of myocardial function. Ejection fractions of 40% to 50% already reflect severe impairment of myocardial contractility. Ejection fractions less than 40% represent advanced cardiac dysfunction and indicate a patient who has a high operative risk and is unlikely to experience any improvement in function following correction of the problem.59
The compliance of the left atrium and the pulmonary venous system will determine the hemodynamic and clinical manifestations of mitral regurgitation. In patients in whom MR occurs suddenly, as with rupture of a chorda tendineae, left atrial compliance is normal. Left atrial size remains normal, but there is a marked elevation of left atrial pressure (large V wave), and pulmonary congestion is predominant. In contrast, in patients with long-standing chronic MR, massive enlargement of the left atrium occurs with normal or only slightly elevated left atrial pressures. Pulmonary artery pressures and pulmonary vascular resistance are normal or only slightly elevated. Atrial fibrillation is almost invariably present.60
The symptoms of patients with mitral regurgitation depend on the acuity and severity of the disease. In patients with chronic MR, symptoms usually do not develop until the left ventricle begins to fail. By the time low-output symptoms, pulmonary congestion, or atrial fibrillation develops, permanent myocardial dysfunction may already be present. The onset of a critical illness may cause rapid deterioration in a previously stable patient if increased systemic vascular resistance augments the regurgitant fraction. Patients with acute MR may present with florid pulmonary edema and low cardiac output. Ischemic symptoms may also be present, since myocardial infarction with papillary muscle dysfunction and rupture is an important cause of acute MR.
On physical examination, the left ventricular impulse is usually dynamic and displaced, with a palpable early diastolic filling impulse (S3). The systolic murmur of mitral regurgitation begins at the first heart sound (frequently obscuring it) and extends throughout systole and beyond the second heart sound to mitral valve opening. The murmur is constant in intensity, is high-pitched, is loudest at the apex, and radiates to the axilla. The intensity of the murmur does not correlate with severity. Patients with acute MR may have barely audible brief murmurs. Murmurs of mitral valve prolapse may begin in mid or late systole and vary in position and intensity depending on left ventricular volume.61
Mitral regurgitation murmurs need to be differentiated from other systolic murmurs (Table 29-5). Tricuspid regurgitation frequently exhibits respiratory variation and does not radiate to the axilla. Ventricular septal defect murmurs tend to be harsher, to be located at the sternal border, and to be heard less well in the axilla. Aortic stenosis murmurs may radiate to the apex, but they are usually accompanied by a delayed carotid upstroke and a decreased intensity of the aortic component of the second heart sound.
Table 29–5. Differential Diagnosis of Systolic Murmurs |Favorite Table|Download (.pdf)
Table 29–5. Differential Diagnosis of Systolic Murmurs
|Feature||Mitral Regurgitation||Tricuspid Regurgitation||Ventricular Septal Defect|
|Location||Apex||Left sternal border||Left sternal border|
|Thrill||At apex||Rare||Left sternal border|
|P2||Normal||Increased||Normal, usually delayed|
|Murmur with inspiration||No change||Increased||No change|
|Jugular venous pulse||Normal||Elevated, prominent V wave||Elevated, prominent A and V waves|
The electrocardiogram in acute mitral regurgitation is usually normal, although it may show signs of acute myocardial infarction. Patients with chronic MR may have signs of left atrial enlargement, right ventricular hypertrophy, or atrial fibrillation. Chest x-ray shows cardiomegaly with left ventricular prominence, left atrial enlargement, and at times evidence of mitral annular calcification.
Two-dimensional echocardiography can help determine the etiology and severity of mitral regurgitation. The underlying cause of the regurgitation, such as rupture of a chorda tendineae, mitral valve prolapse with a flail leaflet, or valvular endocarditis, can readily be determined. Transesophageal echocardiography has improved the diagnostic acumen of echocardiographic studies, especially in determining the presence of valvular vegetations. Doppler echocardiography makes it possible to estimate the severity of MR from the distance the jet travels into the left atrium, the width of the jet at the mitral annulus, and the area of the color Doppler envelope in the left atrium.
Cardiac catheterization is useful in diagnosis and management. Left ventriculography showing opacification of the left atrium is used to quantify severity of the leakage. Effective or forward cardiac output is depressed in severe MR. The pulmonary wedge pressure will show a characteristically tall V wave, reflecting the filling of the left atrium by both pulmonary venous and regurgitant blood during ventricular systole. This tall V wave is frequently seen in the pulmonary artery tracing, and at times little difference between the pulmonary artery tracing and the wedge pressure tracing is evident. Successful treatment of MR will bring about a significant decline in the V wave.
Patients presenting with acute mitral regurgitation should be treated with the same modalities used in patients who present with acute heart failure. Afterload reduction with vasodilators or noninvasive positive pressure ventilation62 will reduce the impedance to ejection into the aorta, diminish the amount of mitral regurgitation, increase forward output, and reduce pulmonary congestion.63 In acute presentations, nitroprusside can achieve these clinical goals and has the advantage of easy titration to blood pressure. If hypotension is present, positive inotropic agents such as dobutamine may need to be combined with the nitroprusside. Diuretics are used to relieve congestion. Digoxin may be useful if left ventricular dysfunction or atrial fibrillation is present. Chronic afterload reduction can then be initiated with ACEIs or other vasodilators.
Unless patients with acute severe MR are treated aggressively, death is almost certain. Emergency surgery should be considered in patients with acute pulmonary edema caused by acute MR due to myocardial infarction and papillary muscle rupture, rupture of a chorda tendineae with a flail mitral leaflet in the mitral valve prolapse syndrome, traumatic MR, or severe MR associated with valvular endocarditis.
Patients with chronic MR should be considered for surgery when they become symptomatic. Exercise testing can precipitate symptoms in patients that are asymptomatic at rest. Asymptomatic patients should be considered for surgical intervention when the ejection fraction falls below 50%, the end-systolic volume index exceeds 50 mL/m2, or pulmonary hypertension develops.64
The decision of whether to replace the mitral valve or to perform valvular reconstruction will depend on the degree of deformity of the valve leaflets and support structures. Mitral valve repair appears to be associated with a lower surgical mortality than is mitral valve replacement, although the patient populations differ.65 Mitral valve repair is most often used in patients with myxomatous mitral valve prolapse and a flail mitral leaflet or with papillary muscle rupture after an acute myocardial infarction. Repair procedures consist of annuloplasty with the use of a prosthetic ring or resection and repair of the valve. Replacement, reimplantation, or shortening of chordae tendineae is performed in selected patients. Patients who are not candidates for repair receive either a mechanical or bioprosthetic valve. Surgeons frequently leave the submitral apparatus in place, as doing so favors a return to a more normal cardiac function after surgery.66
There are two major types of prosthetic heart valve: mechanical valves, which are made of synthetic material, and tissue valves, which are composed at least in part of biologic tissue. The first mechanical valves were ball valves, such as the Starr-Edwards prosthesis. These valves have largely been replaced by the tilting disk valves, which offer a greater orifice area and less resistance to blood flow. Common examples of the disk valves are the Bjork-Shiley and St. Jude Medical valves. The two major types of tissue valves are stented porcine aortic valves (the Carpentier-Edwards and Hancock valves) and a trileaflet valve made with bovine pericardium (Ionescu-Shiley valve). Other tissue valves are under development, including ones that use cryopreserved aortic homografts.
The advantage of tissue valves is a lower risk of thromboembolism than with mechanical valves. Anticoagulation is frequently used during the first few months after implantation, until the sewing ring becomes endothelialized. Anticoagulation is not required after this time; the thromboembolism rate is estimated to be 1 to 2 episodes per 100 patient-years.67
The main problem with the tissue valves concerns durability. The tissue valves are prone to calcification, fibrosis, degeneration, fibrin deposition, and cuspal tears. Valve dysfunction is more common in younger patients and in patients with disordered calcium metabolism. Evidence of degeneration can usually be detected by 5 years after replacement.68 By 15 years, over 50% of tissue valves will have failed.69 Fortunately, valve failure is rarely sudden, and a second operation can frequently be done on an elective basis. Sudden cuspal tears can present as an acute regurgitant lesion.
Mechanical valves have the advantage of durability but require anticoagulation to prevent thromboembolism. Without anticoagulation, major systemic embolisms occur at a rate of about 2% to 3% per year.70 The incidence is higher for valves in the mitral than in the aortic position. With adequate anticoagulation, however, the incidence of thromboembolism is similar to that for tissue valves. The use of a small dose of aspirin plus warfarin anticoagulation may decrease the risk of thromboembolism further, but increases the risk of a bleeding complication.71
For patients who require noncardiac surgery and have a mechanical prosthetic valve, the anticoagulation regimen may be stopped for a few days with minimal risk. Minimizing the time off anticoagulants is essential to avoid thromboembolism. Heparin or low-molecular-weight dextran is frequently administered up to the time of surgery, to protect the patient. Heparin should then be restarted after surgery until warfarin treatment increases the International Normalized Ratio (INR) to the target level of 2.5 to 3.5.
Mechanical valve thrombosis is a serious complication and is associated with a high mortality.72 The tilting disk valves are particularly susceptible to this complication. Thrombosis of mechanical valves is especially common for valves in the tricuspid position, so tissue valves are usually used in this location.73 Inadequate anticoagulation or withdrawal of anticoagulation for surgical procedures accounts for most instances of thrombotic obstruction.74 Thrombosis of the valve may lead to leaflet entrapment with acute regurgitation and circulatory collapse. Some patients, however, may remain asymptomatic or develop gradually worsening symptoms.
Obstruction of a mechanical valve usually necessitates reoperation, although that may be associated with a high risk of operative mortality. Thrombolytic therapy has been used successfully for prosthetic valve obstruction, with a success rate of 73% reported for one series.75 Recurrence rates, however, have averaged 18% regardless of valve position.76
Prosthetic valve obstruction may be difficult to detect. Abnormal auscultatory findings, such as muffled opening or closing sounds or the presence of a new murmur, may indicate thrombosis. Doppler echocardiography can diagnose obstruction by detecting an increased transvalvular gradient. Transesophageal echocardiography can frequently visualize thrombosed mechanical valves that are not well seen with transthoracic approaches owing to signal scatter from the valve structures.
Prosthetic valve endocarditis is a serious complication that occurs in 1% to 9% of patients.77 Early prosthetic valve endocarditis occurs within 60 days of implantation and results from contamination during the perioperative period. Most contamination probably occurs intraoperatively from direct wound inoculation or via the cardiopulmonary bypass machine. Postoperative sources include intravenous lines, pacing wires, and chest tubes. Staphylococcus epidermidis and Staphylococcus aureus are the most common organisms. A preoperative diagnosis of native valve endocarditis represents an increased risk of prosthetic valve involvement following surgery. Mortality is high, with one survey reporting a 64% mortality.77
Late prosthetic valve endocarditis occurs owing to seeding of the valve by transient bacteremia arising from dental, gastrointestinal, or genitourinary tract procedures. Nosocomial bacteremia has been reported to cause prosthetic valve endocarditis in 11% of patients within 45 days after discovery of the bacteremia.78 The bacteria responsible are similar to those found in native valve endocarditis, with viridans streptococci the most common isolates. The prognosis of late prosthetic valve endocarditis is worse than that of native valve endocarditis, with mortality rates between 36% and 53%.79 Complications of prosthetic valve endocarditis include myocardial abscesses, dehiscence of the valve with perivalvular leakage, and embolization (Fig. 29-10). Immediate surgery is indicated in patients who are unstable or have significant prosthetic valve dysfunction.80
Endocarditis involving a St. Jude Medical mechanical valve in the mitral position. Transesophageal echocardiogram showing vegetations on the left atrial (LA) side of the mechanical valve (small arrows). Doppler echocardiography reveals perivalvular mitral regurgitation (large arrow). LV, left ventricle; RV, right ventricle; RA, right atrium.
Antibiotic prophylaxis for medical and dental procedures is recommended for all patients with prosthetic valves. Procedures in which prophylaxis is recommended include bronchoscopy, sclerotherapy for esophageal varices, urethral catheterization if a urinary tract infection is present, incision and drainage of infected tissue, and vaginal delivery in the presence of infection.81 Antibiotic schedules are listed in Table 29-6.
Table 29–6. Antibiotic Prophylaxis for Medical and Dental Procedures |Favorite Table|Download (.pdf)
Table 29–6. Antibiotic Prophylaxis for Medical and Dental Procedures
|Regimens for dental, oral, respiratory tract or esophageal procedures:|
| Standard regimen:|
| Amoxicillin||2 g orally 1 h before procedure|
| Regimen for amoxicillin/ampicillin/penicillin-allergic patients:|
| Clindamycin||600 mg given orally 1 h before procedure, or|
| Cepahalexin or cefadroxil||2 g orally 1 h before procedure, or|
Azithromycin or clarithromycin||500 mg orally 1 h before procedure|
|Regimens for genitourinary/gastrointestinal procedures:|
| Standard regimen: high-risk patients|
| Ampicillin, gentamicin, and amoxicillin||2 g ampicillin plus 1.5 mg/kg gentamicin (120 mg maximum) IV or IM 30 min before procedure; amoxicillin, 1 g orally 6 h after first dose|
|For ampicillin/amoxicillin-allergic patients:|
| Vancomycin and gentamicin||Vancomycin, 1 g IV over 1–2 h, plus gentamicin, 1.5 mg/kg (120 mg maximum) IV or IM; complete infusion 30 minutes before procedure|
| Moderate risk-patients|
| Amoxicillin||Amoxicillin 2 g orally 1 h before procedure or ampicillin 2 g IV or IM within 30 min of starting procedure|
Ampicillin/amoxicillin-allergic||Vancomycin 1 g over 1–2 h|