MR may result from an abnormality or disease process that affects any one or more of the five functional components of the mitral valve apparatus (leaflets, annulus, chordae tendineae, papillary muscles, and subjacent myocardium) (Table 237-1). Acute MR can occur in the setting of acute myocardial infarction (MI) with papillary muscle rupture (Chap. 245), following blunt chest wall trauma, or during the course of infective endocarditis. With acute MI, the posteromedial papillary muscle is involved much more frequently than the anterolateral papillary muscle because of its singular blood supply. Transient, acute MR can occur during periods of active ischemia and bouts of angina pectoris. Rupture of chordae tendineae can result in “acute-on-chronic MR” in patients with myxomatous degeneration of the valve apparatus.
Chronic MR can result from rheumatic disease, mitral valve prolapse (MVP), extensive mitral annular calcification, congenital valve defects, hypertrophic obstructive cardiomyopathy (HOCM), and dilated cardiomyopathy (Chap. 238). The rheumatic process produces rigidity, deformity, and retraction of the valve cusps and commissural fusion, as well as shortening, contraction, and fusion of the chordae tendineae. The MR associated with both MVP and HOCM is usually dynamic in nature. MR in HOCM occurs as a consequence of anterior papillary muscle displacement and systolic anterior motion of the anterior mitral valve leaflet into the narrowed LV outflow tract. Annular calcification is especially prevalent among patients with advanced renal disease and is commonly observed in women >65 years of age with hypertension and diabetes. MR may occur as a congenital anomaly (Chap. 236), most commonly as a defect of the endocardial cushions (atrioventricular cushion defects). A cleft anterior mitral valve leaflet accompanies primum atrial septal defect. Chronic MR is frequently secondary to ischemia and may occur as a consequence of ventricular remodeling, papillary muscle displacement, and leaflet tethering, or with fibrosis of a papillary muscle, in patients with healed myocardial infarction(s) and ischemic cardiomyopathy. Similar mechanisms of annular dilation and ventricular remodeling contribute to the MR that occurs among patients with nonischemic forms of dilated cardiomyopathy once the left ventricular end-diastolic dimension reaches 6 cm.
Irrespective of cause, chronic severe MR is often progressive, since enlargement of the LA places tension on the posterior mitral leaflet, pulling it away from the mitral orifice and thereby aggravating the valvular dysfunction. Similarly, LV dilation increases the regurgitation, which, in turn, enlarges the LA and LV further, causing chordal rupture and resulting in a vicious circle; hence the aphorism, “mitral regurgitation begets mitral regurgitation.”
The resistance to LV emptying (LV afterload) is reduced in patients with MR. As a consequence, the LV is decompressed into the LA during ejection, and with the reduction in LV size during systole, there is a rapid decline in LV tension. The initial compensation to MR is more complete LV emptying. However, LV volume increases progressively with time as the severity of the regurgitation increases and as LV contractile function deteriorates. This increase in LV volume is often accompanied by a reduced forward CO, although LV compliance is often increased and, thus, LV diastolic pressure does not increase until late in the course. The regurgitant volume varies directly with the LV systolic pressure and the size of the regurgitant orifice; as mentioned above, the latter, in turn, is influenced by the extent of LV and mitral annular dilation. Since ejection fraction (EF) rises in severe MR in the presence of normal LV function, even a modest reduction in this parameter (<60%) reflects significant dysfunction.
During early diastole, as the distended LA empties, there is a particularly rapid y descent in the absence of accompanying MS. A brief, early diastolic LA-LV pressure gradient [often generating a rapid filling sound (S3) and mid-diastolic murmur masquerading as MS] may occur in patients with pure MR as a result of the very rapid flow of blood across a normal-sized mitral orifice.
Semi-quantitative estimates of left ventricular ejection fraction (LVEF), CO, PA systolic pressure, regurgitant volume, regurgitant fraction (RF), and the effective regurgitant orifice area can be obtained during a careful Doppler echocardiographic examination. These measurements can also be obtained with CMR. Left and right heart catheterization with contrast ventriculography is used less frequently. Severe, nonischemic MR is defined by a regurgitant volume ≥60 mL/beat, regurgitant fraction (RF) ≥50%, and effective regurgitant orifice area ≥0.40 cm2. Severe ischemic MR is usually associated with an effective regurgitant orifice area of >0.3 cm2.
In acute severe MR, the regurgitant volume is delivered into a normal-sized LA having normal or reduced compliance. As a result, LA pressures rise markedly for any increase in LA volume. The v wave in the LA pressure pulse is usually prominent, LA and pulmonary venous pressures are markedly elevated, and pulmonary edema is common. Because of the rapid rise in LA pressures during ventricular systole, the murmur of acute MR is early in timing and decrescendo in configuration ending well before S2, as a reflection of the progressive diminution in the LV-LA pressure gradient. LV systolic function in acute MR may be normal, hyperdynamic, or reduced, depending on the clinical context.
Patients with chronic severe MR, on the other hand, develop marked LA enlargement and increased LA compliance with little if any increase in LA and pulmonary venous pressures for any increase in LA volume. The LA v wave is relatively less prominent. The murmur of chronic MR is classically holosystolic in timing and plateau in configuration, as a reflection of the near-constant LV-LA pressure gradient. These patients usually complain of severe fatigue and exhaustion secondary to a low forward CO, while symptoms resulting from pulmonary congestion are less prominent initially; AF is almost invariably present once the LA dilates significantly.
Patients with chronic mild-to-moderate isolated MR are usually asymptomatic. This form of LV volume overload is well tolerated. Fatigue, exertional dyspnea, and orthopnea are the most prominent complaints in patients with chronic severe MR. Palpitations are common and may signify the onset of AF. Right-sided heart failure, with painful hepatic congestion, ankle edema, distended neck veins, ascites, and secondary TR, occurs in patients with MR who have associated pulmonary vascular disease and marked pulmonary hypertension. Conversely, acute pulmonary edema is common in patients with acute severe MR.
In patients with chronic severe MR, the arterial pressure is usually normal, although the carotid arterial pulse may show a sharp upstroke owing to the reduced forward cardiac output. A systolic thrill is often palpable at the cardiac apex, the LV is hyperdynamic with a brisk systolic impulse and a palpable rapid-filling wave (S3), and the apex beat is often displaced laterally.
In patients with acute severe MR, the arterial pressure may be reduced with a narrow pulse pressure, the jugular venous pressure and wave forms may be normal or increased and exaggerated, the apical impulse is not displaced, and signs of pulmonary congestion are prominent.
S1 is generally absent, soft, or buried in the holosystolic murmur of chronic MR. In patients with severe MR, the aortic valve may close prematurely, resulting in wide but physiologic splitting of S2. A low-pitched S3 occurring 0.12–0.17 s after the aortic valve closure sound, i.e., at the completion of the rapid-filling phase of the LV, is believed to be caused by the sudden tensing of the papillary muscles, chordae tendineae, and valve leaflets. It may be followed by a short, rumbling, mid-diastolic murmur, even in the absence of structural MS. A fourth heart sound is often audible in patients with acute severe MR who are in sinus rhythm. A presystolic murmur is not ordinarily heard with isolated MR.
A systolic murmur of at least grade III/VI intensity is the most characteristic auscultatory finding in chronic severe MR. It is usually holosystolic (see Fig. 227-5A), but as previously noted it is decrescendo and ceases in mid- to late systole in patients with acute severe MR. The systolic murmur of chronic MR is usually most prominent at the apex and radiates to the axilla. However, in patients with ruptured chordae tendineae or primary involvement of the posterior mitral leaflet with prolapse or flail, the regurgitant jet is eccentric, directed anteriorly, and strikes the LA wall adjacent to the aortic root. In this situation, the systolic murmur is transmitted to the base of the heart and, therefore, may be confused with the murmur of AS. In patients with ruptured chordae tendineae, the systolic murmur may have a cooing or “sea gull” quality, while a flail leaflet may produce a murmur with a musical quality. The systolic murmur of chronic MR not due to MVP is intensified by isometric exercise (handgrip) but is reduced during the strain phase of the Valsalva maneuver because of the associated decrease in LV preload.
In patients with sinus rhythm, there is evidence of LA enlargement, but RA enlargement also may be present when pulmonary hypertension is severe. Chronic severe MR is generally associated with AF. In many patients, there is no clear-cut ECG evidence of enlargement of either ventricle. In others, the signs of eccentric LV hypertrophy are present.
TTE is indicated to assess the mechanism of the MR and its hemodynamic severity. LV function can be assessed from LV end-diastolic and end-systolic volumes and EF. Observations can be made regarding leaflet structure and function, chordal integrity, LA and LV size, annular calcification, and regional and global LV systolic function. Doppler imaging should demonstrate the width or area of the color flow MR jet within the LA, the intensity of the continuous wave Doppler signal, the pulmonary venous flow contour, the early peak mitral inflow velocity, and the quantitative measures of regurgitant volume, RF, and effective regurgitant orifice area. In addition, the PA pressures can be estimated from the TR jet velocity. TTE is also indicated to follow the course of patients with chronic MR and to provide rapid assessment for any clinical change. The echocardiogram in patients with MVP is described in the next section. TEE provides greater detail than TTE (see Fig. 229-5).
The LA and LV are the dominant chambers in chronic MR. Late in the course of the disease, the LA may be massively enlarged and forms the right border of the cardiac silhouette. Pulmonary venous congestion, interstitial edema, and Kerley B lines are sometimes noted. Marked calcification of the mitral leaflets occurs commonly in patients with longstanding, combined rheumatic MR and MS. Calcification of the mitral annulus may be visualized, particularly on the lateral view of the chest. Patients with acute severe MR may have asymmetric pulmonary edema if the regurgitant jet is directed predominantly to the orifice of an upper lobe pulmonary vein.
Treatment: Mitral Regurgitation
(See Fig. 237-4 and Table 237-2) The management of chronic severe MR depends to some degree on its cause. Warfarin should be provided once AF intervenes with a target INR of 2–3. Cardioversion should be considered depending on the clinical context and left atrial size. In contrast to the acute setting, there are no large, long-term prospective studies to substantiate the use of vasodilators for the treatment of chronic, isolated severe MR with preserved LV systolic function in the absence of systemic hypertension. The severity of MR in the setting of an ischemic or nonischemic dilated cardiomyopathy may diminish with aggressive, evidence-based treatment of heart failure, including the use of diuretics, beta blockers, angiotensin-converting enzyme (ACE) inhibitors, digitalis, and biventricular pacing (cardiac resynchronization therapy [CRT]). Asymptomatic patients with severe MR in sinus rhythm with normal LV size and systolic function should avoid isometric forms of exercise.
Management strategy for patients with chronic severe nonischemic mitral regurgitation. *Mitral valve (MV) repair may be performed in asymptomatic patients with normal left ventricular (LV) function if performed by an experienced surgical team and if the likelihood of successful MV repair is >90%. AF, atrial fibrillation; Echo, echocardiography; EF, ejection fraction; ESD, end-systolic dimension; eval, evaluation; HT, hypertension; MVR, mitral valve replacement. (From RO Bonow et al: J Am Coll Cardiol 48:e1, 2006; with permission.)
Patients with acute severe MR require urgent stabilization and preparation for surgery. Diuretics, intravenous vasodilators (particularly sodium nitroprusside), and even intraaortic balloon counterpulsation may be needed for patients with post-MI papillary muscle rupture or other forms of acute severe MR.
In the selection of patients with chronic, nonischemic, severe MR for surgical treatment, the often slowly progressive nature of the condition must be balanced against the immediate and long-term risks associated with operation. These risks are significantly lower for primary valve repair than for valve replacement (Table 237-3). Repair usually consists of valve reconstruction using a variety of valvuloplasty techniques and insertion of an annuloplasty ring. Repair spares the patient the long-term adverse consequences of valve replacement, i.e., thromboembolic and hemorrhagic complications in the case of mechanical prostheses and late valve failure necessitating repeat valve replacement in the case of bioprostheses (p. 1949). In addition, by preserving the integrity of the papillary muscles, subvalvular apparatus, and chordae tendineae, mitral repair and valvuloplasty maintain LV function to a relatively greater degree.
Surgery for chronic, nonischemic, severe MR is indicated once symptoms occur, especially if valve repair is feasible (Fig. 237-4). Other indications for early consideration of mitral valve repair include recent-onset AF and pulmonary hypertension, defined as a PA pressure ≥50 mmHg at rest or ≥60 mmHg with exercise. Surgical treatment of chronic, nonischemic severe MR is indicated for asymptomatic patients when LV dysfunction is progressive, with LVEF falling below 60% and/or end-systolic dimension increasing beyond 40 mm. These aggressive recommendations for surgery are predicated on the outstanding results achieved with mitral valve repair, particularly when applied to patients with myxomatous disease, such as that associated with prolapse or flail leaflet. Indeed, primary valvuloplasty repair of patients younger than 75 years with normal LV systolic function and no CAD can now be performed by experienced surgeons with <1% perioperative mortality risk. Repair is feasible in up to 95% of patients with myxomatous disease. Long-term durability is excellent; the incidence of reoperative surgery for failed primary repair is ∼1% per year for 10 years after surgery. For patients with AF, left or bi-atrial Maze surgery or radiofrequency isolation of the pulmonary veins is often performed to reduce the risk of recurrent, postoperative AF.
The surgical management of patients with ischemic MR is more complicated and almost always involves simultaneous coronary artery revascularization. Although current surgical practice includes annuloplasty repair with an undersized ring for patients with moderate or greater degrees of MR at the time of coronary artery bypass surgery, the efficacy of this approach has not been established in prospective, randomized trials. There is also uncertainty as to whether or not valve repair or replacement is the preferred strategy, given the higher incidence of residual or recurrent MR after repair in this context compared with outcomes in patients with organic (myxomatous) disease. In patients with significantly impaired LV function (EF <30%), the risk of surgery increases, the recovery of LV performance is incomplete, and the long-term survival is reduced. However, conservative management has little to offer these patients, so operative treatment may be indicated, and the clinical and hemodynamic improvement that follows surgical treatment of patients with advanced disease is occasionally dramatic, especially when severe CAD is present and bypass grafting can be performed. The routine performance of valve repair in patients with significant MR in the setting of severe, dilated cardiomyopathy has not been shown to improve long-term survival. Patients with acute severe MR can often be stabilized temporarily with appropriate medical therapy, but surgical correction will be necessary, emergently in the case of papillary muscle rupture and within days to weeks in most other settings.
When surgical treatment is contemplated, left and right heart catheterization and left ventriculography may be helpful in confirming the presence of severe MR in patients in whom there is a discrepancy between the clinical and TTE findings that cannot be resolved with TEE or CMR. Coronary angiography identifies patients who require concomitant coronary revascularization.
Percutaneous Mitral Valve Repair
A transcatheter approach to the treatment of either organic or functional MR may be feasible in selected patients with appropriate anatomy, although the proper role of current techniques remains under active investigation. One approach involves the deployment of a clip delivered via transeptal puncture that grasps the leading edges of the mitral leaflets in their mid-portion (anterior scallop 2–posterior scallop 2 or A2-P2, Fig. 237-5). The length and width of the gap between these leading edges have dictated patient eligibility in the trials reported to date. Preliminary results with this technically demanding technique have been favorable. A second approach involves the deployment of a device within the coronary sinus that can be adjusted to reduce its circumference, thus secondarily decreasing the circumference of the mitral annulus and the effective orifice area of the valve, much like a surgically implanted ring. Variations in the anatomic relationship of the coronary sinus to the mitral annulus and circumflex coronary artery have limited the applicability of this technique. Attempts to reduce the septal-lateral dimension of a dilated annulus using adjustable cords placed across the LV in a subvalvular location have also been investigated.
Clip used to grasp the free edges of the anterior and posterior leaflets in their mid-sections during percutaneous repair of selected patients with mitral regurgitation. (Courtesy of Abbott Vascular. © 2010 Abbott Laboratories. All rights reserved.)