Ischemic mitral regurgitation is a common complication of the healing phase of myocardial infarction. A number of mechanisms have been invoked in its pathogenesis, including alterations of papillary muscle position, annular dynamics, and intraventricular synchrony. The echocardiographic hallmark of ischemic mitral regurgitation is systolic tethering of the mitral valve leaflets away from the annular plane. A number of leaflet tethering parameters have been described (tenting height and area, leaflet angles) that provide insight into the mechanism of tethering as well as prognostic information about the durability of mitral valve repair. Restrictive annuloplasty and coronary artery revascularization promote reverse remodeling and remain the most common surgical treatment. Innovative subannular therapies and a number of percutaneous interventions are under investigation.
Ischemic mitral regurgitation (MR) is a complication of the chronic healing phase of myocardial infarction (MI). As the left ventricle remodels after MI, the normal geometry of the mitral apparatus becomes distorted, resulting in incomplete leaflet closure and valvular regurgitation. Unlike degenerative and infectious disorders, however, the structural integrity of the leaflets and chords remain intact.
Ischemic MR occurs commonly after MI, with an estimated prevalence of 20% to 50%, and its presence has been shown to significantly worsen prognosis independent of ejection fraction. Indeed, a stepwise increase in mortality can be demonstrated as effective regurgitant orifice area (ROA) increases ( Figure 1 ). It is also worthwhile noting that even subjects with otherwise clinically insignificant amounts of MR (effective ROA < 20 mm 2 ) have excess mortality rates.
Despite considerable interest in this disorder, the pathogenesis of ischemic MR remains incompletely understood, and the optimal surgical approach remains largely controversial. Echocardiography has helped facilitate much of our current understanding of the mechanisms involved in ischemic MR and is emerging as a useful tool for surgical planning. In this review, I discuss the pathogenesis, echocardiographic diagnosis, and surgical treatment of this disorder.
Pathogenesis of Ischemic Mitral Regurgitation
Alterations of Left Ventricular (LV) Geometry
In 1963, Burch et al. wrote that “during periods of angina pectoris, reduction in the circulation to a papillary muscle (PM) may result in total or partial failure of the PM to contract producing a murmur of MR. When the circulation is restored, the PM…gradually regains its function and the murmur…slowly disappears.” The long-held notion that ischemic MR is due to PM dysfunction has a sound physiologic basis. In the normal heart, PM contraction prevents the mitral valve leaflets from falling back into the left atrium during systole. When the left ventricle contracts, the annulus descends toward the apex. Were it not for simultaneous contraction of the vertically oriented fibers of the PMs, slackening of the chords might otherwise permit the leaflets to prolapse into the left atrium as the annulus descends. Instead, a constant distance is maintained between the mitral annulus and the tips of the PMs, thereby preventing MR. Notwithstanding these observations, animal models of isolated PM infarction fail to produce MR 6 . The finding that MR does occur when muscle adjacent to the PM is infarcted is significant, particularly in light of the observation that such muscle readily deforms in response to increases in afterload. Taken together, these findings suggest an alternative mechanism for ischemic MR unrelated to myocardial ischemia, providing insight into why ischemic MR worsens with exercise despite the absence of inducible ischemia. It has been proposed that the increase in afterload attending exercise worsens MR through geometric distortion of the infarcted PM-bearing segments, shifting them away from the annular plane. Increased chordal traction, in turn, tethers the leaflets, which become effaced, resulting in incomplete mitral valve closure and worsening regurgitation.
Several additional lines of evidence support the notion that ischemic MR is more related to dynamic changes in loading conditions than to the effects of reversible myocardial ischemia. One study demonstrated that despite surgical revascularization, hemodynamically significant MR persists postoperatively in as many as 40% of patients. Additional evidence suggesting that load plays a role in the pathogenesis of ischemic MR comes from the often-made clinical observation that diuretics and afterload reducing agents, commonly used in the treatment of these patients, reduce MR severity. Reduced afterload during general anesthesia also decreases MR severity, and for this reason, echocardiographic evaluation of ischemic MR should ideally precede valve repair. Not uncommonly, patients with ischemic MR complain of significant effort intolerance but exhibit only minimal MR when studied at rest. Stress echocardiography can be especially useful in such patients and may unmask higher grades of MR from the increased afterload attained with exercise. One study found that an exercise-related increase in effective ROA of ≥0.13 cm 2 significantly worsens prognosis.
Mitral valve closure is a dynamic process in which two opposing forces, a tethering force and a closing force, act simultaneously on the leaflets determining their instantaneous position throughout systole. The tethering force, imparted by the PMs and chords, pulls the leaflets away from the annular plane, and the closing force, generated by LV contraction, drives them in the opposite direction ( Figure 2 ). Ischemic MR results from an imbalance between these forces, tipped in favor of the former. As the left ventricle remodels after MI, increased tethering impairs the systolic excursion of the leaflets toward the annulus, and valvular competence becomes increasingly dependent on closing forces. Figure 3 depicts the dynamic interaction of closing and tethering forces in ischemic MR. Note that the ROA becomes substantially reduced in midsystole, when LV pressure (closing force) is maximal, whereas in early and late systole, when LV pressures are lower, tethering forces are less opposed, allowing the ROA to increase. Excess tethering results in leaflet deformation, producing a characteristic tented appearance readily recognized echocardiographically.
Alterations of Mitral Annular Mechanics
The mitral annulus is thin fibrous membrane separating the left heart chambers. Its shape has been likened to a saddle, with peaks located anteriorly (at the “riding horn”) and posteriorly, and valleys located medially and laterally, at the commissures. This nonplanar shape significantly reduces the stress exerted on the leaflets during ventricular systole. The annulus undergoes conformational changes during the cardiac cycle, reducing its area through dorsiflexion of its fibrous anterior portion and by sphincteric contraction of its muscular posterior portion ( Figure 4 ). Because the annulus is intrinsically noncontractile, its motion is determined by that of the structures surrounding it. Hence, annular flexion results from posterior displacement of the aortomitral curtain as the aortic root expands during systole. Sphincteric contraction of the posterior annulus, which begins in late diastole, is caused by shortening of atrial fibers encircling the annulus. With the onset of ventricular systole, shortening of helical LV fibers causes further contraction, with annular area reaching its nadir in midsystole. These changes in size and shape bring the free margins of the mitral leaflets into contact, and as systolic pressure increases, the leaflets become pressed together, creating a competent overlapping coaptation length, which normally measures about 1 cm ( Figure 5 ).
The annulus undergoes a number of structural changes in ischemic MR, becoming larger and flatter ( Figure 6 ). An increase in size causes effacement of the mitral leaflets compromising coaptation length. In vitro models predict that the coaptation length is sufficiently redundant, permitting an increase in annular area of approximately 1.8 times before MR develops. As the annulus enlarges, exposure of interscallop slits on the posterior mitral leaflet may create additional sites of regurgitation. It has also been shown that the annulus becomes more nonplanar in ischemic MR. This has important pathophysiologic effects, increasing the systolic closing stresses imposed on the mitral leaflets. Alterations in annular contraction, which could interfere with leaflet coaptation, have been described in patients with ischemic MR. Three-dimensional imaging reveals a reduction in the total extent of annular contraction and prolonged contraction extending through late systole. It is important to note that the relative contribution of annular enlargement and dysfunction to the overall regurgitant burden in patients with ischemic MR is minor compared with that imparted by augmented leaflet tethering forces.
Dyssynchronous LV Contraction
Dyssynchronous LV contraction is an important determinant of ischemic MR. In fact, hemodynamically significant MR is nearly twice as common among patients with QRS durations >130 msec compared with those with normal QRS durations. A number of mechanisms have been invoked to account for this. Delayed activation of the lateral PM causes uncoordinated contraction of the PMs, resulting in malalignment of the mitral valve leaflets ( Figure 7 ). Additionally, uncoordinated contraction of the musculature at the base of the left ventricle impairs sphincteric contraction of the posterior mitral annulus, which can interfere with leaflet coaptation. Dyssynchronous LV contraction also blunts the rate of pressure generation (dP/dt) by the left ventricle. The resultant decrease in closing force leaves tethering forces relatively unrestrained, increasing leaflet deformation. Cardiac resynchronization therapy (CRT) has been shown to reverse a number of these abnormalities and is discussed below.
Adaptations to Ischemic MR
Despite comparable amounts of geometric distortion of the left ventricle, significant patient-to-patient differences in MR burden are observed clinically. Several mechanisms can be invoked to account for this heterogeneity. Studies have shown that the mitral valve is capable of remodeling after MI, with adaptive increases in leaflet surface area developing in response to increased tethering forces. This tissue response reduces MR by restoring coaptation length, and it is conceivable that individual variability in the extent of such adaptive leaflet remodeling may account, in part, for the differences in MR severity seen among patients.
Adaptive changes in PM morphology and function may also occur after MI. It has been observed that MR can be attenuated by PM remodeling, with an increase in length from tip to base. Paradoxical systolic elongation of the PMs may further reduce leaflet tethering forces, as depicted in Figure 8 .
Ischemic MR usually worsens in response to the increased tethering forces attending exercise, but patients with preserved contractility of the musculature of the basal inferoposterior segments frequently demonstrate a decrease in MR during exercise. It has been proposed that such patients are able to compensate by recruiting contractile reserve within these myocardial segments, increasing sphincteric contraction of the posterior mitral annulus. In this respect, individuals with separate coronary artery blood supplies to the mid inferoposterior segments, overlying the PMs, and to the basal inferoposterior segments, adjacent to the posterior annulus, may be at some teleologic advantage.
Echocardiographic Recognition of Ischemic Mitral Regurgitation
Echocardiography plays an important role in the evaluation of ischemic MR. Localized or diffuse changes in LV size and shape due to post-MI remodeling can be readily appreciated. Echocardiography is also useful in characterizing deformational changes in the mitral leaflets caused by tethering.
Post-MI Ventricular Remodeling
Ischemic MR is a disease of the left ventricle. As the ventricle remodels after MI, the normal geometric relationship of the PM and mitral valve becomes altered, resulting in increased leaflet tethering and MR. Early after transmural MI, the necrotic myocardium of the affected region thins and enlarges (infarct expansion). Ventricular remodeling, however, frequently does not remain confined to the region of infarction. Echocardiographic studies have demonstrated dilatation of noninfarcted myocardial segments remote from the site of infarction. Such remote remodeling can result in marked and diffuse LV enlargement, thought to represent an adaptive response (using the Frank-Starling mechanism) to maintain stroke volume in the face of lost contractile elements. It is important to recognize that it is the site of LV remodeling, more than its extent, that is the more important determinant of whether ischemic MR will develop. LV dilatation, even when marked, may not cause MR unless accompanied by geometric distortion in the region of the PM. This explains the high prevalence of ischemic MR in patients with localized infarction of inferior wall. Ischemic MR can also develop in the absence of any echocardiographically evident scar, presumably from highly localized remodeling limited to the region of the PM.
Echocardiographic Parameters of Leaflet Tethering
A number of echocardiographic parameters of leaflet tethering have been described ( Figure 9 ). Besides providing quantitative information about leaflet deformation, these offer insight into the mechanism of tethering as well as prognostic information about the durability of mitral valve repair (discussed in the subsequent section). Tenting height is the vertical distance between the mitral annulus and the leaflet coaptation point. The region bound by the annulus and the mitral valve leaflets is referred to as the tenting area . Tenting volume , measured by three-dimensional echocardiography, is less susceptible to foreshortening and therefore correlates better with ROA in patients with ischemic MR. It is important to recognize that all three tenting indices reflect the global tethering burden imposed on the mitral valve, because they integrate a number of otherwise independent geometric factors (i.e., anterior leaflet tethering, posterior leaflet tethering, annular size, and the leaflet coaptation point ). Information about regional leaflet tethering can, however, be obtained by measuring individual mitral leaflet angles. A wide posterior leaflet angle indicates posterior leaflet restriction. Widening of the basal anterior leaflet angle implies restriction limited to the basal portion of the anterior mitral leaflet (AML). The combined effects of tethering of both the basal and distal portions of the AML can be determined by measuring the distal anterior leaflet angle .
The area of the mitral annulus can be estimated by measuring orthogonal annular dimensions assuming an ellipsoid shape. This geometric assumption can be avoided with three-dimensional imaging, which also provides dynamic information about annular folding, contraction, and translation. It should be emphasized that echocardiography measures the projected area of the annulus, not its actual nonplanar surface area. Normal indexed diastolic annular area is approximately 5 cm 2 /m 2 , decreasing by about 25% by midsystole. Coaptation length , a measure of coaptation reserve, can be measured echocardiographically, as shown in Figure 5 .
Echocardiographic Tethering Patterns
Tethering is characterized echocardiographically by displacement of the mitral valve leaflets away from the annular plane during systole and is best appreciated in the apical four-chamber view. Traction exerted by the basal chords on the body of the AML creates a characteristic angulation or “bent knee” appearance. The tension within the basal chords is transmitted from their point of attachment at mid leaflet down to the leaflet base, rendering the proximal portion of the leaflet more or less immobile.
Two echocardiographic tethering patterns have been described, asymmetric and symmetric, on the basis of the disposition of the mitral leaflets with respect to their point of coaptation ( Figure 10 ). With asymmetric tethering ( Figures 10 B and 11 , Videos 1A and 1B [view video clips online]), the anterior leaflet coapts against the atrial surface of the posterior leaflet, creating a “pseudoprolapse” appearance. This is caused by disproportionately greater tethering of the posterior leaflet. The MR jet associated with asymmetric tethering is typically eccentric, oriented along the posterior wall of the left atrium. A symmetric tethering pattern ( Figures 10 C and 12 , Video 2
[view video clips online]) results when there is balanced tethering of both leaflets such that the coaptation point remains at the leaflets’ tips, albeit displaced apically. The MR jet associated with symmetrical tethering is typically oriented centrally.
Echocardiographic Recognition of Ischemic Mitral Regurgitation
Echocardiography plays an important role in the evaluation of ischemic MR. Localized or diffuse changes in LV size and shape due to post-MI remodeling can be readily appreciated. Echocardiography is also useful in characterizing deformational changes in the mitral leaflets caused by tethering.
Post-MI Ventricular Remodeling
Ischemic MR is a disease of the left ventricle. As the ventricle remodels after MI, the normal geometric relationship of the PM and mitral valve becomes altered, resulting in increased leaflet tethering and MR. Early after transmural MI, the necrotic myocardium of the affected region thins and enlarges (infarct expansion). Ventricular remodeling, however, frequently does not remain confined to the region of infarction. Echocardiographic studies have demonstrated dilatation of noninfarcted myocardial segments remote from the site of infarction. Such remote remodeling can result in marked and diffuse LV enlargement, thought to represent an adaptive response (using the Frank-Starling mechanism) to maintain stroke volume in the face of lost contractile elements. It is important to recognize that it is the site of LV remodeling, more than its extent, that is the more important determinant of whether ischemic MR will develop. LV dilatation, even when marked, may not cause MR unless accompanied by geometric distortion in the region of the PM. This explains the high prevalence of ischemic MR in patients with localized infarction of inferior wall. Ischemic MR can also develop in the absence of any echocardiographically evident scar, presumably from highly localized remodeling limited to the region of the PM.
Echocardiographic Parameters of Leaflet Tethering
A number of echocardiographic parameters of leaflet tethering have been described ( Figure 9 ). Besides providing quantitative information about leaflet deformation, these offer insight into the mechanism of tethering as well as prognostic information about the durability of mitral valve repair (discussed in the subsequent section). Tenting height is the vertical distance between the mitral annulus and the leaflet coaptation point. The region bound by the annulus and the mitral valve leaflets is referred to as the tenting area . Tenting volume , measured by three-dimensional echocardiography, is less susceptible to foreshortening and therefore correlates better with ROA in patients with ischemic MR. It is important to recognize that all three tenting indices reflect the global tethering burden imposed on the mitral valve, because they integrate a number of otherwise independent geometric factors (i.e., anterior leaflet tethering, posterior leaflet tethering, annular size, and the leaflet coaptation point ). Information about regional leaflet tethering can, however, be obtained by measuring individual mitral leaflet angles. A wide posterior leaflet angle indicates posterior leaflet restriction. Widening of the basal anterior leaflet angle implies restriction limited to the basal portion of the anterior mitral leaflet (AML). The combined effects of tethering of both the basal and distal portions of the AML can be determined by measuring the distal anterior leaflet angle .
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