Background—Functional mitral regurgitation (FMR) occurs with a structurally normal valve as a complication of systolic left ventricular dysfunction (LVD). Determinants of degree of FMR are poorly defined; thus, mechanistic therapeutic approaches to FMR are hindered. Methods and Results—In a prospective study of 21 control subjects and 128 patients with LVD (defined as ejection fraction <50%, mean 31±9%) in sinus rhythm, we quantified simultaneously by echocardiography the effective regurgitant orifice (ERO) of FMR by using 2 methods: mitral deformation (valve and annulus) and left ventricular (LV) global (volumes, stress, function, and sphericity) and local (papillary muscle displacements and regional wall motion index) remodeling. A wide range of ERO (15±14 mm2, 0 to 87 mm2) was observed, unrelated to ejection fraction (P=0.32). The major determinant of ERO was mitral deformation, ie, systolic valvular tenting and annular contraction in univariate (r=0.74 and r=−0.61, respectively; both P<0.0001) and mul...

Determinants of the degree of functional mitral regurgitation in patients with systolic left ventricular dysfunction: A quantitative clinical study.

Background Recent advances in three-dimensional (3D) echocardiography allow us to address uniquely 3D scientific questions, such as the mechanism of functional mitral regurgitation (MR) in patients with left ventricular (LV) dysfunction and its relation to the 3D geometry of mitral leaflet attachments. Competing hypotheses include global LV dysfunction with inadequate leaflet closing force versus geometric distortion of the mitral apparatus by LV dilatation, which increases leaflet tethering and restricts closure. Because geometric changes generally accompany dysfunction, these possibilities have been difficult to separate. Methods and Results We created a model of global LV dysfunction by esmolol and phenylephrine infusion in six dogs, initially with LV expansion limited by increasing pericardial restraint and then with the pericardium opened. The mid-systolic 3D relations of the papillary muscle (PM) tips and mitral valve were reconstructed. Despite severe LV dysfunction (ejection fraction, 18±6%), only...

Insights From Three-Dimensional Echocardiography Into the Mechanism of Functional Mitral Regurgitation Direct In Vivo Demonstration of Altered Leaflet Tethering Geometry

Acute effects of cardiac resynchronization therapy on functional mitral regurgitation in advanced systolic heart failure

Background— Patients who undergo ring annuloplasty for ischemic mitral regurgitation (MR) often have persistent or recurrent MR. This may relate to persistent leaflet tethering from left ventricle (LV) dilatation that is not relieved by ring annuloplasty. Therefore, the purpose of this study was to test the hypothesis that recurrent MR in patients after ring annuloplasty relates to continued LV remodeling. Methods and Results— Serial echoes were reviewed in 30 patients (aged 72±11 years) who showed recurrent MR late (47±27 months) versus early (3.8±5.8 months) after ring annuloplasty for ischemic MR during coronary artery bypass grafting without interval infarction. Patients with intrinsic mitral valve disease were excluded. Echocardiographic measures of MR (vena contracta and jet area/left atrial area) and LV remodeling (LV dimensions, volumes, and sphericity) were assessed at each stage. The degree of MR increased from mild to moderate, on average, from early to late postoperative stages, without significant change in LV ejection fraction. Changes in MR paralleled increases in LV volumes and sphericity index at end-systole and end-diastole. The only independent predictor of late postoperative MR was LV sphericity index at end-systole. Conclusions— Recurrent MR late after ring annuloplasty is associated with continued LV remodeling, emphasizing its dynamic relation to the LV.

Mechanism of Recurrent Ischemic Mitral Regurgitation After Annuloplasty: Continued LV Remodeling as a Moving Target

“ More than once in history the discovery of paradox has been the occasion for major reconstruction at the foundations of thought .” — W.V. Quine, The Ways 

One thing is certain: Ischemic mitral regurgitation (MR) conveys adverse prognosis, doubling mortality after myocardial infarction (MI), in chronic heart failure, and after surgical or catheter revascularization.1–9 It is common and increases mortality even when mild,3–5 with a graded relationship between severity and reduced survival (Figure 1A).5 



Figure 1. A, Decreased survival after MI with increasing MR. Effective regurgitant orifice (ERO) area of 20 mm2 demarcates mild from moderate. Reprinted with permission from Grigioni et al.5 Copyright 2001, American Heart Association, Inc. B, Decreased survival after cardiogenic shock with increasing MR for comparable LV ejection fraction (LVEF). Reprinted with permission from Picard et al.8 Copyright 2003, American Heart Association, Inc.



In many other respects, however, ischemic MR has been a study in controversy and paradox. Its diagnosis is notoriously elusive, both by auscultation and intraoperatively. It may paradoxically decrease as driving pressure increases. Still commonly referred to as “papillary muscle dysfunction,” it cannot generally be produced by direct papillary muscle damage and may actually decrease with papillary muscle ischemia. Although leaflet motion is typically restricted, it may also be excessive, or both. Treatment benefit is hotly debated and will be difficult to resolve so long as existing therapies are incompletely effective in permanently abolishing MR. New therapeutic opportunities are perplexing in their diversity. By exploring such areas of confusion, we aim to clarify fundamental principles and achieve more effective solutions.

Ischemic MR is convenient shorthand for MR caused by changes in ventricular structure and function related ultimately to ischemia; it is predominantly postinfarction MR. Active ischemia can contribute, for example, creating intermittent “flash” pulmonary edema, …

Ischemic Mitral Regurgitation on the Threshold of a Solution From Paradoxes to Unifying Concepts

Background Functional mitral regurgitation in patients with ischemic or dilated ventricles has been related to competing factors: altered tension on the leaflets due to displacement of their papillary muscle and annular attachments, which restricts leaflet closure, versus global ventricular dysfunction with reduced transmitral pressure to close the leaflets. In vivo, however, geometric changes accompany dysfunction, making it difficult to study these factors independently. Functional mitral regurgitation also paradoxically decreases in midsystole, despite peak transmitral driving pressure, suggesting a change in the force balance acting to create a regurgitant orifice, with rising transmitral pressure counteracting forces that restrict leaflet closure. In vivo, this mechanism cannot be tested independently of annular contraction that could also reduce midsystolic regurgitation. Methods and Results An in vitro model was developed that allows independent variation of papillary muscle position, annular size,...

Integrated mechanism for functional mitral regurgitation: leaflet restriction versus coapting force: in vitro studies.

Studies have concluded that the shape of the human mitral valve annulus is a three-dimensional saddle. The objective of this study was to investigate the effects of a saddle shaped annulus on chordal force distribution and mitral valve function. Eleven human mitral valves were studied in a physiological left heart simulator with a variable shaped annulus (flat versus saddle). Cardiac output and transmitral pressure were analyzed to determine mitral regurgitation volume. In six experiments, force transducers were placed on six chordae tendineae to measure chordal force distribution. Valves were tested in normal and pathophysiologic papillary muscle positions. When comparing the flat and saddle shaped configurations, there was no significant difference in mitral regurgitation volume 11.2% ± 24.7% (p=0.17). In the saddle shaped configuration, the tension on the anterior strut chord was reduced 18.5% #x00B1 16.1% (p < 0.02), the tension on the posterior intermediate chord increased 22.3% #x00B1 17.1% (p < 0.03), and the tension of the commissural chord increased 59.0% #x00B1 32.2% (p < 0.01). Annular shape also altered the tensions on the remaining chords. Annular shape alone does not significantly affect mitral regurgitation caused by papillary muscle displacement. A saddle shaped annulus redistributes the forces on the chords by altering coaptation geometry, leading to an optimally balanced anatomic/physiologic configuration. © 2003 Biomedical Engineering Society.

Effects of a saddle shaped annulus on mitral valve function and chordal force distribution: an in vitro study.

Background—In hypertrophic cardiomyopathy, a spectrum of mitral leaflet abnormalities has been related to the mechanism of mitral systolic anterior motion (SAM), which causes both subaortic obstruc...

Mechanism of Mitral Regurgitation in Hypertrophic Cardiomyopathy: Mismatch of Posterior to Anterior Leaflet Length and Mobility

Effective valve repair in patients with mitral regurgitation (MR) demands an understanding of its mechanism. In patients with ischemic heart disease and functional MR, which doubles late mortality, normal leaflets are apically displaced. This reflects an altered balance of forces acting on the leaflets: increased tethering forces restricting closure, resulting from an altered geometry of leaflet attachments, and decreased ventricular forces acting to close the leaflets. Extensive evidence confirms a central and predominant role of tethering as the final common pathway inducing functional MR; left ventricular (LV) pressure dynamically modulates the orifice area. Because ischemic MR is a disease of the entire mitral complex, including the remodeling LV, reducing annular size alone is often ineffective. Undersizing rings attempts to compensate for tethering; new and potentially more effective strategies directly address tethering by infarct plication, papillary muscle repositioning with a localized patch, or basal chordal cutting to increase coaptational surface area without prolapse. A comprehensive understanding of the valve in its ventricular context, therefore, provides new opportunities for successful valve repair in patients.

Mechanistic insights into functional mitral regurgitation.

Background and aim of the study Perturbations of leaflet geometry are the final end point through which left ventricular (LV) ischemia causes incomplete mitral leaflet closure and resultant mitral regurgitation (MR). Geometric inconsistencies observed with valvular or subvalvular structural alterations raise several questions. Methods A new in-vitro LV flexible bag model was developed in order to visualize and analyze leaflet geometric changes under simulated pathological ischemic MR conditions. Results Papillary muscle (PM) displacement and annular dilatation decreased leaflet coaptation length, leading to significant MR. Symmetrical PM displacement shifted the coaptation line towards the leaflet edges and created central gaps along this line. Asymmetric PM displacement generated diametrically uneven coaptation with a tent-shaped leaflet at the tethered PM side, while the leaflet bulged at the opposite side towards the left atrium. Conclusion Leaflet geometry during systole is affected by subvalvular structures. Asymmetric PM displacement, which may occur in regional or acute myocardial infarction, induces irregular deformation of the leaflet's coaptation line and, as a result, MR at the tethered side. Direct visualization of leaflet perturbation under these simulated pathological conditions may promote understanding of mechanisms present in ischemic MR.

Shengqiu He

Papers

Integrated mechanism for functional mitral regurgitation: leaflet restriction versus coapting force: in vitro studies.

Effects of a saddle shaped annulus on mitral valve function and chordal force distribution: an in vitro study.

Mechanism of Mitral Regurgitation in Hypertrophic Cardiomyopathy: Mismatch of Posterior to Anterior Leaflet Length and Mobility

Mechanistic insights into functional mitral regurgitation.

Mitral leaflet geometry perturbations with papillary muscle displacement and annular dilatation: an in-vitro study of ischemic mitral regurgitation.