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(Circulation. 1995;91:1189-1195.)
© 1995 American Heart Association, Inc.

Articles

Papillary Muscle Displacement Causes Systolic Anterior Motion of the Mitral Valve

Experimental Validation and Insights Into the Mechanism of Subaortic Obstruction

Robert A. Levine, MD; Gus J. Vlahakes, MD; Xavier Lefebvre, PhD; J. Luis Guerrero, BS; Edward G. Cape, PhD; Ajit P. Yoganathan, PhD; Arthur E. Weyman, MD

From the Non-Invasive Cardiology Laboratory (R.A.L., J.L.G., A.E.W.), Department of Medicine, and the Surgical Cardiovascular Unit (G.J.V.), Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Mass; the Cardiovascular Fluid Mechanics Laboratory (X.L., A.P.Y.), School of Chemical Engineering, Georgia Institute of Technology, Atlanta, Ga; and the Division of Pediatric Cardiology (E.G.C.), Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pa.

Correspondence to Robert A. Levine, MD, Cardiac Ultrasound Laboratory, Vincent-Burnham 5, Massachusetts General Hospital, Boston, MA 02114.

	Abstract

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Background Systolic anterior motion (SAM) of the mitral valve in hypertrophic cardiomyopathy (HCM) has generally been explained by a Venturi effect related to septal hypertrophy, causing outflow tract narrowing and high velocities. Patients with HCM, however, also have primary abnormalities of the mitral apparatus, including anterior and inward or central displacement of the papillary muscles, and leaflet elongation. These findings have led to the hypothesis that changes in the mitral apparatus can be a primary cause of SAM by altering the forces acting on the mitral valve and its ability to move in response to them. Despite suggestive observations, however, it has never been prospectively demonstrated that such changes can actually cause SAM.

Methods and Results To test this hypothesis in vivo, anterior papillary muscle displacement was created in 7 dogs studied by echocardiography, with controlled cardiac output and heart rate. In all 7 dogs, papillary muscle displacement caused SAM, with an outflow tract gradient (33±19 mm Hg) and mitral regurgitation in 6. As in patients with HCM, the mitral valve was displaced anteriorly and the coaptation point shifted toward the insertion of the leaflets, creating longer distal residual leaflets that moved anteriorly.

Conclusions Primary changes in the mitral apparatus can cause SAM without septal hypertrophy. In this model, SAM appears to be determined by the ability of the leaflets to move anteriorly (papillary muscle displacement causing slack and increased residual leaflet length) and their interposition into the outflow stream by anterior displacement, determining the direction of this motion. Geometric factors observed in HCM and in patients with SAM without HCM can therefore play a primary role in causing SAM.

Key Words: cardiomyopathy • echocardiography • hypertrophy

	Introduction

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Dynamic subaortic obstruction in hypertrophic cardiomyopathy (HCM) is most commonly related to systolic anterior motion (SAM) of the mitral valve.^{1 2 3 4} Proposed mechanisms for SAM have largely focused on hypertrophy of the interventricular septum,⁵ causing outflow tract narrowing, increased flow velocity and decreased pressure above the valve (the Venturi effect), and therefore, SAM.^{6 7 8 9 10} Such a mechanism, however, leaves us with the question of how sufficient leaflet slack is produced to permit SAM⁵ and cannot explain the onset of SAM at or before aortic valve opening, when outflow velocity is low.^{11 12 13} SAM in patients with primary mitral abnormalities and no septal hypertrophy is also unexplained,^{14 15 16 17 18 19 20 21 22 23} as is the predominance of SAM at the center of the valve.^{2 11 24}

Patients with obstructive HCM also have primary structural abnormalities of the mitral apparatus, including displacement of the papillary muscles anteriorly and toward one another,^{1 11 25 26 27 28 29 30} with a concomitant anterior shift of the mitral valve, as well as leaflet elongation and altered coaptation.^{11 24 27 31 32 33 34 35 36 37 38 39 40} These findings suggest the hypothesis that primary changes in the mitral apparatus and, in particular, papillary muscle displacement, can be a primary cause of SAM, independent of septal hypertrophy, by the following mechanisms (Fig 1)^{11 41 42} : (1) by decreasing the ability of the papillary muscles to restrain the valve posteriorly, (2) by interposing the leaflets anteriorly into the outflow stream, which could then propel them anteriorly into the outflow tract,^{1 11 13 24 42 43} and (3) by creating a geometry of mitral valve coaptation that favors SAM. Specifically, anterior displacement of the papillary muscles could pull the posterior leaflet upward to meet the anterior leaflet closer to its midportion than its tip, creating a long, overlapping distal residual leaflet that is relatively free to move anteriorly, unrestrained by the pressure difference between the left atrium and ventricle that keeps the leaflet bodies closed.¹¹ SAM would be favored by leaflet elongation (increased slack), which could also increase the posterior residual leaflet length.^{27 32} Residual leaflet elongation^{11 24 27 31 34 37} has, in fact, been described as a prerequisite for SAM.³¹ Inward displacement of the papillary muscles toward one another (Fig 2) would allow the central leaflet portions the most slack and therefore the greatest SAM.

View larger version (23K): [in this window] [in a new window]   Figure 1. Drawings of possible mechanisms for systolic anterior motion with anterior displacement of the papillary muscles (PM): (1) the normal posterior component of PM tension is reduced by anterior displacement of the muscle tips; (2) interposing the leaflets into the streamlines of flow causes drag forces with an anterior component; and (3) pulling up the posterior leaflet so that it meets the anterior leaflet closer to its base creates a long, overlapping residual leaflet, as seen clinically. This leaflet portion is relatively free to move anteriorly, unlike the coapted leaflet bodies that are restrained by the balance of ventricular and atrial pressures acting across them. The angle between the posterior leaflet and posterior wall is increased. Ao indicates aorta; IVS, interventricular septum; LA, left atrium; LV, left ventricle; and PW, posterior wall.

View larger version (25K): [in this window] [in a new window]   Figure 2. Diagrams of chordal geometry illustrating effects of papillary muscle malposition on distribution of tension to the mitral leaflets. The mitral apparatus is viewed from above. In hypertrophic cardiomyopathy with systolic anterior motion (right), the papillary muscle tips are displaced toward one another. This geometry can be predicted to produce relative chordal slack in the central leaflet portions. This is indicated by the relatively lax chordae (wavy lines) on the right that are longer than the distance between their papillary and mitral insertions. MV indicates mitral valve; L, lateral edge; and C, central portion. From Reference 11, with permission.

Although primary changes in the mitral apparatus have been observed frequently, the purpose of this study was to test the hypothesis that they can actually cause SAM prospectively in an open chest canine model.

	Methods

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In Vivo Model
Seven dogs (weight, 20 to 23 kg) were anesthetized with 30 mg/kg IV sodium pentobarbital and ventilated. Right thoracotomy was performed to provide wider access to the mitral apparatus by exposing it through the right atrium and atrial septum. A pericardial cradle was created, and micromanometer-tipped Millar catheters were inserted to monitor pressures in the aorta and the left ventricular inflow tract, distal to the mitral leaflet tips.^{44 45} Tygon tubing was sutured into the caval veins and femoral artery, and total cardiopulmonary bypass was instituted using a bubble oxygenator and a 95% oxygen/5% carbon dioxide mixture. The heart was cooled and fibrillated. The right atrial free wall and atrial septum were incised to expose the mitral valve. Because the canine papillary muscles generally adhere to the posterior wall, their tips were mobilized under direct visualization, with the aorta cross-clamped (<10 minutes) to provide a clear view. Prolene mattress sutures (2-0) were inserted into the muscle tips through surrounding pledgets and the sutures brought directly up through the anterior wall of the heart so that pulling them displaced the muscle tips and chordal connections anteriorly.

The atrial incisions were repaired and air drained from the heart. The sinoatrial node was crushed or its region excised, and atrial pacing wires were inserted. Tygon tubing was inserted into the right atrium to permit control of cardiac output, with systemic venous return from the cannulated caval veins and coronary sinus returned by a roller pump mechanism to the right atrium.⁴⁶ The heart was rewarmed and defibrillated. Cardiac output was subsequently held constant in each dog at a value of 2.0±0.1 L/min (1.8 to 2.2), which was typical for such dogs before intervention and provided usual systemic arterial blood pressures. Heart rate was controlled in each dog at 117±10 beats per minute (100 to 130) by atrial pacing to minimize escape rhythms. The papillary muscles then were displaced anteriorly by the suture mechanism while hemodynamics were monitored and mitral valve motion was studied. Echocardiographic observations were made just before papillary muscle displacement and shortly afterward in each view studied. When the muscles were first displaced, ventricular premature contractions sometimes occurred for 5 to 10 seconds, after which a stable rhythm was obtained, SAM observed, and measurements made. Thus, measurements for each view were taken within seconds of each other.

Echocardiography
Mitral valve motion was recorded with an ATL Mark 600 mechanical sector scanner (5 MHz) in long-axis and short-axis views (parasternal orientation) and M-mode scans. SAM was defined as abnormal leaflet motion anterior to a line connecting the papillary muscle tips to the point of leaflet coaptation. Mitral regurgitation was assessed by injecting agitated saline into the left ventricle and observing the relative intensity of atrial opacification by ultrasound.⁴⁷ Mitral valve coaptational geometry was measured with a Sony off-line analysis system: (1) to assess anterior mitral displacement, the ratio of the mitral-septal distance to the anteroposterior ventricular diameter at the base (M/AP) was taken at the onset of mitral coaptation; (2) the residual leaflet portion from the coaptation point to the leaflet tip was measured for both leaflets; and (3) the angle at the base of the posterior leaflet was determined at peak systole (it is increased in patients with SAM¹¹ ; Fig 1). Outflow tract area between the anterior mitral leaflet and the septum was measured at the onset of coaptation by the method of Spirito and Maron.⁶ Ejection time of left ventricular outflow was measured by pulsed Doppler. Doppler color flow mapping was performed in 3 dogs in the parasternal long-axis view with a Toshiba SH65A scanner (3.75 MHz).

Statistical Analysis
Measurements of mitral valve coaptational geometry before and during papillary muscle displacement were compared by paired Student's t test (significance at P<.05).

	Results

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Systolic Anterior Motion
In all 7 dogs, anterior displacement of the papillary muscles caused SAM. Fig 3 (long-axis view) shows the papillary muscle initially posterior with normal coaptation (left); with anterior displacement (right), anterior motion of the distal mitral valve occurred. In the short-axis view (Fig 4), SAM was greatest at the center of the valve, similar to that seen clinically. M-mode scans (Fig 5) showed the progression of SAM to mitral-septal contact with papillary muscle displacement. SAM could be repeatedly and reproducibly generated and eliminated by displacing or releasing the papillary muscles; images and measurements were obtained within seconds of papillary muscle displacement, without change in cardiac output or heart rate. In 6 dogs, mitral-septal contact could be induced,⁴⁸ with peak outflow tract gradients of 10 to 70 mm Hg (mean of 33±19 mm Hg). New mitral regurgitation occurred in 5 dogs with SAM and resolved with release of the sutures; in a sixth dog, mild regurgitation increased with SAM. Doppler color flow mapping (Fig 6) showed an anterior direction of flow proximal and below the mitral leaflets before the full development of outflow tract and regurgitant jets, illustrating interposition of the leaflets into the outflow stream. Comparable SAM and regurgitation could be obtained with the left ventricular catheter withdrawn to the atrium. There was no significant change in left ventricular internal diameter or its fractional shortening, dP/dt, or ejection time (P>.05) with papillary muscle displacement short of inducing mitral-septal contact and full obstruction.

View larger version (79K): [in this window] [in a new window]   Figure 3. Echocardiographs of systolic anterior motion (SAM, right) created in vivo by anterior displacement of the papillary muscles (PM). Arrow and dashed line indicate direction of suture. Other abbreviations as in Fig 1.

View larger version (84K): [in this window] [in a new window]   Figure 4. Echocardiographs: Parasternal short-axis views of systolic anterior motion and hypertrophic cardiomyopathy (left) and in the canine model (right) showing the greatest anterior excursion of the leaflet centrally, with the lateral portions remaining relatively posterior, creating two side pockets for flow.

View larger version (129K): [in this window] [in a new window]   Figure 5. M-mode scans of the in vivo model showing mild systolic anterior motion with mild displacement (top) and septal contact with greater displacement (bottom). IVS indicates interventricular septum; LV, left ventricle; and MV, mitral valve.

View larger version (0K): [in this window] [in a new window]   Figure 6. Dopper color flow mapping images in the parasternal long-axis view of the in vivo model during induction of systolic anterior motion by papillary muscle displacement. An early systolic image (left) shows that flow within the ventricle has an anterior component (orange color, arrow) toward the posterior and apical surface of the anteriorly moving mitral valve, illustrating interposition of the leaflets into the outflow stream. This occurs even before the initial development (in the next videoframe on the right) of high-velocity flow disturbance (indicated by mixed colors) in the left ventricular outflow tract (poststenotic jet) and left atrium (mitral regurgitant jet, arrows). Note that only the initial phase of these flow disturbances is displayed, not the fully developed jets, with the aim of illustrating the sequence of events noted.

Mitral Valve Coaptation
Papillary muscle displacement also reproduced the changes in mitral valve coaptational geometry described clinically (Figs 1 and 3 and Table). The mitral leaflets were shifted anteriorly, decreasing the ratio of the mitral-septal distance to the anteroposterior ventricular diameter (M/AP). The posterior leaflet was pulled more erect, increasing the angle at its base, so that it met the anterior leaflet farther from its tip, leaving a longer distal residual anterior leaflet. The posterior residual leaflet also increased when SAM involved that leaflet (n=3). Despite anterior displacement, outflow tract area at the onset of systole, when SAM began, was decreased by only 31±8% compared with baseline, suggesting that outflow tract narrowing was not a major factor in causing SAM.

View this table: [in this window] [in a new window]   Table 1. In Vivo Model Measurements

	Discussion

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Papillary Muscle Displacement
The in vivo studies demonstrate that anterior papillary muscle displacement alone, in the absence of septal hypertrophy or marked outflow tract narrowing, can cause obstructive SAM that is reversible and accompanied by mitral regurgitation. This maneuver also reproduces the echocardiographic morphology of SAM seen in patients with HCM and their altered mitral valve geometry, including increased anterior and posterior residual leaflet lengths and leaflet interposition into the outflow (Fig 3 and Table). The observed anterior motion can be understood in terms of the decrease in effective posterior restraint (increased leaflet slack) caused by anterior redirection of papillary muscle tension (Fig 1); increased length of the residual leaflet, which is relatively free to move anteriorly, unlike the coapted leaflet bodies; and interposition of the leaflets into the path of outflow, as suggested by Fig 6, with the potential to cause drag forces (forces parallel to flow exerted on an interposed object^{13 42 43} ) acting to propel the leaflet anteriorly. Although papillary muscle shifts have been observed previously in patients with HCM,^{1 11 25 26 27 28 29 30} these studies prospectively demonstrate that such displacement can actually cause SAM.

Systolic Anterior Motion and Prolapse
In this model, SAM appears to be determined by two factors: the ability of the leaflets to move anteriorly (papillary muscle displacement causing slack and increased residual leaflet length) and their interposition into the outflow stream by anterior displacement, determining the direction of this motion. Leaflet slack can permit prolapse (excess superior and posterior motion) or SAM (excess superior and anterior motion), depending on how the papillary muscles shift the orientation of the leaflets relative to the outflow. It is therefore reasonable that SAM and prolapse may coexist in patients,⁴⁹ and both are sensitive to changes in ventricular volume.⁵⁰ Slack can also be increased by leaflet elongation^{11 24 27 31 33 34 35 36 37 38} and annular contraction.⁵¹ The ability to promote SAM by increasing slack has been demonstrated in vitro and computationally as well (basal combined with anterior papillary muscle displacement, central displacement [Fig 2], and leaflet elongation).^{52 53 54 55 56}

Clinical Implications
The results of this study are consistent with growing evidence for primary structural alterations of the mitral apparatus in patients with HCM and obstructive SAM^{1 11 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 49 57 58 59 60} as well as in patients without septal hypertrophy but with obstructive SAM (posterior leaflet elongation shifting coaptation anteriorly after mitral repair^{18 19 20 21 61 62 63 64} ; relatively free or anterior mitral structures^{14 15 16 17 65} ; and anterior displacement of the mitral apparatus caused by annular calcification,^{39 40} posterobasal hypertrophy,⁶⁶ tumor displacing the papillary muscles,²³ and isolated papillary muscle malposition²² ). These concepts have led to new techniques for preventing SAM after mitral valve repair.^{57 62 63} Conversely, these results can help explain why more than two thirds of patients studied with massive septal thickening had no basal outflow obstruction⁶⁷ : They may have normal leaflets and papillary muscle restraint.⁶⁸ The concepts of this study can also potentially help us understand several features of SAM not readily explained by outflow tract narrowing: the observed geometry of SAM, which is greatest at the center of the valve,^{2 11 24} where greatest slack would be predicted (Fig 2),^{52 53 54 55 56} and its early systolic onset,^{11 12 13} which may result from an imbalance of chordal tension caused by contraction of malpositioned papillary muscles as early as isovolumic systole.

Models and Limitations
It is difficult to isolate one causative factor for SAM completely, given the complex interplay of mechanical and flow factors contributing to it. This study did not propose to test the Venturi effect, one mechanism proposed for SAM, or to define its role relative to that of papillary muscle displacement. Such an effect can certainly occur once a high-velocity jet has been generated above the valve by mitral-septal contact and may be another mechanism contributing to SAM in the small, hyperdynamic ventricle (potentially increased outflow tract velocity and increased leaflet slack because of a small cavity and annulus with constant leaflet size). The purpose of this study was to separate changes in the mitral apparatus from the primary alternative, septal hypertrophy. We believe the model effectively did that because septal thickness remained normal. This feature of the model also may provide insight into one of its apparent limitations, namely, the relatively modest gradients generated. Their magnitude may reflect the absence of septal hypertrophy in the model because hypertrophy may act together with SAM to narrow the outflow tract⁶⁹ ; it also may contribute additional Venturi forces to promote SAM and further interpose the leaflets into the posteriorly shifted outflow stream to increase drag forces acting to create SAM.^{1 11 24 60 70} Cardiac output was controlled by a roller pump mechanism used extensively in cardiovascular research, and observations before and during papillary muscle displacement were taken in each view within seconds of each other, without change in ventricular size or contraction. (Changes induced by obstruction^{13 71} cannot be eliminated.) Papillary muscle tension was not controlled in vivo, and it is possible that the manipulations could alter net tension by altering muscle length, although the midportions of the muscle could be seen to thicken normally.⁷² Nevertheless, the results demonstrate that a structural change in the mitral valve and supporting structures, as opposed to septal hypertrophy, can play a primary role in causing SAM, verifying the original hypothesis.

Summary
This study shows that primary structural changes in the mitral valve and its supporting structures and their relation to the outflow tract, as observed in patients with HCM, can cause SAM in the absence of septal hypertrophy. These concepts can help explain why SAM occurs both in HCM and in patients without septal hypertrophy and can therefore be of potential benefit in its reduction or elimination.

	Acknowledgments

 
This study was supported by grant HL-38176 of the National Institutes of Health, Bethesda, Md; by a grant of the Whitaker Foundation, Camp Hill, Pa; by a grant of the American Heart Association, with funds contributed in part by its Massachusetts Affiliate; and by contributions of Rena M. Shulsky, New York, NY. Dr Levine is an Established Investigator of the American Heart Association, Dallas, Tex. We would like to thank Sheila McGinty and Kathleen Sweeney Laing for their expert secretarial assistance and Christopher Slater for his assistance with the experimental studies.

Received June 15, 1994; revision received August 26, 1994; accepted September 23, 1994.

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