Introduction

Systolic anterior motion (SAM) of the mitral valve is defined as the displacement of the mitral valve into the left ventricular outflow tract (LVOT) during systolic ejection. The development of SAM can be associated with hemodynamic instability because the displaced valve leaflet can lead to LVOT obstruction or mitral regurgitation (MR).

SAM has several specific characteristics. First, it has a continuous spectrum with varying severity. The majority of SAM lack clinical symptoms; therefore, they mostly get detected for the first time in an echocardiographic investigation. Thus, SAM can be considered to be a morphological abnormality that rarely requires medical intervention. Occasionally, SAM can evoke clinical symptoms such as cough or effort dyspnea, indicating pulmonary congestion. Symptoms arising from moderate SAM should be managed with medical treatment. Rarely, the most severe form of SAM is manifested in association with the LVOT obstruction and severe MR, which results in hemodynamic collapse with low cardiac output syndrome. Extreme cases of SAM should be managed with intensive critical care with or without surgical intervention.

Second, SAM can be encountered in a wide variety of clinical settings. Initially, SAM was considered to be exclusive to hypertrophic cardiomyopathy (HCM) [1]. However, subsequent studies countered SAM even in cases of mitral valve repair [2], aortic valve replacement [3], hypertension [4], diabetes [5], or acute myocardial infarction [6] or in healthy adults loaded with catecholamine [7]. Furthermore, each clinical setting involves various risk factors such as septal hyperplasia [8], elongated mitral leaflet [9, 10], anterior deviation of papillary muscle [9], tall posterior leaflet [9, 11], small hyperkinetic left ventricle [12], and small prosthetic ring [13]. Until today, several attempts have been made to counteract SAM through negative inotropic administration [14, 15], volume loading [16], septal myectomy [17], leaflet shortening [18], and annular enlargement [19]. Thus, SAM is associated with a multifactorial pathophysiology, making its recognition difficult.

The identification difficulty in SAM stems from the immature elucidation of its mechanism. Previously, a simple hypothesis termed as the “Venturi effect” served as its mechanism, wherein negative pressure produced by high-flow velocity in LVOT pulls the mitral leaflet into LVOT [20]. However, subsequent studies indicated the inadequacy of such a simple hypothesis to describe the multifactorial pathophysiology. Thereafter, several researches have attempted to elucidate its complicated mechanism. This paper reviews articles that attempted to identify the mechanism of SAM and proposes a mechanism-based concept to facilitate easy recognition of SAM.

Attempts to elucidate the mechanism of SAM

Leaflet motion: a step-wise progression of SAM

Figure 1 shows serial echocardiograms of the leaflet motions during SAM in patients suffering from SAM after mitral valve repair. At the early systolic phase, the mitral valve closes; coapting the opposing leaflets (Fig. 1.1, .2). Thereafter, the tip of the anterior leaflet moves anteriorly toward the ventricular septum (Fig. 1.3), and the residual anterior leaflet beyond the coaptation point slackened in LVOT (Fig. 1.4). When the left ventricle began to eject, the residual anterior leaflet was forced out by the ejected blood flow (Fig. 1.5). Finally, the mitral leaflet non-coapted and the displaced anterior leaflet obstructed LVOT, resulting in severe MR and a high pressure gradient in LVOT (Fig. 1.6).

Fig. 1
figure 1

Leaflet motion during SAM after mitral valve repair. AL anterior leaflet, PL posterior leaflet, LA left atrium, LV left ventricle

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As seen in the serial echocardiograms in Fig. 2, the development of SAM comprised three phases (Fig. 2): “Coaptation,” “prepositioning,” and “exacerbating”. At the prepositioning phase, the coaptation point moves toward the septum, resulting in the extension of the residual anterior leaflet beyond the coaptation point. Consequently, the anterior leaflet tip strays into LVOT and becomes relatively free to move in response to the flow-related forces in LVOT. This preceding leaflet positioning in the mechanism of SAM was first proposed by Jebara et al. [18]. The authors reported that the tip of the anterior leaflet locates in LVOT during the early systolic period (or during the “SAM position”). Similarly, Levine et al. [21] proposed the term “prepositioning” to describe the anterior leaflet tip protrusion into LVOT as a precursor to SAM. At the exacerbating phase, the ejected blood flow force the slack anterior leaflet tip in LVOT, leading to further displacement of the coaptation point toward the septum, which accelerates the degree of SAM development. Shah et al. [22] were the first to recognize the important role of the anterior displacement of the coaptation point in the development of SAM.

Fig. 2
figure 2

Stepwise concept of SAM

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Hemodynamic force: lift vs. drag force

As seen in the serial echocardiograms in Fig. 2, SAM begins with the displacement of the anterior leaflet tip into LVOT (or prepositioning), indicating that any force should operate on the leaflet. This force was initially considered lift force due to high-flow velocity in LVOT [20]. This phenomenon is known as the “Venturi effect,” wherein the negative pressure produced by the high-ejecting blood flow on the ventricular surface of the anterior leaflet pulls the mitral valve leaflets into LVOT (Fig. 3a). However, the “Venturi effect” theory assumes the blood flow velocity in LVOT to be high; therefore, this theory does not explain the wide spectrum mechanism of SAM, for instance, the development of SAM in the absence of septal hypertrophy or residual SAM after successful flow velocity reduction by surgical septal myectomy [23]. Moreover, Sherrid et al.’s [24] echocardiographic study demonstrated that SAM begins at normal LVOT velocity, suggesting that the Venturi effect cannot explain the initial displacement of the anterior leaflet. Therefore, any kind of force other than the Venturi effect should be recognized to explain the initiation of SAM.

Levine and Yoganathan’s [25,26,27] group conducted a series of engineering experiments using an in vitro simulator and obtained profound insights to the mechanism of SAM. In morphologically normal mitral valve settings, they could not create SAM even at the highest flow velocity in LVOT, suggesting that such a high-flow velocity is not the only determinant in the development of SAM [26]. The authors could successfully create SAM only after morphological modifications such as the anterior displacement of the papillary muscles or the extension of the mitral leaflets.

In the in vitro simulator, the intraventricular flow can be visualized using light scattering particles [26]. In the normal mitral valve morphology, the diastolic mitral inflow posteriorly courses parallel to the posterior wall and anteriorly turns at the apex; then, the septal wall produces a clockwise circulation motion in the left ventricle (Fig. 3b-1). The morphological predisposition such as the papillary muscle displacement alters the direction of the diastolic inflow. The inflow direction anteriorly deviates toward the septum and posteriorly turns at the apex; then, the posterior wall produces a counter-clockwise circulation motion in the left ventricle (Fig. 3b-2). This counter-clockwise recirculation in the left ventricle affects the posterior leaflet from below and anteriorly displaces the mitral valve. This finding demonstrates that the prepositioning of the mitral valve may be induced by the drag force to push the posterior leaflet from below and anteriorly displace the mitral valve.

Fig. 3
figure 3

Mechanism of SAM ①

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Recently, it has become possible to visualize such intraventricular flow using vector flow-mapping echocardiography. Ro et al. [28] analyzed the intraventricular flow at the time of SAM in patients with HCM using vector flow-mapping echocardiography. According to their study, at the initiation of SAM, a part of mitral valve apparatus overlaps with LVOT. The mechanism of this overlap can be classified into two types. In approximately 60% of the patients, this overlap is caused by deviated ejection flow due to the bulging septum (Fig. 4-①). In the remaining 40% patients, the overlap is caused by a vortical flow due to the mitral valve protrusion toward LVOT (Fig. 4-②). These overlaps induce a part of systolic flow posteriorly, and this flow affects the mitral valve from below and anteriorly displaces the valve.

Fig. 4
figure 4

Mechanism of SAM ②

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These two studies [26, 28] revealed that at the initiation of SAM, a flow is induced into the cul-de-sac space between the posterior leaflet and the posterior left ventricular wall. This flow affects the posterior leaflet from below (drag force) and displaces the anterior leaflet toward LVOT, leading to “prepositioning”. This posterior leaflet’s motion at prepositioning can be identified through serial echocardiograms. After achieving mitral coaptation (Fig. 2.1), the posterior leaflet bulges toward the anterior leaflet (Fig. 2.2). This morphological change in the posterior leaflet shifts the coaptation point anteriorly and extends the residual anterior leaflet length. The extended residual anterior leaflet slackens in LVOT and is blown-off by the ejected blood flow (Fig. 2.3).

Key factors to establish SAM

Considering the diversity in the clinical setting that predispose SAM, the effort in trying to abstract the key factors for the establishment of SAM can significantly help in its comprehensive recognition. A wide variety of studies have elucidated possible key factors as essential requirements to establish SAM. Among them, three factors could be postulated: (1) the distance between the coaptation point and the septum (CS), (2) the residual anterior leaflet length beyond the coaptation point (residual leaflet length), and (3) the ejection flow velocity in LVOT (Fig. 5).

Fig. 5
figure 5

Key factors to establish SAM

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According to the “step-wise” concept, the first step in the mechanism of SAM is considered to be the flow misleading into the cul-de-sac space below the posterior leaflet. CS can contribute to the misleading flow because it functions as a gate for the ejected blood flow to enter LVOT. The shorter the CS is, the more likely it is that the flow would be misled into the space below the posterior leaflet. The significant correlation between CS and the degree of SAM was demonstrated by the engineering experiments using an in vitro simulator [27]. CS was compared with the echocardiography between patients with and without SAM and was found to be shorter in SAM due to HCM [9, 28] as well as after mitral valve repair [11, 29,30,31]. Lee et al. [29] chronologically measured CS in patients undergoing mitral valve repair. They found that CS significantly decreases at the time of SAM and then increases almost to the preoperative level after SAM correction.

The second step in the mechanism of SAM focuses on the force applied by the ejected blood flow. This forced-out pressure by the ejection blood flow can be simulated as the sail in the wind, which hints that the size of the sail and the strength of wind are critical role-players. The residual anterior leaflet length beyond the coaptation point (residual leaflet length) and the flow velocity in LVOT should play a similar role in this leaflet drifting motion. The longer the residual length floating in LVOT, the more intensively the ejected blood flow impacts the leaflet. The significant correlation between the residual leaflet length and the degree of SAM has also been demonstrated by the engineering experiments using an in vitro simulator [27]. The residual leaflet length was compared using echocardiography between patients with and without SAM and was found to be longer in SAM with HCM [9, 28, 32] as well as after the mitral valve repair [11].

As discussed above, the location of the coaptation point plays a critical role in the mechanism of SAM, as it shares a close relationship with both CS and the residual leaflet length. SAM arises from short CS and long residual leaflet; however, simultaneously, the progression of SAM may further reduce CS and further extend the residual leaflet length via the anterior displacement of the coaptation point. Therefore, even a small degree of displacement of the coaptation point can trigger the vicious cycle of its development.

The higher ejection flow velocity in LVOT can determine the intensity of the impact the leaflet would receive in the development of SAM. The engineering experiments demonstrated the correlation between the cardiac output and the degree of SAM [26]. In this in vitro simulator setting, the cardiac output should have a direct relationship with the ejection flow velocity. Pollick et al. [33] reported in their echocardiographic study that the pressure gradient in LVOT (indicative of high-flow velocity) is quantitatively related with the degree of SAM. Sherrid et al. [34] reported that SAM can be attenuated by decreasing the ejection flow velocity using negative inotropic drugs.

Clinical application of the mechanism

Risk factors

Based on the aforementioned mechanism, the next issue to be discussed is the identification of the clinical settings susceptible to meet such key factors. Particularly for patients awaiting mitral valve repair procedures, the risk stratification of SAM is essential in the operative planning. Although the risk factors of SAM stems from various aspects, the mechanism-based concept can be helpful to comprehensively recognize them from the pathophysiological perspectives (Fig. 6).

Fig. 6
figure 6

Pathophysiological basis for the recognition of risk factors

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Morphological factors

Long leaflet length has been identified as a risk factor of SAM because it usually results in a long length of the residual leaflet. He et al. [27] demonstrated through their engineering experiments that the residual leaflet length increases by either anterior or posterior leaflet elongation. The leaflet length was compared using echocardiography between patients with and without SAM and found to be longer in SAM due to HCM [9, 28], as well as after mitral valve repair [10, 11]. Varghese et al. [30] reported that the anterior leaflet length of ≥ 25 mm and posterior leaflet length of ≥ 15 mm are independent predictors of SAM (OR = 5.70 and 3.80, respectively). Particularly, long posterior leaflet is considered to be a strong risk factor [11, 35] because it anteriorly shifts the coaptation point in the body of the anterior leaflet, resulting in a short CS as well as a long residual leaflet length (Fig. 7-b).

Bulging septum has been identified as a risk factor of SAM because it reduces CS and may increase the ejection flow velocity due to LVOT narrowing (Fig. 7-c). Moreover, it may alter the direction of the ejecting blood flow toward the cul-de-sac space below the posterior leaflet. Said et al. [8] reported six cases in which the bulging septum was considered to cause SAM. Miura et al. [36] reported that the prevalence of sigmoid septum was greater in SAM cases. Varghese et al. [30] reported that the septal diameter ≥ 15 mm is an independent predictor of SAM with OR = 3.63.

A small left ventricle is considered as a risk factor for SAM, probably due to its short CS. We previously reported that the incidence of SAM increases with smaller preoperative left ventricular end-systolic dimension [12]. Varghese et al. [30] reported that the end-diastolic diameter < 45 mm is an independent predictor of SAM with OR = 3.90.

The anterior displacement of papillary muscles has been identified as a risk factor of SAM. It displaces the whole mitral apparatus anteriorly, resulting in the shift of the coaptation point toward the septum as well as in the extension of the residual anterior leaflet length (Fig. 7-d). Levine et al. [37] demonstrated in their animal study that the anterior displacement of the papillary muscles inevitably created SAM. Their echocardiographic analysis demonstrated that the anterior displacement of the papillary muscles moved the coaptation point anteriorly, extending the residual leaflet length. Echocardiographic analysis by Pai et al. [9] revealed that the papillary muscles were more anteriorly displaced in SAM cases than in non-SAM cases.

Operative procedural factors

In patients undergoing mitral valve repair, the geometric change resulting from operative procedures can contribute to the development of SAM. According to our morphological analysis with transesophageal echocardiography, the standard mitral valve repair reduced the CS by 6.9 mm and extended the residual anterior leaflet length by 5.4 mm, which were enhanced in SAM cases [38]. To be more specific, Carpentier [35] postulated that a mismatch between the amount of leaflet tissue and the size of the reconstructed mitral annulus is a major risk factor for SAM. Shah et al. [10] also reported that the difference between the annular dimension and the combined anterior and posterior leaflet heights were the strongest predictors of SAM.

Annular reduction has been identified to be a risk factor of SAM because it displaces the whole mitral apparatus anteriorly (Fig. 7-e), as can be seen in papillary muscle deviation. Dagum et al. [39] demonstrated that ring annuloplasty in animals, particularly using prosthetic ring with some rigidity, could displace the whole mitral apparatus anteriorly. The annular size is considered to be a critical issue because several echocardiographic studies have revealed that the annular reduction is larger in patients with SAM than in those without SAM [10, 38]. Kahn et al. presented a case report suggesting that the undersizing of a mitral valve annulus can be attributed for SAM [40]. About the characteristics of annuloplasty ring, Loulmet et al. [41] reported that a complete annuloplasty ring is associated with a higher incidence of SAM than a posterior band.

Fig. 7
figure 7

Risk factors of SAM

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Posterior leaflet resection may contribute to the development of SAM. Although it is yet to be demonstrated, the posterior leaflet resection may immobilize the posterior leaflet motion and fix it at the closed position. Several studies have revealed that SAM rarely occurs in patients with solitary anterior leaflet lesion [30, 42]. Several studies have reported that posterior leaflet resection is associated with a higher risk of SAM [41, 43]. Grossi et al. [44] reported that extensive posterior leaflet resection is associated with SAM.

Hemodynamic factors

A hyperdynamic state of the left ventricle can contribute to SAM as it increases the ejection flow velocity, usually, along with decreased intracardiac cavity. Inotropes are known to induce transient SAM in approximately 17–21% of the healthy candidates [7, 45]. Mitral valve repair for patients with well-preserved left ventricle is considered as a risk factor of SAM. We reported that the incidence of SAM increases with greater preoperative ejection fraction, suggesting the possible contribution of cardiac function to the development of SAM [12]. Loulmet et al. [41] reported that preoperative EF of no less than 60% is a risk factor of SAM (with OR = 2.7). Rescigno et al. [46] reported an interesting case in which SAM developed late after a surgery to recover LV function that had been temporarily deteriorated immediately after the surgery.

Measures to counteract SAM

Several measures have been reported to prevent or treat SAM, varying from medical treatment to surgical interventions. The comprehensive understanding of how each measure affects the attenuation of SAM is an important feature in SAM management. The mechanism-based concept could aid in comprehending the identification of different measures from the pathophysiological perspectives (Fig. 8). Particularly, for the management of SAM after the mitral valve repair, several systematic management strategies have been proposed [42, 43, 47]. It is thus recommended that a stepwise approach be used, including medical treatment as the first therapy, followed by surgical interventions (in refractory cases).

Fig. 8
figure 8

Pathophysiological basis for the recognition of treatment

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Medical treatment

Insights to SAM development indicated the possibility of some medical intervention to successfully counteract SAM. Considering the role of intravascular hypovolemic condition and hyperdynamic cardiac performance as the contributing factors of SAM, volume loading and inotropic drug discontinuation should be attempted as the initial treatment to counteract SAM [42, 43, 47]. Volume loading can be expected to expand the LVOT diameter as well as to distend CS. In addition, inotropic discontinuation can be expected to decrease the flow velocity in LVOT.

Negative inotropic drug is well-known for its effectiveness in counteracting SAM. On the basis of echocardiography in patients with HCM, Sherrid et al. demonstrated that such negative inotropes could slow the average acceleration of the left ventricular ejection by 34% and lead to the attenuation of SAM [34]. Conventionally, it is preferred to initiate the selection of the negative inotropic drug with a beta blocker or verapamil. For a patient refractory to beta blocker, the addition of disopyramide should be considered. Pollick et al. conducted a prospective, randomized, double-blind cross-over study in ten patients with HCM and demonstrated that disopyramide was more effective than propranolol in decreasing the pressure gradient in LVOT [48]. Kehl et al. reported successful management with disopyramide for five cases refractory to beta blockers [49]. Vasoconstriction with phenylephrine is also effective in counteracting SAM [42], probably due to the flow acceleration-lowering effect in LVOT.

These medical treatments have been demonstrated to be remarkably effective in eliminating SAM, particularly for patients after their mitral valve repair [42, 43]. Kuperstein et al. [50] reported the long-term outcomes of medical therapy against SAM after mitral valve repair. Freedom from mortality or reoperation in the SAM group was compatible with that in the non-SAM group, while exercise stress echocardiography revealed low incidence of SAM in the SAM group.

Surgical intervention

Diverse surgical procedures have been reported to counteract SAM, including the interventions on the anterior leaflet, posterior leaflet, annulus, and septum. Although the strategy of selection in each procedure remains to be determined, the identification of the contributing factors in each patient may be useful in the selection of the most suitable surgical procedures.

Posterior leaflet height reduction is the most commonly used procedure to counteract SAM. Reducing the posterior leaflet height can extend CS and shorten the residual anterior leaflet. This procedure is usually performed in patients with > 20-mm posterior leaflet. Two types of procedures are involved in the reduction of the posterior leaflet height: to resect or to fold. The standard procedure is the Carpentier’s sliding leaflet technique [51], wherein in addition to the quadrangular resection, a small triangular resection at the base of the leaflet remnant was added to adjust the posterior leaflet height. Perier et al. reported about 48 patients who underwent this technique without suffering from SAM [52]. Some modifications were made mainly in the shape of the resecting area, such as a butterfly [53] or an hourglass [54]. Asai et al. reported 76 patients undergoing butterfly resection technique without suffering from SAM [55]. Another procedure to adjust the leaflet height was to fold the leaflet without resection. Cevasco et al. recommended suturing the leaflet edge portion to the annulus [56], whereas George et al. recommended suturing the belly of the leaflet to the annulus [57]. Loop technique can also be used to adjust the leaflet height by folding the leaflet toward papillary muscle [58, 59].

Although the procedure of anterior leaflet height reduction is relatively infrequently performed, it is effective in patients with billowing anterior leaflet. Reducing the anterior leaflet height shortens the residual anterior leaflet. Quigley [60] developed elliptical anterior leaflet excision in 47 patients without any case progressing to SAM.

The selection of annuloplasty ring is an important feature. A large annuloplasty ring can extend CS and shorten the residual anterior leaflet. Particularly for patients with billowing leaflet, a large annuloplasty ring should be considered. Adams et al. [19] performed this procedure in 67 patients with Barlow’s disease without any development of SAM later.

The edge-to-edge technique is also considered to be effective in counteracting SAM [61]. This technique securely restricts the anterior leaflet motion by suturing the anterior leaflet and stabilizing the coaptation position. Myers et al. [62] reported only one late recurrence of SAM with this technique from among 65 patients without mitral stenosis.