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provided by Elsevier - Publisher Connector JACC: CARDIOVASCULAR IMAGING VOL. 1, NO. 3, 2008 © 2008 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION ISSN 1936-878X/08/$34.00 PUBLISHED BY ELSEVIER INC. DOI:10.1016/j.jcmg.2008.02.006

FROM PICTURES TO PRACTICE PARADIGMS Twist Mechanics of the Left Principles and Application

Partho P. Sengupta, MBBS, MD, DM, A. Jamil Tajik, MD, Krishnaswamy Chandrasekaran, MD, Bijoy K. Khandheria, MD Scottsdale, Arizona

Left ventricular (LV) twist or torsion represents the mean longitudinal gradient of the net difference in clockwise and counterclockwise rotation of the LV apex and base, as viewed from LV apex. Twist during ejection predominantly deforms the subendocardial fiber matrix, resulting in storage of potential energy. Subsequent recoil of twist deformation is associated with the release of restoring forces, which contributes to LV diastolic relaxation and early diastolic filling. Noninvasive techniques such as magnetic resonance imaging and are useful for understanding LV twist dynamics in clinical settings, and data regarding their relative merits and pitfalls are rapidly accumulating. This review is a focused update on the current and evolving applications of LV twist mechanics in clinical cardiology. First, the theoretical framework for understanding the physiological sequence of LV twist during a cardiac cycle is presented. Second, variations in LV twist encountered in different experimental and clinical situations are discussed. Finally, the review presents an algorithm for routine application of LV twist in clinical differentiation of patterns of LV dysfunction encountered in day-to-day practice. (J Am Coll Cardiol Img 2008;1:366–76) © 2008 by the American College of Cardiology Foundation

ower, in 1669, was the first to describe the resulted into development of innovative tech- twisting motion of the left ventricle (LV) as niques in which LV twists are readily com- “. . . the wringing of a linen cloth to squeeze puted from grayscale cardiac ultrasound images L out the water” (1). Over the past 3 obtained at the bedside. centuries, the twist deformation of the LV has continued to intrigue clinicians and researchers Uniform Definitions for Characterization in their quest to understand the performance of of LV Twist Deformation human . Experimental and clinical explo- rations on LV twist have entailed use of nu- Terms such as LV rotation, twist, and torsion merous techniques such as implanted ra- are often used interchangeably for explaining diopaque markers (2), biplane cine angiography the wringing motion of the LV. For a uniform (3), sonomicrometry (4,5), optical devices (6), description, this review emphasizes that the gyroscopic sensors (7), magnetic resonance im- term rotation be referred to the rotation of a aging (MRI) (8–10), and echocardiography short-axis sections of LV as viewed from the (11–14). Furthermore, growth of interest in the apical end and defined as the angle between quantifying LV twist in clinical settings has radial lines connecting the center of mass of

From the Division of Cardiovascular Diseases, Mayo Clinic Arizona, Scottsdale, Arizona. Manuscript received January 3, 2008; revised manuscript received February 19, 2008, accepted February 29, 2008. JACC: CARDIOVASCULAR IMAGING, VOL. 1, NO. 3, 2008 Sengupta et al. 367 MAY 2008:366–76 Twist Mechanics of the Left Ventricle

that specific cross-sectional plain to a specific point angiographic markers (18), sonomicrometry (11, in the myocardial wall at end diastole and at any 14), rotational devices (6), and echocardiography other time during systole (15). The unit of rotation (11,14) have recorded an initial clockwise motion of is degrees or radians. The base and apex of the LV the LV apex and counterclockwise motion of the rotate in opposite directions. The terms twist and LV base during isovolumic contraction. However, torsion refer to the same phenomenon and should studies with magnetic resonance tagging have re- be used for defining the base-to-apex gradient in ported that both the LV base and the apex rotate in the rotation angle along the longitudinal axis of the a counterclockwise direction during iso- LV, expressed in degrees per centimeter or radians volumic contraction (10,20). The reason ABBREVIATIONS per meter (15). The absolute apex-to-base differ- for this discrepancy remains unclear and AND ACRONYMS ence in LV rotation (also in degrees or radians) is has been attributed to the lower temporal left ventricle/ventricular ؍ stated as the net LV twist angle or the net LV resolution of magnetic resonance tagging LV mitral regurgitation ؍ torsion angle (15). Some investigators have also (14). MR magnetic resonance ؍ expressed torsion as the axial gradient in the rota- MRI tion angle multiplied by the average of the outer Link Between Myofiber Geometry imaging right ventricle/ventricular ؍ radii in apical and basal cross-sectional planes, and Twist Mechanics RV thereby representing the shear deformation angle on the epicardial surface (unit degrees or radians) In the LV myocardial wall, the myofibers geometry (16). It must be emphasized that LV length and changes smoothly from a right-handed helix in the diameter change dynamically during a cardiac cycle, subendocardium to a left-handed helix in the sub- and therefore these normalization schemes permit epicardium such that the helix angle varies contin- comparison of only the peak magnitude of torsion uously from positive at the endocardium to negative for different sizes of LV (15,17). at the epicardium (Fig. 2). To provide a framework for interpreting LV twist, Taber et al. (21) proposed a model of helical layer architecture composed of Temporal Sequence of LV Twist obliquely aligned muscle fibers embedded in an isotropic matrix (Fig. 2A). As shown in the model, Figure 1 shows the temporal sequence of LV twist. on one hand the contraction of the epicardial fibers During isovolumic contraction, the LV apex shows brief clockwise rotation that reverses rapidly and 12 34 becomes counterclockwise during LV ejection 16.0 (18,19). The magnitude of peak rotation varies Apex Rotation depending on the position of the cross-section viewed from the tip of LV apex. For standardiza- 8.0 tion, therefore, the LV apical cross-section should be obtained well beyond the papillary muscle, with either none or the smallest view of the right 0.0 ventricle (RV) in the cross-section. Counterclock- wise twist in ejection is followed by untwisting Base Rotation (clockwise rotation) of the LV apex, which occurs during the isovolumic relaxation and the early 0 200 400 600 800 1000 1200 1400 1600 period of diastole. In contrast to the LV apex, rotation of the LV base is significantly lower in magnitude and oppo- Figure 1. Temporal Sequences of LV Twist During a Cardiac Cycle site in direction. During isovolumic contraction, The left ventricular (LV) rotation from apical and basal cross-sections of LV there is a brief counterclockwise rotation, which is has been obtained by speckle tracking of B-mode cardiac ultrasound images followed by clockwise rotation during ejection and (GE Healthcare, Milwaukee, Wisconsin) in a normal healthy subject. The dif- ference between the 2 rotations provides an estimate of net LV twist angle counterclockwise rotation during isovolumic relax- (black line). During isovolumic contraction (phase 1), the apex shows a brief ation and early diastolic filling. clockwise rotation and the base shows a brief counterclockwise rotation. Interestingly the description of LV apex rotation During ejection (phase 2), the direction of rotation changes to counterclock- during the phase of isovolumic contraction has wise at the LV apex and clockwise at the LV base, respectively. Torsional recoil occurs predominantly during the phase of isovolumic relaxation varied depending on the technique used. Studies (phase 3) and early diastolic filling (phase 4). that have measured LV apex rotation using cine- 368 Sengupta et al. JACC: CARDIOVASCULAR IMAGING, VOL. 1, NO. 3, 2008 Twist Mechanics of the Left Ventricle MAY 2008:366–76

stretch both contribute to a brief clockwise rotation of LV apex (18,22,26,27). The transmural spread of electrical activation results in sequential subendocardial-to-subepicardial fiber shortening (24,25). Although the subendocardial forces exceed subepicardial forces, the larger radius of subepicar- dial region produces higher torque to dominate the direction of rotation. The large subepicardial torque is coupled transmurally to the midwall and suben- docardium and results in global counterclockwise LV rotation near the apex and clockwise rotation near the LV base during ejection. In the subepicar- dium, this twist aids contraction in the principal fiber direction (18). In the midwall, this torque enhances shortening in the circumferential direc- tion (18). In the subendocardium, this torque causes fiber rearrangement such that subendocardial fibers are sheared toward the LV cavity for LV wall thickening, whereas the LV base is pulled toward the apex, shortening the longitudinal axis of the LV. Twisting and shearing of the subendocardial fibers deforms the matrix and result in storage of potential energy, which is subsequently utilized for diastolic recoil (4). Figure 2. Myofiber Architecture of LV and Models for Understanding The torsional recoil during isovolumic relaxation LV Twist Dynamics and early diastole releases the potential energy Myofiber orientation in the left ventricular (LV) changes smoothly from a stored in the deformed matrix of the subendocar- left-handed helix in the subepicardium to a right-handed helix in the suben- dium (4,28,29). This process is facilitated by pres- docardium (A, left). Thick-walled cylindrical myofibers models proposed by Ingels et al. (A, right) and Taber et al. (B), showing the subendocardial fiber ence of lengthening-shortening gradients in the LV wrapped in a right-handed helix and a subepicardial fiber wrapped in a left- wall, which hasten lengthening of relaxed segments. handed helix. Arrows (A) depict the circumferential components of force For example, in experimental animal models, LV that results from force development in each fiber direction. The radii (R1 for epicardium at the base is seen to lengthen while subendocardium and R2 for the subepicardium) are the lever arms, which convert these circumferential components of force into torque about the ongoing shortening occurs near the LV apex. How- long axis of the cylinder. The subepicardial fibers have a longer arm of ever, the subendocardial fibers lengthen near the Ͻ moment than the subendocardial fibers ( R1 R2). Figure illustration done LV apex and recoil in clockwise direction, like a by Rob Flewell. twisted coil that springs open, with ongoing short- ening of the subendocardial region near LV base will rotate the apex in counterclockwise and the (22,23). The presence of simultaneous shortening base in clockwise direction, whereas on the other and lengthening vectors of deformation within the hand, contraction of subendocardial region will LV wall allows diastolic restoration to be initiated rotate the LV apex and base in exactly the opposite without changes in LV volume. direction. When both layers contract simulta- Torsion helps bring a uniform distribution of LV neously, a larger radius of rotation for the outer fiber stress and fiber shortening across the wall (30). epicardial layer results in epicardial fibers having a It has been shown in a mathematical model that mechanical advantage in dominating the overall normal torsion causes sarcomere shortening of 0.20 direction of rotation (21). ␮m in the epicardium and 0.48 ␮m in the endo- With the onset of cardiac electromechanical ac- cardium (31). However, elimination of the torsion tivation, the subendocardial fibers near the mid and would decreases epicardial shortening (0.10 ␮m), apical septal walls are first to be excited with an and increases endocardial shortening (0.55 ␮m). apex-to-base sequence of activation (Fig. 3)(22,23). Thus the disappearance of torsion would increase Subendocardial shortening sequence is accompa- endocardial stress and strain and, therefore, increase nied with subepicardial fiber stretching (24,25). oxygen demand, thereby reducing the efficiency of Subendocardial shortening and subepicardial LV systolic function. JACC: CARDIOVASCULAR IMAGING, VOL. 1, NO. 3, 2008 Sengupta et al. 369 MAY 2008:366–76 Twist Mechanics of the Left Ventricle

Figure 3. Sequence of Twist Mechanics Explained in an Experimental Animal Model Electric and mechanical activation are initiated in the apical subendocardial region. During isovolumic contraction (IVC) (A), the subendo- cardial myofibers (right-handed helix) shorten with stretching of the subepicardial myofibers (left-handed helix), producing a brief clock- wise rotation of the apex and a counterclockwise rotation of the left ventricular base. During ejection (B), the subendocardial and subepicardial layers shorten simultaneously, with shortening strains near the apex exceeding those of the base. The larger arm of moment of the subepicardial fibers dominates the direction of twist, causing rotation of the apex and base in counterclockwise and clockwise directions, respectively. During isovolumic relaxation (IVR) (C), subepicardium lengthens from the base toward the apex and the subendocardium from the apex toward the base. The subsequent period of diastole is characterized by relaxation in both layers with minimumuntwisting(D).ThisfigurereferstotheexperimentalmodelthatwasusedinSenguptaetal.(22).Figureillustrationdoneby Rob Flewell.

Physiological Variables Affecting LV Twist with end-systolic volume held constant, produce higher LV twist. Similarly, afterload affects twist, The LV twists increase gradually from infancy to that is, twist decreases at higher end-systolic vol- adulthood. Counterclockwise apical rotation is con- umes when end-diastolic volumes are held constant. stant in its magnitude during childhood, whereas The effect of preload on twist is about two-thirds as the basal rotation changes over age, initially coun- great as that of afterload. Like changes in loading terclockwise in infancy to neutral in early child- conditions, increasing contractility increases LV hood, and shows the adult clockwise pattern in twist; for example, positive inotropic interventions adolescence (32). This progressive change has been such as dobutamine infusion and paired pacing, attributed to the maturation of the helical myofiber architecture of the LV wall (32). Subsequently, with increasing age in adult life, subendocardial function Table 1. Physiological Variables Influencing Left Ventricular may gradually attenuate, and LV twist increases Twist Mechanics further because of an unopposed increase in LV Physiological Variables Twist Er apical rotation (33,34). Age-related degenerative Increasing preload (35–37) 12 changes reduce the elastic resilience of the myocar- Increasing afterload (35–37) 22* dial wall, and therefore the velocity of untwisting in Increasing contractility (9,36,38,39) 11 early diastole progressively reduces (34). Exercise (40) 11 Physiological variables such as preload, afterload, Increasing age (33,34) 12* and contractility alter the extent of LV twist (Table Numbers in parentheses correspond to the reference number in the Refer- 1)(35–37). Twist is greater with higher preload. ences list. *Delayed onset of untwisting. 2 ϭ 1 ϭ ϭ For example, higher end-diastolic volumes of LV, reduced; increased; Er early diastolic untwisting velocity. 370 Sengupta et al. JACC: CARDIOVASCULAR IMAGING, VOL. 1, NO. 3, 2008 Twist Mechanics of the Left Ventricle MAY 2008:366–76

greatly increase LV twist (9,36,38,39), whereas ularly those with a pacemaker and/or an internal negative inotropic interventions markedly reduce cardioverter-defibrillator. twist (9). Echocardiography has wide availability, and In the intact circulation, changes in contractility therefore is a more feasible technique for bed- are often accompanied by changes in loading con- side assessment of LV twist, including for patients ditions for increasing the twist mechanics of LV. with a pacemaker and/or internal cardioverter- For example, LV systolic twisting and untwisting defibrillator. Applications for measuring twist using can almost double with short-term exercise because echocardiography were initially applied semiquali- of augmented rotation of both apical and basal tatively by studying the rotational motion of papil- levels (40), storing additional potential energy that lary muscles (46). This was followed by attempts to is released for improving diastolic suction (41,42). decipher the rotational mechanics using tissue Long-term exercise training may, however, reduce Doppler imaging (13); however, the angle depen- the LV twist at rest. Soccer players show lower LV dency of Doppler imaging has remained a major twist values and untwisting velocities than non- limitation. Another echocardiographic method for trained individuals (43). It has been postulated that motion estimation has gained recent acceptance and reduced LV twist in soccer players may represent is based on 2-dimensional tracking of unique increased torsional reserves that are used in speckle patterns created by the constructive and increased-demand situations such as high-intensity destructive interference of ultrasound beams within sports. Indeed, a higher resting LV twist value, as tissue (11,12,14). These speckles are cross- seen with advancing age, is associated with attenu- correlated and tracked on a frame-by-frame basis. ation of torsional reserves at peak exercise (44). Because the tracking is fundamentally based on gray-scale B-mode images, it is independent of cardiac translation and angle dependency. The ac- Clinical Techniques for Measuring LV Rotation curacy of speckle-tracking imaging has been vali- dated against sonomicrometry and tagged MRI The LV rotation can be measured in clinical prac- (12,14). However, the quality of tracking is depen- tice noninvasively using MRI and echocardiogra- dent on the image quality and is vulnerable to phy. For several years, MRI examinations were dropouts of ultrasound data and reverberations. considered the reference standard for noninvasive Moreover, clinical studies with speckle-tracking assessment of cardiac biomechanics. The 2 most echocardiography have reported a wide variability in common MRI methods for measuring myocardial the values for resting LV systolic torsion (47). This motion are tagging and phase contrast velocity may be related to the incongruent locations of LV mapping. Conventional analysis of tagged images apical and basal cross-sectional planes, errors re- entails computer-assisted detection of the epicardial lated to through-plane motion, and the variable transmural depth of the region of interest for border, endocardial border, and tag lines (45). measuring LV rotation in each cross-sectional view. Border and tag detection can be performed manu- Methods for improving reproducibility of measure- ally or semiautomatically; however, semiautomatic ments should be addressed in future investigations. techniques generally require some extent of manual correction, and either technique is usually quite time consuming. Tissue phase mapping, on the Clinical Applications other hand, directly encodes the velocity of myo- cardial motion into the MRI signal and offers high Diastolic dysfunction. Assessment of twist and peak spatial resolution of the functional information (1 to untwisting rates were previously proposed to accu- 3 mm) (20). Because both methods in MRI are rately reflect LV relaxation (48). Interestingly, how- based on multiple breath-held 2-dimensional mea- ever, recent studies indicate that LV twist may surements, the temporal resolution is limited by the remain preserved in patients with diastolic dysfunc- length of the breath-hold period to 30 to 80 ms. tion in presence of normal ejection fraction (49). This limitation has been addressed by development For example, Wang et al. (49) studied 67 patients of a respiratory-gated free-breathing method for (34 with LV ejection fraction Ͻ50% and 33 with tissue phase mapping that allows measurements LV ejection fraction Ͼ50%) undergoing simulta- with a temporal resolution comparable to tissue neous right heart catheterization and echocardio- Doppler imaging. A major limitation remains the graphic imaging and compared the LV twist impossibility of routinely studying patients, partic- mechanics with 20 healthy subjects as a control JACC: CARDIOVASCULAR IMAGING, VOL. 1, NO. 3, 2008 Sengupta et al. 371 MAY 2008:366–76 Twist Mechanics of the Left Ventricle

group. The LV twisting and untwisting rates 2). More studies are required to explore the were reduced in patients with LV systolic dys- variability of this observation. function and depressed ejection fraction, but not Myocardial ischemia and the extent of LV infarct. In in those with diastolic dysfunction and normal patients with anterior wall , ejection fraction. The onset of untwisting oc- peak circumferential strain in the apex is signifi- curred just before aortic valve closure in control cantly depressed in patients with LV systolic dys- subjects and was significantly delayed after aortic function compared with those with preserved sys- valve closure in patients with systolic and dia- tolic function (51). In addition, LV twist is severely stolic heart failure (Fig. 4). In another study of 49 depressed in patients who have reduced LV ejection patients with , twist was not differ- fraction, mainly because of the reduced magnitude ent among groups of patients with or without LV of LV apical rotation. With the onset of systolic hypertrophy, although early diastolic LV un- dysfunction, diastolic untwisting is also reduced and twisting and untwisting rates were significantly delayed (51). In contrast, systolic twist is main- delayed and reduced in parallel to the severity of tained in patients with anterior wall myocardial LV hypertrophy, as assessed by LV mass index infarction with relatively preserved LV systolic (50). Thus, LV twist is either preserved or function (51,52). This is associated with a milder augmented in patients with diastolic dysfunction reduction of circumferential strain in the LV apex. and normal systolic performance. However, the The role of measuring LV twist during stress onset of LV untwisting and the magnitude of echocardiography has not been systematically eval- peak untwisting velocities either remain normal uated. Because myocardial perfusion defects in- or are reduced and significantly delayed (Table duced during stress testing are largely subendocar-

A AVC* B AVC* 12.0 12.0

6.0 6.0

0.0 0.0

-6.0 -6.0

-12.0 -12.0 1234 12 34 -18.0 -18.0 0 200 400 600 800 1000 1200 1400 1600 1800 2000 0 200 400 600 800 1000 C AVC* D AVC* 12.0 12.0

6.0 6.0

0.0 0.0

-6.0 -6.0

-12.0 -12.0 12 34 1234 -18.0 -18.0

0 200 400 600 800 1000 1200 1400 0 200 400 600 800

Figure 4. LV Twist in Health and Disease Rotation of the left ventricular (LV) apex, the LV base, and the net LV twist angle (shown in red, green, and black colors, respectively) are assessed by speckle-tracking echocardiography in a normal subject (A), a patient with dilated cardiomyopathy with systolic heart fail- ure (B), a patient with cardiac amyloidosis presenting as heart failure with normal ejection fraction (diastolic heart failure) (C), and a patient with constrictive pericarditis (D). Net ventricular twist is negative in dilated cardiomyopathy because of complete reversal of the LV apex rotation (B). In contrast, a patient with amyloid cardiomyopathy shows relatively preserved magnitude of net LV twist angle. In a normal subject, the onset of untwisting occurs just before the aortic valve closure (AVC) (A); however, in the patient with amyloid cardio- myopathy, the onset of untwisting is delayed after AVC (C). The patient with constrictive pericarditis (D) shows reduced magnitude of netventriculartwistandmarkeddelayintheonsetofuntwisting.Phases1through4aredefinedintheFigure3legend. 372 Sengupta et al. JACC: CARDIOVASCULAR IMAGING, VOL. 1, NO. 3, 2008 Twist Mechanics of the Left Ventricle MAY 2008:366–76

Table 2. Left Ventricular Twist Mechanics in Different systolic twist, delayed time to peak systolic twist Cardiac Diseases (occurring after end-ejection in subjects with MR), and reduction in diastolic recoil. It has been sug- Cardiac Diseases Twist Er gested that chronic MR reduces systolic LV twist Systolic heart failure 22because of a decreased leverage of the epicardial Diastolic heart failure (49,50)Nor1 Nor2 fibers relative to the endocardial muscle fibers. Aortic stenosis (54–56)Nor12Although increased preload will tend to increase 22 Mitral regurgitation (58–60) systolic twist (35), chronic MR is associated with 22 Transmural infarction (51) complex LV adaptive remodeling and eccentric Subendocardial ischemia N N or 2 hypertrophy. The effect of chronic MR on twist Dilated cardiomyopathy (65) 22 probably depends on the extent of subclinical LV Hypertrophic cardiomyopathy (70,71)Nor12 Restrictive cardiomyopathy (73)Nor1 N systolic dysfunction. Peak untwisting velocity in Constrictive pericarditis (73) 22MR remains normal, but correlates negatively with end-systolic dimension and regurgitant volume, Numbers in parentheses correspond to the reference number in the Refer- ences list. suggesting that peak untwisting velocity, like peak 2 ϭ reduced; 1 ϭ increased; Er ϭ early diastolic untwisting velocity; N ϭ normal. systolic twist, depends on the stage of the disease (61). Congenital heart diseases. There is limited informa- dial, it is likely that LV circumferential deformation tion currently regarding the utility of assessing LV and twist, which reflect subepicardial function, may remain unaltered. This postulate is supported by rotation in patients with congenital heart diseases. observations from experimental studies that have Because echocardiography represents the noninva- explored the influence of ischemia on LV rotation sive tool most commonly used in pediatric cardiol- and reported greater-than-normal apical rotation ogy, application of speckle-tracking echocardiogra- with subendocardial ischemia and less-than-normal phy for bedside assessment of LV strain and twist apical rotation with transmural ischemia (9,53). deformation may provide important insights into Transmural heterogeneity of LV mechanics in valvular mechanical adaptive responses of the RV and LV in heart diseases. In aortic valve stenosis, coronary congenital heart diseases. For example, in the nor- flow diminishes in the subendocardial region rela- mal heart, both RV and LV are coupled for twisting tive to the subepicardial region. The LV twist is in the same direction (62). However, in patients significantly increased, although diastolic apical un- with transposition of the great arteries, the mor- twisting is prolonged in comparison with normal phologic RV supports the systemic circulation. It subjects (54–56). The delay in apical untwisting is has been shown recently that the systemic RV associated with diastolic dysfunction and elevated contraction in these patients resembles that of the LV end-diastolic filling pressures (54,55). After normal LV, however, without the ventricular twist aortic , LV twist normalizes. (63). The global performance of the systemic ven- Level of recovery is, however, dependent on under- tricle is dependent more on the circumferential than lying (57). Van der Toorn et the longitudinal free wall contraction, and may al. (56) used the ratio of LV twist to LV shortening represent an adaptive response to the systemic load for assessing LV contractile function in patients (64). As twist contributes to energy-efficient ejec- with aortic stenosis. The twist shortening ratio was tion, reduced twist might represent a potential for significantly higher in aortic stenosis than in a myocardial dysfunction (63). However, this hy- group of healthy volunteers. After aortic valve pothesis requires further prospective evaluation. replacement, the ratio partially returned to normal. LV twist variations in cardiomyopathy. In dilated car- Similarly, subendocardial contractile function was diomyopathy, amplitude of peak LV systolic twist is found to be decreased before aortic valve replace- impaired in proportion to the global LV function ment and significantly recovered 3 months after (65). This reduction in LV twist is accounted for by , even before LV remodel- marked attenuation of LV apical rotation, whereas ing was obvious (56). basal rotation may be spared. In some cases, rota- Changes in LV twist have also been studied in tion of the apex may be abruptly interrupted such patients with mitral regurgitation (MR) (58–60). that in the initial part of systole, the LV base and In an experimental canine model, Tibayan et al. apex rotate in the same direction (Fig. 4). After the (58) showed that the progression from acute to initial part of the systole, the rotation diverges into chronic MR was associated with decreased peak 1 of 2 patterns: either continuation of identical JACC: CARDIOVASCULAR IMAGING, VOL. 1, NO. 3, 2008 Sengupta et al. 373 MAY 2008:366–76 Twist Mechanics of the Left Ventricle

rotation at all levels for the remainder of systole reason for LV diastolic filling impairment in con- (Fig. 4) or a divergence of rotation so that the apex striction. The marked endocardial dysfunction with and base rotate in opposite directions (66,67). relative sparing of epicardial function leads to ab- There is limited information presently on the effects normal longitudinal mechanics with relative sparing of therapeutic measures such as cardiac resynchro- of circumferential and twist mechanics in restrictive nization therapy (68) or LV reduction surgeries cardiomyopathy (73). However, in constrictive peri- (66,67) on LV twist. Preliminary data suggest that carditis, marked epicardial dysfunction leads to LV reduction surgery does not change LV twist, predominant impairment of circumferential short- although the rate of early diastolic untwisting may ening (74) and twist mechanics (73), while rela- improve (66,67). Similarly, LV torsional mechanics tively sparing subendocardial longitudinal mechan- do not change after cardiac resynchronization ther- ics (Fig. 4). Similarly, congenital defects of apy despite improvements in LV circumferential cause a lack of LV twist while main- shortening mechanics (69). This suggests that loss taining LV regional myocardial function (75), sug- of LV torsional mechanics in remodeled may gesting that normal pericardial layers may have be difficult to restore once already established. important roles in modulating LV rotational In contrast to dilated cardiomyopathy, patients mechanics. with hypertrophic cardiomyopathy show relatively preserved net LV twist (70), although the apex-to- A Proposal for Assessing the Pattern base progression of the LV twist sequence is altered. of LV Dysfunction Rotation at the mid-LV level becomes clockwise, similar to the direction of rotation of the LV base Traditional concepts of heart failure have largely (opposite to normal) (71). The area of null rotation, focused on the hemodynamic consequences of LV which represents the region of LV where rotation systolic dysfunction. Using a time-dependent model crosses over from clockwise into a counterclockwise of heart failure, it has been proposed that diastolic direction, is apically displaced. This causes regional and systolic heart failure are phenotypic expressions heterogeneity of LV twist, reducing the gradient of of the same disease process that evolves gradually as LV rotation for the basal aspect of LV, while a continuum of clinical events (76). Assessment of exaggerating it toward the LV apex (71). During mechanics may provide superior alcohol septal ablation, LV twist in hypertrophic pathophysiological insights into the mechanism of cardiomyopathy may decrease transiently with oc- heart failure; however, this remains inadequately clusion of the septal perforator; however, after the addressed. injection of ethanol, twist increases to higher-than- The majority of progressive myocardial diseases, baseline angles. Most of the improvement in twist is including coronary ischemia, tend to predominantly accounted for by an increase in LV apical rotation cause subendocardial dysfunction. This results in an (72). Despite a preserved LV twist magnitude, early preferential involvement of longitudinal LV patients with hypertrophic cardiomyopathy have mechanics, which can be identified even in a sub- reduced efficiency in generating untwisting. At rest, clinical state. The timing of contraction–relaxation peak untwisting velocities are only marginally re- cross-over is the most vulnerable period of myofi- duced in comparison with normal subjects. How- bers mechanics (77,78). In early stages, therefore, ever, these differences became more dramatic with ventricular relaxation either regionally or globally exercise, with the patients showing much lower becomes abnormally slow and impaired with a untwisting velocities when compared with normal progressive loss of the ventricle to modulate the subjects (41). timing of onset of relaxation. The epicardial func- Differentiation of constrictive pericarditis from restric- tion may remain relatively unaffected, and circum- tive cardiomyopathy. Both constrictive pericarditis ferential strain and twist either remains normal or and restrictive cardiomyopathy may have similar shows exaggerated compensation for preserving the clinical presentations related to altered LV diastolic LV systolic performance. Compensatory features function. However, the mechanism leading to the such as myocardial hypertrophy attempt to reduce LV diastolic function is different. In restrictive subendocardial stress; however, such changes are cardiomyopathy, the LV wall is resistant to stretch usually maladaptive and detrimental (79). Further- because of endocardial disease. On the other hand, more, loss of cardiac muscle resilience also causes tethering of subepicardial layers and an altered progressive delay in LV untwisting. Loss of early compliance of thickened pericardium is the main diastolic longitudinal relaxation and delayed un- 374 Sengupta et al. JACC: CARDIOVASCULAR IMAGING, VOL. 1, NO. 3, 2008 Twist Mechanics of the Left Ventricle MAY 2008:366–76

twisting attenuates LV diastolic performance, pro- Final Comments ducing elevation of LV filling pressures. This stage manifests as heart failure with preserved systolic A growing body of evidence suggests that assess- function. With further progression of disease, sub- ment of LV rotation and twist is feasible in clinical epicardial function starts deteriorating, resulting in settings. The relationship between longitudinal and marked reduction of LV circumferential and twist torsional mechanics of the LV provides insight into mechanics. This causes progressive loss of LV the transmural heterogeneity in myocardial contrac- ejection fraction and results in systolic heart failure. tile function. The presence of a subendocardial-to- Acute transmural ischemia or infarction also results subepicardial gradient in LV mechanics may pro- in simultaneous impairment of LV longitudinal and vide a useful clinical measure for early recognition torsional mechanics, resulting in LV systolic dys- of a subclinical state that is likely to progress into function. Pericardial diseases, on the other hand, either systolic or diastolic heart failure. With the cause subepicardial tethering and predominant af- advent of 3-dimensional echocardiography, newer fection of LV torsional mechanics, while relatively algorithms for the characterization of ventricular sparing subendocardial function. A disease process twist mechanics hold promise for better under- such as radiation that affects both the pericardium standing mechanisms of ventricular dysfunction and and the subendocardial region may produce early improving management of heart failure patients. attenuation of both longitudinal and circumferen- tial LV function. Relative differences in longitudi- nal and torsional mechanics therefore may provide pathophysiological insight into the mechanism of Reprint requests and correspondence: Dr. Partho P. Sen- LV dysfunction. Application of such algorithms gupta, Division of Cardiovascular Diseases, Mayo Clinic, requires prospective evaluation in future clinical 13400 East Shea Boulevard Scottsdale, Arizona 85259. trials. E-mail: [email protected].

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