**2. Physiology of left ventricular twist**

**1.1. Left ventricular twist**

30 Cardiomyopathies

**1.2. Assessment of left ventricular twist**

use in routine clinical practice.

In the 16th century, Leonardo daVinci already described the rotational motion of the left ventricle [4,5] and in 1669, Richard Lower observed that myocardial contraction could be compared with 'the wringing of a linen cloth to squeeze out the water' [6]. The mechanistic basis for this wringing motion or twist lies in the complex spiral architecture of the left ventricle as revealed by the anatomical studies of Streeter et al. [7] and Greenbaum et al. [8] The left ventricle consists of obliquely oriented muscle fibres that vary from a smaller-radius, righthanded helix at the subendocardium to a larger-radius, left-handed helix at the subepicardium. The functional consequence of this three-dimensional helical structure is a cyclic systolic twisting deformation, resulting from clockwise basal rotation and counterclockwise apical rotation (as seen from the apex). Left ventricular twist plays a pivotal role in the mechanical efficiency of the heart, making it possible that only 15% fibre shortening results in a 60% reduction in left ventricular volume [9]. Moreover, diastolic untwisting of the left ventricle plays a crucial role in diastolic suction [10]. In the last decades, left ventricular twist has mainly been studied with tagged magnetic resonance imaging (MRI). However, lack of availability, limited temporal resolution, and the time-consuming and complex data analysis have precluded its use in routine clinical practice. More recently, it became possible to study left ventricular twist with tissue Doppler techniques and two-dimensional speckle tracking echocardiography. As mentioned before, this latter technique offers the opportunity to track myocardial deformation independently of both cardiac translation and the insonation angle.

Ever since the description of the rotational motion of the left ventricle by Leonardo da Vinci [4,5] in the 16th century, left ventricular twist has intrigued clinicians and researchers in their quest to understand the performance of the human heart. In the early 1960s, Harrison et al. [11] developed a method to measure external ventricular wall dimensions during the cardiac cycle. Silver tantalum clips were sutured into the human epicardium during cardiac surgery and these markers were viewed by calibrated cineradiographs. Ingels et al. [12] further developed this technique and studies of left ventricular twist continued throughout the 1980s. Unfortu‐ nately, progress was limited due to the invasive nature of the technique with its inherent limitations; the surgical implantation of the clips frequently led to local inflammation, hemorrhage and fibrosis, possibly affecting left ventricular twist. In addition, implantation of the clips could only be done in surgically accessible areas, which limited the left ventricular areas studied. In 1990, Buchalter et al. [13] described for the first time the non-invasive assessment of left ventricular twist with MRI. A tagging technique was employed to label specific areas of the myocardium prior to image acquisition. Tagging is achieved by selective radio-frequency excitation of narrow planes and appears as black lines on the image acquisi‐ tion. Using dedicated software, displacement of these tagging lines can be monitored, allowing quantification of left ventricular deformation. However, the limited availability, the poor temporal resolution, and the time-consuming and complex data analysis have precluded its

According to the Hippocratic treatise "On the Heart", the heart is shaped like a pyramid, has a deep crimson colour, and is an extremely strong muscle. From the top of the heart, rivers that irrigate the "mortal habitation" flow into the body. If these rivers dry up, then the person dies [18]. Leonardo da Vinci's investigations of the heart and circulation began nearly 18 centuries later, in the 1490s. Da Vinci made a number of advances in the understanding of the heart and blood flow. For example, he showed that the heart is indeed a muscle, that it has four chambers an he linked the pulse in the wrist with left ventricular contraction. Further‐ more, as mentioned before, Da Vinci was the first to describe the rotational motion of the left ventricle [4,5]. However, it lasted until the late 1960s before left ventricular twist was described in more detail by Streeter et al. [7] following a study of post-mortem canine hearts. Using a rapid method of fixation, they were able to analyze these hearts in either systole, begin diastole or end-diastole. Fibre angle, representing the angle between the myofibres as projected onto the circumferential-longitudinal plane and the circumferential axis, was introduced for quantification of fibre orientation. This angle changed continuously from the subendocardium to the subepicardium, typically ranging from +60 degrees at the subendocardium to –60 degrees at the subepicardium. Left ventricular twist is supposed to originate from the dynamic interaction between these oppositely wound subepicardial and subendocardial myocardial fibre helices, whereby the direction of left ventricular twist is governed by the subepicardial fibres, mainly owing to their longer arm of movement [19]. Left ventricular twist plays a pivotal role in the mechanical efficiency of the heart, making it possible that only 15% fibre shortening results in a 60% reduction in left ventricular volume [20]. Furthermore, mathematical models have shown that the counterdirectional arrangement of muscle fibres in the heart is energeti‐ cally efficient and important for equal redistribution of stresses and strain in the heart [21]. However, controversy remains present. The group of Buckberg published in 2005 a compre‐ hensive compendium, "Rethinking the cardiac helix; a structure function journey", of the Liverpool meeting: "New concepts of cardiac anatomy & physiology" [22]. Buckberg et al. believe that, based on anatomical studies by Torrent-Guasp [23] the heart is a helix that contains an apex, and that sequential contraction of the basal, descending, and ascending loop of the helix leads to the physiological pattern of myocardial contraction [24]. Although interesting, other anatomical studies have failed to reproduce the findings of Torrent-Guasp, and during the past few years this latter theory seems to gradually lose appreciation as compared to the theory of dynamic interaction between oppositely wound subepicardial and subendocardial myocardial fibres [25]. Taber et al. [19] used a theoretical model to underscore the importance of the arrangement of myocardial fibres for left ventricular function. Peak systolic twist approximately doubled with a change in de epicardial / endocardial fibre angles from +90 degrees / –90 degrees to +60 degrees / –60 degrees. The importance of fibre orientation for left ventricular twist was highlighted in clinical context as well [26]. Left ventricular sphericity index was found to have an independent positive linear relation with peak systolic twist in dilated cardiomyopathy patients. Even in dilated cardiomyopathy patient with similar left ventricular ejection fraction, left ventricular sphericity index remained positively correlated to left ventricular twist. Interestingly, in normal hearts the left ventricular sphericity index had a parabolic relation with apical peak systolic rotation and peak systolic twist. A left ventricular sphericity index of about 2.1 was associated with the highest peak systolic twist, lower and higher sphericity indices were associated with less peak systolic twist. The findings of this study seem to support the hypothesis by Taber et al. that alterations in fibre-orientation influence left ventricular peak systolic twist. Furthermore, the curvature of the left ventricular wall is related to wall tension. Since deformation of myocardial fibres is known to be inversely related to wall tension, changes in cardiac shape may also lead to changes in left ventricular twist by means of alterations in wall tension [21].

afterload. Since left ventricular twist is critically dependent on the arrangement of fibres in the myocardium, the dependence of left ventricular twist on pre- and afterload-induced changes in left ventricular volumes is intuitive. Dong et al. also observed that dobutamine increased left ventricular twist, even at identical pre- and afterload, indicating that there is a direct inotropic effect on left ventricular twist that is not mediated through changes in volume, but

Left Ventricular Twist in Cardiomyopathy http://dx.doi.org/10.5772/55281 33

Finally, several groups investigated the influence of aging on left ventricular twist [30-32]. Nakai et al. [30] and Takeuchi et al. [31] reported increased left ventricular twist with aging. Because left venticular peak systolic twist is calculated as the maximal value of *instantaneous* left ventricular apical rotation minus left ventricular basal rotation, any difference between the timing of left ventricular basal and apical peak systolic rotation (defined as rotational defor‐ mation delay) will result in less left ventricular peak systolic twist. In a study by Van Dalen et al. [32] it was shown that the increase of left ventricular twist with aging results not only from an increase in apical peak systolic rotation but also from a decrease in rotational deformation delay. The function of subendocardial fibres declines with age, even in normal hearts [33,34]. Loss of the opposed action of subendocardial fibres will allow the subepicardial fibres to cause more pronounced left ventricular apical rotation and thereby left ventricular twist. Time-topeak left ventricular basal rotation remained relatively unchanged with aging, whereas left ventricular apical peak rotation occurred later in systole with advancing age, approaching time-to-peak basal rotation and thereby decreasing rotational deformation delay. Although the increase in time-to-peak left ventricular apical rotation may be caused by an increase in collagenous tissue in the conduction system with advancing age [34], this would implicate an increase in time-to-peak left ventricular basal rotation as well, leaving rotational deformation delay unchanged. The increase in time-to-peak left ventricular apical rotation with advancing age may also be explained by prolonged contraction duration, which was previously found in aged myocardium of animals [35,36]. This prolonged contraction duration results from a prolonged active state rather than changes in passive properties or myocardial catecholamine content [37]. Whether this is the true explanation of the increase in time-to-peak left ventricular apical rotation with advancing age, and why time-to-peak left ventricular basal rotation would not be influenced by this phenomenon, still needs to be clarified. Nevertheless, both increased left ventricular apical rotation and decreased rotational deformation delay seem to be charac‐ teristics of "physiological cardiac aging", and may contribute to the preservation of left

Untwisting starts after the peak of left ventricular twist, just before the end of systole. The twisting deformation of the left ventricle during systole results not only in ejection of blood but also in storage of potential energy. During the isovolumic relaxation period the twisted fibres behave like a compressed coil that springs open while abruptly releasing the potential energy. This process may be actively supported by still depolarized subendocardial fibres that are – in contrast to the systolic period – now not opposed by active contraction of the subepi‐

through changes in force.

ventricular ejection fraction in the elderly.

**3. Physiology of left ventricular untwist**

In 1995, Moon et al. [27] investigated the effects of load and inotropic state on left ventricular twist. They studied 6 cardiac transplant recipients 1 year after heart transplantation. At the time of surgery 12 radiopaque midwall left ventricular myocardial markers were implanted. The authors claimed that pressure and volume loading did not affect left ventricular twist. However, in more recent tagged MRI studies by MacGowan et al. [28] and Dong et al. [29] it has been shown that afterload changes do affect left ventricular twist. Dong et al. also inves‐ tigated the influence of preload and contractility. An isolated increase in preload resulted in an increase in left ventricular twist. From a multiple linear regression analysis, they concluded that the effect of preload on left ventricular twist was about two-thirds as great as that of afterload. Since left ventricular twist is critically dependent on the arrangement of fibres in the myocardium, the dependence of left ventricular twist on pre- and afterload-induced changes in left ventricular volumes is intuitive. Dong et al. also observed that dobutamine increased left ventricular twist, even at identical pre- and afterload, indicating that there is a direct inotropic effect on left ventricular twist that is not mediated through changes in volume, but through changes in force.

Finally, several groups investigated the influence of aging on left ventricular twist [30-32]. Nakai et al. [30] and Takeuchi et al. [31] reported increased left ventricular twist with aging. Because left venticular peak systolic twist is calculated as the maximal value of *instantaneous* left ventricular apical rotation minus left ventricular basal rotation, any difference between the timing of left ventricular basal and apical peak systolic rotation (defined as rotational defor‐ mation delay) will result in less left ventricular peak systolic twist. In a study by Van Dalen et al. [32] it was shown that the increase of left ventricular twist with aging results not only from an increase in apical peak systolic rotation but also from a decrease in rotational deformation delay. The function of subendocardial fibres declines with age, even in normal hearts [33,34]. Loss of the opposed action of subendocardial fibres will allow the subepicardial fibres to cause more pronounced left ventricular apical rotation and thereby left ventricular twist. Time-topeak left ventricular basal rotation remained relatively unchanged with aging, whereas left ventricular apical peak rotation occurred later in systole with advancing age, approaching time-to-peak basal rotation and thereby decreasing rotational deformation delay. Although the increase in time-to-peak left ventricular apical rotation may be caused by an increase in collagenous tissue in the conduction system with advancing age [34], this would implicate an increase in time-to-peak left ventricular basal rotation as well, leaving rotational deformation delay unchanged. The increase in time-to-peak left ventricular apical rotation with advancing age may also be explained by prolonged contraction duration, which was previously found in aged myocardium of animals [35,36]. This prolonged contraction duration results from a prolonged active state rather than changes in passive properties or myocardial catecholamine content [37]. Whether this is the true explanation of the increase in time-to-peak left ventricular apical rotation with advancing age, and why time-to-peak left ventricular basal rotation would not be influenced by this phenomenon, still needs to be clarified. Nevertheless, both increased left ventricular apical rotation and decreased rotational deformation delay seem to be charac‐ teristics of "physiological cardiac aging", and may contribute to the preservation of left ventricular ejection fraction in the elderly.
