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Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota
Submitted 16 February 2005 ; accepted in final form 16 May 2005
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ABSTRACT |
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 TOP ABSTRACT METHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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myocardial contraction; mechanics; echocardiography; tissue Doppler imaging; isovolumic contraction; isovolumic relaxation
Investigation of the short-lived and highly localized isovolumic movements demands the use of a high temporal and spatial resolution imaging method. Tissue Doppler imaging (TDI) and strain rate (SR) imaging are relatively recent ultrasonographic techniques that measure myocardial velocities and deformation rates, respectively (4, 9, 12, 23, 26, 35, 49). These techniques are suitable for a quantitative assessment of myocardial function within different phases of a cardiac cycle and selectively within myocardial layers (29, 48).
It has been speculated that IVC waveforms may not reflect regional myocardial shortening but, rather, result from oscillations caused by atrial contraction, mitral valve closure, or isometric tensing of the myocardial wall (27, 38). Likewise, no explanation exists regarding the TDI waveforms during IVR. Whether biphasic waveforms could result from functional nonhomogeneity and the anisotropic properties of the myocardial wall remains to be clarified.
Anatomical dissections have highlighted the helical orientation of myocardial fibers: subepicardial fibers spiral along a left-handed helix, whereas the subendocardial fibers course in a nearly orthogonal right-handed helical direction (8, 13, 15, 20, 43). Mathematical models and experimental observations suggest that this complementary arrangement of myocardial fibers provides increased efficiency and contributes to uniform redistribution of stresses and strains across and along the cardiac wall (45). Limited data exist regarding transmural synchrony of deformation during cardiac isovolumic phases. Shortening of the subendocardium precedes that of the subepicardium (2). Initiation of shortening in the subendocardium during IVC would likely result in transient asynchronous motion, since shortening within the isovolumic period would require compensatory expansion in an adjoining segment or the same segment in a different direction. Asynchronous shortening and lengthening of the LV could explain the occurrence of biphasic TDI waveforms during IVC and IVR (12).
The present study investigated the differences in velocity and deformation rates selectively within the subendocardial and subepicardial layers of apical, mid, and basal segments of the LV wall during isovolumic phases. We hypothesized that the regional biphasic motion observed by TDI during IVC and IVR occurs because of two counterdirectional regional deformations in which shortening in one direction is accompanied with reciprocal lengthening in the other direction or vice versa.
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METHODS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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Based on the knowledge gained from the anatomical studies, we practiced implantation, standardization, and optimization of the arrangement of sonomicrometry crystals in four porcine beating hearts in situ to reproducibly record strains from the oblique right- and left-handed helical directions in the subepicardial and subendocardial regions. The anterior wall was divided into apical, mid, and basal segments. Regional linear myocardial deformation was measured using ultrasonic crystals (Sonometrics, London, Ontario, Canada) implanted subendocardially and subepicardially so that they formed corners of quadrangles in each of the three anterior LV segments (Fig. 1). The long axis of the LV was defined by a crystal implanted on the tip of the LV apex and another implanted at the base of the LV near the bifurcation of the left main coronary artery. Each segment had a quadrangular arrangement, one on the subepicardial and the other on the subendocardial region, with each of the sides measuring 1.5–2 cm in length. Two sides of each quadrangular array of sonomicrometry crystals were parallel to the LV long axis (90°), and the other two were parallel to the circumferential plane (0°). The right and left diagonals defined the directions along 45° and 135°, respectively. It was possible to implant crystals accurately in the subepicardial region since the subepicardial left-handed helical myocardial fiber direction is evident even on the surface of a beating heart. The epicardial crystals were secured with 4-0 polypropylene sutures. For placement of the subendocardial crystal, the end-diastolic thickness of myocardium was measured at the site of implantation using a 13-MHz, high-resolution linear array transducer (GE Healthcare, Milwaukee, WI). The epicardial surface was punctured using a needle with a smaller diameter than the wire of the crystal. The crystals were inserted in the subendocardial region at a desired location using a plastic introducer with a preplaced marker that indicated the desired depth. The relation between the crystal location and subendocardial and subepicardial muscle fiber arrangement was confirmed by dissecting the explanted cardiac specimens. The subepicardial fibers aligned with the left-hand diagonal direction (135°). The subendocardial fiber direction aligned with the crystals placed along the right-hand diagonal direction (45°). The utility of such a grid-like arrangement, which samples oblique deformations from the LV wall within sectors spanning limits of 22.5°, has been previously reported (21).
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Sonomicrometry. Regional linear myocardial deformation was measured using 16 (2 mm) ultrasonic crystals (Sonometrics) implanted in groups of four at equal distances to form corners of quadrangles that defined each segment of the LV wall, following the design developed in the pilot studies. Sonomicrometry data were digitized at a sampling frequency of 250–300 Hz and analyzed offline with dedicated software (Cardiosoft, Sonometrics). The use of sonomicrometry has been validated for direct measurement of motion in cardiac muscles (9, 14).
Echocardiography. Echocardiography was performed using a Vivid 7 ultrasound system (GE Healthcare) and a 2.5-MHz transducer. Two-dimensional color Doppler myocardial imaging data were recorded from the LV using apical views at a scan rate of >200 frames/s. For real-time Doppler myocardial imaging scanning, the sector was limited to 30°. The anterior wall was aligned in parallel with the central axis of the transducer, and the velocity scale was optimized to avoid aliasing. Offline measurements were performed with dedicated software (EchoPAC, GE Healthcare) for analyzing regional myocardial velocities and SRs.
Hemodynamic and bipolar electrical activation. Surface electrocardiography, intracardiac pressures, bipolar regional myocardial electrical potential, and myocardial deformation obtained by sonomicrometry were recorded simultaneously. Heart rate and pressure data were measured and averaged over three continuous cardiac cycles in sinus rhythm for each sampling period.
Four crystals had special bipolar electrodes sealed on the surface. One pair was positioned in the subendocardial and subepicardial region of the apical segment. Another pair was placed in the subendocardial and subepicardial region of the basal segment. Electrical signals from the bipolar electrodes were digitized by an analog-to-digital converter (Sonometrics) and stored in a computer for offline analysis. The onset of the bipolar signals was marked at the steepest portion of the initial deflection of the QRS complex for calculating the electrical activation delay between the subendocardial and subepicardial electrodes.
Sonomicrometry. Optimal sonomicrometry recordings were present in 23 of the 24 LV segments (7 basal, 8 mid, and 8 apical segments). Linear deformations were obtained from six different locations within each segment (4 sides and 2 diagonals of the quadrangular crystal array), and instantaneous linear deformation rate (natural SR) was calculated from sonomicrometry data tracings. After each study, animals were euthanized, and the hearts explanted and were dissected to confirm that the position of crystals closely matched the fiber direction.
IVC was defined from the LV, aortic, and left atrial pressure tracings as the interval between LV and left atrial pressure crossover to LV and aortic pressure crossover. IVR was defined as the interval between the peak negative LV change in pressure over time to the crossover between LV and left atrial pressure in diastole.
Peak shortening and lengthening SRs were measured for each phase, and the net deformation rate was expressed as the difference of the peak shortening and lengthening SRs.
Regional myocardial velocities and SRs. Tracings of mean myocardial velocity and SRs were obtained from the basal, mid, and apical segments of the anterior LV wall. Measurements were taken from the subendocardial region with a sampling area of 3 x 3 mm. Longitudinal SR was estimated by measuring the spatial velocity gradient over a distance of 6 mm. The region of interest was tracked spatially throughout the cardiac cycle for obtaining values from the same region of subendocardium and for avoiding sampling of the LV cavity. Peak contraction and expansion waves during different periods of the cardiac cycle were identified. The IVC phase was identified as the interval between the Q-wave and opening of the aortic valve on the two-dimensional echocardiographic cine loop. IVR was defined as the period between the end of the T-wave on electrocardiography and the opening of the mitral valve. The IVC and IVR time phases were extrapolated on the TDI curves for cardiac cycles with similar R-R interval. SR waveforms were biphasic in 18 of the 24 LV segments during IVC and 20 of the 24 segments during IVR.
Statistical analysis. All data are expressed as means ± SD. After the data for normal distribution were assessed, the SR values obtained in the fiber vs. cross-fiber directions and circumferential vs. longitudinal directions for different phases of the cardiac cycle were compared by using a two-tailed paired t-test. Linear regression was used for comparing SR obtained by TDI and sonomicrometry, and the SRs were expressed with their correlation coefficient (r) and P value. A P value of <0.05 was considered statistically significant.
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RESULTS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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Electrical activation sequence. The earliest electrical activation within the LV free wall was recorded from bipolar electrodes implanted in the apical subendocardium. The apex-to-base endocardial activation delay measured 8.3 ± 4.2 ms. The transmural delay of electrical activation between the subendocardial and the subepicardial region was 9.2 ± 5.8 ms at apex and 9.6 ± 6.2 ms at base (P > 0.99). The time interval between the onset of electrical depolarization in the apical subendocardial and basal subepicardial region was significantly longer than the time interval between electrical depolarization of the apical and basal subendocardial region (18.5 ± 9.3 vs. 8.3 ± 3.5 ms; P = 0.01) (Fig. 2).
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DISCUSSION |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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Earlier studies have described the transmural variations in myocardial fiber and cross-fiber strains and documented substantial transmural tethering of fiber deformation (5, 28, 44, 47). This tethering has been used to explain shortening of the subendocardium in its cross-fiber direction during ejection. An association between subepicardial fiber shortening and subendocardial cross-fiber shortening has also been documented (36). Our results are consistent with the presence of extensive transmural tethering, wherein shortening of fibers in outer layers, which lie orthogonal to the subendocardial fibers, influence cross-fiber SRs in the subendocardial region during LV ejection.
Cardiac isovolumic phases are characterized by transient LV reshaping, which produces rapid variations in regional velocities (26). Rushmer (39) showed that LV geometric changes during the initial phases of systole were not isometric but were characterized by abrupt expansion of the external circumference such that the chamber assumed a more spherical configuration with a rise in LV pressure. Subsequent investigations showed that the external LV could assume a spherical (18, 40) or an elliptical configuration (19, 33) and that this change was a function of the LV volume (37). Advent of TDI facilitated quantification of LV function at the regional level, and positive and negative components of myocardial velocities during IVC and IVR were observed in both open-chest experimental animal models and human studies (11, 12, 26, 31). The isovolumic waveforms were, however, shown to be susceptible to temporal averaging and filtering algorithms (16). It remained unclear whether the negative and positive waves reflect random noise, asynchronous deformations, or oscillations arising elsewhere. Lyseggen et al. (27) hypothesized that IVC waves represented vibrations caused by atrial contraction; however, in their study, IVC signals were recorded even in the absence of atrial contractions. It was further suggested that LV isovolumic movements may only indicate vibrations produced by "isometric" tensing of the LV wall (27, 38). However, our observations, like some earlier investigations (18, 19, 33, 39, 40), confirm that cardiac muscle behavior during IVC and IVR cannot be considered isometric. TDI waves, therefore, most likely capture an asynchronous myocardial wall movement that results from nonuniform deformations of different myocardial layers.
For the first time, there is clarification of the selective contributions of the subendocardial and subepicardial layers during IVC and IVR. IVC is initiated with subendocardial fiber shortening, whereas IVR results from subepicardial fiber lengthening. Because the two layers are tethered and have a near orthogonal fiber arrangement, deformation of one layer in the fiber direction influences the cross-fiber deformation of the other layer and vice versa. The observations regarding subepicardium driving relaxation during IVR is in close agreement with a recent study that used cineangiographic analysis of implanted transmural markers in the LV wall and showed considerable transmural heterogeneity in three-dimensional fiber sheet strains in the LV anterior wall during the isovolumic phases of the cardiac cycle. IVR was characterized with significant stretch along the epicardial myofiber direction and accompanied with shortening and shear along the endocardial fiber sheets (1).
We observed transient endocardial cross-fiber expansions during IVC and transient subendocardial fiber shortening during IVR. These movements during IVC and IVR occurred as part of two orthogonal movements of each layer in which shortening in one direction is accompanied with expansion in the other direction and vice versa. These reciprocal movements, seen more commonly near the mid and basal segments, probably reflect a movement that occurs without a change in LV volume, i.e., displacement in one direction is balanced by an opposite displacement in the orthogonal direction. Because Doppler shift is one dimensional, it registers components of the shortening and lengthening vectors that project along the line of ultrasound propagation.
Variations in subendocardial and subepicardial deformations may reflect the differences in physiological properties of the subendocardial and subepicardial myocytes. Subendocardial compared with subepicardial myocytes have a greater force of contraction and operate on a steeper active tension-sarcomere length relationship (7). Functional asynchrony at different depths has also been demonstrated in isolated papillary muscles (41). During isometric contraction, while the segments in the central portion of the muscle shorten, segments near the end either lengthen or show nonuniform patterns of shortening. This nonuniform pattern of segment length change has also been used for explaining how the central segments of papillary muscle continue to shorten beyond the time at which the developed force begins to fall. A "well-organized" functional heterogeneity is probably a characteristic feature and a prerequisite for normal performance of the cardiac muscle (30).
TDI is being increasingly used for guiding resynchronization therapy for heart failure. A recent study (3) indicated that patients undergoing cardiac resynchronization therapy may have near-normal LV endocardial activation times and a conduction block that is primarily transmural. Understanding the electrical and mechanical sequencing across the myocardial layers and how these phenomena associate with velocity and deformation waveforms seen by TDI would help to further refine the cardiac resynchronization therapy.
Isovolumic indices have also been reported to increase the ability to detect ischemic myocardium. The IVC phase during coronary ischemia may be altered by presystolic myocardial lengthening, whereas the IVR phase is characterized by postsystolic contraction (11, 17, 24, 25, 34). Such functional assessment is, however, nonspecific since postsystolic shortening has been found, for example, in hypertensive hearts (6, 42) and in normal individuals (46). Our sonomicrometry recordings indicate that physiological postsystolic shortening results from shortening along the endocardial fiber direction during IVR, particularly near the base. A positional variation of the ultrasonographic scan plane can result in preferential sampling of the shortening vector and explains the recording of postsystolic shortening in normal individuals.
Limitations. Derumeaux et al. (10) reported a reduction in magnitude of myocardial velocities after opening the chest. Nevertheless, biphasic waves during IVC and IVR have been reported in both open-chest models and clinical studies (11, 12, 26, 31). The variable effects of open-chest surgical preparation and varying loading conditions necessitate further confirmation in future investigations.
The quadrangular grid arrangement resulted in a pair of sonomicrometry crystals sampling SR within 22.5° of the true fiber orientation. Although this angular error would reduce the magnitude of the vector component of the measured deformation, our interpretations regarding the presence of shortening or lengthening should not be affected. SRs measured by sonomicrometry in the apical segment were higher than those measured by TDI. This likely resulted from the curvature of the apical segment and the resulting angle between the Doppler beam and the myocardial wall. Variations in the absolute value of SR measured by the two techniques could also have resulted from subsequent rather than simultaneous data acquisitions by sonomicrometry and echocardiography; this was unavoidable because acoustic signals generated by the two modalities interfere when used simultaneously. In addition, the absolute values of SRs are likely to differ to some extent since sonomicrometry provides the instantaneous vector of deformation, whereas TDI represents only a component of the resultant vector that is subtended along the ultrasonographic scan line.
In conclusion, subendocardial and subepicardial layers of anterior myocardium deform simultaneously during systolic ejection and diastolic filling. During isovolumic phases, however, transitional counterdirectional deformations occur. This is because IVC starts along the subendocardial myocardium, which forms a right-handed helix, whereas IVR is initiated along the subepicardial myocardium, which forms a subepicardial left-handed helix. The features of isovolumic deformation asynchrony confirm our hypothesis and establish the association between asynchronous motion of subendocardial and subepicardial layers and the biphasic isovolumic waves observed on TDI. The results reported here are steps toward improved noninvasive characterization of cardiac mechanical properties during the isovolumic phases of the cardiac cycle.
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GRANTS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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ACKNOWLEDGMENTS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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P. P. Sengupta is Recipient of the Young Investigator Award presented at the Young Investigator Award Sessions of the 15th Annual Scientific Sessions of the American Society of Echocardiography, San Diego, CA, June 26–30, 2004. GE Healthcare provided technical support.
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FOOTNOTES |
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The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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REFERENCES |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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, Peak deformation measured from 1 segment of 1 pig heart. A: peak shortening SRs during IVC measured from sonomicrometry crystals placed along the subendocardial fiber direction vs. peak longitudinal shortening SRs obtained by TDI during IVC. B: peak lengthening SRs during IVR measured from sonomicrometry crystals placed along the subendocardial cross-fiber direction and longitudinal SRs obtained by TDI during IVR.