DOI: 10.1148/radiol.2442060780
(Radiology 2007;244:411-418.)
© RSNA, 2007
Left Ventricular Spherical Remodeling and Apical Myocardial Relaxation: Cardiovascular MR Imaging Measurement of Myocardial Segments1
Monravee Tumkosit, MD,
Carla G. Martin, BS,
Ersin Bayram, PhD,
Timothy M. Morgan, PhD,
Kimberly S. Lane, RDCS,
Pairoj Rerkpattanapipat, MD,
Craig A. Hamilton, PhD,
Kerry M. Link, MD, and
W. Gregory Hundley, MD
1 From the Departments of Internal Medicine (Cardiology Section) (M.T., C.G.M., K.S.L., P.R., W.G.H.), Biomedical Engineering (E.B., C.A.H.), Radiology (K.M.L., W.G.H.), and Public Health Sciences (T.M.M.), Wake Forest University School of Medicine, Bowman Gray Campus, Medical Center Blvd, Winston-Salem, NC 27157-1045. Received May 3, 2006; revision requested June 26; revision received October 13; accepted November 3; final version accepted December 15. Supported in part by American Heart Association Grant-in-Aid 0250239N. M.T. supported by a grant from King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
Address correspondence to W.G.H. (e-mail: ghundley{at}wfubmc.edu).
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ABSTRACT
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Purpose: To prospectively evaluate left ventricular (LV) shape and regional relaxation to determine if rapid, early relaxation of the LV is lost with spherical remodeling of the LV.
Materials and Methods: This HIPAA-compliant study was approved by the institutional review board. All participants gave written informed consent. Cardiovascular magnetic resonance (MR) imaging and transthoracic echocardiography (TTE) were performed in 18 individuals. Each participant was classified into one of three groups according to LV shape and TTE-derived mitral filling parameters. Pairwise comparisons of cardiovascular MR imaging measurements of LV relaxation were made between healthy individuals and those with spherically shaped LVs.
Results: The LV regional relaxation rates were determined in a total of 108 basal, middle, and apical myocardial segments in 18 participants (13 women, five men; age range, 35–76 years). Participants with a spherically shaped LV (sphericity index, <1.5) and a mitral inflow velocity E wave/A wave ratio of less than 1.0 exhibited apical thinning velocities that were lower than those of healthy individuals (sphericity index, 
1.5) (P < .01). The ratio of LV relaxation velocities in the apical versus middle LV segments correlated significantly with sphericity index (R2 = 0.53; P = .0005).
Conclusion: LV apical relaxation velocities in participants with LV spherical remodeling (sphericity index, <1.5) were reduced compared with those of healthy individuals (sphericity index, 1.5).
© RSNA, 2007
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INTRODUCTION
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Left ventricular (LV) filling proceeds from the base to the apex because of a pressure gradient generated by the rapid, early relaxation of the LV apex (1,2). In patients with a dilated LV, the LV is often spherical and exhibits both reduced contraction and filling (1–3). Results of some studies (3) suggest that retarded LV filling is related to impairment of early myocardial relaxation. We hypothesized that rapid, early relaxation of the LV is lost with spherical remodeling because of abnormal relaxation of the LV apex. The purpose of our study was to prospectively evaluate LV shape and regional relaxation to determine if rapid, early relaxation of the LV is lost with spherical remodeling of the LV (4–6).
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MATERIALS AND METHODS
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This cross-sectional study was approved by the institutional review board and met all criteria associated with the Health Insurance Portability and Accountability Act. All participants gave written informed consent.
Study Population
Recruitment of participants who had previously undergone transthoracic echocardiography (TTE) occurred between March 1999 and June 2002. Participants (n = 18) were enrolled prospectively on the basis of (a) no contraindication to cardiovascular magnetic resonance (MR) imaging, including implanted pacemakers, defibrillators, or intracranial metal and (b) absence of a restrictive mitral inflow velocity pattern at TTE. Participants had neither conduction delays on their electrocardiograms (all QRS durations were < 120 msec) nor LV wall thickness of more than 13 mm at end diastole.
Participants were enrolled in one of three groups. The "normal" group consisted of seven healthy participants with an LV in the shape of a prolate ellipse (defined by a sphericity index of 1.5) (7,8) and a mitral inflow velocity E wave/A wave (E/A) ratio of more than 1.0 but less than 3.0 (9). These healthy participants had no cardiovascular illnesses or medical conditions and took no medications. The impaired relaxation group consisted of six participants with a sphericity index of 1.5 or greater and a mitral inflow velocity E/A ratio of less than 1.0. In this group, two of six participants were current smokers, and three of six participants had hypertension. The spherically shaped ventricle group consisted of five participants with a sphericity index of less than 1.5, an LV ejection fraction of less than 40%, and a mitral inflow velocity E/A ratio of less than 1.0 (n = 4) or more than 1.0 (n = 1; pseudonormal pattern). In this final group, two participants smoked, two had hypertension, one had diabetes mellitus, and two had had a prior non–ST segment-elevation myocardial infarction involving segments other than those assessed in this study.
TTE Assessment of Mitral Inflow Velocity
Each participant was scanned while in the left lateral decubitus position by one author (K.S.L.) who had 10 years ofRegistered Diagnostic Cardiac Sonographer certification. Recordings were performed with machines (Agilent Sonos 5500; Philips, Eindhoven, the Netherlands) equipped with a 2.5-MHz transducer. From the apical four-chamber view, mitral inflow velocities were obtained by using a pulse-wave Doppler sample volume placed at the mitral valve leaflet tips according to previously published techniques (7). The amplitude of the E and A waves, as well as their ratio, was determined. Tissue Doppler ultrasonographic (US) images were not acquired in the participants.
Cardiovascular MR Imaging and Detection of LV Regional Myocardial Relaxation
All participants were imaged while in a supine position with a 1.5-T cardiovascular MR system (CV/i; GE Medical Systems, Waukesha, Wis) and a phased-array surface coil placed around the chest. Multisection coronal gradient-echo sequences with breath holding were performed to obtain scout images of the chest and LV. A four-chamber plane, perpendicular to the course of the interventricular septum, was isolated for analysis.
Myocardial thinning and lengthening were quantified with the analysis of myocardial tissue tags placed perpendicular to the long axis of the LV (Fig 1). Approximately six to 10 tags placed parallel to each other and spaced 1.5 cm apart were applied throughout the LV, depending on the size of the ventricle. These tags appeared in late systole and were visible for approximately 700 msec through the remainder of the cardiac cycle in diastole. Triggering for tag introduction in the cardiovascular MR sequence occurred 200 msec after detection of the R wave on the electrocardiogram. This tagging delay allowed diastolic relaxation to be measured without tag fading. Phase-encoding grouping with view sharing and four views per segment were used to achieve a temporal resolution of 14–17 msec (with view sharing) or 28–34 msec (without view sharing) for measurement of LV diastolic relaxation (8). Gradient-echo cardiovascular MR acquisition parameters included a flip angle of 10°, a repetition time msec/echo time msec of 7.2/3.4, a field of view of 36 cm, a percent phase field of view of 0.75, a number of heartbeats per breath hold of 32, a receiver bandwidth of 31 kHz, a number of excitations of 0.75, a matrix of 256 x 256, and a section thickness of 8 mm.
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Figure 1: Top row: Images of mitral inflow velocity E/A ratios acquired with spectral Doppler US imaging at TTE. From apical four-chamber views, velocities were obtained with Doppler sample volumes placed at mitral valve leaflet tips in participants in normal (NML), impaired relaxation (IMP), and spherical LV (SPHR) groups. Bottom row: Four-chamber tagged cardiac MR images acquired with gradient-echo technique (7.2/3.4; flip angle, 10°; field of view, 36 cm; matrix, 256 x 256, section thickness, 8 mm) at late systole. On MR images, vertical white lines demonstrate length determinations (apex to mitral annulus relative to distance across width of LV cavity at level of papillary muscles [horizontal white lines]) used to calculate sphericity index. A = A wave, E = E wave.
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Three tags representing the apex, the middle, and the base of the LV were selected from the septum and lateral wall. The base was defined as 1.5 cm from the mitral annulus. The tag bisecting the middle papillary muscle layer was selected as the middle LV. The apical tag was identified as 1.5 cm from the epicardial surface of the LV apex (Fig 1). The linear dimension of each tag was measured every 15–17 msec from end systole (defined as the closure of the aortic leaflets) to end diastole (defined as the closure of the mitral leaflets). After acquisition, images were transferred to a workstation (Sun Microsystems, Mountain View, Calif) for analysis by using software developed in-house in Interactive Data Language (Research Systems, Boulder, Colo). Each image was magnified with interpolation by a factor of four for more precise placement of fiducial markers.
For assessment of LV regional thinning, the linear dimension from the endocardial to epicardial surface of the basal, middle, and apical tags was measured on each frame in diastole. Components of tags spanning papillary muscle tissue were excluded from analysis. LV regional lengthening was assessed by measuring a line generated perpendicular (90° precisely) from the tag at a distance of 1.5 cm toward an apical tag (Fig 2). The distance along this perpendicular line was assessed at each time point throughout the acquisition. The LV regional thinning and lengthening were assessed and measured by two authors (C.G.M., with 3 years of experience in cardiovascular MR imaging, with approval from W.G.H., with 12 years of experience) (9). Both authors were blinded to patient identifiers and group assignment.
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Figure 2: Cine gradient-echo cardiovascular MR images (7.2/3.4; flip angle, 10°; field of view, 36 cm; matrix, 256 x 256; section thickness, 8 mm) of early (top) and late (bottom) diastolic frame acquired in four-chamber view in participant in normal group. In each image, the moving blood pool in cavities (right atrium [RA], right ventricle [RV], left atrium [LA], left ventricle [LV]) appears white, and gray corresponds to chamber walls. Dark lines represent myocardial tissue tags used to assess regional thinning and lengthening (as shown in inset). Every 15–17 msec, the length of each myocardial tag was determined for assessment of regional myocardial relaxation velocities.
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Cardiovascular MR Imaging LV Ejection Fraction Measurements
LV ejection fraction measurements were calculated by one author (C.G.M.) with approval of another author (W.G.H.), according to previously published techniques (10,11) from a series of multisection, multiphase gradient-echo sequence images positioned perpendicular to the long axis of the LV (short axis); images spanned apex to base. The apical and short-axis sections were 9 mm thick with an intersection gap of 1 mm. Parameters included a 256 x 256 matrix, a temporal resolution of 40 msec, a field of view of 35 cm, a flip angle of 40°, 13.7/8.1, a number of views per segment of four, a percent field of view of 0.75, a number of excitations of 0.75, a number of heartbeats per breath hold of 32, and a receiver bandwidth of 31 kHz.
For LV ejection fraction measurements, the endocardial border of each section was planimetered manually at end diastole and end systole, and volumes were calculated by using the Simpson rule (10,11). End diastole was defined as the first frame in each sequence. To determine end systole, images were reviewed in cine format, and the frame with the smallest endocardial circumference was selected. Basal sections were reviewed in cine format to resolve structures for inclusion (the aortic outflow tract) or exclusion (left atrium and mitral leaflets) from the volume measurements.
Cardiovascular MR Imaging Sphericity Index
The sphericity index (Fig 1) was described according to previously published techniques as the LV long-axis length divided by the LV diameter in end systole and end diastole for each study (12,13). The LV long-axis length was measured from the endocardial border of the tip of the apex to the mitral valve annulus plane, and the diameter was measured at the middle papillary level from the endocardial borders of the lateral wall to the septum. A normal, prolate-ellipsoid LV was defined in this study as one with a sphericity index at end systole of 1.5 or greater; a spherical LV was defined as one with a sphericity index of less than 1.5 (12,13). Each measurement was obtained by one author (C.G.M.) with approval of another author (W.G.H.).
Data Analysis
For all segments, the regional thinning and lengthening velocity in millimeters per second was calculated, and the percentage of thinning and lengthening was defined as follows: percentage thinning and lengthening for each frame = (DF – IDES)/(DES – DED), where DF is distance at each frame, IDES is initial distance at end systole, DES is distance at end systole, and DED is distance at end diastole.
Further analysis included regional relaxation velocity ratios, which were calculated from the slopes of the lines that plotted the total difference in thinning against the time it took for each myocardial segment to reach 50% and 90% of its maximally thinned dimension. Ratios of the slope values to those of corresponding regional segments (apex to middle and apex to base) were calculated to determine the rate of thinning and lengthening of the regions with respect to one another. The ratios of regional relaxation velocity were correlated with sphericity index to determine the relationship between spherical shaped LVs and myocardial relaxation.
Statistical Analysis
All data were expressed as means ± standard deviations. The Fisher exact test was used to compare the proportion of men between pairwise groups. Pairwise comparisons were made between the impaired relaxation and spherically shaped ventricle groups and the normal group. Bonferroni adjustment for these two comparisons was used, and adjusted P values are reported. A P value of .05 or less was considered to indicate a significant difference. Given that the velocities and ratio of velocities were suspected a priori to exhibit a skewed distribution, P values for comparison of velocities and velocity ratios were based on a logarithmic transformation in which the analyses were performed on log (velocity) values. Additional analysis by using analysis of covariance was performed with age, sex, and the angle of the tags with the LV apex as a covariant to ensure that the baseline age and sex differences did not influence the overall difference in lengthening and thinning velocities. All analyses were performed by using software (SAS, version 9, 2003; SAS Institute, Cary, NC).
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RESULTS
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Because all participants successfully completed the imaging protocol, 108 segments were suitable for analysis. Of the 18 participants, 13 were women and five were men, with an overall age range of 35–76 years (Table 1).
Regional Myocardial Thinning and Lengthening Velocities
At 50% thinning, the average apical thinning velocities were lower in the spherically shaped ventricle group (8 mm/sec ± 6) than in the normal group (33 mm/sec ± 17) (P < .01) (Table 2). Because there was a discrepancy in age and sex among our participants, we adjusted our measured relaxation velocities for age and sex (Table 2). The average apical thinning velocity in the spherically shaped ventricle group (8 mm/sec ± 6) remained lower than that in the normal group (33 mm/sec ± 17) (P < .05). After adjustment for age, sex, height, weight, blood pressure, diabetes, and smoking habits, average thinning velocities in the LV apex at 50% thinning (5 mm/sec ± 9) remained significantly different in the spherically shaped ventricle group from those in the normal group (32 mm/sec ± 8) (P = .009). Two of five participants in the spherically shaped ventricle group had experienced prior myocardial infarction; their relaxation velocities in the apex were evenly distributed among those in the spherically shaped ventricle patient subgroup (they had the second and fourth highest values among the five participants with spherically shaped ventricles). The obliquity of the angles of the tags with the cardiac apex ranged from 21° ± 2 in the normal group to 24° ± 3 in the spherically shaped ventricle group (P = .56). After all values in Table 1 were adjusted for the angle of obliquity, the difference in thinning in the apex between the normal and spherically shaped ventricle groups remained significantly different.
Measurements of the lengthening rate of apical and middle segments in individuals with spherically shaped ventricles were different from those in individuals with ventricles in the shape of a prolate ellipse. When the apical segments had achieved 50% of their lengthened distance, velocities in apical, middle, and basal segments for the normal group were 34 mm/sec ± 20, 24 mm/sec ± 12, and 20 mm/sec ± 14, respectively. Apical, middle, and basal segmental velocities were 29 mm/sec ± 30 (median, 28 mm/sec; range, 18–80 mm/sec), 21 mm/sec ± 8, and 18 mm/sec ± 17, respectively, for those in the impaired relaxation group. Apical, middle, and basal segmental velocities were 5 mm/sec ± 2, 4 mm/sec ± 1, and 14 mm/sec ± 10, respectively, for those in the spherically shaped ventricle group. Regardless of whether segments were present in the septal or lateral wall, myocardial lengthening velocities in the apical and middle segments were lower for individuals with spherically shaped ventricles (sphericity index, <1.5) than for healthy individuals (sphericity index, 1.5) (P < .05). There was no significant difference in basal lengthening velocities among the three groups.
Ratios of Regional Relaxation Velocities
Ratios of the apical to middle and apical to basal segment velocities for the septum and lateral wall (Table 3) were more than 1.0 in the normal and impaired relaxation groups and were less than 1.0 in the spherically shaped ventricle group (P < .05) compared with the normal group. The ratios of the apical to middle segment relaxation velocities were significantly correlated (Fig 3) with the sphericity index (P = .0005).
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Figure 3: Graph of relationship between sphericity index and apical to middle segment regional thinning velocity ratio at 50% thinning for 18 participants.  = data from one participant.
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DISCUSSION
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Our results indicate that in participants with a sphericity index of 2.4 ± 0.5 (LV with the shape of a prolate ellipse), LV myocardial relaxation velocities are higher in the apical segment than in the middle and basal segments. In participants with a sphericity index of 1.3 ± 0.2 (spherically remodeled), apical segmental myocardial relaxation (both radial thinning and longitudinal lengthening) velocities are reduced when compared with those of healthy participants after adjustment for age and sex. We observed a disparate reduction in the ratio of apical to middle segment velocity that correlated significantly with sphericity index, which implied that apical relaxation is reduced in participants with LV spherical remodeling compared with that of healthy individuals with an LV in the shape of a prolate ellipse. In addition, the ratio of apical to middle segment relaxation diminishes as the LV sphericity index decreases.
Two other studies (14,15) have focused on regional LV diastolic relaxation. Fonseca et al (14) studied healthy participants and found that LV relaxation was initiated in the apex, followed by middle and basal segments in the anterior, posterior, septal, and lateral walls. Their results also demonstrated a reduction in relaxation of the LV wall velocities as individuals' age increased. Our findings in participants with prolate ellipsoid LV shape and both normal and abnormal mitral inflow corroborate these findings.
Silva et al (15) used Doppler tissue US imaging during TTE to assess regional LV relaxation in participants ranging in age from 12 to 59 years. Their results differ from ours in that peak diastolic relaxation velocities were highest in the base, followed by the middle, and then the apical segments of the LV. There are explanations for the difference. First, many elderly participants with E/A mitral inflow ratios of less than 1.0 and with LV hypertrophy (factors known to impair LV relaxation) were included in the healthy group reported by Silva et al. To eliminate confounding that could be introduced from known causes of altered LV relaxation, none of the participants in our study exhibited LV wall thickness of more than 13 mm, a QRS duration of 120 msec or longer, or a restrictive mitral inflow velocity pattern. Second, in the Silva et al study, a specific time during diastole, 459 msec ± 18 after the E wave, was used to collect the velocity measurements, whereas we analyzed data throughout diastole. Selection of the point in time used in the Silva et al study for our data set indicates that apical and middle segmental thinning velocities had already peaked relative to basal segmental thinning velocity. In this regard, our data are similar to those of Silva et al.
Our findings have clinical importance. In healthy participants with ventricles in the shape of a prolate ellipse, LV filling, an important contributor to forward cardiac output, occurs because of a pressure gradient generated from the apex to the base of the LV (1–3,16). In participants with spherically shaped ventricles, there is abnormal relaxation of the apex. Thus, further investigation is warranted to determine the relevance of impaired apical diastolic relaxation to overall LV dysfunction in participants with spherically shaped ventricles. In addition, surgical remodeling (17,18), myocellular regeneration with stem cells (19,20), and pacing strategies (21,22) have been proposed to restore the prolate ellipsoid shape of spherical ventricles and "reverse remodel" the heart. Perhaps apical relaxation should be considered an outcome measure in these situations.
We recognize the following limitations of our study. First, although numerous myocardial segments were evaluated, the number of participants studied was relatively small, and infarcted tissue or regions of dyskinesis or akinesis were absent. Further studies with larger numbers of participants are warranted to determine the association of sphericity and apical relaxation in participants with these comorbidities. Second, we used tags placed perpendicular to the long axis of the LV in the four-chamber plane to assess both thinning and lengthening rates of relaxation. While this technique is similar to that implemented at TTE (6), it does not account for the torsion or rotation of the LV myocardium during diastole. In addition, the obliquity of the angle of the tags with the LV apex in participants with a spherical ventricle can lead to underestimation of apical thinning and lengthening velocities. In future studies, analysis of data by using three-dimensional techniques, such as tagging with harmonic phase analysis (23,24), phase-contrast velocity mapping (tissue phase mapping) (25), or displacement encoding stimulated echo (26), should be used to quantify the apical relaxation.
In conclusion, in participants with spherical remodeling of the LV (sphericity index, <1.5), LV diastolic relaxation in the apical segments was reduced compared with that in healthy participants with an LV in the shape of a prolate ellipse (sphericity index, 1.5).
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ADVANCES IN KNOWLEDGE
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- Compared with healthy participants with the left ventricle (LV) in the shape of a prolate ellipse, participants with spherically shaped LVs exhibited a significant reduction in apical myocardial relaxation velocity (P < .01).
- Decreased apical myocardial relaxation velocity correlates with LV sphericity index (P = .0005).
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IMPLICATIONS FOR PATIENT CARE
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- In patients with spherically shaped left ventricles (LVs), diastolic relaxation in apical segments is reduced.
- Apical myocardial relaxation can be studied further as an outcome measure for patients undergoing reverse LV remodeling procedures involving myocellular regeneration or pacing strategies.
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FOOTNOTES
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Abbreviations: LV = left ventricle • TTE = transthoracic echocardiography
Authors stated no financial relationship to disclose.
Author contributions:Guarantors of integrity of entire study, K.M.L., W.G.H.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; manuscript final version approval, all authors; literature research, C.G.M., K.S.L., K.M.L., W.G.H.; clinical studies, C.G.M., K.S.L., P.R., K.M.L., W.G.H.; statistical analysis, C.G.M., E.B., T.M.M., K.S.L., C.A.H., W.G.H.; and manuscript editing, M.T., C.G.M., E.B., K.S.L., P.R., C.A.H., K.M.L., W.G.H.
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ABSTRACT
INTRODUCTION
