- Email: [email protected]
Left Ventricular Mechanics in Idiopathic Dilated Cardiomyopathy: Systolic-Diastolic Coupling and Torsion
HEART FAILURE
Left Ventricular Mechanics in Idiopathic Dilated Cardiomyopathy: Systolic-Diastolic Coupling and Torsion Jaroslav Meluzin, MD, PhD, FESC, Lenka Spinarova, MD, PhD, FESC, Petr Hude, MD, Jan Krejci, MD, Hana Poloczkova, MD, Helena Podrouzkova, MD, Martin Pesl, MD, Marek Orban, MD, Ladislav Dusek, MD, PhD, and Josef Korinek, MD, PhD, Brno and Prague, Czech Republic; Rochester, Minnesota
Background: In idiopathic dilated cardiomyopathy (IDC), myocardial deformational parameters and their mutual relationships remain incompletely characterized. Methods: Thirty-seven patients with IDC underwent two-dimensional speckle-tracking echocardiography (2D-STE) to assess left ventricular rotation, torsion, and longitudinal, circumferential, and radial systolic and diastolic strains and strain rates. Additionally, 2D-STE was performed in 14 controls. Results: All deformational parameters on 2D-STE were significantly lower in patients with IDC compared with controls. Seven patients exhibited opposite basal (positive, counterclockwise) and 11 patients exhibited opposite apical (negative, clockwise) rotation at end-systole. Circumferential, radial, and longitudinal early diastolic strain rates were correlated most strongly with the corresponding spatial components of systolic deformation. Conclusion: In patients IDC, all torsional, systolic, and diastolic deformational parameters were decreased. Corresponding three-dimensional components of systolic and diastolic deformations were closely coupled. Considerable variation in the direction of basal and apical rotation exists in a subset of patients with IDC. (J Am Soc Echocardiogr 2009;22:486-493.) Keywords: Left ventricular rotation, Torsion, Two-dimensional strain echocardiography
During the development of congestive heart failure (CHF) in patients with idiopathic dilated cardiomyopathy (IDC), the left ventricle undergoes complex changes in geometry, accompanied by alteration of the left ventricular (LV) chamber and myocardial systolic and/or diastolic function. LV ejection fraction (EF) is the most common clinically used parameter for the quantification of the severity of LV systolic dysfunction in patients with CHF and has been used as a prog-
From the 1st Department of Internal Medicine/Cardioangiology, St Anna Hospital, ICRC, Masaryk University, Brno, Czech Republic (J.M., L.S., P.H., J. Krejci, H. Poloczkova, H. Podrouzkova, M.P., M.O.); the Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, MN (M.O., J. Korinek); the Institute of Biostatistics and Analyses, Masaryk University, Brno, Czech Republic (L.D.); and the Division of Cardiovascular Diseases, 2nd Department of Internal Medicine, General University Hospital, 1st School of Medicine, Charles University, Prague, Czech Republic (J. Korinek). The study was supported in part by a grant of the Ministry of Education of the Czech Republic (no. 0021622402). J.K. was supported by a travel grant from the Czech Society of Cardiology. Reprint requests: Jaroslav Meluzin, MD, 1st Department of Internal Medicine/ Cardioangiology, St Anna Hospital, Pekarska 53, 65691 Brno, Czech Republic (E-mail: [email protected]). 0894-7317/$36.00 Copyright 2009 by the American Society of Echocardiography. doi:10.1016/j.echo.2009.02.022
486
nostic marker.1,2 However, EF describes LV systolic chamber function and does not always reflect global LV myocardial contractile performance or provide information about individual myocardial deformational components, which may have prognostic utility, as shown in hypertensive heart disease and diastolic heart failure.3 Moreover, the quality of life and prognoses of patients with CHF are associated not only with systolic LV chamber or myocardial function but also with changes in LV diastolic function. Indeed, LV diastolic dysfunction has been associated with a high frequency of cardiac events during long-term follow-up in patients with CHF.4,5 Systolic and diastolic LV dysfunction frequently coexist, and it has been suggested that systolic and diastolic heart failure may be two phases of one pathophysiologic process.6 However, the incomplete understanding of systolic-diastolic coupling on regional and global myocardial and chamber level has triggered extensive debate on the relationship and the extent of interplay between various components of systolic and diastolic function.7-9 Initially, the longitudinal component of LV systolic dysfunction was shown to be associated with LV diastolic dysfunction7,8 in patients with CHF. However, myocardial deformation occurs in 3 dimensions and can be characterized not only in longitudinal but also in circumferential and radial directions. Little is known about the relationships between individual spatial components of systolic and diastolic dysfunction. In addition, normal myocardial fiber orientation may change with the alteration of LV geometry in IDC and result in changes in LV rotation or torsion,10-12 both of which characterize different aspects of LV global performance than EF.
Meluzin et al 487
Journal of the American Society of Echocardiography Volume 22 Number 5
The recently introduced and validated modality of high-spatialresolution two-dimensional speckle-tracking echocardiography (2D-STE) has enabled the evaluation of numerous deformational parameters in longitudinal, circumferential, and radial directions characterizing LV systolic and diastolic performance, such as systolic strain,13-21 systolic and early diastolic strain rate,14,19,20,22 and LV basal and apical myocardial rotation and torsion.21,23-31 In this regard, 2D-STE may allow a more detailed analysis of individual components of LV systolic and diastolic function as well as the assessment of their mutual relationships, which remain incompletely characterized. Thus, the aims of our study were to characterize the longitudinal, circumferential, and radial components of LV systolic and diastolic myocardial function and study their mutual relationships and to quantify and characterize LV rotation and torsion in patients with IDC.
METHODS Patient Population We enrolled 52 consecutive patients with symptomatic CHF due to IDC, who were referred to St Anna Hospital (Brno, Czech Republic) for detailed cardiologic assessments, which included histories, physical examinations, routine blood tests, 12-lead electrocardiography, chest radiography, and conventional transthoracic echocardiography prior to right-heart catheterization. The diagnosis of IDC was made on the basis of echocardiography (LV dilation and diffuse hypocontractility), electrocardiography (absence of Q waves), clinical criteria (no angina pectoris, no history of myocardial infarction), and coronary angiography (no significant coronary artery stenosis) or bicycle spiroergometry (no electrocardiographic signs of ischemia). The inclusion criteria of the study were the presence of CHF with LV systolic dysfunction, good-quality conventional transthoracic echocardiographic imaging, and sinus rhythm on electrocardiography. The exclusion criteria included the presence of coronary artery disease, congenital or valvular heart disease, hyperthyroidism, or any systemic or metabolic disease known to induce cardiomyopathy. Of 52 patients with IDC, 47 had acceptable-quality precatheterization conventional echocardiographic images and underwent conventional and speckle-tracking echocardiography. Coronary angiography was performed in 35 of 47 patients (74%; 89% in those aged > 40 years). The remaining 12 patients underwent bicycle spiroergometry. There were 38 men (81%) and 9 women (19%) (mean age, 48.0 6 1.8 years; range, 22-72 years). Sixteen patients (34%) had hypertension and 8 patients (17%) were treated for diabetes mellitus. Medical therapy comprised angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (47 patients [100%]), b-blockers (46 patients [98%]), furosemide (46 patients [98%]), spironolactone (44 patients [94%]), and digoxin (36 patients [77%]). Twenty-two patients (47%) were in New York Heart Association class II, 23 (49%) were in class III, and 2 (4%) were in class IV. Fifteen age-matched and gender-matched healthy volunteers (11 men and 4 women; mean age, 44.9 6 3.1 years; range, 26-64 years; P = NS vs patients with IDC) served as a control group and underwent conventional echocardiography along with 2D-STE. They had normal echocardiographic results and no risk factors for coronary artery disease, and they used no medications. All patients gave their written consent to the investigations. The study complied with the Declaration of Helsinki and was approved by the ethics committees at St Anna Hospital and the Mayo Clinic College of Medicine.
Conventional Echocardiography Both conventional and speckle-tracking echocardiography were performed using Vivid 7 (GE-Vingmed Ultrasound AS, Horten, Norway) with an M3S transducer. Transmitral and aortic flows were recorded using pulsed Doppler echocardiography. The sample volume with a fixed length of 5.1 mm was placed between the tips of the mitral and aortic leaflets. All Doppler recordings were done during shallow respiration or end-expiratory apnea. LV volumes and EFs were calculated using the biplane method according to the modified Simpson’s rule.32 2D-STE The detailed principles and methodology of 2D-STE have been described previously.14,33 In our study, high-spatial-resolution 2D-STE was used, allowing the more accurate evaluation of low deformation values,17 which can be expected in patients with IDC. Grayscale two-dimensional images (frame rate, 44-82 frames/s) were recorded for offline analysis. Apical 4-chamber and 2-chamber views were used for longitudinal strain and strain rate analysis, and parasternal short-axis (SAX) views at the base (clearly depicting the tips of the mitral valve leaflets), at the level of papillary muscles, and at the apex (as close to the tip of the apex as possible, optimally with the minimal circular LV cavity present at end-systole) were used for circumferential and radial strain and strain rate, rotation, and torsion analysis. Three to 5 consecutive cardiac cycles in each view were digitally stored for subsequent offline analysis using EchoPAC PC SW 6.1.0 (GE-Vingmed Ultrasound AS). During the analysis, LV endocardium was traced at end-systole, and if necessary, a software-generated region of interest was adjusted to an ideal width of myocardial wall. The myocardium in each echocardiographic view was automatically divided into 6 predefined segments, and the regional longitudinal, circumferential, and radial strain as well as the mean longitudinal and circumferential strain, strain rate, and rotation curves were displayed in different colors. Except for global radial strains and strain rates, all the deformational parameters were obtained directly from the mean deformational curves (Figure 1), which were provided by the software. At the time of analysis, EchoPAC software did not provide mean radial strain or strain rate, so the mean radial strain rate curves were calculated as an average of 6 segments every time frame and plotted, and strain rate parameters were measured. The mean radial end-systolic strain was calculated for each SAX view as the sum of end-systolic radial strain values in all 6 segments divided by 6. To standardize the parameter analysis, the starting points of rotation and deformation curves were manually placed at the onset of the QRS complex in all patients. To determine the phases of the cardiac cycle, the timings of aortic and mitral valve opening and closure were assessed using pulsed-wave Doppler recordings of aortic and transmitral flows. In addition, the software automatically evaluated the tracking quality of individual segments and defined whether or not they were acceptable for data analysis. Myocardial Strain, Strain Rate, Rotation, and Torsion Parameters Assessed on 2D-STE For the analysis of global strain, strain rate, and rotation parameters, the mean curves created by the software in each echocardiographic view were used. These mean curves represented at any given time point the average of individual curves of all 6 segments into which the myocardium was divided in standard fashion (Figure 1) by the software. Longitudinal strain and strain rate values were obtained from the apical 4-chamber and 2-chamber views and circumferential
488 Meluzin et al
Journal of the American Society of Echocardiography May 2009
Figure 1 Examples of normal and opposite basal and apical rotation curves obtained from a healthy volunteer and from two patients with IDC. Each color of the deformational curve represents one segment of the left ventricle, and the dashed white curve depicts mean rotation of 6 segments. (Top) Normal negative (clockwise) late systolic and end-systolic basal rotation (A) and normal positive (counterclockwise) late systolic and end-systolic apical rotation (B) in a healthy volunteer. (Middle) A patient with IDC with opposite (positive) late systolic and end-systolic basal rotation (C) and normal positive direction of apical end-systolic rotation (D). (Bottom) A patient with IDC with normal negative direction of basal end-systolic rotation (E) and opposite (negative) end-systolic apical rotation (F). and radial values from 3 parasternal SAX views. To obtain functional data from the corresponding time points, the end-systolic values (at the time of aortic valve closure) were used for the determination of global strain, basal and apical rotation, and torsion. Thus, global
circumferential, longitudinal, and radial end-systolic strain were calculated as follows: circumferential ES = (mean basal circumferential ES + mean midcircumferential ES + mean apical circumferential ES)/3, longitudinal ES = (mean longitudinal ES in the apical 4-chamber view
Meluzin et al 489
Journal of the American Society of Echocardiography Volume 22 Number 5
+ mean longitudinal ES in the apical 2-chamber view)/2, and radial ES = (mean basal radial ES + mean midradial ES + mean apical radial ES)/3, where ES is end-systolic strain. The global circumferential, longitudinal, and radial strain rate parameters, including systolic and early and late diastolic strain rates, were calculated using the analogous approach. LV basal and apical rotation were analyzed from the parasternal SAX views at the base and at the apex. LV rotation was expressed in degrees. Negative values indicated clockwise and positive counterclockwise rotation (as viewed from the apex). Mean basal and apical end-systolic rotation were determined as the cross-sections of the mean basal and apical rotation curves with the line defining the time of aortic valve closure. LV end-systolic torsion was defined as the difference between apical end-systolic rotation and basal end-systolic rotation21,34,35 and was divided by the end-diastolic LV longitudinal length between the LV apex and the mitral plane. To better characterize LV basal and apical rotation and their anomalies, LV mechanical asynchrony was quantified. Parasternal SAX views at the level of papillary muscles were used to assess circumferential and radial asynchrony, and apical 4-chamber views were used to determine longitudinal asynchrony. The time from the onset of the QRS complex to peak strain was measured for all 6 regional strain curves in each view. In case of more clearly separated strain peaks, the maximal systolic peak was used. LV mechanical dyssynchrony was defined as the difference between the earliest and the latest strain peaks and was calculated for circumferential, radial, and longitudinal strains. Speckle-tracking analysis was performed offline by two experienced observers (J.M. and M.O.). The results of all parameters were obtained as a mean of 2 or 3 consecutive heart cycles. Statistical Analysis Data are expressed as mean 6 SEM. All parameters were tested prior to any statistical analysis to determine if they were normally distributed. All distribution patterns were normal, and neither transformation nor exclusion of outliers was needed. Comparisons of continuous variables across the groups were made using one-way analysis of variance, and the Tukey-Kramer test was used for multiple comparisons between the groups. The maximum likelihood c2 test was applied to compare differences among the groups of patients in binary or categorical variables. The correlation structure set of metric parameters was inspected using Pearson’s product-moment correlation coefficient. P values < .05 were considered statistically significant. The reproducibility of deformational parameters was assessed in 10 randomly picked subjects. The interobserver and intraobserver variability were analyzed by two observers (J.M. and M.O.) by and one observer (J.M.) on two occasions $1 month apart for global parameters, including basal and apical end-systolic rotation, circumferential and longitudinal end-systolic strain, and circumferential and longitudinal peak systolic and early and late diastolic strain rates. The standard approach of Bland-Altman plotting was applied, numerically supported by the calculation of the mean absolute difference of repeated measurements, its 95% confidence limits, and the range.
RESULTS Of 47 patients and 15 controls enrolled in the study, 10 patients and 1 control were excluded from the final analysis. They had seg-
Table 1 Baseline characteristics of the final cohort of subjects Variable
Patients with IDC (n = 37)
Controls (n = 14)
P value
Age (y) Men Hypertension Diabetes mellitus EDVi (mL/m2) ESVi (mL/m2) LV EF (%)
46.7 6 1.9 32 (87%) 13 (35%) 6 (16%) 119.2 6 6.1 88.4 6 5.4 24.8 6 1.3
44.3 6 3.3 11 (79%) 0 0 52.1 6 2.4 19.7 6 1.1 62.9 6 1.1
.519 .498 .002 .042 <.001 <.001 <.001
EDVi, End-diastolic volume index; ESVi, end-systolic volume index. Data are expressed as mean 6 SEM or number (percentage).
ments of inadequate quality for speckle-tracking analysis in either basal or apical SAX views, not allowing the exact quantification of LV torsion, or in both the apical 4-chamber and 2-chamber views, not allowing the assessment of LV longitudinal function. Thus, the final study group comprised 37 patients with IDC and 14 controls. Their clinical characteristics are shown in Table 1. In 10 patients, in whom segments of poor speckle-tracking quality were confined only to the apical 2-chamber view, longitudinal function was evaluated only in the apical 4-chamber view. In 3 patients, the peak early and late diastolic strain rates could not be analyzed because of their fusion.
Myocardial Strain, Strain Rate, Rotation, and Torsion Parameters Assessed on 2D-STE LV systolic and diastolic deformational parameters derived from 2D-STE are shown in Table 2. Compared with healthy controls, all deformational parameters were significantly lower in patients with IDC. In all control subjects, basal end-systolic rotation had a clockwise direction, resulting in negative basal end-systolic rotation values, whereas apical rotation was opposite (counterclockwise), resulting in positive apical end-systolic rotation values. Nineteen patients with IDC had normal directions of both basal (clockwise) and apical (counterclockwise) rotations. Interestingly and contrary to healthy subjects, 7 patients with IDC had opposite (ie, positive, counterclockwise) basal end-systolic rotation (mean, 1.0 6 0.2 ), and another 11 patients were found to have opposite (ie, negative, clockwise) apical end-systolic rotation (mean, 3.5 6 0.8 ). None of the patients exhibited combined opposite basal and apical endsystolic rotation. Therefore, the group of patients was further analyzed and divided into subgroups according to the direction of apical and/or basal rotation (Table 3). End-systolic torsion differed significantly among all 3 subgroups, being lowest in the subgroup with opposite apical rotation. Compared with patients with the normal direction of rotation, those with opposite basal end-systolic rotation had wider QRS complexes and higher mean aortic pressure. The group of patients with opposite basal end-systolic rotation differed from the group with opposite apical end-systolic rotation in enddiastolic and end-systolic LV volumes and mean aortic pressure. Examples of normal, opposite basal, and opposite apical end-systolic rotation curves obtained in a healthy volunteer and in 2 patients with IDC are demonstrated in Figure 1. The frame rate used to measure deformation parameters was slightly but significantly higher in controls (76.5 6 1.6 frames/s) than in patients with IDC (67.7 6 1.7 frames/s; P < .01 vs controls).
490 Meluzin et al
Journal of the American Society of Echocardiography May 2009
Table 2 Comparison of LV systolic and diastolic myocardial functional parameters between patients with IDC and controls Variable
Rotation and torsion Basal ER ( ) Apical ER ( ) End-systolic torsion ( ) End-systolic torsion/LV length ( /cm) Global circumferential LV function ES (%) SSR (s 1) ESR (s 1) ASR (s 1) Global longitudinal LV function ES (%) SSR (s 1) ESR (s 1) ASR (s 1) Global radial LV function ES (%) SSR (s 1) ESR (s 1) ASR (s 1)
Patients with IDC (n = 37)
Controls (n = 14)
P value
1.93 6 0.36 1.71 6 0.73 3.64 6 0.69 0.35 6 0.07
5.56 6 1.11 9.23 6 1.42 14.81 6 1.65 1.66 6 0.18
<.001 <.001 <.001 <.001
6.17 6 0.59 0.46 6 0.03 0.60 6 0.04 0.23 6 0.03
21.05 6 0.54 1.38 6 0.06 1.87 6 0.06 0.67 6 0.06
<.001 <.001 <.001 <.001
7.28 6 0.64 0.46 6 0.03 0.63 6 0.04 0.40 6 0.03
20.21 6 0.64 1.14 6 0.04 1.56 6 0.06 0.86 6 0.06
<.001 <.001 <.001 <.001
11.35 6 1.46 1.02 6 0.06 1.09 6 0.06 0.66 6 0.05
41.24 6 3.31 1.84 6 0.07 1.95 6 0.10 1.04 6 0.11
<.001 <.001 <.001 <.001
ASR, Strain rate during atrial contraction; ES, end-systolic strain; ESR, strain rate at early diastole; ER, end-systolic rotation; SSR, systolic strain rate. Data are expressed as mean 6 SEM.
Relationship Between Systolic and Diastolic Deformational Parameters in Patients With IDC The relationships between individual components of LV systolic function and early diastolic strain rate in patients with IDC are shown in Table 4. Among multiple significant correlations, the closest correlations were observed between corresponding spatial components of LV systolic and diastolic function. Circumferential early diastolic strain rate was correlated most significantly with circumferential end-systolic strain (r = 0.854) and circumferential systolic strain rate (r = 0.801), radial early diastolic strain rate with radial end-systolic strain (r = 0.577), and longitudinal early diastolic strain rate with longitudinal end-systolic strain (r = 0.689) and longitudinal systolic strain rate (r = 0.639). Reproducibility of Measurements of Deformational Parameters The results of reproducibility testing are demonstrated in Table 5. Assessment revealed no systematic bias in both intraobserver and interobserver testing. Mean differences of repeated measurements were not significantly different from zero in any parameter. The mean absolute difference of intraobserver repeated measurements was acceptable and formed up to 10% of the mean primary values (except for circumferential late diastolic strain rate). Interobserver variability was mildly higher, and interobserver mean absolute differences formed up to 10% of the mean of original measurements in longitudinal end-systolic strain, longitudinal systolic strain rate, and longitudinal late diastolic strain rate, while forming up to 15% for other parameters.
DISCUSSION All the myocardial deformational parameters were depressed in patients with IDC compared with age-matched healthy controls. We identified two subgroups of patients with IDC with either apical or basal end-systolic rotation opposite to the expected direction. These patients did not differ from patients with IDC with normal directions of apical and basal rotation on any of the measured parameters except for QRS duration, mean arterial blood pressure, and the amplitude of end-systolic torsion. We also report close coupling between LV systolic and diastolic myocardial function, with the strongest correlation between spatially corresponding systolic and diastolic components of deformation. To our knowledge, this is the first study to systematically analyze the mutual relationships of the main components of LV systolic and diastolic myocardial function, including longitudinal, circumferential, and radial global systolic and diastolic strains and strain rates as well as apical and basal rotation and torsion in patients with IDC. 2D-STE-Derived Myocardial Strain, Strain Rate, Rotation, and Torsion Parameters in Patients With IDC In our study, all myocardial deformational parameters, including longitudinal, radial, and circumferential strain and strain rate, were significantly lower in patients with IDC than in the control group, which is in agreement with previous reports of depressed longitudinal and global contractility in patients with IDC.5,36 The amplitude of rotation at the base and the apex was found to be decreased, with a resultant decrease in end-systolic LV torsion in patients with IDC, which is also consistent with other reports.37 Interestingly, we found a subset of patients with either opposite basal (ie, positive, counterclockwise) or apical (ie, negative, clockwise) end-systolic rotation, which resulted in lower amplitudes of LV torsion and, in some, opposite direction of LV torsion at end-systole. The exact explanation for this phenomenon is unclear. As demonstrated in Table 3, patients with opposite basal end-systolic rotation had larger LV volumes than those with opposite apical end-systolic rotation. Patients with normal directions of both basal and apical end-systolic rotation and those with opposite basal end-systolic rotation differed in mean aortic pressure and in the duration of the QRS complex, which may suggest a participation of increased afterload or LV dyssynchrony. However, the pressure difference of approximately 10 mm Hg and the QRS duration difference of 0.024 seconds between the groups are unlikely to account for this anomaly, mainly because the magnitude of mechanical contractile asynchrony did not differ significantly. In animal experiments, Rademakers et al38 described significant regional differences in peak torsion or in torsion at mitral valve opening approaching zero or being negative at the middle and apical anterior epicardium. The authors hypothesized that differences in the fiber orientation and relative strength of individual fiber layers, as well as differences in wall curvature, may have played a role. Ingels et al39 highlighted the relations of torsional deformation to the local fiber geometry, sequence of fiber activation, and geometric fiber relations. In addition, the extensive collagen network surrounding the myocytes, coursing in different directions, may also play a role40; in patients with IDC, segmental structural abnormalities may cause considerable variability in the extent of regional contractile function.41 Therefore, several factors may contribute to the development of changes in the direction and magnitude of LV rotation and torsion in patients with IDC. However, specifically designed studies including more patients are required to define the exact contribution of each factor or to elucidate other pathophysiologic mechanisms for this phenomenon.
Meluzin et al 491
Journal of the American Society of Echocardiography Volume 22 Number 5
Table 3 Baseline, echocardiographic, and hemodynamic data of patients with IDC divided into groups according to the direction of apical and basal rotation Variable
Age (y) Men Hypertension Diabetes mellitus EDVi (mL/m2) ESVi (mL/m2) LV EF (%) End-systolic torsion ( ) End-systolic torsion/LV length ( /cm) Electrocardiography QRS duration (s) LBBB LV contractile asynchrony Circumferential (ms) Longitudinal (ms) Radial (ms) Hemodynamic data Heart rate (beats/min) Mean aortic pressure (mm Hg)
Patients with normal direction of ER (n = 19)
Patients with negative apical ER (n = 11)
Patients with positive basal ER (n = 7)
P value
46.3 6 2.9 17 (89%) 7 (37%) 5 (26%) 120.4 6 9.3 88.8 6 8.5 25.29 6 1.73 6.36 6 0.79 0.62 6 0.07
45.5 6 3.7 8 (73%) 3 (27%) 0 104.4 6 6.8 77.8 6 6.4 23.09 6 1.98 0,70 6 0.55* 0.08 6 0.06*
49.7 6 4.2 7 (100.0%) 3 (43%) 1 (14%) 139.0 6 13.4† 103.3 6 11.4† 26.0 6 4.1 3.04 6 0.99*,† 0.29 6 0.10*,†
.763 .163 .773 .076 .043 .046 .694 <.001 <.001
0.107 6 0.005 3 (16%)
0.115 6 0.013 3 (27%)
0.131 6 0.017* 3 (43%)
.041 .161
212.6 6 24.7 203.4 6 21.6 191.6 6 27.3
244.5 6 31.1 223.9 6 28.8 203.5 6 35.4
276.6 6 33.5 275.7 6 49.4 199.0 6 48.9
.357 .289 .965
79.42 6 4.13 89.52 6 2.33
74.36 6 3.77 83.00 6 1.81
69.43 6 5.23 98.43 6 5.03†,*
.343 .012
EDVi, End-diastolic volume index; ESVi, end-systolic volume index; ER, end-systolic rotation; LBBB, left bundle branch block. Data are expressed as mean 6 SEM or number (percentage). *P < .05 vs patients with normal direction of ER. †P < .05 vs patients with negative apical ER.
The Relationship Between LV Systolic and Diastolic Chamber and Myocardial Function During the past two decades, several authors have described a close relationship between parameters reflecting LV myocardial relaxation or filling and parameters assessing longitudinal LV systolic function.7,8 The relationship between longitudinal myocardial and diastolic dysfunction has been mostly reported in patients with preserved LV EFs6,7,42,43 but also in patients with LV EFs ranging from 12% to 84%.44 However, these studies analyzed relationships only between longitudinal components of LV systolic and early diastolic function. We complemented these results with an analysis of circumferential and radial components of systolic and diastolic myocardial function. Moreover, we measured myocardial deformation by angle-independent 2D-STE, which reflects systolic and diastolic function more precisely than the velocity data derived from Doppler tissue imaging, which was predominantly used in previous studies.7,42-44 Recently, using also 2D-STE, Mizuguchi et al45 demonstrated a decrease in peak systolic longitudinal strain and strain rate and a compensatory increase in peak systolic circumferential strain and strain rate in a population of patients with cardiovascular risk factors and LV diastolic dysfunction. In our CHF cohort with markedly depressed LV systolic function, all corresponding spatial components of LV systolic and diastolic function were coupled with one another. This observation can be explained by several factors. Irrespective of the underlying disease, there is a close coupling of myocardial systolic and diastolic function inherent to the physiology of myocardial contraction and relaxation. Therefore, structural alterations of the myocardium characteristic of IDC, such as fibrosis41 or impaired myocardial energetics,46 may worsen both the systolic and diastolic properties of the myocardium to a similar degree. In addition, individual three-dimensional components of early diastolic deformation were most closely coupled with the corresponding
Table 4 Relations between individual components of LV systolic function and of early diastolic deformation in patients with IDC Diastolic parameter
Systolic parameter
Global circumferential ES Global circumferential SSR Global longitudinal ES Global longitudinal SSR Global radial ES Global radial SSR Basal ER Apical ER End-systolic torsion End-systolic torsion/LV length
Global circumferential ESR
0.854† 0.801† 0.746† 0.644† 0.541† 0.419* 0.323 0.254 0.411* 0.431*
Global longitudinal ESR
0.602† 0.517† 0.689† 0.639† 0.399* 0.229 0.476† 0.039 0.197 0.225
Global radial ESR
0.510† 0.456† 0.408* 0.254 0.577† 0.465† 0.026 0.005 0.017 0.013
ES, End-systolic strain; ESR, strain rate at early diastole; ER, end-systolic rotation; SSR, systolic strain rate. Data are Pearson’s correlation coefficients. *P < .05. †P < .01.
spatial components of systolic deformation; that is, circumferential early diastolic strain rate was correlated more closely with circumferential end-systolic strain and circumferential systolic strain rate than with longitudinal or radial end-systolic strain or systolic strain rate and vice versa. We speculate that these findings may reflect specific fiber orientation as well as variable effects of pathologic processes on differently oriented myofibers.39,40
492 Meluzin et al
Journal of the American Society of Echocardiography May 2009
Table 5 Intraobserver and interobserver variability of 2D-STE-derived myocardial functional parameters Intraobserver variability
Parameter
Basal end-systolic rotation Apical end-systolic rotation Global circumferential ES Global longitudinal ES Global circumferential SSR Global circumferential ESR Global circumferential ASR Global longitudinal SSR Global longitudinal ESR Global longitudinal ASR
Interobserver variability
Mean difference* (95% confidence interval)
Mean absolute difference† (%)
0.31 ( 0.07 ( 0.30 ( 0.34 ( 0.01 ( 0.03 ( 0.00 ( 0.04 ( 0.02 ( 0.03 (
0.46 (9.5%) 0.57 (7.9%) 1.08 (7.5%) 0.51 (3.9%) 0.09 (9.1%) 0.10 (8.2%) 0.07 (12.4%) 0.05 (6.8%) 0.07 (6.7%) 0.05 (9.7%)
0.09 to 0.71) 0.47 to 0.61) 0.24 to 0.83) 0.60 to 0.08) 0.03 to 0.05) 0.08 to 0.01) 0.04 to 0.04) 0.07 to 0.01) 0.03 to 0.07) 0.01 to 0.06)
Mean difference* (95% confidence interval)
0.05 ( 0.52 ( 0.83 ( 0.09 ( 0.13 ( 0.17 ( 0.02 ( 0.00 ( 0.05 ( 0.02 (
0.73 to 0.63) 1.34 to 0.30) 1.68 to 0.03) 0.65 to 0.82) 0.17 to 0.09) 0.01 to 0.35) 0.02 to 0.06) 0.05 to 0.05) 0.04 to 0.13) 0.02 to 0.05)
Mean absolute difference† (%)
0.50 (14.1%) 0.95 (11.4%) 1.65 (11.0%) 1.17 (8.7%) 0.11 (12.9%) 0.15 (12.3%) 0.06 (13.0) 0.07 (9.7%) 0.11 (11.0%) 0.05 (9.7%)
ASR, Strain rate during atrial contraction; ES, end-systolic strain; ESR, strain rate at early diastole; SSR, systolic strain rate. *Calculated as mean difference of repeated measurement. †In parentheses: mean of absolute difference as the percentage of the mean of two absolute measurements.
The magnitude and rate of LV systolic torsion (twisting) have been shown to be coupled to LV untwisting, which contributes to LV diastolic suction and thus to optimal and efficient LV filling.35 However, in our study, we did not find any strong correlation between apical and basal rotation or torsion and any of the individual three-dimensional components of early diastolic strain rates. The exact reason for the lack of these correlations is unclear, but the time dissociation of LV untwisting and filling described by Rademakers et al38 can contribute, at least in part, to this finding.
torsion. Two subgroups of patients with IDC with either apical or basal rotation opposite to the normal direction were identified. In patients with IDC, LV systolic myocardial functional parameters were closely coupled with spatially corresponding diastolic components of deformation.
Study Limitations IDC can be caused by many pathologic conditions, and its clinical manifestations can be heterogenous. This fact may have affected our results. The quality of 2D-STE was inadequate in a significant proportion of our patients. Thus, in a subgroup of 10 patients, longitudinal deformation was analyzed only from the apical 4-chamber view. The current speckle-tracking technology using frame rates of approximately 70 frames/s may have led to a mild underestimation of peak strain rate values. This fact may have been more expressed in patients with IDC, in whom the mean frame rate applied was 8.8 frames/sec lower than in controls. This difference was caused by the necessity to use a wider sector for imaging dilated left ventricles in patients with IDC. However, such a small difference in frame rate, even if statistically significant, is unlikely to have significantly contributed to the marked differences in strain rate values between patients with IDC and controls listed in Table 2. End-systolic values rather than peak values were used in the analysis of strain, rotation, and torsion. This approach allowed the minimization of confounding effects of the occurrence of individual segmental peaks at various time intervals due to the significant contractile asynchrony present in the majority of patients with IDC. However, in patients with postsystolic deformation, the use of end-systolic strain values could result in the underestimation of true myocardial deformation.
REFERENCES
CONCLUSIONS Compared with age-matched healthy controls, in patients with IDC, all LV myocardial deformational parameters were depressed, including longitudinal, circumferential, and radial global systolic and diastolic strains and strain rates, as well as apical and basal rotation and
ACKNOWLEDGMENT We thank Michelle M. Riley for editorial assistance.
1. Solomon SD, Anavekar N, Skali H, McMurray JJV, Swedberg K, Yusuf S, et al. Influence of ejection fraction on cardiovascular outcomes in a broad spectrum of heart failure patients. Circulation 2005;112:3738-44. 2. Uriel N, Torre-Amione G, Milo O, Kaluski E, Perchenet L, Blatt A, et al. Echocardiographic ejection fraction in patients with acute heart failure: correlations with hemodynamic, clinical, and neurohormonal measures and short-term outcome. Eur J Heart Fail 2005;7:815-9. 3. De Simone G, Devereux RB, Koren MJ, Mensah GA, Casale PN, Laragh JH. Midwall left ventricular mechanics. An independent predictor of cardiovascular risk in arterial hypertension. Circulation 1996;93:259-65. 4. Brucks S, Little WC, Chao T, Kitzman DW, Wesley-Farrington D, Gandhi S, et al. Contribution of left ventricular diastolic dysfunction to heart failure regardless of ejection fraction. Am J Cardiol 2005;95:603-6. 5. Pinamonti B, Di Lenarda A, Sinagre G, Camerini F. Restrictive left ventricular filling pattern in dilated cardiomyopathy assessed by Doppler echocardiography: Clinical, echocardiographic and hemodynamic correlations and prognostic implications. J Am Coll Cardiol 1993;22:808-15. 6. De Keulenaer GW, Brutsaert DL. Systolic and diastolic heart failure: different phenotypes of the same disease? Eur J Heart Fail 2007;9: 136-43. 7. Vinereanu D, Nicolaides E, Tweddel AC, Fraser AG. Pure diastolic dysfunction is associated with long-axis systolic dysfunction. Implications for the diagnosis and classification of heart failure. Eur J Heart Fail 2005;7: 820-8. 8. Willenheimer R, Israelsson B, Cline C, Rydberg E, Broms K, Erhardt L. Left atrioventricular plane displacement is related to both systolic and diastolic left ventricular performance in patients with chronic heart failure. Eur Heart J 1999;20:612-8. 9. Yoshida T, Ohte N, Narita H, Sakata S, Wakami K, Asada K, et al. Lack of inertia force of late systolic aortic flow is a cause of left ventricular isolated diastolic dysfunction in patients with coronary artery disease. J Am Coll Cardiol 2006;48:983-91.
Journal of the American Society of Echocardiography Volume 22 Number 5
10. Sengupta PP, Korinek J, Belohlavek M, Narula J, Jahangir A, Khandheria BK. Left ventricular structure and function: basic science for cardiac ultrasound imaging. J Am Coll Cardiol 2006;48:1988-2001. 11. Sengupta PP, Khandheria BK, Korinek J, Wang J, Jahangir A, Seward JB, et al. Apex-to-base dispersion in regional timing of left ventricular shortening and lengthening. J Am Coll Cardiol 2006;47:163-72. 12. Sengupta PP, Khandheria BK, Korinek J, Wang J, Belohlavek M. Biphasic tissue Doppler waveforms during isovolumic phases are associated with asynchronous deformation of subendocardial and subepicardial layers. J Appl Physiol 2005;99:1104-11. 13. Amundsen BH, Helle-Valle T, Edvardsen T, Torp H, Crosby J, Lyseggen E, et al. Noninvasive myocardial strain measured by speckle tracking echocardiography. Validation against sonomicrometry and tagged magnetic resonance imaging. J Am Coll Cardiol 2006;47:789-93. 14. Leitman M, Lysyansky P, Sidenko S, Shir V, Peleg E, Binenbaum M, et al. Two-dimensional strain—a novel software for real-time quantitative echocardiographic assessment of myocardial function. J Am Soc Echocardiogr 2004;17:1021-9. 15. Langeland S, D’Hooge J, Wouters PF, Leather A, Claus P, Bijnens B, et al. Experimental validation of a new ultrasound method for the simultaneous assessment of radial and longitudinal myocardial deformation independent of insonation angle. Circulation 2005;112:2157-62. 16. Serri K, Reant P, Lafitte M, Berhouet M, Le Bouffos V, Roudaut R, et al. Global and regional myocardial function quantification by two-dimensional strain. J Am Coll Cardiol 2006;47:1175-81. 17. Korinek J, Kjaergaard J, Sengupta PP, Yoshifuku S, McMahon EM, Cha SS, et al. High spatial resolution speckle tracking improves accuracy of 2-dimensional strain measurements: an update on a new method in functional echocardiography. J Am Soc Echocardiogr 2007;20:165-70. 18. Korinek J, Wang J, Sengupta PP, Miyazaki Ch, Kjaergaard J, McMahon E, et al. Two-dimensional strain—a Doppler-independent ultrasound method for quantitation of regional deformation: validation in vitro and in vivo. J Am Soc Echocardiogr 2005;18:1247-53. 19. Chan J, Hanekom L, Wong Ch, Leano R, Cho GY, Marwick TH. Differentiation of subendocardial and transmural infarction using two-dimensional strain rate imaging to assess short-axis and long-axis myocardial function. J Am Coll Cardiol 2006;48:2026-33. 20. Becker M, Hoffmann R, Kuhl HP, Grawe H, Katoh M, Kramann R, et al. Analysis of myocardial deformation based on ultrasonic pixel tracking to determine transmurality in chronic myocardial infarction. Eur Heart J 2006;27:2560-6. 21. Sun JP, Niu J, Chou D, Chuang HH, Wang K, Drinko J, et al. Alterations of regional myocardial function in a swine model of myocardial infarction assessed by echocardiographic 2-dimensional strain imaging. J Am Soc Echocardiogr 2007;20:498-504. 22. Dogan S, Aydin M, Gursurer M, Dursun A, Onuk T, Madak H. Prediction of subclinical left ventricular dysfunction with strain rate imaging in patients with mild to moderate rheumatic mitral stenosis. J Am Soc Echocardiogr 2006;19:243-8. 23. Helle-Valle T, Crosby J, Edvardsen T, Lyseggen E, Amundsen BM, Smith HJ, et al. New noninvasive method for assessment of left ventricular rotation. Speckle tracking echocardiography. Circulation 2005;112: 3149-56. 24. Notomi Y, Lysyansky P, Setser RM, Shiota T, Popovic ZB, MartinMiklovic MG, et al. Measurement of ventricular torsion by two-dimensional ultrasound speckle tracking imaging. J Am Coll Cardiol 2005;45:2034-41. 25. Kim HK, Sohn DW, Lee SE, Choi SY, Park JS, Kim YJ, et al. Assessment of left ventricular rotation and torsion with two-dimensional speckle tracking echocardiography. J Am Soc Echocardiogr 2007;20:45-53. 26. Takeuchi M, Nishikage T, Nakai H, Kokumai M, Otani S, Lang RM. The assessment of left ventricular twist in anterior wall myocardial infarction using two-dimensional speckle tracking imaging. J Am Soc Echocardiogr 2007;20:36-44. 27. Takeuchi M, Borden WB, Nakai H, Nishikage T, Kokumai M, Nagakura T, et al. Reduced and delayed untwisting of the left ventricle in patients with hypertension and left ventricular hypertrophy: a study using two-dimensional speckle tracking imaging. Eur Heart J 2007;28:2756-62.
Meluzin et al 493
28. Wang J, Khoury DS, Yue Y, Torre-Amione G, Nagueh SF. Left ventricular untwisting rate by speckle tracking echocardiography. Circulation 2007; 116:2580-6. 29. Takeuchi M, Nakai H, Kokumai M, Nishikage T, Otani S, Lang RM. Agerelated changes in left ventricular twist assessed by two-dimensional speckle-tracking imaging. J Am Soc Echocardiogr 2006;19:1077-84. 30. Van Dalen BM, Vletter WB, Soliman OII, ten Cate FJ, Geleijnse ML. Importance of transducer position in the assessment of apical rotation by speckle tracking echocardiography. J Am Soc Echocardiogr 2008;21:895-8. 31. Opdahl A, Helle-Valle T, Remme EW, Vartdal T, Pettersen E, Lunde K, et al. Apical rotation by speckle tracking echocardiography: a simplified bedside index of left ventricular twist. J Am Soc Echocardiogr 2008;21:1121-8. 32. Schiller NB, Shah PM, Crawford M, DeMaria A, Devereux R, Feigenbaum H, et al. Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. J Am Soc Echocardiogr 1989; 2:358-67. 33. Perk G, Tunick PA, Kronzon I. Non-Doppler two-dimensional strain imaging by echocardiography—from technical considerations to clinical application. J Am Soc Echocardiogr 2007;20:234-43. 34. Notomi Y, Setser RM, Shiota T, Martin-Miklovic MG, Weaver JA, Popovic ZB, et al. Assessment of left ventricular torsional deformation by Doppler tissue imaging. Validation study with tagged magnetic resonance imaging. Circulation 2005;111:1141-7. 35. Notomi Y, Martin-Miklovic MG, Oryszak SJ, Shiota T, Deserranno D, Popovic ZB, et al. Enhanced ventricular untwisting during exercise. A mechanistic manifestation of elastic recoil described by Doppler tissue imaging. Circulation 2006;113:2524-33. 36. MacGowan GA, Shapiro EP, Azhari H, Siu CO, Hees PS, Hutchins GM, et al. Noninvasive measurement of shortening in the fiber and cross-fiber directions in the normal human left ventricle and in idiopathic dilated cardiomyopathy. Circulation 1997;96:535-41. 37. Kanzaki H, Nakatani S, Yamada N, Urayama S, Miyatake K, Kitakaze M. Impaired systolic torsion in dilated cardiomyopathy: reversal of apical rotation at mid-systole characterized with magnetic resonance tagging method. Basic Res Cardiol 2006;101:465-70. 38. Rademakers FE, Buchalter MB, Rogers WJ, Zerhouni EA, Weisfeldt ML, Weiss JL, et al. Dissociation between left ventricular untwisting and filling. Accentuation by catecholamines. Circulation 1992;85:1572-81. 39. Ingels NB Jr, Hansen DE, Daughters GT, Stinson EB, Alderman EL, Miller DG. Relation between longitudinal, circumferential, and oblique shortening and torsional deformation in the left ventricle of the transplanted human heart. Circ Res 1989;64:915-27. 40. Waldman LK, Nosan D, Villarreal F, Novell JW. Relation between transmural deformation and local myofiber direction in canine left ventricle. Circ Res 1988;63:550-62. 41. Dec GW, Fuster W. Idiopathic dilated cardiomyopathy. N Engl J Med 1994;331:1564-75. 42. Paraskevaidis IA, Tsiapras D, Kyrzopoulos S, Cokkinos P, Iliodromitis EK, Parissis J, et al. The role of left ventricular long-axis contraction in patients with asymptomatic aortic regurgitation. J Am Soc Echocardiogr 2006;19: 249-54. 43. Yu ChM, Lin H, Yang H, Kong SL, Zhang Q, Lee SWL. Progression of systolic abnormalities in patients with isolated diastolic heart failure and diastolic dysfunction. Circulation 2002;105:1195-201. 44. Yip GW, Zhang Y, Tan PY, Wang M, Ho PY, Brodin LA, et al. Left ventricular long-axis changes in early diastole and systole: impact of systolic function on diastole. Clin Sci 2002;102:515-22. 45. Mizuguchi Y, Oishi Y, Miyoshi H, Iuchi A, Nagase N, Oki T. The functional role of longitudinal, circumferential, and radial myocardial deformation for regulating the early impairment of left ventricular contraction and relaxation in patients with cardiovascular risk factors: a study with two-dimensional strain imaging. J Am Soc Echocardiogr 2008;21:1138-44. 46. Korinek J, Anagnostopoulos PC, Pislaru C, Dzeja PP, Seward JB, Terzic A, et al. Both systolic and diastolic dysfunction characterize nonischemic inhibition of myocardial energy metabolism: an experimental strain rate echocardiographic study. J Am Soc Echocardiogr 2004;17:1239-44.
Left Ventricular Mechanics in Idiopathic Dilated Cardiomyopathy: Systolic-Diastolic Coupling and Torsion Jaroslav Meluzin, MD, PhD, FESC, Lenka Spinarova, MD, PhD, FESC, Petr Hude, MD, Jan Krejci, MD, Hana Poloczkova, MD, Helena Podrouzkova, MD, Martin Pesl, MD, Marek Orban, MD, Ladislav Dusek, MD, PhD, and Josef Korinek, MD, PhD, Brno and Prague, Czech Republic; Rochester, Minnesota
Background: In idiopathic dilated cardiomyopathy (IDC), myocardial deformational parameters and their mutual relationships remain incompletely characterized. Methods: Thirty-seven patients with IDC underwent two-dimensional speckle-tracking echocardiography (2D-STE) to assess left ventricular rotation, torsion, and longitudinal, circumferential, and radial systolic and diastolic strains and strain rates. Additionally, 2D-STE was performed in 14 controls. Results: All deformational parameters on 2D-STE were significantly lower in patients with IDC compared with controls. Seven patients exhibited opposite basal (positive, counterclockwise) and 11 patients exhibited opposite apical (negative, clockwise) rotation at end-systole. Circumferential, radial, and longitudinal early diastolic strain rates were correlated most strongly with the corresponding spatial components of systolic deformation. Conclusion: In patients IDC, all torsional, systolic, and diastolic deformational parameters were decreased. Corresponding three-dimensional components of systolic and diastolic deformations were closely coupled. Considerable variation in the direction of basal and apical rotation exists in a subset of patients with IDC. (J Am Soc Echocardiogr 2009;22:486-493.) Keywords: Left ventricular rotation, Torsion, Two-dimensional strain echocardiography
During the development of congestive heart failure (CHF) in patients with idiopathic dilated cardiomyopathy (IDC), the left ventricle undergoes complex changes in geometry, accompanied by alteration of the left ventricular (LV) chamber and myocardial systolic and/or diastolic function. LV ejection fraction (EF) is the most common clinically used parameter for the quantification of the severity of LV systolic dysfunction in patients with CHF and has been used as a prog-
From the 1st Department of Internal Medicine/Cardioangiology, St Anna Hospital, ICRC, Masaryk University, Brno, Czech Republic (J.M., L.S., P.H., J. Krejci, H. Poloczkova, H. Podrouzkova, M.P., M.O.); the Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, MN (M.O., J. Korinek); the Institute of Biostatistics and Analyses, Masaryk University, Brno, Czech Republic (L.D.); and the Division of Cardiovascular Diseases, 2nd Department of Internal Medicine, General University Hospital, 1st School of Medicine, Charles University, Prague, Czech Republic (J. Korinek). The study was supported in part by a grant of the Ministry of Education of the Czech Republic (no. 0021622402). J.K. was supported by a travel grant from the Czech Society of Cardiology. Reprint requests: Jaroslav Meluzin, MD, 1st Department of Internal Medicine/ Cardioangiology, St Anna Hospital, Pekarska 53, 65691 Brno, Czech Republic (E-mail: [email protected]). 0894-7317/$36.00 Copyright 2009 by the American Society of Echocardiography. doi:10.1016/j.echo.2009.02.022
486
nostic marker.1,2 However, EF describes LV systolic chamber function and does not always reflect global LV myocardial contractile performance or provide information about individual myocardial deformational components, which may have prognostic utility, as shown in hypertensive heart disease and diastolic heart failure.3 Moreover, the quality of life and prognoses of patients with CHF are associated not only with systolic LV chamber or myocardial function but also with changes in LV diastolic function. Indeed, LV diastolic dysfunction has been associated with a high frequency of cardiac events during long-term follow-up in patients with CHF.4,5 Systolic and diastolic LV dysfunction frequently coexist, and it has been suggested that systolic and diastolic heart failure may be two phases of one pathophysiologic process.6 However, the incomplete understanding of systolic-diastolic coupling on regional and global myocardial and chamber level has triggered extensive debate on the relationship and the extent of interplay between various components of systolic and diastolic function.7-9 Initially, the longitudinal component of LV systolic dysfunction was shown to be associated with LV diastolic dysfunction7,8 in patients with CHF. However, myocardial deformation occurs in 3 dimensions and can be characterized not only in longitudinal but also in circumferential and radial directions. Little is known about the relationships between individual spatial components of systolic and diastolic dysfunction. In addition, normal myocardial fiber orientation may change with the alteration of LV geometry in IDC and result in changes in LV rotation or torsion,10-12 both of which characterize different aspects of LV global performance than EF.
Meluzin et al 487
Journal of the American Society of Echocardiography Volume 22 Number 5
The recently introduced and validated modality of high-spatialresolution two-dimensional speckle-tracking echocardiography (2D-STE) has enabled the evaluation of numerous deformational parameters in longitudinal, circumferential, and radial directions characterizing LV systolic and diastolic performance, such as systolic strain,13-21 systolic and early diastolic strain rate,14,19,20,22 and LV basal and apical myocardial rotation and torsion.21,23-31 In this regard, 2D-STE may allow a more detailed analysis of individual components of LV systolic and diastolic function as well as the assessment of their mutual relationships, which remain incompletely characterized. Thus, the aims of our study were to characterize the longitudinal, circumferential, and radial components of LV systolic and diastolic myocardial function and study their mutual relationships and to quantify and characterize LV rotation and torsion in patients with IDC.
METHODS Patient Population We enrolled 52 consecutive patients with symptomatic CHF due to IDC, who were referred to St Anna Hospital (Brno, Czech Republic) for detailed cardiologic assessments, which included histories, physical examinations, routine blood tests, 12-lead electrocardiography, chest radiography, and conventional transthoracic echocardiography prior to right-heart catheterization. The diagnosis of IDC was made on the basis of echocardiography (LV dilation and diffuse hypocontractility), electrocardiography (absence of Q waves), clinical criteria (no angina pectoris, no history of myocardial infarction), and coronary angiography (no significant coronary artery stenosis) or bicycle spiroergometry (no electrocardiographic signs of ischemia). The inclusion criteria of the study were the presence of CHF with LV systolic dysfunction, good-quality conventional transthoracic echocardiographic imaging, and sinus rhythm on electrocardiography. The exclusion criteria included the presence of coronary artery disease, congenital or valvular heart disease, hyperthyroidism, or any systemic or metabolic disease known to induce cardiomyopathy. Of 52 patients with IDC, 47 had acceptable-quality precatheterization conventional echocardiographic images and underwent conventional and speckle-tracking echocardiography. Coronary angiography was performed in 35 of 47 patients (74%; 89% in those aged > 40 years). The remaining 12 patients underwent bicycle spiroergometry. There were 38 men (81%) and 9 women (19%) (mean age, 48.0 6 1.8 years; range, 22-72 years). Sixteen patients (34%) had hypertension and 8 patients (17%) were treated for diabetes mellitus. Medical therapy comprised angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (47 patients [100%]), b-blockers (46 patients [98%]), furosemide (46 patients [98%]), spironolactone (44 patients [94%]), and digoxin (36 patients [77%]). Twenty-two patients (47%) were in New York Heart Association class II, 23 (49%) were in class III, and 2 (4%) were in class IV. Fifteen age-matched and gender-matched healthy volunteers (11 men and 4 women; mean age, 44.9 6 3.1 years; range, 26-64 years; P = NS vs patients with IDC) served as a control group and underwent conventional echocardiography along with 2D-STE. They had normal echocardiographic results and no risk factors for coronary artery disease, and they used no medications. All patients gave their written consent to the investigations. The study complied with the Declaration of Helsinki and was approved by the ethics committees at St Anna Hospital and the Mayo Clinic College of Medicine.
Conventional Echocardiography Both conventional and speckle-tracking echocardiography were performed using Vivid 7 (GE-Vingmed Ultrasound AS, Horten, Norway) with an M3S transducer. Transmitral and aortic flows were recorded using pulsed Doppler echocardiography. The sample volume with a fixed length of 5.1 mm was placed between the tips of the mitral and aortic leaflets. All Doppler recordings were done during shallow respiration or end-expiratory apnea. LV volumes and EFs were calculated using the biplane method according to the modified Simpson’s rule.32 2D-STE The detailed principles and methodology of 2D-STE have been described previously.14,33 In our study, high-spatial-resolution 2D-STE was used, allowing the more accurate evaluation of low deformation values,17 which can be expected in patients with IDC. Grayscale two-dimensional images (frame rate, 44-82 frames/s) were recorded for offline analysis. Apical 4-chamber and 2-chamber views were used for longitudinal strain and strain rate analysis, and parasternal short-axis (SAX) views at the base (clearly depicting the tips of the mitral valve leaflets), at the level of papillary muscles, and at the apex (as close to the tip of the apex as possible, optimally with the minimal circular LV cavity present at end-systole) were used for circumferential and radial strain and strain rate, rotation, and torsion analysis. Three to 5 consecutive cardiac cycles in each view were digitally stored for subsequent offline analysis using EchoPAC PC SW 6.1.0 (GE-Vingmed Ultrasound AS). During the analysis, LV endocardium was traced at end-systole, and if necessary, a software-generated region of interest was adjusted to an ideal width of myocardial wall. The myocardium in each echocardiographic view was automatically divided into 6 predefined segments, and the regional longitudinal, circumferential, and radial strain as well as the mean longitudinal and circumferential strain, strain rate, and rotation curves were displayed in different colors. Except for global radial strains and strain rates, all the deformational parameters were obtained directly from the mean deformational curves (Figure 1), which were provided by the software. At the time of analysis, EchoPAC software did not provide mean radial strain or strain rate, so the mean radial strain rate curves were calculated as an average of 6 segments every time frame and plotted, and strain rate parameters were measured. The mean radial end-systolic strain was calculated for each SAX view as the sum of end-systolic radial strain values in all 6 segments divided by 6. To standardize the parameter analysis, the starting points of rotation and deformation curves were manually placed at the onset of the QRS complex in all patients. To determine the phases of the cardiac cycle, the timings of aortic and mitral valve opening and closure were assessed using pulsed-wave Doppler recordings of aortic and transmitral flows. In addition, the software automatically evaluated the tracking quality of individual segments and defined whether or not they were acceptable for data analysis. Myocardial Strain, Strain Rate, Rotation, and Torsion Parameters Assessed on 2D-STE For the analysis of global strain, strain rate, and rotation parameters, the mean curves created by the software in each echocardiographic view were used. These mean curves represented at any given time point the average of individual curves of all 6 segments into which the myocardium was divided in standard fashion (Figure 1) by the software. Longitudinal strain and strain rate values were obtained from the apical 4-chamber and 2-chamber views and circumferential
488 Meluzin et al
Journal of the American Society of Echocardiography May 2009
Figure 1 Examples of normal and opposite basal and apical rotation curves obtained from a healthy volunteer and from two patients with IDC. Each color of the deformational curve represents one segment of the left ventricle, and the dashed white curve depicts mean rotation of 6 segments. (Top) Normal negative (clockwise) late systolic and end-systolic basal rotation (A) and normal positive (counterclockwise) late systolic and end-systolic apical rotation (B) in a healthy volunteer. (Middle) A patient with IDC with opposite (positive) late systolic and end-systolic basal rotation (C) and normal positive direction of apical end-systolic rotation (D). (Bottom) A patient with IDC with normal negative direction of basal end-systolic rotation (E) and opposite (negative) end-systolic apical rotation (F). and radial values from 3 parasternal SAX views. To obtain functional data from the corresponding time points, the end-systolic values (at the time of aortic valve closure) were used for the determination of global strain, basal and apical rotation, and torsion. Thus, global
circumferential, longitudinal, and radial end-systolic strain were calculated as follows: circumferential ES = (mean basal circumferential ES + mean midcircumferential ES + mean apical circumferential ES)/3, longitudinal ES = (mean longitudinal ES in the apical 4-chamber view
Meluzin et al 489
Journal of the American Society of Echocardiography Volume 22 Number 5
+ mean longitudinal ES in the apical 2-chamber view)/2, and radial ES = (mean basal radial ES + mean midradial ES + mean apical radial ES)/3, where ES is end-systolic strain. The global circumferential, longitudinal, and radial strain rate parameters, including systolic and early and late diastolic strain rates, were calculated using the analogous approach. LV basal and apical rotation were analyzed from the parasternal SAX views at the base and at the apex. LV rotation was expressed in degrees. Negative values indicated clockwise and positive counterclockwise rotation (as viewed from the apex). Mean basal and apical end-systolic rotation were determined as the cross-sections of the mean basal and apical rotation curves with the line defining the time of aortic valve closure. LV end-systolic torsion was defined as the difference between apical end-systolic rotation and basal end-systolic rotation21,34,35 and was divided by the end-diastolic LV longitudinal length between the LV apex and the mitral plane. To better characterize LV basal and apical rotation and their anomalies, LV mechanical asynchrony was quantified. Parasternal SAX views at the level of papillary muscles were used to assess circumferential and radial asynchrony, and apical 4-chamber views were used to determine longitudinal asynchrony. The time from the onset of the QRS complex to peak strain was measured for all 6 regional strain curves in each view. In case of more clearly separated strain peaks, the maximal systolic peak was used. LV mechanical dyssynchrony was defined as the difference between the earliest and the latest strain peaks and was calculated for circumferential, radial, and longitudinal strains. Speckle-tracking analysis was performed offline by two experienced observers (J.M. and M.O.). The results of all parameters were obtained as a mean of 2 or 3 consecutive heart cycles. Statistical Analysis Data are expressed as mean 6 SEM. All parameters were tested prior to any statistical analysis to determine if they were normally distributed. All distribution patterns were normal, and neither transformation nor exclusion of outliers was needed. Comparisons of continuous variables across the groups were made using one-way analysis of variance, and the Tukey-Kramer test was used for multiple comparisons between the groups. The maximum likelihood c2 test was applied to compare differences among the groups of patients in binary or categorical variables. The correlation structure set of metric parameters was inspected using Pearson’s product-moment correlation coefficient. P values < .05 were considered statistically significant. The reproducibility of deformational parameters was assessed in 10 randomly picked subjects. The interobserver and intraobserver variability were analyzed by two observers (J.M. and M.O.) by and one observer (J.M.) on two occasions $1 month apart for global parameters, including basal and apical end-systolic rotation, circumferential and longitudinal end-systolic strain, and circumferential and longitudinal peak systolic and early and late diastolic strain rates. The standard approach of Bland-Altman plotting was applied, numerically supported by the calculation of the mean absolute difference of repeated measurements, its 95% confidence limits, and the range.
RESULTS Of 47 patients and 15 controls enrolled in the study, 10 patients and 1 control were excluded from the final analysis. They had seg-
Table 1 Baseline characteristics of the final cohort of subjects Variable
Patients with IDC (n = 37)
Controls (n = 14)
P value
Age (y) Men Hypertension Diabetes mellitus EDVi (mL/m2) ESVi (mL/m2) LV EF (%)
46.7 6 1.9 32 (87%) 13 (35%) 6 (16%) 119.2 6 6.1 88.4 6 5.4 24.8 6 1.3
44.3 6 3.3 11 (79%) 0 0 52.1 6 2.4 19.7 6 1.1 62.9 6 1.1
.519 .498 .002 .042 <.001 <.001 <.001
EDVi, End-diastolic volume index; ESVi, end-systolic volume index. Data are expressed as mean 6 SEM or number (percentage).
ments of inadequate quality for speckle-tracking analysis in either basal or apical SAX views, not allowing the exact quantification of LV torsion, or in both the apical 4-chamber and 2-chamber views, not allowing the assessment of LV longitudinal function. Thus, the final study group comprised 37 patients with IDC and 14 controls. Their clinical characteristics are shown in Table 1. In 10 patients, in whom segments of poor speckle-tracking quality were confined only to the apical 2-chamber view, longitudinal function was evaluated only in the apical 4-chamber view. In 3 patients, the peak early and late diastolic strain rates could not be analyzed because of their fusion.
Myocardial Strain, Strain Rate, Rotation, and Torsion Parameters Assessed on 2D-STE LV systolic and diastolic deformational parameters derived from 2D-STE are shown in Table 2. Compared with healthy controls, all deformational parameters were significantly lower in patients with IDC. In all control subjects, basal end-systolic rotation had a clockwise direction, resulting in negative basal end-systolic rotation values, whereas apical rotation was opposite (counterclockwise), resulting in positive apical end-systolic rotation values. Nineteen patients with IDC had normal directions of both basal (clockwise) and apical (counterclockwise) rotations. Interestingly and contrary to healthy subjects, 7 patients with IDC had opposite (ie, positive, counterclockwise) basal end-systolic rotation (mean, 1.0 6 0.2 ), and another 11 patients were found to have opposite (ie, negative, clockwise) apical end-systolic rotation (mean, 3.5 6 0.8 ). None of the patients exhibited combined opposite basal and apical endsystolic rotation. Therefore, the group of patients was further analyzed and divided into subgroups according to the direction of apical and/or basal rotation (Table 3). End-systolic torsion differed significantly among all 3 subgroups, being lowest in the subgroup with opposite apical rotation. Compared with patients with the normal direction of rotation, those with opposite basal end-systolic rotation had wider QRS complexes and higher mean aortic pressure. The group of patients with opposite basal end-systolic rotation differed from the group with opposite apical end-systolic rotation in enddiastolic and end-systolic LV volumes and mean aortic pressure. Examples of normal, opposite basal, and opposite apical end-systolic rotation curves obtained in a healthy volunteer and in 2 patients with IDC are demonstrated in Figure 1. The frame rate used to measure deformation parameters was slightly but significantly higher in controls (76.5 6 1.6 frames/s) than in patients with IDC (67.7 6 1.7 frames/s; P < .01 vs controls).
490 Meluzin et al
Journal of the American Society of Echocardiography May 2009
Table 2 Comparison of LV systolic and diastolic myocardial functional parameters between patients with IDC and controls Variable
Rotation and torsion Basal ER ( ) Apical ER ( ) End-systolic torsion ( ) End-systolic torsion/LV length ( /cm) Global circumferential LV function ES (%) SSR (s 1) ESR (s 1) ASR (s 1) Global longitudinal LV function ES (%) SSR (s 1) ESR (s 1) ASR (s 1) Global radial LV function ES (%) SSR (s 1) ESR (s 1) ASR (s 1)
Patients with IDC (n = 37)
Controls (n = 14)
P value
1.93 6 0.36 1.71 6 0.73 3.64 6 0.69 0.35 6 0.07
5.56 6 1.11 9.23 6 1.42 14.81 6 1.65 1.66 6 0.18
<.001 <.001 <.001 <.001
6.17 6 0.59 0.46 6 0.03 0.60 6 0.04 0.23 6 0.03
21.05 6 0.54 1.38 6 0.06 1.87 6 0.06 0.67 6 0.06
<.001 <.001 <.001 <.001
7.28 6 0.64 0.46 6 0.03 0.63 6 0.04 0.40 6 0.03
20.21 6 0.64 1.14 6 0.04 1.56 6 0.06 0.86 6 0.06
<.001 <.001 <.001 <.001
11.35 6 1.46 1.02 6 0.06 1.09 6 0.06 0.66 6 0.05
41.24 6 3.31 1.84 6 0.07 1.95 6 0.10 1.04 6 0.11
<.001 <.001 <.001 <.001
ASR, Strain rate during atrial contraction; ES, end-systolic strain; ESR, strain rate at early diastole; ER, end-systolic rotation; SSR, systolic strain rate. Data are expressed as mean 6 SEM.
Relationship Between Systolic and Diastolic Deformational Parameters in Patients With IDC The relationships between individual components of LV systolic function and early diastolic strain rate in patients with IDC are shown in Table 4. Among multiple significant correlations, the closest correlations were observed between corresponding spatial components of LV systolic and diastolic function. Circumferential early diastolic strain rate was correlated most significantly with circumferential end-systolic strain (r = 0.854) and circumferential systolic strain rate (r = 0.801), radial early diastolic strain rate with radial end-systolic strain (r = 0.577), and longitudinal early diastolic strain rate with longitudinal end-systolic strain (r = 0.689) and longitudinal systolic strain rate (r = 0.639). Reproducibility of Measurements of Deformational Parameters The results of reproducibility testing are demonstrated in Table 5. Assessment revealed no systematic bias in both intraobserver and interobserver testing. Mean differences of repeated measurements were not significantly different from zero in any parameter. The mean absolute difference of intraobserver repeated measurements was acceptable and formed up to 10% of the mean primary values (except for circumferential late diastolic strain rate). Interobserver variability was mildly higher, and interobserver mean absolute differences formed up to 10% of the mean of original measurements in longitudinal end-systolic strain, longitudinal systolic strain rate, and longitudinal late diastolic strain rate, while forming up to 15% for other parameters.
DISCUSSION All the myocardial deformational parameters were depressed in patients with IDC compared with age-matched healthy controls. We identified two subgroups of patients with IDC with either apical or basal end-systolic rotation opposite to the expected direction. These patients did not differ from patients with IDC with normal directions of apical and basal rotation on any of the measured parameters except for QRS duration, mean arterial blood pressure, and the amplitude of end-systolic torsion. We also report close coupling between LV systolic and diastolic myocardial function, with the strongest correlation between spatially corresponding systolic and diastolic components of deformation. To our knowledge, this is the first study to systematically analyze the mutual relationships of the main components of LV systolic and diastolic myocardial function, including longitudinal, circumferential, and radial global systolic and diastolic strains and strain rates as well as apical and basal rotation and torsion in patients with IDC. 2D-STE-Derived Myocardial Strain, Strain Rate, Rotation, and Torsion Parameters in Patients With IDC In our study, all myocardial deformational parameters, including longitudinal, radial, and circumferential strain and strain rate, were significantly lower in patients with IDC than in the control group, which is in agreement with previous reports of depressed longitudinal and global contractility in patients with IDC.5,36 The amplitude of rotation at the base and the apex was found to be decreased, with a resultant decrease in end-systolic LV torsion in patients with IDC, which is also consistent with other reports.37 Interestingly, we found a subset of patients with either opposite basal (ie, positive, counterclockwise) or apical (ie, negative, clockwise) end-systolic rotation, which resulted in lower amplitudes of LV torsion and, in some, opposite direction of LV torsion at end-systole. The exact explanation for this phenomenon is unclear. As demonstrated in Table 3, patients with opposite basal end-systolic rotation had larger LV volumes than those with opposite apical end-systolic rotation. Patients with normal directions of both basal and apical end-systolic rotation and those with opposite basal end-systolic rotation differed in mean aortic pressure and in the duration of the QRS complex, which may suggest a participation of increased afterload or LV dyssynchrony. However, the pressure difference of approximately 10 mm Hg and the QRS duration difference of 0.024 seconds between the groups are unlikely to account for this anomaly, mainly because the magnitude of mechanical contractile asynchrony did not differ significantly. In animal experiments, Rademakers et al38 described significant regional differences in peak torsion or in torsion at mitral valve opening approaching zero or being negative at the middle and apical anterior epicardium. The authors hypothesized that differences in the fiber orientation and relative strength of individual fiber layers, as well as differences in wall curvature, may have played a role. Ingels et al39 highlighted the relations of torsional deformation to the local fiber geometry, sequence of fiber activation, and geometric fiber relations. In addition, the extensive collagen network surrounding the myocytes, coursing in different directions, may also play a role40; in patients with IDC, segmental structural abnormalities may cause considerable variability in the extent of regional contractile function.41 Therefore, several factors may contribute to the development of changes in the direction and magnitude of LV rotation and torsion in patients with IDC. However, specifically designed studies including more patients are required to define the exact contribution of each factor or to elucidate other pathophysiologic mechanisms for this phenomenon.
Meluzin et al 491
Journal of the American Society of Echocardiography Volume 22 Number 5
Table 3 Baseline, echocardiographic, and hemodynamic data of patients with IDC divided into groups according to the direction of apical and basal rotation Variable
Age (y) Men Hypertension Diabetes mellitus EDVi (mL/m2) ESVi (mL/m2) LV EF (%) End-systolic torsion ( ) End-systolic torsion/LV length ( /cm) Electrocardiography QRS duration (s) LBBB LV contractile asynchrony Circumferential (ms) Longitudinal (ms) Radial (ms) Hemodynamic data Heart rate (beats/min) Mean aortic pressure (mm Hg)
Patients with normal direction of ER (n = 19)
Patients with negative apical ER (n = 11)
Patients with positive basal ER (n = 7)
P value
46.3 6 2.9 17 (89%) 7 (37%) 5 (26%) 120.4 6 9.3 88.8 6 8.5 25.29 6 1.73 6.36 6 0.79 0.62 6 0.07
45.5 6 3.7 8 (73%) 3 (27%) 0 104.4 6 6.8 77.8 6 6.4 23.09 6 1.98 0,70 6 0.55* 0.08 6 0.06*
49.7 6 4.2 7 (100.0%) 3 (43%) 1 (14%) 139.0 6 13.4† 103.3 6 11.4† 26.0 6 4.1 3.04 6 0.99*,† 0.29 6 0.10*,†
.763 .163 .773 .076 .043 .046 .694 <.001 <.001
0.107 6 0.005 3 (16%)
0.115 6 0.013 3 (27%)
0.131 6 0.017* 3 (43%)
.041 .161
212.6 6 24.7 203.4 6 21.6 191.6 6 27.3
244.5 6 31.1 223.9 6 28.8 203.5 6 35.4
276.6 6 33.5 275.7 6 49.4 199.0 6 48.9
.357 .289 .965
79.42 6 4.13 89.52 6 2.33
74.36 6 3.77 83.00 6 1.81
69.43 6 5.23 98.43 6 5.03†,*
.343 .012
EDVi, End-diastolic volume index; ESVi, end-systolic volume index; ER, end-systolic rotation; LBBB, left bundle branch block. Data are expressed as mean 6 SEM or number (percentage). *P < .05 vs patients with normal direction of ER. †P < .05 vs patients with negative apical ER.
The Relationship Between LV Systolic and Diastolic Chamber and Myocardial Function During the past two decades, several authors have described a close relationship between parameters reflecting LV myocardial relaxation or filling and parameters assessing longitudinal LV systolic function.7,8 The relationship between longitudinal myocardial and diastolic dysfunction has been mostly reported in patients with preserved LV EFs6,7,42,43 but also in patients with LV EFs ranging from 12% to 84%.44 However, these studies analyzed relationships only between longitudinal components of LV systolic and early diastolic function. We complemented these results with an analysis of circumferential and radial components of systolic and diastolic myocardial function. Moreover, we measured myocardial deformation by angle-independent 2D-STE, which reflects systolic and diastolic function more precisely than the velocity data derived from Doppler tissue imaging, which was predominantly used in previous studies.7,42-44 Recently, using also 2D-STE, Mizuguchi et al45 demonstrated a decrease in peak systolic longitudinal strain and strain rate and a compensatory increase in peak systolic circumferential strain and strain rate in a population of patients with cardiovascular risk factors and LV diastolic dysfunction. In our CHF cohort with markedly depressed LV systolic function, all corresponding spatial components of LV systolic and diastolic function were coupled with one another. This observation can be explained by several factors. Irrespective of the underlying disease, there is a close coupling of myocardial systolic and diastolic function inherent to the physiology of myocardial contraction and relaxation. Therefore, structural alterations of the myocardium characteristic of IDC, such as fibrosis41 or impaired myocardial energetics,46 may worsen both the systolic and diastolic properties of the myocardium to a similar degree. In addition, individual three-dimensional components of early diastolic deformation were most closely coupled with the corresponding
Table 4 Relations between individual components of LV systolic function and of early diastolic deformation in patients with IDC Diastolic parameter
Systolic parameter
Global circumferential ES Global circumferential SSR Global longitudinal ES Global longitudinal SSR Global radial ES Global radial SSR Basal ER Apical ER End-systolic torsion End-systolic torsion/LV length
Global circumferential ESR
0.854† 0.801† 0.746† 0.644† 0.541† 0.419* 0.323 0.254 0.411* 0.431*
Global longitudinal ESR
0.602† 0.517† 0.689† 0.639† 0.399* 0.229 0.476† 0.039 0.197 0.225
Global radial ESR
0.510† 0.456† 0.408* 0.254 0.577† 0.465† 0.026 0.005 0.017 0.013
ES, End-systolic strain; ESR, strain rate at early diastole; ER, end-systolic rotation; SSR, systolic strain rate. Data are Pearson’s correlation coefficients. *P < .05. †P < .01.
spatial components of systolic deformation; that is, circumferential early diastolic strain rate was correlated more closely with circumferential end-systolic strain and circumferential systolic strain rate than with longitudinal or radial end-systolic strain or systolic strain rate and vice versa. We speculate that these findings may reflect specific fiber orientation as well as variable effects of pathologic processes on differently oriented myofibers.39,40
492 Meluzin et al
Journal of the American Society of Echocardiography May 2009
Table 5 Intraobserver and interobserver variability of 2D-STE-derived myocardial functional parameters Intraobserver variability
Parameter
Basal end-systolic rotation Apical end-systolic rotation Global circumferential ES Global longitudinal ES Global circumferential SSR Global circumferential ESR Global circumferential ASR Global longitudinal SSR Global longitudinal ESR Global longitudinal ASR
Interobserver variability
Mean difference* (95% confidence interval)
Mean absolute difference† (%)
0.31 ( 0.07 ( 0.30 ( 0.34 ( 0.01 ( 0.03 ( 0.00 ( 0.04 ( 0.02 ( 0.03 (
0.46 (9.5%) 0.57 (7.9%) 1.08 (7.5%) 0.51 (3.9%) 0.09 (9.1%) 0.10 (8.2%) 0.07 (12.4%) 0.05 (6.8%) 0.07 (6.7%) 0.05 (9.7%)
0.09 to 0.71) 0.47 to 0.61) 0.24 to 0.83) 0.60 to 0.08) 0.03 to 0.05) 0.08 to 0.01) 0.04 to 0.04) 0.07 to 0.01) 0.03 to 0.07) 0.01 to 0.06)
Mean difference* (95% confidence interval)
0.05 ( 0.52 ( 0.83 ( 0.09 ( 0.13 ( 0.17 ( 0.02 ( 0.00 ( 0.05 ( 0.02 (
0.73 to 0.63) 1.34 to 0.30) 1.68 to 0.03) 0.65 to 0.82) 0.17 to 0.09) 0.01 to 0.35) 0.02 to 0.06) 0.05 to 0.05) 0.04 to 0.13) 0.02 to 0.05)
Mean absolute difference† (%)
0.50 (14.1%) 0.95 (11.4%) 1.65 (11.0%) 1.17 (8.7%) 0.11 (12.9%) 0.15 (12.3%) 0.06 (13.0) 0.07 (9.7%) 0.11 (11.0%) 0.05 (9.7%)
ASR, Strain rate during atrial contraction; ES, end-systolic strain; ESR, strain rate at early diastole; SSR, systolic strain rate. *Calculated as mean difference of repeated measurement. †In parentheses: mean of absolute difference as the percentage of the mean of two absolute measurements.
The magnitude and rate of LV systolic torsion (twisting) have been shown to be coupled to LV untwisting, which contributes to LV diastolic suction and thus to optimal and efficient LV filling.35 However, in our study, we did not find any strong correlation between apical and basal rotation or torsion and any of the individual three-dimensional components of early diastolic strain rates. The exact reason for the lack of these correlations is unclear, but the time dissociation of LV untwisting and filling described by Rademakers et al38 can contribute, at least in part, to this finding.
torsion. Two subgroups of patients with IDC with either apical or basal rotation opposite to the normal direction were identified. In patients with IDC, LV systolic myocardial functional parameters were closely coupled with spatially corresponding diastolic components of deformation.
Study Limitations IDC can be caused by many pathologic conditions, and its clinical manifestations can be heterogenous. This fact may have affected our results. The quality of 2D-STE was inadequate in a significant proportion of our patients. Thus, in a subgroup of 10 patients, longitudinal deformation was analyzed only from the apical 4-chamber view. The current speckle-tracking technology using frame rates of approximately 70 frames/s may have led to a mild underestimation of peak strain rate values. This fact may have been more expressed in patients with IDC, in whom the mean frame rate applied was 8.8 frames/sec lower than in controls. This difference was caused by the necessity to use a wider sector for imaging dilated left ventricles in patients with IDC. However, such a small difference in frame rate, even if statistically significant, is unlikely to have significantly contributed to the marked differences in strain rate values between patients with IDC and controls listed in Table 2. End-systolic values rather than peak values were used in the analysis of strain, rotation, and torsion. This approach allowed the minimization of confounding effects of the occurrence of individual segmental peaks at various time intervals due to the significant contractile asynchrony present in the majority of patients with IDC. However, in patients with postsystolic deformation, the use of end-systolic strain values could result in the underestimation of true myocardial deformation.
REFERENCES
CONCLUSIONS Compared with age-matched healthy controls, in patients with IDC, all LV myocardial deformational parameters were depressed, including longitudinal, circumferential, and radial global systolic and diastolic strains and strain rates, as well as apical and basal rotation and
ACKNOWLEDGMENT We thank Michelle M. Riley for editorial assistance.
1. Solomon SD, Anavekar N, Skali H, McMurray JJV, Swedberg K, Yusuf S, et al. Influence of ejection fraction on cardiovascular outcomes in a broad spectrum of heart failure patients. Circulation 2005;112:3738-44. 2. Uriel N, Torre-Amione G, Milo O, Kaluski E, Perchenet L, Blatt A, et al. Echocardiographic ejection fraction in patients with acute heart failure: correlations with hemodynamic, clinical, and neurohormonal measures and short-term outcome. Eur J Heart Fail 2005;7:815-9. 3. De Simone G, Devereux RB, Koren MJ, Mensah GA, Casale PN, Laragh JH. Midwall left ventricular mechanics. An independent predictor of cardiovascular risk in arterial hypertension. Circulation 1996;93:259-65. 4. Brucks S, Little WC, Chao T, Kitzman DW, Wesley-Farrington D, Gandhi S, et al. Contribution of left ventricular diastolic dysfunction to heart failure regardless of ejection fraction. Am J Cardiol 2005;95:603-6. 5. Pinamonti B, Di Lenarda A, Sinagre G, Camerini F. Restrictive left ventricular filling pattern in dilated cardiomyopathy assessed by Doppler echocardiography: Clinical, echocardiographic and hemodynamic correlations and prognostic implications. J Am Coll Cardiol 1993;22:808-15. 6. De Keulenaer GW, Brutsaert DL. Systolic and diastolic heart failure: different phenotypes of the same disease? Eur J Heart Fail 2007;9: 136-43. 7. Vinereanu D, Nicolaides E, Tweddel AC, Fraser AG. Pure diastolic dysfunction is associated with long-axis systolic dysfunction. Implications for the diagnosis and classification of heart failure. Eur J Heart Fail 2005;7: 820-8. 8. Willenheimer R, Israelsson B, Cline C, Rydberg E, Broms K, Erhardt L. Left atrioventricular plane displacement is related to both systolic and diastolic left ventricular performance in patients with chronic heart failure. Eur Heart J 1999;20:612-8. 9. Yoshida T, Ohte N, Narita H, Sakata S, Wakami K, Asada K, et al. Lack of inertia force of late systolic aortic flow is a cause of left ventricular isolated diastolic dysfunction in patients with coronary artery disease. J Am Coll Cardiol 2006;48:983-91.
Journal of the American Society of Echocardiography Volume 22 Number 5
10. Sengupta PP, Korinek J, Belohlavek M, Narula J, Jahangir A, Khandheria BK. Left ventricular structure and function: basic science for cardiac ultrasound imaging. J Am Coll Cardiol 2006;48:1988-2001. 11. Sengupta PP, Khandheria BK, Korinek J, Wang J, Jahangir A, Seward JB, et al. Apex-to-base dispersion in regional timing of left ventricular shortening and lengthening. J Am Coll Cardiol 2006;47:163-72. 12. Sengupta PP, Khandheria BK, Korinek J, Wang J, Belohlavek M. Biphasic tissue Doppler waveforms during isovolumic phases are associated with asynchronous deformation of subendocardial and subepicardial layers. J Appl Physiol 2005;99:1104-11. 13. Amundsen BH, Helle-Valle T, Edvardsen T, Torp H, Crosby J, Lyseggen E, et al. Noninvasive myocardial strain measured by speckle tracking echocardiography. Validation against sonomicrometry and tagged magnetic resonance imaging. J Am Coll Cardiol 2006;47:789-93. 14. Leitman M, Lysyansky P, Sidenko S, Shir V, Peleg E, Binenbaum M, et al. Two-dimensional strain—a novel software for real-time quantitative echocardiographic assessment of myocardial function. J Am Soc Echocardiogr 2004;17:1021-9. 15. Langeland S, D’Hooge J, Wouters PF, Leather A, Claus P, Bijnens B, et al. Experimental validation of a new ultrasound method for the simultaneous assessment of radial and longitudinal myocardial deformation independent of insonation angle. Circulation 2005;112:2157-62. 16. Serri K, Reant P, Lafitte M, Berhouet M, Le Bouffos V, Roudaut R, et al. Global and regional myocardial function quantification by two-dimensional strain. J Am Coll Cardiol 2006;47:1175-81. 17. Korinek J, Kjaergaard J, Sengupta PP, Yoshifuku S, McMahon EM, Cha SS, et al. High spatial resolution speckle tracking improves accuracy of 2-dimensional strain measurements: an update on a new method in functional echocardiography. J Am Soc Echocardiogr 2007;20:165-70. 18. Korinek J, Wang J, Sengupta PP, Miyazaki Ch, Kjaergaard J, McMahon E, et al. Two-dimensional strain—a Doppler-independent ultrasound method for quantitation of regional deformation: validation in vitro and in vivo. J Am Soc Echocardiogr 2005;18:1247-53. 19. Chan J, Hanekom L, Wong Ch, Leano R, Cho GY, Marwick TH. Differentiation of subendocardial and transmural infarction using two-dimensional strain rate imaging to assess short-axis and long-axis myocardial function. J Am Coll Cardiol 2006;48:2026-33. 20. Becker M, Hoffmann R, Kuhl HP, Grawe H, Katoh M, Kramann R, et al. Analysis of myocardial deformation based on ultrasonic pixel tracking to determine transmurality in chronic myocardial infarction. Eur Heart J 2006;27:2560-6. 21. Sun JP, Niu J, Chou D, Chuang HH, Wang K, Drinko J, et al. Alterations of regional myocardial function in a swine model of myocardial infarction assessed by echocardiographic 2-dimensional strain imaging. J Am Soc Echocardiogr 2007;20:498-504. 22. Dogan S, Aydin M, Gursurer M, Dursun A, Onuk T, Madak H. Prediction of subclinical left ventricular dysfunction with strain rate imaging in patients with mild to moderate rheumatic mitral stenosis. J Am Soc Echocardiogr 2006;19:243-8. 23. Helle-Valle T, Crosby J, Edvardsen T, Lyseggen E, Amundsen BM, Smith HJ, et al. New noninvasive method for assessment of left ventricular rotation. Speckle tracking echocardiography. Circulation 2005;112: 3149-56. 24. Notomi Y, Lysyansky P, Setser RM, Shiota T, Popovic ZB, MartinMiklovic MG, et al. Measurement of ventricular torsion by two-dimensional ultrasound speckle tracking imaging. J Am Coll Cardiol 2005;45:2034-41. 25. Kim HK, Sohn DW, Lee SE, Choi SY, Park JS, Kim YJ, et al. Assessment of left ventricular rotation and torsion with two-dimensional speckle tracking echocardiography. J Am Soc Echocardiogr 2007;20:45-53. 26. Takeuchi M, Nishikage T, Nakai H, Kokumai M, Otani S, Lang RM. The assessment of left ventricular twist in anterior wall myocardial infarction using two-dimensional speckle tracking imaging. J Am Soc Echocardiogr 2007;20:36-44. 27. Takeuchi M, Borden WB, Nakai H, Nishikage T, Kokumai M, Nagakura T, et al. Reduced and delayed untwisting of the left ventricle in patients with hypertension and left ventricular hypertrophy: a study using two-dimensional speckle tracking imaging. Eur Heart J 2007;28:2756-62.
Meluzin et al 493
28. Wang J, Khoury DS, Yue Y, Torre-Amione G, Nagueh SF. Left ventricular untwisting rate by speckle tracking echocardiography. Circulation 2007; 116:2580-6. 29. Takeuchi M, Nakai H, Kokumai M, Nishikage T, Otani S, Lang RM. Agerelated changes in left ventricular twist assessed by two-dimensional speckle-tracking imaging. J Am Soc Echocardiogr 2006;19:1077-84. 30. Van Dalen BM, Vletter WB, Soliman OII, ten Cate FJ, Geleijnse ML. Importance of transducer position in the assessment of apical rotation by speckle tracking echocardiography. J Am Soc Echocardiogr 2008;21:895-8. 31. Opdahl A, Helle-Valle T, Remme EW, Vartdal T, Pettersen E, Lunde K, et al. Apical rotation by speckle tracking echocardiography: a simplified bedside index of left ventricular twist. J Am Soc Echocardiogr 2008;21:1121-8. 32. Schiller NB, Shah PM, Crawford M, DeMaria A, Devereux R, Feigenbaum H, et al. Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. J Am Soc Echocardiogr 1989; 2:358-67. 33. Perk G, Tunick PA, Kronzon I. Non-Doppler two-dimensional strain imaging by echocardiography—from technical considerations to clinical application. J Am Soc Echocardiogr 2007;20:234-43. 34. Notomi Y, Setser RM, Shiota T, Martin-Miklovic MG, Weaver JA, Popovic ZB, et al. Assessment of left ventricular torsional deformation by Doppler tissue imaging. Validation study with tagged magnetic resonance imaging. Circulation 2005;111:1141-7. 35. Notomi Y, Martin-Miklovic MG, Oryszak SJ, Shiota T, Deserranno D, Popovic ZB, et al. Enhanced ventricular untwisting during exercise. A mechanistic manifestation of elastic recoil described by Doppler tissue imaging. Circulation 2006;113:2524-33. 36. MacGowan GA, Shapiro EP, Azhari H, Siu CO, Hees PS, Hutchins GM, et al. Noninvasive measurement of shortening in the fiber and cross-fiber directions in the normal human left ventricle and in idiopathic dilated cardiomyopathy. Circulation 1997;96:535-41. 37. Kanzaki H, Nakatani S, Yamada N, Urayama S, Miyatake K, Kitakaze M. Impaired systolic torsion in dilated cardiomyopathy: reversal of apical rotation at mid-systole characterized with magnetic resonance tagging method. Basic Res Cardiol 2006;101:465-70. 38. Rademakers FE, Buchalter MB, Rogers WJ, Zerhouni EA, Weisfeldt ML, Weiss JL, et al. Dissociation between left ventricular untwisting and filling. Accentuation by catecholamines. Circulation 1992;85:1572-81. 39. Ingels NB Jr, Hansen DE, Daughters GT, Stinson EB, Alderman EL, Miller DG. Relation between longitudinal, circumferential, and oblique shortening and torsional deformation in the left ventricle of the transplanted human heart. Circ Res 1989;64:915-27. 40. Waldman LK, Nosan D, Villarreal F, Novell JW. Relation between transmural deformation and local myofiber direction in canine left ventricle. Circ Res 1988;63:550-62. 41. Dec GW, Fuster W. Idiopathic dilated cardiomyopathy. N Engl J Med 1994;331:1564-75. 42. Paraskevaidis IA, Tsiapras D, Kyrzopoulos S, Cokkinos P, Iliodromitis EK, Parissis J, et al. The role of left ventricular long-axis contraction in patients with asymptomatic aortic regurgitation. J Am Soc Echocardiogr 2006;19: 249-54. 43. Yu ChM, Lin H, Yang H, Kong SL, Zhang Q, Lee SWL. Progression of systolic abnormalities in patients with isolated diastolic heart failure and diastolic dysfunction. Circulation 2002;105:1195-201. 44. Yip GW, Zhang Y, Tan PY, Wang M, Ho PY, Brodin LA, et al. Left ventricular long-axis changes in early diastole and systole: impact of systolic function on diastole. Clin Sci 2002;102:515-22. 45. Mizuguchi Y, Oishi Y, Miyoshi H, Iuchi A, Nagase N, Oki T. The functional role of longitudinal, circumferential, and radial myocardial deformation for regulating the early impairment of left ventricular contraction and relaxation in patients with cardiovascular risk factors: a study with two-dimensional strain imaging. J Am Soc Echocardiogr 2008;21:1138-44. 46. Korinek J, Anagnostopoulos PC, Pislaru C, Dzeja PP, Seward JB, Terzic A, et al. Both systolic and diastolic dysfunction characterize nonischemic inhibition of myocardial energy metabolism: an experimental strain rate echocardiographic study. J Am Soc Echocardiogr 2004;17:1239-44.