CLINICAL PERSPECTIVE

This Article Abstract Full Text (PDF) All Versions of this Article: 116/22/2580    most recent CIRCULATIONAHA.107.706770v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wang, J. Articles by Nagueh, S. F. Search for Related Content PubMed PubMed Citation Articles by Wang, J. Articles by Nagueh, S. F. Related Collections Congestive Myocardial cardiomyopathy disease Echocardiography

(Circulation. 2007;116:2580-2586.)
© 2007 American Heart Association, Inc.

Imaging

Left Ventricular Untwisting Rate by Speckle Tracking Echocardiography

Jianwen Wang, PhD, MD; Dirar S. Khoury, PhD; Yong Yue, PhD; Guillermo Torre-Amione, PhD, MD; Sherif F. Nagueh, MD

From the Department of Cardiology, The Methodist DeBakey Heart Center, The Methodist Hospital, Houston, Tex.

Correspondence to Dr Sherif F. Nagueh, Methodist DeBakey Heart Center, 6550 Fannin St, SM-677, Houston, TX 77030. E-mail snagueh{at}tmh.tmc.edu

Received March 31, 2007; accepted September 21, 2007.

	Abstract

Top Abstract Introduction Methods Results Discussion References

 
Background— Recent studies validated the measurement of left ventricular (LV) untwisting rate (UR) by speckle tracking echocardiography. A few reports suggest that it may provide additional noninvasive insight into LV diastolic function.

Methods and Results— Simultaneous echocardiographic imaging and LV pressure measurements (7F Millar catheters) were performed in 8 adult dogs. Loading conditions were altered by caval occlusion, whereas lusitropic state was changed by dobutamine and esmolol infusion. Inferior vena cava occlusion at all experimental stages (baseline, dobutamine, esmolol) led to a significant decrease (P0.01) in LV end-systolic volume (ESV) and a significant increase in UR (P=0.03). The best relation was observed between LV UR and ESV (r=–0.8, P<0.001). The clinical study was conducted in 67 patients (age 57±17 years, 19 women) undergoing simultaneous right heart catheterization and echocardiographic imaging, with 20 healthy subjects as a control group. There were 34 patients with ejection fraction (EF) <50% (25±9%), and 33 patients with normal EF and diastolic dysfunction (64±7%). Patients with LV systolic dysfunction had a significantly lower UR (–55 o/s) in comparison with the control group (–89 o/s) and patients with normal EF (–104 o/s, P<0.05), and the determinants of LV UR were twist, ESV, and (r²=0.83, P<0.001). In patients with diastolic dysfunction and normal EF, twist and ESV were the independent predictors (r²=0.71, P<0.001).

Conclusions— LV UR is reduced in patients with depressed EF, but not in those with diastolic dysfunction and normal EF, and is primarily determined by twist and ESV.

Key Words: diastole • echocardiography • heart failure • mechanics • myocardium

	Introduction

Top Abstract Introduction Methods Results Discussion References

 
Left ventricular (LV) filling results from the positive early diastolic transmitral pressure gradient. Therefore, it depends on both LV pressure drop during the isovolumetric relaxation period and left atrial (LA) driving pressure.^1,2 The rapid decline in LV pressure during this phase of the cardiac cycle is caused by active myocardial relaxation and LV elastic recoil. LV elastic recoil/untwisting generates the suction force for LV filling. Accordingly, LV untwisting rate (UR) may provide an additional noninvasive insight into LV diastolic function. Previous work with cardiac magnetic resonance (MR) in an animal model, has shown that LV UR correlates closely with the time constant of LV relaxation.³ However, there are very limited data on the clinical application of UR for the assessment of LV diastolic function.⁴ Moreover, its hemodynamic determinants in patients with cardiovascular disease have not been examined.

Clinical Perspective p 2586

More recently, speckle tracking echocardiography was applied for the derivation of LV twist and untwisting, with validation against sonomicrometry and cardiac MR.^5,6 We undertook the present study to investigate the hemodynamic determinants and the clinical application of UR measured by speckle tracking echocardiography.

	Methods

Top Abstract Introduction Methods Results Discussion References

 
Animal Preparation
The animal study was approved by the institutional Animal Protocol Review Committee, and animals were treated in compliance with the 1985 National Institutes of Health guidelines for the care and use of laboratory animals. Eight adult mongrel dogs weighing 19 to 30 kg were anesthetized with intravenous sodium pentobarbital (30 mg/kg body weight), intubated, and mechanically ventilated. A high-fidelity pressure catheter (7F Millar), calibrated relative to atmospheric pressure before introduction, was advanced into the LV (retrograde from the right femoral artery through the aortic valve) to record LV pressures continuously. A balloon catheter was advanced into the inferior vena cava (IVC) through the right femoral vein. The balloon was inflated in sequential steps to decrease LV filling. Throughout the procedure, surface ECG (lead II) and ventricular pressure signals were simultaneously acquired on a computer-based data acquisition system (Cardiodynamics BV, Leycom -CFL- 512, Argonstraat, the Netherlands).

Echocardiographic Studies
Dogs were imaged in the standard parasternal and apical views with a GE Vivid 7 ultrasound system. Image acquisition was carried out at a frame rate of 80 to 100 frames/sec, and 3 cardiac cycles were stored in cineloop format, for subsequent offline analysis.

Experimental Protocols
LV filling pressures were decreased with inflation of the balloon placed in the IVC. The occlusions were performed in a sequential manner with data acquired at stepwise decrements of LV end-diastolic pressure. After achieving a stable hemodynamic state at each LV end-diastolic pressure level, LV systolic and diastolic pressures, heart rate, and 2-dimensional images were acquired.

To evaluate the influence of LV relaxation on LV UR, dobutamine was administered at a dose of 5 µg/kg per min with reacquisition of echocardiographic and pressure data. Dobutamine infusion was then terminated, and after the animals returned to their baseline state, esmolol with its negative lusitropic properties was administered (0.5 mg/kg intravenously) with subsequent reacquisition of data. To assess the interaction between LV volume and relaxation on UR, IVC occlusion was repeated during the dobutamine infusion and later with esmolol.

Data Analysis
Hemodynamic Measurements
LV systolic and diastolic pressures were measured in addition to the time constant of LV pressure decay during the isovolumetric relaxation period ().⁷

Analysis of Twist Mechanics
The analysis was performed offline by a single observer without knowledge of hemodynamic data, using an EchoPac workstation (GE Healthcare, Amersham, United Kingdom). The endocardium was traced in the frame, where its complete contour was identified the best. The width of the region of interest was next adjusted to fit the whole myocardium. From these recordings, Echopac selects the speckles and tracks them during the cardiac cycle. The analyst verifies the accuracy of the tracking with the option of subsequent endocardial retracing and adjustment of the size of the region of interest as needed. At the end, the analysis program displays the rotation angle against time during the cardiac cycle in the apical and basal short-axis views. Counterclockwise rotation is marked as a positive value and clockwise rotation as a negative value when viewed from the apex. The tracing of the rotation (in degrees), rotation rate (degrees/s), and echocardiogram at the apical and basal short-axis levels are exported into MATLAB (Mathworks, Natick, Mass), and the difference between apical and basal rotations at each corresponding time point is calculated, including the time derivative of LV twisting and untwisting.⁶

Human Studies
Study Sample
The study protocol was approved by the Patient Advocacy Counsel review board, and patients provided written informed consent. Sixty-seven patients (age 57±17 years, 19 women) in sinus rhythm undergoing right heart catheterization were enrolled in this study. Transthoracic echocardiography and hemodynamic recordings were performed simultaneously. Patients with inadequate images for echocardiographic analysis were excluded (n=9). Otherwise, the patients were consecutive.

The sample was divided into 2 groups on the basis of LV EF. There were 34 patients with EF<50% and increased mean wedge pressure (SHF), and 33 patients with EF50%. Among the 33 patients with preserved EF, there were 24 patients who met the clinical and invasive criteria of diastolic heart failure.⁸ The other 9 patients had impaired LV relaxation but normal mean wedge pressure. In the SHF group, all patients were on diuretics, 8 were on intravenous inotropic/vasodilator therapy, 26 were on oral angiotensin-converting enzyme inhibitor, and 9 were receiving β-blockers. For the other group, 24 patients were on diuretics, 15 were on calcium-channel blocking drugs, 15 were on angiotensin-converting enzyme inhibitor, and 13 were receiving β-blockers. We included 20 subjects without cardiac disease as a control group for comparison purposes (no catheterization performed for the control group).

Echocardiographic Studies
Patients were imaged in a supine position using a GE Vivid 7 ultrasound system. Two-dimensional grayscale images were acquired in the standard parasternal and apical (apical 4, apical 2, and apical long) views at a frame rate of 80 to 100 frames/second, and 3 cardiac cycles were recorded. Care was taken to obtain parasternal circular short-axis tomograms at 3 distinct levels: basal (identified by the mitral valve), papillary, and apical (no papillary muscles noted). In the apical 4-chamber view, conventional Doppler and tissue Doppler velocities were obtained at end expiration as previously described.^1,2 All images were stored digitally for subsequent offline analysis.

Conventional Echocardiographic Analysis
The analysis was performed offline by a single observer using EchoPac workstation without knowledge of hemodynamic data. LV volumes (end-diastolic volume, end-systolic volume (ESV), and EF), and LA volume were measured according to the recent guidelines of the American Society of Echocardiography.⁹ All Doppler values represent the average of 3 consecutive beats. Mitral inflow was analyzed as previously described.^1,2 Ea velocity was measured and the dimensionless ratio E/Ea^1,2 was computed. Similar to the canine experiments, LV twist mechanics was analyzed. Absolute time intervals were measured and also expressed in relation to systolic duration with the time at end-systole marked as 100%.

Reproducibility
Interobserver reproducibility was assessed in 14 cases with the use of previously acquired images but not necessarily the same heart beats. A significant correlation was present (r=0.85, P<0.01, UR rate: 50±21°/s versus 49±22°/s) without a trend for over- or underestimation.

Hemodynamic Measurements
The pressure transducers were balanced before data acquisition with the zero level at mid-axillary line. Pulmonary artery (PA) catheters were used to measure PA pressure, mean right atrial pressure, and mean wedge pressure. The wedge position was verified by changes in waveform and O₂ saturation. The was calculated using the previously validated expression¹⁰: =IVRT/(lnLVSP–lnPCWP), where IVRT is isovolumetric relaxation time, ln is natural logarithm, LVSP is LV end-systolic pressure calculated as 0.9xsystolic blood pressure,¹¹ and PCWP is pulmonary capillary wedge pressure.

Statistical Analyses
Analyses were performed using Sigma Stat (3.1). Continuous data are presented as mean±SD or median (25th to 75th percentiles) for normal/nonnormal data, respectively. Dichotomous data are shown as number (%). A previous study in animals noted a significant correlation coefficient of 0.92 between LV recoil rate and .³ Therefore, the number of animals was selected to detect a similar correlation coefficient at an level of 0.05 and a power of 90%. The hemodynamic and echocardiographic measurements were compared in the experimental stages by use of repeated measures ANOVA with pairwise multiple comparison procedures performed using the Holm-Sidak method.

For human studies, the sample size was selected to detect a minimum difference among the 3 groups (normal, patients with EF<50%, and patients with EF50%) in UR of 30°/s, with a SD of 30°/s, at an =0.05 and a power of 90%. Comparisons between the 3 groups were performed using ANOVA, with subsequent pairwise comparisons carried out using the Holm-Sidak method when the data had a normal distribution. When the normality test failed, Kruskal-Wallis 1-way ANOVA on ranks was applied, with subsequent pairwise comparisons carried out by the Dunn method. The relationship between different continuous variables was analyzed using single and multiple regression analyses. Results were considered significant when P0.05.

The authors had full access to and take full responsibility for the integrity of the data. All authors have read and agree to the manuscript as written.

	Results

Top Abstract Introduction Methods Results Discussion References

 
Animal Experiments
Dobutamine and esmolol infusions led to opposite changes in heart rate (beats/min) (baseline 99±10, dobutamine 119±9, esmolol 91±10; P<0.001), LV systolic pressure (mm Hg) (baseline 91±27, dobutamine 170±38, esmolol 82±26; P<0.001), (ms) (baseline 39±5, dobutamine 29±5, esmolol 64±7 ms; P<0.001), ESV (baseline: 37±14; dobutamine: 26±11; esmolol: 47±15 mL; P<0.001), and untwisting rate (°/s) (baseline 75±31, dobutamine 103±45, esmolol 57±25; P=0.008). LV twist increased with dobutamine, and decreased with esmolol (P<0.001), and was significantly related to ESV and untwisting rate, with several significant correlations between twist, twisting and untwisting rates (r=0.64, P<0.01).

Impact of LV ESV on the Relation Between UR and LV Relaxation
At baseline (without drug infusion), IVC occlusion led to a significant decrease in ESV (baseline 37±14 versus 21±8 mL; P=0.01), and an increase in UR (baseline 75±31 versus 109±31°/s; P=0.03), but without a significant change in (baseline 39±5 versus 35±8 ms; P=0.24). Likewise, IVC occlusion during dobutamine infusion resulted in a significant decrease in ESV (P=0.01) and an increase in UR (P=0.03) despite no significant change in (P=0.4). Similar results were observed with IVC occlusion during esmolol infusion (ESV 47±15 versus 33±16 mL, P=0.01; UR 57±25 versus 73±30°/s, P=0.03; 64±7 versus 60±9 ms, P=0.33). In addition, on examination of experimental stages where LV ESV was comparable (eg, baseline status versus IVC occlusion during the infusion of esmolol (baseline ESV 37±14 mL) versus IVC occlusion during esmolol infusion (ESV 33±16 mL); P=0.5), LV URs were similar (75±31 versus 73±30°/s; P=0.6), despite large and significant differences in (39±5 versus 60±9 ms; P=0.01). On regression analysis, the best correlation was observed between LV UR and ESV (inverse first order where y = y₀+a/x, r=–0.8; P<0.001) (Figure 1).

View larger version (9K): [in this window] [in a new window]   Figure 1. Regression plot (Y versus 1/X) between LV UR and LV ESV in the animal experiments.

Human Studies
Tables 1 and 2 present a summary of the hemodynamic and echocardiographic findings in the study sample. As expected, patients with systolic dysfunction had significantly larger LV and LA volumes and lower EF values. Likewise, they had significantly higher PA and wedge pressures (Table 1). Patients with depressed EF also had significantly higher E/A, and E/Ea ratios in comparison with patients with diastolic dysfunction and normal EF (Table 2).

View this table: [in this window] [in a new window]   Table 1. Clinical Characteristics and Hemodynamic Measurements

View this table: [in this window] [in a new window]   Table 2. Echocardiographic Measurements

LV Twist and Twisting Rate
The control group had a mean LV twist of 12±4°. This was significantly reduced in patients with SHF (P<0.01 versus control group and versus patients with diastolic dysfunction) (Table 2), but not in those with diastolic dysfunction (P>0.2 versus control group). Similar results were observed for LV twisting rate (Table 2), which was significantly lower in patients with SHF than the other 2 groups (Figure 2). Interestingly, patients with diastolic dysfunction who were receiving β-blockers had a significantly lower twist rate than those who were not on this medication (7.6° versus 13.6°; P<0.01).

View larger version (53K): [in this window] [in a new window]   Figure 2. Examples of LV twist and its time derivative from 3 cases. Top left, the twist curve from a subject in the control group (twist=17°). Top middle, from a patient with diastolic dysfunction and normal EF (16°); top right, the reduced twist from a patient with depressed EF (5°). Lower left, the time derivative of LV twist from a normal subject (UR=–90°/s). Lower middle, from a patient with diastolic dysfunction and normal EF (UR=–90°/s); and lower right, from a patient with systolic dysfunction (UR=–50°/s).

Left Ventricular UR
Patients with LV systolic dysfunction had a significantly lower UR (Table 2) in comparison with the control group and patients with diastolic dysfunction. This was caused by differences at the basal (SHF 32, versus control 59, and diastolic dysfunction 57°/s; P<0.05) and apical (SHF –37, versus control –69, and diastolic dysfunction –70°/s; P<0.05) levels. However, no significant differences existed between patients with diastolic dysfunction and the control group. These results were unchanged (P=0.4) when comparison was limited to the control group and patients with heart failure and normal EF (ie, when the 9 patients with impaired LV relaxation and normal mean wedge pressure were excluded). Interestingly, patients with diastolic dysfunction who were receiving β-blockers had a significantly lower UR than those who were not on this medication (90°/s versus 117°/s, P=0.02).

LV untwisting began an average of 15±15 ms before aortic valve closure in the control group. Similar findings were noted in the group with diastolic dysfunction (5±48 ms, P>0.1). However, there were 12 patients with diastolic dysfunction where LV untwisting occurred after aortic valve closure by 26±18 ms. In comparison, LV untwisting was significantly delayed in SHF patients and began 37±63 ms after aortic valve closure (P<0.05 versus the other 2 groups). In relation to mitral inflow, peak LV untwisting (116±10% of systolic duration) occurred before mitral E velocity in all subjects in the control group, whereas it was delayed in patients with SHF (165±23% of systolic duration; P<0.01). In the diastolic dysfunction group, peak untwisting occurred at a time (118±33% of systolic duration) that was not significantly different from that in the control group (P>0.1). However, the 12 patients with delayed onset of untwisting also showed delayed peak untwisting that occurred almost simultaneously with mitral E velocity (133±6% of systolic duration). In the other 21 patients with diastolic dysfunction, peak untwisting preceded mitral E velocity. Interestingly, the 12 patients with delayed untwisting showed a trend of having a larger LA volume (40±13 versus 33±16 mL/m²; P=0.08) and a higher PA systolic pressure (43±11 versus 35±16 mm Hg; P=0.06).

Hemodynamic Determinants of LV UR in Patients With Depressed EF
LV UR was significantly related to systolic twist (r=0.6, P=0.001) (Figure 3), (r=–0.78, P<0.001) (Figure 4), LV end-diastolic volume (r=–0.50, P=0.05), LVESV (r=–0.64, P<0.001) (Figure 5), and LVEF (r=0.55, P=0.03), but not heart rate (P>0.1). A nonsignificant association was present with mean wedge pressure (r=–0.4, P=0.06). On multiple regression analysis, , ESV, and twist were the independent predictors of LV UR (r²=0.83, P<0.001).

View larger version (11K): [in this window] [in a new window]   Figure 3. Regression plots between LV UR and twist. Patients with heart failure and depressed EF (DEF) are shown to the left, whereas patients with normal EF (NEF) are shown to the right.

View larger version (10K): [in this window] [in a new window]   Figure 4. Regression plots between LV UR and . Patients with heart failure and depressed EF (DEF) are shown to the left, whereas patients with normal EF (NEF) are shown to the right.

View larger version (10K): [in this window] [in a new window]   Figure 5. Regression plots between LV UR and ESV. Patients with heart failure and depressed EF (DEF) are shown to the left, whereas patients with normal EF (NEF) are shown to the right.

Hemodynamic Determinants of LV UR in Patients With Diastolic Dysfunction
LV UR was significantly related to systolic twist (r=0.61, P=0.001) (Figure 3), pulmonary capillary wedge pressure (r=–0.5, P=0.05), LV end-diastolic volume (r=–0.50, P=0.05), LVESV (r=–0.8, P<0.001) (Figure 5), and LVEF (r=0.6, P=0.02). No significant relationships were noted between the UR and heart rate (P>0.05) and (r=–0.29, P=0.15) (Figure 4). On multiple regression analysis, ESV and twist were the independent predictors of LV UR (r²=0.71, P<0.001).

	Discussion

Top Abstract Introduction Methods Results Discussion References

 
This study shows that LV twist, twisting rate, and UR are reduced in patients with LV systolic dysfunction and depressed EF, but not in those with diastolic dysfunction and normal EF. In both patient groups, LV twist and ESV had strong and significant relations with the UR.

Hemodynamic Determinants of LV UR
In normal subjects, LV filling occurs as a result of the rapid decline in LV pressure caused by LV relaxation and elastic recoil. The latter term refers to the energy stored during systole that is released in early diastole. In that regard, previous studies with cardiac MR in animals have shown that 40% of systolic twist is released during the isovolumetric relaxation period.³ Similar results were noted in human studies with tissue Doppler–based measurements of LV twist.⁴ Although the previous animal study³ with MR supports the premise that LV UR can be used as a noninvasive index of LV relaxation, there are other factors that affect it and limit its clinical application for that purpose.

These variables include LV contractility/ESV (along with the relation of ESV to the equilibrium volume) and LV twist.¹² Therefore, the significant correlations of LV UR to LV twist and to ESV (Figures 3 and 5) are not surprising. Importantly, the animal experiments show that, at a comparable ESV, LV UR was similar despite large and significant differences in . The results from the animal experiments help explain the lack of a correlation between LV UR and in patients with heart failure and normal EF. However, the results of our animal model, wherein short-term changes were induced in LV relaxation and preload, cannot be extrapolated to patients with chronic systolic heart failure. Therefore, additional insights may be gained by examination of the hemodynamic determinants of the twist mechanics in an animal model of chronic systolic heart failure.

LV UR is also affected by LV preload, in that we observed significant inverse correlations between UR and 2 measurements of preload: end-diastolic volume and mean wedge pressure. In that regard, our observations are similar to previous work in humans in which a different method was used to calculate LV UR.¹³ In that previous study, simultaneous pressure and biplane cinefluoroscopic marker images were used to examine the effect of loading conditions and inotropic stimulation on LV twist mechanics.¹³ The authors noted that volume loading with saline infusion decreases early diastolic untwisting. It is possible to explain this observation when one considers that volume loading can lead to higher ESV and therefore to reduced recoil forces.

LV UR in Patients With Depressed EF
In the presence of systolic heart failure, reduced LV filling exists, in part caused by an impaired ability to utilize suction. This has been shown in animal models^14,15 as well as in patients.¹⁶ As a result of reduced contractility, ESV may not be lower than the equilibrium volume, even though the latter is increased. These changes result in a reduction in the restoring force. In turn, interstitial remodeling and changes in the relative expression of titin isoforms may provide a plausible hypothesis that can explain the reduction in restoring forces. The deformation of titin during systole below slack length generates a restoring force.¹⁷ Titin exists in 2 isoforms, a stiffer N2B isoform and a larger, more compliant N2BA isoform.¹⁸ The N2BA isoform results in a lower passive stiffness as well as a reduced restoring force in comparison with the N2B isoform.¹⁸ In that regard, we have recently shown that the ratio of N2BA to N2B titin isoforms is increased in patients with idiopathic dilated cardiomyopathy, and this ratio was significantly correlated with LV ESV, such that patients with the highest ratio had the largest ESV.¹⁹

LV UR in Patients With Diastolic Dysfunction and Normal EF
Patients with diastolic dysfunction and normal EF have a LV UR that is similar to that observed in the control group, but significantly higher than that in patients with depressed EF. With respect to this finding, our observations with speckle tracking echocardiography are similar to those reported with other techniques. Specifically, Hees et al used cardiac MR to show that diastolic changes with aging occur in the presence of a normal UR.²⁰ Likewise, Notomi et al used tissue Doppler to show that patients with hypertrophic cardiomyopathy (and diastolic dysfunction) have a UR similar to normal subjects.⁴ Collectively, these observations indicate that LV relaxation is not the main determinant of untwisting in this population.

The relation between LV UR and ESV can help explain the above findings. In particular, patients in this group have a normal or reduced ESV and increased restoring forces. A recent study is suggestive of a higher ratio of N2B to N2BA titin isoforms in patients with diastolic heart failure.²¹ When compressed, the N2B isoform results in higher restoring forces¹⁸ and can account for the normal LV UR seen in this group. Finally, the normal UR in patients with diastolic heart failure may be viewed as a compensatory mechanism that helps LV filling, given the presence of abnormalities in diastolic function that can adversely affect LV filling. The presence of a trend toward larger LA volumes and higher PA pressures in patients with delayed untwisting favor this hypothesis, but additional studies with more patients are needed for definitive proof.

Aside from the implications of the present study for LV diastolic function in this population, the presence of normal twist mechanics is indicative that this aspect of systolic function is preserved, and does not contribute to heart failure symptoms.

Limitations
The accurate measurement of LV twist/untwist by speckle tracking is contingent on high-quality recordings, high tracking quality, and the correct recognition of anatomic structures that identify the basal and apical short-axis levels. Our results were obtained using the highest frame rate that allows for accurate tracking and we also verified the tracking accuracy visually, retracing and repositioning the region of interest as needed. Nevertheless, 9 patients (12%) were excluded for technical reasons.

The control group was younger than the other 2 groups, and patients with depressed EF were also younger than those with diastolic dysfunction. However, most recently, Kim et al have shown no significant change with age in basal and apical URs in healthy normal volunteers between <31 to >60 years old.²² Similar results were also reported by cardiac MR where the recoil rate had no significant relation with age (r=0.19, P=0.11) in 122 normal subjects between 21 and 92 years old.²⁰ Furthermore, in consideration of only age-matched patients (depressed and normal EF) and controls (ie, excluding 6 controls, 8 patients with depressed EF, and 6 patients with diastolic dysfunction), the results in Table 2 were still present at a significant level (P<0.05). Finally, it would have been ideal to measure in patients with high-fidelity pressure catheters. However, the method used has been well validated previously.¹⁰ In addition, LV catheterization was not indicated at the time of the study, and it was difficult to subject the patients to the additional risks of such catheterization for the sole purpose of this investigation. Exercise stress testing can show differences between healthy subjects and patients with heart failure and normal EF.⁴ However, stress was not included in the study design, given the fact that these were heart failure patients undergoing invasive hemodynamic measurements and were unable to exercise.

	Acknowledgments

 
Sources of Funding

Dr Nagueh is supported by the Milton Carroll Houston Endowment Cardiovascular Research Fund.

Disclosures

Dr Khoury has received a research grant from St. Jude Medical. Dr Nagueh has received consulting fees from St. Jude Medical and fees for invited lectures from Medtronic. The other authors report no conflicts.

	References

Top Abstract Introduction Methods Results Discussion References

 
1. Quinones MA. Assessment of diastolic function. Prog Cardiovasc Dis. 2005; 47: 340–355.[CrossRef][Medline] [Order article via Infotrieve]

2. Oh JK, Hatle L, Tajik AJ, Little WC. Diastolic heart failure can be diagnosed by comprehensive two-dimensional and Doppler echocardiography. J Am Coll Cardiol. 2006; 47: 500–506.[Abstract/Free Full Text]

3. Dong SJ, Hees PS, Siu CO, Weiss JL, Shapiro EP. MRI assessment of LV relaxation by untwisting rate: a new isovolumic phase measure of tau. Am J Physiol Heart Circ Physiol. 2001; 281: H2002–H2009.[Abstract/Free Full Text]

4. Notomi Y, Martin-Miklovic MG, Oryszak SJ, Shiota T, Deserranno D, Popovic ZB, Garcia MJ, Greenberg NL, Thomas JD. Enhanced ventricular untwisting during exercise: a mechanistic manifestation of elastic recoil described by Doppler tissue imaging. Circulation. 2006; 113: 2524–2533.[Abstract/Free Full Text]

5. Helle-Valle T, Crosby J, Edvardsen T, Lyseggen E, Amundsen BH, Smith HJ, Rosen BD, Lima JA, Torp H, Ihlen H, Smiseth OA. New noninvasive method for assessment of left ventricular rotation: speckle tracking echocardiography. Circulation. 2005; 112: 3149–3156.[Abstract/Free Full Text]

6. Notomi Y, Lysyansky P, Setser RM, Shiota T, Popovic ZB, Martin-Miklovic MG, Weaver JA, Oryszak SJ, Greenberg NL, White RD, Thomas JD. Measurement of ventricular torsion by two-dimensional ultrasound speckle tracking imaging. J Am Coll Cardiol. 2005; 45: 2034–2041.[Abstract/Free Full Text]

7. Weiss JL, Frederiksen JW, Weisfeldt ML. Hemodynamic determinants of the time-course of fall in canine left ventricular pressure. J Clin Invest. 1976; 58: 751–760.[Medline] [Order article via Infotrieve]

8. Quinones MA, Zile MR, Massie BM, Kass DA; Writing Committee of the Dartmouth Diastolic Discourses. Chronic heart failure: a report from the Dartmouth Diastole Discourses. Congest Heart Fail. 2006; 12: 162–165.[CrossRef][Medline] [Order article via Infotrieve]

9. Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, Picard MH, Roman MJ, Seward J, Shanewise JS, Solomon SD, Spencer KT, Sutton MS, Stewart WJ; Chamber Quantification Writing Group; American Society of Echocardiography’s Guidelines and Standards Committee; European Association of Echocardiography. Recommendations for chamber quantification: a report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr. 2005; 18: 1440–1463.[CrossRef][Medline] [Order article via Infotrieve]

10. Scalia GM, Greenberg NL, McCarthy PM, Thomas JD, Vandervoort PM. Noninvasive assessment of the ventricular relaxation time constant (tau) in humans by Doppler echocardiography. Circulation. 1997; 95: 151–155.[Abstract/Free Full Text]

11. Kelly RP, Ting CT, Yang TM, Liu CP, Maughan WL, Chang MS, Kass DA. Effective arterial elastance as index of arterial vascular load in humans. Circulation. 1992; 86: 513–521.[Abstract/Free Full Text]

12. Bell SP, Nyland L, Tischler MD, McNabb M, Granzier H, LeWinter MM. Alterations in the determinants of diastolic suction during pacing tachycardia. Circ Res. 2000; 87: 235–240.[Abstract/Free Full Text]

13. Moon MR, Ingels NB Jr, Daughters GT, Stinson EB, Hansen DE, Miller DC. Alterations in left ventricular twist mechanics with inotropic stimulation and volume loading in human subjects. Circulation. 1994; 89: 142–150.[Abstract/Free Full Text]

14. Cheng CP, Noda T, Nozawa T, Little WC. Effect of heart failure on the mechanism of exercise-induced augmentation of mitral valve flow. Circ Res. 1993; 72: 795–806.[Abstract/Free Full Text]

15. Solomon SB, Nikolic SD, Glantz SA, Yellin EL. Left ventricular diastolic function of remodeled myocardium in dogs with pacing-induced heart failure. Am J Physiol. 1998; 274: H945–H954.[Medline] [Order article via Infotrieve]

16. Nishimura R, Tajik A. Evaluation of diastolic filling of left ventricle in health and disease Doppler echocardiography is the clinician’s Rosetta stone. J Am Coll Cardiol. 1997; 30: 8–18.[Abstract]

17. Helmes M, Trombitas K, Granzier H. Titin develops restoring force in rat cardiac myocytes. Circ Res. 1996; 79: 619–626.[Abstract/Free Full Text]

18. Granzier HL, Labeit S. The giant protein titin: a major player in myocardial mechanics, signaling, and disease. Circ Res. 2004; 94: 284–295.[Abstract/Free Full Text]

19. Nagueh SF, Shah G, Wu Y, Torre-Amione G, King NM, Lahmers S, Witt CC, Becker K, Labeit S, Granzier HL. Altered titin expression, myocardial stiffness and left ventricular function in patients with dilated cardiomyopathy. Circulation. 2004; 110: 155–162.[Abstract/Free Full Text]

20. Hees PS, Fleg JL, Dong SJ, Shapiro EP. MRI and echocardiographic assessment of the diastolic dysfunction of normal aging: altered LV pressure decline or load? Am J Physiol Heart Circ Physiol. 2004; 286: H782–H788.[Abstract/Free Full Text]

21. van Heerebeek L, Borbely A, Niessen HW, Bronzwaer JG, van der Velden J, Stienen GJ, Linke WA, Laarman GJ, Paulus WJ. Myocardial structure and function differ in systolic and diastolic heart failure. Circulation. 2006; 113: 1966–1973.[Abstract/Free Full Text]

22. Kim HK, Sohn DW, Lee SE, Choi SY, Park JS, Kim YJ, Oh BH, Park YB, Choi YS. Assessment of left ventricular rotation and torsion with two-dimensional speckle tracking echocardiography. J Am Soc Echocardiogr. 2007; 20: 45–53.[CrossRef][Medline] [Order article via Infotrieve]

---

 

CLINICAL PERSPECTIVE

Left ventricular (LV) twist and untwist can provide unique insight into myocardial systolic and diastolic function. Speckle tracking echocardiography was recently validated as an accurate method that can assess twist mechanics, which extends the potential application of this measurement to settings where cardiac magnetic resonance imaging is not appropriate. This study was performed to investigate the hemodynamic determinants and the clinical application of LV untwisting rate. In an animal model, LV end-systolic volume was the primary determinant of the untwisting rate, such that LV untwisting best tracked changes in end-systolic volume rather than the time constant of LV relaxation. In 34 patients with ejection fraction <50%, twist and untwisting rate were significantly lower than normal controls, whereas in cardiac patients with ejection fraction 50%, they were similar to the control group. In both groups, the primary determinants of untwisting rate were LV twist and end-systolic volume. These findings indicate that in heart failure patients with normal ejection fraction, LV twist and untwisting rate are preserved, and appear not to contribute to their symptoms.

This article has been cited by other articles:

				H.-J. Nesser, V. Mor-Avi, W. Gorissen, L. Weinert, R. Steringer-Mascherbauer, J. Niel, L. Sugeng, and R. M. Lang Quantification of left ventricular volumes using three-dimensional echocardiographic speckle tracking: comparison with MRI Eur. Heart J., July 1, 2009; 30(13): 1565 - 1573. [Abstract] [Full Text] [PDF]

				V. Ferferieva, P. Claus, K. Vermeulen, C. Missant, M. Szulik, F. Rademakers, and J. D'hooge Echocardiographic assessment of left ventricular untwist rate: comparison of tissue Doppler and speckle tracking methodologies Eur J Echocardiogr, July 1, 2009; 10(5): 683 - 690. [Abstract] [Full Text] [PDF]

				T. Helle-Valle, E. W. Remme, E. Lyseggen, E. Pettersen, T. Vartdal, A. Opdahl, H.-J. Smith, N. F. Osman, H. Ihlen, T. Edvardsen, et al. Clinical assessment of left ventricular rotation and strain: a novel approach for quantification of function in infarcted myocardium and its border zones Am J Physiol Heart Circ Physiol, July 1, 2009; 297(1): H257 - H267. [Abstract] [Full Text] [PDF]

				Y. T. Tan, F. Wenzelburger, E. Lee, G. Heatlie, F. Leyva, K. Patel, M. Frenneaux, and J. E. Sanderson The pathophysiology of heart failure with normal ejection fraction exercise echocardiography reveals complex abnormalities of both systolic and diastolic ventricular function involving torsion, untwist, and longitudinal motion. J. Am. Coll. Cardiol., June 30, 2009; 54(1): 36 - 46. [Abstract] [Full Text] [PDF]

				T. T. Phan, G. N. Shivu, K. Abozguia, M. Gnanadevan, I. Ahmed, and M. Frenneaux Left ventricular torsion and strain patterns in heart failure with normal ejection fraction are similar to age-related changes Eur J Echocardiogr, June 6, 2009; (2009) jep072v1. [Abstract] [Full Text] [PDF]

				A. T. Burns, A. La Gerche, D. L. Prior, and A. I. MacIsaac Left Ventricular Untwisting Is an Important Determinant of Early Diastolic Function J. Am. Coll. Cardiol. Img., June 1, 2009; 2(6): 709 - 716. [Abstract] [Full Text] [PDF]

				I. K. Russel, M. J.W. Gotte, J. G. Bronzwaer, P. Knaapen, W. J. Paulus, and A. C. van Rossum Left ventricular torsion an expanding role in the analysis of myocardial dysfunction. J. Am. Coll. Cardiol. Img., May 1, 2009; 2(5): 648 - 655. [Abstract] [Full Text] [PDF]

				A. E. Weyman The year in echocardiography. J. Am. Coll. Cardiol., April 28, 2009; 53(17): 1558 - 1567. [Full Text] [PDF]

				J. Wang and S. F. Nagueh Current Perspectives on Cardiac Function in Patients With Diastolic Heart Failure Circulation, March 3, 2009; 119(8): 1146 - 1157. [Full Text] [PDF]

				S. F. Nagueh, C. P. Appleton, T. C. Gillebert, P. N. Marino, J. K. Oh, O. A. Smiseth, A. D. Waggoner, F. A. Flachskampf, P. A. Pellikka, and A. Evangelisa Recommendations for the Evaluation of Left Ventricular Diastolic Function by Echocardiography Eur J Echocardiogr, March 1, 2009; 10(2): 165 - 193. [Full Text] [PDF]

				B. T. Esch and D. E. R. Warburton Left ventricular torsion and recoil: implications for exercise performance and cardiovascular disease J Appl Physiol, February 1, 2009; 106(2): 362 - 369. [Abstract] [Full Text] [PDF]

				M Saito, H Okayama, K Nishimura, A Ogimoto, T Ohtsuka, K Inoue, G Hiasa, T Sumimoto, J Funada, Y Shigematsu, et al. Determinants of left ventricular untwisting behaviour in patients with dilated cardiomyopathy: analysis by two-dimensional speckle tracking Heart, February 1, 2009; 95(4): 290 - 296. [Abstract] [Full Text] [PDF]

				G. Dwivedi, M. P. Frenneaux, and J. E. Sanderson Letter by Dwivedi et al Regarding Article, "Left Ventricular Untwisting Rate by Speckle Tracking Echocardiography" Circulation, May 13, 2008; 117(19): e336 - e336. [Full Text] [PDF]

				J. Wang, D. S. Khoury, Y. Yue, G. Torre-Amione, and S. F. Nagueh Response to Letter Regarding Article, "Left Ventricular Untwisting Rate by Speckle Tracking Echocardiography" Circulation, May 13, 2008; 117(19): e337 - e337. [Full Text] [PDF]

				J. Wang, D. S. Khoury, Y. Yue, G. Torre-Amione, and S. F. Nagueh Preserved left ventricular twist and circumferential deformation, but depressed longitudinal and radial deformation in patients with diastolic heart failure Eur. Heart J., May 2, 2008; 29(10): 1283 - 1289. [Abstract] [Full Text] [PDF]

				T. C. Gillebert and N. R. Van de Veire About left ventricular torsion, sex differences, shear strain, and diastolic heart failure Eur. Heart J., May 2, 2008; 29(10): 1215 - 1217. [Full Text] [PDF]

				P. P. Sengupta, A. J. Tajik, K. Chandrasekaran, and B. K. Khandheria Twist mechanics of the left ventricle principles and application. J. Am. Coll. Cardiol. Img., May 1, 2008; 1(3): 366 - 376. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) All Versions of this Article: 116/22/2580    most recent CIRCULATIONAHA.107.706770v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wang, J. Articles by Nagueh, S. F. Search for Related Content PubMed PubMed Citation Articles by Wang, J. Articles by Nagueh, S. F. Related Collections Congestive Myocardial cardiomyopathy disease Echocardiography