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Ventricular Structure and Function Simultaneous Longitudinal Strain in All 4 Cardiac Chambers A Novel Method for Comprehensive Functional Assessment of the Heart Karima Addetia, MD; Masaaki Takeuchi, MD, PhD; Francesco Maffessanti, PhD; Yasufumi Nagata, MD; James Hamilton, PhD; Victor Mor-Avi, PhD; Roberto M. Lang, MD Downloaded from http://circimaging.ahajournals.org/ by guest on May 11, 2017 Background—Simultaneous assessment of longitudinal strain (LS) by 2D speckle-tracking echocardiography in all 4 cardiac chambers has not yet been explored. Our goal was to study LS curves obtained simultaneously from all 4 cardiac chambers in healthy subjects to gain insight into interchamber functional relationships. Methods and Results—We studied 259 healthy subjects (age 44±15; 118 men) in whom it was possible to obtain apical 4-chamber views that contained the entire left and right ventricles and both atria in the same sector. 2D speckle-tracking echocardiography was performed in all 4 chambers in the same cardiac cycle, while considering the interventricular septum as part of the left ventricle and including the interatrial septum in the LS measurements for both atria. LS was measured over time using vendor-independent software (Epsilon), resulting in peak LS and time-to-peak strain. Strain curves of the right ventricle and right atrium were larger in magnitude than those of the left ventricle and left atrium, whereas time-to-peak values were shorter. LS for the ventricles peaked earlier than the LS for the corresponding atria. Peak systolic LS values were larger in magnitude in women than in men. For both atria, LS declined with age and timeto-peak increased. Left ventricle LS declined minimally with age, but right ventricle free-wall LS augmented with age until the sixth decade. Conclusions—Simultaneous measurement of LS provides new insights into interchamber relationships. This new tool may prove useful in evaluating diseases that affect cardiac chambers differently. (Circ Cardiovasc Imaging. 2016;9:e003895. DOI: 10.1161/CIRCIMAGING.115.003895.) Key Words: atrial function ◼ cardiac function ◼ longitudinal strain ◼ strain ◼ ventricular function R ecent technological advancements have enabled direct measurements of myocardial deformation indices, such as strain and strain rate. Over the past decade, a multitude of studies have reported myocardial deformation measurements in a variety of disease states, advancing our knowledge of cardiac physiology and improving prediction of clinical outcomes.1–3 Although it is widely recognized that the ventricles and atria are functionally inter-related, currently, deformation assessment can only be performed for each chamber sequentially using different cardiac cycles. This limitation could affect the ability to study interchamber coupling because of the physiological beat-to-beat variability. Comprehensive functional assessment of the heart by simultaneous strain measurement of all cardiac chambers during the same cardiac cycle would eliminate this limitation and, thus, improve the evaluation of interchamber relationships. Accordingly, new software was recently developed for simultaneous strain measurements of all cardiac chambers using 2-dimensional (2D) speckle-tracking echocardiography from apical 4-chamber views. See Editorial by Baron and Flachskampf See Clinical Perspective It has been shown that left ventricular (LV) deformation indices are age- and sex-dependent.4,5 However, little is known about age- and sex-related differences in deformation measurements of the other cardiac chambers. Our goal was to study the normal interchamber functional relationships in a large group of healthy subjects over a wide age range using this new software and to determine age- and sex-specific differences in combined all-chamber strain assessment. Methods Study Population We studied 259 normal subjects over a wide range of ages (118 men, 141 women; age 44±15), who underwent 2D transthoracic echocardiography. Care was taken to record apical 4-chamber views encompassing the entire LV and right ventricle (RV), as well as the respective left atrium (LA) and right atrium (RA) in the same sector. Study subjects were enrolled at 2 institutions. Normal subjects were defined as healthy volunteers or patients referred for cardiac Received July 20, 2015; accepted January 25, 2016. From the Department of Medicine, Section of Cardiology, University of Chicago, IL (K.A., F.M., V.M.-A., R.M.L.); School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan (M.T., Y.N.); and Epsilon Imaging, Ann Arbor, MI (J.H.). Correspondence to Karima Addetia, MD, Section of Cardiology, University of Chicago Medical Center, 5841 South Maryland Ave, MC5084, Chicago, IL 60637. E-mail [email protected] © 2016 American Heart Association, Inc. Circ Cardiovasc Imaging is available at http://circimaging.ahajournals.org 1 DOI: 10.1161/CIRCIMAGING.115.003895 2 Addetia et al Simultaneous All-4-Chamber Strain ultrasound with no documented cardiovascular history and symptoms and patients on no medications. All participants were nonathletes and had normal echocardiograms defined as normal LV and RV size and function, not more than mild valvular regurgitation, normal right and left atrial sizes, and systolic pulmonary pressure <35 mm Hg. This study was approved by the Institutional Review Board with a waiver of consent. Conventional Echocardiographic Measurements Downloaded from http://circimaging.ahajournals.org/ by guest on May 11, 2017 Comprehensive 2D and color Doppler echocardiograms were performed using the iE33 imaging system equipped with an S5 transducer (Philips Healthcare, Andover, MA; frequency range 1–5 MHz). 2D 4-chamber views were obtained on each participant from the apical transducer position. These views were acquired so as to contain the entire LV and RV and both atria in the same sector. Frame rate was maximized by increasing the depth and decreasing the sector width to the extent possible. The focal point was maintained at the midventricular level. Digital loops were stored and analyzed offline (Xcelera Workstation, Philips). LV ejection fraction was calculated from LV volumes obtained using the Simpson’s biplane method of disks. RV fractional area change was determined from RV chamber area data extracted from Epsilon software. Chamber areas also extracted from the software were indexed to body surface area (BSA)6 and presented in Table 1. Four-Chamber Speckle-Tracking Strain Analysis 2D speckle-tracking echocardiography was used to measure longitudinal strain (LS) simultaneously in all 4 chambers throughout the identical cardiac cycle using vendor-independent software (Epsilon Imaging, Ann Arbor, MI; Figure 1). Strain analysis was performed by manually tracing a region of interest along the endocardial border of each chamber with subsequent adjustment of the region of interest to match the thickness of the individual chamber wall. The software then tracked the endocardial contours throughout the cardiac cycle. Manual adjustments were made to the contours as needed to optimize tracking. Segments that were inadequately tracked despite the adjustments were excluded. The interventricular septum was considered part of the LV, and RV strain was only measured in the free-wall segments.7 In contrast, the interatrial septum was included in the LS measurements of both the LA and RA. Strain measurements were made by 2 level III echocardiographers with extensive experience performing these measurements who met, discussed, compared, and standardized their approaches. The LV, LA, and RA were divided into 6 segments, whereas the RV free-wall was divided into 3 segments (Figure 1). Global strain was measured for each chamber by including only the relevant, well-tracked segments. Global strain curves as well as the time-to-peak (TTP) strain data and chamber area information were exported from the software for further analysis. TTP values were corrected for heart rate by dividing by the R-R interval (in ms) and multiplying by 100% to account for interpatient differences in heart rate. In addition, we calculated the ratios of both left and right atrial/ventricular peak strains, as well as left/right atrial and ventricular peak strains, as potential quantitative measures of interchamber functional relationships. Statistical Analysis Continuous variables were expressed as mean±SD. Categorical variables were expressed in numeric values or percent. A P value <0.05 was considered statistically significant. The association of peak systolic LS and TTP with age and sex was studied using a general linear model, entering sex and number of excluded segments as fixed factors and age as a covariate. Subpopulations studied included males and females and age brackets (20–30, 30–40, 40–50, 50–60, and ≥60 years). To study differences in peak systolic LS values and TTP estimates between age groups, an analysis of variance analysis was performed followed by, when a significant difference was noted, pairwise comparison with 2-tailed student’s t test and Bonferroni correction. Comparison between peak LS and TTP in different chambers were performed using analysis of variance for repeated measures, followed by post hoc test with Bonferroni correction in presence of significant global effect. When comparing chamber differences between populations, unpaired t tests were used, whereas paired t tests were used when making comparisons between chambers. Chi-square analysis was used for categorical variables. In addition, a separate analysis was performed in which chamber areas obtained from Epsilon software were indexed to BSA and allometrically scaled6 by dividing chamber areas by height and height2.7 Regression analysis was then used to study the relationship between allometrically scaled chamber size and strain. Measurement Reproducibility To assess interobserver variability in peak LS, 4-chamber strain measurements were performed in a subset of 22 subjects (8% of the total population) by 2 independent observers at 2 different institutions (K. Addetia and M. Takeuchi), who were blinded to each other’s results and independently selected the best cardiac cycle for analysis. These measurements were also repeated by the same observer who was blinded to the results of the previous measurements and was also free to select the best cardiac cycle each time. Both inter- and intraobserver variability were expressed in terms of intraclass correlation coefficient and percent variability defined as the mean of the absolute differences between pairs of repeated measurements divided by their mean. Table 1. Baseline Characteristics of all Study Subjects and the Subgroups All n Age, y Men, n (%) From US R-R, ms BSA, m2 LVEF, % RVFAC, % LVAi, cm2/m2 RVAi, cm2/m2 LAAi, cm2/m2 RAAi, cm2/m2 259 44±15 118 (46%) 113 (44%) 957±170 1.7±0.3 62±6 37±4 18±3 10±2 11±2 9±2 Sex Men 118 44±16 … 48 (41%) 950±165 1.9±0.2 60±6 39±8 18±2 11±2 11±2 9±2 Women 141 44±14 … 65 (46%) 964±177 1.6±0.2* 64±5* 36±7* 18±3* 10±2* 11±2 8±2* Age groups, y 20–30 52 25±3 25 (48%) 19 (37%) 976±157 1.7±0.3 61±6 36±7 19±2 11±2 11±2 8±1 30–40 60 34±3 31 (52%) 27 (45%) 987±194 1.7±0.3 61±5 36±7 18±3 11±2 11±2 8±1 40–50 51 44±3 19 (37%) 25 (49%) 908±163 1.8±0.3 61±5 39±8 18±2 10±2 10±2 8±2 50–60 51 54±3 24 (47%) 27 (53%) 959±180 1.8±0.3 63±6 41±8 18±2 10±2 11±2 9±2 ≥60 45 68±6 19 (42%) 15 (33%) 946±141 1.6±0.2 64±6 36±8 17±3 10±2 11±2 9±2 BSA indicates body surface area; LAAi, left atrial area indexed to BSA; LVAi, left ventricular area indexed to BSA; LVEF, left ventricular ejection fraction; RAAi, right atrial area indexed to BSA; RVAi, right ventricular area indexed to BSA; RVFAC, right ventricular fractional area change; and US, United States. *P<0.05 between men and women. 3 Addetia et al Simultaneous All-4-Chamber Strain Downloaded from http://circimaging.ahajournals.org/ by guest on May 11, 2017 Figure 1. Measurement of longitudinal strain (LS) in all 4 cardiac chambers. Once the endocardium for all 4 chambers was manually traced, a plot of 4 global LS curves was generated (top, right). Peak strain was obtained from these curves. Note that measurements from the RV septal segments were not used during final analysis. Results Baseline demographic and echocardiographic characteristics of the study population are presented in Table 1. BSA and indexed RV and RA areas were smaller in women than in men, and LV ejection fraction and RV fractional area changes were higher in women. Mean frame rate was 52±6 Hz. Out of a total of 5439 segments traced, 36 (0.7%) were excluded because of poor tracking. Strain curves of the RV and RA were larger in magnitude than those from the corresponding left heart chambers (Figures 2 and 3 and Table 2 top, first row). Also, atrial strains were significantly larger than ventricular strains. LS curves for the RV free wall and RA peaked earlier than the corresponding LV and LA strain curves (Figures 2 and 3 and Table 2 bottom, first row). Normal ranges for peak LS±2SD were −18±4% for the LV, −23±12% for the RV, 38±26% for the LA, and 44±38% for the RA. Ratios in peak strain between chambers were 1.1±0.2 for RV/LV, 2.2±0.7 for LA/LV, 2.4±0.9 for RA/RV, and 1.2±0.4 for RA/LA. In other words, peak RV free-wall peak strain was on average 10% higher in magnitude than LV peak strain. These ratios provide information on interchamber relationships in peak LS in the normal population we studied. Of note, there was no significant correlation between BSA-indexed chamber areas or allometrically scaled chamber areas to strain for any chamber, suggesting that strain measurements were independent of chamber size. Sex Differences in LS Patterns Sex differences were found in the LV, RV free-wall, and LA peak strain values (Figure 4 and Table 2 top, second and third rows). Peak systolic LS values were significantly larger in magnitude in females compared with males (−18±2% versus −17±2%, P<0.01 for the LV; −24±6% versus −22±6%, P<0.01 for the RV free-wall; and 40±13% versus 36±13%, P=0.05 for the LA). Although, on average, females had larger RA peak LS, when compared with males, these differences did not reach statistical significance. Interestingly, LS in all chambers tended to peak later in women compared with men (Figure 4 and Table 2 bottom, second and third rows). Age Differences in LS Patterns Age was associated with peak LS values for LV (0.20% per 10 years), LA (−3.1% per 10 years), and RA (−3.5% per 10 years). For all chambers, age was associated with prolonged TTP (1.0, 0.09, 1.3, and 0.11 ms per decade for LV, RV freewall, LA, and RA, respectively). The number of excluded segments was not associated with peak LS nor with TTP values. When comparing age groups, LV peak LS varied minimally, reaching significance only between the 30 to 40 year and the ≥60 years age groups (Figure 5). RV free-wall LS increased progressively with each decade until the sixth decade when it declined, which was associated with a prolongation of TTP (Figures 5 and 6). LS for both atria progressively declined with increasing age, which was associated with a prolongation of the TTP. Inter- and Intraobserver Variability Interobserver variability for peak LS was low, as reflected by intraclass correlations equal to 0.93, 0.75, 0.90, and 0.83 for the LV, RV free wall, LA, and RA. Percent variability was worst for the atria than for the LV and RV free wall, measuring 3%, 7%, 9%, and 9% for the LV, RV free wall, LA, and RA respectively. Intraobserver variability for peak LS was also low with intraclass correlations of 0.97, 0.96, 0.98, and 0.94 for the LV, RV free wall, LA, and RA and percent variability of 2%, 4%, 4%, and 9%, respectively. Discussion This study is the first to suggest that simultaneous assessment of LS in all 4 cardiac chambers provides new insight into the interchamber relationships. In this study, performed on a large group of normal subjects spanning a wide age range, we found 4 Addetia et al Simultaneous All-4-Chamber Strain Downloaded from http://circimaging.ahajournals.org/ by guest on May 11, 2017 Figure 2. Mean left ventricular (LV; top, left), right ventricular (RV) free wall (top, right), left atrium (LA; bottom, left), and right atrium (RA; bottom, right) longitudinal strain (LS) over time curves (solid lines) with standard deviations (dotted lines). These curves were obtained by averaging data from the whole population of normal subjects (N=259). that LS curves for the right heart chambers were higher in magnitude than the curves for the corresponding left heart chambers. In addition, RA and RV free-wall strain curves peaked earlier than the corresponding left heart chambers. Sex differences were also noted, with women having higher peak LS values for all cardiac chambers compared with men. With aging, LV strain minimally changed, whereas RV free-wall strain progressively increased in magnitude until the sixth decade. In contrast, both LA and RA peak strain progressively decreased with age. Figure 3. Mean longitudinal strain (LS) curves for all 4 cardiac chambers superimposed to show relationships between chambers. 5 Addetia et al Simultaneous All-4-Chamber Strain Table 2. Peak Systolic Longitudinal Strain (Top) and Time to Peak (Bottom) Values for All Four Cardiac Chambers LV* RVFW† LA† RA† RVFW* LA‡ RA‡ LA* RA§ RA* 44±19 Peak longitudinal strain, % All −18±2 <0.01 <0.01 <0.01 −23±6 <0.01 <0.01 38±13 <0.01 Men −17±2 <0.01 <0.01 <0.01 −22±6 <0.01 <0.01 36±13 0.01 42±18 Women −18±2 <0.01 <0.01 <0.01 −24±6 <0.01 <0.01 40±13 <0.01 46±20 Corrected time-to-peak strain (TTP/RR%) All 40±6 <0.01 <0.01 0.08 39±7 <0.01 0.03 41±7 <0.01 40±7 Men 40±6 <0.01 0.06 0.31 37±6 <0.01 <0.01 40±6 <0.01 39±6 Women 41±6 0.67 <0.01 0.77 40±7 <0.01 1.00 42±7 <0.01 41±7 Downloaded from http://circimaging.ahajournals.org/ by guest on May 11, 2017 LA indicates left atrium; LV, left ventricle; RA, right atrium; and RVFW, right ventricular free wall. P values refer to pairwise comparisons between chambers with Bonferroni adjustments for multiple comparisons. *Values for this chamber. †P values indicate comparisons between this chamber and the LV. ‡P values indicate comparisons between this chamber and the RVFW. §P values indicate comparisons between this chamber and the LA. The speckle tracking–based strain analysis used in our study has been validated in several studies ranging from simulated data to human subjects. D’hooge et al compared the performance of EchoInsight against other strain measurements using simulated heart models8 and found good agreement with reference strain values that closely matched measurements of other vendors. Ex-vivo validation was done using sonomicrometry crystals in pump-driven, excised pig hearts,9 which were imaged using 3 different scanners (GE, Philips, and Siemens), and the results showed excellent agreement with strain determined by sonomicrometry (r>0.93). There was also low variation between global strain measurements derived from different scanners (<6%). A large, multivendor comparison human study done under the guidance of the strain standardization task force10 showed good agreement in global LS values with other vendors (r=0.84). Although speckletracking quality can be affected by image quality, frame rate, and heart rate, our testing has shown no strong dependence on frame rate in the range of 40 to 70 Hz. Finally, this software has been used in several studies to distinguish between health and varying degrees of disease, including myocardium scarring11 and diastolic heart failure.12 Assessment of LV LS has been shown to be clinically useful in a variety of cardiac diseases. In all previous studies, deformation imaging has been used for each chamber separately. For example, in the setting of myocardial infarction, LV LS correlates well with scar burden, which has been shown to be associated with outcomes2 providing incremental value for the detection of viable myocardium during dobutamine stress echocardiography.13 LV LS has also been studied in valvular heart disease to better appreciate the impact of load on cardiac function. In patients with severe aortic stenosis and preserved LV ejection fraction, speckle tracking–derived LS has been shown to be abnormal preoperatively and to improve Figure 4. Sex differences in peak longitudinal strain values for women (blue bars) and men (yellow bars). Women had higher peak longitudinal strain (LS) values than men in all cardiac chambers (left). Differences reached statistical significance for the LV, RV free wall, and LA (stars; P<0.05). Right, TTP strain (corrected for R-R interval) for all cardiac chambers in the 2 sex. The corrected TTP strain was significantly higher in women than in men for all chambers. LA indicates left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle; and TTP, time to peak. 6 Addetia et al Simultaneous All-4-Chamber Strain Figure 5. Age differences in peak longitudinal strain (LS) values for the different age groups (see text for details). Colored stars above different columns indicate significance of differences vs other groups depicted in the corresponding color. LA indicates left atrium; LV, left ventricle; RA, right atrium; and RV, right ventricle. Downloaded from http://circimaging.ahajournals.org/ by guest on May 11, 2017 after aortic valve replacement.14 In these patients, LS has been shown to have incremental prognostic value beyond that of standard risk factors.15,16 In addition, subendocardial ischemia17 and cardiotoxicity associated with chemotherapy18 seem to predominantly affect the longitudinal myocardial fibers which are responsible for longitudinal deformation. When evaluating the RV, RV free-wall LS has been shown to provide prognostic information in the setting of pulmonary hypertension.7,19 Recent studies have also suggested that LA strain may be an important predictor of successful radiofrequency catheter ablation of atrial fibrillation.20 LA strain has also been explored as a measure of LA stiffness, which may be important in the transition from hypertensive heart disease to heart failure2 and perhaps also valuable to guide optimization of antihypertensive therapy.21,22 Although there is only sparse data on RA strain in the literature, results published to date suggest that it may be a useful adjunct to functional assessment of the right heart.23 Essentially, multiple studies have shown that when LS is studied individually for each of the 4 cardiac chambers, the information obtained is incrementally useful. The rationale behind our study is that if all this information could be combined for all 4 chambers, it could potentially improve the echocardiographic assessment while providing untapped prognostic information for individual patients. LS and Sex We found that women had higher peak LS values in all cardiac chambers when compared with men. This may be associated with the fact that women have smaller chambers and smaller BSA. In the case of LV and RV strain, this is also in keeping with the higher LV and RV ejection fractions, which have been recently reported in women.6,24,25 Additionally, higher LV mass reported in men may also explain the lower LV LS26 (Table 1). Similar sex differences in LS have previously only been described for the LV using echocardiographic data and CMR.4,27 To our knowledge, this is the first report concerning sex differences in strain in the other 3 chambers. LS and Age Groups The lack of significant difference in LV LS with aging warrants some discussion. Previous published data have been Figure 6. Age differences in corrected time-to-peak (TTP) values for the different age groups (see text for details). Colored stars above different columns indicate significance of differences vs other groups depicted in the corresponding color. LA indicates left atrium; LV, left ventricle; RA, right atrium; and RV, right ventricle. 7 Addetia et al Simultaneous All-4-Chamber Strain Downloaded from http://circimaging.ahajournals.org/ by guest on May 11, 2017 Figure 7. Simultaneous 4-chamber strain assessment in a 62-year-old man with idiopathic pulmonary hypertension treated with Remodulin and Tadalafil. The patient had a supranormal LV ejection fraction. The RV was severely dilated and hypokinetic. There was severe tricuspid regurgitation with no mitral regurgitation. Left atrial size was normal, whereas the right atrium was severely dilated. Estimated systolic pulmonary artery pressure was 89 mm Hg (as obtained from the tricuspid regurgitation gradient and measure of right atrial pressure from the collapsibility of the inferior vena cava). LA indicates left atrium; LV, left ventricle; PSLS, peak systolic longitudinal strain; RA, right atrium; and RV, right ventricle. inconsistent when describing the relationship between age and global LV LS. Some studies reported that there is no difference in LS between age groups,28 whereas others describe that global LS decreases with increasing age.29 Some of these differences have been attributed to intervendor differences in algorithms used to measure strain.5 We used a new software platform for which no previous data exists. In our study, LS for all 4 chambers was measured only in the 4-chamber view. This may be important when attempting to compare our results with those obtained from other studies because most previous studies measured global LV LS in all 3 apical views. The relationship between RV free-wall LS and age has not been well studied. In our cohort, the magnitude of RV freewall LS increased with age. This difference between the 2 ventricles may reflect a differential ventricular adaptation to age-related changes. Age-related structural changes in the LV myocardium lead to systolic and diastolic alterations, which in turn impact RV remodeling.30 Myocardial wall thickness, for instance, increases with age, resulting in a higher myocardial wall-to-cavity ratio.31 This is associated with increased myocardial relaxation time and stiffness and slightly elevated end-diastolic pressures secondary to subclinical diastolic dysfunction and stiffness.32–35 The RV may respond to this afterload increase with a compensatory, more vigorous performance, which declines in the elderly (age >60 years). This finding may reflect interchamber physiological coupling that can only otherwise be appreciated using currently available tools when the R-R interval is not variable. The drop in RV free-wall LS in the oldest age group noted in our study could also probably be explained by the fact that this group included a higher proportion of Japanese subjects, who were found to have lower magnitude RV free-wall LS compared with the US subjects. With respect to the atria, LS decreased progressively with each successive decade of life. The decline in peak LA strain between the youngest and the oldest age groups probably reflects the increased stiffness of the LA with age in response to the changes in the LV outlined earlier.30 In addition, early diastolic filling declines with age to the point that the LV filling depends more on atrial contraction. This may also explain the fall in peak systolic LA LS with age. A similar reasoning can be applied to explain the decrease in RA LS, although our knowledge of right-heart diastology is limited. In summary, these findings in the atria most probably reflect adaptation to age-related changes in the ventricles. These changes become evident only when assessing strain in all 4 chambers simultaneously. Clinical Implications Measurement of LS in all 4 chambers simultaneously is relatively straightforward when suitable images are available. Using this novel tool, it can be possible to assess the interchamber functional relationships in different cardiac diseases states, such as heart failure, pulmonary hypertension, restrictive and infiltrative cardiomyopathies, and ischemic heart disease. As an example, we used this new tool to study a clinically stable patient with idiopathic pulmonary hypertension (Figure 7). His peak strain ratios for RV/LV, LA/LV, RA/RV, and RA/LA were 1.2, 1.7, 2.4, and 1.7, respectively. Compared with the normal values obtained in this study, the peak LS RA/LA and RV/LV ratios were elevated, suggesting that right heart function is hypercontractile when compared with left heart function. It is theoretically possible that if the ratio decreased toward normal, it could mean that the patient is decompensating. Testing this hypothesis requires further study. Indeed, this tool may provide incremental information on outcomes, particularly when incorporating functional information from all 4 chambers because there is already evidence that deformation parameters in the individual chambers have prognostic significance in a multitude of cardiac diseases. Limitations The main limitation of the new tool is that it can best be applied when the images are of adequate quality with all 4 chambers included in the imaging sector, and the software is able to successfully track wall motion in all 4 chambers. We did not assess radial and circumferential strains in this study. We focused on LS only because this index has proven 8 Addetia et al Simultaneous All-4-Chamber Strain Downloaded from http://circimaging.ahajournals.org/ by guest on May 11, 2017 to be the most promising in the clinical arena, with the largest body36 of literature supporting its use, while providing incremental prognostic information in a variety of disease states.2 Subgroup analyses performed in this study involve smaller groups and therefore may not be sufficiently powered to generalize the results. These results need to be confirmed in larger-scale studies. Similar to single-chamber assessment of LS, multichamber simultaneous strain assessment as studied here also falls prey to the universal limitation of 2D strain. Specifically, single plane strain measurement fails to take into account motion outside the imaging plane, resulting in underestimated strain values. This has been previously demonstrated in several publications.37 However, the vast majority of the strain-related publications are based on 2D measurements, which have been validated extensively, including established normal values. Although simultaneous 3D strain measurements in all 4 cardiac chambers are theoretically not impossible, software implementation of this approach has yet to be developed. Conclusions Simultaneous measurement of LS in all 4 cardiac chambers provides new insight into interchamber coupling. This novel tool may prove useful in the evaluation and follow-up of different cardiac disease states. Disclosures Dr Lang serves on the speakers’ and advisory bureau of and has received research grants from Philips Medical Imaging. The remaining authors have no disclosures. References 1.Mor-Avi V, Lang RM, Badano LP, Belohlavek M, Cardim NM, Derumeaux G, Galderisi M, Marwick T, Nagueh SF, Sengupta PP, Sicari R, Smiseth OA, Smulevitz B, Takeuchi M, Thomas JD, Vannan M, Voigt JU, Zamorano JL. Current and evolving echocardiographic techniques for the quantitative evaluation of cardiac mechanics: ASE/EAE consensus statement on methodology and indications endorsed by the Japanese Society of Echocardiography. J Am Soc Echocardiogr. 2011;24:277–313. doi: 10.1016/j.echo.2011.01.015. 2. Shah AM, Solomon SD. Myocardial deformation imaging: current status and future directions. Circulation. 2012;125:e244–e248. doi: 10.1161/ CIRCULATIONAHA.111.086348. 3. Stanton T, Leano R, Marwick TH. Prediction of all-cause mortality from global longitudinal speckle strain: comparison with ejection fraction and wall motion scoring. Circ Cardiovasc Imaging. 2009;2:356–364. doi: 10.1161/CIRCIMAGING.109.862334. 4. Kocabay G, Muraru D, Peluso D, Cucchini U, Mihaila S, PadayattilJose S, Gentian D, Iliceto S, Vinereanu D, Badano LP. Normal left ventricular mechanics by two-dimensional speckle-tracking echocardiography. Reference values in healthy adults. Rev Esp Cardiol (Engl Ed). 2014;67:651–658. doi: 10.1016/j.rec.2013.12.009. 5. Takigiku K, Takeuchi M, Izumi C, Yuda S, Sakata K, Ohte N, Tanabe K, Nakatani S; JUSTICE investigators. Normal range of left ventricular 2-dimensional strain: Japanese Ultrasound Speckle Tracking of the Left Ventricle (JUSTICE) study. Circ J. 2012;76:2623–2632. 6. Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, Flachskampf FA, Foster E, Goldstein SA, Kuznetsova T, Lancellotti P, Muraru D, Picard MH, Rietzschel ER, Rudski L, Spencer KT, Tsang W, Voigt JU. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging. 2015;16:233–270. doi: 10.1093/ehjci/jev014. 7. Fine NM, Chen L, Bastiansen PM, Frantz RP, Pellikka PA, Oh JK, Kane GC. Outcome prediction by quantitative right ventricular function assessment in 575 subjects evaluated for pulmonary hypertension. Circ Cardiovasc Imaging. 2013;6:711–721. doi: 10.1161/CIRCIMAGING.113.000640. 8. D’Hooge J, Barbosa D, Gao H, Claus P, Prater D, Hamilton J, Lysyansky P, Abe Y, Ito Y, Houle H, Pedri S, Baumann R, Thomas J, Badano LP. Two-dimensional speckle tracking echocardiography: standardization efforts based on synthetic ultrasound data. Eur Heart J Cardiovasc Imaging. 2015. [Epub ahead of print]. doi: 10.1093/ehjci/jev197. 9. Lucas SD, Hamilton J, Ashraf M, Sahn D. Platform independent ultrasound strain imaging reproducibility using a novel speckle tracking algorithm. J Am Coll Cardiol. 2011;57:E655. 10. Farsalinos KE, Daraban AM, Ünlü S, Thomas JD, Badano LP, Voigt JU. Head-to-head comparison of global longitudinal strain measurements among nine different vendors: the EACVI/ASE Inter-Vendor Comparison Study. J Am Soc Echocardiogr. 2015;28:1171–1181, e2. doi: 10.1016/j. echo.2015.06.011. 11. Leong DP, Kroner ESJ, Siebelink HM, Auger D, Witkowski TG, Ewe SH, Yiu KH, Lamb HJ, Bax JJ, Delgado V. Vendor-independent echocardiographic quantification of left ventricular circumferential strain: validation with cardiovascular magnetic resonance. Eur Heart J.. 2011;32:514. 12. Kolias TJ, Hagan PG, Chetcuti SJ, Eberhart DL, Kline NM, Lucas SD, Hamilton JD. New universal strain software accurately assesses cardiac systolic and diastolic function using speckle tracking echocardiography. Echocardiography. 2014;31:947–955. doi: 10.1111/echo.12512. 13. Hanekom L, Jenkins C, Jeffries L, Case C, Mundy J, Hawley C, Marwick TH. Incremental value of strain rate analysis as an adjunct to wall-motion scoring for assessment of myocardial viability by dobutamine echocardiography: a follow-up study after revascularization. Circulation. 2005;112:3892–3900. doi: 10.1161/CIRCULATIONAHA.104.489310. 14.Delgado V, Tops LF, van Bommel RJ, van der Kley F, Marsan NA, Klautz RJ, Versteegh MI, Holman ER, Schalij MJ, Bax JJ. Strain analysis in patients with severe aortic stenosis and preserved left ventricular ejection fraction undergoing surgical valve replacement. Eur Heart J. 2009;30:3037–3047. doi: 10.1093/eurheartj/ehp351. 15. Dahl JS, Videbæk L, Poulsen MK, Rudbæk TR, Pellikka PA, Møller JE. Global strain in severe aortic valve stenosis: relation to clinical outcome after aortic valve replacement. Circ Cardiovasc Imaging. 2012;5:613– 620. doi: 10.1161/CIRCIMAGING.112.973834. 16.Kusunose K, Goodman A, Parikh R, Barr T, Agarwal S, Popovic ZB, Grimm RA, Griffin BP, Desai MY. Incremental prognostic value of left ventricular global longitudinal strain in patients with aortic stenosis and preserved ejection fraction. Circ Cardiovasc Imaging. 2014;7:938–945. doi: 10.1161/CIRCIMAGING.114.002041. 17. Jones CJ, Raposo L, Gibson DG. Functional importance of the long axis dynamics of the human left ventricle. Br Heart J. 1990;63:215–220. 18. Ho E, Brown A, Barrett P, Morgan RB, King G, Kennedy MJ, Murphy RT. Subclinical anthracycline- and trastuzumab-induced cardiotoxicity in the long-term follow-up of asymptomatic breast cancer survivors: a speckle tracking echocardiographic study. Heart. 2010;96:701–707. doi: 10.1136/ hrt.2009.173997. 19.Smith BC, Dobson G, Dawson D, Charalampopoulos A, Grapsa J, Nihoyannopoulos P. Three-dimensional speckle tracking of the right ventricle: toward optimal quantification of right ventricular dysfunction in pulmonary hypertension. J Am Coll Cardiol. 2014;64:41–51. doi: 10.1016/j.jacc.2014.01.084. 20. Montserrat S, Gabrielli L, Bijnens B, Borràs R, Berruezo A, Poyatos S, Brugada J, Mont L, Sitges M. Left atrial deformation predicts success of first and second percutaneous atrial fibrillation ablation. Heart Rhythm. 2015;12:11–18. doi: 10.1016/j.hrthm.2014.08.032. 21.Dimitroula H, Damvopoulou E, Giannakoulas G, Dalamanga E, Dimitroulas T, Sarafidis PA, Styliadis H, Hatzitolios A, Karvounis H, Parcharidis G. Effects of renin-angiotensin system inhibition on left atrial function of hypertensive patients: an echocardiographic tissue deformation imaging study. Am J Hypertens. 2010;23:556–561. doi: 10.1038/ ajh.2010.4. 22. Kokubu N, Yuda S, Tsuchihashi K, Hashimoto A, Nakata T, Miura T, Ura N, Nagao K, Tsuzuki M, Wakabayashi C, Shimamoto K. Noninvasive assessment of left atrial function by strain rate imaging in patients with hypertension: a possible beneficial effect of renin-angiotensin system inhibition on left atrial function. Hypertens Res. 2007;30:13–21. doi: 10.1291/ hypres.30.13. 23.Padeletti M, Cameli M, Lisi M, Zacà V, Tsioulpas C, Bernazzali S, Maccherini M, Mondillo S. Right atrial speckle tracking analysis as a novel noninvasive method for pulmonary hemodynamics assessment in patients with chronic systolic heart failure. Echocardiography. 2011;28:658–664. doi: 10.1111/j.1540-8175.2011.01413.x. 9 Addetia et al Simultaneous All-4-Chamber Strain Downloaded from http://circimaging.ahajournals.org/ by guest on May 11, 2017 24. Maffessanti F, Muraru D, Esposito R, Gripari P, Ermacora D, Santoro C, Tamborini G, Galderisi M, Pepi M, Badano LP. Age-, body size-, and sex-specific reference values for right ventricular volumes and ejection fraction by three-dimensional echocardiography: a multicenter echocardiographic study in 507 healthy volunteers. Circ Cardiovasc Imaging. 2013;6:700–710. doi: 10.1161/CIRCIMAGING.113.000706. 25. Natori S, Lai S, Finn JP, Gomes AS, Hundley WG, Jerosch-Herold M, Pearson G, Sinha S, Arai A, Lima JA, Bluemke DA. Cardiovascular function in multi-ethnic study of atherosclerosis: normal values by age, sex, and ethnicity. AJR Am J Roentgenol. 2006;186(6 suppl 2):S357–S365. doi: 10.2214/AJR.04.1868. 26. Bluemke DA, Kronmal RA, Lima JA, Liu K, Olson J, Burke GL, Folsom AR. The relationship of left ventricular mass and geometry to incident cardiovascular events: the MESA (Multi-Ethnic Study of Atherosclerosis) study. J Am Coll Cardiol. 2008;52:2148–2155. doi: 10.1016/j.jacc.2008.09.014. 27. Taylor RJ, Moody WE, Umar F, Edwards NC, Taylor TJ, Stegemann B, Townend JN, Hor KN, Steeds RP, Mazur W, Leyva F. Myocardial strain measurement with feature-tracking cardiovascular magnetic resonance: normal values. Eur Heart J Cardiovasc Imaging. 2015;16:871–881. doi: 10.1093/ehjci/jev006. 28.Kaku K, Takeuchi M, Tsang W, Takigiku K, Yasukochi S, Patel AR, Mor-Avi V, Lang RM, Otsuji Y. Age-related normal range of left ventricular strain and torsion using three-dimensional speckle-tracking echocardiography. J Am Soc Echocardiogr. 2014;27:55–64. doi: 10.1016/j. echo.2013.10.002. 29. Zghal F, Bougteb H, Réant P, Lafitte S, Roudaut R. Assessing global and regional left ventricular myocardial function in elderly patients using the bidimensional strain method. Echocardiography. 2011;28:978–982. doi: 10.1111/j.1540-8175.2011.01476.x. 30. Wei JY. Age and the cardiovascular system. N Engl J Med. 1992;327:1735– 1739. doi: 10.1056/NEJM199212103272408. 31.Kishi S, Reis JP, Venkatesh BA, Gidding SS, Armstrong AC, Jacobs DR Jr, Sidney S, Wu CO, Cook NL, Lewis CE, Schreiner PJ, Isogawa A, Liu K, Lima JA. Race-ethnic and sex differences in left ventricular structure and function: the Coronary Artery Risk Development in Young Adults (CARDIA) Study. J Am Heart Assoc. 2015;4:e001264. doi: 10.1161/ JAHA.114.001264. 32.Lipsitz LA, Jonsson PV, Marks BL, Parker JA, Royal HD, Wei JY. Reduced supine cardiac volumes and diastolic filling rates in elderly patients with chronic medical conditions. Implications for postural blood pressure homeostasis. J Am Geriatr Soc. 1990;38:103–107. 33. Manning WJ, Shannon RP, Santinga JA, Parker JA, Gervino EV, Come PC, Wei JY. Reversal of changes in left ventricular diastolic filling associated with normal aging using diltiazem. Am J Cardiol. 1991;67:894–896. 34. Ogawa T, Spina RJ, Martin WH III, Kohrt WM, Schechtman KB, Holloszy JO, Ehsani AA. Effects of aging, sex, and physical training on cardiovascular responses to exercise. Circulation. 1992;86:494–503. 35. Wei JY, Spurgeon HA, Lakatta EG. Excitation-contraction in rat myocardium: alterations with adult aging. Am J Physiol. 1984;246(6 pt 2):H784–H791. 36.Gorcsan J III, Tanaka H. Echocardiographic assessment of myocar dial strain. J Am Coll Cardiol. 2011;58:1401–1413. doi: 10.1016/j. jacc.2011.06.038. 37. Maffessanti F, Nesser HJ, Weinert L, Steringer-Mascherbauer R, Niel J, Gorissen W, Sugeng L, Lang RM, Mor-Avi V. Quantitative evaluation of regional left ventricular function using three-dimensional speckle tracking echocardiography in patients with and without heart disease. Am J Cardiol. 2009;104:1755–1762. doi: 10.1016/j.amjcard.2009.07.060. CLINICAL PERSPECTIVE Longitudinal strain has been studied for each cardiac chamber individually, and, at least for the left ventricle, the right ventricular free wall, and the left atrium, strain assessment has been shown to be of potential clinical value in a variety of disease states. We explored the concept of simultaneous all-4-chamber strain assessment within a single cardiac cycle in a large population of normal subjects as a means for understanding normal interchamber functional relationships. We were able to show that when combined, strain curves for all 4 chambers followed specific patterns. Peak longitudinal strain for the right ventricle was 10% higher in magnitude, on average, than that for the left ventricle, whereas left and right atrial peak longitudinal strain was 70% and 90% higher than measured in the left and right ventricles, respectively. Right atrial peak longitudinal strain was 4% higher in magnitude than left atrial peak strain. Peak longitudinal strain values were larger in women than in men. Longitudinal strain declined with age for both atria. Right ventricular free-wall strain augmented with age until the sixth decade, whereas left ventricular strain changed minimally with age. This initial study provides insight into normal interchamber relationships which can, in the future, be used to study atrial and ventricular coupling in diseases, such as pulmonary arterial hypertension, cardiomyopathy, and valvular heart disease. Simultaneous Longitudinal Strain in All 4 Cardiac Chambers: A Novel Method for Comprehensive Functional Assessment of the Heart Karima Addetia, Masaaki Takeuchi, Francesco Maffessanti, Yasufumi Nagata, James Hamilton, Victor Mor-Avi and Roberto M. Lang Downloaded from http://circimaging.ahajournals.org/ by guest on May 11, 2017 Circ Cardiovasc Imaging. 2016;9:e003895 doi: 10.1161/CIRCIMAGING.115.003895 Circulation: Cardiovascular Imaging is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 2016 American Heart Association, Inc. All rights reserved. Print ISSN: 1941-9651. 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