Timing and Magnitude of Regional Right Ventricular Function: A Speckle Tracking-Derived Strain Study of Normal Subjects and Patients with Right Ventricular Dysfunction

RIGHT VENTRICULAR FUNCTION

Timing and Magnitude of Regional Right Ventricular Function: A Speckle Tracking-Derived Strain Study of Normal Subjects and Patients with Right Ventricular Dysfunction Alessandra Meris, MD, Francesco Faletra, MD, Cristina Conca, MD, Catherine Klersy, MD, Franc¸ois Regoli, MD, Julia Klimusina, MD, Maria Penco, MD, Elena Pasotti, MD, Giovanni B. Pedrazzini, MD, Tiziano Moccetti, MD, and Angelo Auricchio, MD, Lugano, Switzerland; Pavia and L’Aquila, Italy

Background: The aim of this study was to evaluate the timing and magnitude of global and regional right ventricular (RV) function by means of speckle tracking–derived strain in normal subjects and patients with RV dysfunction. Methods: Peak longitudinal systolic strain (PLSS) and time to PLSS in 6 RV segments (the basal, mid, and apical segments of the RV free wall and septum) were obtained in 100 healthy volunteers and 76 patients with RV dysfunction by tracking speckles inside the myocardium using grayscale images. Global PLSS and time to PLSS were based on the average of the 6 regional values. Results: There was a significant and close correlation between RV contractility as measured by PLSS and tricuspid annular plane systolic excursion (r = 0.83, P < .001). In normal subjects, PLSS was significantly greater in the free wall than in the septum ( 28.7 6 4.1% vs 19.8 6 3.4%, P < .001), whereas time to PLSS was similar in the different regions of the right ventricle. In patients with RV dysfunction, global and regional PLSS was significantly less than in normal subjects ( 13.7 6 3.6% vs 24.2 6 2.9%, P < .001), and a global PLSS cutoff value of 19% was helpful in distinguishing the two groups. Furthermore, time to PLSS in all of the RV septal segments and dispersion in RV contraction timing were significantly longer. Global PLSS in the patients with RV dysfunction was also significantly less in the presence of moderate to severe pulmonary hypertension ( 12.7 6 3.6% vs 14.4 6 3.4%, P = .038). Conclusions: Speckle tracking not only makes it possible to quantify global RV function but also illustrates the physiology of RV contraction and the pattern of activation at regional level. Speckle tracking–derived strain could become an important new means of assessing and following up patients with impaired RV function and increased pulmonary pressure. (J Am Soc Echocardiogr 2010;23:823-31.) Keywords: Strain, Speckle tracking, Right ventricular function, Pulmonary hypertension

The assessment of right ventricular (RV) function is of paramount importance in many cardiovascular and pulmonary diseases.1-6 However, conventional two-dimensional echocardiography does not allow a comprehensive evaluation because of the right ventricle’s complex, crescent-shaped structure, wrapped around the left ventricle.7 Global RV function is most frequently assessed by From the Division of Cardiology, Fondazione Cardiocentro Ticino, Lugano, Switzerland (A.M., F.F., C.C., F.R., J.K. E.P., G.B.P., T.M., A.A.); Biometry and Clinical Epidemiology, Research Department, IRCCS Fondazione Policlinico San Matteo, Pavia, Italy (C.K.); and the Division of Cardiology, Department of Internal Medicine and Public Health, University of L’Aquila, L’Aquila, Italy (M.P.). Reprint requests: Alessandra Meris, MD, Fondazione Cardiocentro Ticino, Division of Cardiology, Via Tesserete 48, CH-6900 Lugano, Switzerland (E-mail: a.meris@ hotmail.com). 0894-7317/$36.00 Copyright 2010 by the American Society of Echocardiography. doi:10.1016/j.echo.2010.05.009

means of RV fractional area change (FAC) and tricuspid annular plane systolic excursion (TAPSE), although both techniques have intrinsic limitations.7,8 The new echocardiographic method of speckle tracking assesses myocardial deformation or strain by tracking speckles in the myocardium on grayscale (B-mode) images9 and can be used to evaluate both global and regional myocardial strain without being limited by the Doppler beam angle.10 A number of studies have used speckle tracking–derived strain to evaluate the left ventricle,9,10 but there is relatively little information concerning the assessment of RV performance. Its feasibility and reproducibility have been demonstrated in selected populations of athletes11-13 and in subjects with congenital heart diseases,14-17 systemic sclerosis,18 acute pulmonary thromboembolism,19 and pulmonary arterial hypertension.20 However, the magnitude and timing of regional RV contraction in patients with RV dysfunction associated with left-sided heart failure have not been investigated and compared with these values in normal subjects. 823

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The aims of this study were (1) to compare global RV sysCAD = Coronary artery tolic function as evaluated on disease the basis of speckle tracking–derived strain with that revealed FAC = Fractional area change by the conventional parameters LV = Left ventricular of RV contractility (TAPSE and RV FAC), (2) to assess the timPLSS = Peak longitudinal ing and magnitude of speckle systolic stress tracking–derived regional RV RV = Right ventricular strain in normal subjects and paTAPSE = Tricupsid annular tients with RV dysfunction, and plane systolic excursion (3) to compare the timing and magnitude of global and regional RV strain in patients with RV dysfunction with and without pulmonary hypertension. Abbreviations

METHODS Study Population Between January and December 2007, 100 healthy volunteers (defined as having no histories of cardiac disease, alcohol or drug abuse, and pathologic physical examinations or abnormal 12-lead electrocardiographic findings) were prospectively enrolled at Fondazione Cardiocentro Ticino in Lugano, Switzerland. Subjects aged >40 years were eligible only if they had negative results on scintigraphy, or the absence of coronary artery disease (CAD) was documented by angiography or 64-multislice computed tomography. Subjects with any evidence of abnormal global or regional left ventricular (LV) and/or RV wall motion or any hemodynamically relevant valve abnormalities were also excluded. From a larger group of consecutive patients with LV dysfunction (defined by an ejection fraction of <35%), 85 consecutive patients with RV dysfunction were identified on the basis of TAPSE < 2 cm.6,21 These patients were further divided into those with or without pulmonary hypertension using a cutoff value of pulmonary artery pressure in systole of 35 mm Hg.22-24 Subjects with atrial fibrillation or who had undergone previous tricuspid valve surgery were excluded. Nine patients were excluded from the analyses because the quality of their echocardiographic studies was found to be insufficient upon review. In the remaining population, it was not possible to analyze the RV apical free wall segment in 4 patients and the apical septum in 2 patients. The final study population therefore consisted of 100 healthy subjects and 76 patients with RV dysfunction, 45 (59%) with normal or only slightly high pulmonary pressure and 31 (41%) with moderate or severe pulmonary hypertension. All subjects gave informed consent to participate in the study, which was approved by our institutional review board. Echocardiographic Measurements Echocardiographic examinations were performed using a GE Vivid 7 machine (GE Healthcare, Milwaukee, WI) with the subjects in the left lateral position. Images were acquired during breath holds with stable electrocardiographic recordings and were then digitally stored for subsequent offline analysis using EchoPAC software (GE Healthcare). LV volume and the ejection fraction were measured using Simpson’s biplane method in accordance with current guidelines.7 RV FAC was obtained by measuring RV area at end-diastole and end-systole in the 4-chamber view and calculating the ratio between the difference

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between end-diastolic and end-systolic area divided by the end-diastolic area ([end-diastolic area end-systolic area]/end-diastolic area).25 TAPSE was obtained by drawing a straight line (M-mode) through the lateral tricuspid valve annulus and was quantified as the length of the excursion of the tricuspid annular plane during systole in millimeters.6 RV strain was analyzed using conventional two-dimensional echocardiographic grayscale apical 4-chamber images and a frame rate of 70 to 80 frames/s, which seems to be the best compromise between appropriate temporal resolution and acceptable spatial definition of the LV lateral wall and RV free wall.11,26 In postprocessing analysis, the region of interest was obtained by tracing the RV endocardial borders at the level of the septum and the free wall in a still frame at end-systole. An automated software program calculated the frame-to-frame displacements of speckle patter within the region of interest throughout the cardiac cycle.26 Longitudinal strain curves were obtained for 6 RV segments (the basal, mid, and apical segments of the RV free wall and septum), and the global RV strain curve was based on the average of the 6 regional strain curves (Figure 1); longitudinal strain curves of the lateral LV wall were obtained by repeating the same analysis. The extent of myocardial deformation (defined as the peak longitudinal systolic strain [PLSS]) was expressed as a percentage of the longitudinal shortening in systole compared with diastole for each segment of interest. The temporal pattern of RV mechanical contraction was evaluated as the time needed to reach peak strain (time to PLSS) using the beginning of the QRS complex as a reference point. The dispersion in contraction timing (calculated as the SD of the time to PLSS in the different RV regions) therefore represented right intraventricular synchronicity. Interventricular synchronicity was defined as the maximum difference in time to PLSS between lateral LV and the free RV wall. Statistical Analyses Continuous baseline data are expressed as mean 6 SD and discrete variables as absolute numbers and percentages. The normality ranges of PLSS and timing were defined as 62 SDs of the mean in the normal subjects. The groups were compared using 2-sample Wilcoxon’s rank-sum (Mann-Whitney) tests and multivariate linear regression analyses, as appropriate. The relationships between RV strain and the traditional measurements of RV function (ie, TAPSE and RV FAC) were tested by means of Pearson’s correlation. The cutoff value for RV strain that was most sensitive and specific in measuring the RV systolic function was determined by means of receiver operating characteristic curve analysis. Twenty of the normal subjects and 20 of the patients with RV dysfunction were randomly selected, and the measurements were repeated after 1 month by the same echocardiographer to assess intraobserver reproducibility. Interobserver reproducibility was assessed by having a second echocardiographer repeat the measurements of PLSS and time to PLSS in 15 of the subjects from each group. Intraobserver and interobserver reproducibility (with 95% agreement limits) were analyzed using method of Bland and Altman. All P values were 2 sided, and values < .05 were considered statistically significant. All statistical analyses were performed using Stata software (StataCorp LP, College Station, TX). RESULTS Baseline Characteristics Table 1 shows the baseline characteristics of the normal subjects and the patients with RV dysfunction. The normal subjects were younger

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Figure 1 Two examples of speckle tracking strain imaging. After the RV endocardial border has been manually delineated, a 6-segment model is created, and speckle tracking–derived RV longitudinal strain curves are automatically generated. In normal subjects, the longitudinal strain curves are synchronous and have considerable amplitude; in patients with RV dysfunction, they are dyssynchronous and flatter.

RV Global Function

The receiver operating characteristic curves showed that with TAPSE as the reference parameter, the most sensitive and specific global PLSS cutoff value was 19%, with sensitivity of 95% (95% confidence interval [CI], 87%-98%) and specificity of 85% (95% CI, 77%-91%). With RV FAC as the reference parameter, the best cutoff value was 16%, with sensitivity of 90% (95% CI, 77%-97%) and specificity of 83% (95% CI, 76%-88%) (Figure 3).

The normal subjects’ mean global PLSS of the 6 RV segments (basal, mid, and apical septum and free wall) was –24.2 6 2.9% (range, 30.0% to 17.7%), significantly higher than in patients with RV dysfunction (mean, 13.7 6 3.6%; P < .001). There were good correlations between global PLSS and TAPSE (r = 0.83, P < .001) and between global PLSS and RV FAC (r = 0.73, P < .001) in the study population as a whole, as well as in the group of normal subjects (PLSS and TAPSE, r = 0.37, P < .001; PLSS and RV FAC, r = 0.16, P = .119) and the group with RV dysfunction (PLSS and TAPSE, r = 0.33, P = .004; PLSS and RV FAC, r = 0.38, P < .001) (Figure 2).

RV Regional Function Table 2 shows the ranges of regional PLSS in the normal subjects. PLSS was significantly higher in the free wall than in the septum ( 28.7 6 4.1% vs 19.8 6 3.4%, P < .001). There was no significant difference between the apical and basal RV segments ( 24.2 6 6.1% vs 23.5 6 4.1%, P = .375). Figure 4A shows a comparison of global and regional PLSS between normal subjects and patients with RV dysfunction. PLSS of the free wall and septal segments was significantly lower in the group with RV dysfunction (P < .001). On multivariate analyses using

and more likely to be female. As expected, the patients with RV dysfunction had larger left and right ventricles and depressed LV function. Among the patients with reduced TAPSE, RV FAC and RV fractional shortening were equally abnormal, and about 40% had pulmonary hypertension.

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Table 1 Baseline clinical and echocardiographic characteristics of the study population

Variable

Clinical variables Age (y) Women Echocardiographic variables LV dimensions and function LV ESV (mL) LV EDV (mL) LV EF (%) RV dimensions and function RV diastolic diameter (cm) RV systolic diameter (cm) RV FS (%) RV diastolic area (cm2) RV systolic area (cm2) RV FAC (%) TAPSE (cm) Tricuspid valve and pulmonary pressure Moderate to severe TR Systolic PAP > 35 mm Hg

Normal subjects (n = 100)

Patients with RV dysfunction (n = 76)

P

43 6 13 46 (46%)

68 6 12 13 (17%)

<.001 <.001

29 6 9 84 6 22 66 6 5

131 6 47 180 6 57 28 6 6

<.001 <.001 <.001

3.0 6 0.3 1.9 6 0.3 34 6 5 21 6 4 11 6 3 45 6 6 2.5 6 0.4

3.0 6 0.4 2.3 6 0.4 26 6 8 23 6 5 16 6 4 31 6 7 1.4 6 0.3

.185 <.001 <.001 .005 <.001 <.001 <.001

0 (0%) 0 (0%)

4 (5%) 31 (41%)

.570 <.001

EDV, End-diastolic volume; EF, ejection fraction; ESV, end-systolic volume; FS, fractional shortening; PAP, pulmonary artery pressure; TR, tricuspid regurgitation. Data are expressed as mean 6 SD or as number (percentage).

age, gender, and LV end-diastolic volume as covariates, PLSS of the free wall and septum and global PLSS were all lower than in normal subjects (P = .018, P = .044, and P = .059, respectively). Time to PLSS Table 2 also shows the ranges of global and regional time to PLSS in the normal subjects. RV strain usually peaked between 302 and 474 ms after the beginning of QRS, and contraction of the free wall and septum occurred approximately simultaneously (388 6 43 vs 385 6 42 ms, P = .351); similarly, there was no significant difference in RV activation between the apex and base (384 6 38 vs 391 6 46 ms, P = .073). As shown in Figure 4B, time to PLSS was generally longer in patients with RV dysfunction (416 6 75 vs 387 6 39 ms, P < .001). There was no significant difference in the mean free wall time to PLSS between normal subjects and patients with RV dysfunction (388 6 43 vs 394 6 73 ms, P = .515), except at the apex, whereas the mean time to PLSS in all of the septal segments was significantly shorter in normal subjects (385 6 43 vs 438 6 99 ms, P < .001). However, multivariate analyses using age, gender, and LV end-diastolic volume as covariates showed that global and regional time to PLSS were no longer independent determinants of differences between the two groups. The SD of time to PLSS was significantly larger in the patients with RV dysfunction (81 6 29 vs 26 6 14 ms, P < .001) and was an independent determinant of between-group differences on multivariate analysis (P = .013). The RV free wall contracted earlier than the LV lateral wall in normal subjects but significantly later in patients with RV dysfunction ( 11 6 62 vs 91 6 153 ms, P < .001).

Figure 2 Correlations between PLSS and the traditional parameters of RV contraction in the study population as a whole (blue triangles = normal subjects; red circles = patients with RV dysfunction). In both cases, the correlations are significant. Electrocardiographic Conduction Disturbances The duration of the QRS interval was <100 ms in the normal subjects and 133 6 33 ms in patients with RV dysfunction, of whom 50 (66%) had QRS intervals > 120 ms and 26 (34%) had QRS intervals < 120 ms. There were no differences in global PLSS, time to PLSS, or the SD of time to PLSS between patients with QRS intervals < 120 ms or > 120 ms, but interventricular dyssynchrony was significantly greater in the patients with QRS intervals > 120 ms (121 6 137 vs 52 6 117 ms, P = .032). Etiology of RV Dysfunction As stated in the inclusion criteria, all patients with RV dysfunction had concomitant left-sided heart failure: 46 (60%) had CAD, 22 (29%) had idiopathic cardiomyopathy, and 8 (11%) had biventricular dysfunction due to other etiologies (valvular disease [n = 4], hypertrophic cardiomyopathy [n = 2], and toxic cardiomyopathy [n = 2]). Global and septal PLSS were significantly greater in patients with CAD than in nonischemic patients ( 14.7 6 4.1% vs 12.9 6 3.1%, P = .041; and 10.6 6 4.0% vs 8.4 6 3.1%, P = .012), but the differences in TAPSE, RV FAC, and free wall PLSS were not statistically significant. There were no significant differences in global or regional time to PLSS between these subgroups.

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Figure 3 Receiver-operating characteristic curve analysis showing the PLSS cutoff value distinguishing a normal right ventricle from on with reduced systolic function. (A) TAPSE; (B) RV FAC.

Table 2 Ranges of normality for global and regional PLSS and time to PLSS in normal subjects Variable

Global Basal free wall Mid free wall Apical free wall Basal septum Mid septum Apical septum Free wall segments Septal segments Apical segments Basal segments SD Interventricular time

PLSS (%)

30.0 to 43.2 to 40.9 to 39.01 to 26.8 to 27.3 to 33.6 to 37.7 to 27.0 to 35.5 to 33.5 to

17.7 14.9 20.1 13.1 12.5 12.7 9.7 19.8 12.8 12.2 14.6

In the study population as a whole, global and regional PLSS were significantly lower, and the SD of time to PLSS significantly higher, in subjects with systolic pulmonary artery pressure > 35 mm Hg.

Time to PLSS (ms)

302 to 474 284 to 511 284 to 505 285 to 468 283 to 494 291 to 484 294 to 467 287 to 482 288 to 480 293 to 460 300 to 491 4.29 to 68.09 158 to +94

Magnitude and Timing of RV Strain in the Presence of Pulmonary Hypertension On the basis of a cutoff value of 35 mm Hg, 45 of the patients with RV dysfunction (59%) had normal or only slightly high pulmonary pressure, and 31 (41%) had moderate to severe pulmonary hypertension (Table 3). Both univariate and multivariate analysis (with age, LV end-diastolic volume, LVejection fraction, the etiology of biventricular failure, and QRS duration as covariates) showed that the patients with pulmonary hypertension had significantly lower global PLSS but no significant segmental reductions or any significant differences in time to global and regional PLSS.

Intraobserver and Interobserver Reproducibility The limits of agreement for intraobserver reproducibility in normal subjects were 2.4% to 1.9% for PLSS and 22 to 19 ms for time to PLSS; the corresponding figures in patients with RV dysfunction were 2.3% to 2.3% and 21 to 19 ms. The limits of agreement for interobserver reproducibility were, respectively, 3.9% to 4.6% and 24 to 19 ms and 4.5% to 4.3% and 29 to 24 ms.

DISCUSSION A number of the findings of this study shed new light on RV performance: (1) there was a good correlation between global PLSS and the traditional measurements of global RV systolic function; (2) normal subjects showed significantly greater global and regional PLSS and shorter times to PLSS with less dispersion in contraction timing than patients with RV dysfunction; (3) when TAPSE was used as a reference parameter, a global PLSS cutoff value of 19% identified impaired RV contractility; (4) patients with CAD showed significantly greater global and septal PLSS than those with nonischemic RV dysfunction; (5) a prolonged QRS complex did not affect time to PLSS or the dispersion in contraction timing in patients with RV dysfunction; and (6) global PLSS was significantly lower in patients with systolic pulmonary artery pressures > 35 mm Hg than in patients without pulmonary hypertension. RV function is an important prognostic factor in a variety of cardiopulmonary diseases,1-6 but its echocardiographic evaluation is

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Figure 4 Box plots showing PLSS and time to PLSS in normal subjects (blue boxes) and patients with RV dysfunction (red boxes). The size of the box is determined by the 25th and 75th percentiles, the line in the middle of the box is the median, and the small square is the mean; the whiskers indicate the 5th and 95th percentiles. Global and regional PLSS were significantly higher in the normal subjects than in the group with RV dysfunction (A), and global and regional time to PLSS was shorter (B) (all of these differences were statistically significant except at the RV basal and mid free wall).

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Table 3 Global and regional PLSS and time to PLSS in patients with RV dysfunction with or without pulmonary hypertension Systolic PAP (mm Hg) Variable

PLSS (%) Global Basal free wall Mid free wall Apical free wall Basal septum Mid septum Apical septum Time to PLSS (ms) Global Basal free wall Mid free wall Apical free wall Basal septum Mid septum Apical septum SD Traditional parameters of RV contraction TAPSE (cm) RV FAC (%)

P

<35

>35

Unadjusted

Adjusted *

14.4 6 3.4 18.8 6 7.3 19.3 6 5.7 17.3 6 6.2 10.3 6 4.9 9.2 6 3.7 11.5 6 4.7

12.7 6 3.6 18.6 6 7.2 16.2 6 6.3 15.4 6 6.0 8.6 6 5.3 7.7 6 4.2 9.5 6 7.0

.038 .913 .030 .183 .149 .105 .129

.037 .864 .058 .239 .061 .084 .497

425 6 71 378 6 89 380 6 78 421 6 89 449 6 122 457 6 120 465 6 87 78 6 30

403 6 79 391 6 76 379 6 85 425 6 116 371 6 129 391 6 138 470 6 98 86 6 27

.217 .512 .928 .842 .009 .029 .820 .230

.299 .788 .549 .809 .045 .131 .832 .167

1.4 6 0.2 33 6 7

1.3 6 0.3 28 6 7

.047 .008

.167 .013

PAP, Pulmonary artery pressure. Multivariate linear regression, with age, LV end-diastolic volume, LV ejection fraction, etiology of biventricular failure, and QRS as covariates.

often challenging because of the particular nature of RV anatomy.7 Traditional echocardiographic parameters (TAPSE and RV FAC) provide information concerning global RV function but miss potentially important regional variations in contractility and do not assess contraction synchronicity. Moreover, the interpretation of TAPSE and RV FAC data may be affected by coexisting RV wall motion abnormalities.15 The use of the more recent and sophisticated imaging of myocardial systolic strain by means of speckle tracking may therefore be advantageous. Previous Studies Although a number of studies have previously demonstrated the usefulness of this technique in the assessment of LV performance,9,26,27 only a few have used it to measure global and regional RV contractility.11-13,17,28 Teske et al12 and Stefani et al13 mainly studied RV strain and ventricular response to exercise in athletes, finding that PLSS was significantly greater in the RV free wall than in the LV lateral wall and that athletes with RV dilatation showed less strain in the RV free wall. They also found a significant correlation between PLSS measured by means of speckle tracking or tissue Doppler (r = 0.73 in Teske et al) and good reproducibility.11,28 Jategaonkar et al17 analyzed speckle tracking–derived RV strain in adult patients before and after atrial septal defect closure and demonstrated that the procedure reduced strain by abolishing the left-to-right shunt. Speckle tracking–derived strain has also been used to assess myocardial performance and RV timing in children and in patients with congenital heart disease.14-16 Finally, speckle tracking has been found to be useful in measuring global and longitudinal strain in normal and pressureoverloaded animal right ventricles.29 However, to the best of our knowledge, there are no published studies concerning patients with RV dysfunction associated with LV dysfunction, the most frequent scenario in clinical practice. Our study

confirms the usefulness of speckle tracking–derived strain in assessing RV performance, provides a complete analysis of the magnitude and timing of global and regional RV strain in normal subjects (which could be used as reference values in further studies), and extends our knowledge of RV speckle tracking–derived strain to patients with biventricular dysfunction. Magnitude of RV Strain Using TAPSE and RV FAC as reference methods, we found that speckle tracking–derived strain accurately identified reduced global RV function and that a global PLSS cutoff value of 19% can be considered a useful means of differentiating normal and impaired right ventricles. We are aware that TAPSE and RV FAC have a number of intrinsic limitations, but they are widely used in clinical practice and can be considered validated indices of global RV contractility.6-8 Speckle tracking–derived strain has added value over TAPSE and RV FAC, because it also allows the regional analysis of RV contractility and, as in the case of the left ventricle, it is essential to understand whether reduced RV performance is due to a global failure or to localized impaired contraction. Furthermore, it identifies discrete and localized losses in contractility that are still insufficient to affect global systolic function and thus has potential diagnostic and prognostic implications. Rather than the rough estimates of global RV function provided by TAPSE and RV FAC, we can now look at the right ventricle at the regional level and acquire more information concerning the pathophysiologic mechanisms leading to RV failure. We found that septal PLSS values in normal subjects were similar to those reported for LV strain,30,31 but, in agreement with the findings of Stefani et al,13 RV free wall PLSS was significantly greater. One possible explanation for this is that the thin RV free wall contracts against low pulmonary resistance, thus leading to significantly higher strain. On the other hand, the septum consists of the same fibers as those forming the left ventricle and must deal not only with loading

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conditions in the right ventricle but also with the higher LV afterload. Nevertheless, like the authors of other published studies of Dopplerderived and speckle tracking–derived RV strain,19,20,22 we chose to analyze the septum as part of the right ventricle, because it cannot be considered simply a part of the LV because its shortening contributes to the ejection phase of the right ventricle and any impairment in its contractility reduces RV performance.32 Global and septal PLSS were both greater in patients with CAD than in those with nonischemic RV dysfunction. One possible explanation could be that ischemic heart disease causes a more localized loss in contraction, whereas other pathologic conditions globally impair both ventricles. However, this hypothesis needs to be confirmed by further studies.

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confirm this by showing that global PLSS was reduced in the presence of pulmonary hypertension but also extend the findings to patients with concomitant RV and LV dysfunction. The magnitude of RV strain was lower in patients with RV dysfunction than in normal subjects and was further reduced in those with pulmonary hypertension. When each RV segment was considered individually, there was a clear trend toward less regional PLSS in patients with RV dysfunction and pulmonary hypertension than in those without pulmonary hypertension, although the differences were not statistically significant, probably because of the small number of patients. Our data not only show significantly greater RV dyssynchrony in the presence of pulmonary hypertension (in line with the previous findings of Kalogeropoulos et al20) but also that this is true in patients with RV dysfunction.

Timing of RV Strain Some previous studies have extensively assessed LV dyssynchrony27,33 by means of Doppler tissue imaging and speckle tracking in an attempt to identify candidates for resynchronization therapy, and others have mainly evaluated the timing between septum and RV free wall activation or between LV lateral and RV free wall activation using tissue Doppler.34 However, little is known about the intraventricular dyssynchrony of different RV segments assessed by means of speckle tracking, and it is not clear whether patients with isolated RV dyssynchrony benefit from cardiac resynchronization.20,35 We used speckle tracking–derived strain to compare the timing of RV contraction (time to PLSS) between patients with RV dysfunction and normal subjects. Kalogeropoulos et al20 previously showed that RV dyssynchrony correlated with global RV strain in patients with pulmonary arterial hypertension, but we extended these findings by showing that global and regional time to PLSS and the dispersion of contraction timing were both greater in patients with RV dysfunction than in normal subjects. We also found that the RV free wall contracted earlier than the LV lateral wall in normal subjects, whereas it contracted later in patients with RV dysfunction. Our findings indicate that although QRS duration is helpful when assessing interventricular dyssynchrony, it does not help identify intraventricular RV dyssynchrony, as there was no difference in the dispersion of contraction timing between the patients with QRS intervals < 120 ms and those with QRS intervals > 120 ms. Intraventricular RV dyssynchrony therefore needs to be further evaluated by means of speckle tracking–derived strain. Contraction timing and its dispersion provide fundamental information for the characterization of RV myocardial function that complements the information provided by the magnitude of RV contraction. Uncoordinated longitudinal contraction may decrease RV function to a greater extent than that which might be expected from loss of contractility alone.20 Pulmonary Hypertension A few studies have assessed speckle tracking–derived strain in patients with pulmonary hypertension.18-20,22 It has been shown that acute RV pressure overload reduces global and regional RV strain and increases the regional heterogeneity of PLSS in patients with acute pulmonary thromboembolism.19 It has also been found that speckle tracking–derived indices can identify the development of pulmonary hypertension in patients with systemic sclerosis and reflect an adaptive response to higher levels of pulmonary vascular resistance.18 Pirat et al22 showed that in comparison with normal controls, PLSS was impaired in patients with pulmonary hypertension and was most altered in the presence of severe pulmonary hypertension. Our data

Study Limitations This study had a number of limitations. First of all, RV strain was assessed only in the 4-chamber view of the 6 segments of the right ventricle, but RV longitudinal function measured in the inlet chamber accounts for about 80% of RV function.12,36 Second, we did not compare our results with those of magnetic resonance imaging. However, previous studies of LV speckle tracking–derived strain have already validated its use against magnetic resonance imaging.9 Furthermore, although magnetic resonance imaging is considered the gold standard for determining RV volumes and function, it is currently limited by its cost and availability and is deemed unsuitable after the implantation of a cardiac pacemaker. Third, we did not compare our findings with those obtained using real-time three-dimensional echocardiography. However, although real-time three-dimensional echocardiography is currently used to assess the left ventricle in clinical practice, there is still little published evidence concerning its feasibility and reliability in assessing the right ventricle with dedicated software. Finally, the optimal PLSS cutoff value for distinguishing normal and reduced RV systolic function obtained by means of receiver-operating characteristic analyses was not validated in an independent sample and therefore needs further validation before it can be used in clinical practice.

CONCLUSIONS Global RV PLSS is a reliable means of measuring global RV function because it correlates well with other more established measurements of global RV systolic function (ie, TAPSE and RV FAC). Furthermore, regional RV PLSS makes it possible to study regional RV function, and the time to PLSS allows the assessment of intraventricular RV dyssynchrony. RV strain derived from B-mode images by means of speckle tracking can therefore be considered a new and useful method of studying RV function and identifying patients with subclinical RV dysfunction. REFERENCES 1. D’Alonzo GE, Barst RJ, Ayres SM, Bergofsky EH, Brundage BH, Detre KM, et al. Survival in patients with primary pulmonary hypertension. Results from a national prospective registry. Ann Intern Med 1991;115:343-9. 2. Mehta SR, Eikelboom JW, Natarajan MK, Diaz R, Yi C, Gibbons RJ, et al. Impact of right ventricular involvement on mortality and morbidity in patients with inferior myocardial infarction. J Am Coll Cardiol 2001;37:37-43.

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