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Severe Tricuspid Regurgitation Shows Significant Impact in the Relationship Among Peak Systolic Tricuspid Annular Velocity, Tricuspid Annular Plane Systolic Excursion, and Right Ventricular Ejection Fraction
Severe Tricuspid Regurgitation Shows Significant Impact in the Relationship Among Peak Systolic Tricuspid Annular Velocity, Tricuspid Annular Plane Systolic Excursion, and Right Ventricular Ejection Fraction Shih-Hung Hsiao, MD, Shih-Kai Lin, MD, Wen-Chin Wang, MD, Shu-Hsin Yang, MD, Pei-Lan Gin, MD, and Chun-Peng Liu, MD, Kaohsiung, Taiwan
Objectives: Peak systolic mitral annular velocities correlate with left ventricular ejection fraction (EF) regardless of mitral regurgitation severity. Peak systolic tricuspid annular velocity (RV-Sm) and tricuspid annular plane systolic excursion (TAPSE) are used to assess right ventricular (RV) EF (RVEF). We investigated whether tricuspid regurgitation (TR) affects the relationship among RV-Sm, TAPSE, and RVEF. Methods: Patients (n ⴝ 625) underwent echocardiography and Doppler tissue studies. Left ventricular EF and RVEF were estimated by Simpson’s rule. Because of confounding, we excluded patients with diseases that influence mitral annular motion or left ventricular function. We finally enrolled 225 patients: 125 with mild TR, 50 with moderate TR, and 50 with severe TR. Forty study patients (20 with mild TR, 10 with moderate TR, and 10 with severe TR) received radionuclide ventriculography.
Analysis of right ventricular (RV) function is con-
sidered to be difficult and burdened with inaccuracies. The major difficulty relates to the complex shape of the RV chamber, which is crescent-shaped in cross section and triangular from a lateral view. In addition, RV contraction has been thought to be different from that of the left ventricle (LV). Because of the shape of the RV, which has large sides in comparison with the space between them, contraction of the RV has been believed to be mainly based on inward movement of the RV free wall, with slight movement of the long RV walls toward each other,
From the Cardiovascular Center, Department of Internal Medicine, Kaohsiung Veterans General Hospital. Reprint requests: Shih-Hung Hsiao, MD, Cardiovascular Center, Department of Internal Medicine, Kaohsiung Veterans General Hospital, 386, Da-Chung First Rd, Kaohsiung 813, Taiwan (E-mail: [email protected]). 0894-7317/$32.00 Copyright 2006 by the American Society of Echocardiography. doi:10.1016/j.echo.2006.01.014
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Results: The RVEF estimated by Simpson’s method correlated strongly to that estimated by the radionuclide method (r ⴝ 0.793, r 2 ⴝ 0.629, P < .0001). With mild or moderate TR, RV-Sm correlated well to RVEF (mild TR group: r ⴝ 0.765, r 2 ⴝ 0.59, P < .0001; moderate TR group: r ⴝ 0.756, r 2 ⴝ 0.57, P < .0001). RV-Sm had no significant correlation to RVEF in patients with severe TR (r ⴝ 0.212, r 2 ⴝ 0.05, P ⴝ .167). Over a range of TR severities, the relationship between TAPSE and RVEF showed a similar trend to that between RV-Sm and RVEF. Conclusion: Severe TR has a significant impact on the relationship between RV-Sm and RVEF and between TAPSE and RVEF. TAPSE and RV-Sm in patients with severe TR show poor correlation to RVEF. When applying Doppler tissue method or TAPSE to assess RV function, severe TR is a significantly confounding factor. (J Am Soc Echocardiogr 2006;19: 902-910.)
causing displacement of a large volume from within. Shortening of the ventricle, considered to be an important factor of LV contraction, has only recently been demonstrated to be an essential part of RV function. Analysis of RV function using 2-dimensional echocardiography is time-consuming and likely to result in unreliable data. Three-dimensional echocardiography promises accurate determination of LV and RV function. However, the technique is time-consuming and still far from being clinically applicable. New echocardiographic techniques, namely Doppler tissue imaging (DTI), can provide information about regional myocardial systolic and diastolic function. DTI of the mitral annulus has been repetitively shown to accurately and reproducibly represent global LV systolic or diastolic function.1-15 The investigation by Alam et al16 also concluded that mitral annular velocity could be used to assess LV function regardless of significant mitral regurgitation. Myocardial DTI has been used to assess RV function, and peak systolic velocity of the tricuspid
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lateral annulus was well correlated with RV ejection fraction (EF) (RVEF).17-23 Many studies show the usefulness of DTI for the analysis of the changes in RV function occurring in several pathologic conditions and for a better understanding of the mechanisms underlying RV dysfunction in diseases directly or indirectly involving this chamber. Another study24 proposed measurement of the tricuspid annular plane systolic excursion (TAPSE) as an accurate index of RV systolic function. TAPSE highlighted strong correlations with RVEF measured by both radionuclide ventriculography and RV catheterization. They are simple, reproducible, and accurate methods to evaluate RV function. However, until now, there has been no evidence to prove whether tricuspid regurgitation (TR) was a confounding factor affecting the relationship among systolic tricuspid annular velocity (RV-Sm), TAPSE, and RVEF. We designed this study to evaluate this possible confounding effect of TR.
METHODS Study Population From October 2004 to July 2005, 625 patients were selected to receive routine echocardiography and myocardial Doppler tissue studies after informed consent. They were scheduled for echocardiographic examination for any purpose. Of special interest to us was the severity of TR in these patients. Patients were evaluated for the presence of TR using inspection of the color Doppler jet area in the right atrium (RA). Considering jet geometry and jet area in multiple views, the extent of the regurgitation jet was described on a 0-to-4⫹ scale, where 0 was absence of regurgitation, 1⫹ was mild, 2 to 3⫹ was moderate, and 4⫹ was severe regurgitation. Severe TR was also confirmed by systolic reverse flow in pulsed wave Doppler tracings over the hepatic vein. After exclusion of: (1) any evidence of LV dysfunction; (2) any evidence of LV hypertrophy; (3) history of diabetes or hypertension; (4) moderate or severe left-sided valvular disease; (5) any type of cardiomyopathy; (6) history of myocardial infarction or evidence of ischemic heart disease by any stress test, myocardial perfusion scan, or coronary angiography; (7) intracardiac shunt; (8) bundle branch block; (9) any rhythm other than in sinus rhythm; and (10) inadequate performance of echocardiograms, 225 patients were enrolled. We wished to exclude any confounding factors from the left heart. Patients were separated into 3 groups according to TR severity: 125 with mild TR, 50 with moderate TR, and 50 with severe TR. The causes of severe TR are shown in Table 1. Standard Echocardiographic Examination Standard echocardiography was performed with the patients in the partial left decubitus position, using a com-
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Table 1 All causes of severe tricuspid regurgitation Causes of severe tricuspid regurgitation
Case No.
Chronic obstructive pulmonary disease Infective endocarditis Pulmonary embolism Systemic lupus erythematosus with pulmonary hypertension Primary pulmonary hypertension Scleroderma with pulmonary hypertension Bronchiectasis Tuberculosis destroyed lung Adult Still’s syndrome with pulmonary hypertension Renal cell carcinoma with multiple lung metastasis Ebstein’s anomaly
11 8 7 6 5 4 3 3 1 1 1
mercially available ultrasound system (Sonos 7500, Philips, Andover, Mass) and a 2.5- or 2.0-MHz phased-array transducer. We examined the participants with standard parasternal long-axis, short-axis, and apical views. All measurements were done by one of the authors (S-H. H.) following the recommendations of the American Society of Echocardiography. Baseline 2-dimensional echocardiography followed generally accepted procedures, and Doppler measurements were made at end expiration, ensuring that the participant was not straining at that time. Transmitral flow was measured by pulsed wave Doppler echocardiography. We measured early diastolic (mitral E) velocity and late diastolic (mitral A) velocity of mitral inflow. Early diastolic (tricuspid E) and late diastolic (tricuspid A) velocities of tricuspid inflow were also obtained. LV EF (LVEF) was estimated by Simpson’s method. To assess RVEF, a modification of Simpson’s method was used.18 Two orthogonal echocardiographic views from the apex and subcostal windows were obtained to assess Simpson’s RVEF. Tracing of the RV endocardium at end systole and end diastole were performed by either identifying the opening and closing of the tricuspid valve or by visually assessing the smallest and largest RV chamber size. The Simpson’s method was used to determine RV volumes and the RVEF was calculated by subtracting end-systolic volume from end-diastolic volume (EDV) divided by EDV: RVEF% ⫽ 100 ⫻ (EDV ⫺ end-systolic volume)/EDV. All data were recorded on VHS videotape and stored on magnetic optical disks. Electrocardiography was recorded simultaneously. At apical 4-chamber view, M-mode recording of the long axis was taken from the lateral side of the tricuspid annulus. The maximal distance of endocardial motion during systolic phase was defined as TAPSE. Estimated Pulmonary Artery Systolic Pressure A systematic search was performed using 2-dimensional and color flow Doppler to identify the most complete TR jet followed by continuous wave Doppler acquisition of spectral envelopes of the greatest maximal velocity and density. The systolic transtricuspid pressure gradient was
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calculated using the modified Bernoulli equation: P ⫽ 4 ⫻ V2 where V represents the maximal regurgitant velocity in meters per second. To estimate RA pressure, measurements of inferior vena cava diameters were made from long-axis subxiphoid views. RA pressure was estimated using the caval respiratory index as described by Kircher et al.25 When the caval respiratory index exceeded 50%, we assumed that the RA pressure was 5 mm Hg. When the caval index was less than 50%, we assumed that the RA pressure was 15 mm Hg. An estimation of pulmonary artery systolic pressure was obtained by calculating the sum of the transtricuspid gradient and the estimated RA pressure. Pulsed Wave Doppler Myocardial Imaging Pulsed DTI was performed using spectral pulsed Doppler signal filters, adjusting the Nyquist limit to 15 to 20 cm/s (approximately equal to myocardial velocities) and using the minimal optimal gain. In the apical 4-chamber view, a 3-mm pulsed Doppler sample volume was placed at the level of the RV tricuspid annulus, and septal and lateral mitral annulus (LV lateral wall). The apical view was chosen to obtain a quantitative assessment of the regional wall motion and to minimize the incidence angle between the Doppler beam and the longitudinal wall motion. Pulsed DTI was characterized by a myocardial systolic wave (Sm) and two diastolic waves: early diastolic (Em) and atrial contraction (Am). The pulsed wave DTI tracing was recorded over 5 cardiac cycles at a sweep speed of 100 mm/s and was used for offline calculation. Isovolumic contraction time, isovolumic relaxation time, and ejection time derived by DTI were obtained. Those time intervals were required for calculation of the myocardial performance index. Myocardial performance index was calculated as (B ⫺ A)/A (Figure 1), where B denoted time interval from onset of isovolumic contraction to the end of isovolumic relaxation and A was ventricular ejection time. Velocities and time interval measurements were performed with software of the digital system. First-pass Radionuclide Ventriculography Forty study patients were selected to receive radionuclide ventriculography: 20 with mild TR, 10 with moderate TR, and 10 with severe TR. The purpose was to check the correlation between RVEF estimated by Simpson’s rule and the radionuclide method. The investigation was performed after a rapid bolus injection of 740 MBq of technetium 99m pertechnetate in a right antecubital vein with a polyethylene catheter, followed by 20 mL of saline solution. First-pass radionuclide ventriculography was acquired in the 30-degree right anterior oblique projection, in the supine position, using a single photon emission computed tomography gamma camera. The camera was equipped with a low-energy high-resolution collimator, and a 15% window was centered at the 140-keV photo peak of technetium 99m. The bolus quality was tested using a time activity curve in the region of interest drawn on the superior caval vein. The study was acquired in the
Figure 1 Myocardial Doppler tissue imaging (DTI), including systolic (Sm), early diastolic (Em), and late diastolic (Am) waves. Myocardial performance index calculated as: [time interval from onset of isovolumic contraction to end of isovolumic relaxation (B) ⫺ ventricular ejection time (A)]/A. ECG, Electrocardiogram; IVCT, isovolumic contraction time derived from DTI; IVRT, isovolumic relaxation time derived from DTI.
frame mode of 0.200 s/frame using a zoom factor of 1.48. In all, 250 frames were collected. RVEF was calculated from end-diastolic and end-systolic counts using background-corrected radionuclide time activity curves emanating from the RV chamber. Statistical Analysis Analyses were performed using software (SPSS 12.0 for Windows, Chicago, Ill). Variables are presented as mean ⫾ SD. Analysis of variance and post hoc tests for unpaired data were used to estimate differences between groups. Differences were considered statistically significant if the P value was less than .05 with a 95% confidence interval. The reproducibility of the measurements of DTI parameters, RVEF and LVEF, was determined. To determine interobserver variability, the average value of the first observer (S-H. H.) was compared with the reading of the second observer (S-K. L.), who was unaware of the initial results. The mean difference between the measurements of the two observers was calculated and the percentage variability was derived as the absolute difference between the two sets of measurements divided by the mean of the two observations. Intraobserver variability (S-K. L.) was also calculated following this method. Linear regression analyses and partial correlation tests (either Pearson’s or Spearman’s method) were performed to assess univariate relations.
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Table 2 Baseline characteristics and echocardiographic parameters of different groups Age, y Sex, M/F Smoking, % Heart rate, beats/min PASP, mm Hg LA, mm IVS, mm LVIDd, mm LVIDs, mm Mitral E, cm/s Mitral A, cm/s LVEF, % IVS flattening, % RVDd, mm Tricuspid E, cm/s Tricuspid A, cm/s RVEF, % TAPSE, cm RV Sm, cm/s Em, cm/s Am, cm/s IVCT, ms IVRT, ms MPI Septum Sm, cm/s Em, cm/s Am, cm/s IVCT, ms IVRT, ms MPI LV lateral wall Sm, cm/s Em, cm/s Am, cm/s IVCT, ms IVRT, ms MPI
Mild TR (n ⴝ 125)
Moderate TR (n ⴝ 50)
Severe TR (n ⴝ 50)
58.3 ⫾ 18.8 63/62 24% 74.4 ⫾ 15.3 32.1 ⫾ 10.0 36.3 ⫾ 5.7 10.5 ⫾ 2.0 48.3 ⫾ 3.5 25.9 ⫾ 4.8 86.0 ⫾ 32.1 77.7 ⫾ 24.6 61.3 ⫾ 6.5 5% 28 ⫾ 5 43 ⫾ 10 35 ⫾ 8 46.5 ⫾ 8.2 2.2 ⫾ 0.5
63.6 ⫾ 15.4 26/24 22% 81.2 ⫾ 16.5 53.7 ⫾ 12.6 42.9 ⫾ 10.3 10.7 ⫾ 1.4 48.2 ⫾ 7.0 26.2 ⫾ 8.1 84.4 ⫾ 32.2 77.8 ⫾ 29.0 56 ⫾ 9.3 38% 31 ⫾ 7 47 ⫾ 9 36 ⫾ 8 43.8 ⫾ 10.0 1.8 ⫾ 0.6
61.8 ⫾ 15.7 24/26 31% 83 ⫾ 17.2 66.4 ⫾ 17.5 48.4 ⫾ 12.1 10.3 ⫾ 1.4 46.0 ⫾ 6.0 25.6 ⫾ 7.1 77.3 ⫾ 24.6 82.3 ⫾ 29.1 55.1 ⫾ 9.4 96% 38 ⫾ 9 53 ⫾ 12 38 ⫾ 9 41.8 ⫾ 8.1 1.6 ⫾ 0.5
.094
ANOVA P value
.001 .0001 .0001 .286 .058 .063 .022 .415 .0001 .0001 .0001 .198 .002 .001
12.4 10.0 12.7 64.8 58.6 0.42
⫾ ⫾ ⫾ ⫾ ⫾ ⫾
2.6 3.1 3.4 13.3 14.6 0.09
10.7 10.4 13.0 61.6 72.5 0.49
⫾ ⫾ ⫾ ⫾ ⫾ ⫾
3.1 3.6 5.0 10.3 18.6 0.11
10.2 11.0 9.5 71.1 77.8 0.57
⫾ ⫾ ⫾ ⫾ ⫾ ⫾
2.7 2.8 3.3 18.6 21.3 0.13
.0001 .411 .0001 .295 .0001 .0001
7.6 7.3 8.7 61.3 64.7 0.42
⫾ ⫾ ⫾ ⫾ ⫾ ⫾
1.4 2.5 2.0 15.2 14.9 0.09
7.2 7.0 8.2 57.5 72.1 0.45
⫾ ⫾ ⫾ ⫾ ⫾ ⫾
2.6 2.3 3.0 15.0 18.3 0.12
6.6 7.5 6.3 73.3 71.1 0.51
⫾ ⫾ ⫾ ⫾ ⫾ ⫾
2.1 2.5 2.0 20.2 16.0 0.13
.08 .764 .002 .018 .122 .013
9.3 9.2 10.0 62.5 64.9 0.42
⫾ ⫾ ⫾ ⫾ ⫾ ⫾
2.4 3.2 2.7 13.6 12.5 0.08
8.9 9.3 9.7 61.3 65.0 0.43
⫾ ⫾ ⫾ ⫾ ⫾ ⫾
2.7 3.3 3.2 15.4 15.5 0.09
9.1 9.8 10.1 65.4 66.6 0.46
⫾ ⫾ ⫾ ⫾ ⫾ ⫾
2.9 3.0 2.5 15.5 14.3 0.10
.782 .175 .871 .264 .93 .219
Am, peak late diastolic myocardial velocity derived by pulsed wave Doppler tissue; ANOVA, analysis of variance; Em, peak early diastolic myocardial velocity derived by pulsed wave Doppler tissue; F, female; IVCT, isovolumic contraction time derived from Doppler tissue imaging; IVRT, isovolumic relaxation time derived from Doppler tissue imaging; IVS, wall thickness of intraventricular septum; LA, diameter of left atrium; LVEF, left ventricular ejection fraction; LVIDd, left ventricular end-diastolic dimension; LVIDs, left ventricular end-systolic dimension; LV lateral wall, lateral mitral annulus; M, male; mitral A, peak velocity of late diastolic mitral inflow; mitral E, peak velocity of early diastolic mitral inflow; MPI, myocardial performance index, defined as the sum of isovolumetric contraction time and isovolumetric relaxation time divided by the ejection time obtained by tissue Doppler image; PASP, pulmonary artery systolic pressure; RV, lateral tricuspid annulus; RVDd, right ventricular end-diastolic dimension; RVEF, right ventricular ejection fraction; septum, basal segment of intraventricular septum; Sm, peak systolic myocardial velocity derived by pulsed wave Doppler tissue; TAPSE, tricuspid annular plane systolic excursion; TR, tricuspid regurgitation; tricuspid A, peak velocity of late diastolic tricuspid inflow; tricuspid E, peak velocity of early diastolic tricuspid inflow. *Statistically significant.
RESULTS Baseline characteristics were similar among groups except for higher heart rate and pulmonary artery systolic pressure in the severe TR group (Table 2). The echocardiographic parameters of the LV in these 3 groups were also similar except for left atrial size, mitral E velocity, and LVEF (Table 2). After controlling for possible confounding factors from
the left heart, we think the differences among left atrial size, mitral E, and LVEF among groups were a result of interactions between the left and right heart. All causes of severe TR were associated with underlying lung conditions or tricuspid valvular problems (Table 1). As TR severity increased, enddiastolic RV dimension and tricuspid E velocity increased, but RVEF and TAPSE decreased significantly (Table 2). Most patients (96%) with severe TR
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showed flattening of the intraventricular septum (IVS). The parameters derived from DTI were significantly different among the 3 groups, especially over the lateral tricuspid annulus (RV) and IVS. Peak systolic velocity (RV-Sm) and late-diastolic velocity (RV-Am) of tricuspid annulus were significantly lower in the severe TR group (P ⬍ .0001). The isovolumic relaxation time and myocardial performance index of the RV obtained by DTI were higher in the severe TR group than in the mild or moderate TR groups (P ⬍ .0001). Relation of RVEF Obtained by Radionuclide Ventriculography and Echocardiographic Simpson’s Method Forty patients (20 with mild TR, 10 with moderate TR, and 10 with severe TR) received simultaneous RVEF assessment by radionuclide ventriculography and echocardiography using Simpson’s method. Simple linear regression analysis revealed a significant correlation between RVEF obtained by those two methods regardless of TR severity (all patients: r ⫽ 0.793, r 2 ⫽ 0.63, and P ⬍ .0001; patients with severe TR: r ⫽ 0.76, r 2 ⫽ 0.57, and P ⫽ .007) (Figure 2). The Relation of TAPSE and RVEF According to the Severity of TR In the mild and moderate TR groups, TAPSE was as an accurate index of RV systolic function with a reasonably strong correlation. We found reliable relationships between TAPSE and RVEF in patients with mild TR (r ⫽ 0.728, r 2 ⫽ 0.53, P ⬍ .0001) and moderate TR (r ⫽ 0.678, r 2 ⫽ 0.46, P ⬍ .0001). However, the close relation was not observed in patients with severe TR (r ⫽ 0.301, r 2 ⫽ 0.091, P ⫽ .056) (Figure 3). After pooling data from all 3 groups, the equation: RVEF% ⫽ 10.3 ⫻ TAPSE ⫹ 24, was obtained by simple linear regression analysis with r ⫽ 0.672, r 2 ⫽ 0.45, and P ⬍ .0001. Using this equation to assess RVEF in patients with severe TR, there was a poor correlation between RVEF assessed by Simpson’s rule and by this equation (r 2 ⫽ 0.08). The Relation of RV-Sm and RVEF According to the Severity of TR In patients with severe TR, we did not find a strong correlation between RV-Sm and RVEF derived by Simpson’s rule (r ⫽ 0.212, r 2 ⫽ 0.045, P ⫽ .167). But, RV-Sm showed a strong linear relationship to RVEF in the mild TR group (r ⫽ 0.765, r 2 ⫽ 0.59, P ⬍ .0001); this was also seen in the moderate TR group (r ⫽ 0.756, r 2 ⫽ 0.57, P ⬍ .0001) (Figure 4). From simple linear regression analysis of data from all patients, we obtained the equation: RVEF% ⫽ 2.1 ⫻ RV-Sm ⫹ 21, with r ⫽ 0.69, r 2 ⫽ 0.48, and P ⬍ .0001. Applying this equation to patients with severe TR, we
Figure 2 Strong correlation between right ventricular ejection fraction (RVEF) obtained by radionuclide ventriculography and echocardiographic Simpson’s method regardless of tricuspid regurgitation (TR) severity. A, All patients (Y ⫽ 16.6 ⫹ 0.6X, r 2 ⫽ 0.63, P ⬍ .0001). B, Patients with severe TR (Y ⫽ 11.8 ⫹ 0.75X, r 2 ⫽ 0.57, P ⫽ .007).
found only a poor correlation between RVEF estimated by Simpson’s method and this equation (r 2 ⫽ 0.09). Reproducibility The intraobserver differences for RVEF and LVEF were 4.5 ⫾ 3.5% and 3.5 ⫾ 3.1%, respectively. The intraobserver differences for TAPSE was 0.1 ⫾ 0.1 with a variability of 5.1 ⫾ 4.7%. The interobserver variabilities for Sm, Em, and Am were 3.9 ⫾ 3.2%, 2.6 ⫾ 1.9%, and 4.2 ⫾ 3.0%, with intraobserver differences of 0.3 ⫾ 0.3, 0.2 ⫾ 0.2, and 0.4 ⫾ 0.3, respectively. The interobserver differences for RVEF and LVEF were 5.6 ⫾ 4.5% and 4.5 ⫾ 3.7%, respec-
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Figure 3 Relationship of tricuspid annular plane systolic excursion (TAPSE) and right ventricular ejection fraction (RVEF) in patients with mild (A), moderate (B), and severe (C) tricuspid regurgitation (TR).
tively. The interobserver differences for TAPSE was 0.2 ⫾ 0.2 with a variability of 8.1 ⫾ 7.6%. The interobserver difference for Sm was 0.5 ⫾ 0.4, with a variability of 5.8 ⫾ 4.7%. The interobserver differences for Em and Am were 0.4 ⫾ 0.4 and 0.5 ⫾ 0.4 with variabilities of 5.8 ⫾ 4.9% and 5.3 ⫾ 5.1%, respectively.
DISCUSSION Although interest in the assessment of myocardial function has long been focused on the LV, recent investigations of the importance of RV function for outcomes in patients with severely depressed LV function has increased attention on RV function. The impact of RV function on survival in patients with severe left heart failure has been emphasized by studies showing that LV function loses its prognostic value in patients with an LVEF less than 25%,
whereas a preserved RVEF proved to be predictive for exercise capacity and survival even in advanced heart failure.26 These studies26-29 indicate the need for a method that allows simple and rapid evaluation of RV function. Kaul et al24 demonstrated in 1984 that systolic shortening of the RV from apex to base, referred to as TAPSE, is an echocardiographic index that correlates with radionuclide RVEF. Another approach by Meluzin et al,23 to use pulsed DTI for analysis of the systolic velocity of tricuspid annular motion, may yield a parameter that is more easily and quickly determined. This may make analysis of tricuspid annular motion more attractive and spread its application in clinical practice. Meluzin et al23 concluded that a low peak RV-Sm has high predictive accuracy for RV dysfunction established by radionuclide ventriculography. A series of studies following the above-mentioned methods investigated RV in different disease entities.19,20,30-33 However, although as-
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Figure 4 Relationship of peak systolic tricuspid annular velocity (RV-Sm) and right ventricular ejection fraction (RVEF) in patients with mild (A), moderate (B), and severe (C) tricuspid regurgitation (TR).
sessment of annular systolic excursion is intuitively attractive, it has limitations. It fails to account for any base-to-apex motion of the entire heart as it contracts, and it will yield differing results in proportion to the angle between the transducer and the annular point of motion. For the tricuspid valve, a particular limitation may also be encountered in cases of elevated RV pressure. Moustapha et al19 demonstrated a significantly elevated RV pressure in decreased tricuspid annular motion. TR may be another cause of an impaired relationship between tricuspid annular motion and RVEF. It is conceivable that tricuspid annular motion increases with TR independent of RV function. Furthermore, mitral and tricuspid annular motions are interrelated and a depressed LV function is indirectly reflected by a depressed tricuspid annular motion. Our study was designed to overcome these problems and we excluded most confounding factors that influence mitral annular motion or LV function, including coronary
artery disease,32 cardiomyopathy, LV hypertrophy,23,34 intracardiac shunt, hypertension,35 diabetes mellitus,36 and any evidence of LV dysfunction.23 Our aim was to investigate whether the severity of pure TR affects the relationship between tricuspid annular motion and RVEF. In the beginning of this study, we showed that RVEF obtained by Simpson’s rule is well correlated to RVEF obtained by radionuclide ventriculography regardless of TR severity. This allowed us to subsequently evaluate RVEF by Simpson’s method, which is easier to perform. Our study demonstrates a strong correlation among RV-Sm, TAPSE, and RVEF in patients with mild or moderate TR. This correlation was not strong for patients with severe TR, possibly because of RV dilatation. In these patients, findings are controversial and inaccurate probably because of the angle occurring between the transducer and the annular point of the same tricuspid motion. The progression of RV dilatation after a
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distinct degree of TR has developed makes larger angles between transducer and tricuspid annulus, and does not take into account the base-to-apex movement of the entire tricuspid annulus. We think that the interpretation of DTI parameters over the IVS should be done with caution. RV volume overloading produces RV dilatation and paradoxical motion of the IVS, mainly a result of a reversal of the end-diastolic pressure gradient between the two ventricles.37 In our study, 38% patients with moderate TR and 96% with severe TR displayed paradoxical motion and flattening of the IVS. We believe the DTI of the LV lateral wall represents LV function rather than DTI of the IVS. Regardless of the severity of TR, the DTI parameters over the LV lateral wall clearly show that all of our patients had normal LV function. In the study by Alam et al,16 the systolic mitral annular velocity was correlated relatively well with LVEF in patients with or without severe mitral regurgitation. But in our study, severe TR had a significant impact on the relation between tricuspid annular motion and RVEF. There are a number of possible explanations for this difference. First, severe TR is almost always combined with pulmonary hypertension. Pulmonary hypertension influences tricuspid annular motion.19 Second, the cohort studied by Alam et al16 was mostly patients with ischemic heart disease (66 of 96, 69%) and dilated cardiomyopathy (25 of 96, 26%). In addition, 11 patients (11%) with bundle branch block and 11 patients (11%) with atrial fibrillation were enrolled. As we know, those characteristics can affect Doppler tissue parameters and influence the interpretation of results. Third, there are different physiologic characteristics of LV and RV in the face of significant hemodynamic regurgitation. In patients with severe mitral regurgitation, the impact of regurgitation into the LV is associated frequently with volume overloading. But the impact of severe TR on RV is always a combination of volume and pressure overloading. The detailed mechanisms for these different results should be investigated by further studies. Studies applying DTI and TAPSE to the investigation of RV function appear very encouraging. However, DTI and TAPSE evaluation of tricuspid annular motion still have potential limitations. In conclusion, although measurement of tricuspid annular motion seems to provide an appealing, uncomplicated approach to determine RV systolic function, its accuracy in severe TR is disappointing. Using these methods to assess RV, severe TR should be considered a potential confounding factor. Limitations Our study has some limitations. Although we were careful to exclude patients with concomitant conditions that would potentially confound interpreta-
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tion, our cohort was relatively older and aging seems to affect RVEF and LVEF. The echocardiographic and radionuclide ventriculographic parameters were not obtained simultaneously; there was an interval of less than 1 week between studies. However, in view of the stable condition of our cohort, we do not think that this short time interval significantly influenced our results. Another limitation is that only a few patients received radionuclide ventriculography. We used Simpson’s method to assess RVEF and the accuracy of RVEF estimated by this method is still doubtful, although a strong correlation between Simpson’s RVEF and radionuclide RVEF has been demonstrated. Conclusion Severe TR has a significant impact on the relationship between RV-Sm and RVEF and between TAPSE and RVEF; RV-Sm and TAPSE in patients with severe TR shows poor correlation to RVEF. When applying Doppler tissue method or TAPSE to assess RV function, severe TR is a significantly confounding factor.
REFERENCES 1. Oki T, Tabata T, Yamada H. Clinical application of pulsed Doppler tissue imaging for assessing abnormal left ventricular relaxation. Am J Cardiol 1997;79:921-8. 2. Sohn DW, Chai IH, Lee DJ. Assessment of mitral annulus velocity by Doppler tissue imaging in the evaluation of left ventricular diastolic function. J Am Coll Cardiol 1997;30: 474-80. 3. Farias CA, Rodriguz L, Garcia MJ, et al. Assessment of diastolic function by tissue Doppler echocardiography: comparison with standard transmitral and pulmonary venous flow. J Am Soc Echocardiogr 1999;12:609-17. 4. Nagueh SF, Middleton KJ, Kopelen HA, et al. Doppler tissue imaging: a noninvasive technique for evaluation of left ventricular relaxation and estimation of filling pressure. J Am Coll Cardiol 1997;30:1527-33. 5. Garcia MJ, Rodriguez L, Ares M, et al. Differentiation of constrictive pericarditis from restrictive cardiomyopathy: assessment of left ventricular diastolic velocities in longitudinal axis by Doppler tissue imaging. J Am Coll Cardiol 1996;27: 108-14. 6. Peteiro J, Garcia-Lara J, Garrido I, et al. A new simple method to assess global left ventricular systolic function based on the sum of regional myocardial velocities. Am J Cardiol 2005;95: 550-2. 7. Cardim N, Oliveira AG, Longo S, et al. Doppler tissue imaging: regional myocardial function in hypertrophic cardiomyopathy and in athlete’s heart. J Am Soc Echocardiogr 2003; 16:223-32. 8. Zoncu S, Pelliccia A, Mercuro G. Assessment of regional systolic and diastolic wall motion velocities in highly trained athletes by pulsed wave Doppler tissue imaging. J Am Soc Echocardiogr 2002;15:900-5. 9. Ommen SR, Nishimura RA, Appleton CP, et al. Clinical utility of Doppler echocardiography and tissue Doppler imaging in the estimation of left ventricular filling pressures: a compara-
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tive simultaneous Doppler-catheterization study. Circulation 2000;102:1788-94. Palmes PP, Masuyama T, Yamamoto K, et al. Myocardial longitudinal motion by tissue velocity imaging in the evaluation of patients with myocardial infarction. J Am Soc Echocardiogr 2000;13:818-26. Mishiro Y, Oki T, Yamada H, et al. Evaluation of left ventricular contraction abnormalities in patients with dilated cardiomyopathy with the use of pulsed tissue Doppler imaging. J Am Soc Echocardiogr 1999;12:913-20. Oki T, Iuchi A, Tabata T, Mishiro Y, et al. Left ventricular systolic wall motion velocities along the long and short axes measured by pulsed tissue Doppler imaging in patients with atrial fibrillation. J Am Soc Echocardiogr 1999;12:121-8. Fukuda K, Oki T, Tabata T, et al. Regional left ventricular wall motion abnormalities in myocardial infarction and mitral annular descent velocities studied with pulsed tissue Doppler imaging. J Am Soc Echocardiogr 1998;11:841-8. Yamada H, Oki T, Tabata T, et al. Assessment of left ventricular systolic wall motion velocity with pulsed tissue Doppler imaging: comparison with peak dP/dt of the left ventricular pressure curve. J Am Soc Echocardiogr 1998;11:442-9. Gulati VK, Katz WE, Follansbee WP, et al. Mitral annular descent velocity by tissue Doppler echocardiography as an index of global left ventricular function. Am J Cardiol 1996; 77:979-84. Alam M, Wardell J, Andersson E, et al. Assessment of left ventricular function using mitral annular velocities in patients with congestive heart failure with or without the presence of significant mitral regurgitation. J Am Soc Echocardiogr 2003; 16:240-5. Dokainish H, Abbey H, Gin K, et al. Usefulness of tissue Doppler imaging in the diagnosis and prognosis of acute right ventricular infarction with inferior wall acute left ventricular infarction. Am J Cardiol 2005;95:1039-42. Miller D, Farah MG, Liner A, et al. The relation between quantitative right ventricular ejection fraction and indices of tricuspid annular motion and myocardial performance. J Am Soc Echocardiogr 2004;17:443-7. Moustapha A, Lim M, Saikia S, et al. Interrogation of the tricuspid annulus by Doppler tissue imaging in patients with chronic pulmonary hypertension: implications for the assessment of right-ventricular systolic and diastolic function. Cardiology 2001;95:101-4. Alam M, Wardell J, Andersson E, et al. Right ventricular function in patients with first inferior myocardial infarction: assessment by tricuspid annular motion and tricuspid annular velocity. Am Heart J 2000;139:710-5. Ozdemir K, Altunkeser BB, Icli A, et al. New parameters in identification of right ventricular myocardial infarction and proximal right coronary artery lesion. Chest 2003;124: 219-26. Ueti OM, Camargo EE, Ueti Ade A, et al. Assessment of right ventricular function with Doppler echocardiographic indices derived from tricuspid annular motion: comparison with radionuclide angiography. Heart 2002;88:244-8.
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23. Meluzin J, Spinarova L, Bakala J, et al. Pulsed Doppler tissue imaging of the velocity of tricuspid annular systolic motion; a new, rapid, and non-invasive method of evaluating right ventricular systolic function. Eur Heart J 2001;22:340-8. 24. Kaul S, Tei C, Hopkins JM, et al. Assessment of right ventricular function using two-dimensional echocardiography. Am Heart J 1984;128:301-7. 25. Kircher BJ, Himelman RB, Schiller NB. Noninvasive estimation of right atrial pressure from the inspiratory collapse of the inferior vena cava. Am J Cardiol 1990;66:493-6. 26. Di Salvo TG, Mathier M, Semigran MJ, et al. Preserved right ventricular ejection fraction predicts exercise capacity and survival in advanced heart failure. J Am Coll Cardiol 1995;25: 1143-53. 27. Mendes LA, Dec GW, Picard MH, et al. Right ventricular dysfunction: an independent predictor of adverse outcome in patients with myocarditis. Am Heart J 1994;128:301-7. 28. Karatasakis GT, Karagounis LA, Kalyvas PA, et al. Prognostic significance of echocardiographically estimated right ventricular shortening in advanced heart failure. Am J Cardiol 1998; 82:329-34. 29. Ghio S, Recusani F, Klersy C, et al. Prognostic usefulness of the tricuspid annular plane systolic excursion in patients with congestive heart failure secondary to idiopathic or ischemic dilated cardiomyopathy. Am J Cardiol 2000;85:837-42. 30. Oguzhan A, Abaci A, Eryol NK, et al. Color tissue Doppler echocardiographic evaluation of right ventricular function in patients with right ventricular infarction. Cardiology 2003; 100:41-6. 31. Alam M, Hedman A, Nordlander R, et al. Right ventricular function before and after an uncomplicated coronary bypass graft as assessed by pulsed wave Doppler tissue imaging of the tricuspid annulus. Am Heart J 2003;146:520-6. 32. Rambaldi R, Poldermans D, Fioretti PM, et al. Usefulness of pulse-wave Doppler tissue sampling and dobutamine stress echocardiography for the diagnosis of right coronary artery narrowing. Am Heart J 1998;81:1411-5. 33. Caso P, Galderisi M, Cicala S, et al. Association between myocardial right ventricular relaxation time and pulmonary artery pressure in chronic obstructive lung disease: analysis by pulsed Doppler tissue imaging. J Am Soc Echocardiogr 2001; 14:970-7. 34. Severino S, Caso P, Cicala S, et al. Involvement of right ventricle in left ventricular hypertrophic cardiomyopathy: analysis by pulsed Doppler tissue imaging. Eur J Echocardiogr 2000;1:281-8. 35. Galderisi M, Severino S, Caso P, et al. Right ventricular myocardial diastolic dysfunction in different kinds of cardiac hypertrophy: analysis by pulsed Doppler tissue imaging. Ital Heart J 2001;2:912-20. 36. Boyer JK, Thanigaraj S, Schechtman KB, et al. Prevalence of ventricular diastolic dysfunction in asymptomatic, normotensive patients with diabetes mellitus. Am J Cardiol 2004;93: 870-5. 37. Weyman AE, Wann S, Feigenbaum H, et al. Mechanism of abnormal septal motion in patients with right ventricular volume overload. Circulation 1976;54:179-86.
Objectives: Peak systolic mitral annular velocities correlate with left ventricular ejection fraction (EF) regardless of mitral regurgitation severity. Peak systolic tricuspid annular velocity (RV-Sm) and tricuspid annular plane systolic excursion (TAPSE) are used to assess right ventricular (RV) EF (RVEF). We investigated whether tricuspid regurgitation (TR) affects the relationship among RV-Sm, TAPSE, and RVEF. Methods: Patients (n ⴝ 625) underwent echocardiography and Doppler tissue studies. Left ventricular EF and RVEF were estimated by Simpson’s rule. Because of confounding, we excluded patients with diseases that influence mitral annular motion or left ventricular function. We finally enrolled 225 patients: 125 with mild TR, 50 with moderate TR, and 50 with severe TR. Forty study patients (20 with mild TR, 10 with moderate TR, and 10 with severe TR) received radionuclide ventriculography.
Analysis of right ventricular (RV) function is con-
sidered to be difficult and burdened with inaccuracies. The major difficulty relates to the complex shape of the RV chamber, which is crescent-shaped in cross section and triangular from a lateral view. In addition, RV contraction has been thought to be different from that of the left ventricle (LV). Because of the shape of the RV, which has large sides in comparison with the space between them, contraction of the RV has been believed to be mainly based on inward movement of the RV free wall, with slight movement of the long RV walls toward each other,
From the Cardiovascular Center, Department of Internal Medicine, Kaohsiung Veterans General Hospital. Reprint requests: Shih-Hung Hsiao, MD, Cardiovascular Center, Department of Internal Medicine, Kaohsiung Veterans General Hospital, 386, Da-Chung First Rd, Kaohsiung 813, Taiwan (E-mail: [email protected]). 0894-7317/$32.00 Copyright 2006 by the American Society of Echocardiography. doi:10.1016/j.echo.2006.01.014
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Results: The RVEF estimated by Simpson’s method correlated strongly to that estimated by the radionuclide method (r ⴝ 0.793, r 2 ⴝ 0.629, P < .0001). With mild or moderate TR, RV-Sm correlated well to RVEF (mild TR group: r ⴝ 0.765, r 2 ⴝ 0.59, P < .0001; moderate TR group: r ⴝ 0.756, r 2 ⴝ 0.57, P < .0001). RV-Sm had no significant correlation to RVEF in patients with severe TR (r ⴝ 0.212, r 2 ⴝ 0.05, P ⴝ .167). Over a range of TR severities, the relationship between TAPSE and RVEF showed a similar trend to that between RV-Sm and RVEF. Conclusion: Severe TR has a significant impact on the relationship between RV-Sm and RVEF and between TAPSE and RVEF. TAPSE and RV-Sm in patients with severe TR show poor correlation to RVEF. When applying Doppler tissue method or TAPSE to assess RV function, severe TR is a significantly confounding factor. (J Am Soc Echocardiogr 2006;19: 902-910.)
causing displacement of a large volume from within. Shortening of the ventricle, considered to be an important factor of LV contraction, has only recently been demonstrated to be an essential part of RV function. Analysis of RV function using 2-dimensional echocardiography is time-consuming and likely to result in unreliable data. Three-dimensional echocardiography promises accurate determination of LV and RV function. However, the technique is time-consuming and still far from being clinically applicable. New echocardiographic techniques, namely Doppler tissue imaging (DTI), can provide information about regional myocardial systolic and diastolic function. DTI of the mitral annulus has been repetitively shown to accurately and reproducibly represent global LV systolic or diastolic function.1-15 The investigation by Alam et al16 also concluded that mitral annular velocity could be used to assess LV function regardless of significant mitral regurgitation. Myocardial DTI has been used to assess RV function, and peak systolic velocity of the tricuspid
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lateral annulus was well correlated with RV ejection fraction (EF) (RVEF).17-23 Many studies show the usefulness of DTI for the analysis of the changes in RV function occurring in several pathologic conditions and for a better understanding of the mechanisms underlying RV dysfunction in diseases directly or indirectly involving this chamber. Another study24 proposed measurement of the tricuspid annular plane systolic excursion (TAPSE) as an accurate index of RV systolic function. TAPSE highlighted strong correlations with RVEF measured by both radionuclide ventriculography and RV catheterization. They are simple, reproducible, and accurate methods to evaluate RV function. However, until now, there has been no evidence to prove whether tricuspid regurgitation (TR) was a confounding factor affecting the relationship among systolic tricuspid annular velocity (RV-Sm), TAPSE, and RVEF. We designed this study to evaluate this possible confounding effect of TR.
METHODS Study Population From October 2004 to July 2005, 625 patients were selected to receive routine echocardiography and myocardial Doppler tissue studies after informed consent. They were scheduled for echocardiographic examination for any purpose. Of special interest to us was the severity of TR in these patients. Patients were evaluated for the presence of TR using inspection of the color Doppler jet area in the right atrium (RA). Considering jet geometry and jet area in multiple views, the extent of the regurgitation jet was described on a 0-to-4⫹ scale, where 0 was absence of regurgitation, 1⫹ was mild, 2 to 3⫹ was moderate, and 4⫹ was severe regurgitation. Severe TR was also confirmed by systolic reverse flow in pulsed wave Doppler tracings over the hepatic vein. After exclusion of: (1) any evidence of LV dysfunction; (2) any evidence of LV hypertrophy; (3) history of diabetes or hypertension; (4) moderate or severe left-sided valvular disease; (5) any type of cardiomyopathy; (6) history of myocardial infarction or evidence of ischemic heart disease by any stress test, myocardial perfusion scan, or coronary angiography; (7) intracardiac shunt; (8) bundle branch block; (9) any rhythm other than in sinus rhythm; and (10) inadequate performance of echocardiograms, 225 patients were enrolled. We wished to exclude any confounding factors from the left heart. Patients were separated into 3 groups according to TR severity: 125 with mild TR, 50 with moderate TR, and 50 with severe TR. The causes of severe TR are shown in Table 1. Standard Echocardiographic Examination Standard echocardiography was performed with the patients in the partial left decubitus position, using a com-
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Table 1 All causes of severe tricuspid regurgitation Causes of severe tricuspid regurgitation
Case No.
Chronic obstructive pulmonary disease Infective endocarditis Pulmonary embolism Systemic lupus erythematosus with pulmonary hypertension Primary pulmonary hypertension Scleroderma with pulmonary hypertension Bronchiectasis Tuberculosis destroyed lung Adult Still’s syndrome with pulmonary hypertension Renal cell carcinoma with multiple lung metastasis Ebstein’s anomaly
11 8 7 6 5 4 3 3 1 1 1
mercially available ultrasound system (Sonos 7500, Philips, Andover, Mass) and a 2.5- or 2.0-MHz phased-array transducer. We examined the participants with standard parasternal long-axis, short-axis, and apical views. All measurements were done by one of the authors (S-H. H.) following the recommendations of the American Society of Echocardiography. Baseline 2-dimensional echocardiography followed generally accepted procedures, and Doppler measurements were made at end expiration, ensuring that the participant was not straining at that time. Transmitral flow was measured by pulsed wave Doppler echocardiography. We measured early diastolic (mitral E) velocity and late diastolic (mitral A) velocity of mitral inflow. Early diastolic (tricuspid E) and late diastolic (tricuspid A) velocities of tricuspid inflow were also obtained. LV EF (LVEF) was estimated by Simpson’s method. To assess RVEF, a modification of Simpson’s method was used.18 Two orthogonal echocardiographic views from the apex and subcostal windows were obtained to assess Simpson’s RVEF. Tracing of the RV endocardium at end systole and end diastole were performed by either identifying the opening and closing of the tricuspid valve or by visually assessing the smallest and largest RV chamber size. The Simpson’s method was used to determine RV volumes and the RVEF was calculated by subtracting end-systolic volume from end-diastolic volume (EDV) divided by EDV: RVEF% ⫽ 100 ⫻ (EDV ⫺ end-systolic volume)/EDV. All data were recorded on VHS videotape and stored on magnetic optical disks. Electrocardiography was recorded simultaneously. At apical 4-chamber view, M-mode recording of the long axis was taken from the lateral side of the tricuspid annulus. The maximal distance of endocardial motion during systolic phase was defined as TAPSE. Estimated Pulmonary Artery Systolic Pressure A systematic search was performed using 2-dimensional and color flow Doppler to identify the most complete TR jet followed by continuous wave Doppler acquisition of spectral envelopes of the greatest maximal velocity and density. The systolic transtricuspid pressure gradient was
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calculated using the modified Bernoulli equation: P ⫽ 4 ⫻ V2 where V represents the maximal regurgitant velocity in meters per second. To estimate RA pressure, measurements of inferior vena cava diameters were made from long-axis subxiphoid views. RA pressure was estimated using the caval respiratory index as described by Kircher et al.25 When the caval respiratory index exceeded 50%, we assumed that the RA pressure was 5 mm Hg. When the caval index was less than 50%, we assumed that the RA pressure was 15 mm Hg. An estimation of pulmonary artery systolic pressure was obtained by calculating the sum of the transtricuspid gradient and the estimated RA pressure. Pulsed Wave Doppler Myocardial Imaging Pulsed DTI was performed using spectral pulsed Doppler signal filters, adjusting the Nyquist limit to 15 to 20 cm/s (approximately equal to myocardial velocities) and using the minimal optimal gain. In the apical 4-chamber view, a 3-mm pulsed Doppler sample volume was placed at the level of the RV tricuspid annulus, and septal and lateral mitral annulus (LV lateral wall). The apical view was chosen to obtain a quantitative assessment of the regional wall motion and to minimize the incidence angle between the Doppler beam and the longitudinal wall motion. Pulsed DTI was characterized by a myocardial systolic wave (Sm) and two diastolic waves: early diastolic (Em) and atrial contraction (Am). The pulsed wave DTI tracing was recorded over 5 cardiac cycles at a sweep speed of 100 mm/s and was used for offline calculation. Isovolumic contraction time, isovolumic relaxation time, and ejection time derived by DTI were obtained. Those time intervals were required for calculation of the myocardial performance index. Myocardial performance index was calculated as (B ⫺ A)/A (Figure 1), where B denoted time interval from onset of isovolumic contraction to the end of isovolumic relaxation and A was ventricular ejection time. Velocities and time interval measurements were performed with software of the digital system. First-pass Radionuclide Ventriculography Forty study patients were selected to receive radionuclide ventriculography: 20 with mild TR, 10 with moderate TR, and 10 with severe TR. The purpose was to check the correlation between RVEF estimated by Simpson’s rule and the radionuclide method. The investigation was performed after a rapid bolus injection of 740 MBq of technetium 99m pertechnetate in a right antecubital vein with a polyethylene catheter, followed by 20 mL of saline solution. First-pass radionuclide ventriculography was acquired in the 30-degree right anterior oblique projection, in the supine position, using a single photon emission computed tomography gamma camera. The camera was equipped with a low-energy high-resolution collimator, and a 15% window was centered at the 140-keV photo peak of technetium 99m. The bolus quality was tested using a time activity curve in the region of interest drawn on the superior caval vein. The study was acquired in the
Figure 1 Myocardial Doppler tissue imaging (DTI), including systolic (Sm), early diastolic (Em), and late diastolic (Am) waves. Myocardial performance index calculated as: [time interval from onset of isovolumic contraction to end of isovolumic relaxation (B) ⫺ ventricular ejection time (A)]/A. ECG, Electrocardiogram; IVCT, isovolumic contraction time derived from DTI; IVRT, isovolumic relaxation time derived from DTI.
frame mode of 0.200 s/frame using a zoom factor of 1.48. In all, 250 frames were collected. RVEF was calculated from end-diastolic and end-systolic counts using background-corrected radionuclide time activity curves emanating from the RV chamber. Statistical Analysis Analyses were performed using software (SPSS 12.0 for Windows, Chicago, Ill). Variables are presented as mean ⫾ SD. Analysis of variance and post hoc tests for unpaired data were used to estimate differences between groups. Differences were considered statistically significant if the P value was less than .05 with a 95% confidence interval. The reproducibility of the measurements of DTI parameters, RVEF and LVEF, was determined. To determine interobserver variability, the average value of the first observer (S-H. H.) was compared with the reading of the second observer (S-K. L.), who was unaware of the initial results. The mean difference between the measurements of the two observers was calculated and the percentage variability was derived as the absolute difference between the two sets of measurements divided by the mean of the two observations. Intraobserver variability (S-K. L.) was also calculated following this method. Linear regression analyses and partial correlation tests (either Pearson’s or Spearman’s method) were performed to assess univariate relations.
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Table 2 Baseline characteristics and echocardiographic parameters of different groups Age, y Sex, M/F Smoking, % Heart rate, beats/min PASP, mm Hg LA, mm IVS, mm LVIDd, mm LVIDs, mm Mitral E, cm/s Mitral A, cm/s LVEF, % IVS flattening, % RVDd, mm Tricuspid E, cm/s Tricuspid A, cm/s RVEF, % TAPSE, cm RV Sm, cm/s Em, cm/s Am, cm/s IVCT, ms IVRT, ms MPI Septum Sm, cm/s Em, cm/s Am, cm/s IVCT, ms IVRT, ms MPI LV lateral wall Sm, cm/s Em, cm/s Am, cm/s IVCT, ms IVRT, ms MPI
Mild TR (n ⴝ 125)
Moderate TR (n ⴝ 50)
Severe TR (n ⴝ 50)
58.3 ⫾ 18.8 63/62 24% 74.4 ⫾ 15.3 32.1 ⫾ 10.0 36.3 ⫾ 5.7 10.5 ⫾ 2.0 48.3 ⫾ 3.5 25.9 ⫾ 4.8 86.0 ⫾ 32.1 77.7 ⫾ 24.6 61.3 ⫾ 6.5 5% 28 ⫾ 5 43 ⫾ 10 35 ⫾ 8 46.5 ⫾ 8.2 2.2 ⫾ 0.5
63.6 ⫾ 15.4 26/24 22% 81.2 ⫾ 16.5 53.7 ⫾ 12.6 42.9 ⫾ 10.3 10.7 ⫾ 1.4 48.2 ⫾ 7.0 26.2 ⫾ 8.1 84.4 ⫾ 32.2 77.8 ⫾ 29.0 56 ⫾ 9.3 38% 31 ⫾ 7 47 ⫾ 9 36 ⫾ 8 43.8 ⫾ 10.0 1.8 ⫾ 0.6
61.8 ⫾ 15.7 24/26 31% 83 ⫾ 17.2 66.4 ⫾ 17.5 48.4 ⫾ 12.1 10.3 ⫾ 1.4 46.0 ⫾ 6.0 25.6 ⫾ 7.1 77.3 ⫾ 24.6 82.3 ⫾ 29.1 55.1 ⫾ 9.4 96% 38 ⫾ 9 53 ⫾ 12 38 ⫾ 9 41.8 ⫾ 8.1 1.6 ⫾ 0.5
.094
ANOVA P value
.001 .0001 .0001 .286 .058 .063 .022 .415 .0001 .0001 .0001 .198 .002 .001
12.4 10.0 12.7 64.8 58.6 0.42
⫾ ⫾ ⫾ ⫾ ⫾ ⫾
2.6 3.1 3.4 13.3 14.6 0.09
10.7 10.4 13.0 61.6 72.5 0.49
⫾ ⫾ ⫾ ⫾ ⫾ ⫾
3.1 3.6 5.0 10.3 18.6 0.11
10.2 11.0 9.5 71.1 77.8 0.57
⫾ ⫾ ⫾ ⫾ ⫾ ⫾
2.7 2.8 3.3 18.6 21.3 0.13
.0001 .411 .0001 .295 .0001 .0001
7.6 7.3 8.7 61.3 64.7 0.42
⫾ ⫾ ⫾ ⫾ ⫾ ⫾
1.4 2.5 2.0 15.2 14.9 0.09
7.2 7.0 8.2 57.5 72.1 0.45
⫾ ⫾ ⫾ ⫾ ⫾ ⫾
2.6 2.3 3.0 15.0 18.3 0.12
6.6 7.5 6.3 73.3 71.1 0.51
⫾ ⫾ ⫾ ⫾ ⫾ ⫾
2.1 2.5 2.0 20.2 16.0 0.13
.08 .764 .002 .018 .122 .013
9.3 9.2 10.0 62.5 64.9 0.42
⫾ ⫾ ⫾ ⫾ ⫾ ⫾
2.4 3.2 2.7 13.6 12.5 0.08
8.9 9.3 9.7 61.3 65.0 0.43
⫾ ⫾ ⫾ ⫾ ⫾ ⫾
2.7 3.3 3.2 15.4 15.5 0.09
9.1 9.8 10.1 65.4 66.6 0.46
⫾ ⫾ ⫾ ⫾ ⫾ ⫾
2.9 3.0 2.5 15.5 14.3 0.10
.782 .175 .871 .264 .93 .219
Am, peak late diastolic myocardial velocity derived by pulsed wave Doppler tissue; ANOVA, analysis of variance; Em, peak early diastolic myocardial velocity derived by pulsed wave Doppler tissue; F, female; IVCT, isovolumic contraction time derived from Doppler tissue imaging; IVRT, isovolumic relaxation time derived from Doppler tissue imaging; IVS, wall thickness of intraventricular septum; LA, diameter of left atrium; LVEF, left ventricular ejection fraction; LVIDd, left ventricular end-diastolic dimension; LVIDs, left ventricular end-systolic dimension; LV lateral wall, lateral mitral annulus; M, male; mitral A, peak velocity of late diastolic mitral inflow; mitral E, peak velocity of early diastolic mitral inflow; MPI, myocardial performance index, defined as the sum of isovolumetric contraction time and isovolumetric relaxation time divided by the ejection time obtained by tissue Doppler image; PASP, pulmonary artery systolic pressure; RV, lateral tricuspid annulus; RVDd, right ventricular end-diastolic dimension; RVEF, right ventricular ejection fraction; septum, basal segment of intraventricular septum; Sm, peak systolic myocardial velocity derived by pulsed wave Doppler tissue; TAPSE, tricuspid annular plane systolic excursion; TR, tricuspid regurgitation; tricuspid A, peak velocity of late diastolic tricuspid inflow; tricuspid E, peak velocity of early diastolic tricuspid inflow. *Statistically significant.
RESULTS Baseline characteristics were similar among groups except for higher heart rate and pulmonary artery systolic pressure in the severe TR group (Table 2). The echocardiographic parameters of the LV in these 3 groups were also similar except for left atrial size, mitral E velocity, and LVEF (Table 2). After controlling for possible confounding factors from
the left heart, we think the differences among left atrial size, mitral E, and LVEF among groups were a result of interactions between the left and right heart. All causes of severe TR were associated with underlying lung conditions or tricuspid valvular problems (Table 1). As TR severity increased, enddiastolic RV dimension and tricuspid E velocity increased, but RVEF and TAPSE decreased significantly (Table 2). Most patients (96%) with severe TR
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showed flattening of the intraventricular septum (IVS). The parameters derived from DTI were significantly different among the 3 groups, especially over the lateral tricuspid annulus (RV) and IVS. Peak systolic velocity (RV-Sm) and late-diastolic velocity (RV-Am) of tricuspid annulus were significantly lower in the severe TR group (P ⬍ .0001). The isovolumic relaxation time and myocardial performance index of the RV obtained by DTI were higher in the severe TR group than in the mild or moderate TR groups (P ⬍ .0001). Relation of RVEF Obtained by Radionuclide Ventriculography and Echocardiographic Simpson’s Method Forty patients (20 with mild TR, 10 with moderate TR, and 10 with severe TR) received simultaneous RVEF assessment by radionuclide ventriculography and echocardiography using Simpson’s method. Simple linear regression analysis revealed a significant correlation between RVEF obtained by those two methods regardless of TR severity (all patients: r ⫽ 0.793, r 2 ⫽ 0.63, and P ⬍ .0001; patients with severe TR: r ⫽ 0.76, r 2 ⫽ 0.57, and P ⫽ .007) (Figure 2). The Relation of TAPSE and RVEF According to the Severity of TR In the mild and moderate TR groups, TAPSE was as an accurate index of RV systolic function with a reasonably strong correlation. We found reliable relationships between TAPSE and RVEF in patients with mild TR (r ⫽ 0.728, r 2 ⫽ 0.53, P ⬍ .0001) and moderate TR (r ⫽ 0.678, r 2 ⫽ 0.46, P ⬍ .0001). However, the close relation was not observed in patients with severe TR (r ⫽ 0.301, r 2 ⫽ 0.091, P ⫽ .056) (Figure 3). After pooling data from all 3 groups, the equation: RVEF% ⫽ 10.3 ⫻ TAPSE ⫹ 24, was obtained by simple linear regression analysis with r ⫽ 0.672, r 2 ⫽ 0.45, and P ⬍ .0001. Using this equation to assess RVEF in patients with severe TR, there was a poor correlation between RVEF assessed by Simpson’s rule and by this equation (r 2 ⫽ 0.08). The Relation of RV-Sm and RVEF According to the Severity of TR In patients with severe TR, we did not find a strong correlation between RV-Sm and RVEF derived by Simpson’s rule (r ⫽ 0.212, r 2 ⫽ 0.045, P ⫽ .167). But, RV-Sm showed a strong linear relationship to RVEF in the mild TR group (r ⫽ 0.765, r 2 ⫽ 0.59, P ⬍ .0001); this was also seen in the moderate TR group (r ⫽ 0.756, r 2 ⫽ 0.57, P ⬍ .0001) (Figure 4). From simple linear regression analysis of data from all patients, we obtained the equation: RVEF% ⫽ 2.1 ⫻ RV-Sm ⫹ 21, with r ⫽ 0.69, r 2 ⫽ 0.48, and P ⬍ .0001. Applying this equation to patients with severe TR, we
Figure 2 Strong correlation between right ventricular ejection fraction (RVEF) obtained by radionuclide ventriculography and echocardiographic Simpson’s method regardless of tricuspid regurgitation (TR) severity. A, All patients (Y ⫽ 16.6 ⫹ 0.6X, r 2 ⫽ 0.63, P ⬍ .0001). B, Patients with severe TR (Y ⫽ 11.8 ⫹ 0.75X, r 2 ⫽ 0.57, P ⫽ .007).
found only a poor correlation between RVEF estimated by Simpson’s method and this equation (r 2 ⫽ 0.09). Reproducibility The intraobserver differences for RVEF and LVEF were 4.5 ⫾ 3.5% and 3.5 ⫾ 3.1%, respectively. The intraobserver differences for TAPSE was 0.1 ⫾ 0.1 with a variability of 5.1 ⫾ 4.7%. The interobserver variabilities for Sm, Em, and Am were 3.9 ⫾ 3.2%, 2.6 ⫾ 1.9%, and 4.2 ⫾ 3.0%, with intraobserver differences of 0.3 ⫾ 0.3, 0.2 ⫾ 0.2, and 0.4 ⫾ 0.3, respectively. The interobserver differences for RVEF and LVEF were 5.6 ⫾ 4.5% and 4.5 ⫾ 3.7%, respec-
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Figure 3 Relationship of tricuspid annular plane systolic excursion (TAPSE) and right ventricular ejection fraction (RVEF) in patients with mild (A), moderate (B), and severe (C) tricuspid regurgitation (TR).
tively. The interobserver differences for TAPSE was 0.2 ⫾ 0.2 with a variability of 8.1 ⫾ 7.6%. The interobserver difference for Sm was 0.5 ⫾ 0.4, with a variability of 5.8 ⫾ 4.7%. The interobserver differences for Em and Am were 0.4 ⫾ 0.4 and 0.5 ⫾ 0.4 with variabilities of 5.8 ⫾ 4.9% and 5.3 ⫾ 5.1%, respectively.
DISCUSSION Although interest in the assessment of myocardial function has long been focused on the LV, recent investigations of the importance of RV function for outcomes in patients with severely depressed LV function has increased attention on RV function. The impact of RV function on survival in patients with severe left heart failure has been emphasized by studies showing that LV function loses its prognostic value in patients with an LVEF less than 25%,
whereas a preserved RVEF proved to be predictive for exercise capacity and survival even in advanced heart failure.26 These studies26-29 indicate the need for a method that allows simple and rapid evaluation of RV function. Kaul et al24 demonstrated in 1984 that systolic shortening of the RV from apex to base, referred to as TAPSE, is an echocardiographic index that correlates with radionuclide RVEF. Another approach by Meluzin et al,23 to use pulsed DTI for analysis of the systolic velocity of tricuspid annular motion, may yield a parameter that is more easily and quickly determined. This may make analysis of tricuspid annular motion more attractive and spread its application in clinical practice. Meluzin et al23 concluded that a low peak RV-Sm has high predictive accuracy for RV dysfunction established by radionuclide ventriculography. A series of studies following the above-mentioned methods investigated RV in different disease entities.19,20,30-33 However, although as-
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Figure 4 Relationship of peak systolic tricuspid annular velocity (RV-Sm) and right ventricular ejection fraction (RVEF) in patients with mild (A), moderate (B), and severe (C) tricuspid regurgitation (TR).
sessment of annular systolic excursion is intuitively attractive, it has limitations. It fails to account for any base-to-apex motion of the entire heart as it contracts, and it will yield differing results in proportion to the angle between the transducer and the annular point of motion. For the tricuspid valve, a particular limitation may also be encountered in cases of elevated RV pressure. Moustapha et al19 demonstrated a significantly elevated RV pressure in decreased tricuspid annular motion. TR may be another cause of an impaired relationship between tricuspid annular motion and RVEF. It is conceivable that tricuspid annular motion increases with TR independent of RV function. Furthermore, mitral and tricuspid annular motions are interrelated and a depressed LV function is indirectly reflected by a depressed tricuspid annular motion. Our study was designed to overcome these problems and we excluded most confounding factors that influence mitral annular motion or LV function, including coronary
artery disease,32 cardiomyopathy, LV hypertrophy,23,34 intracardiac shunt, hypertension,35 diabetes mellitus,36 and any evidence of LV dysfunction.23 Our aim was to investigate whether the severity of pure TR affects the relationship between tricuspid annular motion and RVEF. In the beginning of this study, we showed that RVEF obtained by Simpson’s rule is well correlated to RVEF obtained by radionuclide ventriculography regardless of TR severity. This allowed us to subsequently evaluate RVEF by Simpson’s method, which is easier to perform. Our study demonstrates a strong correlation among RV-Sm, TAPSE, and RVEF in patients with mild or moderate TR. This correlation was not strong for patients with severe TR, possibly because of RV dilatation. In these patients, findings are controversial and inaccurate probably because of the angle occurring between the transducer and the annular point of the same tricuspid motion. The progression of RV dilatation after a
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distinct degree of TR has developed makes larger angles between transducer and tricuspid annulus, and does not take into account the base-to-apex movement of the entire tricuspid annulus. We think that the interpretation of DTI parameters over the IVS should be done with caution. RV volume overloading produces RV dilatation and paradoxical motion of the IVS, mainly a result of a reversal of the end-diastolic pressure gradient between the two ventricles.37 In our study, 38% patients with moderate TR and 96% with severe TR displayed paradoxical motion and flattening of the IVS. We believe the DTI of the LV lateral wall represents LV function rather than DTI of the IVS. Regardless of the severity of TR, the DTI parameters over the LV lateral wall clearly show that all of our patients had normal LV function. In the study by Alam et al,16 the systolic mitral annular velocity was correlated relatively well with LVEF in patients with or without severe mitral regurgitation. But in our study, severe TR had a significant impact on the relation between tricuspid annular motion and RVEF. There are a number of possible explanations for this difference. First, severe TR is almost always combined with pulmonary hypertension. Pulmonary hypertension influences tricuspid annular motion.19 Second, the cohort studied by Alam et al16 was mostly patients with ischemic heart disease (66 of 96, 69%) and dilated cardiomyopathy (25 of 96, 26%). In addition, 11 patients (11%) with bundle branch block and 11 patients (11%) with atrial fibrillation were enrolled. As we know, those characteristics can affect Doppler tissue parameters and influence the interpretation of results. Third, there are different physiologic characteristics of LV and RV in the face of significant hemodynamic regurgitation. In patients with severe mitral regurgitation, the impact of regurgitation into the LV is associated frequently with volume overloading. But the impact of severe TR on RV is always a combination of volume and pressure overloading. The detailed mechanisms for these different results should be investigated by further studies. Studies applying DTI and TAPSE to the investigation of RV function appear very encouraging. However, DTI and TAPSE evaluation of tricuspid annular motion still have potential limitations. In conclusion, although measurement of tricuspid annular motion seems to provide an appealing, uncomplicated approach to determine RV systolic function, its accuracy in severe TR is disappointing. Using these methods to assess RV, severe TR should be considered a potential confounding factor. Limitations Our study has some limitations. Although we were careful to exclude patients with concomitant conditions that would potentially confound interpreta-
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tion, our cohort was relatively older and aging seems to affect RVEF and LVEF. The echocardiographic and radionuclide ventriculographic parameters were not obtained simultaneously; there was an interval of less than 1 week between studies. However, in view of the stable condition of our cohort, we do not think that this short time interval significantly influenced our results. Another limitation is that only a few patients received radionuclide ventriculography. We used Simpson’s method to assess RVEF and the accuracy of RVEF estimated by this method is still doubtful, although a strong correlation between Simpson’s RVEF and radionuclide RVEF has been demonstrated. Conclusion Severe TR has a significant impact on the relationship between RV-Sm and RVEF and between TAPSE and RVEF; RV-Sm and TAPSE in patients with severe TR shows poor correlation to RVEF. When applying Doppler tissue method or TAPSE to assess RV function, severe TR is a significantly confounding factor.
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