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Patterns of the Interventricular Septal Motion Can Predict Conditions of Patients with Pulmonary Hypertension
MISCELLANEOUS CLINICAL STUDIES
Patterns of the Interventricular Septal Motion Can Predict Conditions of Patients with Pulmonary Hypertension Shumpei Mori, MD, Satoshi Nakatani, MD, PhD, FACC, Hideaki Kanzaki, MD, Kenichiro Yamagata, MD, Yutaka Take, MD, Yunosuke Matsuura, MD, Shingo Kyotani, MD, PhD, Norifumi Nakanishi, MD, PhD, and Masafumi Kitakaze, MD, PhD, FACC, Osaka, Japan
Objectives: We sought to investigate the clinical and hemodynamic implications of interventricular septal motion in patients with pulmonary hypertension. Background: In patients with pulmonary hypertension, we have noticed two types of peculiar motions of the interventricular septum by M-mode echocardiography: marked early systolic anterior motion (type A) and marked early diastolic posterior motion (type B). Methods: We performed echocardiography on 32 patients (age 42 ⫾ 13 years) with pulmonary hypertension within 1 week of cardiac catheterization. Type A was found in 14 patients (group A) and type B was found in 18 patients (group B). Results: There was no difference between two groups in left ventricular eccentricity index at early diastole (2.4 ⫾ 0.6 vs 2.1 ⫾ 0.7) and mean pulmonary arterial pressure (54 ⫾ 10 vs 53 ⫾ 13 mm Hg). However, New York Heart Association functional class (2.7 ⫾ 0.4 vs 2.2 ⫾ 0.3) and serum levels of brain natriuretic peptide (271 ⫾ 155 vs 74 ⫾ 55 pg/mL) were significantly higher and cardiac index (1.7 ⫾ 0.3 vs 2.3 ⫾ 0.4 L/min/m2) was significantly lower in group A (P ⬍ .001). Simultaneous recordings of both ventricular pressures showed that right ventricular pressure was higher than left ventricular pressur during whole diastole in group A, but in group B, during only early diastole. By multiple linear regression analysis, type A motion independently predicted low cardiac index. Conclusions: Interventricular septal motion could predict patients’ conditions. Patients with type A motion were more morbid clinically and hemodynamically than patients with type B motion.
Pulmonary hypertension (PH) is characterized by a progressive increase in pulmonary vascular resistance from various causes leading to right ventricular (RV) failure and death.1,2 Previous studies have shown that morbidity and mortality in primary PH correlate well with invasive indexes such as cardiac index (CI), mean pulmonary arterial (PA) pressure, mean right atrial (RA) pressure, and mixed venous oxygen saturation.3-6 Echocardiography is a noninvasive, readily repeatable diagnostic tool for patients with PH. It can also detect the preclinical stage of the disease, confirm the differential diagnosis, and monitor the efficacy of specific therapeutic interventions.5,7,8 However, the
From the Division of Cardiology, Department of Internal Medicine, National Cardiovascular Center, Osaka, Japan. Supported by the Research Grant for Cardiovascular Diseases (18A-1) from the Ministry of Health, Labor, and Welfare. Reprint requests: Satoshi Nakatani, MD, PhD, FACC, Division of Cardiology, Department of Internal Medicine, National Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan (E-mail: [email protected]). 0894-7317/$34.00 Copyright 2008 by the American Society of Echocardiography. doi:10.1016/j.echo.2007.05.037
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usefulness of echocardiographic variables to evaluate the detailed severity of the disease, and to predict the prognosis of the patients with PH, is not established sufficiently. The estimated PA systolic pressure and severity of tricuspid regurgitation do not have predictive value in any of the previous studies.4,9,10 Only the pericardial effusion and Doppler RV index were recommended to be used to predict a worse prognosis in the American College of Chest Physicians evidence-based clinical practice guidelines.4 There are a few reports that described M-mode echocardiographic features of PH such as “公 (root)-like motion” of the interventricular septum (IVS).11-13 In routine echocardiographic study, we have noticed two types of IVS motions in patients with PH; marked early systolic brisk anterior motion (typical 公-like IVS motion) (type A) and marked early diastolic posterior motion (atypical 公-like IVS motion) (type B). The purposes of this study were to clarify clinical significance of these two motions and to predict the severity of the disease using the patterns. METHODS Patients and Study Design From May to September 2005, we performed transthoracic echocardiography on 32 consecutive patients with PH admitted to our institution
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Figure 1 Two types of interventricular septal motions in patients with right ventricular pressure overload. Type A: marked early systolic brisk anterior motion. Type B: marked early diastolic posterior motion. for evaluation of symptomatic PH. PH was defined as mean PA pressure greater than 25 mm Hg. Patients with Eisenmenger’s syndrome and atrial or ventricular septal defect were excluded because our purpose was to evaluate the clinical significance of typical IVS motion of patients with PH without intracardiac shunt. The study group was composed of 11 men and 21 women with a mean age of 42 ⫾ 13 years (range: 19-68 years). New York Heart Association (NYHA) functional class was assessed at admission. All patients underwent transthoracic echocardiography within 1 week of right heart catheterization. Serum levels of brain natriuretic peptide and 6-minute walk distance was measured before catheterization.
The velocity of IVS motion was measured using pulsed tissue Doppler echocardiography. From the short-axis view at the level of chorda tendinae, a 10-mm sample volume was placed at the center of the IVS perpendicularly and 3 to 5 cycles were recorded. There were 4 major waves as shown in Figure 3: a positive early systolic wave (rightward [RW]) reflecting brisk anterior motion at the phase of QRS, a negative systolic wave reflecting the systolic contraction of the LV at the phase of ST, a negative early diastolic wave (leftward [LW]) reflecting early diastolic bulging of the IVS at the phase just after T, and a positive early diastolic wave (septal E wave [Es]) just after LW reflecting the rebound anterior motion of the IVS.
Echocardiography An echocardiographic system with tissue Doppler capabilities was used (Aplio 80 SSA-770A, Toshiba Medical Systems Corp, Tokyo, Japan) with a 3.0-MHz transducer. We examined patients in the left decubitus position with standard parasternal long-axis, short-axis, and apical views. Left ventricular (LV) dimensions were measured in the standard parasternal view according to the guidelines of the American Society of Echocardiography.14 Setting the cursor perpendicularly to the upper IVS in the short-axis view, M-mode echocardiogram was recorded because the abnormal motion of the IVS was more prominent in the upper portion compared with the lower IVS.12,15-18 We classified patients into two groups based on the pattern of the IVS motion in M-mode echocardiogram as follows: group A, patients with type A motion, that is, marked early systolic brisk anterior motion, and group B, patients with type B motion, that is, marked early diastolic posterior motion, respectively (Figure 1). There were 14 patients in group A and 18 patients in group B. To quantify these motions, we set the lower margin of the IVS at end diastole just before the anterior systolic brisk motion on M-mode echocardiogram as the baseline. We measured the maximum anterior moving distance from the baseline at early systole (a) and the maximum posterior moving distance from the baseline at early diastole (b) and defined type A as a/b greater than or equal to 1.0, and type B as a/b less than 1.0 (Figure 2). LV eccentricity index was derived from the ratio of two short-axis diameters measured at early diastole. One diameter (D2) was drawn parallel and the other (D1) was perpendicular to the IVS, bisecting D2. The eccentricity index was defined as D2/D1.19 Peak velocities of early and late diastolic waves and deceleration time of early wave were derived from transmitral pulsed wave Doppler recordings in the standard apical 4-chamber view. Peak pressure gradient of tricuspid regurgitation was measured by continuous wave Doppler echocardiography in the apical 4-chamber view. Diameter of the inferior vena cava was measured by M-mode echocardiography at the most distended point usually at end expiration.
Catheterization Right heart catheterization was performed in the standard manner in the cardiac catheterization laboratory with a 7F balloon-tipped, largelumen pulmonary wedge catheter (CI-607T, Harmac Medical Products Inc, New York, NY). Pulmonary capillary wedge, PA, RV, and RA pressures were obtained and phasic and mean pressures were recorded on paper at 100 mm/s. Cardiac output was determined by the estimated Fick principle. Mixed venous oxygen saturation was measured from the blood taken from the main PA. Total pulmonary resistance was derived from mean PA pressure divided by the cardiac output. Pulmonary vascular resistance was derived from the difference between mean PA pressure and mean pulmonary capillary wedge pressure divided by the cardiac output. The simultaneous pressure recordings of the LV and RV were performed on 6 patients (1 from group A and 5 from group B) who needed left heart catheterization with suggestion of dilated cardiomyopathy (1 patient) and to evaluate coronary artery and LV function before pulmonary thromboendarterectomy (5 patients). We could not use high-fidelity micromanometer-tipped catheters in this measurement because of limited source. To obtain ventricular pressures, we used two 110-cm 5F fluid-filled pigtail catheters (CX-754U-II, Cathex, Kanagawa, Japan) and pressure transducers (DX-100, Nihon Kohden, Tokyo, Japan). One catheter was inserted into the RV from the femoral or jugular vein and another one was inserted into the LV from the radial or femoral artery. The distances from the tip of each catheter to the pressure transducer were completely equalized using 31-cm pressure-monitoring line (Namic, Boston Scientific Corp, New York, NY). Statistical Analysis Continuous variables were expressed as mean ⫾ SD and categorical data as percentages. Student t test was used to compare continuous variables, and 2 statistics or Fisher exact test was used to compare categorical values. Stepwise multiple linear regression analysis was
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Figure 2 Comparison and definition of interventricular septal (IVS) motion of groups A and B. We defined a as maximum anterior moving distance from baseline at early diastole, and b as maximum posterior moving distance from baseline at early diastole. We defined type A as a/b greater than or equal to 1.0, and type B as a/b less than 1.0. Dd, End-diastolic dimension; Ds, end-systolic dimension; ECG, electrocardiogram; PW, posterior wall.
Figure 3 Four major waves recorded from Doppler tissue imaging: rightward wave (RW), systolic wave (S), leftward wave (LW), and septal E wave (Es). Tissue Doppler sample volume was set on interventricular septum (right). ECG, Electrocardiogram. used to determine the relationship between CI and echocardiographic variables. All statistical analyses were performed with software (JMP 4.0, SAS Institute, Cary, NC). A P value less than .05 was considered statistically significant. RESULTS Patient Characteristics Table 1 compares patients’ characteristics. NYHA functional class and BNP were significantly higher in group A. Six-minute walk distance
tended to be longer in type B group but the difference was not statistically significant. Echocardiographic Parameters As shown in Table 2, LV end-diastolic dimension was significantly larger in patients with type B, but there were no significant differences in LV end-systolic dimension and diameter of the inferior vena cava. No significant difference was found in the eccentricity index at early diastole between two groups. Thus, the same concave configuration of the LV was observed at this phase in both groups. Pressure
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Table 1 Comparison of baseline characteristics Group A (n ⴝ 14) (mean ⴞ SD)
Age, y 39.7 ⫾ 11.3 Male, n (%) 5 (35.7) NYHA class (mean) 2.7 ⫾ 0.4 BNP (pg/mL) 270.9 ⫾ 155.4 6MWD (m) 364.6 ⫾ 96.8 Disease PPH, n (%) 6 (42.9) CTEPH, n (%) 3 (21.4) Others (CHD, etc.), n (%) 5 (35.7) 6 (42.9) PGI2 treatment, n (%) RBBB, n (%) 5 (35.7)
Table 3 Comparison of measured variables
Group B (n ⴝ 18) (mean ⴞ SD)
P value
43.3 ⫾ 14.9 6 (33.3) 2.1 ⫾ 0.3 74.1 ⫾ 54.6 395.2 ⫾ 78.5
.4585 ⬎.9999 .0003 ⬍.0001 .3383
8 5 5 4 5
(44.4) (27.8) (27.8) (22.2) (27.8)
.9285 ⬎.9999 .7120 .2665 .7120
SD, Standard deviation; 6MWD, 6 min walk distance; PPH, primary pulmonary hypertension; CTEPH, chronic thromboembolic pulmonary hypertension; CHD, congenital heart disease; PGI2, prostaglandin I2; RBBB, right bundle branch block.
Table 2 Comparison of measured variables Group A (n ⴝ 14) (mean ⴞ SD)
Echocardiographic data LVDd (mm) LVDs (mm) FS (%) TRPG (mm Hg) IVCD (mm) Eccentricity index (early diastole) a (mm) b (mm) a/b Tissue Doppler velocity RW (cm/s) LW (cm/s) Es (cm/s) RW/Es Es/LW RW/LW Transmitral flow E (m/s) A (m/s) E/A DcT (ms)
30.9 22.0 28.8 73.2 16.2 2.4
⫾ ⫾ ⫾ ⫾ ⫾ ⫾
5.8 5.8 13.7 24.9 6.4 0.6
6.9 ⫾ 1.4 3.7 ⫾ 0.8 2.0 ⫾ 0.8
Group B (n ⴝ 18) (mean ⴞ SD)
38.1 24.8 34.2 80.7 12.6 2.1
⫾ ⫾ ⫾ ⫾ ⫾ ⫾
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8.3 5.2 9.5 24.9 4.9 0.7
3.0 ⫾ 1.4 7.9 ⫾ 2.1 0.4 ⫾ 0.1
Group A (n ⴝ 14) (mean ⴞ SD)
Group B (n ⴝ 18) (mean ⴞ SD)
P value
Right heart catheterization and hemodynamic data PCWP (mm Hg) 7.2 ⫾ 3.0 5.7 ⫾ 2.8 mean PA pressure (mm Hg) 54.0 ⫾ 9.6 53.1 ⫾ 12.7 mean RA pressure (mm Hg) 6.8 ⫾ 4.6 4.4 ⫾ 3.1 RVSP (mm Hg) 87.9 ⫾ 15.4 89.9 ⫾ 23.5 RVEDP (mm Hg) 10.6 ⫾ 3.7 8.1 ⫾ 4.2 1.7 ⫾ 0.3 2.3 ⫾ 0.4 CI (L/min/m2) SvO2 (%) 57.6 ⫾ 7.3 66.9 ⫾ 4.6 TPR index (Wood U/m2) 32.2 ⫾ 6.5 23.8 ⫾ 8.5 PVR index (Wood U/m2) 27.7 ⫾ 6.2 21.3 ⫾ 7.9 SBP (mm Hg) 109.7 ⫾ 8.5 109.9 ⫾ 10.1 DBP (mm Hg) 69.9 ⫾ 9.1 64.2 ⫾ 9.9 HR (bpm) 76.4 ⫾ 14.3 72.7 ⫾ 13.4
.1605 .8358 .0907 .7815 .0860 ⬍.0001 .0001 .0052 .0184 .9462 .1098 .4591
SD, Standard deviation; PCWP, pulmonary capillary wedge pressure; PA, pulmonary arterial; RA, right atrial; RVSP, right ventricular systolic pressure; RVEDP, right ventricular end-diastolic pressure; CI, cardiac index; SvO2, mixed venous oxygen saturation; TPR, total pulmonary resistance; PVR, pulmonary vascular resistance; SBP, systolic blood pressure; DBP, diastolic blood pressure; HR, heart rate.
P value
.0101 .1693 .2070 .4023 .0797 .3310 ⬍.0001 ⬍.0001 ⬍.0001
14.9 9.7 7.7 2.4 0.8 1.6
⫾ ⫾ ⫾ ⫾ ⫾ ⫾
5.1 2.9 3.5 1.5 0.5 0.5
10.7 6.9 11.5 1.0 1.8 1.6
⫾ ⫾ ⫾ ⫾ ⫾ ⫾
4.4 2.6 4.3 0.4 0.8 0.5
.0194 .0077 .0131 .0006 .0005 .9445
0.53 0.61 0.99 211.6
⫾ ⫾ ⫾ ⫾
0.15 0.14 0.66 63.7
0.61 0.54 1.09 214.1
⫾ ⫾ ⫾ ⫾
0.23 0.14 0.27 52.9
.2830 .2197 .5977 .9045
SD, Standard deviation; Dd, end diastolic dimension; Ds, end systolic dimension; FS, fractional shortening; TRPG, pressure gradient of tricuspid regurgitation; IVCD, diameter of inferior vena cava; RW, rightward wave; LW, leftward wave; Es, septal E wave; E, E wave; A, A wave; DcT, deceleration time.
gradient of tricuspid regurgitation was not different significantly between both groups consistent with catheterization data. RW was significantly higher in type A group reflecting fast brisk anterior motion. Es was significantly higher in type B reflecting fast rebound anterior motion after early diastolic bulging, which suggested the inversion of pressure gradient between two ventricles. RW/Es was significantly higher and Es/LW was significantly lower in type A.
Figure 4 Simultaneous pressure recording of patient with type A motion presented in Figure 2. Pressure gradient curve (thick black line) was extremely similar to interventricular septal motion. ECG, Electrocardiogram; LV, left ventricle; RV, right ventricle.
Es/LW greater than 1.0 differentiated these two groups with sensitivity of 93% and specificity of 94%. Invasive Hemodynamics Mean PA, mean RA, RV systolic, and RV end-diastolic pressures were not different significantly, but CI and mixed venous oxygen saturation were significantly lower in type A (Table 3). Type A motion of the IVS predicted CI less than 1.9 L/min/m2 with sensitivity of 80%
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Figure 5 Comparison of simultaneous pressure recording curves recorded from patients with type A and type B motion. In type A, left ventricular (LV) pressure (solid line) is higher than right ventricular (RV) pressure (dotted line) during whole systole, and RV pressure is higher than LV pressure during whole diastole. However, in type B, RV pressure is higher than LV pressure during only early diastole. Table 4 Independent predictors of cardiac index (L/min/m2) Variable
Regression coefficient
P value
LVDd (mm) Eccentricity Index (early diastole) Es (cm/s) Type A motion of the IVS
0.012 ⫺0.155 0.021 ⫺0.211
.1950 .1197 .1485 .0044
Ds, End systolic dimension; Es, septal E wave; IVS, interventricular septum.
and specificity of 88%. Total pulmonary resistance index and pulmonary vascular resistance index were significantly higher in type A. Simultaneous Ventricular Pressures Figure 4 shows the simultaneous pressure recording of a patient with type A motion whose IVS motion is shown in Figure 2. The pressure gradient curve resembles the IVS motion presented in Figure 2. Figure 5 shows the comparison of pressure curves between types A and B. In type A, RV pressure is higher than LV pressure during whole diastole. However, in a patient with type B, RV pressure is higher than LV pressure during only early diastole. This was a common finding in all 5 patients with type B who had simultaneous pressure recordings. Multivariate Analysis To investigate the relationship between echocardiographic parameters and CI, stepwise multiple regression analysis was done. Eleven of 19 parameters were selected on the basis of a significant univariate relation to CI (P ⱕ .05). To avoid multicollinearity, a, b, and a/b were excluded because of their significant correlations to type A motion. As a result, the independent echocardiographic variables used in this study were LV end-diastolic dimension, an eccentricity index, RW, LW, Es, RW/Es, Es/LW, and type A motion. Multiple linear regression analysis was then performed by stepwise forward selection. All variables with a probability value less than .25 remained in the final model. The results of the multiple linear regression analysis are given in Table 4. The model had an overall F statistic of 10.58 (P ⬍ .0001) and the R2 was 0.6105. Only type A motion was an independent predictor of low CI.
early systolic brisk anterior motion (type A) and marked early diastolic posterior motion (type B). These motions were too rapid and too subtle to be picked up by B-mode echocardiography, but M-mode echocardiography was useful in detecting such motions.18,20 We found that patients with type A motion were more morbid clinically and hemodynamically than patients with type B motion. In addition, type A motion predicted low CI independently. This is the first study to show the significance of these peculiar IVS motions detected by M-mode echocardiography in patients with PH. Normal Configuration of the IVS Generally, the LV pressure is always higher than the RV pressure during a cardiac cycle, so that pressure curves of both ventricles never cross over each other13,21-24 and a positive left-to-right transseptal pressure gradient exists throughout the cycle. Under this condition, the round configuration of the septum is observed in healthy individuals.20,25,26 During systole, the normal systolic IVS curvature represents the effect of the transseptal pressure gradient acting in opposition to the natural tendency of the septum to be stiff and straighten as it contracts.15 However, during diastole, because the IVS is independent of the restraining effect generated by active musculature contraction,15,25 it is more flaccid and freely responsive to the transseptal pressure gradient alone.15 Therefore, it behaves as a membrane between two fluid-filled chambers and readily changes its position in response to even minor alterations in the transseptal pressure gradient.15,27 We considered the peculiar IVS motion found in patients with PH were a result of subtle differences in RV and LV pressures during a cardiac cycle. Comparison of Type A and Type B Motion Figure 6 is a comparison of the IVS motion of the two types. In type A, the IVS moves largely anteriorly at systole then it is pushed back posteriorly at early diastole and continues this position during whole diastole. It makes anterior motion conspicuous in type A. In type B, anterior motion is not as remarkable as type A at early systole, but it is pushed back strongly at early diastole similar to type A. However, just after this posterior motion, it moves rapidly anteriorly. It makes posterior motion conspicuous in type B. Thus, IVS bulging toward the LV during whole diastole or early diastole is the difference between type A and type B.
DISCUSSION In routine echocardiographic study, we have noticed that there are two types of IVS motions in patients with RV pressure overload: marked
Mechanism of Peculiar IVS Motions Under RV pressure overload, the peak of RV pressure curve slightly delays with a prolongation of RV isovolumic contraction and relax-
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Figure 6 Comparison of interventricular septal (IVS) motion of type A (dotted line) and B (solid line). IVS bulging toward left ventricle during whole diastole or early diastole is difference between type A and type B. ECG, Electrocardiogram.
Figure 7 A representative patient whose interventricular septal motion changed from type A to type B after prostaglandin I2 (PGI2) treatment. PH, Pulmonary hypertension; ASD, atrial septal defect; NYHA, New York Heart Association; BNP, brain natriuretic peptide; mPAP, mean pulmonary arterial pressure; mRAP, mean right atrial pressure; CI, cardiac index; PVRI, pulmonary vascular resistence index; Dd, end diastolic dimension; Ds, end systolic dimension; TRPG, pressure gradient of tricuspid regurgitation.
ation.28 As a result, RV and LV pressure curves cross over each other on their descending limbs at early diastole and the RV pressure becomes higher than the LV pressure at this phase.13,28 This results in IVS leftward bulging at early diastole observed in both group A and B in the current study. As RV failure progresses as a result of PH, pulmonary blood flow decreases, and RV end-diastolic pressure and mean RA pressure increase subsequently.29-32 In consequence, the transseptal pressure gradient reverses during whole diastole, which results in IVS bulging during this phase observed in group A. In addition, when the atrial kick in the RV pressure exceeds that in the
LV pressure,13 end-diastolic IVS bulging is observed in group A. Thus, type A motion should be a sensitive sign of RV systolic and diastolic dysfunction, which cannot be clearly recognized by simple B-mode echocardiography or right heart pressures. Clinical Implications The IVS motion may be helpful in assessing the improvement of hemodynamics to treatment noninvasively. Figure 7 is a patient whose IVS motion changed from type A to type B after prostaglandin I2 treatment. This dramatic change suggested that the RV diastolic
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Figure 8 Temporal changes in short-axis views obtained from patients in groups A and B. At early diastole, concave left ventricle (LV) configurations are observed in both groups. However, at end diastole, concave LV configuration is observed in group A, but convex circular LV configuration is observed in group B.
pressure became lower than that of the LV after the treatment. The patient’s NYHA class improved from IV to II with a decrease in BNP and an increase in CI. In multiple linear regression analysis, it was demonstrated that type A motion of the IVS was the significant predictive factor of low CI. Of course it will need a further evaluation, but type A and B motions may have not only the hemodynamic value but also the prognostic value because reduced CI is an independent predictor of worse prognosis of patients with primary PH.4 In routine echocardiographic examination, we have traditionally measured eccentricity index only at early diastole when the LV is most compressed. However, this study revealed that the proper timing to measure it to assess hemodynamics of RV pressure overload is end diastole. Figure 8 shows temporal changes in short-axis views obtained from type A and type B motion. At early diastole, the concave LV configurations are observed in both groups. However, at end diastole, the concave LV configuration is observed in group A, but the convex circular LV configuration is observed in group B. These findings strongly suggest that the configuration of the LV at end diastole can differentiate the two groups. In addition, this study demonstrated that M-mode echocardiography still played a useful role in today’s imaging world because of good temporal resolution especially for small and rapid cardiac motions. Limitations Evaluation of the pattern and the velocity of the IVS motion with M-mode and Doppler tissue imaging used in this study cannot avoid
the effects of translation, rotation, or tethering of the LV. Strain method may be able to overcome these limitations because it is based on two points’ velocities and is free from these confounding factors. Type A motion of the IVS has been proven to reflect the interventricular pressure gradient between the LV and RV.13 However, the interventricular pressure gradient in type B motion has not been reported before this study. It will need further experimental examination to confirm our findings, because we could not perform simultaneous pressure measurement on all patients and could not use high-fidelity micromanometer-tipped catheters. Conclusions In patients with PH, early systolic anterior motion and early diastolic posterior motion of the IVS were observed by M-mode echocardiography. The IVS motions reflecting interventricular pressure gradient were classified into two types: type A, marked anterior motion at early systole; and type B, marked posterior motion at early diastole. Patients with type A motion were more morbid clinically and hemodynamically than patients with type B motion. In stepwise multiple linear regression analysis, type A motion predicted low CI independently. The patterns of the IVS motion can predict clinical and hemodynamic conditions of patients with PH. REFERENCES 1. Rich S, Dantzker DR, Ayres SM, et al. Primary pulmonary hypertension: a national prospective study. Ann Intern Med 1987;107:216-23.
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2. Fuster V, Steele PM, Edwards WD, Gersh BJ, McGoon MD, Frye RL. Primary pulmonary hypertension: natural history and the importance of thrombosis. Circulation 1984;70:580-7. 3. Eysmann SB, Palevsky HI, Reichek N, Hackney K, Douglas PS. Twodimensional and Doppler-echocardiographic and cardiac catheterization correlates of survival in primary pulmonary hypertension. Circulation 1989;80:353-60. 4. McLaughlin VV, Presberg KW, Doyle RL, et al; American College of Chest Physicians. Prognosis of pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines. Chest 2004;126:78-92S. 5. Bossone E, Bodini BD, Mazza A, Allegra L. Pulmonary arterial hypertension: the key role of echocardiography. Chest 2005;127:1836-43. 6. Okada O, Tanabe N, Yasuda J, et al. Prediction of life expectancy in patients with primary pulmonary hypertension: a retrospective nationwide survey from 1980-1990. Intern Med 1999;38:12-6. 7. Galie N, Hinderliter AL, Torbicki A, et al. Effects of the oral endothelinreceptor antagonist bosentan on echocardiographic and Doppler measures in patients with pulmonary arterial hypertension. J Am Coll Cardiol 2003;41:1380-6. 8. Hinderliter AL, Willis PW IV, Barst RJ, et al. Effects of long-term infusion of prostacyclin (epoprostenol) on echocardiographic measures of right ventricular structure and function in primary pulmonary hypertension: primary pulmonary hypertension study group. Circulation 1997;95: 1479-86. 9. Yeo TC, Dujardin KS, Tei C, Mahoney DW, McGoon MD, Seward JB. Value of a Doppler-derived index combining systolic and diastolic time intervals in predicting outcome in primary pulmonary hypertension. Am J Cardiol 1998;81:1157-61. 10. Raymond RJ, Hinderliter AL, Willis PW, et al. Echocardiographic predictors of adverse outcomes in primary pulmonary hypertension. J Am Coll Cardiol 2002;39:1214-9. 11. Morioka S, Tomonaga G, Hoshino T, et al. Abnormal systolic motion of the ventricular septum mimicking “公 (square)” [in Japanese with English abstract]. J Cardiogr 1978;8:333-40. 12. Pearlman AS, Clark CE, Henry WL, Morganroth J, Itscoitz SB, Epstein SE. Determinants of ventricular septal motion: influence of relative right and left ventricular size. Circulation 1976;54:83-91. 13. Tanaka H, Tei C, Nakao S, et al. Diastolic bulging of the interventricular septum toward the left ventricle: an echocardiographic manifestation of negative interventricular pressure gradient between left and right ventricles during diastole. Circulation 1980;62:558-63. 14. Sahn DJ, DeMaria A, Kisslo J, Weyman A. Recommendations regarding quantitation in M-mode echocardiography: results of a survey of echocardiographic measurements. Circulation 1978;58:1072-83. 15. King ME, Braun H, Goldblatt A, Liberthson R, Weyman AE. Interventricular septal configuration as a predictor of right ventricular systolic hypertension in children: a cross-sectional echocardiographic study. Circulation 1983;68:68-75.
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16. Kerber RE, Dippel WF, Abboud FM. Abnormal motion of the interventricular septum in right ventricular volume overload: experimental and clinical echocardiographic studies. Circulation 1973;48:86-96. 17. Hagan AD, Francis GS, Sahn DJ, Karliner JS, Friedman WF, O’Rourke RA. Ultrasound evaluation of systolic anterior septal motion in patients with and without right ventricular volume overload. Circulation 1974;50:24854. 18. Dillon JC, Chang S, Feigenbaum H. Echocardiographic manifestations of left bundle branch block. Circulation 1974;49:876-80. 19. Ryan T, Petrovic O, Dillon JC, Feigenbaum H, Conley MJ, Armstrong WF. An echocardiographic index for separation of right ventricular volume and pressure overload. J Am Coll Cardiol 1985;5:918-27. 20. Kaul S. The interventricular septum in health and disease. Am Heart J 1986;112:568-81. 21. Guzman PA, Maughan WL, Yin FC, et al. Transseptal pressure gradient with leftward septal displacement during the Mueller maneuver in man. Br Heart J 1981;46:657-62. 22. Little WC, Reeves RC, Arciniegas J, Katholi RE, Rogers EW. Mechanism of abnormal interventricular septal motion during delayed left ventricular activation. Circulation 1982;65:1486-91. 23. Tei C, Tanaka H, Kashima T, Nakao S, Tahara M, Kanehisa T. Echocardiographic analysis of interatrial septal motion. Am J Cardiol 1979;44: 472-7. 24. Leeuwenburgh BP, Steendijk P, Helbing WA, Baan J. Indexes of diastolic RV function: load dependence and changes after chronic RV pressure overload in lambs. Am J Physiol Heart Circ Physiol 2002;282:H1350-8. 25. Lima JA, Guzman PA, Yin FC, et al. Septal geometry in the unloaded living human heart. Circulation 1986;74:463-8. 26. Louie EK, Rich S, Levitsky S, Brundage BH. Doppler echocardiographic demonstration of the differential effects of right ventricular pressure and volume overload on left ventricular geometry and filling. J Am Coll Cardiol 1992;19:84-90. 27. Kingma I, Tyberg JV, Smith ER. Effects of diastolic transseptal pressure gradient on ventricular septal position and motion. Circulation 1983;68: 1304-14. 28. Elzinga G, Piene H, de Jong JP. Left and right ventricular pump function and consequences of having two pumps in one heart: a study on the isolated cat heart. Circ Res 1980;46:564-74. 29. Nakamura Y, Nishikawa Y, Miyazaki T, Ohnishi S. Behavior of the right ventricle against pressure loading: on its plasticity. Jpn Circ J 1985;49: 255-60. 30. Guyton AC, Lindsey AW, Gillury JJ. The limits of right ventricular compensation following acute increase in pulmonary circulatory resistance. Circ Res 1954;2:326-32. 31. Taquini AC, Fermoso JD, Aramendia P. Behavior of the right ventricle following acute constriction of the pulmonary artery. Circ Res 1960;8: 315-8. 32. Salisbury PF. Coronary artery pressure and strength of right ventricular contraction. Circ Res 1955;3:633-8.
Patterns of the Interventricular Septal Motion Can Predict Conditions of Patients with Pulmonary Hypertension Shumpei Mori, MD, Satoshi Nakatani, MD, PhD, FACC, Hideaki Kanzaki, MD, Kenichiro Yamagata, MD, Yutaka Take, MD, Yunosuke Matsuura, MD, Shingo Kyotani, MD, PhD, Norifumi Nakanishi, MD, PhD, and Masafumi Kitakaze, MD, PhD, FACC, Osaka, Japan
Objectives: We sought to investigate the clinical and hemodynamic implications of interventricular septal motion in patients with pulmonary hypertension. Background: In patients with pulmonary hypertension, we have noticed two types of peculiar motions of the interventricular septum by M-mode echocardiography: marked early systolic anterior motion (type A) and marked early diastolic posterior motion (type B). Methods: We performed echocardiography on 32 patients (age 42 ⫾ 13 years) with pulmonary hypertension within 1 week of cardiac catheterization. Type A was found in 14 patients (group A) and type B was found in 18 patients (group B). Results: There was no difference between two groups in left ventricular eccentricity index at early diastole (2.4 ⫾ 0.6 vs 2.1 ⫾ 0.7) and mean pulmonary arterial pressure (54 ⫾ 10 vs 53 ⫾ 13 mm Hg). However, New York Heart Association functional class (2.7 ⫾ 0.4 vs 2.2 ⫾ 0.3) and serum levels of brain natriuretic peptide (271 ⫾ 155 vs 74 ⫾ 55 pg/mL) were significantly higher and cardiac index (1.7 ⫾ 0.3 vs 2.3 ⫾ 0.4 L/min/m2) was significantly lower in group A (P ⬍ .001). Simultaneous recordings of both ventricular pressures showed that right ventricular pressure was higher than left ventricular pressur during whole diastole in group A, but in group B, during only early diastole. By multiple linear regression analysis, type A motion independently predicted low cardiac index. Conclusions: Interventricular septal motion could predict patients’ conditions. Patients with type A motion were more morbid clinically and hemodynamically than patients with type B motion.
Pulmonary hypertension (PH) is characterized by a progressive increase in pulmonary vascular resistance from various causes leading to right ventricular (RV) failure and death.1,2 Previous studies have shown that morbidity and mortality in primary PH correlate well with invasive indexes such as cardiac index (CI), mean pulmonary arterial (PA) pressure, mean right atrial (RA) pressure, and mixed venous oxygen saturation.3-6 Echocardiography is a noninvasive, readily repeatable diagnostic tool for patients with PH. It can also detect the preclinical stage of the disease, confirm the differential diagnosis, and monitor the efficacy of specific therapeutic interventions.5,7,8 However, the
From the Division of Cardiology, Department of Internal Medicine, National Cardiovascular Center, Osaka, Japan. Supported by the Research Grant for Cardiovascular Diseases (18A-1) from the Ministry of Health, Labor, and Welfare. Reprint requests: Satoshi Nakatani, MD, PhD, FACC, Division of Cardiology, Department of Internal Medicine, National Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan (E-mail: [email protected]). 0894-7317/$34.00 Copyright 2008 by the American Society of Echocardiography. doi:10.1016/j.echo.2007.05.037
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usefulness of echocardiographic variables to evaluate the detailed severity of the disease, and to predict the prognosis of the patients with PH, is not established sufficiently. The estimated PA systolic pressure and severity of tricuspid regurgitation do not have predictive value in any of the previous studies.4,9,10 Only the pericardial effusion and Doppler RV index were recommended to be used to predict a worse prognosis in the American College of Chest Physicians evidence-based clinical practice guidelines.4 There are a few reports that described M-mode echocardiographic features of PH such as “公 (root)-like motion” of the interventricular septum (IVS).11-13 In routine echocardiographic study, we have noticed two types of IVS motions in patients with PH; marked early systolic brisk anterior motion (typical 公-like IVS motion) (type A) and marked early diastolic posterior motion (atypical 公-like IVS motion) (type B). The purposes of this study were to clarify clinical significance of these two motions and to predict the severity of the disease using the patterns. METHODS Patients and Study Design From May to September 2005, we performed transthoracic echocardiography on 32 consecutive patients with PH admitted to our institution
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Figure 1 Two types of interventricular septal motions in patients with right ventricular pressure overload. Type A: marked early systolic brisk anterior motion. Type B: marked early diastolic posterior motion. for evaluation of symptomatic PH. PH was defined as mean PA pressure greater than 25 mm Hg. Patients with Eisenmenger’s syndrome and atrial or ventricular septal defect were excluded because our purpose was to evaluate the clinical significance of typical IVS motion of patients with PH without intracardiac shunt. The study group was composed of 11 men and 21 women with a mean age of 42 ⫾ 13 years (range: 19-68 years). New York Heart Association (NYHA) functional class was assessed at admission. All patients underwent transthoracic echocardiography within 1 week of right heart catheterization. Serum levels of brain natriuretic peptide and 6-minute walk distance was measured before catheterization.
The velocity of IVS motion was measured using pulsed tissue Doppler echocardiography. From the short-axis view at the level of chorda tendinae, a 10-mm sample volume was placed at the center of the IVS perpendicularly and 3 to 5 cycles were recorded. There were 4 major waves as shown in Figure 3: a positive early systolic wave (rightward [RW]) reflecting brisk anterior motion at the phase of QRS, a negative systolic wave reflecting the systolic contraction of the LV at the phase of ST, a negative early diastolic wave (leftward [LW]) reflecting early diastolic bulging of the IVS at the phase just after T, and a positive early diastolic wave (septal E wave [Es]) just after LW reflecting the rebound anterior motion of the IVS.
Echocardiography An echocardiographic system with tissue Doppler capabilities was used (Aplio 80 SSA-770A, Toshiba Medical Systems Corp, Tokyo, Japan) with a 3.0-MHz transducer. We examined patients in the left decubitus position with standard parasternal long-axis, short-axis, and apical views. Left ventricular (LV) dimensions were measured in the standard parasternal view according to the guidelines of the American Society of Echocardiography.14 Setting the cursor perpendicularly to the upper IVS in the short-axis view, M-mode echocardiogram was recorded because the abnormal motion of the IVS was more prominent in the upper portion compared with the lower IVS.12,15-18 We classified patients into two groups based on the pattern of the IVS motion in M-mode echocardiogram as follows: group A, patients with type A motion, that is, marked early systolic brisk anterior motion, and group B, patients with type B motion, that is, marked early diastolic posterior motion, respectively (Figure 1). There were 14 patients in group A and 18 patients in group B. To quantify these motions, we set the lower margin of the IVS at end diastole just before the anterior systolic brisk motion on M-mode echocardiogram as the baseline. We measured the maximum anterior moving distance from the baseline at early systole (a) and the maximum posterior moving distance from the baseline at early diastole (b) and defined type A as a/b greater than or equal to 1.0, and type B as a/b less than 1.0 (Figure 2). LV eccentricity index was derived from the ratio of two short-axis diameters measured at early diastole. One diameter (D2) was drawn parallel and the other (D1) was perpendicular to the IVS, bisecting D2. The eccentricity index was defined as D2/D1.19 Peak velocities of early and late diastolic waves and deceleration time of early wave were derived from transmitral pulsed wave Doppler recordings in the standard apical 4-chamber view. Peak pressure gradient of tricuspid regurgitation was measured by continuous wave Doppler echocardiography in the apical 4-chamber view. Diameter of the inferior vena cava was measured by M-mode echocardiography at the most distended point usually at end expiration.
Catheterization Right heart catheterization was performed in the standard manner in the cardiac catheterization laboratory with a 7F balloon-tipped, largelumen pulmonary wedge catheter (CI-607T, Harmac Medical Products Inc, New York, NY). Pulmonary capillary wedge, PA, RV, and RA pressures were obtained and phasic and mean pressures were recorded on paper at 100 mm/s. Cardiac output was determined by the estimated Fick principle. Mixed venous oxygen saturation was measured from the blood taken from the main PA. Total pulmonary resistance was derived from mean PA pressure divided by the cardiac output. Pulmonary vascular resistance was derived from the difference between mean PA pressure and mean pulmonary capillary wedge pressure divided by the cardiac output. The simultaneous pressure recordings of the LV and RV were performed on 6 patients (1 from group A and 5 from group B) who needed left heart catheterization with suggestion of dilated cardiomyopathy (1 patient) and to evaluate coronary artery and LV function before pulmonary thromboendarterectomy (5 patients). We could not use high-fidelity micromanometer-tipped catheters in this measurement because of limited source. To obtain ventricular pressures, we used two 110-cm 5F fluid-filled pigtail catheters (CX-754U-II, Cathex, Kanagawa, Japan) and pressure transducers (DX-100, Nihon Kohden, Tokyo, Japan). One catheter was inserted into the RV from the femoral or jugular vein and another one was inserted into the LV from the radial or femoral artery. The distances from the tip of each catheter to the pressure transducer were completely equalized using 31-cm pressure-monitoring line (Namic, Boston Scientific Corp, New York, NY). Statistical Analysis Continuous variables were expressed as mean ⫾ SD and categorical data as percentages. Student t test was used to compare continuous variables, and 2 statistics or Fisher exact test was used to compare categorical values. Stepwise multiple linear regression analysis was
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Figure 2 Comparison and definition of interventricular septal (IVS) motion of groups A and B. We defined a as maximum anterior moving distance from baseline at early diastole, and b as maximum posterior moving distance from baseline at early diastole. We defined type A as a/b greater than or equal to 1.0, and type B as a/b less than 1.0. Dd, End-diastolic dimension; Ds, end-systolic dimension; ECG, electrocardiogram; PW, posterior wall.
Figure 3 Four major waves recorded from Doppler tissue imaging: rightward wave (RW), systolic wave (S), leftward wave (LW), and septal E wave (Es). Tissue Doppler sample volume was set on interventricular septum (right). ECG, Electrocardiogram. used to determine the relationship between CI and echocardiographic variables. All statistical analyses were performed with software (JMP 4.0, SAS Institute, Cary, NC). A P value less than .05 was considered statistically significant. RESULTS Patient Characteristics Table 1 compares patients’ characteristics. NYHA functional class and BNP were significantly higher in group A. Six-minute walk distance
tended to be longer in type B group but the difference was not statistically significant. Echocardiographic Parameters As shown in Table 2, LV end-diastolic dimension was significantly larger in patients with type B, but there were no significant differences in LV end-systolic dimension and diameter of the inferior vena cava. No significant difference was found in the eccentricity index at early diastole between two groups. Thus, the same concave configuration of the LV was observed at this phase in both groups. Pressure
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Table 1 Comparison of baseline characteristics Group A (n ⴝ 14) (mean ⴞ SD)
Age, y 39.7 ⫾ 11.3 Male, n (%) 5 (35.7) NYHA class (mean) 2.7 ⫾ 0.4 BNP (pg/mL) 270.9 ⫾ 155.4 6MWD (m) 364.6 ⫾ 96.8 Disease PPH, n (%) 6 (42.9) CTEPH, n (%) 3 (21.4) Others (CHD, etc.), n (%) 5 (35.7) 6 (42.9) PGI2 treatment, n (%) RBBB, n (%) 5 (35.7)
Table 3 Comparison of measured variables
Group B (n ⴝ 18) (mean ⴞ SD)
P value
43.3 ⫾ 14.9 6 (33.3) 2.1 ⫾ 0.3 74.1 ⫾ 54.6 395.2 ⫾ 78.5
.4585 ⬎.9999 .0003 ⬍.0001 .3383
8 5 5 4 5
(44.4) (27.8) (27.8) (22.2) (27.8)
.9285 ⬎.9999 .7120 .2665 .7120
SD, Standard deviation; 6MWD, 6 min walk distance; PPH, primary pulmonary hypertension; CTEPH, chronic thromboembolic pulmonary hypertension; CHD, congenital heart disease; PGI2, prostaglandin I2; RBBB, right bundle branch block.
Table 2 Comparison of measured variables Group A (n ⴝ 14) (mean ⴞ SD)
Echocardiographic data LVDd (mm) LVDs (mm) FS (%) TRPG (mm Hg) IVCD (mm) Eccentricity index (early diastole) a (mm) b (mm) a/b Tissue Doppler velocity RW (cm/s) LW (cm/s) Es (cm/s) RW/Es Es/LW RW/LW Transmitral flow E (m/s) A (m/s) E/A DcT (ms)
30.9 22.0 28.8 73.2 16.2 2.4
⫾ ⫾ ⫾ ⫾ ⫾ ⫾
5.8 5.8 13.7 24.9 6.4 0.6
6.9 ⫾ 1.4 3.7 ⫾ 0.8 2.0 ⫾ 0.8
Group B (n ⴝ 18) (mean ⴞ SD)
38.1 24.8 34.2 80.7 12.6 2.1
⫾ ⫾ ⫾ ⫾ ⫾ ⫾
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8.3 5.2 9.5 24.9 4.9 0.7
3.0 ⫾ 1.4 7.9 ⫾ 2.1 0.4 ⫾ 0.1
Group A (n ⴝ 14) (mean ⴞ SD)
Group B (n ⴝ 18) (mean ⴞ SD)
P value
Right heart catheterization and hemodynamic data PCWP (mm Hg) 7.2 ⫾ 3.0 5.7 ⫾ 2.8 mean PA pressure (mm Hg) 54.0 ⫾ 9.6 53.1 ⫾ 12.7 mean RA pressure (mm Hg) 6.8 ⫾ 4.6 4.4 ⫾ 3.1 RVSP (mm Hg) 87.9 ⫾ 15.4 89.9 ⫾ 23.5 RVEDP (mm Hg) 10.6 ⫾ 3.7 8.1 ⫾ 4.2 1.7 ⫾ 0.3 2.3 ⫾ 0.4 CI (L/min/m2) SvO2 (%) 57.6 ⫾ 7.3 66.9 ⫾ 4.6 TPR index (Wood U/m2) 32.2 ⫾ 6.5 23.8 ⫾ 8.5 PVR index (Wood U/m2) 27.7 ⫾ 6.2 21.3 ⫾ 7.9 SBP (mm Hg) 109.7 ⫾ 8.5 109.9 ⫾ 10.1 DBP (mm Hg) 69.9 ⫾ 9.1 64.2 ⫾ 9.9 HR (bpm) 76.4 ⫾ 14.3 72.7 ⫾ 13.4
.1605 .8358 .0907 .7815 .0860 ⬍.0001 .0001 .0052 .0184 .9462 .1098 .4591
SD, Standard deviation; PCWP, pulmonary capillary wedge pressure; PA, pulmonary arterial; RA, right atrial; RVSP, right ventricular systolic pressure; RVEDP, right ventricular end-diastolic pressure; CI, cardiac index; SvO2, mixed venous oxygen saturation; TPR, total pulmonary resistance; PVR, pulmonary vascular resistance; SBP, systolic blood pressure; DBP, diastolic blood pressure; HR, heart rate.
P value
.0101 .1693 .2070 .4023 .0797 .3310 ⬍.0001 ⬍.0001 ⬍.0001
14.9 9.7 7.7 2.4 0.8 1.6
⫾ ⫾ ⫾ ⫾ ⫾ ⫾
5.1 2.9 3.5 1.5 0.5 0.5
10.7 6.9 11.5 1.0 1.8 1.6
⫾ ⫾ ⫾ ⫾ ⫾ ⫾
4.4 2.6 4.3 0.4 0.8 0.5
.0194 .0077 .0131 .0006 .0005 .9445
0.53 0.61 0.99 211.6
⫾ ⫾ ⫾ ⫾
0.15 0.14 0.66 63.7
0.61 0.54 1.09 214.1
⫾ ⫾ ⫾ ⫾
0.23 0.14 0.27 52.9
.2830 .2197 .5977 .9045
SD, Standard deviation; Dd, end diastolic dimension; Ds, end systolic dimension; FS, fractional shortening; TRPG, pressure gradient of tricuspid regurgitation; IVCD, diameter of inferior vena cava; RW, rightward wave; LW, leftward wave; Es, septal E wave; E, E wave; A, A wave; DcT, deceleration time.
gradient of tricuspid regurgitation was not different significantly between both groups consistent with catheterization data. RW was significantly higher in type A group reflecting fast brisk anterior motion. Es was significantly higher in type B reflecting fast rebound anterior motion after early diastolic bulging, which suggested the inversion of pressure gradient between two ventricles. RW/Es was significantly higher and Es/LW was significantly lower in type A.
Figure 4 Simultaneous pressure recording of patient with type A motion presented in Figure 2. Pressure gradient curve (thick black line) was extremely similar to interventricular septal motion. ECG, Electrocardiogram; LV, left ventricle; RV, right ventricle.
Es/LW greater than 1.0 differentiated these two groups with sensitivity of 93% and specificity of 94%. Invasive Hemodynamics Mean PA, mean RA, RV systolic, and RV end-diastolic pressures were not different significantly, but CI and mixed venous oxygen saturation were significantly lower in type A (Table 3). Type A motion of the IVS predicted CI less than 1.9 L/min/m2 with sensitivity of 80%
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Figure 5 Comparison of simultaneous pressure recording curves recorded from patients with type A and type B motion. In type A, left ventricular (LV) pressure (solid line) is higher than right ventricular (RV) pressure (dotted line) during whole systole, and RV pressure is higher than LV pressure during whole diastole. However, in type B, RV pressure is higher than LV pressure during only early diastole. Table 4 Independent predictors of cardiac index (L/min/m2) Variable
Regression coefficient
P value
LVDd (mm) Eccentricity Index (early diastole) Es (cm/s) Type A motion of the IVS
0.012 ⫺0.155 0.021 ⫺0.211
.1950 .1197 .1485 .0044
Ds, End systolic dimension; Es, septal E wave; IVS, interventricular septum.
and specificity of 88%. Total pulmonary resistance index and pulmonary vascular resistance index were significantly higher in type A. Simultaneous Ventricular Pressures Figure 4 shows the simultaneous pressure recording of a patient with type A motion whose IVS motion is shown in Figure 2. The pressure gradient curve resembles the IVS motion presented in Figure 2. Figure 5 shows the comparison of pressure curves between types A and B. In type A, RV pressure is higher than LV pressure during whole diastole. However, in a patient with type B, RV pressure is higher than LV pressure during only early diastole. This was a common finding in all 5 patients with type B who had simultaneous pressure recordings. Multivariate Analysis To investigate the relationship between echocardiographic parameters and CI, stepwise multiple regression analysis was done. Eleven of 19 parameters were selected on the basis of a significant univariate relation to CI (P ⱕ .05). To avoid multicollinearity, a, b, and a/b were excluded because of their significant correlations to type A motion. As a result, the independent echocardiographic variables used in this study were LV end-diastolic dimension, an eccentricity index, RW, LW, Es, RW/Es, Es/LW, and type A motion. Multiple linear regression analysis was then performed by stepwise forward selection. All variables with a probability value less than .25 remained in the final model. The results of the multiple linear regression analysis are given in Table 4. The model had an overall F statistic of 10.58 (P ⬍ .0001) and the R2 was 0.6105. Only type A motion was an independent predictor of low CI.
early systolic brisk anterior motion (type A) and marked early diastolic posterior motion (type B). These motions were too rapid and too subtle to be picked up by B-mode echocardiography, but M-mode echocardiography was useful in detecting such motions.18,20 We found that patients with type A motion were more morbid clinically and hemodynamically than patients with type B motion. In addition, type A motion predicted low CI independently. This is the first study to show the significance of these peculiar IVS motions detected by M-mode echocardiography in patients with PH. Normal Configuration of the IVS Generally, the LV pressure is always higher than the RV pressure during a cardiac cycle, so that pressure curves of both ventricles never cross over each other13,21-24 and a positive left-to-right transseptal pressure gradient exists throughout the cycle. Under this condition, the round configuration of the septum is observed in healthy individuals.20,25,26 During systole, the normal systolic IVS curvature represents the effect of the transseptal pressure gradient acting in opposition to the natural tendency of the septum to be stiff and straighten as it contracts.15 However, during diastole, because the IVS is independent of the restraining effect generated by active musculature contraction,15,25 it is more flaccid and freely responsive to the transseptal pressure gradient alone.15 Therefore, it behaves as a membrane between two fluid-filled chambers and readily changes its position in response to even minor alterations in the transseptal pressure gradient.15,27 We considered the peculiar IVS motion found in patients with PH were a result of subtle differences in RV and LV pressures during a cardiac cycle. Comparison of Type A and Type B Motion Figure 6 is a comparison of the IVS motion of the two types. In type A, the IVS moves largely anteriorly at systole then it is pushed back posteriorly at early diastole and continues this position during whole diastole. It makes anterior motion conspicuous in type A. In type B, anterior motion is not as remarkable as type A at early systole, but it is pushed back strongly at early diastole similar to type A. However, just after this posterior motion, it moves rapidly anteriorly. It makes posterior motion conspicuous in type B. Thus, IVS bulging toward the LV during whole diastole or early diastole is the difference between type A and type B.
DISCUSSION In routine echocardiographic study, we have noticed that there are two types of IVS motions in patients with RV pressure overload: marked
Mechanism of Peculiar IVS Motions Under RV pressure overload, the peak of RV pressure curve slightly delays with a prolongation of RV isovolumic contraction and relax-
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Figure 6 Comparison of interventricular septal (IVS) motion of type A (dotted line) and B (solid line). IVS bulging toward left ventricle during whole diastole or early diastole is difference between type A and type B. ECG, Electrocardiogram.
Figure 7 A representative patient whose interventricular septal motion changed from type A to type B after prostaglandin I2 (PGI2) treatment. PH, Pulmonary hypertension; ASD, atrial septal defect; NYHA, New York Heart Association; BNP, brain natriuretic peptide; mPAP, mean pulmonary arterial pressure; mRAP, mean right atrial pressure; CI, cardiac index; PVRI, pulmonary vascular resistence index; Dd, end diastolic dimension; Ds, end systolic dimension; TRPG, pressure gradient of tricuspid regurgitation.
ation.28 As a result, RV and LV pressure curves cross over each other on their descending limbs at early diastole and the RV pressure becomes higher than the LV pressure at this phase.13,28 This results in IVS leftward bulging at early diastole observed in both group A and B in the current study. As RV failure progresses as a result of PH, pulmonary blood flow decreases, and RV end-diastolic pressure and mean RA pressure increase subsequently.29-32 In consequence, the transseptal pressure gradient reverses during whole diastole, which results in IVS bulging during this phase observed in group A. In addition, when the atrial kick in the RV pressure exceeds that in the
LV pressure,13 end-diastolic IVS bulging is observed in group A. Thus, type A motion should be a sensitive sign of RV systolic and diastolic dysfunction, which cannot be clearly recognized by simple B-mode echocardiography or right heart pressures. Clinical Implications The IVS motion may be helpful in assessing the improvement of hemodynamics to treatment noninvasively. Figure 7 is a patient whose IVS motion changed from type A to type B after prostaglandin I2 treatment. This dramatic change suggested that the RV diastolic
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Figure 8 Temporal changes in short-axis views obtained from patients in groups A and B. At early diastole, concave left ventricle (LV) configurations are observed in both groups. However, at end diastole, concave LV configuration is observed in group A, but convex circular LV configuration is observed in group B.
pressure became lower than that of the LV after the treatment. The patient’s NYHA class improved from IV to II with a decrease in BNP and an increase in CI. In multiple linear regression analysis, it was demonstrated that type A motion of the IVS was the significant predictive factor of low CI. Of course it will need a further evaluation, but type A and B motions may have not only the hemodynamic value but also the prognostic value because reduced CI is an independent predictor of worse prognosis of patients with primary PH.4 In routine echocardiographic examination, we have traditionally measured eccentricity index only at early diastole when the LV is most compressed. However, this study revealed that the proper timing to measure it to assess hemodynamics of RV pressure overload is end diastole. Figure 8 shows temporal changes in short-axis views obtained from type A and type B motion. At early diastole, the concave LV configurations are observed in both groups. However, at end diastole, the concave LV configuration is observed in group A, but the convex circular LV configuration is observed in group B. These findings strongly suggest that the configuration of the LV at end diastole can differentiate the two groups. In addition, this study demonstrated that M-mode echocardiography still played a useful role in today’s imaging world because of good temporal resolution especially for small and rapid cardiac motions. Limitations Evaluation of the pattern and the velocity of the IVS motion with M-mode and Doppler tissue imaging used in this study cannot avoid
the effects of translation, rotation, or tethering of the LV. Strain method may be able to overcome these limitations because it is based on two points’ velocities and is free from these confounding factors. Type A motion of the IVS has been proven to reflect the interventricular pressure gradient between the LV and RV.13 However, the interventricular pressure gradient in type B motion has not been reported before this study. It will need further experimental examination to confirm our findings, because we could not perform simultaneous pressure measurement on all patients and could not use high-fidelity micromanometer-tipped catheters. Conclusions In patients with PH, early systolic anterior motion and early diastolic posterior motion of the IVS were observed by M-mode echocardiography. The IVS motions reflecting interventricular pressure gradient were classified into two types: type A, marked anterior motion at early systole; and type B, marked posterior motion at early diastole. Patients with type A motion were more morbid clinically and hemodynamically than patients with type B motion. In stepwise multiple linear regression analysis, type A motion predicted low CI independently. The patterns of the IVS motion can predict clinical and hemodynamic conditions of patients with PH. REFERENCES 1. Rich S, Dantzker DR, Ayres SM, et al. Primary pulmonary hypertension: a national prospective study. Ann Intern Med 1987;107:216-23.
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