- Email: [email protected]
Comparative tissue Doppler and catheterization study for assessing left ventricular diastolic dysfunction
j o u r n a l o f i n d i a n c o l l e g e o f c a r d i o l o g y 3 ( 2 0 1 3 ) 9 3 e9 8
Available online at www.sciencedirect.com
journal homepage: www.elsevier.com/locate/jicc
Original Article
Comparative tissue Doppler and catheterization study for assessing left ventricular diastolic dysfunction Haritha N.S. Parvathaneni a, Vidya Sagar Akula a,*, Latheef Kasala b, Rajasekhar Durgaprasad c, Vanajakshamma Velam d a
Senior Resident, Department of Cardiology, Sri Venkateswara Institute of Medical Sciences, Tirupati 517507, Andhra Pradesh, India b Research Scholar, Department of Cardiology, Sri Venkateswara Institute of Medical Sciences, Tirupati 517507, Andhra Pradesh, India c Dean, Professor & HOD, Department of Cardiology, Sri Venkateswara Institute of Medical Sciences, Tirupati 517507, Andhra Pradesh, India d Professor, Department of Cardiology, Sri Venkateswara Institute of Medical Sciences, Tirupati 517507, Andhra Pradesh, India
article info
abstract
Article history:
Background: Diastolic dysfunction is common in cardiac diseases and contributes to the
Received 3 September 2012
signs and symptoms of heart failure. Mitral inflow velocities have been proposed to
Accepted 9 July 2013
identify the diastolic dysfunction. But due to variable factors influencing the mitral inflow
Available online 30 July 2013
velocities, tissue Doppler imaging is considered to be the best predictor of diastolic dysfunction.
Keywords:
Methods: We measured tissue Doppler velocities of mitral valve and compared to cathe-
Tissue Doppler imaging
terization values, Left Ventricular End Diastolic Pressure in one hundred consecutive pa-
Left ventricular end diastolic
tients in sinus rhythm referred for clinically indicated left heart catheterization. Patients
pressure
with acute coronary syndrome, organic mitral or aortic valve disease, heart transplant
Early diastolic mitral inflow velocity
recipients, mechanical valvular prosthesis or technically difficult transthoracic imaging
Early diastolic mitral annulus
window were excluded.
velocity
Results: There was significant correlation between age (48.0 9.2 years), E/Em
Ejection fraction
(18.3 11.9), E/A (1.475 0.798) and LVEDP (15.9 7.0 mmHg). E/Em has 82% sensitivity and 94% specificity. E/A has 53% sensitivity and 77% specificity. E/Em is more sensitive and specific than E/A. As age increased E/Em and LVEDP also increased. There was significant correlation between LVEDP and E/Em ( p < 0.0001). As the LVEDP increases E/Em also increases. There was significant negative correlation between EF and E/Em. As EF decreased E/Em increased ( p ¼ 0.0001). LVEDP and E/Em were significantly higher in diabetics
and
hypertensives
than
non-diabetic
and
non-hypertensive
patients
respectively. Conclusions: Tissue Doppler is more accurate than conventional Doppler for detecting diastolic dysfunction in patients with EF > 50% and EF < 50%. The E/Em ratio is the single
* Corresponding author. Tel.: þ91 9866154310. E-mail address: [email protected] (V.S. Akula). 1561-8811/$ e see front matter Copyright ª 2013, Indian College of Cardiology. All rights reserved. http://dx.doi.org/10.1016/j.jicc.2013.07.002
94
j o u r n a l o f i n d i a n c o l l e g e o f c a r d i o l o g y 3 ( 2 0 1 3 ) 9 3 e9 8
best predictor of LV filling pressure with highest sensitivity and specificity when compared with all other parameters. E/Em can be used as a screening test for detection of diastolic dysfunction. Copyright ª 2013, Indian College of Cardiology. All rights reserved.
1.
Introduction
Doppler echocardiography is widely used for the noninvasive assessment of diastolic filling of the left ventricle (LV). Analysis of the mitral inflow velocity curve can provide useful information for determination of filling pressures and prediction of prognosis in selected patients.1,2 However, mitral flow is dependent on multiple interrelated factors,3 including the rate and extent of ventricular relaxation, suction, atrial and ventricular compliance, and left atrial pressure. These factors may have confounding effects on the mitral inflow; thus, it has not been possible to determine diastolic function from the mitral flow velocity curves in many subsets of patients. To overcome these limitations of the mitral inflow parameters, combinations of the mitral flow velocity curves with other Doppler parameters were used. These include the pulmonary venous velocity curves,1 color M-mode, and Tissue Doppler imaging (TDI).4e7 Tissue Doppler imaging of mitral annular motion has been proposed to correct for the influence of myocardial relaxation on transmitral flows. This has been shown to be an excellent predictor of diastolic filling in subsets of patients.8
2.
Materials and methods
One hundred consecutive patients in sinus rhythm referred for clinically indicated left heart catheterization were included in the study group. Patients with acute coronary syndrome, organic mitral or aortic valve disease, or heart transplant recipients, mechanical valvular prosthesis or technically difficult transthoracic imaging window were excluded. Informed consent was taken from all patients.
2.1.
Doppler echocardiographic studies
Two-dimensional and Doppler echocardiographic examinations were performed with an ultra sonographic system (Philips Sonos 7500, The Netherlands) equipped with multifrequency transducer. Left ventricular ejection fraction (LVEF) was calculated from apical two- and four-chamber views using a modified Simpson rule. Transmitral flow patterns were recorded from apical four-chamber windows with 2- to 3-mm pulsed-sample Doppler volume placed between mitral valve tips in diastole during five consecutive cardiac cycles. Maximal velocities of E- and late diastolic velocity (A)waves, deceleration time of E wave (DT), and isovolumic relaxation time (IVRT) were measured.9 Pulmonary venous flow was assessed on right upper pulmonary vein, with sample volume positioned 5e10 mm proximal to its junction with the left atrium; velocities of the systolic wave (PVs) and diastolic wave (PVd) were measured.9
The measurement of propagation velocity (Vp) was performed in apical four-chamber view by color Doppler echocardiography in M-mode. Then, adjustment of Doppler window and Nyquist velocity to two thirds of blood flow peak velocity was done to display the average velocity of mitral early wave from the mitral annulus to 4 cm toward the apex of the left ventricle. Vp of the early wave was measured as the slope of the line parallel to the recorded border between blue and red colors (which illustrates Nyquist velocity). M-mode color and pulsed Doppler signals were recorded at a horizontal sweep of 100 mm/sec.
2.2.
Tissue Doppler measurements
The Tissue Doppler program was set in pulsed-wave Doppler mode. Motion of mitral annulus was recorded in the apical four-chamber view. Sample volume was positioned sequentially at the lateral and septal corners of the mitral annulus.9 Two major negative velocities were recorded with the movement of the annulus toward the base of the heart during diastole, as follows: one during the early phase of diastolic myocardial velocity (Em), and another during the late phase of diastolic myocardial velocity (late diastolic velocity of the mitral annulus [Am]). All velocities were recorded for five consecutive cardiac cycles, and the results were averaged. TDI measurements of peak Em and Am were made for each cycle, and the mean was calculated. All Tissue Doppler signals were recorded at horizontal time sweep set at 100 mm/sec. Doppler and Tissue Doppler measurements were done immediately before the cardiac catheterization.
2.3.
Pressure measurements
Baseline LV end-diastolic pressure (LVEDP) recordings were acquired before coronary angiography and ventriculography. LV pressure measurements were done invasively with a 6F, fluid-filled pigtail catheter (Cordis Corporation; Miami, FL) with pressure transducers after calibration. The fourth intercostal space in the anterior axillary line was used as the zero level. LV diastolic pressures were recorded as follows: minimal pressure, catheterization investigated pre-A-wave pressure and LVEDP. We defined LVEDP as maximal pressure drop after pressure increase due to atrial contraction and before the rise of systolic pressure. Pressure data were collected at endexpiration. Three consecutive heart cycles were evaluated, and the mean value of LVEDP was calculated. LV filling pressures were considered elevated in case of LVEDP >15 mmHg.
2.4.
Statistical analysis
SAS software was used for statistical analysis. Quantitative variables were expressed in mean and standard deviation. Categorical variables were expressed in percentages. Means of
j o u r n a l o f i n d i a n c o l l e g e o f c a r d i o l o g y 3 ( 2 0 1 3 ) 9 3 e9 8
continuous variables were compared by unpaired student’s ttest. Correlation analysis between Doppler variables and LVEDP was done using Pearson correlation coefficients. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were determined for Doppler and tissue Doppler variables. Receiver-operating characteristic (ROC) curves were constructed for the individual Doppler variables for the prediction of LVEDP >15 mmHg. Statistical significance was defined as P < 0.05.
3.
Results
Mean age of patients in the study group was 48.0 9.2 years. 79% of the study population were males. In the study population 43% had Ejection fraction <50%. Mean systolic blood pressure was 128.0 23.0 mmHg. Diastolic blood pressure was 88.0 12.0 mmHg. The baseline characteristics are presented in Table 1. In patients with EF < 50, EDP > 15 the E/A was 2.3 1.1, DT was 127.0 18.9 msec, IVRT was 72.0 8.7 msec, E/Vp was 2.9 1.0, E/Emmed was 28.6 15.2, E/Emlat was 31.9 12.8. The E/A was 1.0 0.2, DT was 195.4 37.7 msec, IVRT was 87.2 11.9 msec, E/Vp was 1.9 0.5, E/Emmed was 13.9 4.6, E/ Emlat was 12.9 1.9 in patients with EF < 50, EDP < 15. In patients with EF > 50, EDP > 15 the E/A was 1.3 0.5, DT was 157.0 29.6 msec, IVRT was 81.6 10.4 msec, E/Vp was 2.0 0.4, E/Emmed was 20.6 5.0, E/Emlat was 15.1 3.4. The E/A was 1.4 0.5, DT was 172.4 32.8, IVRT was 81.6 7.3, E/Vp was 2.2 0.7, E/Emmed was 11.4 3.9, E/Emlat was 11.3 3.2 in patients with EF > 50, EDP < 15 (Table 2). There was significant correlation between age and LVEDP. As the age increased LVEDP also increased (p ¼ 0.0001). There was significant correlation between age and E/Em. As age increased E/Em also increased (p ¼ 0.0001). There was significant correlation between LVEDP and E/Em. As the LVEDP increased E/Em also increased ( p < 0.0001). There was significant negative correlation between EF and E/Em. As EF decreased E/Em increased ( p ¼ 0.0001). There was significant
Table 1 e Baseline characteristics. Variable Mean age (years) Females (n) Males (n) Coronary artery disease SVD 2VD 3VD Ejection fraction < 50% LVEDP > 15 mmHg Heart rate (beats/min) Systolic BP, mmHg Diastolic BP, mmHg LVEDP, mmHg
Mean SD 48.0 9.2 79 21 35% 15% 25% 43% 52% 86 23 128 23 88 12 15.9 7.0
SVD: Single vessel disease, 2VD: Two vessel disease, TVD: Triple vessel disease, BP: Blood pressure; LVEDP: Left ventricular end diastolic pressure.
95
negative correlation between LVEDP and deceleration time. There was significant correlation between LVEDP and E/A, E/ Vp and IVRT. There was no significant correlation between LVEDP and PVs/PVd. LVEDP and E/Em were significantly higher in hypertensive than non-hypertensive patients (17.1 4.1 vs 14.4 3.6; 21.4 6.3 vs 15.6 3.9 respectively). There was no significant difference in E vel in two groups. LVEDP and E/Em were significantly higher in diabetic than non-diabetic patients (22.2 8.6 vs 13.8 5.3; 24.6 5.8 vs 16.1 4.3 respectively). There was no significant difference in E vel in two groups. E/Emmed had high specificity 94%, sensitivity 82% and high positive predictive value 93% in patients with EF > 50%. E/Vp had high sensitivity 98% and high negative predictive value 98% in patients with EF > 50%. E/Vp had also high sensitivity 87% in patients with EF < 50%. E/Emmed had 83% sensitivity and 84% specificity in patients with EF < 50%. E/A had 88% specificity in patients with EF < 50%. Pulmonary venous Doppler had 70% specificity and 58% sensitivity in patients with EF < 50% (Tables 3 and 4).
4.
Discussion
The noninvasive assessment of LV filling pressures can be an important clinical tool. In diseased ventricles, progressive shortening of the transmitral DT and increasing E/A ratio can be seen with decreasing ventricular compliance and increasing left atrial pressure. Transmitral parameters have been shown to be useful in patients with LV systolic dysfunction.1,2,10e12 The present study confirms that DT and the E/A ratio correlate with LV filling pressure when EF is <50%. However, healthy ventricles that maintain nearly diastolic suction forces may also manifest a relatively short DT and high E/A ratio. Thus, as shown in this study and others13,14 transmitral parameters alone do not correlate with LV filling pressure in patients with preserved systolic function. TDI of the mitral annulus during diastole has been proposed as a method for assessment of cardiac function. With systolic contraction, there is long-axis shortening of the LV manifested by mitral annular descent toward a relatively fixed apex. In patients in sinus rhythm, the annulus ascends in 2 phases. Pulsed-wave TDI provides the velocity profile of these movements. The velocity of the earliest diastolic motion may reflect the rate of myocardial relaxation, and these velocities may not be as dependent on pressure gradients as is blood flow.3,4 TDI has been applied to several subsets of patients to show a correlation with systolic and diastolic cardiac function.4e8 Combining transmitral flow velocity with annular velocity (E/Em) has been proposed as a tool for assessing LV filling pressures that combines the influence of transmitral driving pressure and myocardial relaxation.15e17 In the present study, this combined variable was the best single Doppler predictor of elevated filling pressures. TDI is easier to obtain and, in the present study, more accurate than other methods in determining LV filling pressures. The E/Em ratio can be used as the initial measurement for estimation of LV filling pressures, particularly in those patients with preserved systolic function. There is significant correlation between E/Em, DT, E/A and IVRT with LVEDP in the study group. Previous studies done by
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Table 2 e Summarized baseline and echocardiographic data comparison between groups classified according to LV EF and measurements of invasive LV filling pressures. EF < 50, EDP > 15
Variable
103.9 55.1 2.3 127.0 72.2 57.9 53.8 1.2 35.7 2.9 3.6 5.7 28.6 31.9
E (cm/sec) A (cm/sec) E/A DT (msec) IVRT (msec) PVs (cm/sec) PVd (cm/sec) PVs/PVd Vp (cm/sec) E/Vp Em (cm/sec) Am (cm/sec) E/Emmed E/Emlat
EF < 50, EDP < 15 65.1 65.9 1.0 195.4 87.2 43.6 35.8 1.2 35.4 1.9 5.0 7.4 13.9 12.9
29.5 16.9 1.1 18.9 8.7 27.6 21.2 0.7 4.5 1.0 1.2 1.8 15.2 12.9
6.9 12.9 0.2 37.7 11.9 8.7 5.8 0.2 5.9 0.5 1.1 0.6 4.7 1.9
EF > 50, EDP > 15 84.7 75.5 1.3 157.0 81.6 62.7 47.3 1.4 42.3 2.0 5.9 9.2 20.6 15.1
EF > 50, EDP < 15
12.6 17.7 0.5 29.6 10.4 8.4 8.1 0.3 4.6 0.4 1.6 1.2 5.0 3.4
87.3 70.5 1.4 172.4 81.6 58.0 53.7 1.1 40.8 2.2 9.1 9.2 11.4 11.3
23.3 13.0 0.5 32.8 7.3 11.6 6.9 0.3 4.9 0.7 5.5 0.9 3.9 3.2
EF: Ejection fraction; EDP: End-diastolic pressure.
Srivastava et al18 showed that traditional Doppler measurements for the groups exhibit the expected U shaped parabolic curve from normal to worsening diastolic dysfunction. Peak E velocity decreased significantly in the abnormal relaxation group, but was unchanged from normal in the pseudo normal group. The E/A ratio, IVRT and DT exhibited similar parabolic patterns. In those studies the number of patients with normal EF were 75e80%. In our study the percentage of patients with normal EF was 56%. In patients with EF< 50% there was significant correlation between DT, E/A and IVRT in study done by Srivastava et al.18 As, the percentage of patients with EF < 50% is almost equal in this study, the correlation is near linear. The sensitivity and specificity of E/Emmed and E/Emlat was almost similar in both groups with EF < 50% and EF > 50%. The medial annulus provided improved sensitivity and specificity for the diagnosis of diastolic dysfunction compared to E/Emlat. For E/Emlat and E/Emmed the Area under curve (AUC) was 0.88 and 0.90 respectively. These results were similar to the results of Srivastava et al18 and Kidawa et al.19 This is likely to be due to the fact that Emmed is less affected by translational movement of the heart due to the apex being relatively fixed throughout the cardiac cycle. In addition, Doppler beam angle errors are less likely to occur since the motion of the base of the heart is in an axial plane and parallel to the Doppler cursor when compared to sampling for the lateral annulus. Emlat
myocardial velocities may also be affected by myocardial ischemia and/or infarction, which is less likely to occur at Emmed. Indeed, a recent invasive hemodynamic study in normal healthy volunteers showed that Emmed TDI velocities in subjects with preserved LV systolic function had a good correlation with LV filling pressure, whilst Emlat did not.20
Table 3 e Sensitivity, specificity, positive predictive value and negative predictive value of E/Emmed, E/Emlat, E/A and PVs/PVd in patients with EF > 50%.
The sensitivity for detecting an elevated LVEDP in patients with normal EF is poor, especially for E/Vp. Other studies,18e21,23 also performed direct comparison of E/Em and E/Vp indexes in estimating pulmonary capillary wedge pressure and found better correlation with the E/Vp index. However, most of their patients were receiving mechanical ventilation with different underlying diseases, including valvular disease and acute coronary events, and were in ICUs. Several factors might affect the relationship between pulmonary capillary wedge pressure and filling pressures, particularly in critically ill patients with regional variations in pulmonary vasculature,
Variable
Sensitivity (%)
Specificity (%)
PPV
NPV
E/Emmed E/Emlat E/Vp E/A PVs/PVd
82 79 98 53 43
94 89 23 77 94
93 87 56 65 87
85 82 98 66 64
PPV: Positive predictive value; NPV: Negative predictive value.
Trials Kidaw et al19 EF > 50 E/Emlat > 8 EF < 50 E/Emlat > 9 EF < 50 E/Vp > 2 EF > 50 E/Vp > 2 Gonazalez et al21 E/Ea > 8 E/Vp > 2.6 E/A Srivastava et al18 E/Emlat > 8 Doroz et al22 E/Emlat > 8 E/Emmed > 8 E/Vp > 1.9 Ommen et al9 E/Em E/A E/Emlat
Sensitivity Specificity PPV NPV AUC % % 76 86 85 48
76 83 83 76
e e e e
e e e e
e e e e
87 74 50
66 95 94
61 89 75
89 86 84
0.9 0.7 e
56
93
91
e
0.68
67 86 88
98 79 74
86 43 41
93 97 97
e e e
e e e
86 e e
64 e e
97 e e
0.82 0.72 0.75
j o u r n a l o f i n d i a n c o l l e g e o f c a r d i o l o g y 3 ( 2 0 1 3 ) 9 3 e9 8
Table 4 e Sensitivity, specificity, positive predictive value and negative predictive value of E/Emmed, E/Emlat, E/A and PVs/PVd in patients with EF < 50%. Variable
Sensitivity
Specificity
PPV
NPV
E/Emmed E/Emlat E/Vp E/A PVs/PVd
83 75 87 75 58
85 90 75 88 70
84 87 77 83 64
84 80 85 81 65
97
annulus are better predictors of LVEDP when compared to lateral annular parameters. E/Em can be used as a screening test for detection of diastolic dysfunction. The reliability of E/ Em may be increased if supplemented by other parameters.
Conflicts of interest All authors have none to declare.
PPV: Positive predictive value; NPV: Negative predictive value.
references thus making applying these results to a widespread population difficult. Firstenberg et al20 observed that TDI indexes could be affected by changes in loading conditions, while Vp was not, and that E/Em ratio was less accurate than E/Vp in predicting of LV filling pressures. However, these results concerned only healthy volunteers and not patients with underlying cardiac disease. We also observed higher variability in the measurements of Vp as compared to Em between two independent observers in agreement with previous studies.24 Our study results correlated with that of Doroz et al.22
5.
Study limitations
The motion of the mitral annulus is not entirely due to myocardial contraction but rather is the summation of contraction, rotation, and translation. The effects of each of these may vary from patient to patient. The use of the apical transducer position to sample the mitral annulus is an attempt to minimize the translational and rotational effects and focus on long-axis excursions of the LV cavity. We have not accounted for differences in the length of the long axis, which may inherently be related to total annular plane displacement. Nor was any adjustment made for regional wall motion abnormalities, although there was clearly more data scatter in patients with known CAD. The septal annulus appeared more sensitive to this heterogeneity, although there was a strong correlation between the septal and lateral annulus velocities. The effects of regional dysfunction on the motion of the annular plane are not yet known, and we did not examine the anterior or posterior annulus motion. The LVEDP and Doppler measurements were not done simultaneously, instead were done immediately before the catheterization.
6.
Conclusions
Tissue Doppler is more accurate than conventional Doppler for detecting diastolic dysfunction in patients with EF > 50% and EF < 50%. The E/Em ratio is the single best predictor of LV filling pressure with highest sensitivity and specificity when compared with all other parameters. Conventional Doppler parameters like E/A, E/Vp and pulmonary velocities had high sensitivity and specificity in patients with EF < 50%. Diastolic dysfunction is more common in diabetics and hypertensives and it correlates with the E/Em values. E/Em values of medial
1. Brunazzi MC, Chirillo F, Pasqualini M, et al. Estimation of left ventricular diastolic pressures from precordial pulsedDoppler analysis of pulmonary venous and mitral flow. Am Heart J. 1994;128:293e300. 2. Chenzbraun A, Keren A, Stern S. Doppler echocardiographic patterns of left ventricular filling in patients early after acute myocardial infarction. Am J Cardiol. 1992;70:711e714. 3. Aranda Jr JM, Weston MW, Puleo JA, et al. Effect of loading conditions on myocardial relaxation velocities determined by Doppler tissue imaging in heart transplant recipients. J Heart Lung Transplant. 1998;17:693e697. 4. Sohn DW, Chai IH, Lee DJ, et al. Assessment of mitral annulus velocity by Doppler tissue imaging in the evaluation of left ventricular diastolic function. J Am Coll Cardiol. 1997;30: 474e480. 5. Garcia MJ, Rodriguez L, Ares M, et al. Myocardial wall velocity assessment by pulsed Doppler tissue imaging: characteristic findings in normal subjects. Am Heart J. 1996;132:648e656. 6. 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;27:108e114. 7. Bach DS. Quantitative Doppler tissue imaging as a correlate of left ventricular contractility. Int J Card Imaging. 1996;12: 191e195. 8. 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;77:979e984. 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 comparative simultaneous Doppler-catheterization study. Circulation. 2000;102:1788e1794. 10. Eriksson SV, Bjorkander I, Held C, et al. Age and gender differences in left ventricular function among patients with stable angina and a matched control group: a report from the Angina Prognosis Study in Stockholm. Cardiology. 1996;87: 287e293. 11. Rihal CS, Nishimura RA, Hatle LK, et al. Systolic and diastolic dysfunction in patients with clinical diagnosis of dilated cardiomyopathy: relation to symptoms and prognosis. Circulation. 1994;90:2772e2779. 12. Temporelli PL, Corra U, Imparato A, et al. Reversible restrictive left ventricular diastolic filling with optimized oral therapy predicts a more favorable prognosis in patients with chronic heart failure. J Am Coll Cardiol. 1998;31:1591e1597. 13. Yamamoto K, Nishimura RA, Chaliki HP, et al. Determination of left ventricular filling pressure by Doppler echocardiography in patients with coronary artery disease: critical role of left ventricular systolic function. J Am Coll Cardiol. 1997;30:1819e1826.
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14. Nishimura RA, Appleton CP, Redfield MM, et al. Noninvasive Doppler echocardiographic evaluation of left ventricular filling pressures in patients with cardiomyopathies: a simultaneous Doppler echocardiographic and cardiac catheterization study. J Am Coll Cardiol. 1996;28:1226e1233. 15. Nagueh S, Middleton K, Koplen H, et al. Doppler tissue imaging: a noninvasive technique for evaluation of left ventricular relaxation and estimation of filling pressures. J Am Coll Cardiol. 1997;30:1527e1533. 16. Nagueh SF, Mikati I, Kopelen HA, et al. Doppler estimation of left ventricular filling pressure in sinus tachycardia: a new application of tissue Doppler imaging. Circulation. 1998;98:1644e1650. 17. Nagueh SF, Lakkis NM, Middleton KJ, et al. Doppler estimation of left ventricular filling pressures in patients with hypertrophic cardiomyopathy. Circulation. 1999;99:254e261. 18. Srivastava PM, Burrell LM, Calafiore P, et al. Lateral vs medial mitral annular tissue Doppler in the echocardiographic assessment of diastolic function and filling pressures: which should we use? Eur J Echocardiogr. 2005;6:97e106. 19. Kidawa M, Coignard L, Drobinski G, et al. Comparative value of tissue Doppler imaging and M-mode color Doppler mitral
20.
21.
22.
23.
24.
flow propagation velocity for the evaluation of left ventricular filling pressure. Chest. 2005;128:2544e2550. Firstenberg MS, Greenberg NL, Main ML, et al. Determinants of diastolic myocardial tissue Doppler velocities: influences of relaxation and preload. J Appl Physiol. 2001;90:299e307. Gonzalez-Vilchez F, Ayuela J, Ares M, Mata NS, Gonzalez AG, Duran RM. Comparison of Doppler echocardiography, color M-mode Doppler, and Doppler tissue imaging for the estimation of pulmonary capillary wedge pressure. J Am Soc Echocardiogr. 2002;15:1245e1250. Dorosz JL, Lehmann KG, Stratton JR. Comparison of tissue Doppler and propagation velocity to invasive measures for measuring left ventricular filling pressures. Am J Cardiol. 2005;95:33e40. Garcia MJ, Ares MA, Asher C, et al. An index of early left ventricular filling that combined with pulsed Doppler peak E velocity may estimate capillary wedge pressure. J Am Coll Cardiol. 1997;29:448e454. Seo Y, Ishimitsu T, Moriyama N, et al. Estimating pulmonary capillary wedge pressures using Doppler variables of early diastolic left ventricular inflow. Jpn Circ J. 2001;65:33e39.
Available online at www.sciencedirect.com
journal homepage: www.elsevier.com/locate/jicc
Original Article
Comparative tissue Doppler and catheterization study for assessing left ventricular diastolic dysfunction Haritha N.S. Parvathaneni a, Vidya Sagar Akula a,*, Latheef Kasala b, Rajasekhar Durgaprasad c, Vanajakshamma Velam d a
Senior Resident, Department of Cardiology, Sri Venkateswara Institute of Medical Sciences, Tirupati 517507, Andhra Pradesh, India b Research Scholar, Department of Cardiology, Sri Venkateswara Institute of Medical Sciences, Tirupati 517507, Andhra Pradesh, India c Dean, Professor & HOD, Department of Cardiology, Sri Venkateswara Institute of Medical Sciences, Tirupati 517507, Andhra Pradesh, India d Professor, Department of Cardiology, Sri Venkateswara Institute of Medical Sciences, Tirupati 517507, Andhra Pradesh, India
article info
abstract
Article history:
Background: Diastolic dysfunction is common in cardiac diseases and contributes to the
Received 3 September 2012
signs and symptoms of heart failure. Mitral inflow velocities have been proposed to
Accepted 9 July 2013
identify the diastolic dysfunction. But due to variable factors influencing the mitral inflow
Available online 30 July 2013
velocities, tissue Doppler imaging is considered to be the best predictor of diastolic dysfunction.
Keywords:
Methods: We measured tissue Doppler velocities of mitral valve and compared to cathe-
Tissue Doppler imaging
terization values, Left Ventricular End Diastolic Pressure in one hundred consecutive pa-
Left ventricular end diastolic
tients in sinus rhythm referred for clinically indicated left heart catheterization. Patients
pressure
with acute coronary syndrome, organic mitral or aortic valve disease, heart transplant
Early diastolic mitral inflow velocity
recipients, mechanical valvular prosthesis or technically difficult transthoracic imaging
Early diastolic mitral annulus
window were excluded.
velocity
Results: There was significant correlation between age (48.0 9.2 years), E/Em
Ejection fraction
(18.3 11.9), E/A (1.475 0.798) and LVEDP (15.9 7.0 mmHg). E/Em has 82% sensitivity and 94% specificity. E/A has 53% sensitivity and 77% specificity. E/Em is more sensitive and specific than E/A. As age increased E/Em and LVEDP also increased. There was significant correlation between LVEDP and E/Em ( p < 0.0001). As the LVEDP increases E/Em also increases. There was significant negative correlation between EF and E/Em. As EF decreased E/Em increased ( p ¼ 0.0001). LVEDP and E/Em were significantly higher in diabetics
and
hypertensives
than
non-diabetic
and
non-hypertensive
patients
respectively. Conclusions: Tissue Doppler is more accurate than conventional Doppler for detecting diastolic dysfunction in patients with EF > 50% and EF < 50%. The E/Em ratio is the single
* Corresponding author. Tel.: þ91 9866154310. E-mail address: [email protected] (V.S. Akula). 1561-8811/$ e see front matter Copyright ª 2013, Indian College of Cardiology. All rights reserved. http://dx.doi.org/10.1016/j.jicc.2013.07.002
94
j o u r n a l o f i n d i a n c o l l e g e o f c a r d i o l o g y 3 ( 2 0 1 3 ) 9 3 e9 8
best predictor of LV filling pressure with highest sensitivity and specificity when compared with all other parameters. E/Em can be used as a screening test for detection of diastolic dysfunction. Copyright ª 2013, Indian College of Cardiology. All rights reserved.
1.
Introduction
Doppler echocardiography is widely used for the noninvasive assessment of diastolic filling of the left ventricle (LV). Analysis of the mitral inflow velocity curve can provide useful information for determination of filling pressures and prediction of prognosis in selected patients.1,2 However, mitral flow is dependent on multiple interrelated factors,3 including the rate and extent of ventricular relaxation, suction, atrial and ventricular compliance, and left atrial pressure. These factors may have confounding effects on the mitral inflow; thus, it has not been possible to determine diastolic function from the mitral flow velocity curves in many subsets of patients. To overcome these limitations of the mitral inflow parameters, combinations of the mitral flow velocity curves with other Doppler parameters were used. These include the pulmonary venous velocity curves,1 color M-mode, and Tissue Doppler imaging (TDI).4e7 Tissue Doppler imaging of mitral annular motion has been proposed to correct for the influence of myocardial relaxation on transmitral flows. This has been shown to be an excellent predictor of diastolic filling in subsets of patients.8
2.
Materials and methods
One hundred consecutive patients in sinus rhythm referred for clinically indicated left heart catheterization were included in the study group. Patients with acute coronary syndrome, organic mitral or aortic valve disease, or heart transplant recipients, mechanical valvular prosthesis or technically difficult transthoracic imaging window were excluded. Informed consent was taken from all patients.
2.1.
Doppler echocardiographic studies
Two-dimensional and Doppler echocardiographic examinations were performed with an ultra sonographic system (Philips Sonos 7500, The Netherlands) equipped with multifrequency transducer. Left ventricular ejection fraction (LVEF) was calculated from apical two- and four-chamber views using a modified Simpson rule. Transmitral flow patterns were recorded from apical four-chamber windows with 2- to 3-mm pulsed-sample Doppler volume placed between mitral valve tips in diastole during five consecutive cardiac cycles. Maximal velocities of E- and late diastolic velocity (A)waves, deceleration time of E wave (DT), and isovolumic relaxation time (IVRT) were measured.9 Pulmonary venous flow was assessed on right upper pulmonary vein, with sample volume positioned 5e10 mm proximal to its junction with the left atrium; velocities of the systolic wave (PVs) and diastolic wave (PVd) were measured.9
The measurement of propagation velocity (Vp) was performed in apical four-chamber view by color Doppler echocardiography in M-mode. Then, adjustment of Doppler window and Nyquist velocity to two thirds of blood flow peak velocity was done to display the average velocity of mitral early wave from the mitral annulus to 4 cm toward the apex of the left ventricle. Vp of the early wave was measured as the slope of the line parallel to the recorded border between blue and red colors (which illustrates Nyquist velocity). M-mode color and pulsed Doppler signals were recorded at a horizontal sweep of 100 mm/sec.
2.2.
Tissue Doppler measurements
The Tissue Doppler program was set in pulsed-wave Doppler mode. Motion of mitral annulus was recorded in the apical four-chamber view. Sample volume was positioned sequentially at the lateral and septal corners of the mitral annulus.9 Two major negative velocities were recorded with the movement of the annulus toward the base of the heart during diastole, as follows: one during the early phase of diastolic myocardial velocity (Em), and another during the late phase of diastolic myocardial velocity (late diastolic velocity of the mitral annulus [Am]). All velocities were recorded for five consecutive cardiac cycles, and the results were averaged. TDI measurements of peak Em and Am were made for each cycle, and the mean was calculated. All Tissue Doppler signals were recorded at horizontal time sweep set at 100 mm/sec. Doppler and Tissue Doppler measurements were done immediately before the cardiac catheterization.
2.3.
Pressure measurements
Baseline LV end-diastolic pressure (LVEDP) recordings were acquired before coronary angiography and ventriculography. LV pressure measurements were done invasively with a 6F, fluid-filled pigtail catheter (Cordis Corporation; Miami, FL) with pressure transducers after calibration. The fourth intercostal space in the anterior axillary line was used as the zero level. LV diastolic pressures were recorded as follows: minimal pressure, catheterization investigated pre-A-wave pressure and LVEDP. We defined LVEDP as maximal pressure drop after pressure increase due to atrial contraction and before the rise of systolic pressure. Pressure data were collected at endexpiration. Three consecutive heart cycles were evaluated, and the mean value of LVEDP was calculated. LV filling pressures were considered elevated in case of LVEDP >15 mmHg.
2.4.
Statistical analysis
SAS software was used for statistical analysis. Quantitative variables were expressed in mean and standard deviation. Categorical variables were expressed in percentages. Means of
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continuous variables were compared by unpaired student’s ttest. Correlation analysis between Doppler variables and LVEDP was done using Pearson correlation coefficients. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were determined for Doppler and tissue Doppler variables. Receiver-operating characteristic (ROC) curves were constructed for the individual Doppler variables for the prediction of LVEDP >15 mmHg. Statistical significance was defined as P < 0.05.
3.
Results
Mean age of patients in the study group was 48.0 9.2 years. 79% of the study population were males. In the study population 43% had Ejection fraction <50%. Mean systolic blood pressure was 128.0 23.0 mmHg. Diastolic blood pressure was 88.0 12.0 mmHg. The baseline characteristics are presented in Table 1. In patients with EF < 50, EDP > 15 the E/A was 2.3 1.1, DT was 127.0 18.9 msec, IVRT was 72.0 8.7 msec, E/Vp was 2.9 1.0, E/Emmed was 28.6 15.2, E/Emlat was 31.9 12.8. The E/A was 1.0 0.2, DT was 195.4 37.7 msec, IVRT was 87.2 11.9 msec, E/Vp was 1.9 0.5, E/Emmed was 13.9 4.6, E/ Emlat was 12.9 1.9 in patients with EF < 50, EDP < 15. In patients with EF > 50, EDP > 15 the E/A was 1.3 0.5, DT was 157.0 29.6 msec, IVRT was 81.6 10.4 msec, E/Vp was 2.0 0.4, E/Emmed was 20.6 5.0, E/Emlat was 15.1 3.4. The E/A was 1.4 0.5, DT was 172.4 32.8, IVRT was 81.6 7.3, E/Vp was 2.2 0.7, E/Emmed was 11.4 3.9, E/Emlat was 11.3 3.2 in patients with EF > 50, EDP < 15 (Table 2). There was significant correlation between age and LVEDP. As the age increased LVEDP also increased (p ¼ 0.0001). There was significant correlation between age and E/Em. As age increased E/Em also increased (p ¼ 0.0001). There was significant correlation between LVEDP and E/Em. As the LVEDP increased E/Em also increased ( p < 0.0001). There was significant negative correlation between EF and E/Em. As EF decreased E/Em increased ( p ¼ 0.0001). There was significant
Table 1 e Baseline characteristics. Variable Mean age (years) Females (n) Males (n) Coronary artery disease SVD 2VD 3VD Ejection fraction < 50% LVEDP > 15 mmHg Heart rate (beats/min) Systolic BP, mmHg Diastolic BP, mmHg LVEDP, mmHg
Mean SD 48.0 9.2 79 21 35% 15% 25% 43% 52% 86 23 128 23 88 12 15.9 7.0
SVD: Single vessel disease, 2VD: Two vessel disease, TVD: Triple vessel disease, BP: Blood pressure; LVEDP: Left ventricular end diastolic pressure.
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negative correlation between LVEDP and deceleration time. There was significant correlation between LVEDP and E/A, E/ Vp and IVRT. There was no significant correlation between LVEDP and PVs/PVd. LVEDP and E/Em were significantly higher in hypertensive than non-hypertensive patients (17.1 4.1 vs 14.4 3.6; 21.4 6.3 vs 15.6 3.9 respectively). There was no significant difference in E vel in two groups. LVEDP and E/Em were significantly higher in diabetic than non-diabetic patients (22.2 8.6 vs 13.8 5.3; 24.6 5.8 vs 16.1 4.3 respectively). There was no significant difference in E vel in two groups. E/Emmed had high specificity 94%, sensitivity 82% and high positive predictive value 93% in patients with EF > 50%. E/Vp had high sensitivity 98% and high negative predictive value 98% in patients with EF > 50%. E/Vp had also high sensitivity 87% in patients with EF < 50%. E/Emmed had 83% sensitivity and 84% specificity in patients with EF < 50%. E/A had 88% specificity in patients with EF < 50%. Pulmonary venous Doppler had 70% specificity and 58% sensitivity in patients with EF < 50% (Tables 3 and 4).
4.
Discussion
The noninvasive assessment of LV filling pressures can be an important clinical tool. In diseased ventricles, progressive shortening of the transmitral DT and increasing E/A ratio can be seen with decreasing ventricular compliance and increasing left atrial pressure. Transmitral parameters have been shown to be useful in patients with LV systolic dysfunction.1,2,10e12 The present study confirms that DT and the E/A ratio correlate with LV filling pressure when EF is <50%. However, healthy ventricles that maintain nearly diastolic suction forces may also manifest a relatively short DT and high E/A ratio. Thus, as shown in this study and others13,14 transmitral parameters alone do not correlate with LV filling pressure in patients with preserved systolic function. TDI of the mitral annulus during diastole has been proposed as a method for assessment of cardiac function. With systolic contraction, there is long-axis shortening of the LV manifested by mitral annular descent toward a relatively fixed apex. In patients in sinus rhythm, the annulus ascends in 2 phases. Pulsed-wave TDI provides the velocity profile of these movements. The velocity of the earliest diastolic motion may reflect the rate of myocardial relaxation, and these velocities may not be as dependent on pressure gradients as is blood flow.3,4 TDI has been applied to several subsets of patients to show a correlation with systolic and diastolic cardiac function.4e8 Combining transmitral flow velocity with annular velocity (E/Em) has been proposed as a tool for assessing LV filling pressures that combines the influence of transmitral driving pressure and myocardial relaxation.15e17 In the present study, this combined variable was the best single Doppler predictor of elevated filling pressures. TDI is easier to obtain and, in the present study, more accurate than other methods in determining LV filling pressures. The E/Em ratio can be used as the initial measurement for estimation of LV filling pressures, particularly in those patients with preserved systolic function. There is significant correlation between E/Em, DT, E/A and IVRT with LVEDP in the study group. Previous studies done by
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Table 2 e Summarized baseline and echocardiographic data comparison between groups classified according to LV EF and measurements of invasive LV filling pressures. EF < 50, EDP > 15
Variable
103.9 55.1 2.3 127.0 72.2 57.9 53.8 1.2 35.7 2.9 3.6 5.7 28.6 31.9
E (cm/sec) A (cm/sec) E/A DT (msec) IVRT (msec) PVs (cm/sec) PVd (cm/sec) PVs/PVd Vp (cm/sec) E/Vp Em (cm/sec) Am (cm/sec) E/Emmed E/Emlat
EF < 50, EDP < 15 65.1 65.9 1.0 195.4 87.2 43.6 35.8 1.2 35.4 1.9 5.0 7.4 13.9 12.9
29.5 16.9 1.1 18.9 8.7 27.6 21.2 0.7 4.5 1.0 1.2 1.8 15.2 12.9
6.9 12.9 0.2 37.7 11.9 8.7 5.8 0.2 5.9 0.5 1.1 0.6 4.7 1.9
EF > 50, EDP > 15 84.7 75.5 1.3 157.0 81.6 62.7 47.3 1.4 42.3 2.0 5.9 9.2 20.6 15.1
EF > 50, EDP < 15
12.6 17.7 0.5 29.6 10.4 8.4 8.1 0.3 4.6 0.4 1.6 1.2 5.0 3.4
87.3 70.5 1.4 172.4 81.6 58.0 53.7 1.1 40.8 2.2 9.1 9.2 11.4 11.3
23.3 13.0 0.5 32.8 7.3 11.6 6.9 0.3 4.9 0.7 5.5 0.9 3.9 3.2
EF: Ejection fraction; EDP: End-diastolic pressure.
Srivastava et al18 showed that traditional Doppler measurements for the groups exhibit the expected U shaped parabolic curve from normal to worsening diastolic dysfunction. Peak E velocity decreased significantly in the abnormal relaxation group, but was unchanged from normal in the pseudo normal group. The E/A ratio, IVRT and DT exhibited similar parabolic patterns. In those studies the number of patients with normal EF were 75e80%. In our study the percentage of patients with normal EF was 56%. In patients with EF< 50% there was significant correlation between DT, E/A and IVRT in study done by Srivastava et al.18 As, the percentage of patients with EF < 50% is almost equal in this study, the correlation is near linear. The sensitivity and specificity of E/Emmed and E/Emlat was almost similar in both groups with EF < 50% and EF > 50%. The medial annulus provided improved sensitivity and specificity for the diagnosis of diastolic dysfunction compared to E/Emlat. For E/Emlat and E/Emmed the Area under curve (AUC) was 0.88 and 0.90 respectively. These results were similar to the results of Srivastava et al18 and Kidawa et al.19 This is likely to be due to the fact that Emmed is less affected by translational movement of the heart due to the apex being relatively fixed throughout the cardiac cycle. In addition, Doppler beam angle errors are less likely to occur since the motion of the base of the heart is in an axial plane and parallel to the Doppler cursor when compared to sampling for the lateral annulus. Emlat
myocardial velocities may also be affected by myocardial ischemia and/or infarction, which is less likely to occur at Emmed. Indeed, a recent invasive hemodynamic study in normal healthy volunteers showed that Emmed TDI velocities in subjects with preserved LV systolic function had a good correlation with LV filling pressure, whilst Emlat did not.20
Table 3 e Sensitivity, specificity, positive predictive value and negative predictive value of E/Emmed, E/Emlat, E/A and PVs/PVd in patients with EF > 50%.
The sensitivity for detecting an elevated LVEDP in patients with normal EF is poor, especially for E/Vp. Other studies,18e21,23 also performed direct comparison of E/Em and E/Vp indexes in estimating pulmonary capillary wedge pressure and found better correlation with the E/Vp index. However, most of their patients were receiving mechanical ventilation with different underlying diseases, including valvular disease and acute coronary events, and were in ICUs. Several factors might affect the relationship between pulmonary capillary wedge pressure and filling pressures, particularly in critically ill patients with regional variations in pulmonary vasculature,
Variable
Sensitivity (%)
Specificity (%)
PPV
NPV
E/Emmed E/Emlat E/Vp E/A PVs/PVd
82 79 98 53 43
94 89 23 77 94
93 87 56 65 87
85 82 98 66 64
PPV: Positive predictive value; NPV: Negative predictive value.
Trials Kidaw et al19 EF > 50 E/Emlat > 8 EF < 50 E/Emlat > 9 EF < 50 E/Vp > 2 EF > 50 E/Vp > 2 Gonazalez et al21 E/Ea > 8 E/Vp > 2.6 E/A Srivastava et al18 E/Emlat > 8 Doroz et al22 E/Emlat > 8 E/Emmed > 8 E/Vp > 1.9 Ommen et al9 E/Em E/A E/Emlat
Sensitivity Specificity PPV NPV AUC % % 76 86 85 48
76 83 83 76
e e e e
e e e e
e e e e
87 74 50
66 95 94
61 89 75
89 86 84
0.9 0.7 e
56
93
91
e
0.68
67 86 88
98 79 74
86 43 41
93 97 97
e e e
e e e
86 e e
64 e e
97 e e
0.82 0.72 0.75
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Table 4 e Sensitivity, specificity, positive predictive value and negative predictive value of E/Emmed, E/Emlat, E/A and PVs/PVd in patients with EF < 50%. Variable
Sensitivity
Specificity
PPV
NPV
E/Emmed E/Emlat E/Vp E/A PVs/PVd
83 75 87 75 58
85 90 75 88 70
84 87 77 83 64
84 80 85 81 65
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annulus are better predictors of LVEDP when compared to lateral annular parameters. E/Em can be used as a screening test for detection of diastolic dysfunction. The reliability of E/ Em may be increased if supplemented by other parameters.
Conflicts of interest All authors have none to declare.
PPV: Positive predictive value; NPV: Negative predictive value.
references thus making applying these results to a widespread population difficult. Firstenberg et al20 observed that TDI indexes could be affected by changes in loading conditions, while Vp was not, and that E/Em ratio was less accurate than E/Vp in predicting of LV filling pressures. However, these results concerned only healthy volunteers and not patients with underlying cardiac disease. We also observed higher variability in the measurements of Vp as compared to Em between two independent observers in agreement with previous studies.24 Our study results correlated with that of Doroz et al.22
5.
Study limitations
The motion of the mitral annulus is not entirely due to myocardial contraction but rather is the summation of contraction, rotation, and translation. The effects of each of these may vary from patient to patient. The use of the apical transducer position to sample the mitral annulus is an attempt to minimize the translational and rotational effects and focus on long-axis excursions of the LV cavity. We have not accounted for differences in the length of the long axis, which may inherently be related to total annular plane displacement. Nor was any adjustment made for regional wall motion abnormalities, although there was clearly more data scatter in patients with known CAD. The septal annulus appeared more sensitive to this heterogeneity, although there was a strong correlation between the septal and lateral annulus velocities. The effects of regional dysfunction on the motion of the annular plane are not yet known, and we did not examine the anterior or posterior annulus motion. The LVEDP and Doppler measurements were not done simultaneously, instead were done immediately before the catheterization.
6.
Conclusions
Tissue Doppler is more accurate than conventional Doppler for detecting diastolic dysfunction in patients with EF > 50% and EF < 50%. The E/Em ratio is the single best predictor of LV filling pressure with highest sensitivity and specificity when compared with all other parameters. Conventional Doppler parameters like E/A, E/Vp and pulmonary velocities had high sensitivity and specificity in patients with EF < 50%. Diastolic dysfunction is more common in diabetics and hypertensives and it correlates with the E/Em values. E/Em values of medial
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