Characteristics of Left Ventricular Diastolic Function in Patients with Systolic Heart Failure: A Doppler Tissue Imaging Study

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1 Characteristics of Left Ventricular Diastolic Function in Patients with Systolic Heart Failure: A Doppler Tissue Imaging Study Bassem A. Samad, MD, PhD, Jens M. Olson, MD, and Mahbubul Alam, MD, PhD, FESC, Stockholm, Sweden Objective: Our aim was to characterize myocardial velocity profiles in different types of diastolic dysfunction for patients with severely decreased left ventricular (LV) systolic function. Methods: A total of 126 patients with congestive heart failure and an LV ejection fraction of 35% or less were included. Patients underwent an echocardiographic Doppler examination, with measurement of the transmitral inflow pattern, and Doppler tissue imaging of the mitral annulus. Results: Compared with age-matched control subjects, the patients had decreased systolic (9.5 vs 4.9 cm/s, P <.001) and early diastolic (11.6 vs 5.6 cm/s, P <.001) mitral annular velocities. According to the transmitral inflow pattern, 56 patients had signs of a LV restrictive pattern, 36 had a pseudonormalization pattern, and 34 had an abnormal relaxation pattern. The peak systolic and early diastolic mitral annular velocities were quite similarly reduced in different diastolic groups (systolic velocities of 4.6, 5.0, and 5.3 cm/s, and early diastolic velocities of 5.7, 5.8, and 5.1 cm/s at restrictive, pseudonormal, and abnormal relaxation, respectively). The ratio of the transmitral early wave and mitral annular early velocity, an expression of LV filling pressure, was highest in the restrictive group compared with other groups (17.0, 14.6, and 11.7 in the above 3 groups, respectively, P <.001 among groups). The ratio of the transmitral early wave and mitral annular early velocity was also higher in the pseudonormal group than in a control group of patients with ejection fraction of 35% or more with signs of a normal/pseudonormal pattern (14.6 vs 9.0, P <.001). Conclusion: Doppler tissue imaging may enhance the estimates of diastolic dysfunction in patients with decreased LV systolic function, and help to disclose abnormal diastolic function especially in a pseudonormal group. (J Am Soc Echocardiogr 2005; 18: ) It is a well-known fact that abnormalities of diastolic function of the left ventricle (LV) may contribute to symptoms of congestive heart failure (CHF) with or without ventricular systolic dysfunction and are an important predictor of outcome in these patients. 1-3 Diastolic function has traditionally been assessed by pulsed Doppler echocardiographic measurements of the transmitral flow pattern. 4 However, measurements of the transmitral flow have limitations especially because it is dependent on load conditions and the technique may not recognize the pseudonormalization of the flow in some patients with advanced From the Department of Cardiology, Karolinska Institute at South Hospital (Södersjukhuset). Supported in part by the Swedish Heart-Lung Foundation. Reprint requests: Bassem A. Samad, MD, Department of Cardiology, Södersjukhuset, S Stockholm, Sweden ( bassem.samad@sodersjukhset.se) /$30.00 Copyright 2005 by the American Society of Echocardiography. doi: /j.echo diastolic dysfunction. 5 Use of pulmonary venous flow measurements might help to identify different types of diastolic dysfunction. However, the echocardiographic quality obtained in recordings of the pulmonary vein flow may not be optimal in many cases. By recording the myocardial velocity using Doppler tissue imaging (DTI), it may be possible to avoid the limitations of conventional Doppler flow measurements in assessing the diastolic function. 6,7 This relatively new method has been studied in patients with ischemic heart disease, hypertension, and dilated cardiomyopathy, 8-10 but the value of DTI for assessing diastolic function in patients with established systolic heart failure has not been fully tested. Using myocardial velocity, the aim of this study was to characterize diastolic function for patients with a significantly reduced ejection fraction (EF) and clinical signs of CHF, and to determine whether the parameters of the myocardial velocities differ in different patterns of diastolic dysfunction measured by conventional transmitral Doppler methods. 896

2 Volume 18 Number 9 Samad, Olson, Alam 897 METHODS Patients The study was initiated with a population of 200 patients with CHF. Patients with an EF greater than 35%, a previous coronary artery bypass graft, atrial fibrillation, or lack of an echocardiogram of good quality were excluded. None of the patients were excluded because of unsatisfactory DTI quality. Ultimately, 126 patients were included in the study. All the patients were admitted to the hospital because of signs and symptoms of CHF. The studies were conducted before discharge when the patients were in a stable clinical condition. The cause of CHF was as follows: 60% ischemic heart disease; 32% without known genesis and classified as having dilated cardiomyopathy; and 8% hypertension. Twenty age-matched healthy individuals without a history of heart disease, systemic hypertension, or diabetes mellitus and having normal findings at rest electrocardiography and echocardiography served as control subjects. In addition, 36 patients with acute myocardial infarction and an EF of 35% or more and signs of a normal/pseudonormal transmitral flow pattern served as another control group. Informed consent was obtained from the patients. The study was approved by the regional ethical committee. Echocardiography A machine (Sonos 5500, Hewlett-Packard, Palo Alto, Calif) was used to obtain echocardiograms. The LV dimensions and EF were measured according to the recommendations of the American Society of Echocardiography. 11 Transmitral flow was recorded by pulsed wave Doppler placed between the mitral leaflet tips in an apical 4-chamber view. Early transmitral flow velocity (E) and late transmitral flow velocity (A) were obtained. The ratio of E to A (E/A) and the deceleration time were calculated. A relaxation abnormality was defined as an E/A ratio less than 1. A normal pattern or pseudonormalization was defined as an E/A ratio equal to or greater than 1 and equal to or greater than 2 combined with a deceleration time longer than 140 milliseconds. A restrictive pattern was defined as an E/A ratio greater than 2 or an E/A ratio greater than 1 and a deceleration time less than 140 milliseconds. 12 Mitral Annular Velocity by DTI Pulsed wave DTI was performed by activating the DTI function in the same echocardiography machine. Images were acquired by using a variable frequency phased-array transducer ( MHz). The filter settings were kept low (50 Hz) and gains were adjusted at the lowest possible level to minimize noise and eliminate the signals produced by the transmitral flow. A 1.7-mm sample volume was used. Four different sites at the mitral annulus were selected. In the apical 4-chamber view, the DTI cursor was placed at the septal side of the mitral annulus in such a way that the mitral annulus at the septum moved along the sample volume line. A Doppler velocity range of 20 to 20 cm/s was selected for this study. Three major velocities were recorded: the positive systolic velocity when the mitral ring moved toward the cardiac apex; and two negative diastolic velocities when the mitral annulus moved toward the base away from the apex, one during the early phase of diastole and the other in the late phase of diastole. The peak systolic and peak early and late diastolic velocities were measured. By moving the sample volume at the lateral site of the mitral annulus, systolic and diastolic velocities of the LV lateral wall were also recorded. In a similar way, the velocities at the anterior and inferior sites of the mitral annulus were recorded in the apical 2-chamber view. A mean value for the above 4 sites was used to assess global systolic and diastolic function. The tricuspid annular velocities were also measured similarly by placing the sampling volume at the tricuspid ring of the right ventricular free wall in the apical 4-chamber view. A mean of 3 consecutive cycles was used to calculate all echocardiographic Doppler parameters. Statistics The results are expressed as the mean value SD. Comparisons of the results were made using Student t test. A P value less than.05 was considered statistically significant. RESULTS The characteristics of the patients and the healthy population are shown in Table 1. The patients with CHF had severely decreased systolic and diastolic mitral annular velocities compared with the control subjects. A similar trend was also noted regarding the tricuspid annular velocities. According to the pulsed Doppler transmitral flow pattern we found 34 patients with relaxation abnormalities, 36 showing pseudonormalization, and 56 showing a restrictive diastolic pattern. Compared with patients with abnormal relaxation, patients with signs of restrictive LV function had a larger LV and a more severely depressed EF. The results for transmitral flow velocity parameters in different groups are shown in Table 2. The results of myocardial velocities in different groups of patients are shown in Table 3. There was very little difference in the systolic and diastolic mitral annular velocities between the groups. Similar results have also been noted between different groups regarding the tricuspid annular velocities. The ratio between the transmitral early wave and the DTI-recorded early diastolic mitral annular velocity (E/E-DTI), a parameter used in assessing LV filling pressure, was calculated in different groups of patients. The E/E-DTI was lowest in abnormal relaxation and was highest in patients with a restrictive pattern (Table 3). Compared with the control group of patients with myocardial infarction and signs of a

3 898 Samad, Olson, Alam September 2005 Table 1 Echocardiographic parameters in the patients with severe systolic dysfunction and in control subjects normal/pseudonormal diastolic flow pattern, the subgroup of patients with CHF having a pseudonormal LV flow showed a decrease in early diastolic mitral annular velocity and an increase in E/E-dti (Table 4). DISCUSSION Patients n 126 Control subjects n 20 P value Age, y LVDD, mm LVEF, % Mitral annular velocities, cm/s Systolic Early diastolic Late diastolic Ratio of early to late diastolic E/E-DTI Tricuspid annular velocities, cm/s Systolic Early diastolic Late diastolic Ratio of early to late diastolic E/E-DTI, Ratio between transmitral early wave and Doppler tissue imaging recorded peak early mitral annular velocity; LVDD, left ventricular enddiastolic diameter; LVEF, left ventricular ejection fraction. Table 2 Standard echocardiographic and Doppler parameters in different subgroups of patients Restrictive Pseudonormal Abnormal relaxation LVEDd, mm 62 7* LVEF, % 22 5* Transmitral flow E/A ratio * * E-dec, ms * E/A, Ratio of transmitral early to late flow velocity; E-dec, transmitral early wave deceleration time; LVEDd, left ventricular end-diastolic dimension; LVEF, left ventricular ejection fraction. *P.001 and P.01 compared with abnormal relaxation, P.001 compared with pseudonormal. Recording of myocardial velocities with DTI has been used increasingly in clinical practice during the last decade. Myocardial velocities can be recorded both online and offline from the 2-dimensional color-coded maps or only online using pulsed wave DTI. In this study, we used the latter and succeeded in recording and analyzing the systolic and diastolic annular velocities in all the patients irrespective of the quality of the standard echocardiogram. Previous studies have described the different findings of myocardial velocities in assessments of systolic and diastolic functions. Up until now, a consensus has been lacking regarding the reference values in clinical conditions. However, it is generally accepted that the mitral annular velocity represents LV function along the long axis. Reduced systolic and early diastolic mitral annular velocities reflect decreased LV systolic and diastolic functions, respectively. 7,10,13 Therefore, in the current study, we used agematched control subjects to compare the myocardial velocities for patients with CHF. In the presence of a severely reduced EF, significantly decreased systolic and early diastolic mitral annular velocities were noted for patients as compared with control subjects. This is an expression of decreased LV function along the long axis. Assessment of diastolic function is important. In previous studies, it has been shown that patients with similar LV systolic dysfunction may have different outcomes, 14 which may complicate risk stratification of individual patients. Diastolic dysfunction has been shown to have prognostic value for patients with dilated cardiomyopathy 15 and CHF, 16 and patients with a restrictive pattern have the poorest prognosis For simple assessments of diastolic dysfunction, most of the previous studies divided the patients with CHF into only two groups: restrictive versus nonrestrictive. One explanation for this selection may be difficulties in detecting pseudonormalization. In this study, the early diastolic mitral annular velocity for patients with a restrictive pattern was severely reduced compared with values in control subjects. Similar findings were also observed for patients with a relaxation abnormality. In the presence of a decreased EF for patients with CHF, recording of the transmitral flow velocity profiles might not disclose patients with diastolic dysfunction. In this study, more than every fourth patient had an E/A ratio within normal limits (and, therefore, probably pseudonormalization) as assessed by conventional transmitral flow pattern. Using DTI we could disclose the severely decreased early diastolic mitral annular velocity in these patients, and the decrease in velocity was similar to the reduction for patients with restrictive LV filling. In other words, for patients with CHF and a significantly reduced EF the diastolic dysfunction is severe irrespective of the findings obtained by conventional transmitral flow. Some previous studies have reported that the ratio of E/E-dti provides better estimates of LV filling pressure than other methods (eg, pulmonary vein flow measurements). 7,20 A high value reflects an abnormally elevated LV filling pressure. E/E-dti less than 8 could accurately predict normal mean LV diastolic pressure and E/E-DTI greater than 15 rep-

4 Volume 18 Number 9 Samad, Olson, Alam 899 Table 3 Mitral and tricuspid annular velocities in different subgroups of patients with diastolic dysfunction Restrictive pattern Pseudonormal Abnormal relaxation Mitral annular velocities, cm/s Systolic Early diastolic Late diastolic Ratio of early/late diastolic E/E-DTI * Tricuspid annular velocities, cm/s Systolic Early diastolic Late diastolic Ratio of early/late diastolic E/E-DTI, Ratio between the transmitral early wave velocity and mitral annular early diastolic velocity. *P.001 compared with abnormal relaxation group, P.001 compared with pseudonormal group, P.05 compared with abnormal relaxation group. Table 4 Echocardiographic Doppler parameters in patients with congestive heart failure with ejection fraction less than 35% and a normal/pseudonormal pattern of transmitral flow (n 36) compared with the control group of patients with ejection fraction of 35% or more and transmitral normal/pseudonormal flow (n 38) LV, mm EF, % E/A E-dec, ms MAV-S, cm/s MAV-E, cm/s E/E-DTI EF 35% EF 35% 52 6* 48 * * * * LV, left ventricular end-diastolic dimension; E/A, Ratio between transmitral early and late velocities; E-dec, transmitral early diastolic deceleration time; MAV-S, mitral annular systolic velocity; MAV-E, mitral annular early diastolic velocity; E/E-DTI, ratio between transmitral early diastolic flow and mitral annular early diastolic velocity. EF, ejection fraction. Results are given as means SD. *P.001. resented an increased mean LV diastolic pressure. 20 In the current study E/E-DTI was increased for patients with CHF compared with control subjects. The increased E/E-DTI was noted especially for patients with signs of a restrictive pattern. The patients with a pseudonormal pattern also had a relatively higher E/E-DTI than patients with an abnormal relaxation pattern and the control group of patients with EF greater than 35%. These findings confirm that the pseudonormalization is a sign of more advanced LV diastolic dysfunction in the presence of a severely depressed EF. The interpretation of echocardiographic measurements of diastolic function is complex. Research is still ongoing to formulate guidelines for the diagnosis of diastolic heart failure. Ventricular diastolic function has been investigated invasively, and with new methods including magnetic resonance imaging and computed tomography. However, in routine clinical practice, echocardiography and Doppler techniques including the analysis of mitral inflow velocities are most widely used for the evaluation of LV diastolic function. Unfortunately, these indices depend on too many factors such as preload, age, and heart rate. In contrast to standard transmitral Doppler filling indices, Doppler tissue early diastolic velocities are not significantly affected by loading conditions. Thus, Doppler tissue velocities during early LV diastole may provide a better index of diastolic function by providing an assessment of LV filling independent of preload. 21,22 In our study population, systolic and diastolic dysfunction coexisted, and the severity of diastolic dysfunction covered a wide spectrum. Systolic and diastolic phases and function of the LV are interdependent. Thus, the entire study population with a decreased systolic LV EF less than 35% is likely to have a diastolic dysfunction, and the normal finding of the ratio of transmitral early and late velocities observed in some of the patients in our study was a matter of pseudonormalization. The results of this study demonstrate that pseudonormalization may be defined as a combination of a normal transmitral inflow and decreased early diastolic mitral velocity for patients with CHF and severe systolic dysfunction. Study Limitations In this study, diastolic function was assessed using Doppler echocardiographic techniques. The absence of data from invasive measurements to determine diastolic dysfunction could be a limitation of the study. No data regarding the pulmonary vein flow and diastolic function were provided in this study. However, in practice, optimal recording of pulmonary vein flow is not easy. No interobserver and intraobserver variations were made in this

5 900 Samad, Olson, Alam September 2005 study. However, these parameters were found to be nonsignificant in a previous study. 13 The lack of prognostic data limits our understanding of the clinical significance of different diastolic dysfunctional patterns. Conclusion The results of our study demonstrate that DTI may enhance the estimates of diastolic function for patients with severely decreased LV systolic function, and help to disclose diastolic dysfunction for patients with a pseudonormal pattern. REFERENCES 1. McDermott MM, Feinglass J, Sy J, Gheorghiade M. Hospitalized congestive heart failure patients with preserved versus abnormal left ventricular systolic function: clinical characteristics and drug therapy. Am J Med 1995;99: Senni M, Tribouilloy CM, Rodeheffer RJ, Steven J, Evans JM, Bailey KR, et al. 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