Eur J Echocardiography (2007) 8, 252e258 Potential use of isovolumic contraction velocity in assessment of left ventricular contractility in man: A simultaneous pulsed Doppler tissue imaging and cardiac catheterization study Per Lindqvist a, Anders Waldenström a, Gerhard Wikström b, Elsadig Kazzam c, * a Department of Cardiology, Heart Centre, University Hospital, Umeå, Sweden b Department of Cardiology, Uppsala University Hospital, Uppsala, Sweden c Department of Internal Medicine, Faculty of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al-Ain, United Arab Emirates Received 23 November 2005; received in revised form 6 April 2006; accepted 23 April 2006 Available online 19 June 2006 KEYWORDS Cardiac catheterization; Doppler tissue imaging; Isovolumic contraction velocity; Left ventricular contractility Abstract Aims: Echocardiographic techniques have so far provided suboptimal estimates of myocardial contractility in humans. Longitudinal myocardial motion during the isovolumic contraction (IVC) phase, measured by colour tissue Doppler imaging (TDI), has recently been shown in experimental animal models to reflect the state of myocardial contractility. The aim of the present study was to investigate the relationship between left ventricular (LV) isovolumic contraction velocities (IVCv) using pulsed Doppler tissue imaging (DTI) and global LV contractility as measured during cardiac catheterization. Methods and results: Cardiac catheterization and pulsed DTI were simultaneously performed in 16 consecutive patients (13 males, mean age 55 10 years) with a variety of cardiac diseases. Relationships between the peak positive IVCv as measured at basal levels of the lateral, septal, anterior and posterior walls and the first derivative of LV pressure (þdp/dt max ), were investigated. Peak IVCv measurements were obtainable in 81e100% of the four LV wall segments. Statistically significant linear relationships were found between IVCv and þdp/dt max at the lateral (r ¼ 0.58, P < 0.05), septal (r ¼ 0.66, P < 0.01), anterior (r ¼ 0.73, P < 0.01) and posterior (r ¼ 0.81, P < 0.001) segments of the LV. Conclusion: IVCv of the basal four LV walls correlates strongly with peak þdp/dt. IVCv is a readily obtainable non-invasive parameter, which correlates with the classical * Corresponding author. Tel.: þ971 3 713 7654; fax: þ971 3 767 2995. E-mail address: kazzam@uaeu.ac.ae (E. Kazzam). 1525-2167/$32 ª 2006 The European Society of Cardiology. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.euje.2006.04.006
Isovolumic contraction velocity and ventricular state of contractility 253 invasive measurement of global LV contractility. It appears likely that there are regional differences in wall motion when DTI is used to determine state of LV contractility. ª 2006 The European Society of Cardiology. Published by Elsevier Ltd. All rights reserved. Introduction In common clinical practice, 2D and M-mode echocardiography provide qualitative and semiquantitative measurements of ventricular systolic function. Such data are generated from the ejection phase which is load dependent and therefore not ideal for the determination of ventricular contractility. 1 However, the load independent state of ventricular contractility can only be assessed by high temporal resolution techniques timed to record during the isovolumic contraction (IVC) period which normally occurs over a brief time interval (approximately 80 ms), 2 although this may vary in disease states. 3 Furthermore, wall motion during IVC shows a biphasic pattern in normals 4 but this may be altered when ventricular contractility is impaired. 5 Currently, tissue Doppler imaging (TDI) provides information regarding regional myocardial function with high spatial and temporal resolution. 6 Vogel et al. showed that myocardial acceleration during IVC was a sensitive marker of the global state of contractility and was not particularly dependent on pre- or afterload. 7 A number of other studies have supported this observation. 5,8,9 More recently however, Lyseggen et al. showed that there was no consistent relationship between peak IVC acceleration and regional myocardial contractility as measured by sonomicrometry. 1 All of the above studies were carried out in animal models and have not been validated in healthy human volunteers or in patients with diseased ventricles. 10 Therefore, the aim of the present study was to investigate the relationship between myocardial peak isovolumic contraction velocity and invasive indices of global left ventricular contractility in a consecutive series of patients with a variety of cardiac diseases by using simultaneous DTI and cardiac catheterization measurements. Material and methods Study population Sixteen consecutive patients (13 of whom were males) referred for routine cardiac catheterization were studied. Their mean age was 55 10 (SD; range 35e70) years. Two patients had hypertrophic cardiomyopathy, 5 dilated cardiomyopathy, 4 heart transplantations, 1 atrial septum defect, 1 primary pulmonary hypertension, 1 combined mitral and tricuspid valve disease, and 2 ischemic heart diseases (Table 1). Ten patients were in sinus rhythm, 4 had atrial fibrillation or atrial flutter, 1 had a pacemaker implanted and 1 had left bundle branch block. All patients gave written consent to participate in the study, which was approved by the local ethics committee. Echocardiographic examination Doppler echocardiographic examinations were performed simultaneously with cardiac catheterization with patients lying in the supine position. All patients were stable haemodynamically. All tracings were recorded during expiration. A commercially available ultrasound system (HP, Sonos 5500, Philips, Andover, MA, USA) equipped with a multi frequency phased array transducer and pulsed Doppler tissue imaging technique was used. Parasternal and apical views were obtained according to the recommendations of the American Society of Echocardiography. 11 All recordings were made with a simultaneous superimposed ECG and phonocardiogram (PCG). 12,13 Recordings were made at a sweep speed of 50 and 100 mm/s and stored on magnetic optical discs. Values are presented as means from three consecutive cardiac cycles. Peak myocardial velocities were recorded using the pulsed Doppler tissue imaging technique. The sample volume was 6 mm. The acoustic power and filter frequencies were adjusted and optimized for detecting myocardial velocities. Cardiac catheterization One experienced investigator (G.W.) performed all the cardiac catheterization studies. Briefly, retrograde left ventricular catheterization was performed via the brachial or radial artery (Becton Dickinson Criticath SP5 107 HTD catheter). Pressures were registered using a Cathcor â system 3.3 (Siemens Elema AB, Electromedical Systems Divisions, Solna, Sweden).
254 P. Lindqvist et al. Table 1 Patient characteristics Patient Cardiac disease Age (years) HR (b/m) SBP (mmhg) DBP (mmhg) Gender NYHA LVEF (%) N1 DCM 60 62 118 73 M 3 26 N2 DCM 50 72 120 85 F 3 38 N3 DCM 35 86 110 70 F 3 44 N4 XP 64 68 165 92 M 1 e N5 XP 44 78 135 90 M 2 60 N6 ASD 65 80 155 90 F 2 e N7 MR þ TR 58 95 140 75 M 2 47 N8 DCM 43 55 90 60 M 3 40 N9 PPHT 70 72 190 90 M 2 e N10 HCM 57 78 125 90 M 3 e N11 DCM 63 57 105 65 M 3 20 N12 XP 59 80 120 90 M 1 42 N13 HCM 68 83 150 80 M 3 49 N14 IHD 45 48 97 75 M 2 46 N15 IHD 53 53 110 70 M 4 31 N16 XP 55 56 190 95 M 2 e DCM, dilated cardiomyopathy; XP, heart transplantation; ASD, atrial septum defect; MR, mitral regurgitation; TR, tricuspid regurgitation; PPHT, primary pulmonary hypertension; HCM, hypertrophic cardiomyopathy; IHD, ischemic heart disease; b/m, beats per minute; HR, heart rate; SBP, systolic blood pressure; DBP, diastolic blood pressure; NYHA, New York Heart Association class; LVEF, left ventricular ejection fraction. Measurements The following measurements were made from the 2D and M-mode echocardiography recordings: left ventricular (LV) internal diameter at end-diastole (onset of the Q wave), and fractional shortening as recommended by the American Society of Echocardiography. 14 Using 2D echocardiography, ejection fraction was derived from Simpson s modified single plane method using a 4-chamber view. Left ventricular long axis motion was measured from the Q-wave on the ECG to the highest amplitude of the second heart sound from the PCG at lateral, septal, anterior and posterior basal segments of the left ventricle. 15 Velocity time integrals were measured at the LV outflow tract. All catheter measurements of þdp/dt max were compared and correlated with indices of the ejection phase of left ventricular systolic function. Doppler tissue imaging was used to measure left ventricular longitudinal myocardial segmental function. 16,17 The systolic and isovolumic contraction peak positive velocities were measured at left lateral, septal, anterior and posterior basal levels of the left ventricle (Fig. 1). Statistical analysis A commercially available statistical program (SPSS 10.1 and 11.1) was used. All data are presented as mean SD. Spearman s correlation and linear regression analyses were utilized to display relationships. A P value of less then 0.05 was considered statistically significant. Results General characteristics of the study population The patient s characteristics are presented in Table 1. Left ventricular regional myocardial functional and global left ventricular contractility A significant positive relationship was found between þdp/dt max and peak positive isovolumic contraction velocity at all four left ventricular segments: basal lateral (r ¼ 0.58, P < 0.05), septal (r ¼ 0.66, P < 0.01), anterior (r ¼ 0.73, P < 0.01) and basal posterior segments (r ¼ 0.81, P < 0.001) (Fig. 2). We found a significant positive correlation between all single measurements of IVCv and þdp/ dt max at all segments (r ¼ 0.66, P < 0.001) (Fig. 3). We also found a robust correlation between þdp/dt max and systolic peak positive velocities at the posterior segments (r ¼ 0.72, P < 0.01).
Isovolumic contraction velocity and ventricular state of contractility 255 81% for lateral, 100% for septal, 88% for anterior and 94% for posterior segments. Pressure Ejection IVCv Sv Discussion The main finding of the present study Tissue Velocity IVCt IVRt Ev However, correlation between IVCv and SV was seen only at the posterior segment (r ¼ 0.63, P < 0.05). Left ventricular systolic function and global left ventricular contractility A statistically significant though weak correlation was noted between þdp/dt max and LV fractional shortening (r ¼ 0.59, P < 0.05). There was no significant relationship between þdp/dt max and long-axis motion at any segment, left ventricular outflow velocity time integral or LV ejection fraction. Peak positive isovolumic contraction velocity and its relation to indices of pre- and afterload IVCv did not correlate significantly with either left ventricular end diastolic pressure or systemic vascular resistance at any of the left ventricular segments. Reproducibility and feasibility LV filling Reproducibility as coefficient of variation for interobserver variability was found to be 6% for lateral, 6% for septal, 9% for anterior and 7% for posterior walls. Intra-observer variability was 3% for lateral, 3% for septal, 4% for anterior and 2% for posterior walls. Feasibility of measurements was found to be Av ECG Figure 1 Schematic relation between Doppler tissue imaging tracings and invasive haemodynamic variables. ECG, electrocardiogram; Sv, peak systolic myocardial velocity; Ev, peak early diastolic myocardial velocity; Av, peak late atrial myocardial velocity; IVCt, isovolumic contraction time; IVRt, isovolumic relaxation time; LV, left ventricular. We have demonstrated for the first time in patients that peak positive myocardial velocity of the left ventricular free walls, measured by pulsed Doppler tissue imaging during the IVC phase, correlates well with left ventricular global contractility. These observations have the potential to be of clinical value since disturbances of myocardial motion occur predominantly during the isovolumic phases, (i.e. during contraction and/or relaxation), and such non-invasive recordings might therefore be a sensitive marker of myocardial dysfunction. 5 Left ventricular contractility Myocardial systolic function depends upon the interaction of myocardial contractility, preload and afterload. Myocardial contractility refers to the property of the heart muscle that accounts for alternations in performance induced by biochemical and hormonal changes and has classically been regarded as independent of preload and afterload. Isovolumic indices such as the maximum rate of raise LV systolic pressure, dp/dt, has been used as a measure of myocardial contractility. In clinical practice this is difficult since it require simultaneous recording of ventricular pressure and volume. In our study we found no relationship between IVCv to either end-diastolic pressure or systemic vascular resistance. In an animal study, Vogel et al. showed that IVC acceleration is a reliable measurement of right ventricular contractility and is relatively load independent. 7 These authors concluded that IVC acceleration was a more sensitive marker of contractility than IVC peak positive velocity. We found it difficult to measure accurately the acceleration of isovolumic contraction velocity as this was commonly multidirectional which supports the anatomical explanations of Buckberg. 18 Therefore, we propose that the peak positive isovolumic contraction velocity may be the most appropriate measure of contractility in humans. Recently, Hashimoto et al. used a computerized method to measure acceleration 9 and this approach might improve the accuracy of such measurements.
256 P. Lindqvist et al. dpdt = 470,01 + 243,71 * ivcvsep R-Square = 0,48 r=0.66, p<0.01 r=0.58, p<0.05 dpdt = 920,16 + 136,35 * ivcvlat R-Square = 0,26 4,00 8,00 12,00 IVCv lateral (cm/s) 2,00 4,00 6,00 8,00 IVCv septal (cm/s) dpdt = 633,36 + 208,79 * ivcvant R-Square = 0,45 r=0.73, p<0.01 dpdt = 196,19 + 253,49 * ivcvpost R-Square = 0,69 r=0.81, p<0.00 1 2,00 4,00 6,00 8,00 1 IVCv anterior (cm/s) 2,50 5,00 7,50 1 IVCv posterior (cm/s) Figure 2 segments. Correlation between positive peak isovolumic contraction velocity and þdp/dt at the four left ventricular Isovolumic contraction velocity In the present study and in clinical setting, we demonstrate the feasibility and reproducibility of IVC peak positive velocities for measurement of the left ventricular contractile state, which was found to be significant in particular for the septal and posterior segments. Differences in regional contractility have previously been shown. 9 The reason why the relationship between IVCv and þdp/dt varied according to the ventricular segment might be explained by segmental differences of the biphasic positive and negative IVCv, which is hypothesized to be due to asynchronous deformation patterns of subendocardial and subepicardial layers. 4,19 We measured only peak positive velocities and the results might have differed had we measured both positive and negative velocities. Recent studies have shown that myocardial acceleration during IVC did not correlate with the state of contractility. 1 However, that study compared acceleration during IVC with regional contractility where as we measured global contractility. It is important to mention that we did not perform visual assessment of regional wall motion abnormalities in the studied population (normal; hypokinetic, akinetic, dyskinetic). We believe that wall motion score is strongly limited by a low frame rate (20e30 frames/s), which limits the sensitivity. In contrast pulsed Doppler tissue imaging is preferable in wall motion analysis because it is related to a very high frame rate (>200 frames/s).
Isovolumic contraction velocity and ventricular state of contractility 257 alldpdt = 605,35 + 200,59 * allivcv R-Square = 0,44 tissue imaging indices may complete the conventional analysis of the left ventricular function in different cardiac diseases. We propose IVCv as an additional non-invasive tool to be taken into consideration for complete assessment of left ventricular contractility. However, the usefulness of IVCv in the early detection of myocardial dysfunction needs to be clarified. Conclusion 4,00 8,00 12,00 IVCv (cm/s) r=0.66, p<0.001 Figure 3 Correlation between all single measurements of positive peak isovolumic contraction velocity and þdp/dt at all left ventricular segments. Left ventricular contractility can be determined by measuring peak positive isovolumic contraction velocity, which is relatively load independent. The positive IVCv is a readily obtainable, noninvasive parameter. It seems that there are regional differences in wall motion during IVCv when Doppler tissue imaging is used to determine the state of LV contractility. Study limitations The study has a number of limitations: 1. We acknowledged that a relatively small number of patients were investigated and confirmatory data is needed. Nevertheless, we were able to disclose statistically significant relationships between peak positive IVC v and global LV contractility. Also our study population was heterogeneous; it would have been better if our patient group had been homogeneous. 2. We did not measure myocardial acceleration during IVC and we measured only the peak positive velocity during IVC. It may have been more accurate to measure both positive and negative velocities and this again requires formal assessment. 3. Four of our patients had atrial fibrillation or flutter so the mean of three beats is suboptimal and at least six consecutive beats should have been averaged. 4. Finally, in this study we used a thermo-dilution catheter, whereas a tip manometer catheter with higher frequency responses would be expected to have strengthened the results. The latter premise, however, needs to be assessed formally. Clinical implications of our study Doppler tissue imaging could provide a useful tool for early detection of cardiac dysfunction. Doppler Acknowledgements This study was supported by, the Swedish Heart and Lung Foundation, The Heart Foundation of Northern Sweden and Uppsala Academic Hospital Research Fond. Ulla-Marie Andersson, Mona Andrén, Karin Fagerbrink, Kjell Karlström, Berit Lowén and Elisabeth Lindström are acknowledged for skilful assistance during the catheterization procedures. Johan Landelius was of invaluable support. References 1. Lyseggen E, Rabben SI, Skulstad H, Urheim S, Risoe C, Smiseth OA. Myocardial acceleration during isovolumic contraction: relationship to contractility. Circulation 2005;111(11):1362e9. 2. Naqvi TZ, Neyman G, Broyde A, Mustafa J, Siegel RJ. Comparison of myocardial tissue Doppler with transmitral flow Doppler in left ventricular hypertrophy. J Am Soc Echocardiogr 2001;14(12):1153e60. 3. Moreno R, Zamorano J, Almeria C, Perez-Gonzalez JA, Mataix L, et al. Isovolumic contraction time by pulsedwave Doppler tissue imaging in aortic stenosis. Eur J Echocardiogr 2003;4(4):279e85. 4. Lind B, Nowak J, Cain P, Quintana M, Brodin LA. Left ventricular isovolumic velocity and duration variables calculated from colour-coded myocardial velocity images in normal individuals. Eur J Echocardiogr 2004;5(4):284e93. 5. Edvardsen T, Urheim S, Skulstad H, Steine K, Ihlen H, Smiseth OA. Quantification of left ventricular systolic function by tissue Doppler echocardiography: added value of measuring pre- and postejection velocities in ischemic myocardium. Circulation 2002;105(17):2071e7.
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