Little is known about the degree and time course of

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1 Differential Changes in Regional Right Ventricular Function Before and After a Bilateral Lung Transplantation: An Ultrasonic Strain and Strain Rate Study Virginija Dambrauskaite, MD, Lieven Herbots, MD, Piet Claus, PhD, Geert Verleden, MD, Dirk Van Raemdonck, MD, Marion Delcroix, MD, PhD, and George R. Sutherland, FESC, Leuven, Belgium The evaluation of regional right ventricular function by ultrasound remains a challenge. This case report demonstrates the potential value of the new cardiac deformation indices, strain and strain rate imaging, in determining the differing regional abnormalities in longitudinal right ventricular function before and after bilateral lung transplantation. These indices were measured in a patient with severe right ventricular dysfunction as a result of primary pulmonary hypertension. (J Am Soc Echocardiogr 2003;16: ) Little is known about the degree and time course of recovery in regional function (RF) of a failing right ventricle (RV) after lung transplantation (LT). The recent introduction of ultrasound methods to measure the regional myocardial deformation parameters, strain rate (SR) and strain ( ), potentially allows the measurement of such changes. 1,2 This article demonstrates: (1) how these indices provide new insights into abnormalities in the free wall (FW) and interventricular septum (IVS) RF in a failing RV; and (2) that recovery in function may be heterogeneous in morphologically different portions of the RV after bilateral LT. CASE REPORT In 1998, a 38-year-old man was given the diagnosis of primary pulmonary hypertension. During 3 years, his disease progressed relentlessly despite optimal medical therapy. This deterioration was associated with the development of progressive RV failure. Before LT, right heart catheterization revealed an increased mean pulmonary artery pressure of 54 mm Hg and a pulmonary vascular From the Departments of Cardiology, the Department of Pulmonology (G.V., M.D.), and the Department of Thoracic Surgery (D.V.R.), University Hospital Gasthuisberg. Reprint requests: George R. Sutherland, FESC, University Hospital Gasthuisberg, Department of Cardiology, Herestraat 49, B-3000, Leuven, Belgium. ( George.Sutherland@uz. kuleuven.ac.be). Copyright 2003 by the American Society of Echocardiography /2003/$ doi: /s (03) resistance index of 28 mm Hg/L 1 /min/m 2. After successful bilateral LT in 2001, his immediate clinical course was uncomplicated. Pretransplant Echocardiography Transthoracic echocardiography showed a severely dilated, hypertrophied, and hypocontractile RV; a moderately dilated right atrium (Figure 1, A); mild tricuspid valve regurgitation; and an increased pulmonary artery peak systolic (ps) pressure (105 mm Hg). There was the typical marked paradoxical IVS motion as a result of the RV pressure overload. A color Doppler myocardial velocity imaging study demonstrated reduced regional ps longitudinal velocities in the RV basal and apical segments of the FW (basal 2.8 cm/s, apical 3.6 cm/s) (Figure 2). However, ps velocities in the 3 segments of IVS were borderline normal (basal 4.0 cm/s, mid 3.2 cm/s, apical 2.1 cm/s). Subsequent offline analysis of the velocity data sets was performed using dedicated software (Speqle 4, KU, Leuven, Belgium) to derive regional SR/ curves. 1 The timing of the pulmonary and tricuspid valve opening and closure click was imported into the SR/ curves from pulsed Doppler blood pool tracings. The resultant deformation curves showed very abnormal longitudinal function in the RV FW (ps SR in the basal segment was 0.53 seconds 1 and ps 3%; in the apical 0.13 seconds 1 and 2%, respectively) (Figure 3, A). For IVS the ps SR was reduced in the basal ( 0.9 seconds 1 ) and apical ( 0.9 seconds 1 ) segments and normal in the mid segment ( 1.8 seconds 1 ) (Figure 3, B). Shortening was reduced in the basal and apical segments (ps 7% and 8%, respectively) and normal in the middle segment ( 24%). 432

2 Volume 16 Number 5 Dambrauskaite et al 433 Figure 1 Two-dimensional apical 4-chamber view recorded: (A) before lung transplantation (LT) (right ventricular [RV] longitudinal dimension [ld] 7.3 cm, transverse dimension [td] 5.8 cm, right atrial [RA] ld 6.4 cm, RAtd 5.9 cm); (C) 6 weeks after LT (RVld 7.0 cm, RVtd 2.9 cm, RAld 5.7 cm, RAtd 3.3 cm); and (E) 12 weeks after LT (RVld 6.6 cm, RVtd 2.0 cm, RAld 3.7 cm, RAtd 2.7 cm). Parasternal M-mode long-axis view recorded: (B) before LT (RV diastolic diameter [dd] 6.33 cm, RV systolic diameter [sd] 5.3 cm, RV free wall (FW) 0.8 cm), note paradoxical radial septal motion; (D) 6 weeks after LT (RVdd 2.6 cm, RVsd 1.9 cm, RV FW 0.7 cm), hypocinetic septum; and (F) 12 weeks after LT. Improved radial thickening of septum (RVdd 1.9 cm, RVsd 1.3 cm, RV FW 0.8 cm). There was no change at 25 weeks follow up study. LV, Left ventricle. Echocardiography Six Weeks After LT Transthoracic echocardiography 6 weeks after bilateral LT showed a significant reduction in RV size and a marked change in RV geometry (Figure 1, C). Tricuspid valve regurgitation remained minimal; pulmonary artery ps pressure was estimated at 28 mm Hg. The paradoxical IVS motion had disappeared. A color Doppler myocardial imaging velocity study showed a slight increase in (but still low) RV FW ps longitudinal velocities (Figure 2). However, there was a marked improvement in regional RV FW deformation in the apical trabecular component which now had normal systolic shortening ( 1.9 seconds 1 and 19%). Deformation of the smooth inlet basal segment remained abnormal (1.1 seconds 1 and 8%). In contrast, deformation of the basal segment of IVS was unchanged ( 0.9 seconds 1 and 7%); but the middle segment now showed a reduction in ps SR ( 1.0 seconds 1 ) and ( 24%) values. In the apical segment systolic deformation had improved ( 18%), but not ps SR ( 1.0 seconds 1 ). There were no significant changes in regional velocity values (Figure 2). Echocardiography Twelve Weeks After LT By 12 weeks there was a marked improvement in IVS radial thickening in the basal and middle segments (Figure 1, F). This was mirrored by an increase in longitudinal SR and values (basal segment 2.1 seconds 1 and 26%; middle 1.4 seconds 1 and 22%). The RV FW apical segment continued to maintain normal deformation values ( 1.8 seconds 1 and 26%) whereas deformation in the

3 434 Dambrauskaite et al May 2003 Figure 2 Maximal systolic velocity, strain rate, and strain values in basal (bas) and apical (api) segments of right ventricular (RV) free wall and bas, middle (mid), and api segments of septum pretransplantation and 6 weeks (w) and 12 w posttransplantation compared with normal reference values ( SD). 3 basal segment remained abnormal ( 0.7 seconds 1 and 13%). Echocardiography Twenty-five Weeks After LT The findings at 25 weeks did not differ significantly from those at 12 weeks. Deformation in the basal FW segment remained abnormal (SR 1.1 seconds 1, 14%) whereas that in the apical segment was normal. DISCUSSION This case report describes the potential clinical value of using the new ultrasound-based quantitative regional deformation indices in studying sequential changes in RV RF before and after bilateral LT. The underlying background for the possible differences in the response of the different segments most probably is a result of the complex anatomy of the RV. The RV is comprised of 3 morphologically distinct units: a smooth inlet portion, a more trabeculated apical portion, and a tubular infundibulum. The inlet and trabecular portions together provide the pump function. As a result of their differing muscular arrangements, each could respond differently to both changes in preload and afterload, and fiber stretch as a result of dilatation. The pretransplantation 2-dimensional echocardiography showed a markedly dilated hypertrophied RV with greatly reduced FW systolic function and marked paradoxical IVS motion as a result of pressure overload. Pretransplant long-axis deformation imaging of the 2 morphologically distinct portions (smooth inlet and trabecular apex) of the RV FW showed that the basal FW lengthened (as opposed to the normal shortening) in systole, and the apical trabecular portion showed only minimal shortening. Neither was contributing significantly to RV ejection. In contrast, IVS was the only part of RV that was shortening significantly and, thus, by being driven like a piston into the RV cavity by the left ventricle, was the major factor producing RV ejection. After acute RV afterload reduction after bilateral LT, RV FW stress fell acutely, thus, allowing the expression of any residual intramural contractile function as an increase in systolic deformation.

4 Volume 16 Number 5 Dambrauskaite et al 435 Figure 3 A, Strain curves from right ventricular (RV) free wall (FW) basal and apical segments before and after lung transplantation (LT). Note markedly abnormal deformation in both FW segments with systolic lengthening in basal segment and only minimal shortening in apical segment (negative strain value). After LT early recovery in regional deformation in apical segment was observed. Basal segment remained abnormal even after 6 months follow-up. B, Strain curves from basal, middle, and apical segments of interventricular septum (IVS) before and after LT. Pretransplantation, shortening is reduced in basal and apical segments but is normal in middle segment. Six weeks posttransplantation apical segment has normal systolic deformation, mid segment has reduced peak systolic strain, and basal segment still displays markedly abnormal deformation. Plots on bottom show deformation pattern from a normal IVS. AVc, Aortic valve closure; MVo, mitral valve opening; PVc, pulmonary valve closure; TVo, tricuspid valve opening. However, the degree of recovery in longitudinal function differed for each of the morphologically different RV FW segments. Systolic longitudinal deformation indices in the apical RV segment returned to near normal (Figure 3, A) by 6 weeks whereas systolic deformation in the basal segment had not recovered even after 6 months. The above finding would suggest that recovery of contractile function occurred earlier in the trabecular portion of the RV than in the smooth-wall inlet portion. A similar nonhomogeneity in longitudinal RF of the RV FW had already been reported by Fayad et al 4 in a 1-dimensional magnetic resonance imaging myocardial-tagging study comparing healthy subjects with those who had chronic pulmonary hypertension. In the latter group, there was reduced regional long-axis shortening observed in all segments but function was best preserved in the apical trabecular part of the RV FW and most decreased in the RV outflow tract. In our case this differential recovery in RF within the RV FW could not be detected in changes in regional velocity profiles. In conclusion, SR and indices could provide new, clinically relevant information on regional changes in RV function in failing RVs and add to the understanding how the differing structural components of the RV recover after LT.

5 436 Dambrauskaite et al May 2003 REFERENCES 1. D hooge J, Heimdal A, Jamal F, Kukulski T, Bijnens B, Rademakers F, et al. Regional strain and strain rate measurements by cardiac ultrasound: principles, implementation and limitations. Eur J Echocardiogr 2000;1: Heimdal A, Stoylen A, Torp H, Skjaerpe T. Real-time strain rate imaging of the left ventricle by ultrasound. J Am Soc Echocardiogr 1998;11: Kowalski M, Kukulski T, Jamal F, D hooge J, Weidemann F, Rademakers F, et al. Can natural strain and strain rate quantify regional myocardial deformation? A study in healthy subjects. Ultrasound Med Biol 2001;27: Fayad ZA, Ferrari VA, Kraitchman DL, Young AA, Palevsky HI, Bloomgarden DC, et al. Right ventricular regional function using MR tagging: normals versus chronic pulmonary hypertension. Magn Reson Med 1998;39: