Echocardiography Versus Right-Sided Heart Catheterization Among Lung Transplantation Candidates

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1 Echocardiography Versus Right-Sided Heart Catheterization Among Lung Transplantation Candidates Itsik Ben-Dor, MD, Mordechai R. Kramer, MD, Avraham Raccah, MD, Zaza Iakobishvilli, MD, David Shitrit, MD, Gideon Sahar, MD, and David Hasdai, MD Department of Cardiology, Pulmonology Institute and Cardiothoracic Surgery, Rabin Medical Center and Tel Aviv University, Israel Background. Right-heart-catheterization and transthoracic echocardiography are routine tests to measure pulmonary artery systolic pressure among lung transplantation candidates. Echocardiography may be as accurate as right-heart-catheterization, without the inherent risks of an invasive test. Methods. We examined the correlation between pulmonary pressures estimated by echocardiography versus right-heart-catheterization among lung transplantation candidates and their correlation to measurements during lung transplantation. Our cohort included all lung transplantation candidates during 1997 through 2004 who initially underwent pulmonary pressure evaluation by right-heart-catheterization and echocardiography, as well as measurements during lung transplantation. Results. Of the 106 candidates, evaluation by transthoracic echocardiography was possible in 79 (74.5%). Median pulmonary systolic pressures by right-heart-catheterization was 44.0 [ ] mm Hg and by echocardiography 40.0 [ ] mm Hg (r 0.80, p < ). In 14 (17.7%) patients the difference between the 2 methods was >20 mm Hg. The median time interval between echocardiography and right-heart-catheterization was 65 [40 155] days. The median value of pulmonary systolic pressure measured during lung transplantation in 44 (70.1%) of 62 patients was 39.5 [ ] mm Hg. The time interval right-heart-catheterization-to-lung transplantation was 143 [87 339] days and echocardiography-to-lung transplantation 229 [ ] days. The correlation between measurements during lung transplantation and initial measurements by rightheart-catheterization and echocardiography were r 0.50 and r 0.31, respectively, with corresponding p values of p and p Conclusions. For lung transplantation candidates and a suitable transthoracic echocardiography estimate of pulmonary systolic pressure, the need for right-heart catheterization, with its inherent risks for complications, may be foregone. The weak correlation between the initial and intraoperative measurements, probably stemming from the significant time interval, suggests that serial measurements may be needed. (Ann Thorac Surg 2006;81: ) 2006 by The Society of Thoracic Surgeons Lung transplantation (LTx) has emerged as a successful therapeutic modality for end-stage pulmonary disease in recent years. Estimating pulmonary artery systolic pressure (PASP) is crucial, because decisions regarding single versus bilateral LTx procedures and the need for cardiopulmonary bypass are often made based on PASP. In the absence of marked pulmonary hypertension, cardiopulmonary bypass can usually be avoided [1]. The current guidelines [2] for the evaluation of LTx candidates recommend an echocardiogram in all LTx candidate in their preoperative evaluation. At many LTx centers, right heart catheterization (RHC) and transthoracic echocardiography (TTE) are routine tests to measure PASP among LTx candidates. Doppler echocardiography is the most reliable noninvasive estimation of Accepted for publication July 22, Address correspondence to Dr Hasdai, Department of Cardiology, Rabin Medical Center, 39 Jabotinsky St, Petah Tikva, Israel 49100; dhasdai@post.tau.ac.il. PASP, by measuring the maximal velocity of the regurgitant jet of tricuspid regurgitation, if the jet can be detected. In patients with end stage lung disease, the ability to detect an adequate tricuspid regurgitant jet may be limited in particular, given the narrow acoustic windows, which stem from hyperinflation or marked respiratory variations in intrathoracic pressure. Indeed, in a recent study [3] the estimation of PASP using TTE was possible in only 44% of LTx candidates. However, others [4 7] have reported rates approaching 66%. RHC assesses hemodynamic parameters accurately, and is not influenced by the above-mentioned technical problems. However, it is an invasive procedure that portends certain rare, yet significant, risks. The aims of our study were to examine the feasibility of TTE for the measurement of PASP among LTx candidates, the correlation between PASP estimate by TTE versus RHC in this cohort, and their correlation to PASP measurements during LTx operation by The Society of Thoracic Surgeons /06/$32.00 Published by Elsevier Inc doi: /j.athoracsur

2 Ann Thorac Surg BEN-DOR ET AL 2006;81: PULMONARY PRESSURES IN LUNG TRANSPLANT CANDIDATES 1057 Table 1. Hemodynamic Variables a Variable Obstructive Lung Disease (N 45) Interstitial Lung Disease (N 51) Others (N 10) All (N 106) TTE PASP 38.0 [ ] 40.5 [ ] 90.0 [ ] 40.0 [ ] Left atrium diameter (mm) 34.0 [ ] 36.0 [ ] 36.0 [ ] 36.0 [ ] Normal systolic LV function (%) 42 (93.3) 47 (92.1) 9 (90.0) 98 (92.4) Tricuspid regurgitation (%) b 17 (37.7) 29 (56.8) 7 (70.0) 53 (50.0) RHC Right atrium A wave 12.5 [ ] 10.0 [ ] 8.0 [ ] 10.0 [ ] Right atrium V wave 12.0 [ ] 9.0 [ ] 8.0 [ ] 10.0 [ ] Right atrium mean pressure 10.0 [ ] 6.0 [ ] 7.5 [ ] 8.0 [ ] Right ventricle systolic pressure 40.0 [ ] 45.0 [ ] 85 [ ] 44.0 [ ] Right ventricle diastolic pressure 12.0 [ ] 10.0 [ ] 10.0 [ ] 10.0 [ ] PASP 40.0 [ ] 45.0 [ ] 77.0 [ ] 44.0 [ ] Pulmonary artery diastolic pressure 20.0 [ ] 18.0 [ ] 30.0 [ ] 20.0 [ ] Mean pulmonary pressure 28.0 [ ] 28.0 [ ] 54.0 [ ] 28.0 [ ] Pulmonary artery wedge pressure A 18.0 [ ] 17.5 [ ] 16.0 [ ] 18.0 [ ] wave Pulmonary artery wedge pressure V 17.0 [ ] 15.5 [ ] 17 [ ] 17.0 [ ] wave Mean pulmonary artery wedge 14.0 [ ] 12.0 [ ] 14.0 [ ] 13.0 [ ] pressure Cardiac output (L/min) 4.4 [ ] 4.8 [ ] 4.1 [ ] 4.4 [ ] Cardiac index (L/min/BSA) 2.6 [ ] 2.6 [ ] 2.3 [ ] 2.6 [ ] Pulmonary vascular resistance (Wood units) 2.6 [ ] 2.6 [ ] 8.7 [ ] 2.7 [ ] a Values are medians [25th to 75th interquartiles] or number (%). b Greater than mild tricuspid regurgitation. BSA body surface area; LV left ventricular; PASP pulmonary artery systolic pressure. Patients and Methods Patients At the time this database was formed, no formal ethics review process was required in our institution. As of June 2005 such a process is prospectively required in our institution. Accordingly, individual consent was waived in our cohort. We performed a thorough retrospective review of the medical records of all LTx candidates at Rabin Medial Center during the years 1997 through 2004 that underwent RHC and TTE during their pre-ltx evaluation. Transthoracic Echocardiogram Doppler tracings and two-dimensional images were obtained from parasternal long-and short-axis, apical fourchamber, and subcostal four-chamber views. TTE were reviewed to assess the pericardium, valvular anatomy and function, and cardiac function. Tricuspid regurgitant flow was identified by color flow Doppler techniques, and continuous wave Doppler measured the maximum jet velocity. Right ventricular systolic pressure was estimated based on the modified Bernoulli equation and was considered to be equal to the PASP in the absence of right ventricular outflow obstruction. Adding the transtricuspid pressure gradient to the mean right atrial pressure, estimated empirically as 10 mm Hg, the PASP was estimated. We chose a constant of 10 mm Hg as an estimate of right atrial pressure, because it has been shown to result in the most accurate prediction of PASP across the whole range of PASP encountered clinically [8]. Right Heart Catheterization RHC was performed with a balloon-tipped, flow-directed pulmonary artery catheter introduced via the femoral vein using the Seldinger technique under local anesthesia (without systemic sedation). We measured right atrial pressures (amplitude of the a and v waves and the mean pressure), right ventricular systolic and diastolic pressures, pulmonary artery (systolic, diastolic and mean) pressures, and pulmonary capillary wedge pressures (a and v waves and the mean pressure). Intraoperative Measurements Of the LTx candidates who underwent LTx, we measured PASP intra-operatively via the right internal jugular or the right subclavian veins using Swan-Ganz catheter with a flow-directed balloon-tipped catheter measuring

3 1058 BEN-DOR ET AL Ann Thorac Surg PULMONARY PRESSURES IN LUNG TRANSPLANT CANDIDATES 2006;81: Fig 1. The correlation between PASP estimated by TTE and measured by RHC based on the different etiologies of lung disease. (PASP pulmonary artery systolic pressure; RHC right heart catheterization; TTE transthoracic echocardiography.) the systolic, diastolic and mean pulmonary artery pressures. The first measurement obtained, usually after general anesthesia was induced, was recorded. Statistical Analysis Statistical analyses were done using SPSS statistical software version 11. Continuous variables are expressed as median (25 th, 75 th interquartiles). Using the Students t-test we assessed differences between continuous variables. Categorical variables were compared using the 2 -test. For examination of patterns of disagreement between two measurements we used the Bland-Altman Plot. Significance was set at p Bivariate correlations were assessed using the bivariate correlation test. Fig 3. The correlation between PASP measured intraoperatively and previously measured by RHC. (PASP pulmonary artery systolic pressure; RHC right heart catheterization.) Results Our cohort included 106 LTx candidates. Their mean age was 57 [53-61] years, of whom were males 70 (66.0%). Their median body mass index was 25.3 [ ] Kg/m 2 and their VO 2 max 8.9 [ ] ml/kg/min. The causes of end-stage lung disease were obstructive lung disease in 45 (42.5%) candidates, interstitial lung disease in 51 Fig 2. Mean ( ) PASP in the sub-groups according to etiology of lung disease and modality of measurement. (PASP pulmonary artery systolic pressure; RHC right heart catheterization; TTE transthoracic echocardiography.) Fig 4. The correlation between PASP measured intraoperatively and previously estimated by TTE. (PASP pulmonary artery systolic pressure; TTE transthoracic echocardiography.)

4 Ann Thorac Surg BEN-DOR ET AL 2006;81: PULMONARY PRESSURES IN LUNG TRANSPLANT CANDIDATES 1059 (48.1%), and other causes in 10 (9.1%) patients (7- pulmonary vascular disease, 2-bronchiectasis, 1-histiocytosis). Of the 106, 62 (58.5%) subsequently underwent LTx. PASP evaluation by TTE was possible in 79 (74.5%), although only half the patients had hemodynamically significant tricuspid regurgitation (Table 1). The estimation of PASP using TTE was achieved less frequently in patients with obstructive lung disease compared with those with interstitial lung disease or other etiologies (29 (64.4%) vs 42 (82.3%) vs 7 (70.0%), respectively), but this difference did not achieve statistical significance (p 0.2). Of the 27 patients without TTE-derived PASP evaluation, only 3 (11.1%) patients had PASP 60 mm Hg during RHC. The hemodynamic parameters measured by TTE and RHC of the whole population and according to the etiology are presented in Table 1. The median time interval between TTE and RHC was 65 [40 155] days. Of note, the median pulmonary vascular resistance, as measured during RHC, was 2.7 Wood units (Table 1), with a good correlation between PASP and pulmonary vascular resistance (r 0.8, p 0.001). Median PASP by RHC was 44.0 [ ] mm Hg and by TTE 40.0 [ ] mm Hg, with a strong correlation between the two modalities (r 0.80, p ) (Fig 1), with a similar trend for all etiologies of pulmonary disease. Using Bland-Altman plots between PASP measurement by RHC and estimated by TEE, only 5 measurements were outside the range of mean difference 2 standard deviations, and the disagreement between the two measurements did not increase as the value of PASP increased. In 14 (17.7%) patients, the difference between the two methods was 20 mm Hg; TTE overestimated PASP compared to RHC in 4 (23.5%) and underestimated PASP in 10 (71.5%). Mean PASPs in the sub-groups according to etiology of lung disease are presented in Fig 2. There was no significant difference between obstructive lung disease and interstitial lung disease in mean PSAP measured by TTE (40.1 mm Hg vs 42.5 mm Hg, p 0.50) or RHC (41.8 mm Hg vs 47.0 mm Hg, p 0.11). The PASP was measured during LTx operation in 44 (70.1) of 62 LTx patients, with a median value of PASP of 39.5 [ ] mm Hg. The time interval RHC-LTx was 143 [87 339] days and TTE-LTx 229 [ ] days. The correlation between PASP measured during LTx and PASP previously measured by RHC and TTE were r 0.50 and r 0.31 respectively, with corresponding p values of p and p 0.07 (Fig 3 and Fig 4, respectively). Comment In our cohort of candidates for LTx, we found a very good correlation between PASP estimated by TTE and measured by RHC. In patients with end-stage lung disease, the efficacy of TTE may be limited by the inability to identify an adequate tricuspid regurgitant jet. In previous studies [3 5, 7] TTE successfully estimated PASP in a proportion of LTx candidates, with a range of 44% to 66%. In our study, PASP evaluation by TTE was possible in 74.5%. These differences may be attributed to the difference in the relative weight of each etiology of lung disease in each study. Among patients with obstructive lung disease, it may be more difficult to obtain acceptable TTE images, as demonstrated in our cohort, and thus the proportion of patients with obstructive lung disease may affect the success rates reported in the different studies. Indeed, Tramarin and colleagues [9] and Bach and colleagues [6] reported only 30% ability to estimate the regurgitant jet in chronic obstructive lung disease, but Laaban and colleagues [10] obtained estimates of PASP in 66%. The estimation of PASP is most crucial among patients with suspected pulmonary hypertension. Patients with pulmonary hypertension frequently have tricuspid regurgitation. Thus, the ability of TTE to measure PASP is much higher in the presence of pulmonary hypertension, and it is unlikely that the diagnosis of pulmonary hypertension will be missed by TTE. The correlation between PASP measured by RHC and estimated by TTE has been evaluated in patients with cardiac disease, and revealed a correlation coefficient of [11 14]. Tramarin and colleagues [9] reported a correlation index of 0.73 between TTE and RHC when using the tricuspid regurgitant jet method in patients with obstructive lung disease. Two previous studies had evaluated this correlation in LTx candidates: Homma and colleagues [4] reported a moderate correlation (r 0.5) in a small group (n 19) of LTx candidates, whereas Arcasoy and colleagues [3] found a good correlation (r 0.69), although 52% of the pressure estimates were found to be inaccurate (more than 10 mm Hg difference compared with measured pressure), mostly due to overestimation. In our study, the correlation was excellent (r 0.8) with only 17.7% pressure difference between the 2 methods being 20 mm Hg, most of them underestimations using TTE. This may be due to inaccuracy in the Doppler measurement, as the direction of flow of the regurgitant tricuspid jet of blood is variable, and even a skilled operator may have difficulty in identify the maximal velocity. However, the differences in the measurements of PASP between the two techniques may also be due to real changes in the systolic pressures between the two tests, especially given the time interval between the two modalities. In primary pulmonary hypertension [15] and other parenchymal lung diseases [16], PASP has been shown to fluctuate widely in a single patient over the course of 6 hours due to spontaneous variability of cardiac output and pulmonary vascular resistance. In addition, in our study we chose a constant of 10 mm Hg as an estimate of right atrial pressure. Some patients may have had higher right atrial pressures that could easily be appreciated by a concomitant physical examination. By adding a higher constant value in those patients, the underestimations of PASP would be reduced, increasing the correlation between TTE and RHC. Based on our results, we propose that in a LTx candidate with a suitable TTE measurement of PASP, RHC be foregone, in the absence of severely elevated PASP.

5 1060 BEN-DOR ET AL Ann Thorac Surg PULMONARY PRESSURES IN LUNG TRANSPLANT CANDIDATES 2006;81: Although RHC can measure other hemodynamic parameters, and may be used to determine the potential reversibility of pulmonary arterial hypertension, most of these measured indices are irrelevant for LTx. In our center and others [3, 4], RHC is used mainly for measuring PASP, and the reversibility of the elevated pulmonary pressures is seldom assessed. In contrast, TTE gives additional information regarding structural and functional cardiac abnormalities that cannot be obtained from RHC and that may influence the candidacy for LTx and the pre- and peri-operative management. Moreover, repeated TTE examinations can be performed, allowing for an analysis of trends in PASP over a long time period. This is the first study that also evaluated the correlation of antecedent PASP estimates or measurements to intraoperative PASP measurements. The intra-operative measurements correlated only fairly with prior TTE estimates of PASP (r 0.31) and RHC measurements of PASP (r 0.5). This may be partially explained by the long time intervals between the antecedent measurements and LTx (229 day and 143 day for TTE and RHC, respectively) and the hemodynamic effect of anesthesia on PASP. In conclusion, among LTx candidates there is a very good correlation between PASP estimated by TTE and measured by RHC. Thus, for LTx candidates and a suitable TTE estimate of PASP, the need for RHC measurement, with its inherent risks for complications, may be foregone. The weaker correlation between the index measurements of PASP and the intra-operative measurements further challenges the need for an invasive evaluation of PASP in this population. However, given the retrospective nature of our study, our findings and recommendations need to be confirmed in larger, prospective studies specifically designed to examine this issue. Until then, it may be prudent to consider the diagnostic modality to assess pulmonary pressure based on an individual basis, taking into account the quality of the echocardiographic examination and the perceived risk of an invasive test. References 1. Arcasoy SM, Kotloff RM. Lung transplantation. N Engl J Med 1999;340: Maurer JR, Frost AE, Estenne M, Higenbottam T, Glanville AR. International guidelines for the selection of lung transplant candidates. The International Society for Heart and Lung Transplantation, the American Thoracic Society, the American Society of Transplant Physicians, the European Respiratory Society. Transplantation 1998;66: Arcasoy SM, Christie JD, Ferrari VA, et al. Echocardiographic assessment of pulmonary hypertension in patients with advanced lung disease. Am J Respir Crit Care Med 2003;167: Homma A, Anzueto A, Peters JI, et al. Pulmonary artery systolic pressures estimated by echocardiogram vs cardiac catheterization in patients awaiting lung transplantation. J Heart Lung Transplant 2001;20: Vigneswaran WT, McDougall JC, Olson LJ, Breen JF, McGregor CG, Rumberger JA. Right ventricular assessment in patients presenting for lung transplantation. Transplantation 1993;55: Bach DS, Curtis JL, Christensen PJ, et al. Preoperative echocardiographic evaluation of patients referred for lung volume reduction surgery. Chest 1998;114: Denton CP, Cailes JB, Phillips GD, Wells AU, Black CM, Bois RM. Comparison of Doppler echocardiography and right heart catheterization to assess pulmonary hypertension in systemic sclerosis. Br J Rheumatol 1997;36: McQuillan BM, Picard MH, Leavitt M, Weyman AE. Clinical correlates and reference intervals for pulmonary artery systolic pressure among echocardiographically normal subjects. Circulation 2001;104: Tramarin R, Torbicki A, Marchandise B, Laaban JP, Morpurgo M. Doppler echocardiographic evaluation of pulmonary artery pressure in chronic obstructive pulmonary disease. A European multicentre study. Working Group on Noninvasive Evaluation of Pulmonary Artery Pressure. European Office of the World Health Organization, Copenhagen. Eur Heart J 1991;12: Laaban JP, Diebold B, Zelinski R, Lafay M, Raffoul H, Rochemaure J. Noninvasive estimation of systolic pulmonary artery pressure using Doppler echocardiography in patients with chronic obstructive pulmonary disease. Chest 1989;96: Berger M, Haimowitz A, Van Tosh A, Berdoff RL, Goldberg E. Quantitative assessment of pulmonary hypertension in patients with tricuspid regurgitation using continuous wave Doppler ultrasound. J Am Coll Cardiol 1985;6: Currie PJ, Seward JB, Chan KL, et al. Continuous wave Doppler determination of right ventricular pressure: a simultaneous Doppler-catheterization study in 127 patients. J Am Coll Cardiol 1985;6: Skjaerpe T, Hatle L. Noninvasive estimation of systolic pressure in the right ventricle in patients with tricuspid regurgitation. Eur Heart J 1986;7: Yock PG, Popp RL. Noninvasive estimation of right ventricular systolic pressure by Doppler ultrasound in patients with tricuspid regurgitation. Circulation 1984;70: Rich S, D Alonzo GE, Dantzker DR, Levy PS. Magnitude and implications of spontaneous hemodynamic variability in primary pulmonary hypertension. Am J Cardiol 1985;55: Raeside DA, Chalmers G, Clelland J, Madhok R, Peacock AJ. Pulmonary artery pressure variation in patients with connective tissue disease: 24 hour ambulatory pulmonary artery pressure monitoring. Thorax 1998;53:

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