A Simple Method for Noninvasive Estimation of Pulmonary Vascular Resistance

Transcription

1 Journal of the American College of Cardiology Vol. 41, No. 6, by the American College of Cardiology Foundation ISSN /03/$30.00 Published by Elsevier Science Inc. doi: /s (02)02973-x A Simple Method for Noninvasive Estimation of Pulmonary Vascular Resistance Pulmonary Hypertension Amr E. Abbas, MD,* F. David Fortuin, MD,* Nelson B. Schiller, MD, FACC, Christopher P. Appleton, MD, FACC,* Carlos A. Moreno, BS,* Steven J. Lester, MD, FACC* San Francisco, California; and Scottsdale, Arizona OBJECTIVES BACKGROUND METHODS We sought to test whether the ratio of peak tricuspid regurgitant velocity (TRV, ms) to the right ventricular outflow tract time-velocity integral (TVI RVOT, cm) obtained by Doppler echocardiography (TRV/TVI RVOT ) provides a clinically reliable method to determine pulmonary vascular resistance (PVR). Pulmonary vascular resistance is an important hemodynamic variable used in the management of patients with cardiovascular and pulmonary disease. Right-heart catheterization, with its associated disadvantages, is required to determine PVR. However, a reliable noninvasive method is unavailable. Simultaneous Doppler echocardiographic examination and right-heart catheterization were performed in 44 patients. The ratio of TRV/TVI RVOT was then correlated with invasive PVR measurements using regression analysis. An equation was modeled to calculate PVR in Wood units (WU) using echocardiography, and the results were compared with invasive PVR measurements using the Bland-Altman analysis. Using receiver-operating characteristics curve analysis, a cutoff value for the Doppler equation was generated to determine PVR 2WU. RESULTS As calculated by Doppler echocardiography, TRV/TVI RVOT correlated well (r 0.929, 95% confidence interval 0.87 to 0.96) with invasive PVR measurements. The Bland-Altman analysis between PVR obtained invasively and that by echocardiography, using the equation: PVR TRV/TVI RVOT , showed satisfactory limits of agreement (mean ). A TRV/TVI RVOT cutoff value of had a sensitivity of 77% and a specificity of 81% to determine PVR 2WU. CONCLUSIONS Doppler echocardiography may provide a reliable, noninvasive method to determine PVR. (J Am Coll Cardiol 2003;41:1021 7) 2003 by the American College of Cardiology Foundation Pulmonary vascular resistance (PVR) is a hemodynamic variable that contributes to the management of patients with advanced cardiovascular and pulmonary conditions. It is used to evaluate the response to pharmacologic therapy in patients with congestive heart failure (1). Also, PVR is an essential component of heart- and liver- transplant candidate evaluation (2) and in predicting both early and late clinical outcomes (3,4). Moreover, PVR is an important variable in deciding the surgical outcome of patients with congenital heart disease (5). Pulmonary vascular resistance is calculated invasively by the ratio of transpulmonary pressure gradient ( p) to transpulmonary flow (Qp) (6). Doppler echocardiography has significantly impacted clinical medicine by its ability to determine intracardiac hemodynamics noninvasively. Since flow and pressure variables can be measured, we hypothesized that a measure of PVR might be accurately obtained by Doppler-derived variables. From the *Division of Cardiovascular Diseases, Mayo Clinic, Scottsdale, Arizona; and the Division of Cardiology, University of California, San Francisco, California. Manuscript received June 20, 2002; revised manuscript received October 15, 2002, accepted November 11, METHODS This study was approved by the Institutional Review Board. A sample of 44 patients who had a pulmonary artery catheter in place was evaluated. Each subject provided written, informed consent. The patients demographic and clinical characteristics are shown in Table 1. Doppler and invasive measurements were obtained within 45 min of each other. Tricuspid regurgitation grade 2, as determined by Doppler echocardiography, was exclusionary. Invasive measurements. A Swan-Ganz catheter was used for hemodynamic measurements. Pulmonary capillary wedge pressure (PCWP), pulmonary artery systolic pressure (PASP), pulmonary artery diastolic pressure, and mean pulmonary artery pressure (MPAP) were measured. Cardiac output was calculated by thermodilution as a mean of three consecutive measurements not varying by more than 10%. The PVR in Wood units (WU) was calculated using the equation: PVR MPAP PCWP/cardiac output Doppler measurements. Doppler echocardiography was performed using the GE Vivid FiVe (GEMS, Milwaukee,

2 1022 Abbas et al. JACC Vol. 41, No. 6, 2003 Doppler Evaluation of PVR March 19, 2003: Abbreviations and Acronyms CI confidence interval ICC intraclass correlation coefficient MPAP mean pulmonary artery pressure PASP pulmonary artery systolic pressure PCWP pulmonary capillary wedge pressure PVR pulmonary vascular resistance PVR CATH invasive pulmonary vascular resistance PVR ECHO pulmonary vascular resistance calculated by echocardiography Qp transpulmonary flow p transpulmonary pressure gradient RAP right atrial pressure TRV peak tricuspid regurgitant velocity TVI RVOT right ventricular outflow tract time-velocity integral WU Wood units Wisconsin) or Acuson Sequoia (Acuson, Mountain View, California) ultrasound systems. The right ventricular outflow tract time-velocity integral (TVI RVOT ) (cm) was obtained by placing a 1- to 2-mm pulsed wave Doppler sample volume in the proximal right ventricular outflow tract just within the pulmonary valve when imaged from the parasternal short-axis view. The sample volume was placed so that the closing but not opening click of the pulmonary valve was visualized. Pulsed wave Doppler was used rather than continuous wave Doppler to eliminate cases with increased pulmonary velocities secondary to either pulmonary valve or peripheral pulmonary artery stenosis. Continuous wave Doppler was used to determine the Table 1. Clinical and Demographic Characteristics of the Patients Characteristics Findings Gender (M/F) 32/12 Mean age (range) in yrs 67 (47 90) Mean ejection fraction (range) (%) 54 (20 75) Mean of the mean pulmonary artery pressure (range) 25 (10 57) (mm Hg) Pulmonary capillary wedge pressure Mean (range) (mm Hg) 14 (3 38) 12 mm Hg (n) mm Hg (n) 8 20 mm Hg (n) 12 Right atrial pressure 8 mmhg(n) 31 8 mmhg(n) 13 Mean PVR CATH (range) (WU) 2 (0.7 6) Referral diagnosis Valvular heart disease (n 12) Chest pain and exertional dyspnea (n 9) CAD and exertional dyspnea (n 8) Renal and liver transplant (n 6) Acute respiratory failure (n 4) Postoperative (n 3) Cardiomyopathy (n 2) CAD coronary artery disease; PVR CATH invasive pulmonary vascular resistance; WU Woods unit. peak tricuspid regurgitant velocity (TRV) (m/s). The highest velocity obtained from multiple views was used. Agitated saline was used to enhance suboptimal Doppler signals (7). In patients with atrial fibrillation (n 3), the average of five measurements were used. The TRV/TVI RVOT ratio was then calculated (Figs. 1A, 1B, 2A, and 2B). Individuals in whom both invasive measurements and Doppler variables were obtained were blinded to each other s calculations. Statistical analysis. SAS version 8.0 software was used for statistical computations (SAS Institute Inc., Cary, North Carolina). Linear regression analysis was generated between invasive PVR (WU) (PVR CATH ) and TRV/TVI RVOT, and Pearson s correlation coefficient was obtained. A regression equation was derived in which a value for PVR (WU) was modeled based on TRV/TVI RVOT (PVR ECHO ). Furthermore, a plot of PVR ECHO compared with PVR CATH was generated using the Bland-Altman analysis. Using receiver-operating characteristics curves, a dichotomized PVR was analyzed based on TRV/TVI RVOT.A logistic model was generated, and a cutoff value for TRV/ TVI RVOT with balanced sensitivity and specificity values was obtained to predict elevated PVR values (PVR 2 WU). Confidence intervals were calculated for the sensitivity and specificity values by using the exact binomial method. Another cutoff value was then generated to determine a higher specificity of predicting PVR 2 WU. Twenty percent of the Doppler images were re-evaluated to quantify the intra- and interobserver reliability by calculating the intraclass correlation coefficient (ICC 2 patients/ [ 2 patients 2 error]). Confidence intervals for the ICC were calculated using the method of Shrout and Fleiss (8). RESULTS Thirteen of our patients had increased right atrial pressure (RAP) ( 8 mm Hg), whereas 20 had elevated mean left atrial pressure (PCWP 12 mm Hg). The linear regression analysis between PVR CATH and TRV/TVI RVOT revealed a good correlation (r 0.93, 95% confidence interval [CI] 0.87 to 0.96) for all patients (Fig. 3). The equation derived from the linear regression was: PVR ECHO TRV/TVI RVOT error Patients with elevated PCWP and RAP were evenly distributed among the patient population (Fig. 4). Using the Bland-Altman analysis, PVR ECHO measurements derived from this equation showed satisfactory limits of agreement with PVR CATH (Fig. 5), with a mean value of (SD). The PVR ECHO and PVR CATH values were well within one standard deviation (Figs. 1 and 2). The area under the receiver-operating characteristics curve was calculated at (Fig. 6). A TRV/TVI RVOT cutoff value of provided the best-balanced sensitivity (77%; 95% CI 46% to 96%) and specificity (81%; 95% CI 63% to 93%) to determine PVR 2 WU. A TRV/TVI RVOT cutoff value of 0.2 provided a speci-

3 JACC Vol. 41, No. 6, 2003 March 19, 2003: Abbas et al. Doppler Evaluation of PVR 1023 Figure 1. Images showing peak tricuspid regurgitant velocity (TRV) and right ventricular outflow time-velocity integral (TVI RVOT ) in a patient with normal pulmonary vascular resistance (PVR). (A) TRV is 2.86 m/s. (B) TVI RVOT is 20.8 cm. The ratio of TRV/TVI RVOT 2.86/ PVR ECHO Woods units (WU). This patient s invasive PVR measurement was within 0.4 WU of the echocardiographic value (PVR CATH 1.3 WU). PVR ECHO PVR in WU calculated based on the linear regression equation in which a value for PVR in WU was modeled based on TRV/TVI RVOT. PVR CATH invasive PVR. Figure 2. Images showing TRV and TVI RVOT in a patient with elevated PVR. (A) TRV is 3.64 m/s. (B) TVI RVOT shows a clear deceleration of pulmonary flow before the pulmonic valve closure click and is calculated at 6.5 cm. The ratio of TRV/TVI RVOT 3.64/ PVR ECHO WU. This patient s invasive PVR measurement is also within 0.4 WU of the echocardiographic value (PVR CATH 6.0 WU). Abbreviations as in Figure 1.

4 1024 Abbas et al. JACC Vol. 41, No. 6, 2003 Doppler Evaluation of PVR March 19, 2003: Figure 3. Linear regression analysis between PVR CATH and TRV/TVI RVOT. The circle highlights the PVR cutoff value of 2 WU (r 0.929, 95% confidence interval 0.87 to 0.96). Abbreviations as in Figure 1. Figure 4. Linear regression analysis between PVR CATH and TRV/TVI RVOT. The correlation remained robust among all groups of patients. Patients with normal left atrial pressure (LAP) and right atrial pressure (RAP) (open squares), elevated LAP and RAP (solid squares), elevated LAP and normal RAP (solid triangles), and elevated RAP and normal LAP (open triangles) were evenly distributed among the study population. Abbreviations as in Figure 1.

5 JACC Vol. 41, No. 6, 2003 March 19, 2003: Abbas et al. Doppler Evaluation of PVR 1025 Figure 5. Bland-Altman analysis showing the limits of agreement between PVR ECHO and PVR CATH. Abbreviations as in Figure 1. Figure 6. Receiver-operating characteristics curve. A TRV/TVI RVOT cutoff value of provided the best-balanced sensitivity (77%) and specificity (81%) to determine patients with a PVR value 2 WU. (Area under the curve ) Abbreviations as in Figure 1.

6 1026 Abbas et al. JACC Vol. 41, No. 6, 2003 Doppler Evaluation of PVR March 19, 2003: ficity of 94% and a sensitivity of 70% to determine PVR 2 WU. Thus, by using a TRV/TVI RVOT cutoff value of 0.2, the PVR could have been determined noninvasively to be 2 WU in 94% of patients. The ICC and CI for inter- and intraobserver reliabilities were 0.99 (95% CI 0.95 to 1.0) and 0.99 (95% CI 0.98 to 1.0), respectively. DISCUSSION Pulmonary vascular resistance is directly related to p and inversely related to Qp (6). Thus, TRV and TVI RVOT can be used as correlates of p and Qp, respectively (9,10). As PVR increases, changes in TVI RVOT and TRV occur in opposite directions (9,11). In accordance with the Bernoulli equation, TRV will increase as the PASP increases (9,12,13). However, both hyperdynamic flow states and true pulmonary vascular disease can elevate PASP; therefore, a measure of Qp is crucial. As PVR increases, there is earlier and enhanced reflection of the pressure wave propagated from the RVOT into the pulmonary trunk. This is reflected by a conformational change in TVI RVOT, where midsystolic notching and premature deceleration of pulmonary flow occur, leading to a decreased right ventricular ejection time (11,14 17). The Doppler-derived ratio of TRV/ TVI RVOT was hence hypothesized as a good correlate of PVR. Previous investigators have described the use of various Doppler parameters to evaluate PVR (11,15 23). These efforts have focused primarily on the timing of events such as right ventricular pre-ejection and ejection times, acceleration time of the RVOT velocity, and flow propagation velocities. These studies support the notion that a conformational change in TVI RVOT occurs with increasing PVR. However, these methods require obtaining additional information than routinely acquired with less robust test characteristics. Based on our results, we propose a simplified equation for noninvasive calculation of PVR: PVR(WU) 10 TRV/TVI RVOT We also propose that in patients with increased PASP on Doppler echocardiography and TRV/TVI RVOT 0.2, an elevated PVR is suggested, and these patients may require further invasive workup. However, in patients with TRV/ TVI RVOT 0.2, PVR values are likely to be normal, even in the presence of Doppler evidence of increased PASP. Study limitations. Proper alignment of the ultrasound beam is a crucial factor to ensure adequate determination of TRV and TVI RVOT. Detection of TRV is crucial. The TRV signal could not be obtained in only one patient and was excluded. Agitated saline and ultrasound contrast agents can also enhance the Doppler signal when needed (7). A correction for heart rate in TVI RVOT was not made, as all patients had a heart rate between 60 and 100 beats/min. Heart rate correction may be required for extreme variations. Possible confounding hemodynamic variables that were not included in our Doppler equation include correlates of RAP and PCWP. Patients in whom the results of this study may be beneficial will likely have elevated RAP and PCWP. However, despite the presence of these patients in our study, the correlation remained robust (Fig. 4). Thermodilution was used to calculate cardiac output, which may be inaccurate in the presence of moderate or severe tricuspid regurgitation; thus, those patients were excluded. Further studies will be needed to determine the applicability of this formula to those groups of patients in whom the Fick method was used for calculation of cardiac output. Anatomic variations of the right-heart structures may interfere with Doppler variables. Further studies will be needed to determine the applicability of this formula to patients with congenital heart disease, shunts, or pulmonary artery dilation who were not included in our study. Conclusions. Noninvasive determination of PVR is possible using variables that are routinely obtained by Doppler echocardiography. Increased PASP may be secondary to increased transpulmonary flow or abnormal PVR. Patients with TRV/TVI RVOT 0.2 are likely to have low PVR values ( 2 WU), and pulmonary vascular disease may be excluded despite increased PASP by Doppler. We propose that the term increased pulmonary pressures may be preferred to describe all patients with increased PASP. However, the term pulmonary hypertension may be more appropriately used in patients who also have increased PVR. Acknowledgments We thank the Echocardiography Laboratory (Rochelle Loftus, Ronald Buono, Steven Schneck, and Rose Simpson), Biostatistics Department, and Library Department (Eliane Purchase) for their assistance. Reprint requests and correspondence: Dr. Steven J. Lester, Division of Cardiovascular Diseases, Mayo Clinic, East Shea Boulevard, Scottsdale, Arizona lester.steven@ mayo.edu. REFERENCES 1. Braunwald E, Colucci WS. Vasodilator therapy of heart failure: has the promissory note been paid? N Engl J Med 1984;310: Addonizio LJ, Gersony WM, Robbins RC, et al. Elevated pulmonary vascular resistance and cardiac transplantation. Circulation 1987;76 Suppl V:V Kirklin JK, Naftel DC, McGiffin DC, et al. Analysis of morbid events and risk factors for death after cardiac transplantation. J Am Coll Cardiol 1988;11: Kirklin JK, Naftel DC, Kirklin JW, et al. Pulmonary vascular resistance and the risk of heart transplantation. J Heart Transplant 1988;7: DiSesa VJ, Cohn LH, Grossman W. Management of adults with congenital bidirectional cardiac shunts, cyanosis, and pulmonary vas-

7 JACC Vol. 41, No. 6, 2003 March 19, 2003: Abbas et al. Doppler Evaluation of PVR 1027 cular obstruction: successful operative repair in 3 patients. Am J Cardiol 1983;51: Willard JEL, Richard A, Hillis LD. Cardiac catheterization. In: Kloner RA, editor. The Guide to Cardiology. 3rd ed. Greenwich, CT: Le Jacq Communications, 1995: Himelman RB, Stulbarg M, Kircher B, et al. Noninvasive evaluation of pulmonary artery pressure during exercise by saline-enhanced Doppler echocardiography in chronic pulmonary disease. Circulation 1989;79: Shrout PE, Fleiss JL. Intraclass correlations: uses in assessing rater reliability. Psychol Bull 1979;86: Yock PG, Popp RL. Noninvasive estimation of right ventricular systolic pressure by Doppler ultrasound in patients with tricuspid regurgitation. Circulation 1984;70: Ihlen H, Amlie JP, Dale J, et al. Determination of cardiac output by Doppler echocardiography. Br Heart J 1984;51: Okamoto M, Miyatake K, Kinoshita N, et al. Analysis of blood flow in pulmonary hypertension with the pulsed Doppler flowmeter combined with cross-sectional echocardiography. Br Heart J 1984;51: Berger M, Haimowitz A, Van Tosh A, et al. Quantitative assessment of pulmonary hypertension in patients with tricuspid regurgitation using continuous wave Doppler ultrasound. J Am Coll Cardiol 1985;6: Hatle L, Angelsen BA, Tromsdal A. Non-invasive estimation of pulmonary artery systolic pressure with Doppler ultrasound. Br Heart J 1981;45: Curtiss EI, Reddy PS, O Toole JD, Shaver JA. Alterations of right ventricular systolic time intervals by chronic pressure and volume overloading. Circulation 1976;53: Hirschfeld S, Meyer R, Schwartz DC, et al. The echocardiographic assessment of pulmonary artery pressure and pulmonary vascular resistance. Circulation 1975;52: Matsuda M, Sekiguchi T, Sugishita Y, et al. Reliability of non-invasive estimates of pulmonary hypertension by pulsed Doppler echocardiography. Br Heart J 1986;56: Chan KL, Currie PJ, Seward JB, et al. Comparison of three Doppler ultrasound methods in the prediction of pulmonary artery pressure. J Am Coll Cardiol 1987;9: Murata I, Sonoda M, Morita T, et al. The clinical significance of reversed flow in the main pulmonary artery detected by Doppler color flow imaging. Chest 2000;118: Riggs T, Hirschfeld S, Borkat G, et al. Assessment of the pulmonary vascular bed by echocardiographic right ventricular systolic time intervals. Circulation 1978;57: Scapellato F, Temporelli PL, Eleuteri E, et al. Accurate noninvasive estimation of pulmonary vascular resistance by Doppler echocardiography in patients with chronic failure heart failure. J Am Coll Cardiol 2001;37: Shandas R, Weinberg C, Ivy DD, et al. Development of a noninvasive ultrasound color M-mode means of estimating pulmonary vascular resistance in pediatric pulmonary hypertension: mathematical analysis, in vitro validation, and preliminary clinical studies. Circulation 2001; 104: Tahara M, Tanaka H, Nakao S, et al. Hemodynamic determinants of pulmonary valve motion during systole in experimental pulmonary hypertension. Circulation 1981;64: Ebeid MR, Ferrer PL, Robinson B, et al. Doppler echocardiographic evaluation of pulmonary vascular resistance in children with congenital heart disease. J Am Soc Echocardiogr 1996;9: