Doppler echocardiography is currently the

Doppler Echocardiography of 119 Normal-functioning St Jude Medical Mitral Valve Prostheses: A Comprehensive Assessment Including Time-velocity Integral Ratio and Prosthesis Performance Index* Joseph F. Malouf, MD, Manfredi Ballo, MD, Heidi M. Connolly, MD, David O. Hodge, MS, Regina M. Herges, BS, Charles J. Mullany, MD, and Fletcher A. Miller, Jr, MD, Rochester, Minnesota The purpose of this study was to provide, in a large number of patients, comprehensive Doppler echocardiographic assessment of normal St Jude Medical mitral valve prosthesis function using Doppler-derived hemodynamic variables, including the mitral valve prosthesis to left ventricular outflow tract time-velocity integral ratio and prosthesis performance index. The pressure half-time was less than 130 milliseconds in all patients, and all but one patient had either a peak early mitral diastolic velocity of 2 m/s or less or a mitral valve prosthesis to left ventricular outflow tract time-velocity integral ratio of less than 2.2. There was a significant (P <.001) negative correlation between the prosthesis performance index and prosthesis size. This negative correlation suggests that there is more efficient use of the in vitro geometric orifice area with smaller prostheses. (J Am Soc Echocardiogr 2005;18: 252-6.) Doppler echocardiography is currently the method of choice for assessing normal and abnormal prosthetic valve hemodynamics. Normal Dopplerderived values for mean gradients and effective orifice area (EOA) for different sizes of St Jude Medical (SJM) mitral valve prostheses (mvp) have been reported. 1-4 However, the collective experience is limited to a few relatively small series and case reports. 1-4 A large series is needed because of the large variability in Doppler-derived EOA for each prosthesis size. Moreover, the Doppler indices that have been recently proposed to separate normal from abnormal prosthesis function have not been validated in a large number of patients with normalfunctioning SJM prostheses. Data are limited on the correlation between Doppler-derived EOAs and the actual geometric orifice area (GOA), as provided by the manufacturer. 5,6 From the Divisions of Cardiovascular Diseases (J.F.M., M.B., H.M.C., F.A.M.), Biostatistics (D.O.H., R.M.H.), and Cardiovascular Surgery (C.J.M.), Mayo Clinic. * Nothing in this article implies endorsement of the products of St Jude Medical Inc. Reprint requests: Joseph F. Malouf, MD, Division of Cardiovascular Diseases, Mayo Clinic, 200 First St SW, Rochester, MN 55905. 0894-7317/$30.00 Copyright 2005 by the American Society of Echocardiography. doi:10.1016/j.echo.2004.11.011 The purpose of this study was 2-fold: first, to define, in a large number of patients, normal SJM mvp function using all the important Doppler-derived hemodynamic variables that have been described; and, second, to study the correlation between in vivo Doppler-derived EOA and in vitro GOA. METHODS Patient Selection From our institutional cardiac surgical database, we identified 122 patients aged 18 years or older, who underwent isolated mitral valve replacement with an SJM prosthesis between 1993 and 2001, and who had 2-dimensional (2D) and Doppler echocardiographic studies within 4 weeks after operation. Three patients with more than mild aortic regurgitation were excluded. The remaining 119 patients formed the final study population. The physical examination and appearance of the prosthesis by both intraoperative transesophageal echocardiography (TEE) and follow-up transthoracic echocardiography (TTE) were normal in each of these patients. Routine intraoperative TEE and postoperative TTE evaluation of mitral prosthesis function included 2D imaging of the sewing ring and disk occluders to assess morphologic abnormalities, color-flow Doppler imaging to detect flow alteration, and spectral Doppler assessment of prosthesis hemodynamics. This 252

Volume 18 Number 3 Malouf et al 253 study was approved by the institutional review board, and all patients had consented to have their medical records accessed. Doppler Data Doppler data were obtained from review of the postoperative TTE reports. Missing measurements were obtained using offline analysis (Digiview Release 3.0, Digisonics, Houston, Tex) by two investigators (M.B., F.A.M.). The prosthesis EOA was measured using both pressure halftime (PHT) and continuity (CON) methods. Prosthesis size ranged from 25 to 33 mm. Because the GOAs and hemodynamics of the 31- and 33-mm prostheses are identical, they were evaluated together. The prosthesis performance index (PPI) was calculated as the ratio of the EOA derived from the CON method to the GOA as provided by the manufacturer (3.09 cm 2, 3.67 cm 2, 4.52 cm 2, and 5.18 cm 2 for the 25-mm, 27-mm, 29-mm, and the 31- or 33-mm prosthesis size, respectively). 2,5 Other calculated variables included mean diastolic gradient, EOA indexed to body surface area, EOA/prosthesis size, mvp to left ventricular (LV) outflow tract (LVOT) time-velocity integral (TVI) ratio (TVI mvp /TVI LVOT ), peak early mitral diastolic velocity (E velocity), and E velocity/tvi LVOT. LV ejection fraction (LVEF) was obtained by visual estimate in 63 patients (53%), 6-10 2D measurements in 47 patients (40%), and M-mode measurements in 9 patients (8%). Standard practice in our laboratory is to average the Doppler measurements of 3 cycles if a patient is in sinus rhythm and 5 cycles or more when a patient is in atrial fibrillation or other irregular rhythm. Statistical Methods Measurements were compared between the CON and PHT methods using a paired t test. Continuous variables were compared among the 4 valve size groups using the analysis of variance procedure. Significant differences were investigated, adjusting for multiple comparisons using the Student-Newman-Keuls procedure. RESULTS Table Overall baseline characteristics (N 119) Characteristic Finding* Range Age, y 58 13 18-89 Female, No. (%) 81 (68)... Heart rate, beats/min 82 14 50-120 Hemoglobin, g/dl 10.4 1.4 8.4-14.1 Hematocrit, % 30.8 4.1 24.1-41.6 BSA, m 2 1.82 0.24 0.74-2.46 LVEF, % 56 10 30-75 LVEF 50%, No. (%) 28 (24)... SV LVOT, ml 60 13 36-97 PHT, ms 71 16 41-116 MG, mm Hg 4.49 1.77 1.9-12 EVLCTY, m/s 1.66 0.33 0.9-2.6 TVI mvp,cm 33 8 17-55 EVLCTY/TVI LVOT 0.09 0.02 0.05-0.15 TVI mvp /TVI LVOT 1.72 0.46 0.86-3.45 EOA CON, cm 2 1.91 0.44 0.9-3.29 EOA PHT, cm 2 3.28 0.76 1.9-5.37 IEOA CON, cm 2 /m 2 1.07 0.3 0.48-2.31 IEOA PHT, cm 2 /m 2 1.85 0.53 0.94-3.58 EOA CON/prosth 0.07 0.02 0.04-0.11 size ratio EOA PHT/prosth 0.11 0.03 0.06-0.19 size ratio PPI CON 0.44 0.11 0.25-0.76 BSA, Body surface area; CON, continuity method; EOA, effective orifice area; EVLCTY, E velocity; IEOA, indexed effective orifice area; LVEF, left ventricular ejection fraction; LVOT, left ventricular outflow tract; MG, mean gradient; mvp, mitral valve prosthesis; PHT, pressure half-time; PPI, prosthesis performance index; prosth, prosthesis; SV, stroke volume; TVI, timevelocity integral. *Values are mean SD unless indicated otherwise. Baseline Clinical Characteristics Patient characteristics are listed in the Table. A standard bileaflet SJM prosthesis was implanted in all but one patient who received a 25-mm Hemodynamic-Plus SJM prosthesis (St. Jude Medical, St. Paul, Minn). A total of 99 patients (85%) had their TTE within a week from mitral valve replacement. The rhythm was sinus in 69 patients (58%), atrial fibrillation or flutter (one patient) in 41 patients (34%), and paced or junctional in 9 patients (8%). The indications for mitral valve replacement were mitral regurgitation in 53 patients (45%), mitral stenosis in 33 patients (28%), and mixed stenosis and regurgitation in 33 patients (28%). At the time of echocardiography, mean SD heart rate was 82 14/min (median, 83/min; range, 50-120/min). Complete Doppler hemodynamic data were available in 109 patients (92%), and missing data were limited to the TVI LVOT. A total of 51 patients (43%) had either trivial or mild aortic regurgitation, and 30 patients (25%) had trivial to mild mitral prosthesis regurgitation, including one patient with mild periprosthetic regurgitation. Hemodynamic data, grouped by valve size, are detailed in Figures 1 through 6. The EOA and indexed EOA were significantly lower by the CON method than by the PHT method (P.001). E velocity did not exceed 2 m/s in 104 patients (87%) and in all but 1 of the 28 patients with an LVEF less than 50%. TVI mvp /TVI LVOT was less than 2.2 in 91 of the 109 patients (83%) with complete TVI data, including 11 of the 12 patients with an E velocity exceeding 2 m/s. Among the 18 patients with a TVI mvp /TVI LVOT of 2.2 or higher, 8 patients had an LVEF lower than 50%. The PHT was less than 130 milliseconds in all patients, and all but one patient (99%) had either an E velocity of 2 m/s or less or a TVI mvp /TVI LVOT of less than 2.2. The combination of E velocity less than 1.9 m/s, TVI mvp /TVI LVOT less than 2.2, and PHT less than 130

254 Malouf et al March 2005 Figure 1 Plot of mean prosthesis gradient versus valve size. Error bars, Mean 2 SD. Figure 3 Plot of mitral valve prosthesis to left ventricular outflow tract time-velocity integral ratio (TVI mvp /TVI L - VOT) versus valve size. Error bars, Mean 2 SD. Figure 2 Plot of E velocity versus valve size. Error bars, Mean 2 SD. milliseconds 11 was found in 67 of the 109 patients (61%) with complete data. The mean mitral gradient exceeded 5 mm Hg in 28 patients (6 mm Hg in 16 patients, 7 mm Hg in 5 patients, 8 mm Hg in 2 patients, 9 mm Hg in 3 patients, and 10 and 12 mm Hg in 1 patient each). Among these patients, the heart rate was 90/min or higher in 14 patients (50%), and 24 patients (86%) had a TVI mvp /TVI LVOT of less than 2.2 (16 patients), LVEF less than 50% (6 patients), or both (two patients). There was a significant negative correlation between severity of anemia, as measured by either the hemoglobin level or hematocrit reading, and the mitral gradient (P.001). Effect of Prosthesis Size Valve size was 25 mm in 7 patients (6%), 27 mm in 30 patients (25%), 29 mm in 38 patients (32%), and 31 or 33 mm in 44 patients (37%). There was no significant difference in the mean mitral gradient Figure 4 Plot of prosthesis effective orifice area (EOA) by continuity method versus valve size. Error bars, Mean 2 SD. among the 4 valve size groups after adjusting for multiple comparisons. There was a trend of increasing EOA by the CON method with increasing valve size, but the mean measurements of the EOA and indexed EOA for the different valve sizes by either the PHT or CON method were not significantly different. The mean PPI decreased with increasing valve size (0.55 0.18, 0.5 0.11, 0.42 0.08, and 0.39 0.10 for the 25-mm, 27-mm, 29-mm, and 31- or 33-mm groups, respectively). This difference was significant among the 4 groups (P.001). The 29-mm and 31- or 33-mm groups were significantly different from the 25-mm and 27-mm groups. No other groups were significantly different from one another. There was no significant difference among the different valve sizes with respect to the mean

Volume 18 Number 3 Malouf et al 255 Figure 5 Plot of prosthesis effective orifice area (EOA) by continuity method indexed to body surface area versus valve size. Error bars, Mean 2 SD. Figure 6 Plot of prosthesis performance index (PPI) versus valve size. Error bars, Mean 2 SD. TVI mvp /TVI LVOT or the mean E velocity TVI LVOT ratio. DISCUSSION To our knowledge, this is the largest single-center study profiling normal Doppler hemodynamics of SJM mvp. The PHT was less than 130 milliseconds in all patients, and all but one patient had either an E velocity that did not exceed 2 m/s or a TVI mvp / TVI LVOT less than 2.2, regardless of prosthesis size or LV systolic function. The previous collective experience is limited to 4 studies with a total of 102 prostheses of different sizes, 4 and only the study by Bitar et al 3 provided normal values for EOA using the CON equation. The EOA is a measure of the physiologic area occupied by blood flow and not the true anatomic orifice area of the prosthesis. Importantly, EOA, not GOA, determines the mitral diastolic gradient, hence the persistence or progression of pulmonary hypertension. 12 EOA by the PHT method has serious limitations. Dumesnil et al 13 showed that EOA by the CON and not the PHT method correlates best with the in vitro EOA of normal mitral bioprostheses and that EOA by the PHT method tends to grossly overestimate the in vitro EOA. Both our study and that of Bitar et al 3 demonstrate that EOAs for SJM prostheses by the PHT method are significantly larger than those obtained by the CON method, and Bitar et al 3 showed more variability in the EOA by the PHT method. PPI, the ratio between the in vivo mitral prosthesis EOA and the in vitro GOA, has not been well studied. 2,5 In the report by Bitar et al, 3 the mean PPI was less than 0.5, irrespective of prosthesis size. The significant negative correlation we found between the PPI and prosthesis size suggests that smaller prostheses use the in vitro GOA more efficiently. The EOA for the same SJM valve size has been shown to increase with increasing flow rates. 3 Therefore, higher flow rates across smaller SJM mitral prostheses may have contributed to a more sustained opening of the valve leaflets compared with larger prostheses, 3 thus, accounting for the decreasing PPI with increasing prosthesis valve size. More data are needed, however. Several studies have attempted to define the Doppler hemodynamic profile that best describes normal SJM prosthesis function. In the study by Panidis et al 1 of 44 normal-functioning SJM prostheses, E velocity did not exceed 2.2 m/s among patients with either 27-mm or 29-mm prostheses and did not exceed 2.5 m/s among patients with 31-mm prostheses. In their study, the mean of the mean gradients was 5 mm Hg or less, regardless of prosthesis size, but peak mean gradients of 7 mm Hg, 8 mm Hg, and 14 mm Hg were recorded for the 27-mm, 29-mm, and 31-mm prostheses, respectively. In the report by Bitar et al, 3 E velocity exceeded 2 m/s in only one of the 40 patients with SJM mitral prostheses, and the mean gradient exceeded 5 mm Hg in only 5 patients, all of whom had a heart rate higher than 90/min. Fernandes et al 11 were first to propose TVI mvp / TVI LVOT as an important clue to mechanical prosthesis obstruction or regurgitation. The TVI mvp can be increased by obstruction, regurgitation, or increased cardiac output. With the latter, the TVI LVOT also increases, keeping the ratio less than 2.2. The study by Fernandes et al 11 included 73 normal mechanical mvp. Although the majority were bileaflet prostheses, the number of SJM prostheses was not specified. They found the combination of E velocity less than 1.9 m/s, TVI mvp /TVI LVOT less than 2.2, and PHT less than 130 milliseconds to be highly predictive of normal prosthesis function, verified by TEE, with less than 2% probability of valve dysfunction. In

256 Malouf et al March 2005 contrast, fewer than two-thirds of the patients in our study had all 3 of these characteristics. Potential Limitations This was a retrospective study. Significant (moderate or severe) mitral regurgitation can influence mitral prosthesis forward flow hemodynamics. These prostheses were defined as normally functioning on the basis of normal physical examination findings, the short time between implant and TTE, and normal 2D and color Doppler appearance of the valves by both intraoperative TEE and postoperative TTE. Although we think it is unlikely, significant mitral regurgitation may have been overlooked in a few of these patients by these screening criteria. It was impossible to be certain that the lengths of the cardiac cycle that were used for LVOT and mitral flow measurements were matched for patients with atrial fibrillation. However, measurement of multiple cycles for such patients makes significant error from varying R-R intervals unlikely. Conclusions Ascertaining normal heart prosthesis function remains a challenge. The intent of this study was to provide in vivo data from TTE on a large number of normally functioning SJM mvp, including all the important Doppler variables described to date. The findings can be used for comparison when assessing patients with SJM mitral prostheses. Outlier Doppler data should prompt further evaluation, including TEE, for possible prosthesis dysfunction. In particular, PHT of 130 milliseconds or higher warrants TEE to evaluate bileaflet motion and to check for thrombus, pannus, or both. Either E velocity greater than 2 m/s or TVI mvp /TVI LVOT of 2.2 or higher in the presence of a PHT less than 130 milliseconds warrants consideration of TEE to check for significant prosthetic or periprosthetic regurgitation. REFERENCES 1. Panidis IP, Ross J, Mintz GS. Normal and abnormal prosthetic valve function as assessed by Doppler echocardiography. J Am Coll Cardiol 1986;8:317-26. 2. Reisner SA, Harpaz D, Skulski R, Borenstein D, Milo S, Meltzer RS. Hemodynamic performance of four mechanical bileaflet prosthetic valves in the mitral position: an echocardiographic study. Eur J Ultrasound 1998;8:193-200. 3. Bitar JN, Lechin ME, Salazar G, Zoghbi WA. Doppler echocardiographic assessment with the continuity equation of St Jude Medical mechanical prostheses in the mitral valve position [erratum in Am J Cardiol 1995;76:642]. Am J Cardiol 1995;76:287-93. 4. Rosenhek R, Binder T, Maurer G, Baumgartner H. Normal values for Doppler echocardiographic assessment of heart valve prostheses. J Am Soc Echocardiogr 2003;16:1116-27. 5. Rashtian MY, Stevenson DM, Allen DT, Yoganathan AP, Harrison EC, Edmiston WA, et al. Flow characteristics of four commonly used mechanical heart valves. Am J Cardiol 1986; 58:743-52. 6. Stamm RB, Carabello BA, Mayers DL, Martin RP. Twodimensional echocardiographic measurement of left ventricular ejection fraction: prospective analysis of what constitutes an adequate determination. Am Heart J 1982;104: 136-44. 7. Rich S, Sheikh A, Gallastegui J, Kondos GT, Mason T, Lam W. Determination of left ventricular ejection fraction by visual estimation during real-time two-dimensional echocardiography. Am Heart J 1982;104:603-6. 8. Amico AF, Lichtenberg GS, Reisner SA, Stone CK, Schwartz RG, Meltzer RS. Superiority of visual versus computerized echocardiographic estimation of radionuclide left ventricular ejection fraction. Am Heart J 1989;118:1259-65. 9. Mueller X, Stauffer JC, Jaussi A, Goy JJ, Kappenberger L. Subjective visual echocardiographic estimate of left ventricular ejection fraction as an alternative to conventional echocardiographic methods: comparison with contrast angiography. Clin Cardiol 1991;14:898-902. 10. Enriquez-Sarano M, Tajik AJ, Schaff HV, Orszulak TA, Bailey KR, Frye RL. Echocardiographic prediction of survival after surgical correction of organic mitral regurgitation. Circulation 1994;90:830-7. 11. Fernandes V, Olmos L, Nagueh SF, Quinones MA, Zoghbi WA. Peak early diastolic velocity rather than pressure half-time is the best index of mechanical prosthetic mitral valve function. Am J Cardiol 2002;89:704-10. 12. Dumesnil JG, Yoganathan AP. Valve prosthesis hemodynamics and the problem of high transprosthetic pressure gradients. Eur J Cardiothorac Surg 1992;6 (Suppl 1):S34-8. 13. Dumesnil JG, Honos GN, Lemieux M, Beauchemin J. Validation and applications of mitral prosthetic valvular areas calculated by Doppler echocardiography. Am J Cardiol 1990; 65:1443-8.