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1 Planimetry of Mitral Valve Stenosis in Rheumatic Heart Disease by Magnetic Resonance Imaging Charan Lanjewar 1, Biju Ephrem 1, Nidhish Mishra 2, Bhaven Jhankariya 1, Prafulla Kerkar 1 1 Department of Cardiology, King Edward VII Memorial Hospital, Acharya Donde Marg, Parel, Mumbai, 2 MRI Jhankariya Centre, Mumbai, India Background and aim of the study: To date, no investigations have been made on the role of magnetic resonance imaging (MRI) in evaluating mitral stenosis (MS) in Asian countries such as India, where rheumatic MS is more common. An accurate assessment of the mitral valve area (MVA) is particularly important when managing patients with valvular stenosis. Current standard techniques to assess the severity of MS include echocardiography and cardiac catheterization, the former of which represents the most practical approach. The study aim was to evaluate the accuracy and clinical utility of planimetry of the MVA and peak gradient, assessed by MRI in comparison with echocardiography, in rheumatic heart disease (RHD) patients with MS. Methods: Among a group of 30 patients with suspected or known MS, planimetry of the MVA and mitral valve gradient (MVG) was performed with a 1.5 Tesla MRI scanner, using a breath-hold balanced gradient echo sequence (true FISP) and velocity-encoded MRI, respectively. The data obtained were compared with the echocardiographically determined MVA (ECHO-MVA). Results: The correlation between the MRI-MVA and ECHO-MVA was 0.81 (p <0.0001), and between the MRI-MVG and ECHO-MVG was 0.81 (p <0.0001). The MRI-MVA slightly overestimated the ECHO- MVA by 8.1% (1.61 ± 0.42 cm 2 versus 1.48 ± 0.42 cm 2 ; p <0.05). Conclusion: To the present authors knowledge, this study is the first in which MRI has been used to evaluate MVA by planimetry, particularly in RHD. MRI is capable of adequately evaluating patients with rheumatic MS with respect to the peak gradient and MVA by planimetry. Thus, MRI planimetry of the mitral valve orifice in MS offers a reliable and safe method for the quantification of MS. Further studies are required to standardize the procedure in those patients with atrial fibrillation, or who are more symptomatic. The Journal of Heart Valve Disease 2010;19: Echocardiography represents the cornerstone of diagnostic assessment in patients with mitral stenosis (MS), and is the most accurate non-invasive technique available to quantify the severity of the condition. New developments in magnetic resonance imaging (MRI) techniques have enabled its use in the diagnosis of a variety of cardiovascular disorders. Indeed, the advent of velocity-encoded MRI (VEC-MRI) has made it possible to evaluate the gradients across stenotic valves. While MRI is currently used routinely to evaluate regurgitant valvular lesions, the available data relating to stenotic lesions, and in particular to MS, are limited (1). Since VEC-MRI is non-invasive, non-ionizing, Address for correspondence: Dr. Charan Lanjewar, Department of Cardiology, CVTC Bldg., King Edward VII Memorial Hospital, Acharya Donde Marg, Parel, Mumbai , India charanlanjewar@hotmail.com reproducible, not limited by air and bone conduction, more sensitive in detecting thrombus, and has a high three-dimensional spatial resolution and freedom of access to any location in any direction, the technique might contribute to the assessment of MS (2). Recently, the feasibility of VEC-MRI, which correlates closely with echocardiography (ECHO), has been demonstrated in the assessment of stenotic aortic (3) and mitral valves (4,5). However, with new balanced gradientecho sequences, a direct visualization of the valve area is also possible; indeed, in patients with aortic stenosis it has been shown that the valve area, as assessed by MRI planimetry, corresponds closely to the invasively assessed valve area, as assessed by cardiac catheterization (CATH) (6,7). Thus, planimetry of the mitral valve area (MVA) using MRI might also offer an alternative non-invasive method for the diagnosis of MS. To date, no studies have been conducted to investigate the role of MRI for evaluating MS in developing countries such Copyright by ICR Publishers 2010

2 358 Planimetry of MV stenosis in RHD by MRI J Heart Valve Dis Figure 1: Echocardiography features. A) The mitral valve area of a patient with severe MS by planimetry on echocardiography. B) Estimation of the mitral valve gradient by Doppler velocities on echocardiography. as India, where rheumatic MS is more common. The study aim was to evaluate the accuracy and clinical utility of planimetry of the MVA and peak gradient by MRI, in comparison with the echocardiography in rheumatic heart disease (RHD), with mitral valve stenosis. Clinical material and methods Patients A total of 30 consecutive patients (18 females, 12 males; mean age 29 ± 10 years; range: 18 to 53 years) who had visited the present authors hospital and were diagnosed echocardiographically with rheumatic MS, were included in the study. The majority (75%) of the patients were aged between 18 and 35 years. Each patient provided their written, informed consent to participate, all tolerated the procedure well, and no adverse effects were observed. Patients with moderate or severe mitral regurgitation, with aortic valve disease, age <18 years, atrial fibrillation (AF), NYHA functional class III, left ventricular dysfunction, coronary artery disease and those with contradictions for MRI, were excluded from the study. After providing a detailed history, each patient underwent a physical examination, electrocardiography (ECG) and chest radiography, followed by echocardiography (Hewlett Packard Ultrasound scanner; SONOS 1000). After having established the diagnosis, the MVA was calculated using planimetry (Fig. 1A). By using continuous-wave Doppler, the pressure gradients were obtained across the mitral valve (Fig. 1B). All patients underwent imaging with a 1.5 Tesla echoplanar ECG gated MRI (Siemens), with a maximal gradient strength of 40 mt/m and a maximal ramp rate of 10 T/m/s, with facilities for velocity encoding. Slices of 5 mm thickness with VEC-MRI sequences, using a repetition time of 40 ms and an echo time of ms, were obtained. Flow and respiratory compensations were also performed. The mitral valve was localized in the vertical and horizontal long axes. The MVA was measured at the time of maximal leaflet separation in the parasternal short-axis view (Fig. 2A). The mitral inflow velocity and gradient were measured in the short-axis view, perpendicular to the jet. The MRI parameters were measured by an investigator who had been blinded to the results of the echocardiography studies. Statistical analysis Results were expressed as mean ± SD. The agreement between the two methods of MVA quantification was assessed using a univariate regression analysis and the Bland-Altman method. Differences in mean values between the two groups were analyzed using Student s t-test, and a chi-square test was performed to compare frequencies between groups. A p-value <0.05 was considered to be statistically significant.

3 J Heart Valve Dis Planimetry of MV stenosis in RHD by MRI 359 Figure 2: MRI features. A) The mitral valve area of a patient with severe MS by planimetry on MRI. B) Estimation of the mitral valve gradient by Doppler velocities on MRI. Results The MRI investigations were performed successfully in all patients, with the study time ranging between 40 and 50 min. None of the patients reported any effects of claustrophobia during the investigations. MVA and peak gradient The mean MRI-MVA, determined by planimetry, was 1.71 ± 0.44 cm 2 (range: 0.5 to 2.40 cm 2 ); as assessed by ECHO, the mean ECHO-MVA was 1.31 ± 0.30 cm 2 (range: 0.6 to 2.50 cm 2 ). The peak gradient was 12 ± 6 mmhg (range: 15 to 35 mmhg) when assessed by MRI, and 16 ± 9 mmhg (range: 18 to 38 mmhg) when assessed by ECHO. When comparing MRI with ECHO, the correlation between planimetry of the MRI and ECHO-MVA and peak gradient by the two methods was very good (r = 0.81, p <0.05). The mean absolute difference between MVA derived by MRI and ECHO was 0.12 ± 0.23 cm 2 (p < 0.05), and resulted in a slight overestimation (by 7.6%) of the MRI-MVA when compared to ECHO-MVA (Fig. 3). The mean absolute difference between the peak gradient derived by MRI and ECHO was 4.1 ± 1 mmhg (p <0.12), which resulted in a slight underestimation (by 7.1%) of the MRI-peak gradient as compared to the ECHO-peak gradient (Fig. 4). Discussion Currently, RHD represents one of the most common causes of cardiovascular morbidity and mortality worldwide (8), with a prevalence among Indian schoolchildren of between 2 and 11 per 1,000 population, and adult values varying between 1.2 and 2 per 1,000 (9). Approximately 25% of all patients with RHD have pure MS, while an additional 40% have MS and mitral regurgitation (10). In RHD, transthoracic echocardiography with Doppler represents an excellent means of confirming the diagnosis, characterizing the severity of obstruction, and detecting and quantifying any associated abnormalities in the pulmonary circulation and in other valves (11). Echocardiography is also helpful in the selection of patients for valvuloplasty, by predicting the likelihood of procedural success (12). Although, transesophageal echocardiography reveals the valve anatomy in greater detail, as well as the presence of a thrombus in the left atrium or its appendage (13), it has certain limitations (14). The use of planime-

4 360 Planimetry of MV stenosis in RHD by MRI J Heart Valve Dis Figure 3: A) Scattergram of mitral valve area (MVA) determined by MRI and echocardiography (ECHO) in 30 patients. B) Bland-Altman plot of the average mean versus the differences between MRI planimetry and MVA derived at ECHO. The solid line is the mean difference; the dotted lines mark the standard deviations of the differences. try can lead to an underestimation of the valve area when dense fibrosis and calcification broaden the echo from the orifices, while an overestimation may be caused by echo dropouts. Likewise, incorrect gain settings can either enlarge or reduce the measured area. Doppler gradients require correct alignment, as tachycardia and mitral regurgitation can lead to overestimations of the gradients, whereas a decreased left ventricular compliance and aortic regurgitation will cause a decrease in the pressure half-time (PHT). Poor echocardiographic windows often pose diagnostic and therapeutic questions; indeed, in some patients with MS the symptoms of dyspnea and fatigue are often difficult to correlate with the severity of the stenosis, and do not always reflect genuine reductions in the mitral orifice area (15). Yet, because of the continuous and progressive nature of MS, the repeated assessment of the valve area is often necessary, and consequently an ability to assess the valve area both accurately and non-invasively is of major importance. In this respect, the excellent correlation values of MRI and ECHO suggest that MRI, as a non-invasive method, might prove highly useful for the stratification of patients with suspected MS. In addition to the assessment of valve area, MRI is also able to detect the subvalvular apparatus, leaflet thickness, mobility, calcification or fusion of the commissures, distribution of calcium, and left atrial or atrial appendage thrombi, and also allows an assessment of the presence and severity of concomitant regurgitation. In the present study, these parameters were not examined using MRI. A consideration of the valve area, as well as these important aspects, is of pivotal importance for therapeutic decision-making and the subsequent conservative, percutaneous or surgical management of patients with MS. Today, MRI is an accepted technique for the non-invasive evaluation of cardiac structures, and three imaging approaches are available to assess valvular heart disease, namely spin-echo imaging, gradient-echo imaging, and phase-velocity mapping. The results of the present study have demonstrated that the visualization and planimetry of the MVA by MRI is not only possible but also reliable in patients with MS. Indeed, a very good correlation was found between MVA planimetry and ECHO planimetry. The results of the present study correlated with those of Djavidani et al. (5), in which planimetry of the MVA was performed in 22 patients with MS. The data were compared with echocardiographically determined MVA (ECHO-MVA; n = 22), as well as with invasively calculated MVA by the Gorlin formula (CATH-MVA, n = 17). A good correlation was found between the MRI- MVA and CATH-MVA (r = 0.89; p <0.0001), and also between MRI-MVA and ECHO-MVA (r = 0.81; p <0.0001). The MRI-MVA slightly overestimated CATH- MVA by 5.0% (1.60 ± 0.45 cm 2 versus 1.52 ± 0.49 cm 2, p = NS) and ECHO-MVA by 8.1% (1.61 ± 0.42 cm 2 versus 1.48 ± 0.42 cm 2, p <0.05). Thus, these authors demonstrated a reliability and safety of estimation of MVA by MRI, even though a slight overestimation of MVA was observed. The results of the present study also demonstrated the ability of echoplanar MRI to measure, non-invasively, the transmitral peak gradient along with the MVA; indeed, a good correlation was found between the peak mitral valve gradient (MVG) by ECHO and

5 J Heart Valve Dis Planimetry of MV stenosis in RHD by MRI 361 Figure 4: A) Scattergram of mitral valve gradient (MVG) determined by MRI and echocardiography (ECHO) in 30 patients. B) Bland-Altman plot of the average mean versus the differences between MRI MVG and MVG derived at ECHO. The solid line is the mean difference; the dotted lines mark the standard deviations of the differences. MRI (r = 0.86). There was a statistically non-significant underestimation of peak gradient by MRI compared to ECHO. Heidenreich et al. (16) were the first to evaluate patients with MS by VEC-MRI, and demonstrated an excellent correlation between VEC-MRI and echo- Doppler measurements for peak velocity. Lin et al. (4) have also demonstrated a close and robust correlation of estimation of MVA by the PHT method with ECHO and MRI. In these two studies, however, the patient population had non-rheumatic mitral valve stenosis, while the present study population had RHD. In the current study, a slightly higher mean MVA by MRI was reported in comparison to ECHO (7.6%). An overestimation of MVA by MRI was also reported by Djavidani et al. (5), which was of the same magnitude as in the present study. Hence, during clinical assessment it should be borne in mind that MRI slightly overestimates the MVA. Although, in routine clinical practice, ECHO is used to assess MS, cardiac catheterization remains the standard procedure for calculating the MVA. However, because of the indirect measurements, the accuracy of MVA calculation has often been challenged (17-19), and consequently the MRI and ECHO findings have been compared. The visualization and planimetry of MVA, using ECHO, provide a non-invasive measurement that is widely used for the estimation of MVA (20-22). Although the Doppler PHT method used in the present study has proven valuable for the noninvasive assessment of the severity of MS in a variety of circumstances, its accuracy may also be limited under certain conditions (23). Taken together, this variability in MVA measurements by different methods underscores the importance of understanding the assumptions and limitations of each method, and supports a non-invasive method for the direct determination of MVA by planimetry, such as MRI. As the results of the present study have indicated that MRI planimetry is accurate, this new method should complement established MRI methods of valve assessment, such as the mitral valve gradient. The advantage of a larger slice thickness is that it limits the background noise, so that the velocity can be estimated with greater accuracy. However, this is at the expense of limited lateral and temporal resolution, thereby preventing the accurate assessment of MVA by planimetry (24). Nonetheless, the use of 5 mm slices and a temporal resolution of <40 ms permitted estimation of the MVA. None of the present patients had AF. The widely varying R-R interval in such patients leads to variations in beat-to-beat velocity, and complicates the localization of the mitral valve annulus and artifacts (24). Consequently, as this was the first study of its type and standardization was a major issue, any patients with AF were excluded. Echocardiography, as a standard technique for assessing MS, is widely used, easy to repeat, relatively inexpensive, and therefore used routinely for the diagnosis, assessment and follow up of patients with MS. In the present study, MRI was used to detect, evaluate and quantitate MS. Moreover, with the advent of newer techniques the long acquisition time has been significantly reduced, and with improved temporal and spatial resolution it is now possible to measure the velocity, gradient and MVA. Nevertheless, MRI is an

6 362 Planimetry of MV stenosis in RHD by MRI expensive investigation and cannot be recommended for the regular follow up of these patients. Neither can MRI be considered an alternative technique to echocardiography in the routine study of patients with MS, although it may be of clinical relevance for the noninvasive assessment of those patients with poor echocardiographic windows, and in whom Doppler studies are inconsistent with catheterization and clinical data. The MRI technique might also be considered in those patients in whom a left atrial thrombus is suspected but cannot be demonstrated by echocardiography. The ability of MRI to display the mitral valve apparatus and blood flow in any plane or direction is unique to this imaging modality, and the ability to display the jet shape and volume flow may prove useful in the future management of patients with MS. Further studies with larger populations of patients are required to establish MRI as a standard tool in the evaluation of patients with MS. In conclusion, the present study was the first to use MRI to evaluate MVA by planimetry in RHD. Magnetic resonance imaging allows for the non-invasive planimetry of MVA with good imaging quality, and also provides additional information on valve structure and function. MRI is able to adequately evaluate patients with rheumatic MS with respect to peak gradient and MVA by planimetry. However, further studies are required to standardize this procedure in patients with AF, or in more symptomatic patients. J Heart Valve Dis References 1. Reichek N. Cardiac magnetic resonance imaging. Cardiol Clin 1998;16: Kilner PJ, Firmin DN, Rees RSD, et al. Valve and great vessel stenosis: Assessment with MR jet velocity mapping. Radiology 1991;178: Caruthers SD, Lin SJ, Brown P, et al. Practical value of cardiac magnetic resonance imaging for clinical quantification of aortic valve stenosis comparison with echocardiography. Circulation 2003;108: Lin SJ, Brown PA, Watkins MP, et al. Quantification of stenotic mitral valve area with magnetic resonance imaging and comparison with Doppler ultrasound. J Am Coll Cardiol 2004;44: Djavidani B, Kurt D, Lenhart M, et al. Planimetry of mitral valve stenosis by magnetic resonance imaging. J Am Coll Cardiol 2005;45: Friedrich MG, Schulz-Menger J, Poetsch T, et al. Quantification of valvular aortic stenosis by magnetic resonance imaging Am Heart J 2002;144: John AS, Dill T, Brandt RR, et al. Magnetic resonance to assess the aortic valve area in aortic stenosis J Am Coll Cardiol 2003;42: Aggarwal BL. Rheumatic heart disease unabated in developing countries. Lancet 1981;2: Padmavati S. Rheumatic fever and rheumatic heart disease in developing countries. Bull WHO 1978;56: Dare A, Harrity P, Tazelaar H, et al. Evaluation of surgically excised mitral valves: Revised recommendations, based on changing operative procedures in the 1990s. Hum Pathol 1993;24: Pride RB, Oakley CM. Echocardiographic evaluation of the mitral valve. Prog Cardiovasc Dis 1978;21: Nobuyoshi M, Hamasaki N, Kimura T, et al. Indications, complications, and short-term clinical outcome of percutaneous transvenous mitral commissurotomy. Circulation 1989;80: Come PC, Riley MF. M-mode and cross-sectional echocardiographic recognition of fibrosis and calcification of the mitral valve chordae and left ventricular papillary muscles. Am J Cardiol 1982;49: Henry WL, et al. Measurement of mitral orifice area in patients with mitral valve disease by real-time two dimensional echocardiography. Circulation 1975;51: Hugenholtz PG, Ryan TJ, Stein SW, et al. The spectrum of pure mitral stenosis hemodynamic studies in relation to clinical disability. Am J Cardiol 1962;10: Heidenreich PA, Steffens J, Fujita N, et al. Evaluation of mitral stenosis with velocity-encoded cine magnetic resonance imaging. Am J Cardiol 1995;75: Gorlin R, Gorlin SG. Hydraulic formula for calculation of the area of the stenotic mitral valve, other cardiac valves and central circulatory shunts. Am Heart J 1951;41: Bryg RJ, Williams GA, Labovitz AJ, et al. Effect of atrial fibrillation and mitral regurgitation on calculated MVA in mitral stenosis. Am J Cardiol 1986;57: Axler O, Tousignant C, Thompson CR, et al. Comparison of transesophageal echocardiography, Fick, and thermodilution in cardiac output in critically ill patients. J Crit Care 1996;11: Nichol PM, Gilbert BW, Kisslo JA. Two-dimensional echocardiographic assessment of mitral stenosis Circulation 1977;55: Wann LS, Weyman AE, Feigenbaum H, et al. Determination of mitral valve area by cross-sectional echocardiography. Ann Intern Med 1978;88: Henry WL, Griffith J, Michaelis LL, et al. Measurement of mitral orifice area in patients with

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