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Cardiovascular magnetic resonance assessment of the aortic valve stenosis: an in vivo and ex vivo study

Cardiovascular magnetic resonance assessment of the aortic valve stenosis: an in vivo and ex vivo... Background: Aortic valve area (AVA) estimation in patients with aortic stenosis may be obtained using several methods. This study was undertaken to verify the cardiovascular magnetic resonance (CMR) planimetry of aortic stenosis by comparing the findings with invasive catheterization, transthoracic (TTE) as well as tranesophageal echocardiography (TEE) and anatomic CMR examination of autopsy specimens. Methods: Our study was performed in eight patients with aortic valve stenosis. Aortic stenosis was determined by TTE and TEE as well as catheterization and CMR. Especially, after aortic valve replacement, the explanted aortic valves were examined again with CMR ex vivo model. 2 2 Results: The mean AVA determined in vivo by CMR was 0.75 ± 0.09 cm and ex vivo by CMR was 0.65 ± 0.09 cm and was closely correlated (r = 0.91, p < 0.001). The mean absolute difference between AVA derived by CMR ex vivo and in vivo was −0.10 ± 0.04 cm . The mean AVA using TTE was 0.69 ± 0.07 with a significant correlation between CMR ex vivo (r = 0.85, p < 0.007) and CMR in vivo (r = 0.86, p < 0.008). CMR ex vivo and in vivo had no significant correlation with AVA using Gorlin formula by invasive catheterization or using planimetry by TEE. Conclusion: In this small study using an ex vivo aortic valve stenosis model, the aortic valve area can be reliably planimetered by CMR in vivo and ex vivo with a well correlation between geometric AVA by CMR and the effective AVA calculated by TTE. Keywords: Aortic valve, Aortic stenosis, Magnetic resonance imaging, Anatomy Background reference (“gold standard”) whereas the Gorlin-formula is Aortic valve stenosis is the most common cardiac valve the historical reference. disease resulting in valve therapy [1]. Exact determination Cardiovascular magnetic resonance (CMR) is a noninva- of the severity of stenosis is essential to guide therapy [2]. sive method that allows visualization of cardiac function, Standard methods, such as cardiac catheterization and structure and valves [5, 6]. Recently, we and others have transthoracic echocardiography (TTE) have to calculate reported the success of planimetry by CMR in aortic valve the effective orifice area by measurement of the transvalv- [7–14]. ular pressure gradient [3, 4], as they do not allow a direct However, to date, no studies have been published and precise measurement of the geometric orifice area. describing ex vivo CMR stenotic aortic valves. It there- Therefore it seems desirable to directly determine the fore seemed useful to compare anatomic data with CMR geometric orifice area by a flow independent technique imaging. such as planimetry. Several cardiologists take the view that We hypothesized that direct planimetry of the stenotic TTE using the Doppler-technique is now the best aortic valve in an autopsy human valve as a standard of reference using CMR corresponds to the planimetry of the stenotic aortic valve in vivo using CMR. To address * Correspondence: stefan.buchner@ukr.de 1 this hypothesis, we performed a head-to-head comparison Klinik und Poliklinik für Innere Medizin II, Universitätsklinikum Regensburg, between aortic valve area (AVA) planimetry preoperatively Franz-Josef-Strauss-Allee 11, 93042 Regensburg, Germany Full list of author information is available at the end of the article © 2015 Buchner et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Buchner et al. BMC Medical Imaging (2015) 15:34 Page 2 of 8 by CMR and postoperatively of the explanted aortic valve Transesophageal Echocardiography by CMR in a series of eight patients with aortic valve Multiplane TEE was performed using a 5-Mhz annular stenosis. In addition, CMR measurements were compared phased array probe. For examination of the aortic valve, with TTE and transesophageal echocardiography (TEE) as the imaging plane was rotated from 0° to 180° until the well as catheterization data best imageoftheaortic valveopening in theshort axis view was obtained (usually around 60°). Minimal probe manipulation was performed to ensure that the smallest Methods orifice of the aortic valve at the leaflet tips was identi- Patients fied. Planimetry of the smallest orifice at the time of Eight patients referred to our institution for evaluation of maximum opening in early systole (triggered by the aortic valve stenosis and were prospectively included in electrocardiogram) was performed. At least three con- the study undergoing aortic valve replacement. All diag- secutive measurements were averaged. nostic procedures and measurements were performed by experienced observers, who were blinded to the results of Catheterization the other imaging modalities. Informed consent was A standard cardiac catheterization procedure was obtained in all patients. The study approved by local ethics performed via the percutaneous femoral approach, in- committee of the Universität Regensburg. cluding right and left heart pressure measurement. Peak to peak and mean pressure gradients were determined between left ventricle and ascending aorta. Cardiac Clinical characteristics of the patients output was measured by thermodilution, averaging at Clinical data of the eight patients are summarized in least 3 measurements. AVA was estimated using the Table 1. Mean age was 76 ± 6 (62 to 82) years. The Gorlin formula [16]. majority of patients presented with clinical symptoms of severe aortic stenosis, such as systolic murmur, dyspnea, Surgery and autopsy chest pain or syncope. Concomitant aortic regurgitation The description of the aortic valve was obtained from was present in 5 patients and was defined as mild/trivial one surgeon. We obtained human valves from patients (n = 4) or moderate (n = 1) by CMR and echocardiog- with aortic valve stenosis at the time of surgical valve raphy. TEE planimetry of AVA was not possible in one replacement. Despite the heavy calcification, all valves patient because of heavy calcifications. Planimetry of could be explanted totally. Specimens were originally AVA was possible in all patients undergoing CMR. An preserved in formaldehyde solution. impaired image quality was observed in one patient due to trigger problems by cardiac arrhythmia. Cardiovascular magnetic resonance studies – in vivo All patient studies were performed on a 1.5 T scanner Transthoracic echocardiography (Sonata, Siemens Medical Solutions, Erlangen, Germany). Standardized transthoracic echocardiography was per- CMR studies were performed in supine position with a formed with measurements of the left ventricular outflow phased-array receiver coil and breath-hold acquisitions tract diameter, the velocity of across the aortic valve and prospectively gated to the ECG. Cine images were ac- flow data of the left ventricular outflow tract to calculate quired in multiple short axis and long axis views with fast the AVA using the continuity equation [15]. imaging with steady state free precession (trueFISP, slice thickness 8 mm, echo time 1.53 ms, readout bandwidth 1.085 Hz/pixel, repetition time 3.14 ms, matrix 256*202). Table 1 Patient characteristics Image analysis was performed off-line using the semi- Patient Age Sex Rhythm HR SBP NYHA CCS Syncope automatic ARGUS evaluation program (Siemens Medical 1 80 female SR 71 130 4 0 0 Solutions, Erlangen, Germany), which is a part of the 2 82 female AF 77 158 3 1 0 commercially available cardiac package of the scanner 3 74 female SR 91 125 2 0 0 software. 4 75 female SR 67 115 3 0 1 The imaging plane of the aortic valve was defined by ac- 5 79 female SR 83 120 3 2 0 quiring a systolic 5-chamber view parallel to the long axis of the left ventricular outflow tract and a long axis view of 6 75 male AF 97 116 4 3 0 the left ventricular outflow tract and the proximal aorta, 7 62 female SR 63 130 3 4 0 perpendicular to the 5-chamber view, as described previ- 8 77 female SR 80 130 3 2 0 ously [7]. In brief, the subsequent slices were defined SR, sinus rhythm; AF, atrial fibrillation; HR, heart rate; SBP, systolic blood parallel to the valvular plane and, additionally, in cases of pressure; NYHA, New York Heart Association, CCS, Canadian Cardiovascular Society orifices with an eccentric outlet, perpendicularly to the Buchner et al. BMC Medical Imaging (2015) 15:34 Page 3 of 8 direction of the jet. At least 4 slices (range 4–7) at differ- Statistical analysis ent levels of the aortic valve were acquired and the im- Data expressed as mean ± standard deviation. Linear re- aging plane with the smallest orifice was chosen. gression analysis was performed to describe correlations Planimetry of the smallest orifice at the time of maximum between the different techniques. The mean AVA of the opening in early systole in the acquisitions prospectively different techniques was compared by student's t-Test triggered to the electrocardiogram was performed by two for paired samples. Intra- and interobserver variability independent observers, who were unaware of the echocar- (n = 8) were expressed as the percentage of variability diographic, catheterization and ex vivo results. We placed (absolute value of the difference between 2 measure- our traces at the point of the bright pixels. Three measure- ments divided by the mean of 2 measurements). Agree- ments were performed and average for calculating the ment between the different techniques was assessed as AVA. Intraobserver and interobserver variabilities regard- described by Bland and Altman. A level of significance ing AVA were 3 % and 6 % for in vivo CMR, respectively. of below 0.05 was defined as statistically significant. SPSS version 21 (SPSS Institute, Chicago) was used for Cardiovascular magnetic resonance studies – ex vivo statistical analysis. All specimens were examined on a 1.5 T scanner (Magnetom Sonata, Siemens Medical Solutions, Erlangen, Results Germany). The CMR imaging protocol included a 3D- CMR planimetry of AVA in vivo and ex vivo CISS protocol (TR/TE/flip angle 17/8.08 ms/70° ms, band The measurements of all patients by the various modal- width 130 Hz/pixel, effective slice thickness 1 mm pixel ities are depicted in Table 2. Six valves were tricuspid size 0.6 × 0.45 mm). The aortic valve was placed on a rack and two valves were bicuspid. Images of aortic valve spe- into a water container. Then the container with the aortic cimen, in vivo and ex vivo CMR are depicted in Fig 3. valve was placed in the gantry. Slices in the orthogonal The mean AVA determined ex vivo by CMR was 0.65 ± planes (transverse, coronal and sagittal) were obtained 0.09 cm . Mean AVA determined in vivo by CMR was 0.75 (Fig. 1). Serial angulated-axis views from the base to tip of ±0.09 cm . The mean absolute difference between AVA the valve were acquired with 3D sequence (Fig. 2). derived by CMR ex vivo and in vivo was 0.10 ± 0.04 cm Planimetry of the smallest orifice was performed by two (p<0.001,Fig.4and Table 3). The AVA in vivo and ex vivo independent observers, who were unaware of the echo- by CMR was closely correlated (r = 0.91, p < 0.001). cardiographic, catheterization and in vivo results. We The mean absolute difference between AVA derived by placed our traces at the edge of the bright pixels. Three CMR ex vivo and calculated using the continuity equa- measurements were performed and average for calcu- tion by TTE was −0.04 ± 0.05 cm (p = 0.066). The mean lating the AVA. Intraobserver and interobserver vari- absolute difference between AVA derived by CMR in abilities were 1 % and 4 % for ex vivo CMR, respectively. vivo and calculated using the continuity equation by AB CD Fig. 1 Position of the ex vivo aortic valve fixed in a water container and planning the slices. a, overview; b, coronar view; c, angulation for planning the orthograd view; d, the resulting orthograd view Buchner et al. BMC Medical Imaging (2015) 15:34 Page 4 of 8 Fig. 2 To avoid assessing the aortic valve area beyond or above the leaflet tips, the imaging plane was moved shift wise in one mm steps in an orthograd direction. Planimetry was chosen on the slice where the smallest orifice was surrounded totally by the edge of the valve TTE was +0.07 ± 0.04 cm . In linear regression analysis between CMR in vivo and Gorlin formula by the correlation between CMR ex vivo and TTE (r = 0.85, catheterization was r = −0.03, p = 0.952. p < 0.007) was similar to that between CMR in vivo and TTE (r = 0.86, p < 0.008). AVA with other methods The mean absolute difference between aortic valve The mean of the aortic valve area calculated using the area derived by CMR ex vivo and TEE was +0.12 ± Gorlin formula by catheterization was 0.60 ± 0.27 cm . 0.09 cm (p = 0.012). The mean absolute difference be- The mean aortic valve area determined by TEE was 0.79 tween aortic valve area derived by CMR in vivo and ± 0.15 cm . The mean of the aortic valve area calculated TEE was −0.02 ± 0.10 cm (p = 0.75). In linear regres- by TTE was 0.69 ± 0.07 (Table 3). sion analysis the correlation between CMR ex vivo and The mean absolute difference between AVA derived TEE was r = 0.44, p = 0.323) and between CMR in vivo calculated using the Gorlin formula by catheterization and and TEE r = 0.28, p = 0.551. calculated using the continuity equation by TTE was Themeanabsolutedifferencebetween AVAderived by −0.11 ± 0.25 cm (p =0.278). The mean absolute differ- CMR ex vivo and calculated using the Gorlin formula by ence between AVA using the Gorlin formula by 2 2 catheterization was +0.07 ± 0.26 cm (p = 0.498). The mean catheterization and TEE was −0.13 ± 0.19 cm (p =0.122). absolute difference between AVA derived by CMR in vivo The mean absolute difference between AVA calculated and calculated using the Gorlin formula by catheterization using the continuity equation by TTE and TEE was −0.08 2 2 was +0.17 ± 0.27 cm (p = 0.117). In linear regression ana- ±0.10 cm (p = 0.97). In linear regression analysis the cor- lysis the correlation between CMR ex vivo and Gorlin relation between Gorlin formula by catheterization and formula by catheterization was r = 0.09, p = 0.835 and TEE was r = 0.71, p = 0.073 and between Gorlin Buchner et al. BMC Medical Imaging (2015) 15:34 Page 5 of 8 Table 2 Results Patient Aortic Aortic AVA in vivo AVA ex vivo AVA by AVA by AVA by PG mean by PG mean by LV EF LV Mass LV SV valve valve type by CMR by CMR TEE TTE CATH Doppler CATH by CMR by CMR by CMR 2 2 2 2 2 type CMR surgery (cm ) (cm ) (cm ) (cm ) (cm ) (mmHg) (mmHg) (%) (g) (ml) 1 BAV BAV 0.84 0.76 - 0.74 0.29 65 77 50 151 61 2 TAV TAV 0.70 0.55 0.65 0.65 0.36 59 65 41 126 36 3 TAV TAV 0.84 0.73 0.70 0.75 0.64 53 45 81 177 81 4 TAV TAV 0.86 0.70 0.80 0.75 0.52 76 76 59 178 73 5 TAV TAV 0.62 0.50 0.70 0.55 0.34 44 46 19 134 40 6 BAV BAV 0.76 0.69 1.10 0.65 0.85 40 35 45 210 72 7 TAV TAV 0.72 0.68 0.75 0.73 0.67 49 55 77 113 57 8 TAV TAV 0.71 0.59 0.80 0.69 1.08 30 20 71 120 50 AVA, aortic valve area; BAV, bicuspid aortic valve; CMR, cardiovascular magnetic resonance; CATH, cardiac catheterization; TEE, transesophageal echocardiography; TTE, transthoracic echocardiography; LV EF, left ventricular ejection fraction; LV mass, left ventricular mass; LV SV, left ventricular stroke volume; PG, pressure gradient; TAV, tricuspid aortic valve formula by catheterization and the continuity equa- ability of CMR to accurately and precisely planimetry tion by TTE was r = 0.17, p = 0.639 and between TEE aortic valve stenosis in vivo comparing by ex vivo CMR. and catheterization and the continuity equation by Characterization of the severity of aortic stenosis is TTE was r = 0.15, p = 0.748. among the most difficult problems in valvular heart dis- ease. Exact determination of the severity of stenosis is Discussion essential to guide therapy [18]. In evaluating the severity The results of this study demonstrate that aortic valve of the aortic valve stenosis, it is ideally desirable to de- stenosis can be accurately planimetered by using CMR termine geometric orifice area On the other hand, the in vivo compared with ex vivo model. Precise assess- opening of the aortic valve is though highly dependent ment of aortic valveareain aorticstenosisiscrucial for of the flow and gradient. Because planimetry only pro- optimal patient treatment [17]. However, no compari- vides geometric orifice area and does not characterize son of planimetry of the aortic valve area has made the flow property, this could be a challenge in low-flow/ with in vivo and ex vivo aortic valves by CMR or other low-gradient aortic stenosis [19–21]. The guidelines allow modality. The present study is the first to validate the various methods to determine the AVA. However, the Fig. 3 Images derived from the in vivo CMR (a), from the aortic valve specimen (b) and from the ex vivo CMR (c) in a bicuspid stenotic valve (top) and in a tricuspid stenotic valve (bottom) Buchner et al. BMC Medical Imaging (2015) 15:34 Page 6 of 8 Table 3 Comparison of methods of planimetry and calculation potential imprecision introduced by the hemodynamic pa- of aortic valve area rameters. Finally, CMR has its limitation in valve motion Aortic valve area (cm ) and exact slice orientation or in contraindication for CMR (e.g. claustrophia or metallic implants). Method Mean Range Prior to our study, several other investigators have de- CMR ex vivo 0.65 ± 0.09 0.50 – 0.76 termined the accuracy of several methods for CMR and CMR in vivo 0.75 ± 0.09 0.62 – 0.86 cardiac computed tomography planimetry of the aortic TEE 0.80 ± 0.16 0.65 – 1.10 valve using an angiographic reference standard or Doppler TTE 0.69 ± 0.07 0.50 – 0.70 derived data [7–9, 22, 23]. However, the ultimate test of CATH 0.59 ± 0.27 0.29 – 1.08 the value of the method seems to be comparison with CMR, cardiovascular magnetic resonance; CATH, cardiac catheterization; TEE, anatomy. The current study extends these findings as it transesophageal echocardiography; TTE, transthoracic echocardiography demonstrates that CMR allows to accurately visualizing the anatomic valve area in vivo compared to ex vivo. different available techniques often might lead to discrep- To date, most CMR studies for the quantification of ancy results. This could demonstrate in the current study stenotic aortic valves have focused on direct planimetry and previous studies which show that the planimtery of the [24], although the dimensions of CMR voxels relative to AVA was systematically higher than the calculated AVA by the size and shape of stenotic orifices sometimes influ- Gorlin in catheterization or continuity equation in TTE. ence this approach. Therefore, an ex vivo study was This is due to the fact that direct planimetry reflects the deemed as an essential intermediate study for assessing anatomical orifice while the calculated valve area reflects sources of errors in CMR aortic valve estimation prior theeffective orificearea. Despitethe different available to in vivo experiments. Ex vivo estimates eliminate techniques for the assessment of the AVA all available errors due to motion blurring, which includes errors techniques have their limitations and this should be keep resulting from irregular heart rates and images acquired in mind. In TTE, the inexact measurement of the diameter during motion. Furthermore, ex vivo determinations also of the left ventricular outflow tract or missed peak trans- minimize uncertainties due to edge definition and pro- valvular velocity might lead to a false AVA. In TEE, heavily duced high-contrast edges in which the aortic valve calcification of the aortic valve could lead to impaired boundary is defined to be pixel values above back- image quality e.g. by the acoustic shadowing, thus exact ground. The results of this study should, therefore, be delineation of the cusps and planimetry of the AVA are interpreted as the minimum errors which can be impossible or the potential inability to identify the accur- achieved using CMR. ate imaging plane for planimetry. Hemodynamic assess- Despite the close correlation between ex vivo and in ment of the aortic valve area by invasive cardiac vivo planimetry by CMR, we observed an underestima- catheterization has often been challenged because of tion of the aortic valve area by CMR ex vivo.The Fig. 4 Agreement between aortic valve area assessed by CMR in vivo and by CMR ex vivo (a). According to Bland-Altman (b), the difference between the two comparative measurements is plotted against their mean. The continuous line represents the mean difference and dashed lines represent the limits of agreement (mean difference ± 2SD) Buchner et al. BMC Medical Imaging (2015) 15:34 Page 7 of 8 underlying reason for underestimation of the aortic valve Acknowledgment The authors thank Marion Merdian and Heike Koitsch for excellent technical area by CMR may be related to valve motion and slice assistance. orientation. Specifically, transplanar valve motion during systole might lead to overestimation of valve area when Author details Klinik und Poliklinik für Innere Medizin II, Universitätsklinikum Regensburg, the imaging plane misses the smallest orifice area. Franz-Josef-Strauss-Allee 11, 93042 Regensburg, Germany. Institut für Taking measurement from CMR, one has to make sure Röntgendiagnostik, Universitätsklinikum Regensburg, Regensburg, Germany. that the plane is orthogonal and on the edge of the leaf- Klinik und Poliklinik für Herz-, Thorax- und herznahe Gefäßchirurgie, Universitätsklinikum Regensburg, Regensburg, Germany. lets. Ex vivo imaging, however, eliminates potential errors caused by cardiac and respiratory motion. Received: 23 March 2015 Accepted: 11 August 2015 Limitations Several limitations of our study should be noted. The References 1. Selzer A. Changing aspects of the natural history of valvular aortic stenosis. sample size of the current study was small. Most of the N Engl J Med. 1987;317:91–8. patients had been diagnosed with high-grade aortic valve 2. Vahanian A, Alfieri O, Andreotti F, Antunes MJ, Baron-Esquivias G, stenosis, resulting in a selection bias. However, because Baumgartner H, et al. Guidelines on the management of valvular heart disease (version 2012): The joint task force on the management of valvular we decided to use combined left and right heart heart disease of the european society of cardiology (esc) and the european catheterization and study the explanted aortic valve, we association for cardio-thoracic surgery (eacts). Eur J Cardiothorac Surg. were unable to include patients with mild aortic stenosis, 2012;42:S1–44. 3. Leborgne L, Tribouilloy C, Otmani A, Peltier M, Rey JL, Lesbre JP. Comparative because, in these patients these would not be justified. value of doppler echocardiography and cardiac catheterization in the decision Furthermore, only the static area of the aortic valve was to operate on patients with aortic stenosis. Int J Cardiol. 1998;65:163–8. measured and do not reflect the hemodynamic condi- 4. Garcia D, Dumesnil JG, Durand LG, Kadem L, Pibarot P. Discrepancies between tions in vivo. However, it is difficult to assess the dy- catheter and doppler estimates of valve effective orifice area can be predicted from the pressure recovery phenomenon: Practical implications with regard to namic change of stenotic aortic valve area in ex vivo quantification of aortic stenosis severity. J Am Coll Cardiol. 2003;41:435–42. specimens. In this study only due to the heavy calcifica- 5. Schmidt M, Crnac J, Dederichs B, Theissen P, Schicha H, Sechtem U. tion of the aortic valve, it was possible to explant the Magnetic resonance imaging in valvular heart disease. Int J Card Imaging. 1997;13:219–31. valve as a unit and we presume that the shape of the 6. Lee SC, Ko SM, Song MG, Shin JK, Chee HK, Hwang HK. Morphological valve represent the maximum opening of the valve in assessment of the aortic valve using coronary computed tomography systole. Consequently, the aortic valve area of the angiography, cardiovascular magnetic resonance, and transthoracic echocardiography: Comparison with intraoperative findings. Int J Cardiovasc explanted aortic valve corresponds by the calcification Imaging. 2012;28 Suppl 1:33–44. the smallest maximal orifice may merely influenced by 7. Debl K, Djavidani B, Seitz J, Nitz W, Schmid FX, Muders F, et al. Planimetry of ejection and diastolic valve closing. aortic valve area in aortic stenosis by magnetic resonance imaging. Invest Radiol. 2005;40:631–6. 8. John AS, Dill T, Brandt RR, Rau M, Ricken W, Bachmann G, et al. Conclusion Magnetic resonance to assess the aortic valve area in aortic stenosis: How does it compare to current diagnostic standards? J Am Coll In conclusion, this is the first study to validate planim- Cardiol. 2003;42:519–26. etry in aortic valve stenosis using CMR in an ex vivo 9. Friedrich MG, Schulz-Menger J, Poetsch T, Pilz B, Uhlich F, Dietz R. model. CMR in vivo slightly overestimates the valve area Quantification of valvular aortic stenosis by magnetic resonance imaging. Am Heart J. 2002;144:329–34. in aortic stenosis compared to CMR ex vivo. Further- 10. Kupfahl C, Honold M, Meinhardt G, Vogelsberg H, Wagner A, Mahrholdt H, more, planimetry of AVA using CMR in vivo and ex vivo et al. Evaluation of aortic stenosis by cardiovascular magnetic resonance model correlated well with calculated AVA by TTE, in imaging: Comparison with established routine clinical techniques. Heart. 2004;90:893–901. contrast to TEE and invasive measurements of AVA. 11. Garcia J, Pibarot P, Capoulade R, Le Ven F, Kadem L, Larose E. Usefulness of These certain methodical discrepancies between these cardiovascular magnetic resonance imaging for the evaluation of valve methods must be taken into account when grading the opening and closing kinetics in aortic stenosis. Eur Heart J Cardiovasc Imaging. 2013;14:819–26. severity of aortic stenosis by AVA. 12. von Knobelsdorff-Brenkenhoff F, Rudolph A, Wassmuth R, Bohl S, Buschmann EE, Abdel-Aty H, et al. Feasibility of cardiovascular magnetic Abbreviations resonance to assess the orifice area of aortic bioprostheses. Circ Cardiovasc AVA: Aortic valve area; CMR: Cardiac magnetic resonance; Imaging. 2009;2:397–404. 392 p following 404. TEE: Transoseophageal echocardiography. 13. Buchner S, Hulsmann M, Poschenrieder F, Hamer OW, Fellner C, Kobuch R, et al. Variable phenotypes of bicuspid aortic valve disease: Classification by Competing interests cardiovascular magnetic resonance. Heart. 2010;96:1233–40. The authors declare that they have no competing interests. 14. Buchner S, Debl K, Haimerl J, Djavidani B, Poschenrieder F, Feuerbach S, et al. Electrocardiographic diagnosis of left ventricular hypertrophy in aortic valve disease: Evaluation of ecg criteria by cardiovascular magnetic Authors’ contributions resonance. J Cardiovasc Magn Reson. 2009;11:18. SB: study design, acquisition of the data, image analysis, statistical analysis, manuscript drafting. KD, AL: study design, image analysis, manuscript 15. Baumgartner H, Hung J, Bermejo J, Chambers JB, Evangelista A, Griffin BP, et revising. FS: acquisition of the data, manuscript revising. BD: study design, al. Echocardiographic assessment of valve stenosis: Eae/ase acquisition of the data, image analysis, manuscript drafting. recommendations for clinical practice. Eur J Echocardiogr. 2009;10:1–25. Buchner et al. BMC Medical Imaging (2015) 15:34 Page 8 of 8 16. Gorlin R, Gorlin SG. Hydraulic formula for calculation of the area of the stenotic mitral valve, other cardiac valves, and central circulatory shunts. I Am Heart J. 1951;41:1–29. 17. Baumgartner H. Aortic stenosis: medical and surgical management. Heart. 2005; 91(11):1483–1488. 18. Vahanian A, Alfieri O, Andreotti F, Antunes MJ, Baron-Esquivias G, Baumgartner H, et al. Guidelines on the management of valvular heart disease (version 2012). Eur Heart J. 2012;33:2451–96. 19. Minners J, Allgeier M, Gohlke-Baerwolf C, Kienzle RP, Neumann FJ, Jander N. Inconsistencies of echocardiographic criteria for the grading of aortic valve stenosis. European Heart Journal. 2008;29:1043–8. 20. Hachicha Z, Dumesnil JG, Bogaty P, Pibarot P. Paradoxical low-flow, low- gradient severe aortic stenosis despite preserved ejection fraction is associated with higher afterload and reduced survival. Circulation. 2007;115:2856–64. 21. Jander N, Minners J, Holme I, Gerdts E, Boman K, Brudi P, et al. Outcome of patients with low-gradient "severe" aortic stenosis and preserved ejection fraction. Circulation. 2011;123:887–95. 22. 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Cardiovascular magnetic resonance assessment of the aortic valve stenosis: an in vivo and ex vivo study

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Springer Journals
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Copyright © 2015 by Buchner et al.
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Medicine & Public Health; Imaging / Radiology
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1471-2342
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10.1186/s12880-015-0076-x
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Abstract

Background: Aortic valve area (AVA) estimation in patients with aortic stenosis may be obtained using several methods. This study was undertaken to verify the cardiovascular magnetic resonance (CMR) planimetry of aortic stenosis by comparing the findings with invasive catheterization, transthoracic (TTE) as well as tranesophageal echocardiography (TEE) and anatomic CMR examination of autopsy specimens. Methods: Our study was performed in eight patients with aortic valve stenosis. Aortic stenosis was determined by TTE and TEE as well as catheterization and CMR. Especially, after aortic valve replacement, the explanted aortic valves were examined again with CMR ex vivo model. 2 2 Results: The mean AVA determined in vivo by CMR was 0.75 ± 0.09 cm and ex vivo by CMR was 0.65 ± 0.09 cm and was closely correlated (r = 0.91, p < 0.001). The mean absolute difference between AVA derived by CMR ex vivo and in vivo was −0.10 ± 0.04 cm . The mean AVA using TTE was 0.69 ± 0.07 with a significant correlation between CMR ex vivo (r = 0.85, p < 0.007) and CMR in vivo (r = 0.86, p < 0.008). CMR ex vivo and in vivo had no significant correlation with AVA using Gorlin formula by invasive catheterization or using planimetry by TEE. Conclusion: In this small study using an ex vivo aortic valve stenosis model, the aortic valve area can be reliably planimetered by CMR in vivo and ex vivo with a well correlation between geometric AVA by CMR and the effective AVA calculated by TTE. Keywords: Aortic valve, Aortic stenosis, Magnetic resonance imaging, Anatomy Background reference (“gold standard”) whereas the Gorlin-formula is Aortic valve stenosis is the most common cardiac valve the historical reference. disease resulting in valve therapy [1]. Exact determination Cardiovascular magnetic resonance (CMR) is a noninva- of the severity of stenosis is essential to guide therapy [2]. sive method that allows visualization of cardiac function, Standard methods, such as cardiac catheterization and structure and valves [5, 6]. Recently, we and others have transthoracic echocardiography (TTE) have to calculate reported the success of planimetry by CMR in aortic valve the effective orifice area by measurement of the transvalv- [7–14]. ular pressure gradient [3, 4], as they do not allow a direct However, to date, no studies have been published and precise measurement of the geometric orifice area. describing ex vivo CMR stenotic aortic valves. It there- Therefore it seems desirable to directly determine the fore seemed useful to compare anatomic data with CMR geometric orifice area by a flow independent technique imaging. such as planimetry. Several cardiologists take the view that We hypothesized that direct planimetry of the stenotic TTE using the Doppler-technique is now the best aortic valve in an autopsy human valve as a standard of reference using CMR corresponds to the planimetry of the stenotic aortic valve in vivo using CMR. To address * Correspondence: stefan.buchner@ukr.de 1 this hypothesis, we performed a head-to-head comparison Klinik und Poliklinik für Innere Medizin II, Universitätsklinikum Regensburg, between aortic valve area (AVA) planimetry preoperatively Franz-Josef-Strauss-Allee 11, 93042 Regensburg, Germany Full list of author information is available at the end of the article © 2015 Buchner et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Buchner et al. BMC Medical Imaging (2015) 15:34 Page 2 of 8 by CMR and postoperatively of the explanted aortic valve Transesophageal Echocardiography by CMR in a series of eight patients with aortic valve Multiplane TEE was performed using a 5-Mhz annular stenosis. In addition, CMR measurements were compared phased array probe. For examination of the aortic valve, with TTE and transesophageal echocardiography (TEE) as the imaging plane was rotated from 0° to 180° until the well as catheterization data best imageoftheaortic valveopening in theshort axis view was obtained (usually around 60°). Minimal probe manipulation was performed to ensure that the smallest Methods orifice of the aortic valve at the leaflet tips was identi- Patients fied. Planimetry of the smallest orifice at the time of Eight patients referred to our institution for evaluation of maximum opening in early systole (triggered by the aortic valve stenosis and were prospectively included in electrocardiogram) was performed. At least three con- the study undergoing aortic valve replacement. All diag- secutive measurements were averaged. nostic procedures and measurements were performed by experienced observers, who were blinded to the results of Catheterization the other imaging modalities. Informed consent was A standard cardiac catheterization procedure was obtained in all patients. The study approved by local ethics performed via the percutaneous femoral approach, in- committee of the Universität Regensburg. cluding right and left heart pressure measurement. Peak to peak and mean pressure gradients were determined between left ventricle and ascending aorta. Cardiac Clinical characteristics of the patients output was measured by thermodilution, averaging at Clinical data of the eight patients are summarized in least 3 measurements. AVA was estimated using the Table 1. Mean age was 76 ± 6 (62 to 82) years. The Gorlin formula [16]. majority of patients presented with clinical symptoms of severe aortic stenosis, such as systolic murmur, dyspnea, Surgery and autopsy chest pain or syncope. Concomitant aortic regurgitation The description of the aortic valve was obtained from was present in 5 patients and was defined as mild/trivial one surgeon. We obtained human valves from patients (n = 4) or moderate (n = 1) by CMR and echocardiog- with aortic valve stenosis at the time of surgical valve raphy. TEE planimetry of AVA was not possible in one replacement. Despite the heavy calcification, all valves patient because of heavy calcifications. Planimetry of could be explanted totally. Specimens were originally AVA was possible in all patients undergoing CMR. An preserved in formaldehyde solution. impaired image quality was observed in one patient due to trigger problems by cardiac arrhythmia. Cardiovascular magnetic resonance studies – in vivo All patient studies were performed on a 1.5 T scanner Transthoracic echocardiography (Sonata, Siemens Medical Solutions, Erlangen, Germany). Standardized transthoracic echocardiography was per- CMR studies were performed in supine position with a formed with measurements of the left ventricular outflow phased-array receiver coil and breath-hold acquisitions tract diameter, the velocity of across the aortic valve and prospectively gated to the ECG. Cine images were ac- flow data of the left ventricular outflow tract to calculate quired in multiple short axis and long axis views with fast the AVA using the continuity equation [15]. imaging with steady state free precession (trueFISP, slice thickness 8 mm, echo time 1.53 ms, readout bandwidth 1.085 Hz/pixel, repetition time 3.14 ms, matrix 256*202). Table 1 Patient characteristics Image analysis was performed off-line using the semi- Patient Age Sex Rhythm HR SBP NYHA CCS Syncope automatic ARGUS evaluation program (Siemens Medical 1 80 female SR 71 130 4 0 0 Solutions, Erlangen, Germany), which is a part of the 2 82 female AF 77 158 3 1 0 commercially available cardiac package of the scanner 3 74 female SR 91 125 2 0 0 software. 4 75 female SR 67 115 3 0 1 The imaging plane of the aortic valve was defined by ac- 5 79 female SR 83 120 3 2 0 quiring a systolic 5-chamber view parallel to the long axis of the left ventricular outflow tract and a long axis view of 6 75 male AF 97 116 4 3 0 the left ventricular outflow tract and the proximal aorta, 7 62 female SR 63 130 3 4 0 perpendicular to the 5-chamber view, as described previ- 8 77 female SR 80 130 3 2 0 ously [7]. In brief, the subsequent slices were defined SR, sinus rhythm; AF, atrial fibrillation; HR, heart rate; SBP, systolic blood parallel to the valvular plane and, additionally, in cases of pressure; NYHA, New York Heart Association, CCS, Canadian Cardiovascular Society orifices with an eccentric outlet, perpendicularly to the Buchner et al. BMC Medical Imaging (2015) 15:34 Page 3 of 8 direction of the jet. At least 4 slices (range 4–7) at differ- Statistical analysis ent levels of the aortic valve were acquired and the im- Data expressed as mean ± standard deviation. Linear re- aging plane with the smallest orifice was chosen. gression analysis was performed to describe correlations Planimetry of the smallest orifice at the time of maximum between the different techniques. The mean AVA of the opening in early systole in the acquisitions prospectively different techniques was compared by student's t-Test triggered to the electrocardiogram was performed by two for paired samples. Intra- and interobserver variability independent observers, who were unaware of the echocar- (n = 8) were expressed as the percentage of variability diographic, catheterization and ex vivo results. We placed (absolute value of the difference between 2 measure- our traces at the point of the bright pixels. Three measure- ments divided by the mean of 2 measurements). Agree- ments were performed and average for calculating the ment between the different techniques was assessed as AVA. Intraobserver and interobserver variabilities regard- described by Bland and Altman. A level of significance ing AVA were 3 % and 6 % for in vivo CMR, respectively. of below 0.05 was defined as statistically significant. SPSS version 21 (SPSS Institute, Chicago) was used for Cardiovascular magnetic resonance studies – ex vivo statistical analysis. All specimens were examined on a 1.5 T scanner (Magnetom Sonata, Siemens Medical Solutions, Erlangen, Results Germany). The CMR imaging protocol included a 3D- CMR planimetry of AVA in vivo and ex vivo CISS protocol (TR/TE/flip angle 17/8.08 ms/70° ms, band The measurements of all patients by the various modal- width 130 Hz/pixel, effective slice thickness 1 mm pixel ities are depicted in Table 2. Six valves were tricuspid size 0.6 × 0.45 mm). The aortic valve was placed on a rack and two valves were bicuspid. Images of aortic valve spe- into a water container. Then the container with the aortic cimen, in vivo and ex vivo CMR are depicted in Fig 3. valve was placed in the gantry. Slices in the orthogonal The mean AVA determined ex vivo by CMR was 0.65 ± planes (transverse, coronal and sagittal) were obtained 0.09 cm . Mean AVA determined in vivo by CMR was 0.75 (Fig. 1). Serial angulated-axis views from the base to tip of ±0.09 cm . The mean absolute difference between AVA the valve were acquired with 3D sequence (Fig. 2). derived by CMR ex vivo and in vivo was 0.10 ± 0.04 cm Planimetry of the smallest orifice was performed by two (p<0.001,Fig.4and Table 3). The AVA in vivo and ex vivo independent observers, who were unaware of the echo- by CMR was closely correlated (r = 0.91, p < 0.001). cardiographic, catheterization and in vivo results. We The mean absolute difference between AVA derived by placed our traces at the edge of the bright pixels. Three CMR ex vivo and calculated using the continuity equa- measurements were performed and average for calcu- tion by TTE was −0.04 ± 0.05 cm (p = 0.066). The mean lating the AVA. Intraobserver and interobserver vari- absolute difference between AVA derived by CMR in abilities were 1 % and 4 % for ex vivo CMR, respectively. vivo and calculated using the continuity equation by AB CD Fig. 1 Position of the ex vivo aortic valve fixed in a water container and planning the slices. a, overview; b, coronar view; c, angulation for planning the orthograd view; d, the resulting orthograd view Buchner et al. BMC Medical Imaging (2015) 15:34 Page 4 of 8 Fig. 2 To avoid assessing the aortic valve area beyond or above the leaflet tips, the imaging plane was moved shift wise in one mm steps in an orthograd direction. Planimetry was chosen on the slice where the smallest orifice was surrounded totally by the edge of the valve TTE was +0.07 ± 0.04 cm . In linear regression analysis between CMR in vivo and Gorlin formula by the correlation between CMR ex vivo and TTE (r = 0.85, catheterization was r = −0.03, p = 0.952. p < 0.007) was similar to that between CMR in vivo and TTE (r = 0.86, p < 0.008). AVA with other methods The mean absolute difference between aortic valve The mean of the aortic valve area calculated using the area derived by CMR ex vivo and TEE was +0.12 ± Gorlin formula by catheterization was 0.60 ± 0.27 cm . 0.09 cm (p = 0.012). The mean absolute difference be- The mean aortic valve area determined by TEE was 0.79 tween aortic valve area derived by CMR in vivo and ± 0.15 cm . The mean of the aortic valve area calculated TEE was −0.02 ± 0.10 cm (p = 0.75). In linear regres- by TTE was 0.69 ± 0.07 (Table 3). sion analysis the correlation between CMR ex vivo and The mean absolute difference between AVA derived TEE was r = 0.44, p = 0.323) and between CMR in vivo calculated using the Gorlin formula by catheterization and and TEE r = 0.28, p = 0.551. calculated using the continuity equation by TTE was Themeanabsolutedifferencebetween AVAderived by −0.11 ± 0.25 cm (p =0.278). The mean absolute differ- CMR ex vivo and calculated using the Gorlin formula by ence between AVA using the Gorlin formula by 2 2 catheterization was +0.07 ± 0.26 cm (p = 0.498). The mean catheterization and TEE was −0.13 ± 0.19 cm (p =0.122). absolute difference between AVA derived by CMR in vivo The mean absolute difference between AVA calculated and calculated using the Gorlin formula by catheterization using the continuity equation by TTE and TEE was −0.08 2 2 was +0.17 ± 0.27 cm (p = 0.117). In linear regression ana- ±0.10 cm (p = 0.97). In linear regression analysis the cor- lysis the correlation between CMR ex vivo and Gorlin relation between Gorlin formula by catheterization and formula by catheterization was r = 0.09, p = 0.835 and TEE was r = 0.71, p = 0.073 and between Gorlin Buchner et al. BMC Medical Imaging (2015) 15:34 Page 5 of 8 Table 2 Results Patient Aortic Aortic AVA in vivo AVA ex vivo AVA by AVA by AVA by PG mean by PG mean by LV EF LV Mass LV SV valve valve type by CMR by CMR TEE TTE CATH Doppler CATH by CMR by CMR by CMR 2 2 2 2 2 type CMR surgery (cm ) (cm ) (cm ) (cm ) (cm ) (mmHg) (mmHg) (%) (g) (ml) 1 BAV BAV 0.84 0.76 - 0.74 0.29 65 77 50 151 61 2 TAV TAV 0.70 0.55 0.65 0.65 0.36 59 65 41 126 36 3 TAV TAV 0.84 0.73 0.70 0.75 0.64 53 45 81 177 81 4 TAV TAV 0.86 0.70 0.80 0.75 0.52 76 76 59 178 73 5 TAV TAV 0.62 0.50 0.70 0.55 0.34 44 46 19 134 40 6 BAV BAV 0.76 0.69 1.10 0.65 0.85 40 35 45 210 72 7 TAV TAV 0.72 0.68 0.75 0.73 0.67 49 55 77 113 57 8 TAV TAV 0.71 0.59 0.80 0.69 1.08 30 20 71 120 50 AVA, aortic valve area; BAV, bicuspid aortic valve; CMR, cardiovascular magnetic resonance; CATH, cardiac catheterization; TEE, transesophageal echocardiography; TTE, transthoracic echocardiography; LV EF, left ventricular ejection fraction; LV mass, left ventricular mass; LV SV, left ventricular stroke volume; PG, pressure gradient; TAV, tricuspid aortic valve formula by catheterization and the continuity equa- ability of CMR to accurately and precisely planimetry tion by TTE was r = 0.17, p = 0.639 and between TEE aortic valve stenosis in vivo comparing by ex vivo CMR. and catheterization and the continuity equation by Characterization of the severity of aortic stenosis is TTE was r = 0.15, p = 0.748. among the most difficult problems in valvular heart dis- ease. Exact determination of the severity of stenosis is Discussion essential to guide therapy [18]. In evaluating the severity The results of this study demonstrate that aortic valve of the aortic valve stenosis, it is ideally desirable to de- stenosis can be accurately planimetered by using CMR termine geometric orifice area On the other hand, the in vivo compared with ex vivo model. Precise assess- opening of the aortic valve is though highly dependent ment of aortic valveareain aorticstenosisiscrucial for of the flow and gradient. Because planimetry only pro- optimal patient treatment [17]. However, no compari- vides geometric orifice area and does not characterize son of planimetry of the aortic valve area has made the flow property, this could be a challenge in low-flow/ with in vivo and ex vivo aortic valves by CMR or other low-gradient aortic stenosis [19–21]. The guidelines allow modality. The present study is the first to validate the various methods to determine the AVA. However, the Fig. 3 Images derived from the in vivo CMR (a), from the aortic valve specimen (b) and from the ex vivo CMR (c) in a bicuspid stenotic valve (top) and in a tricuspid stenotic valve (bottom) Buchner et al. BMC Medical Imaging (2015) 15:34 Page 6 of 8 Table 3 Comparison of methods of planimetry and calculation potential imprecision introduced by the hemodynamic pa- of aortic valve area rameters. Finally, CMR has its limitation in valve motion Aortic valve area (cm ) and exact slice orientation or in contraindication for CMR (e.g. claustrophia or metallic implants). Method Mean Range Prior to our study, several other investigators have de- CMR ex vivo 0.65 ± 0.09 0.50 – 0.76 termined the accuracy of several methods for CMR and CMR in vivo 0.75 ± 0.09 0.62 – 0.86 cardiac computed tomography planimetry of the aortic TEE 0.80 ± 0.16 0.65 – 1.10 valve using an angiographic reference standard or Doppler TTE 0.69 ± 0.07 0.50 – 0.70 derived data [7–9, 22, 23]. However, the ultimate test of CATH 0.59 ± 0.27 0.29 – 1.08 the value of the method seems to be comparison with CMR, cardiovascular magnetic resonance; CATH, cardiac catheterization; TEE, anatomy. The current study extends these findings as it transesophageal echocardiography; TTE, transthoracic echocardiography demonstrates that CMR allows to accurately visualizing the anatomic valve area in vivo compared to ex vivo. different available techniques often might lead to discrep- To date, most CMR studies for the quantification of ancy results. This could demonstrate in the current study stenotic aortic valves have focused on direct planimetry and previous studies which show that the planimtery of the [24], although the dimensions of CMR voxels relative to AVA was systematically higher than the calculated AVA by the size and shape of stenotic orifices sometimes influ- Gorlin in catheterization or continuity equation in TTE. ence this approach. Therefore, an ex vivo study was This is due to the fact that direct planimetry reflects the deemed as an essential intermediate study for assessing anatomical orifice while the calculated valve area reflects sources of errors in CMR aortic valve estimation prior theeffective orificearea. Despitethe different available to in vivo experiments. Ex vivo estimates eliminate techniques for the assessment of the AVA all available errors due to motion blurring, which includes errors techniques have their limitations and this should be keep resulting from irregular heart rates and images acquired in mind. In TTE, the inexact measurement of the diameter during motion. Furthermore, ex vivo determinations also of the left ventricular outflow tract or missed peak trans- minimize uncertainties due to edge definition and pro- valvular velocity might lead to a false AVA. In TEE, heavily duced high-contrast edges in which the aortic valve calcification of the aortic valve could lead to impaired boundary is defined to be pixel values above back- image quality e.g. by the acoustic shadowing, thus exact ground. The results of this study should, therefore, be delineation of the cusps and planimetry of the AVA are interpreted as the minimum errors which can be impossible or the potential inability to identify the accur- achieved using CMR. ate imaging plane for planimetry. Hemodynamic assess- Despite the close correlation between ex vivo and in ment of the aortic valve area by invasive cardiac vivo planimetry by CMR, we observed an underestima- catheterization has often been challenged because of tion of the aortic valve area by CMR ex vivo.The Fig. 4 Agreement between aortic valve area assessed by CMR in vivo and by CMR ex vivo (a). According to Bland-Altman (b), the difference between the two comparative measurements is plotted against their mean. The continuous line represents the mean difference and dashed lines represent the limits of agreement (mean difference ± 2SD) Buchner et al. BMC Medical Imaging (2015) 15:34 Page 7 of 8 underlying reason for underestimation of the aortic valve Acknowledgment The authors thank Marion Merdian and Heike Koitsch for excellent technical area by CMR may be related to valve motion and slice assistance. orientation. Specifically, transplanar valve motion during systole might lead to overestimation of valve area when Author details Klinik und Poliklinik für Innere Medizin II, Universitätsklinikum Regensburg, the imaging plane misses the smallest orifice area. Franz-Josef-Strauss-Allee 11, 93042 Regensburg, Germany. Institut für Taking measurement from CMR, one has to make sure Röntgendiagnostik, Universitätsklinikum Regensburg, Regensburg, Germany. that the plane is orthogonal and on the edge of the leaf- Klinik und Poliklinik für Herz-, Thorax- und herznahe Gefäßchirurgie, Universitätsklinikum Regensburg, Regensburg, Germany. lets. Ex vivo imaging, however, eliminates potential errors caused by cardiac and respiratory motion. Received: 23 March 2015 Accepted: 11 August 2015 Limitations Several limitations of our study should be noted. The References 1. Selzer A. Changing aspects of the natural history of valvular aortic stenosis. sample size of the current study was small. Most of the N Engl J Med. 1987;317:91–8. patients had been diagnosed with high-grade aortic valve 2. Vahanian A, Alfieri O, Andreotti F, Antunes MJ, Baron-Esquivias G, stenosis, resulting in a selection bias. However, because Baumgartner H, et al. 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