Role of MDCT Imaging in Planning Mitral Valve ... - Springer Link

Current Cardiology Reports (2018) 20:16 https://doi.org/10.1007/s11886-018-0960-4

CARDIAC PET, CT, AND MRI (F PUGLIESE AND SE PETERSEN, SECTION EDITORS)

Role of MDCT Imaging in Planning Mitral Valve Intervention Rominder Grover 1 & Mickael Ohana 1 & Chesnal Dey Arepalli 1 & Stephanie L. Sellers 1,2 & John Mooney 1 & Shaw-Hua Kueh 1 & Ung Kim 1 & Philipp Blanke 1 & Jonathon A. Leipsic 1,2,3,4

# Springer Science+Business Media, LLC, part of Springer Nature 2018

Abstract Purpose of Review Recent advancements in transcatheter valvular interventions have resulted in a growing demand for advanced cardiac imaging to help guide these procedures. Recent Findings Both echocardiography and multi-detector computed tomography have played essential roles in the maturation of transcatheter aortic valve replacement and are now building on these experiences and helping inform the nascent field of transcatheter mitral interventions. Summary Advanced imaging is essential to aid in the diagnosis and determination of the mechanism of mitral regurgitation. In addition, they are integral to annular sizing, determination of the suitability of patient anatomy for specific devices and increasingly important in the determination of the risk of left ventricular outflow tract obstruction and providing appropriate patientspecific fluoroscopic angulation in advance of the procedure. Keywords Transcatheteraorticvalve replacement . Aortic stenosis . Mitralregurgitation . Computedtomography . Left ventricular outflow tract . Annulus

Introduction The past decade has seen rapid development in multi-detector computed tomography (MDCT) technology with significant improvements in spatial and temporal resolution. In addition to coronary artery assessment, new-generation MDCT scanners also allow for high-quality detailed analysis of the cardiac valves. Echocardiography remains the first line investigation for valvular evaluation; however, limitations include the operator dependency of transthoracic echocardiography (TTE) and the invasive

This article is part of the Topical Collection on Cardiac PET, CT, and MRI * Jonathon A. Leipsic [email protected] 1

Department of Radiology, St Paul’s Hospital and University of British Columbia, Vancouver, Canada

2

Centre for Heart Lung Innovation, St Paul’s Hospital and University of British Columbia, Vancouver, Canada

3

Division of Cardiology, Department of Medicine, University of British Columbia, Vancouver, Canada

4

Department of Radiology, St. Paul’s Hospital, 1081 Burrard St, Vancouver, BC V6Z 1Y6, Canada

nature of transesophageal echocardiography (TEE), with image acquisition restricted to a finite number of planes/projections. Three-dimensional (3D) MDCT imaging enables efficient acquisition of volumetric datasets which can be subsequently manipulated in an unlimited number of 2D planes. These advances have occurred concurrently with the increasing application of transcatheter valvular therapies in symptomatic but inoperable patients suffering from severe valvular heart disease. As the most prevalent valvular diseases, mitral regurgitation (MR) and aortic stenosis (AS) constitute a significant health burden [1, 2]. Not infrequently, the elderly patients suffering with these valvular conditions are often unable to undergo surgical therapy due to comorbidities and transcatheter interventions that aim to resolve this clinical dilemma [3, 4]. Transcatheter aortic valve replacement (TAVR) is now widely performed for patients considered to be high and now intermediate risk for traditional surgical intervention with a large body of supporting evidence [5]. Whilst surgical mitral valve replacement for MR carries a decreased recurrence risk, superior clinical outcomes are observed with repair strategies that maintain the sub-valvular anatomy [6]. Developed along similar lines to TAVR, transcatheter mitral valve implantation (TMVI) aims to replace the valve while still preserving chordal integrity [7–12].

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High-quality non-invasive imaging is an essential component of transcatheter therapeutics and guides the assessment of patient suitability, prosthesis sizing and access planning [13]. Advanced imaging has undergone rapid integration in the TMVI domain building on the years of experience and maturation in the field of TAVR. The need for supportive advance imaging for TMVR is, however, even greater given the complex 3D anatomy and function of the mitral valve with its nonplanar annulus, the lack of a circular, fibrous annular structure, the variability of leaflet and sub-valvular apparatus anatomy as well as the proximity of the mitral valve to the left ventricular outflow tract [14•]. This review aims to describe these advances and developments in detail.

Curr Cardiol Rep (2018) 20:16

suppression of surrounding structures such as abdominal organs and ribs. Quantitative analysis involves both length measurements (e.g., mitral leaflet length) and segmentation-based measurements (e.g., planimetry of mitral valvular orifice area) from the MPRs, as described in further detail in the following sections.

Incremental Role of MDCT for Mitral Valve Assessment in the Context of TMVI Multi-Modality Imaging

Technical Aspects of MDCT Imaging for Mitral Valve Analysis Current generation scanners, with at least 64-slice technology capable of generating images with sub-millimetric spatial resolution, must be utilised for the purposes of cardiac valvular analysis [13]. The resulting 3D volumetric data sets are isotropic, permitting image reconstruction in any imaging plane—allowing for a comprehensive anatomical analysis [15]. Source MDCT data is presented in the transverse axial plane requiring post-processing of the data by the interpreting physician on a workstation platform. Physician review of the raw acquired axial images is recommended before removing the patient from the scanner, to ensure that a complete and high-quality dataset is obtained. Post-processing of source CT datasets utilises advanced 3D software packages for valvular assessment. The most commonly employed analysis tools include the following: a) Multiplanar reconstruction (MPR) for derivation of 2D images from the 3D volumetric dataset, which reproduce standardised views obtained on echocardiography and angiography. With the exception of performing annular measurements, the mitral apparatus is optimally evaluated with MPR views mimicking the commissural, threechamber, four-chamber and short axis echocardiographic windows. Newer segmentation algorithms have been developed for depiction of the complex saddle shaped mitral annulus for the purposes of TMVI planning as described in detail below in section “Mitral annular assessment for TMVI” [14•]. b) Volume rendering (VR) for 3D anatomical depiction of valvular surfaces including prosthetic valves, based on colour display shading algorithms derived from differential tissue voxel densities. Use of VR can be limited by the presence of significantly calcified structures. In addition, VR can be time consuming due to the need for

The etiologies of mitral regurgitation (MR) can be divided into degenerative (primary) and functional (secondary) categories. Comprehensive valvular evaluation, including assessment of the aetiology and severity of regurgitation, is of critical importance in guiding therapy. Echocardiography (TTE and TEE) is the first line imaging investigation for this purpose with 3D techniques now widely practiced and preferred [16]. Nevertheless, both clinician and patient-dependent limitations of echocardiography underlie the need for complementary 3D imaging modalities for the purposes of mitral assessment, particularly for TMVI planning. In comparison to both echocardiography and cardiac MRI, the superior spatial resolution of MDCT enables detailed illustration of the anatomy, geometry and spatial relationships of the mitral valve apparatus. Qualitative and quantitative information can be derived which is crucial for TMVI pre-procedural planning and candidate selection.

Validation of MDCT for Mitral Valvular Assessment with Echocardiography and Cardiac MRI The hallmark imaging manifestation of MR on MDCT is systolic leaflet mal-coaptation with formation of a regurgitant orifice. MPR analysis is used to derive oblique short-axis images of the mitral valve from which the inner contour of the regurgitant orifice can be traced via planimetry. Modest data is available evaluating the correlation between MDCT and echocardiographic grading of MR, with studies showing strong correlation between MDCT-measured geometric orifice area and echocardiography-derived effective regurgitant orifice area; however, the reproducibility of this technique and its pervasion in clinical practice is unknown [17, 18]. Thin-section MPRs permit direct evaluation of the mitral leaflets, annulus and sub-valvular apparatus with studies demonstrating good correlation with 3D TOE for quantitative assessment of mitral valve geometry including leaflet lengths and angles [19].


MDCT quantification of biventricular volumes and systolic function is possible. Discrepancy in left and right-ventricular stroke volumes from such quantitative analysis can further be utilised to extrapolate the mitral regurgitant volume and regurgitant fraction, assuming that no other significant valvular regurgitation or intracardiac shunt is present. In this regard, MDCT also shows good correlation with CMR which is considered the gold standard for ventricular volumetric analysis [20].

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valve leaflet insertion and the atrioventricular junction, is readily depicted on MDCT (Fig. 2). Mitral valve geometrical assessment, including measurement of the tenting heights (coaptation depth) and leaflet angles, can also be performed with high accuracy and reproducibility in patients with functional MR [23]. An interesting study by Beaudoin offers insight into the role of mitral valve leaflet adaptation in the pathophysiology of functional MR, suggesting that MV leaflet length is not static but able to adaptively enlarge to minimise the development of functional MR [24].

Mechanism of Mitral Regurgitation Determining the aetiology of MR is critical for guiding management. Traditionally, surgical options include valve repair or replacement for primary MR and annuloplasty for secondary MR [21]. In spite of these approaches, complete resolution of MR is often difficult to achieve. When compared to surgical options, TMVI can potentially address a broader range of mitral pathologies. MDCT offers comprehensive anatomical assessment of the mitral valvular and sub-valvular apparatus to aid in assessment of the underlying mechanisms contributing to MR, which is of benefit in guiding candidate selection and pre-procedural planning. Recently, a multi-centre study of 112 patients showed that MDCT has a robust diagnostic performance in the identification of mitral valve prolapse (MVP) [22]. MPR images reproducing the traditional echocardiographic 3-and 2-chamber views were most reliable for the assessment of MVP (Fig. 1). Relative to TTE, the accuracy of CT was excellent with a sensitivity of 96%, specificity of 93%, positive predictive value of 93% and negative predictive value of 96%. MDCT accurately identified the prolapsed leaflet scallop and discriminated between flail segments VS billowing leaflets. Mitral leaflet thickening (maximum leaflet thickness > 2 mm) was also used to characterise myxomatous and degenerative pathological manifestations of MVP. An anatomical hallmark of MVP, disjunction between the posterior mitral

Mitral Annular Assessment for TMVI

Fig. 1 Two-chamber (left image) and 3_chamber (mid image) MPR demonstrating prolapse of the P2 leaflet (red arrows). A slightly offaxis para-sagittal view in the same patient (right image) made the

prolapse completely disappear; this stresses the importance of a rigorous analysis using standardised views to detect mitral valve prolapse

CT-guided sizing of the mitral annulus has proven to be highly important for TMVI in a fashion similar to aortic assessment for TAVI. This pre-procedural assessment allows for appropriate patient screening and determination of patient suitability for the procedure. Assessment of the native mitral annulus can be challenging due to its relatively complex geometry. Unlike the aortic annulus, the mitral annulus is a non-planar, 3D saddle-shaped structure with an anterior and posterior peak. The anterior peak is continuous with the aortic valve and the posterior peak is formed by the insertion of the posterior mitral leaflet (PML), with the nadirs located at the level of the fibrous trigones [25•]. The major and minor 2D mitral annular diameters can be derived from the two-chamber and three-chamber views, respectively, on both echocardiography and MDCT. Such 2D measurements may be an over-simplification in terms of the complex 3D geometry of the mitral annulus and hence their utility is limited in TMVI planning. MDCT 3D segmentation of the mitral annulus directly addresses these shortcomings [14•]. Recently, a D-shaped model of the mitral annulus has been proposed based on MDCT analysis of the mitral valve which allows for TMVI planning. This model involves truncation of the saddle-shaped mitral annular contour at a virtual interconnecting line between both fibrous trigones, referred to as

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Fig. 2 Three-chamber MPR demonstrating disjunction of the posterior mitral valve leaflet (red arrow) with atrialization of the posterior mitral annular insertion (green arrow representing the physiological usual insertion)

the trigone-to-trigone (TT) distance [25•]. The model is derived from the observation that device sizing and selection based on a two-dimensional projected area including the anterior horn of the saddle-shaped contour would protrude and encroach into the left ventricular outflow tract (LVOT) as compared to the more planar D-shaped mitral annulus which would not. The TT-distance signifies an anterior border which if passed by a TMVI device represents encroachment upon the native LVOT. Akin to the entire mitral valve complex, the aorto-mitral junction is a highly dynamic structure with the potential for systolic bulging into the D-shaped contour and diastolic motion towards the LVOT [14•]. This segmentation approach requires derivation of long- and short-axis MPRs in alignment with the left ventricular long axis via placement of seeding points for the cubic spline along the PML insertion. Segmentation of the anterior horn is undertaken by placing seeding points along the insertion of the aortic noncoronary and right coronary cusps into the intervalvular fibrosa. Following identification of the trigones, the D-shaped annulus is then formed via truncation along the TT-distance (Fig. 3) [26]. The annular area and perimeter are subsequently derived via postprocessing. The total D-shaped perimeter equates to the posterior annular perimeter (P.Pe) and the TT-distance. The geometry of the mitral annulus is further quantified by measurement of the septal-to-lateral (SL) distance (A2-to-P2 distance), representing the minor annular diameter, and the intercommissural (IC) distance, representing the major annular diameter.

Assessment of Annular and Landing Zone Geometry for TMVI Wide variation exists for normative data on mitral annular dimensions, attributable mainly to discrepancies between


different imaging modalities and segmentation methodology. Relatively smaller normal annular areas have been obtained on older 2D echocardiographic studies [27]. Newer 3D echocardiographic and MDCT studies report mean annular areas ranging between 8.4 and 11.8 cm2 [24, 28–32]. A recent investigation by our group demonstrated a mean D-shaped mitral annular area of 9.0 ± 1.5 cm2 in normal subjects with pronounced inter-individual variation [33]. Overall, mitral annular dimensions are larger in subjects with mitral regurgitation though significant differences exist between etiologies of MR, with increased annular dimensions in MVP compared to FMR [14•]. A distinct reduction in saddle height exists in FMR with a more planar annular contour [25•, 28]. Interestingly, with respect to in-plane geometry, there is a relatively greater increase in the SL compared to the IC distance seen in both FMR and MVP patients [23, 24, 33]. Of particular relevance to TMVI, important differences in landing-zone anatomy exist between FMR and MVP. Regional wall motion abnormalities and/or left ventricular dilation in FMR result in marked mitral leaflet tethering and annular dilation which account for the hallmark anatomical features including increased leaflet tenting height, reduced coaptation length and basal myocardial remodelling with fashioning of a posterior atrioventricular myocardial shelf identifiable on both echocardiography and MDCT (Fig. 4) [33]. This posterior shelf is larger and more pronounced in ischaemic FMR often related to a co-existing inferolateral circumflex territory infarction. In comparison, the key anatomical finding in primary MR, chiefly MVP, is atrial displacement of the posterior leaflet as seen on a 2- or 3-chamber MPR (Fig. 1). As described previously, the insertion of the mitral valve leaflet may be displaced into the left atrium, referred to as mitral annular dysjunction (Fig. 2) [34, 35].

Annular Calcification MDCT is superior to both echocardiography and MRI for the assessment of calcification. Degenerative mitral annular calcification (MAC) is commonly seen in the elderly population and present in approximately 6% of the general population [36]. MAC is most frequently limited to the posterior rim although its extent can vary from mild localised to exuberant circumferential involvement (Fig. 5). Caseous annular calcification is a rare variant of MAC which typically manifests along the posterior rim as large-volume space-occupying lesions [37]. In comparison to typical MAC, caseous MAC appears less echodense on echocardiography. On contrastenhanced CT, caseous MAC may exhibit focal areas of similar attenuation to blood-pool, but these can be readily differentiated on non-contrast-enhanced sequences [38]. Severe MAC is a relative contraindication to TMVI in the majority of


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Fig. 3 Segmentation of the D-shaped mitral annulus: seeding points are placed along the leaflets insertion (left image) following rotation along the LV centreline; then, the anterior horn is truncated by exclusion of the interspace between the LVOT (middle image). The right image represents an “en face” view of the final segmentation: the blue double-headed

arrow represents the trigone to trigone distance (TT), the yellow double-headed arrow illustrates the intercomissural distance (IC), the green double-headed arrow depicts the septal to lateral distance (SL) and the red line represents the insertion of the posterior mitral leaflet

current feasibility studies due to the expected interference with the apposition of self-expandable TMVI systems [14•].

assessed with MDCT. Assessment of structural suitability for device-specific anchoring mechanisms is vital. Sufficient leaflet length should be documented via accurate measurement for devices which anchor via paddles grasping onto the leaflets, e.g., at A2-P2. MVP and annular disjunction at P2 should also be excluded as these are factors which could possibly interfere with stable device deployment [11]. MDCT clearly depicts the anatomy of the sub-valvular apparatus. The papillary muscles and chordae should be evaluated to exclude anomalies such as false bands and directly inserting papillary muscles which may also interfere with device deployment. For devices anchoring via tabs in the basal inferolateral myocardium, the persistence of a myocardial shelf (Fig. 2) should be documented throughout the cardiac cycle [10]. Basal myocardial hypertrophy or exuberant annular calcification can potentially interfere with the anchoring mechanisms for such devices. Leaflet length and pathology are of less relevance for TMVI devices anchoring via an apical tether [9]. A universal requirement for all TMVI devices is that the basal LV cavity must be able to accommodate the device [14•]. In particular, transapical access can be contraindicated in case of a severely remodelled apex with a thinned myocardial infarction scar (Fig. 4).

Determination of TMVI Feasibility and Safety MDCT evaluation of the various TMVI device-specific anatomic criteria aids with optimal pre-procedural planning and may result in a significant shortening of fluoroscopy and procedure timings.

Anatomical Factors TMVI devices display a wide range of anchoring mechanisms with different anatomical requirements which should be

Predicting LVOT Obstruction

Fig. 4 Tethering of the posterior mitral valve leaflet and a posterior shelf (red arrows) are identified in the context of a dilated ischemic cardiomyopathy with remodelling of the left ventricle (blue arrows highlighting multiple areas of prior myocardial infarction)

LVOT obstruction (LVOTO) is a serious potential TMVI complication associated with a high rate of resultant mortality. TMVI devices currently being validated in early feasibility studies include circumferentially covered stent struts with the potential to protrude into the left ventricular cavity, interfere with the anterior mitral leaflet (AML) and encroach upon the LVOT [10, 11, 39]. To address this risk, the concept of the “neo-LVOT” which is fashioned by the device itself along with both the AML and interventricular septum [40••].

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Fig. 5 Short-axis view demonstrating smooth mitral annular calcification extending from P1 to P3 (left image), offering no anterior landing zone for anchoring in a potential valve-in-MAC candidate. Middle image is a short-axis view in a different patient demonstrating an extensive MAC

with exuberant circumferential caseous calcifications. This patient was successfully treated with a valve-in-MAC procedure using a 26-mm Sapien 3 TAVI valve (right images)

Theoretically, LVOTO can refer to either narrowing of the native LVOT above the level of the TT-distance or formation of a narrow neo-LVOT below the level of the TT-distance towards the left ventricle [40••]. Both anatomical and device-related factors predispose to LVOTO. Wide inter-individual variability exists in LVOT anatomy with the major structural determinants including the interventricular septum, left ventricular cavity size and aortomitral angulation. Of these, the LVOT and neo-LVOT crosssectional areas are most negatively impacted by a hypertrophied interventricular septum. The major devicerelated factors are device protrusion and flaring [14•]. MDCT is of great potential value in this context as postTMVI neo-LVOT geometry may be predicted by device simulation and modelling, e.g., by embedding a cylindrical or device specific contour into the CT-data set, followed by segmentation and planimetrical assessment of the neo-LVOT cross-sectional area (Fig. 6) [14•].

permit visualisation of anchoring elements during deployment. Two views are considered relevant in light of the asymmetric mitral annulus: a septal-to-lateral view parallel to the SL-line (along with a TT-view parallel to the TT-line. Projection angles are limited by physical restraints of the C-arm and suitable access is imperative. The SL-view can be derived with projected angulations which are generally in the practical range of C-arm working angles, as opposed to angulations for the TT-view which are usually not (51). Alternatively, a compromise view in between the TT-view and SLview has been derived and demonstrated efficacy in the context of TMVI deployment [41].

Prediction of Fluoroscopic Angulations Co-planar fluoroscopic projections ensure co-axial device deployment. Similar to TAVR, MDCT provides these projection angulations based on the mitral annular plane yielding an optimal viewing curve, providing the corresponding cranial-caudal angle for any given LAO/ RAO angle. The relatively vertical orientation of the mitral annulus results in a steep slope with proportionally higher variation in cranial/caudal angulation for any given change in LAO/RAO angulation. C-arm projections for TMVI must be orthogonal to the mitral annulus and aligned with defined anatomical structures to

Mitral Valve-in-Valve Procedures With functional impedance and eventual failure of bioprosthetic valves commonly occurring over time, valvein-valve (VIV) replacement is a viable management strategy. This involves reimplantation of a secondary replacement valve within the neo-annulus of the primary device. The main experience with this procedure has been with aortic VIV replacement [42]. MDCT has shown utility in identifying patients at risk of coronary occlusion, an adverse outcome from VIV procedures whereby proximity of the prosthesis to the coronary ostia can result in occlusion and carries a high rate of mortality. Mitral VIVand valve in MAC (Fig. 5) procedures have also been described within the literature and may benefit from preprocedural CT. Procedural experience with mitral VIV has been described in 23 patients at a single centre with no deaths


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Fig. 6 Concept of the “neo-LVOT”: a simulated device (green mesh) is virtually positioned within the mitral annulus to predict the risk of LVOT obstruction. The left images represent the three-chamber view that are used for the planning, and the right images are MPR perpendicular to the LVOT centreline, positioned where the LVOT diameter is the most

reduced by the device. In the top panel, the neo-LVOT (shadowed in green) is large, while in the bottom panel, it is small (shadowed in red), indicating a high risk of LVOT obstruction if the procedure was indeed performed

at 30-day follow-up [43]. However, a larger global registry reported the experience to date of valve replacement for mitral stenosis in the setting of severe MAC [44•]. This registry assessed a total of 64 patients with severe mitral annular calcification undergoing deployment of a balloon expandable prosthesis. The device was deployed successfully in 72% of cases, with 11 requiring a second valve. A total of six patients had severe left ventricular outflow tract obstruction causing hemodynamic compromise with two patients experiencing procedure-related mortality. With an increasing rate of mitral VIV and valve in MAC procedures, CT has a potential role in identifying patients at risk of complications. CT can define the extent of calcification in the case of MAC and define the pre-existing prosthesis for VIV procedures. From this, the intended prosthesis can be modelled to assess the risk of obstruction of the LVOT, in a similar fashion to what has been already described for native valve. CT can also play a role in the follow-up after the procedure. Paralleling what has been recently described in TAVR [45••, 46], there is a concern for the possibility of subclinical leaflet thrombosis occurring also in the mitral space after valve implantation. This is diagnosed by CT as a hypodense leaflet thickening with restricted motion of the prosthetic leaflets involved. The potential clinical consequence of this entity is, however, not yet known.

Conclusion Similar to what has been established in the aortic space in regards to TAVI [47, 48], cardiac MDCT enables a comprehensive assessment of the complex anatomy of the mitral valve and sub-valvular apparatus, yielding information of significant clinical value in the context of MR evaluation and in particular, pre-procedural planning for TMVI.

Compliance with Ethical Standards Conflict of Interest Rominder Grover, Mickael Ohana, Chesnal Dey Arepalli, Stephanie L. Sellers, John Mooney, Shaw-Hua Kueh and Ung Kim declare that they have no conflict of interest. Jonathon A. Leipsic is a consultant to Heartflow, Circle CVI, and Edwards Lifesciences. He provides Institutional Core Lab Support to Edwards Lifesciences, Neovasc, Tendyne, Ancora, Medtronic, and LASSO; and he has stock options in Heartflow, PI Cardia, and Circle CVI. Philipp Blanke has received honoraria from HeartFlow, Edwards Lifesciences, Tendyne Holdings, and Circle Imaging. And he provides Institutional corelab services to: Edwards Lifesciences, Medtronic, Tendyne, and Neovasc. Human and Animal Rights and Informed Consent This article does not contain any studies with human or animal subjects performed by any of the authors.

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