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STATE-OF-THE-ART PAPERS

Role of CMR in TAVR

Toby Rogers, BM, BCH,a,b Ron Waksman, MDb

ABSTRACT

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Multimodality imaging plays a critical role in planning, performing, and evaluating transcatheter aortic valve replacement

(TAVR). Cardiovascular magnetic resonance (CMR) has been underutilized in this patient population to date, but there

is increasing evidence that it can offer equivalent or even superior information to more commonly used imaging mo-

dalities, such as echocardiography or computed tomography for specific applications. In addition, CMR can provide in-

cremental information, including advanced tissue characterization with late gadolinium enhancement and T1 mapping.

In this paper, we review the evidence for CMR in TAVR and explore whether CMR should still be considered a research

tool, or whether it is now ready for implementation into clinical practice. (J Am Coll Cardiol Img 2016;9:593–602)

© 2016 by the American College of Cardiology Foundation.

T ranscatheter aortic valve replacement(TAVR) is an effective treatment for patientswith severe symptomatic aortic stenosis who

are at high or prohibitive surgical risk (1,2). TAVRoperators have embraced multimodality imaging toplan procedures, guide implantation, and evaluatepatients post-procedure. However, it is not yet clearwhether cardiovascular magnetic resonance (CMR)has a role in the everyday management of these com-plex patients.

Pre-procedure, TAVR patients undergo a combi-nation of invasive cardiac catheterization; trans-thoracic, transesophageal, or dobutamine stressechocardiography; and cardiac and aortoiliaccomputed tomography (CT) (Table 1). Each imagingmodality informs specific heart team decisionsincluding: 1) overall suitability for TAVR; 2) choiceof access; 3) valve selection and sizing; and 4) theneed for adjunctive interventions (e.g., percuta-neous coronary intervention). The actual valve

m the aCardiovascular and Pulmonary Branch, Division of Intramural R

thesda, Maryland; and the bSection of Interventional Cardiology, MedS

. Waksman has served as a consultant for Abbott Vascular, Biotronik, B

ved on the Speakers Bureau for AstraZeneca, Boston Scientific, an

traZeneca, Biotronik, and Boston Scientific. Dr. Rogers has reported that

s paper to disclose.

nuscript received December 9, 2015; revised manuscript received January

implantation is guided by x-ray fluoroscopy andechocardiography. Some centers use rotational cone-beam CT in the catheterization laboratory to deter-mine optimal valve implantation projection anglesand perform last-minute aortic root measurements.Post-procedure, echocardiography serves to evaluateprosthesis function, specifically to measure residualgradients and assess for paravalvular leak. CT isthe preferred modality to diagnose suspectedvascular access complications (e.g., retroperitonealhemorrhage).

In this review, we explore the current evidence forCMR in TAVR patients and weigh the advantages anddisadvantages of CMR versus other imagingmodalitiesat each stage of the procedure (Central Illustration).

WHICH TAVR PATIENTS CAN UNDERGO CMR?

TAVR patients are subject to the usual exclusions forCMR. TAVR prostheses are classified as magnetic

esearch, National Heart Lung and Blood Institute,

tar Washington Hospital Center, Washington, DC.

oston Scientific, Medtronic, and St. Jude Medical;

d Merck; and has received grant support from

he has no relationships relevant to the contents of

15, 2016, accepted January 19, 2016.

ABBR EV I A T I ON S

AND ACRONYMS

CMR = cardiovascular magnetic

resonance

CT = computed tomography

MRI = magnetic resonance

imaging

TAVR = transcatheter aortic

valve replacement

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resonance imaging (MRI) conditional and arenot a contraindication to MRI (see the Insti-tute for Magnetic Resonance Safety, Educa-tion, and Research web site [3] for details ofeach individual prosthesis). A significantproportion of TAVR patients receive pace-makers for post-procedural conduction de-fects, which would preclude further CMRstudies unless MRI-conditional pacemakers

are used. It is important to recognize that MRI-conditional pacing leads and boxes only haveapproval for scanning at 1.5-T field strength and cancause CMR imaging artifacts.

DETERMINATION OF SEVERITY OF

AORTIC STENOSIS

Through-plane velocity-encoded phase-contrastCMR enables measurement of peak aortic valve jetvelocity to determine the severity of aortic stenosis(4). The user sets the imaging parameters on thebasis of the anticipated peak aortic valve velocity toensure accurate measurements. Peak velocities insevere aortic stenosis are usually in excess of 400cm/s. The imaging plane should be positioned in theaortic root, a few millimeters distal to the tips of theaortic valve leaflets (5). Care must be taken to ensurethat the imaging plane is orthogonal to the aorticflow jet, as an offset >20� can lead to inaccuratemeasurements (6). In patients with mixed aorticvalve disease, aortic regurgitation can be quantifiedfrom the same images. The anatomic aortic valveorifice area can be planimetered from orthogonalsteady state free precession cine images through theaortic valve. To account for through-plane cardiacmotion, a stack of cines should be acquired to ensurethat the smallest orifice is captured. However, it isimportant to recognize that accuracy of planimetryby CMR will be affected by heavy calcification of theaortic valve leaflets. The more physiological effec-tive orifice area can be calculated from aortic valveand left ventricular outflow tract flow CMR andoutflow tract area using the continuity equation (7).In this respect, CMR has a distinct advantage overCT, which can only measure the anatomic aorticvalve orifice area (8). In patients with low-flow, low-gradient aortic stenosis, measurements can berepeated during administration of low-dose dobut-amine to assess for contractile reserve and identifypatients with true aortic stenosis. Pre-TAVR CMR alsoallows for measurement of left and right ventricularvolumes and ejection fraction, but cannot estimatepulmonary artery pressure, which is an importantpredictor of poor outcome if elevated (9).

VALVE SIZING

Cardiac CT has become the reference standard foraortic annulus measurements for valve sizing, but itrequires administration of iodinated contrast and istherefore contraindicated in patients with severe renaldysfunction. TAVR patients are elderly with a highprevalence of renal dysfunction, which is associatedwith increased midterm mortality after TAVR (10).Three-dimensional (3D) transesophageal echocardi-ography is themost common alternativemodality usedto obtain annulus measurements in patients with se-vere renal dysfunction, but is an invasive test. Gopalet al. (11) elegantly describe in a step-by-step fashionhow respiratory navigator-gated 3D noncontrast CMRwith submillimeter resolution can be used as an alter-native to CT, without the need for nephrotoxic con-trast. In head-to-head comparisons of CMR and CT,there are no differences and there is excellent corre-lation between CMR and CT measurements for allstandard aortic root metrics (12,13) (Figure 1). CMRmayalso be used in patients with prosthetic aortic valveswho are being considered for valve-in-valve TAVR,although artifacts can prevent accurate imaging of theaortic root if the original prosthesis has metal struts(14). The main difference between CMR and CT is thatcalcium appears as a negative signal void rather than apositive signal, which in practice can lead to underes-timation of annular and leaflet calcification. Never-theless, 3D CMR should be considered in patientsundergoing workup for TAVR with severe renaldysfunction.

ASSESSMENT OF TRANSFEMORAL VERSUS

ALTERNATE ACCESS OPTIONS

The main limitation of CMR in the assessment of theperipheral vasculature to determine suitability fortransfemoral access for TAVR is suboptimal visuali-zation of calcification, which is common in elderlypatients. Contrast-enhanced iliofemoral MRI angiog-raphy can provide vessel lumen dimensions, but itdoes require contrast administration. Although gad-olinium contrast does not directly cause kidneyinjury, there is a risk of nephrogenic systemic fibrosisin patients with pre-existing severe renal dysfunc-tion, and therefore, gadolinium should be avoided inthese patients. However, novel noncontrast CMR se-quences still under investigation may prove to beuseful alternatives to CT in patients with renaldysfunction who are at risk of contrast nephropathy(15). If transfemoral access is contraindicated due tosevere peripheral artery disease, 3D noncontrast CMRis a practical alternative to CT to assess suitability of

TABLE 1 Role of Commonly Used Imaging Modalities for TAVR and Relative Advantages and Disadvantages of CMR

Role Advantages of CMR Disadvantages of CMR

Pre-Procedure

Cardiac CT � Measure aortic annulus and root, coronaryartery ostia heights

� Determine optimal valve implantationprojection angles

� Assess location and severity of aorticvalve and ascending aorta calcification

� Determine suitability of alternateaccess (e.g., transaortic or transapical)

� No contrast required (11–13) � Suboptimal visualizationof calcification

� Longer scan time

Aortoiliac CT � Measure aorta, common iliac, externaliliac, and common femoral artery diameters todetermine suitability for transfemoral access

� Assess location and severity ofperipheral artery calcification

� Noncontrast imaging isfeasible (15)

� Suboptimal visualizationof calcification

Transthoracic echocardiography � Measure peak aortic valve velocity,mean gradient, valve area, and left ventricularejection fraction; estimate pulmonaryartery pressure

� Quantify diffuse myocardialfibrosis and focal scar (39,41)

� Accurate measurements ofright and left ventricular volumesand ejection fraction

� Cannot estimate pulmonary arterypressure

Transesophageal echocardiography � Measure aortic annulus and root,coronary artery ostia heights

� Noninvasive test

Dobutamine stress echocardiography � Measure peak aortic valve velocity,mean gradient, and valve area in patients withreduced ejection fraction and suspectedlow-flow low-gradient aortic stenosis

� Not limited by echo windows

Cardiac catheterization � Define coronary artery anatomy andseverity of disease

� Perfusion CMR to identifyischemia due to coronaryartery disease as adjunct tocardiac catheterization

� Cannot visualize coronary arteries(i.e., functionalvs. anatomical assessment)� Measure right heart and pulmonary

artery pressures

Intraprocedure

X-ray fluoroscopy � Guide valve implantation � Excellent soft tissuevisualization

� Pre-clinical only todate (17,18)

� Suboptimaldevice visualization

� Lower spatial andtemporal resolution

Transthoracic or transesophagealechocardiography

� Guide valve implantation� Qualitatively and semiquantitatively

assess severityof paravalvularaortic regurgitation

� Assess for pericardial effusion

� Not limited by echo windows � Can only be performed indedicated x-ray/MRIcatheterization laboratories

Rotational cone-beam CT � Measure aortic annulusand root, coronary artery ostia heights

� Determine optimal valveimplantation projection angles

Post-Procedure

Transthoracic echocardiography � Qualitatively and semiquantitatively assessseverity of paravalvularaortic regurgitation

� Assess prosthetic valve function� Measure left ventricular

ejection fraction

� Accurate quantification oftransvalvular and paravalvularaortic regurgitation (20,22,23)

� Assess for left ventricularremodeling (26)

� Assess for TAVR procedure-related myocardial injury (36)

� Quantify diffuse myocardialfibrosis (39,41)

� Cannot be performedat the bedside

CT � Investigate suspected vascular access compli-cations (e.g., retroperitoneal hemorrhage)

� Noncontrast CMR is feasible

CMR ¼ cardiovascular magnetic resonance; CT ¼ computed tomography; MRI ¼ magnetic resonance imaging; TAVR ¼ transcatheter aortic valve replacement.

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thoracic anatomy for transaortic or transapical access,although noncontrast CT may still be required toevaluate the ascending aorta to identify an appro-priate calcium-free window through which to enterthe ascending aorta in patients who are being

considered for transaortic access. Porcelain aorta,which precludes transaortic access, is found in up to10% of TAVR patients (16). CT remains the bestimaging modality to identify porcelain aorta and canbe performed in all patients, regardless of renal

CENTRAL ILLUSTRATION The Role of CMR in TAVR

Rogers, T. et al. J Am Coll Cardiol. 2016;9(5):593–602.

CMR ¼ cardiovascular magnetic resonance; MRI ¼ magnetic resonance imaging; TAVR ¼ transcatheter aortic valve replacement.

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FIGURE 1 Noncontrast High-Resolution 3-Dimensional CMR of the Aortic Root for Valve Sizing

(A and B) Orthogonal long-axis views of the aortic valve. (C) Short-axis view of the aortic annulus. Small and large diameters and area are

measured for transcatheter aortic valve replacement valve sizing. (D) Measurement of the height of the left coronary ostium from the

aortic annulus. CMR ¼ cardiovascular magnetic resonance. Image provided by G. Pontone and M. Guglielmo (2015), Centro Cardiologico

Monzino, IRCCS, Milan, Italy.

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function, because contrast is not required for thisspecific application.

REAL-TIME CMR-GUIDED TAVR

Several groups have demonstrated implantation ofcommercial transcatheter valves in the aortic positionunder real-time CMR guidance in animal models us-ing custom-engineered delivery systems with allferromagnetic materials removed (17,18). However, itis not clear whether the improved soft tissue visual-ization and lack of ionizing radiation confer genuinebenefit over x-ray fluoroscopy and echocardiographyfor TAVR. It is doubtful whether the stiff inter-ventional guidewires that are required to safelyperform TAVR from nonferromagnetic materials canbe engineered. Balloon-expandable valves require

rapid pacing during deployment, and at present,there are no commercially available MRI-conditionaltemporary pacing wires. Furthermore, managingcomplications in the MRI environment is a logisticalchallenge, usually requiring patient evacuation intoan adjacent room where MRI-unsafe surgical tools canbe used. For now, real-time guided TAVR remainsfirmly within the research domain.

QUANTIFICATION OF PARAVALVULAR

AORTIC REGURGITATION

The persistence of paravalvular aortic regurgitationfollowing TAVR is associated with worse outcome(19). As a rule of thumb, regurgitation that is morethan mild in severity has clinical significance. Clas-sification of severity of regurgitation is therefore

FIGURE 2 Velocity-Encoded Phase-Contrast Flow CMR Quantification of Post-Implantation Paravalvular Aortic Regurgitation

The positioning of the scan plane is demonstrated for the balloon-expandable prosthesis in the aortic root 2 to 3 mm above the valve stent frame (A). The regions

of interest are traced in blue on the magnitude images (anatomical scan) (B) and the phase images (flow scan) (C). The regions of interest include the entire intraluminal,

cross-sectional area of flow just above the transcatheter valve. The flow through the region of interest is calculated throughout the cardiac cycle (D), with the area

under the curve (above baseline) representing forward flow volume and the area above the curve (below baseline) representing reverse flow volume. The aortic

regurgitant fraction is calculated by dividing the reverse flow volume by the forward flow volume (mild #20%, moderate 21% to 39%, severe $40%). CMR ¼cardiovascular magnetic resonance. Reprinted from Hartlage et al. (22).

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important, and yet, echocardiography tends to un-derestimate severity (20,21). This is likely dueto suboptimal echocardiographic windows, use of2-dimensional imaging, artifact from calcium andprosthesis, and eccentricity of paravalvular regur-gitant jets. In contrast, through-plane velocity-encoded phase-contrast CMR with the imaging planepositioned in the ascending aorta just beyond theaortic valve prosthesis potentially offers superioraccuracy and reproducibility for quantification ofregurgitant volume and regurgitant fraction (Figure 2).Compared with qualitative echocardiography, CMRreclassifies paravalvular regurgitation severity inalmost 50% of patients, with most patients reclassifiedat least 1 grade higher (22,23). This underestimationmay, in part, explain the findings of increasedmortality associated with mild or greater aortic regur-gitation in some of the landmark trials, because para-valvular aortic regurgitation post-TAVR that isassessed as mild by transthoracic echocardiography

may in fact be moderate or severe. Interobserver vari-ability is also greater with echocardiography. In ahead-to-head comparison of echocardiography versusCMR to quantitatively assess severity of paravalvularaortic regurgitation after TAVR, interobserver vari-ability for quantification of regurgitant volume was74%, 7%, and 2% for 2-dimensional transthoracicechocardiography, 3D transthoracic echocardiogra-phy, and CMR, respectively (24). CMRmore accuratelyclassifies severity of paravalvular aortic regurgitation,providing superior prognostic value compared withechocardiography, as patients with greater than mildparavalvular regurgitation by CMR, defined as regur-gitant fraction>20%, had a higher incidence of adverseevents (22).

Aortic root angiography is commonly used in thecatheterization laboratory as a complementary tool toassess severity of paravalvular aortic regurgitation,but there is only a moderate correlation with CMR inthe classification of aortic regurgitation severity after

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TAVR (25). In practice, operators use a combination ofechocardiography, angiography, and hemodynamicsto assess paravalvular aortic regurgitation. PerformingCMR to measure regurgitant fraction immediatelypost-implantation is not logistically realistic. How-ever, in practice, the true severity of aortic regurgita-tion may be underestimated, because patients aresedated or fully anesthetized during implantationwith lower than normal blood pressure. A more accu-rate assessment by CMR pre-discharge could informprognosis and identify patients with significant para-valvular aortic regurgitation who are at risk of heartfailure for more aggressive medical management.

ASSESSMENT OF

VENTRICULAR REMODELING

CMR is the gold standard noninvasive imagingmodality to assess left ventricular function and theextent and patterns of left ventricular hypertrophy inpatients with severe aortic stenosis (26). Severalgroups have studied the effect of TAVR on left ven-tricular remodeling using serial CMR, and have showna reduction in left ventricular mass of 18% to 22% andsmaller reductions in left ventricular end-systolicvolume and ejection fraction (27,28). CMR tech-niques such as myocardial tagging and featuretracking may be useful to characterize changes inmyocardial motion and strain in patients undergoingTAVR (29). CMR is superior to echocardiography forevaluation of the right ventricle and may, therefore,provide a useful tool to study the response of theright heart to TAVR. Interestingly, early indicationssuggest that right ventricular function may be worseafter TAVR compared with surgical aortic valvereplacement (30). This finding may be attributable toincreased incidence of paravalvular regurgitationwith early-generation TAVR prostheses comparedwith surgical valves. However, the sample size in thisstudy was small, and no long-term follow-up imagingwas performed. It is, therefore, not yet clear whetherserial assessment of left and right ventricularremodeling using CMR or echocardiography has valuein routine clinical practice.

MYOCARDIAL INJURY

Late gadolinium enhancement CMR is the gold stan-dard technique to identify myocardial scar in vivo(31). Presence of late gadolinium enhancement byCMR has prognostic valve in TAVR patients. Up to50% of patients with severe aortic stenosis have evi-dence of focal fibrosis or unrecognized infarct by CMRat baseline, which is an independent predictor ofmortality in patients undergoing surgical aortic valve

replacement or TAVR and could inform pre-procedural risk stratification (32,33). Furthermore,the presence of significant late gadolinium enhance-ment is an independent predictor of left ventricularejection fraction recovery following TAVR (34).

Elevated troponin levels have been observed inup to 99% of patients after TAVR, suggesting thatperiprocedural myocardial injury does occur (35). Agreater degree of injury is associated with highermidterm cardiac mortality. Kim et al. (36) observednew myocardial late gadolinium enhancement withan ischemic pattern in almost 20% of patients un-dergoing TAVR. Importantly, these patients had onaverage 10% reduction in left ventricular ejectionfraction, whereas in patients without new late gado-linium enhancement, no change in ejection fractionwas observed. This ischemic-type late gadoliniumenhancement is assumed to be of embolic origin,although other patterns have been described. Apicalscarring, defined by evidence of late gadoliniumenhancement, can occur in patients undergoingtransapical TAVR, involving up to 5% of the myocar-dium (37,38). This finding may inform decision mak-ing on the choice of access in patients with baselineimpaired left ventricular function.

ADVANCED MYOCARDIAL

TISSUE CHARACTERIZATION

Quantitative CMR tissue characterization techniquessuch as T1 mapping and extracellular volume providean insight into pathologies that result in diffusemyocardial fibrosis and that are not apparent withlate gadolinium enhancement CMR (Figure 3). Thereis a correlation between extracellular volume andhistologically determined extent of diffuse fibrosis inpatients with severe aortic stenosis (39), which issimilar to that of patients with dilated or hypertrophiccardiomyopathy (40). There is also a correlation be-tween pre-contrast T1 values and endomyocardialbiopsy-quantified fibrosis (41). Pre-contrast T1 valuesare increased in patients with severe aortic stenosiscompared with control subjects and are even higherin symptomatic versus asymptomatic patients. At1.5-T field strength, T1 values in control subjects andin asymptomatic and symptomatic aortic stenosispatients were 944 � 16 ms, 972 � 33 ms, and 1,014 �38 ms, respectively. How TAVR or surgical aorticvalve replacement affects the fibrotic process is yet tobe determined, but T1 mapping techniques mayrepresent a useful biomarker to monitor progressionof disease and response to treatment and can offer analternative to invasive endomyocardial biopsy tomonitor changes in diffuse myocardial fibrosis.

FIGURE 3 Native T1 and ECV Mapping in Patients With Severe Aortic Stenosis and a Normal Control Subject

(A) A 47-year-old female healthy volunteer; native T1 1,030 ms, extracellular volume (ECV) 24%. (B) An 82-year-old female with severe,

symptomatic aortic stenosis prior to surgical aortic valve replacement; native T1 1,045 ms, ECV 24%. (C) A 56-year-old male with critical aortic

stenosis and acute heart failure prior to urgent surgical aortic valve replacement; native T1 1,110 ms, ECV 29%. (Top) Native T1 maps using

motion-corrected 5s(3s)3s Modified Look-Locker imaging. (Middle) Late gadolinium enhancement images confirm no focal scar. (Bottom) ECV

maps. Images acquired as part of RELIEF-AS study (NCT02174471). Provided by T.A. Treibel, S. Rosmini, and J.C. Moon (2015), University

College London and Barts Heart Centre, United Kingdom. T1/ECV mapping tools provided by P. Kellman (46).

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DIFFUSION-WEIGHTED MRI OF THE BRAIN

A number of cerebral embolic protection devices tocapture debris released from the aortic valve or aorticarch during TAVR are now under investigation (42).Clinical endpoints of stroke and transient ischemicattack are thankfully rare, so most studies usediffusion-weighted MRI of the brain as a surrogateendpoint, looking for new cerebral lesions (43). Earlyevidence suggests that new lesions occur in 40% of

patients undergoing surgical aortic valve replacementand up to 90% of patients undergoing TAVR (44).However, these lesions do not cause neurologicaldeficit in up to 97% of patients, so their clinical rele-vance and prognostic value is not yet clear. There issome data to suggest that a higher number ofischemic lesions by diffusion-weighted MRI is asso-ciated with cognitive impairment, evidenced bychanges in neurocognitive tests (45). At present,diffusion-weighted MRI of the brain remains a useful

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research tool in TAVR, but there is insufficient evi-dence to support routine clinical use.

CONCLUSIONS

Multimodality imaging has fundamentally enabledthe rapidly developing field of structural heartintervention, particularly transcatheter aortic valvereplacement. Techniques unique to CMR, includingvelocity-encoded phase-contrast flow imaging, lategadolinium enhancement, advanced tissue character-ization, and high-resolution noncontrast 3D imaging,are already useful research tools. To date however,CMR has been underutilized in routine clinical prac-tice. CMR certainly cannot replace all other imagingmodalities, but there is growing evidence that it isequivalent or even superior to echocardiography and

CT for specific elements of the TAVR patient workupand post-implantation evaluation. On the basis of theavailable evidence, CMR can be carefully implementedinto clinical practice for valve sizing and access selec-tion when renal dysfunction precludes contrast-enhanced CT and for quantification of paravalvularaortic regurgitation (Central Illustration). More studiesare needed to determine whether the additional in-formation provided by CMR, for example myocardialinjury, ventricular remodeling, and advanced tissuecharacterization, has genuine value in routine clinicalpractice.

REPRINT REQUESTS AND CORRESPONDENCE: Dr.Ron Waksman, MedStar Washington Hospital Center,110 Irving Street Northwest, Suite 4B-1, Washington,DC 20010. E-mail: ron.waksman@medstar.net.

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KEY WORDS aortic stenosis, cardiovascularmagnetic resonance, transcatheter aorticvalve replacement