Cardiac MRI in hypertrophic cardiomyopathy

doi:10.1016/j.jcmg.2011.06.022 2011;4;1123-1137 J. Am. Coll. Cardiol. Img.

Andrew C.Y. To, Ashwat Dhillon, and Milind Y. Desai Cardiac Magnetic Resonance in Hypertrophic Cardiomyopathy

This information is current as of November 21, 2011

http://imaging.onlinejacc.org/cgi/content/full/4/10/1123located on the World Wide Web at:

The online version of this article, along with updated information and services, is

by on November 21, 2011 imaging.onlinejacc.orgDownloaded from

http://imaging.onlinejacc.org/cgi/content/full/4/10/1123

http://imaging.onlinejacc.org

S

CH

A

JI

Tai

AT(fp

aCmt

MCT1

Fr

M

J A C C : C A R D I O V A S C U L A R I M A G I N G V O L . 4 , N O . 1 0 , 2 0 1 1

© 2 0 1 1 B Y T H E A M E R I C A N C O L L E G E O F C A R D I O L O G Y F O U N D A T I O N I S S N 1 9 3 6 - 8 7 8 X / $ 3 6 . 0 0

P U B L I S H E D B Y E L S E V I E R I N C . D O I : 1 0 . 1 0 1 6 / j . j c m g . 2 0 1 1 . 0 6 . 0 2 2

T A T E - O F - T H E - A R T P A P E R i R E V I E W S

ardiac Magnetic Resonance inypertrophic Cardiomyopathy

ndrew C. Y. To, MBCHB, Ashwat Dhillon, MD, Milind Y. Desai, MD

Cleveland, Ohio

ACC: CARDIOVASCULARMAGING CME

his article has been selected as this issue’s CME activity,vailable online at www.imaging.onlinejacc.org by select-ng the CME tab on the top navigation bar.

ccreditation and Designation Statementhe American College of Cardiology Foundation

ACCF) is accredited by the Accreditation Councilor Continuing Medical Education (ACCME) torovide continuing medical education for physicians.

The ACCF designates this Journal-based CMEctivity for a maximum of 1 AMA PRA Category 1redit(s)™. Physicians should only claim credit com-ensurate with the extent of their participation in

he activity.

ethod of Participation and Receipt of CMEertificateo obtain credit for this CME activity, you must:. Be an ACC member or JACC: Cardiovascular

Imaging subscriber.2. Carefully read the CME-designated article avail-

able online and in this issue of the journal.3. Answer the post-test questions. At least two out

of the three questions provided must be answered

anuscript received November 10, 2010; revised manuscript received

imaging.onlinejacc.orgDownloaded from

4. Complete a brief evaluation.5. Claim your CME credit and receive your certif-

icate electronically by following the instructionsgiven at the conclusion of the activity.

CME Objective for This Article: At the completionof this article, the reader should be able to: recognizethe MR appearance of hypertrophic cardiomyopa-thy; determine when to utilize cardiac MRI proce-dures into clinical management of hypertrophiccardiomyopathy; assess the benefits and pitfalls ofcardiac MRI in the evaluation of hypertrophic car-diomyopathy; and discuss the utility of cardiac MRIin the screening of hypertrophic cardiomyopathy.

CME Editor Disclosure: JACC: CardiovascularImaging CME Editor Ragaven Baliga, MD, hasreported that he had no relationships to disclose.

Author Disclosure: The authors have reported thatthey have no relationships relevant to the contents ofthis paper to disclose.

Medium of Participation: Print (article only); on-line (article and quiz).

CME Term of Approval:Issue Date: October 2011

correctly to obtain CME credit. Expiration Date: September 30, 2012

rom the Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio. The authors have reported that they have noelationships relevant to the contents of this paper to disclose.

May 27, 2011, accepted June 29, 2011.

by on November 21, 2011

http://www.imaging.onlinejacc.org


J A C C : C A R D I O V A S C U L A R I M A G I N G , V O L . 4 , N O . 1 0 , 2 0 1 1

O C T O B E R 2 0 1 1 : 1 1 2 3 – 3 7

To et al.

CMR in HCM

1124

Cardiac Magnetic Resonance in Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy is a complex genetic cardiovascular disorder with substantial variability in

phenotypic expression and natural progression. Recent research demonstrates the incremental utility of

cardiac magnetic resonance in the diagnosis, therapeutic planning, and prognostication of this disease.

The increasing incorporation of multimodality imaging of hypertrophic cardiomyopathy in clinical prac-

tice will continue to improve our understanding of the subtle morphologic differences and their prognos-

tic implications. (J Am Coll Cardiol Img 2011;4:1123–37) © 2011 by the American College of Cardiology

Foundation

Hidfiiv(gp

asb(avrsmmrhstppprdrlatta(

dpob

ypertrophic cardiomyopathy (HCM) isthe most common genetic cardiovasculardisorder, with an estimated prevalence of1:500 in the general population (1,2). It

s typically inherited as a Mendelian autosomalominant trait, with over 600 mutations identi-ed in sarcomeric genes (3,4). Recently, mutations

n genes encoding Z-disc proteins and proteins in-olved in calcium regulation have also been implicated5). This genetic diversity together with modifierenes and environmental factors form the basis of itshenotypic heterogeneity.Symptoms of HCM can develop from childhood

nd include exertional dyspnea, chest pain, pre-yncope, and syncope, resulting from differing com-inations of dynamic left ventricular outflow tractLVOT) obstruction, left ventricular (LV) diastolicnd systolic dysfunction, and supraventricular/entricular arrhythmias. Although many patientsemain asymptomatic with a benign natural history,udden cardiac death (SCD) might be the initialanifestation in many otherwise asymptomatic orildly symptomatic young people (1,6). Current

isk prediction models include prior SCD, familyistory of SCD, unexplained syncope, spontaneousustained ventricular tachycardia, nonsustained ven-ricular tachycardia on continuous electrocardiogra-hy (ECG) monitoring, abnormal exercise bloodressure, and LV thickness �30 mm (6). Suchrediction models are far from perfect for severaleasons. Although a low risk of SCD has beenemonstrated in those without the aforementionedisk markers (7), the negative predictive value isikely overestimated, because not all cases of SCDre captured in retrospective studies. Conversely,he positive predictive value of individual risk fac-ors is low, with the exception of prior aborted SCDnd spontaneous sustained ventricular tachycardia
8). The concern remains that, if implantable car-
by oimaging.onlinejacc.orgDownloaded from

ioverter defibrillators (ICDs) were inserted in allatients with any “high-risk” feature, the incidencef device complications would surpass the potentialenefits.

Emergence of Cardiac Magnetic Resonance in HCM

Traditionally, the diagnosis of HCM relies uponclinical assessment and transthoracic echocardi-ography (TTE) to identify features such as leftventricular hypertrophy (LVH), systolic anteriormotion of the mitral valve, and LVOT obstruc-tion. In many clinical scenarios, technical limita-tions of echocardiography and heterogeneousphenotypic expression made such evaluation dif-ficult, and cardiac magnetic resonance (CMR)has emerged as a useful adjunctive imaging mo-dality to complement routine TTE (9). CMR isunique in its high spatial and temporal resolutionwith excellent contrast between blood pool andmyocardium, without limitation of either imag-ing window or imaging plane. Late gadoliniumenhancement (LGE) sequences enable the iden-tification of myocardial fibrosis, which is associ-ated with poor outcome (10 –14). In our centerand many others, CMR imaging is routinelyperformed in all new patients with suspected orknown HCM as part of a comprehensive workupthat also includes TTE with provocative maneu-vers, exercise stress echocardiography, and trans-esophageal echocardiography (TEE) in selectcases. Indeed, comprehensive CMR in the diag-nostic workup of HCM is considered an appro-priate use of technology (15,16). Although defin-itive cost-effectiveness data are unavailable, dataare likely to be available in specific clinicalscenarios where CMR aids in further refinementof the current strategies of diagnosis, screening,
treatment, and prognosis. Table 1 summarizes
n November 21, 2011


oitsIpOtemaac

asptmlre

tL2hamdLsicCotpotwtLtgoi

LcngeflnPhpdqpCmtpa

ardiography


O C T O B E R 2 0 1 1 : 1 1 2 3 – 3 7

To et al.

CMR in HCM

1125

the details and limitations of the typical CMRstudy for HCM.

In this review article, we discuss the role ofCMR in the diagnosis, treatment, and prognosisof HCM, with a focus on the complementaryvalue of CMR in relation to standard imagingmodalities, and we examine some of the emergingroles of CMR.

CMR and Diagnosis

The phenotypic heterogeneity of HCM is well-recognized. This is further complicated because notall patients with LVH have HCM, whereas HCM-like pathophysiology with dynamic LVOT obstruc-tion can be observed without LVH, in a subgroupof patients with mitral valve and/or papillary muscleabnormalities. Figure 1 summarizes the diagnosticchallenges faced by clinicians in both establishedand suspected HCM. Figure 2 highlights the areaswhere CMR potentially has incremental utility.Although a more comprehensive algorithm detail-ing the step-by-step diagnostic approach in HCMhas been detailed elsewhere (17), a simplified ap-proach to the differential diagnosis of HCM hasbeen outlined in Figure 3. CMR enables the precisecharacterization of subtle disease phenotypic varia-tions (Figs. 4, 5, 6, and 7, Online Videos 1, 2, and3), especially important for characterizing LVOT,papillary muscle, subvalvular anatomy, and diagnos-ing of atypical HCM. High image quality andtissue characterization accurately identify the vari-ous conditions that mimic the morphological ap-pearance of HCM (Figs. 8 and 9, Online Videos 4and 5). Reproducible volume and mass quantificationmight also identify at-risk individuals with a familyhistory of HCM and can be used to screen forpre-clinical disease.Disease characterization: LVOT, papillary muscle, andsubvalvular anatomy. Resting or provocable LVOTbstruction is present in 70% of cases and is anmportant manifestation of HCM (18). It relates tohe complex anatomical relationships between theeptum, LVOT, mitral valve, and papillary muscles.n the majority of HCM patients, septal hypertro-hy leads directly to LVOT obstruction (Fig. 4,nline Video 1). However, some present with hyper-

rophy without obstruction, whereas others pres-nt with dynamic LVOT obstruction and mini-al septal hypertrophy. The latter is likely due tovariety of papillary muscle and subvalvular

bnormalities (19) (Fig. 5, Online Video 2). Such
omplexity highlights the importance of accurate an- U
imagingDownloaded from

tomical assessment. TTE and TEE are the currenttandards in assessing LVOT anatomy and flowrofile. The main advantage of CMR is in iden-ifying the anatomy of the septal-systolic anteriorotion contact and subvalvular apparatus. Iso-

ated or concomitant mid-ventricular obstructionelated to mid-ventricular hypertrophy is alsoasily demonstrated.

The CMR studies have illustrated the contribu-ion of abnormal mitral subvalvular morphology inVOT obstruction (20,21) (Fig. 6, Online Video). Compared with control subjects, HCM patientsave a higher incidence of papillary muscle anom-lies such as bifid or multiple accessory papillaryuscles, as well as anteroapical papillary muscle

isplacement that encroaches into theVOT during systole (19,22). Figure 7

chematically illustrates the common pap-llary muscle anatomical variations thatontribute to LVOT obstruction. DuringMR acquisition, careful attention is paidn the short-axis cine images, with addi-ional long-axis cine images specificallylanned to demonstrate subvalvular anat-my. This is especially important in pa-ients with dynamic LVOT obstructionithout classic asymmetric septal hyper-

rophy. A 3-dimensional dataset of theV with high spatial resolution is ob-

ained with a respiratory navigator ECG-ated whole-heart sequence that allowsffline multiplanar reconstruction of pap-llary and subvalvular anatomy.

Although CMR assessment of theVOT is primarily anatomical, LVOT ac-eleration and flow turbulence can be diag-osed as systolic signal void in flow-sensitiveradient echo sequences, and LVOT gradi-nt can be quantified with phase contrastow-sensitive sequences. However, this is often tech-ically challenging in HCM for a variety of reasons.roper alignment of the imaging plane to obtain theighest flow velocities can be time consuming androne to errors. Intravoxel dephasing and signal lossue to phase offset errors also make the accurateuantification of turbulent flow difficult. Imaging withrovocation and during exercise is also difficult withMR. New CMR sequences under developmentight allow the routine 3-dimensional acquisition of

he flow pattern and velocities not limited by imaginglanes (23), real-time velocity encoding (24), as well asccurate measurement of turbulent jet velocities (25).

A B B

A N D

CMR �

reson

ECG �

HCM

cardio

ICD �

defibr

LGE �

enhan

LV �

LVH �

hyper

LVOT

tract

RV �

SCD �

TEE �

echoc

TTE �

echoc

ntil then, echocardiography remains the “gold

by on November 21, 2011 .onlinejacc.org

R E V I A T I O N S

A C R O N YM S

cardiac magnetic

ance

electrocardiography

� hypertrophic

myopathy

implantable cardioverter

illator

late gadolinium

cement

left ventricle/ventricular

left ventricular

trophy

� left ventricular outflow

right ventricle/ventricular

sudden cardiac death

transesophageal

ardiography

transthoracic

stan-

http://jaccimage.cardiosource.com/vol4/issue10/0397_VID1-vol4iss10.avi










outflow tract; SCD � sudd y sta


O C T O B E R 2 0 1 1 : 1 1 2 3 – 3 7

To et al.

CMR in HCM

1126

dard” for flow quantification of LVOT obstruction inHCM.

CMR assesses mitral regurgitation with diversetechniques. Gauging severity on the basis ofturbulence-related signal void in various cinesequences is fraught with errors, because it ishighly dependent on pulse sequence parameters.Most commonly, visualizing the regurgitant jeton flow-sensitive gradient echo sequences is com-

cated CMR Study for HCM: Potential Advantages and Limitations

Technical Details Information Obtained

e Balanced SSFP Septal thickness Im

Optionally, 3D SSFP Relationship between theseptum, mitral valve, andsubvalvular apparatus in theLVOT obstruction

N

Global and regionalventricular function

Q

Ventricular mass C

Phase-sensitiveinversion recoverygradient echosequence

Extent and location ofmyocardial fibrosis

T

Respiratory navigatorgated ECG gated 3DSSFP sequences

Papillary muscle anatomy L

Coronary artery anatomy E

SPAMM sequence Regional wall deformation A

Velocity-encoded cinesequences

Aortic flow velocities,profile, and volume

Q

LVOT flow velocities and profile Q

Mitral regurgitant volumes andfractions

t 90° saturation recoverypre-pulse followedby gradient echoreadout sequences

Myocardial perfusion In

� cardiac magnetic resonance; ECG � electrocardiography; HCM � hypertrophen cardiac death; SPAMM � spatial modulation of magnetization; SSFP � stead

plemented with quantification, by subtracting t


forward aortic flow derived from the velocity-encoded phase contrast sequence, from strokevolume derived from LV volume measurements(26,27). Although CMR also demonstrates mi-tral leaflet abnormalities, echocardiography re-mains the test of choice because of superiortemporal resolution and various Doppler tech-niques for hemodynamic information.Disease characterization: atypical forms of HCM. In

otential Advantages OverEchocardiography

Limitations of CMRTechniques

e quality superior tohocardiography

Availability and portability ofechocardiography is unlikelyto be matched by CMR

itation of imaging windowd imaging plane

3D cine sequences are currentlylimited by acquisition time,inferior spatial and temporalresolution

tification of ventricularlumes, function, and massth excellent reproducibility

Functional information ondynamic LVOT obstructionmight not be easily obtained

ared with transesophagealhocardiography, CMR isninvasive

e characterization forocardial fibrosis isique to CMR

Limited role in patients withchronic renal failure due toconcern over nephrogenicsystemic fibrosis

Quantification of myocardialfibrosis is time consuming

Detection of diffuse myocardialfibrosis remains challenging

Selection of wrong nulling timeon LGE might makemeasurement of myocardialfibrosis inaccurate

ization of papillary musclember, extent, proximal andtal attachments

3D information with a highspatial resolution is not easilyobtainable

sion of coronary anomalies asernative cause of cardiachythmia and SCD

rate characterization of regionalformation: strain and strain rate

Data analysis to obtain strainand strain rate remains timeconsuming

Limited clinical utility

tification of flow velocitiesd volume

Accuracy of flow measurementsin HCM has not beenvalidated

tification of mitral regurgitation

ation on myocardial perfusioneasily obtained with CMR, attime of contrast injection for

E assessment

Data analysis to quantifymyocardial perfusion remainsthe realm of advancedresearch laboratory

Clinical implications ofabnormal findings notwell-established

rdiomyopathy; LGE � late gadolinium enhancement; LVOT � left ventricularte free precession.

Table 1. Typical Dedi

Typical SequencesP

Bright blood cine imag agec

o liman

uanvowi

ompecno

LGE images issumyun

3D SSFP wholeheart dataset

ocalnudis

xclualtarr

Tagged cine images ccude

Flow quantificationsequences

uanan

uan

Perfusion images—res formistheLG

3D � 3-dimensional; CMR ic ca

he past, it was presumed that HCM is synonymous

n November 21, 2011


Hwmr

sevntt

phy


O C T O B E R 2 0 1 1 : 1 1 2 3 – 3 7

To et al.

CMR in HCM

1127

with asymmetric septal hypertrophy, and hence aseptal to posterior wall ratio �1.3 is diagnostic of

CM (28,29). Subsequent studies, including thoseith CMR, showed that atypical cases of HCM areore common than previously thought (30,31). These

ange from diffuse global hypertrophy on 1 end of the

Geno

Pheno

GenotypicHeterogeneity

PhenotypicHeterogeneity

Other conditions maymimic the hypertrophic

cardiomyopathy

Atypical distribution

of hypertrophy

HYPERTROPHY

Non-obstructive hypertrophic

cardiomyopathy

HypeObst

Cardio

Figure 1. Diagnostic Challenges Faced by Clinicians in Suspecte

This figure demonstrates the potential difficulties in diagnosis of hyheterogeneity. Patients within the same family might have differenleft ventricular outflow tract (LVOT) obstruction to minimal hypertro

Potential Utility of C

Diagnosis

If diagnosis ofHCM is

established

If diagnosisof HCM isuncertain

If there is afamily histor

of HCM

Diseasecharacterization and

phenotypic expression

LVOT obstruction,mitral valve andpapillary muscle

anatomy

•Asymptomati positive gene carrier

•Asymptomati suspected gene carrier

Screening forpreclinical

disease

Differentialdiagnosis

•Hypertensive heart diseaseAtypical forms of HCM

•Apical HCM

•Apical aneurysm

•Atypical non-contiguous pattern of hypertrophy

•Right ventricular involvement

•Aortic stenosis

•Athlete’s heart

•Asymmetric septal hypertrophy of the elderly

•Non-compaction

•Infiltrative heart disease

Figure 2. Potential Role of CMR in Management of HCM

This figure explains the potential utility of cardiac magnetic resopotential role in establishing the diagnosis, pre-procedural plann
as in Figure 1.

pectrum to focal segmental hypertrophy on the othernd. The focal hypertrophy variant sometimes in-olves only 1 to 2 myocardial segments, often with aoncontiguous pattern of hypertrophy where hyper-rophied segments are separated by regions of normalhickness (30). Normal LV mass does not exclude

Concurrent mitralvalve abnormalities

Concurrent papillarymuscle abnormalities

LVOT OBSTRUCTION

Delayed disease expression in gene carriers,hence issues with screening

Classic LVOT obstructionmay occure withoutseptal hypertrophy

Obstructive cardiomyopathy without

hypertrophy

phictivepathy

d Established HCM

rophic cardiomyopathy (HCM) due to phenotypic and genotypicenotypic expressions, ranging from gross hypertrophy with severeand no LVOT obstruction.

Evaluation of HCM

Treatment Prognosis

Pre-proceduralplanning

Post-proceduralplanning

Riskprediction

LV septaldimension

LVOTanatomy

Mitral valveand papillary

muscleanatomy

Papillarymuscle

remodeling

Mitral valverepair

Myectomy

LV mass

LV function

Late gadoliniumenhancement

ce (CMR) in the diagnosis and management of HCM. It has a, and prognostication. LV � left ventricular; other abbreviations

type

type

rtrorucmyo

d an

pertt ph

MR

y

c

c

naning



ia

ures


O C T O B E R 2 0 1 1 : 1 1 2 3 – 3 7

To et al.

CMR in HCM

1128

HCM in these patients. Such a focal noncontiguouspattern of hypertrophy is not usually seen in secondaryforms of hypertrophy (e.g., hypertension). In 12% ofHCM patients, focal segmental LV hypertrophy islimited to the anterolateral free wall, posterior septum,or apex (30,32). These areas are technically challeng-ing for TTE, due to imaging window limitation, andin 1 study, the diagnosis of HCM was missed in 6%of patients by echocardiography (32).

Apical HCM (Fig. 6, Online Video 3) withpredominantly LV apical hypertrophy is commonlymissed on TTE, because of limited acoustic windowsand foreshortening, and CMR has incremental utilityhere (33). Similarly, apical aneurysm can be missed onnoncontrast TTE in 40% of cases and is best visual-ized on CMR (34). Apical aneurysms present asdyskinesis or akinesis with a thin rim of myocardium,often with transmural scarring on LGE, and areassociated with adverse outcomes with an annualevent rate of 11%. In addition, recent reports foundthat HCM patients often have significant right ven-tricular (RV) involvement with increased RV wallthickness and mass compared with control subjects(35). Assessment of RV by CMR is superior toechocardiography.Differential diagnosis. Accurate diagnosis of HCMs important, because of the significant lifestyle

Figure 3. Simplified Approach to the Differential Diagnosis of H

This figure is a simplified diagnostic approach in a patient with incrcessful, multimodality imaging is necessary. Abbreviations as in Fig

ltering and familial implications. i


HYPERTENSIVEHEARTDISEASEANDAORTICSTENOSIS.

Hypertensive heart disease and aortic stenosis bothpresent with concentric rather than asymmetricalLVH. HCM and hypertensive heart disease occa-sionally might be difficult to differentiate, but ingeneral, LV wall thickness of hypertensive heartdisease is �15 to 16 mm. Specific studies compar-ing hypertensive heart disease and HCM withCMR are sparse, although with improved imagequality, CMR is more sensitive in detecting differ-ences in segmental wall thickness. Interestingly,although myocardial fibrosis on LGE has tradition-ally been considered rare in hypertensive heartdisease and aortic stenosis, a recent study demon-strated patchy LGE in more than 50% of hyper-tensive heart disease and aortic stenosis patientswith significant LVH (36). Another report alsosuggested a potential prognostic role for LGE inaortic stenosis (37). As such, LGE itself might notbe specific for HCM, and its prognostic utility inother disorders needs to be studied further. Inaddition, in a small group of patients with concom-itant valvular aortic stenosis and LVOT obstructionfrom asymmetric septal hypertrophy, CMR canidentify the site of jet turbulence and distinguish therelative contributions of the 2 disease processes.

ATHLETE’S HEART. Athlete’s heart is character-

d LV thickness. Please note that for such an approach to be suc-1 and 2.

CM

ease

zed by a mildly enlarged LV cavity, symmetric

n November 21, 2011



accviidsaoi

dce

sgcpaV

ures


O C T O B E R 2 0 1 1 : 1 1 2 3 – 3 7

To et al.

CMR in HCM

1129

thickening of the LV wall—typically �15 mm—nd normal diastolic function on Doppler echo-ardiography. CMR complements TTE in thisondition, because it accurately measures LVolumes, mass, and function, with high reproduc-bility (9,38). Researchers used wall thicknessndexed to end-diastolic ventricular volume toistinguish athlete’s heart from HCM (39). De-pite this, such differentiation remains difficult,nd some subjects might have to undergo a periodf deconditioning to document reverse remodel-ng as a definitive proof of athlete’s heart (40).

NONCOMPACTION. Noncompaction is character-ized by prominent LV trabeculations, and differenti-ation of compacted and noncompacted layers is oftendifficult in echocardiography, especially without con-trast. CMR is ideal for delineating compacted andnoncompacted layers. An end-diastolic ratio betweennoncompacted and compacted layers of more than2.4:1.0 is a proposed imaging criterion for noncom-paction. CMR also precisely delineates the character-

Figure 4. Patient With “Typical” HCM and LVOT Obstruction

(A) Patient with “typical” HCM with marked basal septal hypertrophraphy after amyl nitrite. Patient with “garden-variety” hypertrophicLVOT obstruction. Also note the myocardial fibrosis. Late gadoliniumcardial fibrosis (arrows). See Online Video 1. Abbreviations as in Fig

istic abrupt transition zone between affected and


nonaffected segments as well as diagnoses the com-monly associated LV thrombus.

INFILTRATIVE HEART DISEASES. Infiltrative heartiseases mimic HCM with LVH and its functionalonsequences. CMR plays an important role inxcluding these conditions.Fabry’s disease. Fabry’s disease is an X-linked reces-ive glycolipid storage disease with deficient alpha-alactosidase activity. The resulting phenotype is ofoncentric hypertrophy, with LGE found in 50% ofatients, typically in the basal inferolateral segment inmid-myocardial distribution (41) (Fig. 8, Onlineideo 4).

Hypereosinophilic syndrome. Hypereosinophilic syn-drome presents with apical fibrosis and muralthrombus, frequently leading to apical cavity oblit-eration, and therefore can sometimes mimic apicalHCM on TTE (42). Areas of increased subendo-cardial signal intensity are often observed.Sarcoidosis. Sarcoidosis usually presents with a re-strictive cardiomyopathy with generalized LV thick-

CMR and (B) LVOT obstruction (arrow) on Doppler echocardiog-ructive cardiomyopathy with severe basal septal hypertrophy andhancement in long-axis (C) and short-axis (D) views showed myo-1 and 2.

y onobsten

ening, but asymmetric basal septal involvement can







O C T O B E R 2 0 1 1 : 1 1 2 3 – 3 7

To et al.

CMR in HCM

1130

mimic HCM (43). The LGE pattern is variable, mostcommonly affecting the basal and lateral segments.Amyloidosis. Amyloidosis presents with diffuse LVwall thickening and diffuse LGE associated with acharacteristic shortening of myocardial nulling timeon inversion recovery sequences (44,45) (Fig. 9,Online Video 5).Screening. Despite advances in gene testing in HCM,mutations are only identified in 60% of index HCMcases (3,4). Phenotypic heterogeneity, incomplete

Figure 5. Patient With “Obstructive Cardiomyopathy” With Min

The main pathology is the abnormal hypermobile bifid papillarythe anterior mitral valve leaflet (arrow, C), seen on CMR (diastolpost exercise LVOT obstruction (D). See Online Videos 1 andFigures 1 and 2.

Figure 6. Apical HCM

Apical HCM with marked mid and apical hypertrophy on cine CMR
hypertrophied apex on late gadolinium enhancement sequences (B). Se

penetrance, and delayed disease presentation some-times until adulthood also make it challenging toscreen for suspected carriers and detect preclinical diseasein definite carriers. Current strategy involves a combina-tion of clinical assessment, ECG, and TTE at 12- to18-month intervals from age 12 to adulthood, althoughnegative clinical and imaging tests cannot fully excludethe risks of future disease development (46).

Although a large prospective study of HCMscreening with CMR has not been performed, CMR

l LVH

scle (arrows, A and B) resulting in systolic anterior motion of] and systole [B]) and echocardiography (C). This causes severeLVH � left ventricular hypertrophy; other abbreviations as in

Patchy late gadolinium enhancement (arrow) is observed in the

ima

mue [A2.

(A).
e Online Videos 1 and 3. Abbreviations as in Figures 1 and 2.
n November 21, 2011







1.


O C T O B E R 2 0 1 1 : 1 1 2 3 – 3 7

To et al.

CMR in HCM

1131

might detect subtle abnormalities and/or serialchanges that are otherwise not observed on echocar-diography, enabling the detection of pre-clinical dis-ease. In small studies, CMR detected abnormal wallthickening in approximately 20% of asymptomaticgene carriers not appreciated by echocardiography.Pre-hypertrophic crypts in the basal and mid infero-septum have been suggested as a sign of a mutationcarrier (47,48). In a recent study, high levels of serumC-terminal propeptide of type I procollagen werefound in subjects with HCM-mutations without

Figure 7. Schematic Diagram of the Common Variations in Pap

Schematic diagram of the common variations in papillary muscle aduring diastole, the right image represents systole. (A) Normal papment of the papillary muscles; (D) hypertrophied papillary muscleschordal attachment to the mid-portion of the mitral valve (MV); andLA � left atrium; LV � left ventricle; other abbreviation as in Figure

Figure 8. Patient With Fabry’s Disease

Cine sequence in the 3-chamber view demonstrates the concentric
(arrow) late gadolinium enhancement (B). See Online Video 4.

LVH, as compared with control subjects (49). Parallelto the research in strain imaging by echocardiography todetect subclinical contractile dysfunction in carriers(50,51), CMR myocardial tagging techniques have alsobeen investigated; however, studies remain sparse (52).

CMR and Treatment Strategies

Symptomatic patients with obstructive HCM intrac-table to medical therapy can either undergo surgicalmyectomy or alcohol septal ablation. CMR is an

y Muscle Anatomy in HCM

my in HCM (arrows). The left image represents the myocardiummuscle orientation; (B) bifid papillary muscles; (C) apical displace-mainly mid-cavity obstruction during systole; (E) abnormalelongated anterior MV leaflet. See Online Video 2. Ao � aorta;

ertrophy (A), associated with the basal posterolateral segment

illar

natoillarywith(F)

hyp





pshm

cmastmiTtsttlm

cbfmtpfip

(fkctgHms

B). S


O C T O B E R 2 0 1 1 : 1 1 2 3 – 3 7

To et al.

CMR in HCM

1132

important adjunct in the pre-procedural planningfor both procedures. We perform pre-operativeCMR and perioperative TEE to precisely measurethe degree and extent of the anteroseptal andinferoseptal hypertrophy as well as the relationshipof the septum with the anterior mitral valve leaflet,subvalvular apparatus, and papillary muscle mor-phology. Accurate pre-operative anatomical assess-ment of the subvalvular anatomy has led to theincreasing recognition that septal myectomy mightneed to be combined with mitral valve and chordaeremodeling and/or papillary muscle reorientation tooptimally relieve LVOT obstruction (53,54).

CMR is extensively used to assess the effective-ness of alcohol septal ablation (55,56). CMR aftersurgical myectomy or alcohol septal ablation pro-vides insights on the effect of the respective proce-dures on the interventricular septum (55). Surgicalmyectomy predictably leads to a discrete resectedarea in the anteroseptum, whereas alcohol septalablation leads to a variable pattern of myocardialscar, usually inferiorly in the basal septum withextension to the RV side of the septum. Theimprovement of LVOT obstruction is also morevariable after alcohol septal ablation.

CMR and Prognosis

LGE. There is a growing body of published re-orts on the role of LGE on CMR in HCM risktratification, but a large prospective study onow the data should be interpreted to alter

Figure 9. Patient With Cardiac Amyloidosis

Cine sequence in the 4-chamber view demonstrates diffuse concenimages showed extensive amyloid infiltration (arrows) with generalreduced myocardial nulling time on inversion recovery sequences (

anagement is still lacking. The histological a


orrelate of LGE in HCM seems to be increasedyocardial collagen rather than myocardial dis-

rray, which is also observed on histologicalpecimens. Increased myocardial collagen is pos-ulated to reflect microvascular ischemia andicroscopic replacement fibrosis due to small

ntramural coronary arteriole dysplasia (57,58).he latter finding correlates with LGE in myec-

omy specimens from patients who underwenturgery for LVOT obstruction (58). An alterna-ive hypothesis for LGE in HCM suggested thathe causative sarcomeric gene mutations mightead to a phenotypic expression of increased

yocardial connective tissue deposition (59).The prevalence of LGE is variable in different

ohorts. In those with manifest HCM, it variesetween 40% and 80% (10–14,60). The commonlyound LGE pattern is patchy, multifoci mid-yocardial fibrosis, especially in regions of hyper-

rophy (Figs. 4B, 4D, and 6B). Other observedatterns include diffuse confluent transmural septalbrosis and patchy septal fibrosis at RV insertionoints.LGE correlates with LV wall thickening

10,61) and inversely correlates with LV ejectionraction (61– 63). It also correlates with othernown clinical markers of SCD (64). The asso-iation between LGE and the detection of ven-ricular arrhythmia on Holter monitoring sug-ests the potential pathophysiologic link betweenCM, myocardial fibrosis, arrhythmia, and ulti-ately SCD (10 –14,60). Recent longitudinal

tudies suggest a strong association between LGE

left ventricular hypertrophy (A). Late gadolinium enhancementgadolinium uptake, resulting in high signal intensity and aee Online Video 5.

tricized

nd SCD (Table 2) (12–14). LGE shows prom-

n November 21, 2011




O C T O B E R 2 0 1 1 : 1 1 2 3 – 3 7

To et al.

CMR in HCM

1133

ise, but there is insufficient evidence for insertingan ICD on the basis of LGE alone. Furtherstudies should establish the role of LGE inidentifying high-risk patients from among thosewho are currently classified as intermediate-riskwith clinical criteria and do not otherwise qualifyfor ICD insertion.

Certain aspects of LGE in HCM prognostica-tion are technically challenging and worthy ofmention. Error in the appropriate myocardial null-ing time might over- or underestimate true fibrosisburden. The use of phase sensitive inversion recov-ery sequences has greatly improved this aspect (65).Although LGE is assessed qualitatively in routineclinical practice, LGE in relation to overall LVmyocardial volume can be quantified with auto-mated software. Various methods exist and mostcommonly calculate the total areas of signal inten-sity above a certain number of SDs (n � 2 to 6) overthat of the mean signal intensity of nulled myo-cardium (61,66 – 68). These differences in meth-odology translate into differences in the quanti-fied area of LGE and potentially impact on theability to generalize individual research studies.The current assessment of myocardial fibrosiscontrasts areas of LGE with areas of presumed“normal” nulled myocardium. Histological stud-ies, however, suggest a global increase in myocar-dial fibrosis that current LGE imaging tech-niques cannot detect. New techniques such as T1mapping (69) and equilibrium contrast CMR(70) might offer alternatives to quantify the

Table 2. Summary of the Recent Prognostic Studies on the Role

O’Hanlon

N (% women) 217

Follow-up, yrs 3

Clinical (%)

NYHA functional class III/IV 14

Wall thickness �30 mm 6

History of syncope 16

History of sustained VT/VF 3

CMR

Prevalence of LGE (%) 63

Quantification of LGE FWH

Outcome

Primary endpoint: LGE vs. no LGE Primary combined endpoCardiovascular deaths (5.9

FWHM � full-width at half maximum; HR � hazard ratio; ICD � implantable caventricular tachycardia; other abbreviations as in Table 1.

overall extent of myocardial fibrosis.


With respect to LGE and prognosis, the relativeimportance of the severity, extent, and location ofLGE as well as whether there is a threshold effectbelow which fibrosis does not impact on prognosisis uncertain.Septal thickness and LV mass. The current guidelinesinclude LV thickness �30 mm on TTE as animportant prognostic criterion (6). The improvedaccuracy of CMR in measuring LV thickness willlikely refine this. In addition, CMR provides accu-rate and reproducible information on overall LVmass. Investigators have studied the relative prog-nostic value of LV wall thickness and mass byCMR. HCM patients typically have a “thickness-mass” mismatch because of the differing extent ofhypertrophy in individual LV segments. It wasfound that LV mass indexed to body surface areaabove 2 SDs of a healthy control cohort is asensitive but not specific predictor of outcome,whereas an LV wall thickness �30 mm is a morespecific but less sensitive predictor (71). Futurestudies will clarify how best to use this informationin management.

New Developments in CMR Imaging of HCM

Several new developments in CMR imaging ofHCM are worth discussing, but their clinical ap-plications remain undecided.

There has been increasing awareness of theimportance of ventricular vascular interactions in

LGE in HCM

l. (13) Bruder et al. (14) Rub

243 (39)

3.0

8

4

6

6

61

2 SD Quali

25% vs. 7%); HR 3.37s. 1.2%); HR 4.45

LGE is associated with all-causemortality (OR: 5.47) andcardiac mortality (OR: 8.01)

SCDdis0.0

erter defibrillator; NYHA � New York heart association; OR � odds ratio; VF � ve

of

et a inshtein et al. (12)

(29) 424 (41)

.1 3.6

53

7

16

10

56

M tative manual tracing

int (% v

and appropriate ICDcharge (3.4% vs.%)

rdiov ntricular fibrillation; VT �

various cardiac disorders. HCM patients were



TaE


O C T O B E R 2 0 1 1 : 1 1 2 3 – 3 7

To et al.

CMR in HCM

1134

found to have a higher pulse wave velocity thanmatched control subjects, indicating increasedaortic stiffness (72). This was independently as-sociated with lower peak oxygen consumption oncardiopulmonary exercise testing (73). Whole-heart CMR sequences also provided insight thatHCM patients have a steep angle between theaortic root and the LV long axis, compared withcontrol subjects. The acuteness of this LV-aorticroot angle correlates with age and the observedLVOT gradient (74). These early findings high-light the potential impact HCM has on the aorticvasculature and the usefulness of CMR in inves-tigating this relationship.

CMR perfusion studies in HCM investigatedthe role of microvascular dysfunction in intramu-ral coronary arteriole dysplasia and subsequentlymyocardial fibrosis as well as in blunting myocar-dial blood flow during vasodilator stress, whichhas been observed in HCM, especially subendo-cardially (75). Furthermore, CMR spectroscopywith 31-phosphorus demonstrated an alteredmyocardial energy metabolic profile in HCM thatcorrelated with the severity of LGE (76). WithCMR spectroscopy, perhexiline, a modulator ofsubstrate metabolism, was shown to amelioratecardiac energetic impairment, correct diastolicdysfunction, and increase exercise capacity insymptomatic HCM patients (77).

Myocardial tagging quantifies myocardial me-chanics parameters such as strain, strain rate, andtorsion and has been studied in HCM. Not

GK, et al. American College of Cardi- magnetic resonance


myocardial segments and is inversely related toseverity (52,78). These findings are analogous tostrain measured by speckle tracking on echocar-diography, where impaired longitudinal strainwas shown to correlate with fibrosis severity (79).

Conclusions

HCM is a heterogeneous disease with complex mor-phological expression that requires accurate diseasecharacterization for optimal therapeutic planning andrisk-stratification. CMR has emerged as a usefuladjunct for these purposes. With the increasing incor-poration of multimodality imaging in the clinicalassessment of HCM, our understanding of the signif-icance of subtle morphological differences will con-tinue to grow, and further research will define newprognostic markers and improve current treatmentstrategies.

AcknowledgmentsThe authors would like to acknowledge MarionTomasko for her graphical support and KathrynBrock for her editorial support. Dr. To acknowl-edges the support from the Overseas FellowshipAward from the National Heart Foundation ofNew Zealand.

Reprint requests and correspondence: Dr. Milind Y. Desai,omsich Department of Cardiovascular Medicine, Heart

nd Vascular Institute, Cleveland Clinic, J1-5, 9500uclid Avenue, Cleveland, Ohio 44195. E-mail:

unexpectedly, strain is reduced in hypertrophied [email protected].

1

1

1

R E F E R E N C E S

1. Maron BJ. Hypertrophic cardiomyop-athy: a systematic review. JAMA2002;287:1308–20.

2. Elliott P, McKenna WJ. Hypertro-phic cardiomyopathy. Lancet 2004;363:1881–91.

3. Marian AJ, Roberts R. The moleculargenetic basis for hypertrophic cardio-myopathy. J Mol Cell Cardiol 2001;33:655–70.

4. Seidman JG, Seidman C. The geneticbasis for cardiomyopathy: from muta-tion identification to mechanistic par-adigms. Cell 2001;104:557–67.

5. Bos JM, Towbin JA, Ackerman MJ.Diagnostic, prognostic, and therapeu-tic implications of genetic testing forhypertrophic cardiomyopathy. J AmColl Cardiol 2009;54:201–11.

6. Maron BJ, McKenna WJ, Danielson

ology/European Society of Cardiologyclinical expert consensus document onhypertrophic cardiomyopathy. A reportof the American College of CardiologyFoundation Task Force on Clinical Ex-pert Consensus Documents and theEuropean Society of Cardiology Com-mittee for Practice Guidelines. J AmColl Cardiol 2003;42:1687–713.

7. Elliott PM, Poloniecki J, Dickie S, etal. Sudden death in hypertrophic car-diomyopathy: identification of highrisk patients. J Am Coll Cardiol 2000;36:2212–8.

8. Christiaans I, van Engelen K, vanLangen IM, et al. Risk stratificationfor sudden cardiac death in hypertro-phic cardiomyopathy: systematic re-view of clinical risk markers. Europace2010;12:313–21.

9. Lima JA, Desai MY. Cardiovascular
imaging: current
n November 21, 20

and emerging applications. J Am CollCardiol 2004;44:1164–71.

0. Kwon DH, Setser RM, Popovic ZB,et al. Association of myocardial fibro-sis, electrocardiography and ventricu-lar tachyarrhythmia in hypertrophiccardiomyopathy: a delayed contrastenhanced MRI study. Int J CardiovascImaging 2008;24:617–25.

1. Adabag AS, Maron BJ, Appelbaum E, etal. Occurrence and frequency of arrhyth-mias in hypertrophic cardiomyopathy inrelation to delayed enhancement on car-diovascular magnetic resonance. J AmColl Cardiol 2008;51:1369–74.

2. Rubinshtein R, Glockner JF, OmmenSR, et al. Characteristics and clinical sig-nificance of late gadolinium enhancementby contrast-enhanced magnetic resonanceimaging in patients with hypertrophic car-diomyopathy. Circ Heart Fail 2010;3:
51–8.
11

mailto:[email protected]


2

2

2

2

2

2

2

2

3

3

3

3

3

3

3

3

3

3

4

4

4

4


O C T O B E R 2 0 1 1 : 1 1 2 3 – 3 7

To et al.

CMR in HCM

1135

13. O’Hanlon R, Grasso A, Roughton M,et al. Prognostic significance of myo-cardial fibrosis in hypertrophic cardio-myopathy. J Am Coll Cardiol 2010;56:867–74.

14. Bruder O, Wagner A, Jensen CJ, etal. Myocardial scar visualized by car-diovascular magnetic resonance im-aging predicts major adverse eventsin patients with hypertrophic cardio-myopathy. J Am Coll Cardiol 2010;56:875– 87.

15. Hendel RC, Patel MR, Kramer CM,et al. ACCF/ACR/SCCT/SCMR/ASNC/NASCI/SCAI/SIR 2006 ap-propriateness criteria for cardiac com-puted tomography and cardiac magneticresonance imaging: a report of theAmerican College of Cardiology Foun-dation Quality Strategic DirectionsCommittee Appropriateness CriteriaWorking Group, American College ofRadiology, Society of CardiovascularComputed Tomography, Society forCardiovascular Magnetic Resonance,American Society of Nuclear Cardiol-ogy, North American Society for Car-diac Imaging, Society for Cardiovascu-lar Angiography and Interventions, andSociety of Interventional Radiology.J Am Coll Cardiol 2006;48:1475–97.

16. Nagueh SF, Bierig SM, Budoff MJ, etal. American Society of Echocardiog-raphy clinical recommendations formultimodality cardiovascular imagingof patients with hypertrophic cardio-myopathy endorsed by the AmericanSociety of Nuclear Cardiology, Soci-ety for Cardiovascular Magnetic Res-onance, and Society of CardiovascularComputed Tomography. J Am SocEchocardiogr 2011;24:473–98.

17. Desai MY, Ommen SR, McKennaWJ, Lever HM, Elliott PM. Imagingphenotype versus genotype in hyper-trophic cardiomyopathy. Circ Cardio-vasc Imaging 2011;4:156–68.

18. Maron MS, Olivotto I, Betocchi S, etal. Effect of left ventricular outflow tractobstruction on clinical outcome in hy-pertrophic cardiomyopathy. N EnglJ Med 2003;348:295–303.

19. Kwon DH, Setser RM, ThamilarasanM, et al. Abnormal papillary musclemorphology is independently associ-ated with increased left ventricularoutflow tract obstruction in hypertro-phic cardiomyopathy. Heart 2008;94:1295–301.

20. Klues HG, Roberts WC, Maron BJ.Anomalous insertion of papillary mus-cle directly into anterior mitral leafletin hypertrophic cardiomyopathy. Sig-nificance in producing left ventricularoutflow obstruction. Circulation 1991;84:1188–97.

21. Kon MW, Grech ED, Ho SY, BennettJG, Collins PD. Anomalous papillary
muscle as a cause of left ventricular
Down

outflow tract obstruction in an adult.Ann Thorac Surg 1997;63:232–4.

2. Harrigan CJ, Appelbaum E, MaronBJ, et al. Significance of papillarymuscle abnormalities identified bycardiovascular magnetic resonance inhypertrophic cardiomyopathy. Am JCardiol 2008;101:668–73.

3. Hope MD, Meadows AK, HopeTA, et al. Clinical evaluation ofaortic coarctation with 4D flow MRimaging. J Magn Reson Imaging2010;31:711– 8.

4. Macgowan CK, Kellenberger CJ,Detsky JS, Roman K, Yoo SJ. Real-time Fourier velocity encoding: an invivo evaluation. J Magn Reson Imag-ing 2005;21:297–304.

5. O’Brien KR, Myerson SG, CowanBR, Young AA, Robson MD. Phasecontrast ultrashort TE: a more reliabletechnique for measurement of high-velocity turbulent stenotic jets. MagnReson Med 2009;62:626–36.

6. Fujita N, Chazouilleres AF, HartialaJJ, et al. Quantification of mitralregurgitation by velocity-encodedcine nuclear magnetic resonance im-aging. J Am Coll Cardiol 1994;23:951– 8.

7. Hundley WG, Li HF, Willard JE, etal. Magnetic resonance imaging as-sessment of the severity of mitralregurgitation. Comparison with in-vasive techniques. Circulation 1995;92:1151– 8.

8. Henry WL, Clark CE, Epstein SE.Asymmetric septal hypertrophy (ASH):the unifying link in the IHSS diseasespectrum. Observations regarding itspathogenesis, pathophysiology, andcourse. Circulation 1973;47:827–32.

9. Henry WL, Clark CE, Epstein SE.Asymmetric septal hypertrophy. Echo-cardiographic identification of the pa-thognomonic anatomic abnormality ofIHSS. Circulation 1973;47:225–33.

0. Maron MS, Maron BJ, Harrigan C, etal. Hypertrophic cardiomyopathyphenotype revisited after 50 years withcardiovascular magnetic resonance.J Am Coll Cardiol 2009;54:220–8.

1. Olivotto I, Girolami F, AckermanMJ, et al. Myofilament protein genemutation screening and outcome ofpatients with hypertrophic cardiomy-opathy. Mayo Clin Proc 2008;83:630–8.

2. Rickers C, Wilke NM, Jerosch-HeroldM, et al. Utility of cardiac magneticresonance imaging in the diagnosis ofhypertrophic cardiomyopathy. Circula-tion 2005;112:855–61.

3. Moon JC, Fisher NG, McKenna WJ,Pennell DJ. Detection of apical hyper-trophic cardiomyopathy by cardiovas-
cular magnetic resonance in patients
by oimaging.onlinejacc.orgloaded from

with non-diagnostic echocardiogra-phy. Heart 2004;90:645–9.

4. Maron MS, Finley JJ, Bos JM, et al.Prevalence, clinical significance, andnatural history of left ventricular apicalaneurysms in hypertrophic cardiomy-opathy. Circulation 2008;118:1541–9.

5. Maron MS, Hauser TH, Dubrow E,et al. Right ventricular involvement inhypertrophic cardiomyopathy. Am JCardiol 2007;100:1293–8.

6. Rudolph A, Abdel-Aty H, Bohl S, etal. Noninvasive detection of fibrosisapplying contrast-enhanced cardiacmagnetic resonance in different formsof left ventricular hypertrophy relationto remodeling. J Am Coll Cardiol2009;53:284–91.

7. Azevedo CF, Nigri M, Higuchi ML,et al. Prognostic significance of myo-cardial fibrosis quantification by histo-pathology and magnetic resonanceimaging in patients with severe aorticvalve disease. J Am Coll Cardiol 2010;56:278–87.

8. Grothues F, Smith GC, Moon JC, etal. Comparison of interstudy repro-ducibility of cardiovascular magneticresonance with two-dimensionalechocardiography in normal subjectsand in patients with heart failure orleft ventricular hypertrophy. Am JCardiol 2002;90:29–34.

9. Petersen SE, Selvanayagam JB, Fran-cis JM, et al. Differentiation of ath-lete’s heart from pathological forms ofcardiac hypertrophy by means of geo-metric indices derived from cardiovas-cular magnetic resonance. J Cardio-vasc Magn Reson 2005;7:551–8.

0. Basavarajaiah S, Wilson M, JunagdeS, et al. Physiological left ventricularhypertrophy or hypertrophic cardio-myopathy in an elite adolescent ath-lete: role of detraining in resolving theclinical dilemma. Br J Sports Med2006;40:727–9, discussion 729.

1. Moon JC, Sachdev B, ElkingtonAG, et al. Gadolinium enhancedcardiovascular magnetic resonancein Anderson-Fabry disease. Evi-dence for a disease specific abnor-mality of the myocardial intersti-tium. Eur Heart J 2003;24:2151–5.

2. Puvaneswary M, Joshua F, Ratnara-jah S. Idiopathic hypereosinophilicsyndrome: magnetic resonance im-aging findings in endomyocardial fi-brosis. Australas Radiol 2001;45:524 –7.

3. Smedema JP, Snoep G, van Kroonen-burgh MP, et al. Evaluation of theaccuracy of gadolinium-enhanced car-diovascular magnetic resonance in thediagnosis of cardiac sarcoidosis. J Am
Coll Cardiol 2005;45:1683–90.
n November 21, 2011


4

4

4

4

4

5

5

5

5

5

5

5

5

5

5

6

6

6

6

6

6

6

6

6

6

7

7

7

7

7

7


O C T O B E R 2 0 1 1 : 1 1 2 3 – 3 7

To et al.

CMR in HCM

1136

44. Austin BA, Tang WH, Rodriguez ER,et al. Delayed hyper-enhancement mag-netic resonance imaging provides in-cremental diagnostic and prognosticutility in suspected cardiac amyloid-osis. J Am Coll Cardiol Img 2009;2:1369 –77.

5. Maceira AM, Joshi J, Prasad SK, et al.Cardiovascular magnetic resonance incardiac amyloidosis. Circulation 2005;111:186–93.

6. Maron BJ, Seidman JG, Seidman CE.Proposal for contemporary screeningstrategies in families with hypertro-phic cardiomyopathy. J Am Coll Car-diol 2004;44:2125–32.

7. Germans T, Wilde AA, Dijkmans PA,et al. Structural abnormalities of theinferoseptal left ventricular wall detectedby cardiac magnetic resonance imagingin carriers of hypertrophic cardiomyo-pathy mutations. J Am Coll Cardiol2006;48:2518–23.

8. Moon JC, Mogensen J, Elliott PM,et al. Myocardial late gadoliniumenhancement cardiovascular mag-netic resonance in hypertrophic car-diomyopathy caused by mutations introponin I. Heart 2005;91:1036 – 40.

9. Ho CY, Lopez B, Coelho-FilhoOR, et al. Myocardial fibrosis as anearly manifestation of hypertrophiccardiomyopathy. N Engl J Med2010:552– 63.

0. Ho CY, Sweitzer NK, McDonoughB, et al. Assessment of diastolic func-tion with Doppler tissue imaging topredict genotype in preclinical hyper-trophic cardiomyopathy. Circulation2002;105:2992–7.

1. Nagueh SF, McFalls J, Meyer D, etal. Tissue Doppler imaging predictsthe development of hypertrophiccardiomyopathy in subjects withsubclinical disease. Circulation 2003;108:395–8.

2. Ennis DB, Epstein FH, Kellman P,Fananapazir L, McVeigh ER, AraiAE. Assessment of regional systolicand diastolic dysfunction in familialhypertrophic cardiomyopathy usingMR tagging. Magn Reson Med 2003;50:638–42.

3. Austin BA, Kwon DH, Smedira NG,Thamilarasan M, Lever HM, DesaiMY. Abnormally thickened papillarymuscle resulting in dynamic left ven-tricular outflow tract obstruction: anunusual presentation of hypertrophiccardiomyopathy. J Am Soc Echocar-diogr 2009;22:105.e5–6.

4. Kwon DH, Smedira NG, Thamila-rasan M, Lytle BW, Lever H, DesaiMY. Characteristics and surgical out-comes of symptomatic patients withhypertrophic cardiomyopathy withabnormal papillary muscle morphol-
ogy undergoing papillary muscle reori-
Down

entation. J Thorac Cardiovasc Surg2010;140:317–24.

5. Valeti US, Nishimura RA, HolmesDR, et al. Comparison of surgicalseptal myectomy and alcohol septalablation with cardiac magnetic reso-nance imaging in patients with hy-pertrophic obstructive cardiomyopa-thy. J Am Coll Cardiol 2007;49:350 –7.

6. van Dockum WG, Beek AM, tenCate FJ, et al. Early onset and pro-gression of left ventricular remodelingafter alcohol septal ablation in hyper-trophic obstructive cardiomyopathy.Circulation 2005;111:2503–8.

7. Moon JC, Reed E, Sheppard MN, etal. The histologic basis of late gado-linium enhancement cardiovascularmagnetic resonance in hypertrophiccardiomyopathy. J Am Coll Cardiol2004;43:2260–4.

8. Kwon DH, Smedira NG, RodriguezER, et al. Cardiac magnetic resonancedetection of myocardial scarring inhypertrophic cardiomyopathy: corre-lation with histopathology and preva-lence of ventricular tachycardia. J AmColl Cardiol 2009;54:242–9.

9. Kitamura M, Shimizu M, Ino H, et al.Collagen remodeling and cardiac dys-function in patients with hypertrophiccardiomyopathy: the significance oftype III and VI collagens. Clin Car-diol 2001;24:325–9.

0. Teraoka K, Hirano M, Ookubo H,et al. Delayed contrast enhancementof MRI in hypertrophic cardiomy-opathy. Magn Reson Imaging 2004;22:155– 61.

1. Choudhury L, Mahrholdt H, WagnerA, et al. Myocardial scarring inasymptomatic or mildly symptomaticpatients with hypertrophic cardiomy-opathy. J Am Coll Cardiol 2002;40:2156–64.

2. Olivotto I, Maron BJ, Appelbaum E,et al. Spectrum and clinical signifi-cance of systolic function and myocar-dial fibrosis assessed by cardiovascularmagnetic resonance in hypertrophiccardiomyopathy. Am J Cardiol 2010;106:261–7.

3. Maron MS, Appelbaum E, HarriganCJ, et al. Clinical profile and signifi-cance of delayed enhancement in hyper-trophic cardiomyopathy. Circ HeartFail 2008;1:184–91.

4. Moon JC, McKenna WJ, McCrohonJA, Elliott PM, Smith GC, PennellDJ. Toward clinical risk assessment inhypertrophic cardiomyopathy withgadolinium cardiovascular magneticresonance. J Am Coll Cardiol 2003;41:1561–7.

5. Kellman P, Arai AE, McVeigh ER,Aletras AH. Phase-sensitive inversion
recovery for detecting myocardial in-

farction using gadolinium-delayed hy-perenhancement. Magn Reson Med2002;47:372–83.

6. Aquaro GD, Positano V, Pingitore A,et al. Quantitative analysis of late gad-olinium enhancement in hypertrophiccardiomyopathy. J Cardiovasc MagnReson 2010;12:21.

7. Spiewak M, Biernacka EK, MalekLA, et al. Quantitative assessment ofpulmonary regurgitation in patientswith and without right ventriculartract obstruction. Eur J Radiol 2010August 7 [E-pub ahead of print].

8. Amado LC, Gerber BL, Gupta SN, etal. Accurate and objective infarct siz-ing by contrast-enhanced magneticresonance imaging in a canine myo-cardial infarction model. J Am CollCardiol 2004;44:2383–9.

9. Amano Y, Takayama M, Kumita S.Contrast-enhanced myocardial T1-weighted scout (Look-Locker) imag-ing for the detection of myocardialdamages in hypertrophic cardiomyop-athy. J Magn Reson Imaging 2009;30:778–84.

0. Flett AS, Hayward MP, AshworthMT, et al. Equilibrium contrast car-diovascular magnetic resonance forthe measurement of diffuse myocar-dial fibrosis: preliminary validationin humans. Circulation 2010;122:138 – 44.

1. Olivotto I, Maron MS, Autore C, etal. Assessment and significance of leftventricular mass by cardiovascularmagnetic resonance in hypertrophiccardiomyopathy. J Am Coll Cardiol2008;52:559–66.

2. Boonyasirinant T, Rajiah P, SetserRM, et al. Aortic stiffness is increasedin hypertrophic cardiomyopathy withmyocardial fibrosis: novel insights invascular function from magnetic reso-nance imaging. J Am Coll Cardiol2009;54:255–62.

3. Austin BA, Popovic ZB, Kwon DH,et al. Aortic stiffness independentlypredicts exercise capacity in hyper-trophic cardiomyopathy: a multimo-dality imaging study. Heart 2010;96:1303–10.

4. Kwon DH, Smedira NG, PopovicZB, et al. Steep left ventricle to aorticroot angle and hypertrophic obstruc-tive cardiomyopathy: study of a novelassociation using three-dimensionalmultimodality imaging. Heart 2009;95:1784–91.

5. Petersen SE, Jerosch-Herold M,Hudsmith LE, et al. Evidence formicrovascular dysfunction in hyper-trophic cardiomyopathy: new in-sights from multiparametric mag-netic resonance imaging. Circulation
2007;115:2418 –25.
n November 21, 2011


7

7g


O C T O B E R 2 0 1 1 : 1 1 2 3 – 3 7

To et al.

CMR in HCM

1137

76. Esposito A, De Cobelli F, Perseghin G,et al. Impaired left ventricular energymetabolism in patients with hypertro-phic cardiomyopathy is related to theextension of fibrosis at delayedgadolinium-enhanced magnetic reso-nance imaging. Heart 2009;95:228–33.

77. Abozguia K, Elliott P, McKenna W,et al. Metabolic modulator perhexilinecorrects energy deficiency and im-proves exercise capacity in symptom-atic hypertrophic cardiomyopathy.
Circulation 2010;122:1562–9.
Down

8. Dong SJ, MacGregor JH, CrawleyAP, et al. Left ventricular wall thick-ness and regional systolic function inpatients with hypertrophic cardio-myopathy. A three-dimensionaltagged magnetic resonance imagingstudy. Circulation 1994;90:1200 –9.

9. Popovic ZB, Kwon DH, Mishra M, etal. Association between regional ven-tricular function and myocardial fibrosisin hypertrophic cardiomyopathy as-sessed by speckle tracking echocardiog-
raphy and delayed hyperenhancement

magnetic resonance imaging. J Am SocEchocardiogr 2008;21:1299–305.

Key Words: cardiac magneticresonance y hypertrophiccardiomyopathy y lateadolinium enhancement.

A P P E N D I X

For supplementary videos and their legends,

please see the online version of this article.

To participate in this CME activity by taking the quizand claiming your CME credit certificate, please go to

www.imaging.onlinejacc.organd select the CME tab on the top navigation bar.

n November 21, 2011


doi:10.1016/j.jcmg.2011.06.022 2011;4;1123-1137 J. Am. Coll. Cardiol. Img.

Andrew C.Y. To, Ashwat Dhillon, and Milind Y. Desai Cardiac Magnetic Resonance in Hypertrophic Cardiomyopathy

This information is current as of November 21, 2011

& ServicesUpdated Information

http://imaging.onlinejacc.org/cgi/content/full/4/10/1123including high-resolution figures, can be found at:

Supplementary Material http://imaging.onlinejacc.org/cgi/content/full/4/10/1123/DC1

Supplementary material can be found at:

References

http://imaging.onlinejacc.org/cgi/content/full/4/10/1123#BIBLfree at: This article cites 77 articles, 54 of which you can access for

Rights & Permissions

http://imaging.onlinejacc.org/misc/permissions.dtltables) or in its entirety can be found online at: Information about reproducing this article in parts (figures,

Reprints http://imaging.onlinejacc.org/misc/reprints.dtl

Information about ordering reprints can be found online:

by on November 21, 2011 imaging.onlinejacc.orgDownloaded from

http://imaging.onlinejacc.org/cgi/content/full/4/10/1123

http://imaging.onlinejacc.org/cgi/content/full/4/10/1123/DC1

http://imaging.onlinejacc.org/misc/permissions.dtl

http://imaging.onlinejacc.org/misc/reprints.dtl


Health & Medicine

Cardiac MRI in hypertrophic cardiomyopathy