Cardiac MRI in hypertrophic cardiomyopathy
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Transcript of 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
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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-
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anuscript received November 10, 2010; revised manuscript received
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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.
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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
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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 summarizesn November 21, 2011
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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- UimagingDownloaded 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
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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-
outflow tract; SCD � sudd y sta
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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
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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
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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.imagingDownloaded from
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
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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
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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
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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
imagingDownloaded from
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
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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). Seby oimaging.onlinejacc.orgDownloaded from
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
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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.imagingDownloaded from
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
by on November 21, 2011 .onlinejacc.org
pshm
cmastmiTtsttlm
cbfmtpfip
(fkctgHms
B). S
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O C T O B E R 2 0 1 1 : 1 1 2 3 – 3 7
To et al.
CMR in HCM
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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
by oimaging.onlinejacc.orgDownloaded from
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
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CMR in HCM
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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.
imagingDownloaded from
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
by on November 21, 2011 .onlinejacc.org
TaE
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
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
by oimaging.onlinejacc.orgDownloaded from
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
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Key Words: cardiac magneticresonance y hypertrophiccardiomyopathy y lateadolinium enhancement.
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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
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