Restrictive Cardiomyopathies: Evaluation Using Cardiac MRI and Multidetector CT

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1 Restritive Crdiomyopthies: Evlution Using Crdi MRI nd Multidetetor CT Miordioptís restritivs: Vlorión por resonni mgnéti rdi y tomogrfí multiorte Alejndro Zulug S. 1 Ntli Aldn S. 1 Sestián Bustmnte Z. 2 Crolin Gutiérrez M. 2 Erik Enrique Blno D. 2 Niolás Zulug 3 Key words (MeSH) Perirditis, onstritive Crdiomyopthy, restritive Mgneti resonne imging Multidetetor omputed tomogrphy Summry Crdiomyopthies re onditions tht ffet the myordium nd use ltertion in the rdi funtion. Within the rdiomyopthies, the restritive sugroup hs s min finding the derese in the ventriulr filling. In this mnusript we will review the restritive rdiomyopthies nd disuss their min uses, s well s their imging findings on rdi mgneti resonne nd omputed tomogrphy. We will lso inlude imging signs tht helps to differentite restritive rdiomyopthies from onstritive perirditis. Plrs lve (DeCS) Perirditis onstritiv Crdiomioptí restritiv Imgen por resonni mgnéti Tomogrfí omputrizd multidetetor Resumen Ls miordioptís son ondiiones que fetn l miordio y genern lterión en l funión rdi. Dentro de ls miordioptís, el sugrupo de ls restritivs tiene omo prinipl hllzgo l disminuión en el llendo ventriulr. A ontinuión se expone un revisión er de ls miordioptís restritivs, se nlizn sus priniples uss, y los hllzgos por resonni mgnéti rdi y por tomogrfí omputrizd. Tmién se inluyen signos por imgen que yudn diferenir ls miordioptís restritivs de l perirditis onstritiv. 1 Rdiologist, CEDIMED, Rdiology professor UPB nd CES. Medellin, Colomi. 2 Rdiology residents, Universidd Pontifi Bolivrin. Medellin, Colomi. 3 Mediine student, Universidd CES. Medellin, Colomi. Introdution Restritive rdiomyopthies re hrterized y derese in distoli volume, limittion of ventriulr filling, nd funtion norml systoli or lose to norml. Although in the imge evlution there re hrteristis ommon to ll restritive rdiomyopthies, there re some findings tht differentite them. Therefore, rdi mgneti resonne imging (CMRI), thnks to etter tissue hrteriztion, hs eome the tehnique of hoie in the ssessment of these ptients, to rry out n etiologil pproh nd diret the tretment. The following is review of the topi of restritive rdiomyopthy with emphsis on the min uses nd their hrteristis in CMRI nd omputed tomogrphy (CT) ssessment. Crdiomyopthies re myordil diseses ssoited with rdi dysfuntion tht n e divided into ishemi or non-ishemi, ording to the ommitment oronry rtery (1-3). Restritive rdiomyopthies (RCM) re prt of the non-ishemi group nd re hrterized y restrition in filling nd ventriulr distoli volume with susequent tril dilttion nd venous stsis, norml or ner-norml systoli funtion nd thikness of the preserved wll (4,5). MRI plys fundmentl role in the pproh of ptients with RCM, euse it defines those who suffer from this ondition, whih helps determine the use nd therpeuti pln. It lso llows differentition of onstritive perirditis (CP), whih presents similr linil mnifesttions, ut unlike RCMs tht re usully medilly mnged, CPs generlly require surgil mngement. Rev. Colom. Rdiol. 2017; 28(3):

2 Imge modlities Dignosti tehniques in the evlution of RCM inlude: eletrordiogrm, ehordiogrphy, rdi mgneti resonne imging (MRI), omputed tomogrphy (CT), nd ngiogrphy. RCM ehordiogrphy typilly shows norml or diminished-size ventrile with norml or slightly deresed ventriulr funtion in the erly stges of the disese. The tri re dilted nd ventriulr filling is limited (distoli dysfuntion) in the Doppler evlution. With the progress of the disese, the pulmonry rteril pressure rises. Ehordiogrphy, unfortuntely, is limited in tissue hrteriztion nd therefore its use is limited to determine the etiology of the RCM. In the lst dede, CMRI hs eome noninvsive tehnique tht llows n dequte morphologil evlution of perfusion, ventriulr funtion nd llows tissue hrteriztion. In ddition, it helps to differentite the RCM from the CP. CT is lso useful for differentiting the RCM from the CP, sine it llows the detetion of lifitions in the perirdium, frequent finding in the CP. Angiogrphy llows ssessment of the lumen of the ventriles, their funtion, wll motility, nd is the referene tehnique in the ssessment of rdi hemodynmis. However, it is not very useful to identify the use of the hemodynmi ltertion, exept for some diseses tht hve fetures y ngiogrphy, suh s endomyordil firosis. The mjor dvntge of perutneous ngiogrphy is tht it llows to tke histologil smple. Findings ommon to ll RCM Típimente, pree omo ventríulos de tmño norml, o distypilly, it ppers s norml-sized or diminished ventriles with enlrged tri. The ontours of the ventriulr vities re mintined nd do not pper indented, unlike the CP, in whih the vities pper tuulr or indented due to the extrinsi use of this disese. The degree of inrese in tril size is muh greter in the RCM thn in onstritive perirditis (CP) (6). The myordil thikness is frequently inresed in the RCM ut norml in the CP. In RCM, the perirdil thikness is usully norml, hving norml vlue of 2 mm or less (7), wheres in CP it is inresed nd sometimes with low signl lifitions in ll the pulse sequenes y CMRI. In some types of RCM there my e perirdil fluid, suh s myloidosis, ut, unlike CP, the fluid in the RCM usully hs free distriution (8). The RCM nd CP hve similr linil nd hemodynmi hrteristis, ut it is importnt to differentite them sine the mngement of eh one is different: surgil nd urle for the CP, wheres for the RCM, the tretment is medil or with hert trnsplnt (6, 9, 10). Currently, to distinguish them one n use imging findings from non-invsive studies (CMRI, CT, ehordiogrphy) for perirdil thikness mesurement, septl motility nlysis (inluding nlysis of respi- rphoni hnges of the interventriulr septum), evlution of systoli or distoli myordil funtion, myordil firosis in lte enhnement sequenes, myordil iopsy, mong others. Both entities re hrterized y norml or deresed volume in the two ventriles, ssoited with inresed inurl size, ltered ventriulr filling (restritive physiology), nd norml or ner-norml systoli funtion (Figure 1) (11,12). The following re some ommon uses of RCM nd their imging hrteristis. Amyloidosis It is the extrellulr deposit of insolule proteins with ltertion in the folding. Of the different uses, primry, senile nd hereditry myloidosis led to linilly signifint rdi ompromise (13). In primry myloidosis, 50% of ptients hve rdi mnifesttions nd 25% hve ongestive hert filure (14). Crdi myloidosis n e isolted or ssoited with systemi ompromise, in either form representing poor prognosis. Clinil mnifesttions re non-speifi nd inlude ftigue, wekness, ngin, hert filure symptoms, nd rrhythmis (15-17); n even elevte troponins (18). There re multiple mehnisms y whih the myloid deposit uses myordil dysfuntion. One of them is the inrese in myordil mss nd hrdening of the ventriulr wlls y n inrese in the interstitil spe, whih leds to ltertion in ventriulr filling. Also, it lters the myordil rhiteture nd uses diret toxi effet on the myoyte, whih lters the ontrtility (19). The dignosti stndrd is the endomyordil iopsy. However, in some ses it is not possile euse of its invsive nture nd its possile omplitions (20). CMRI is highly speifi nd non-invsive tehnique, nd therefore represents n lterntive to iopsy. In study of 33 ptients with suspeted rdi myloidosis who underwent endomyordil iopsy nd CMRI. A sensitivity of 94% nd 80% speifiity were found for CMRI to perform the dignosis (21). Using CMRI one n identify the onentri myordil iventriulr thikening ssoited with tril nd tril thikening of the intertril septum. Other findings inlude pleurl nd perirdil effusions. Some uthors hve reported thikening of the interrtiulr septum s hrteristi finding of myloidosis (22). In lte-enhnement imges, this is usully glol nd predominntly suendordil, ut my lso e trnsmurl (23-25). Lte enhnement is elieved to e used y interstitil expnsion y deposition of the myloid protein (26); however, the mount of myloid hs no diret reltionship to the intensity of the lte enhnement (27). The pttern of lte enhnement in myloidosis is diffuse nd wek. This is elieved to e due to systemi myloid inding to gdolinium y reduing its effetive volume of distriution. This genertes low ontrst etween the suppressed myordium nd the pool of lood, euse of diffiulty in suppressing the myordium without suppressing the pool of lood (26). Amyloidosis uses n ltertion in the gdolinium hemodynmis with n inrese in the extrellulr deposit through the ody, resulting in n erlier lvge of the lood pool (21, 26). Lte myordil enhnement my e diffuse or suendordil (Figure 2). The degree of myordil enhnement hs een diretly orrelted with ltertion in segmentl nd glol ontrtility, distoli dysfuntion nd inrese in tril size (28, 29) Restritive Crdiomyopthies: Evlution Using Crdi MRI nd Multidetetor CT. Zulug A., Aldn N., Bustmnte S., Gutiérrez C., Blno E., Zulug N.

3 * Figure 1. Constritive perirditis. ) CMRI HASTE sequene with 4 mers. ) Sequene SSFP 4 mers. ) Crdi tomogrphy with imge in 4 hmers. Mrked thikening of the perirdium (greter thn 3 mm), minly surrounding the ventriles, with lifition (rrow in ), indenttion of lterl lterl right ventrile (rrows in nd ) nd inurl growth (*). Figure 2. Amyloidosis. ) CMRI with short-xis lte enhnement sequenes. ) In 2 hmers. ) SSFP in 4 hmers. Suendordil enhnement (rrows in nd ) nd thikening of the iventriulr myordium (rrow in ) with inurl dilttion. In SSFP, perirdil effusion nd left pleurl effusion (* en ) re identified. * d Figure 3. Sroidosis. nd ) CMRI with shortxis lte enhnement imges. ) Longitudinl 2 hmers. nd d) in 4 hmers. Suepirdil enhnement of sl predominne (white rrows in nd ) with involvement of the right ventrile roof (rrowhed in ). In the imge of 4 hmers there is lso enhnement of the intertril septum nd the wlls of the tri (thik rrow in d). Rev. Colom. Rdiol. 2017; 28(3):

4 Sroidosis Grnulomtous, non-seizing, multisystemi disese. Pulmonry involvement is the most frequent in 90% of ptients (30). Crdi involvement is frequently found in utopsies (20-27%) (30,31), lthough linilly it is only deteted in 5% of ptients (32). Crdi sroidosis n our efore, fter or simultneously with the involvement of other orgns (33). Crdi involvement indites poor prognosis nd my e ssoited with rdi filure, ondution normlities: trioventriulr lok (26-62%) nd sudden deth (12-65%) (34). This is the most ommon use of deth in sroidosis (35). The definitive test for dignosis is the histopthologil test y endomyordil iopsy. However, euse of fol involvement, iopsy is reltively unresponsive with only 10% of positive iopsies in ptients with sroidosis nd rrhythmis (36). There re 3 suessive histologil stges: edem, nonseiform grnulomtous infiltrtion nd pthed myordil firosis (30). In the ute inflmmtory phse, there re fol res of high T2 signling nd myordil thikening due to edem. Grnuloms re seen s low-signl foi in T1 nd T2 within the res of signl inrese in T2. In the erly perfusion imges, norml or inresed enhnement is seen. These res my show enhnement in lte enhnement imges nd regionl normlities in motility in film sequenes. In ptients undergoing tretment with steroids, these hrteristis n e ltered nd pper only s high T2 sign, without myordil thikening or enhnement. The pthophysiology of enhnement in the ute phse is y fol myorditis nd in the lte phse y firosis (37). The enhnement tends to e pthed into non-oronry distriution, nd ompromises the se more thn the pex (38); more frequently the enhnement is suepirdil, non-trnsmurl (Figure 3) (37). Lte enhnement imges help guide the endomyordil iopsy nd define the prognosis. The degree of enhnement orreltes with poor volume t the end of distole in the left ventrile, volume t the end of systole in the left ventrile, inrese in tril ntriureti peptide B, nd negtive orreltion with ejetion frtion (37,39). Due to its gret vriety of morphologil mnifesttions, sroidosis n simulte other entities: for exmple, when suendordil enhnement my mimi ishemi lesions (40) nd in dvned stges, when srring res present thinning of the wll nd impired motility, simulte other nonishemi rdiomyopthies (35,41). Per tomogrphy the findings re not speifi nd inlude rdiomegly, perirdil effusion nd ventriulr neurysms. In the thorx there re usully findings relted to the disese, suh s ilterl medistinl nd hilr lymphdenopthy, involvement of the pulmonry prenhym with nodulr thikening of the interstitium, or predominnt firosis in the upper loes (42-45). Löffler s Endorditis (LE) nd endomyordil firosis The geogrphil distriution nd linil hrteristis of these two entities re different; however, the pthologil outome is similr. LE is ssoited with hypereosinophili tht my e ssoited with neoplsis, infetions, llergies or idiopthi wy (46). Endomyordil firosis is found in tropil ountries nd is typilly not ssoited with hypereosinophili. Oslen desried 3 stges of LE: neroti, neroti thromoti nd firoti (47). In the neroti phse there is eosinophili infiltrtion of the myordium, predominntly suendordil in the pex nd in the entry regions of oth ventriles; generlly respets the output trts. Inflmmtion leds to myordil nerosis nd formtion of mirosesses. As the proess progresses, suendordil denudtion leds to the formtion of thromi in the ventriulr vity. As the disese eomes hroni, suendordil firosis nd thromus formtion pper (48). Firosis leds to deresed ompline nd restritive physiology. The involvement of the ppillry musles in the entry regions n use vlvulr insuffiieny (49). It n ompromise one or oth ventriles, nd when it omes to one is usully the right side. CMRI is very useful for dignosing endomyordil firosis nd defining the stge of disese. It is importnt to reognize the disese in erly stges, sine the timely dministrtion of steroids helps prevent progression to firoti stges (50). Endomyordil infiltrtion is seen s high intensity signl in T2 or STIR in the endordil nd suendordil portion of the ventriulr pies nd inlet regions. In the erly stges this my e the only finding ssoited with normlity of motility. As the disese progresses thromus formtion my pper, whih re seen s low signl nd in grdient eho sequene. In the lte enhnement sequenes, the thromus gives rise to the sign of the sndwih, euse it is low signl etween the enhning endordium nd the lood pool (Figure 4). The ompromised segments hve hypokinesi or quinisi in the inem sequenes. Endomyordil firosis hs poor prognosis, nd medil tretment is usully ineffetive (51). Some ptients enefit from surgil tretment with endordil resetion nd trioventriulr vlve replement. A series of surgery reported survivl of 68% 10 yers fter surgery (49). Iron overlod rdiomyopthy Iron deposition my e due to hemohromtosis, either primry or seondry. Common iron deposit sites inlude the liver, spleen nd endorine orgns. Crdi involvement is unommon nd is usully found in more dvned stges. Exessive iron deposition leds to distoli nd systoli dysfuntion, initilly the first. Hert filure is the leding use of deth in these ptients (52,53). CMRI plys n importnt role in the detetion nd quntifition of rdi ompromise. The iron deposit uses shortening in the relxtion time in T2 str sequenes (T2 str), whih n e deteted in grdient eho sequenes. Mesurements re performed on the short xis in the middle ventrile nd in the interventriulr septum, nd it is lulted with signl dey urve (54) Restritive Crdiomyopthies: Evlution Using Crdi MRI nd Multidetetor CT. Zulug A., Aldn N., Bustmnte S., Gutiérrez C., Blno E., Zulug N.

5 Figure 4. Eosinophili rdiomyopthy (Löffler s endorditis). nd ) CMRI with lte enhnement imges in 4 nd 2 hmers. ) Imge in SSFP in 2 mers. In the lte enhnement imges we see n pil suendordil enhnement with underlying thromus (white rrow in nd ), the SSFP imge shows derese in size in the left ventrile vity y inflmmtory proess nd pil thromus (rrowhed in ). Figure 5. Asymmetri hypertrophi rdiomyopthy, sl nteroseptl vriety. ) RMC with short-xis SSFP sequenes. ) Lte enhnement in short xis. ) Left ventriulr outflow trt. In the imges y CMR there is n symmetri nteroseptl myordil thikening (white rrows in ) with lte enhnement inditing firosis (rrow heds in nd ). In rdiomyopthy due to iron overlod the T2-weighted vlue typilly is less thn 20 milliseonds, nd overloding is onsidered severe when the vlue is less thn 10 milliseonds, so shorter dey time represents less rdi funtion (55). The ility of CMRI to detet iron deposition in the erly-stge myordium helps to diret iron heltion therpy nd to monitor nd follow up tretment, whih hs een shown to redue moridity nd mortlity in these ptients (56). Hypertrophi rdiomyopthy Es l enfermedd rdiovsulr hereditri más omún, on unit is the most ommon hereditry rdiovsulr disese, with prevlene of 1:500, nd is the leding use of sudden deth in young people nd thletes (57). It is n utosoml dominnt disese used y the muttion of genes tht ode the proteins of the sromere; however, it s penetrne is inomplete nd ge dependent (58,59). Rev. Colom. Rdiol. 2017; 28(3): Symptoms inlude dyspnoe nd hest pin with exerise, whih re relted to distoli dysfuntion, ostrutive physiology nd ishemi seondry to imlne etween supply nd demnd or mirovsulr disese (60,61). There re multiple morphologil vrints tht n e identified y CMRI ording to the degree of wll hypertrophy (57), whih, when not homogeneous, is desried s symmetril (Figure 5). The dignosis is sed on the morphologil hrteristis when finding wll thikness of the left ventrile t the end of the distole greter or equl to 15 mm or rtio of the thikness of the septl wll with the lterl wll greter thn 1.3 in ventrile left non-dilted nd in the sene of onditions using this normlity (Figure 5) (57). The disproportionte thikening in the suorti septum leds to stenosis in the left ventriulr outflow trt during systole, whih inreses the veloity of lood ejeted in redued spe nd genertes Venturi effet tht pulls the nterior lef of the mitrl vlve; nterior movement of the mitrl vlve during systole further 4729

6 redues the left ventriulr outflow trt y predisposing to sudden deth (2,58). Lte enhnement is not onsidered dignosti riterion; however, it provides prognosti informtion. Survivl is inversely proportionl to the plnimetri quntifition of lte enhnement nd helps to define the need for implnttion of rdiodesfirilltor (2). Other onditions Some diseses my led to deposition of sustnes in the intrellulr spe, whih inreses myordil mss with inresed wll thikness nd restritive physiology. These onditions inlude glyogenosis types I nd II, Anderson-Fry disese, Guher, Neimnn-Pik nd gltosidosis. Other rre onditions tht use restritive rdiomyopthy inlude rdition injury nd neoplsms (inluding rdi rinoid) (62-64). Conlusions In ptients with ongestive hert filure nd restritive physiology of unknown etiology, CMRI is the dignosti modlity invsive of hoie. CMRI helps to define the use of the disese, quntify myordil ompromise, nd mesure ventriulr funtion. It is lso useful in monitoring these ptients, to define response to tretment nd prognosis; nd, ording to the ove, to estlish the need for some speifi tretment, suh s the implnttion of rdio defirilltor. CMRI nd CT re very useful in the differentition etween RCM nd CP, whih is importnt euse of the implitions nd prognosis of these ptients, sine, lthough the linil piture is similr, the tretment is different: surgil for CP nd dotor for the RCM. Referenes 1. Gupt A, Singh Gulti G, Seth S, Shrm S. Crdi MRI in restritive rdiomyopthy. Clin Rdiol. 2012;67(2): Jh S, Golderg A, et l. MR imging of nonishemi rdiomyopthy. PET linis. 2011;6: Belloni E, De Coelli F, Esposito A, Mellone R, Perseghin G, Cnu T, Del Mshio A. MRI of rdiomyopthy. AJR Am J Roentgenol. 2008;191(6): Rihrdson PJ, MKenn W, Bristow M, et l. Re- port of the 1995 World Helth Orgniztion. 5. Interntionl Soiety nd Federtion of Crdiology Tsk Fore on the Definition nd Clssifition of Crdiomyopthies. Cirultion. 1996;93: Hnok EW. 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