cardiovascular disease

Transcription

1 SA Journl of Rdiology ISSN: (Online) , (Print) X Pge 1 of 10 Review of crdiovsculr mgnetic resonnce in humn immunodeficiency virus-ssocited crdiovsculr disese Authors: Vishesh Sood 1,2 Stephen Jermy 3,4 Hdil Sd 3,4 Petronell Smuels 3,4 Sulimn Moos 1 Ntoeko Ntusi 3,4,5 Affilitions: 1 Division of Rdiology, Deprtment of Rdition Medicine, University of Cpe Town 2 Groote Schuur Hospitl, Cpe Town, South Afric 3 Cpe Universities Body Imging Centre, University of Cpe Town, South Afric 4 Deprtment of Medicine, University of Cpe Town, South Afric 5 Htter Institute of Crdiovsculr Reserch in Afric, Deprtment of Medicine, University of Cpe Town, South Afric Corresponding uthor: Ntoeko Ntusi, Ntoeko.Ntusi@uct.c.z Dtes: Received: 28 June 2017 Accepted: 28 Aug Pulished: 14 Nov How to cite this rticle: Sood V, Jermy S, Sd H, Smuels P, Moos S, Ntusi N. Review of crdiovsculr mgnetic resonnce in humn immunodeficiency virus-ssocited crdiovsculr disese. S Afr J Rd. 2017;21(2), v21i Despite ongoing dvnces in the tretment of ptients with humn immunodeficiency virus (HIV) or cquired immunodeficiency syndrome (AIDS), they remin mjor glol pulic helth concern conferring n incresed risk of moridity nd mortlity in ffected individuls. This is, in prt, ecuse of the widespred dysfunction imposed y HIV nd its tretment on the crdiovsculr system, including the myocrdium, vlvulr pprtus, pericrdium nd coronry, pulmonry nd peripherl vsculture. In recent times, crdiovsculr mgnetic resonnce (CMR) imging hs emerged s the gold stndrd tool for ssessment of vriety of indictions, llowing comprehensive chrcteristion of functionl, morphologicl, metolic nd hemodynmic sequele of severl crdiovsculr pthologies. Furthermore, continued dvncement in imging techniques hs yielded novel insights into the underlying pthophysiology nd guides future therpeutic strtegies. In this rticle, we review the vrious clinicl phenotypes of HIV-ssocited crdiovsculr disese nd highlight the utility of CMR in their ssessment. Introduction As of lte 2015, there were pproximtely 36.7 million people worldwide living with humn immunodeficiency virus (HIV) or cquired immunodeficiency syndrome (AIDS), with n estimted 2.1 million people ecoming newly infected in tht sme yer. 1 Despite the decresing incidence of de novo infections seen over the pst decde, HIV infection remins mjor glol pulic helth concern, with most infected individuls living in low- to middle-income countries, prticulrly in su-shrn Afric. 1 As consequence of the introduction of comintion ntiretrovirl therpy (ART), the survivl of people living with HIV infection hs improved sustntilly. 2 South Afric hs the lrgest numer of people living with HIV infection nd lso the lrgest ART roll-out progrmme glolly. 3 However, despite our improved understnding of the disese nd erly initition of ART, HIV infection is ssocited with significnt complictions, including crdiovsculr disese (CVD). HIV-ssocited CVD results from complex interply of fctors, including, ut not limited to, chronic inflmmtory processes resulting from HIV infection itself, opportunistic infections, concurrent metolic chnges resulting from the use of ART nd conventionl risk fctors for therosclerotic CVD. 4 Consequently, HIV-ssocited CVD involves ll segments of the crdiovsculr tree, commonly ffecting the left ventriculr (LV) myocrdium, vlvulr pprtus, pericrdium nd coronry, pulmonry nd peripherl vsculture. 4 Vrious modlities of crdiovsculr imging re integrl to the ssessment of CVD, nd mny re ingrined into the modern prctice of crdiovsculr medicine. Crdiovsculr mgnetic resonnce (CMR) hs emerged s the gold stndrd technique for mny indictions, llowing comprehensive chrcteristion of functionl, morphologicl, metolic nd hemodynmic sequele of vrious crdiovsculr mnifesttions. In this rticle, we review phenotypes of HIVssocited CVD long clinicl continuum nd highlight the utility of CMR in their ssessment. Red online: Scn this QR code with your smrt phone or moile device to red online. Crdiovsculr mgnetic resonnce techniques Severl unique properties of CMR contriute to its widespred utility in the ssessment of the crdiovsculr system. The reltively high sptil nd temporl resolution coupled with excellent tissue contrst enles comprehensive ssessment of multiple prmeters pertining to Copyright: The Authors. Licensee: AOSIS. This work is licensed under the Cretive Commons Attriution License.

2 Pge 2 of 10 crdiovsculr morphology nd function, without exposure to ionising rdition. 5 Furthermore, the ility to otin imges in ny tomogrphic plne regrdless of ody hitus confers significnt dvntge in ptients with limited sonogrphic coustic windows. 5 Chrcteristion of myocrdil tissue is unique feture of CMR, trditionlly chieved through lte gdoliniumenhnced imging nd sed on the reltive difference in volume of distriution of intrvenously dministered contrst [nd susequent ltertion of longitudinl relxtion (T1) times] etween norml nd norml myocrdium. 5 More recently, ntive (precontrst) T1 nd T2 mpping techniques hve llowed direct mesurement of myocrdil relxtion times on pixel-wise sis, prmeters which hve een extensively vlidted offering similr dignostic performnce nd superior sensitivity for inflmmtion, infiltrtion, cute injury nd firosis s compred with delyed enhncement imging in detecting myocrdil pthology. 5,6,7 T1 mps re most commonly cquired using modified look-locker inversion recovery (MOLLI)-sed or sturtion recovery single-shot cquisition (SASHA)-sed sequences in the shortxis plne t the sl, mid nd picl LV levels. The underlying principle involves the ppliction of n inversion or sturtion pulse followed y successive smpling of the relxtion curve s myocrdil longitudinl mgnetistion returns to its originl level. The entire relxtion curve is then extrpolted from the cquired dt nd the ntive T1 vlues extrcted. For ese of interprettion, these vlues re displyed s colour mp superimposed on ntomic imges, llowing glol nd segmentl quntifiction of T1 vlues using trgeted regionsof-interest (ROIs). The further cquisition of T1 mps following contrst dministrtion llows for the estimtion of myocrdil extrcellulr volume (ECV), mrker of myocrdil tissue remodelling which hs een shown to e roust mesure of the degree of myocrdil firosis. 7 In ddition to the ssessment of iventriculr function using ejection frction (EF), severl CMR techniques hve een developed to quntify myocrdil deformtion (i.e. strin) throughout the crdic cycle. In essence, this is chieved using multiple mgnetic lels (in the form of lck lines or tgs) which re superimposed on nd emedded into the myocrdium t the strt of cine sequence (see Figure 1). The susequent deformtion of these tgs is ssessed throughout the crdic cycle nd llows for inferences to e mde out myocrdil strin in vrious (circumferentil, rdil nd longitudinl) plnes. Left ventriculr dysfunction Left ventriculr systolic nd distolic dysfunction re well documented in HIV-infected persons, with most dt emerging from echocrdiogrphy-sed studies. 8,9 Conventionl indices ville for the ssessment of LV function include the EF, volumes, wll motion, thickness nd mss. 5 The mesurement of systolic nd distolic strin nd strin rte prmeters provides more sensitive informtion out glol nd regionl crdic function nd crdic deformtion properties, nd chnges in strin prmeters often predte the development of overt LV systolic dysfunction. 10 Severl studies using CMR hve consistently demonstrted the presence of regionl LV systolic nd distolic dysfunction in symptomtic individuls. 10,11,12 In the setting of preserved EF, impirment ws detected on CMR s reduced circumferentil, 10 longitudinl 11 nd rdil 12 strin nd strin rte mesurements. A cross-sectionl study of 698 HIV-infected persons showed tht 48% hd distolic dysfunction, which ws ssocited with the co-existence of conventionl crdiovsculr risk fctors (including ge, elevted ody mss index, elevted FIGURE 1: Short-xis imges through the mid-left ventricle with ppliction of myocrdil tgging t end-distole (). Tg lines follow myocrdil deformtion () during the crdic cycle nd llow quntifiction of myocrdil strin prmeters in the circumferentil, longitudinl nd rdil directions.

3 Pge 3 of 10 totl cholesterol nd presence of hypertension nd dietes mellitus). 13 Another study of 129 HIV-infected ptients showed 47% higher medin myocrdil lipid content nd 76% prevlence of myocrdil firosis, using MR spectroscopic nd prmetric mpping techniques, respectively, rising suspicion tht these morphologic normlities my underlie crdic dysfunction in this suset of ptients. 11 Myocrditis Inflmmtory chnges within the myocrdium hve een extensively studied in the context of HIV infection nd contriute significntly to the eventul decline in crdiovsculr function nd the development of crdiomyopthy in ffected individuls. 4,14 Direct invsion of crdiomyocytes y HIV hs een descried, though this occurs in hphzrd fshion with no cler ssocition etween virl lod nd extent of myocrdil involvement. 15 Worsening immunosuppression predisposes to crdiotropic virl infection (herpes simplex virus, cytomeglovirus, prvovirus nd Coxsckie B3 most commonly implicted) nd infection y opportunistic pthogens including Mycocterium tuerculosis, Toxoplsm gondii, Cryptococcus neoformns nd Histoplsm cpsultum. 4 It is worth noting, however, tht no specific pthogen is identified in up to 80% of ffected ptients, nd clinicl presenttion is heterogeneous with lrge proportion of ptients remining symptomtic despite ongoing suclinicl myocrdil oedem nd inflmmtion. 16 Crdiovsculr mgnetic resonnce is powerful tool for dignosing myocrditis ecuse of its ility to ccurtely delinete res of myocrdil oedem, necrosis, infiltrtion nd firosis. Stndrd cine lnced stedy-stte free precession (SSFP) sequences my show regionl wll motion normlities, res of incresed wll thickness ssocited with cute inflmmtion nd the presence of coexistent pthologies, which includes chrcteristion of the extent, loction nd hemodynmic significnce of ny pericrdil effusions. Myocrdil oedem ppers s high signl on T2-weighted short tu inversion recovery sequences (STIR) (see Figure 2), nd more recently, prolongtion of ntive T1 nd T2 vlues s detected through mpping techniques hs een shown to e sensitive imging iomrker of ctive myocrdil inflmmtion. 6 The cquisition of post-contrst imges yields further insight s regionl vsodiltion nd cute myocrdil necrosis result in ltered gdolinium kinetics, with n incresed uptke nd rpid distriution of gdolinium cheltes into the expnded interstitil spce. The cquisition of T1-weighted imges cquired pproximtely 2 5 min following contrst dministrtion llows for the quntittive ssessment of the myocrdil erly gdolinium enhncement rtio (EGEr), rtio etween myocrdil nd musculoskeletl enhncement, which highlights the vrition in gdolinium distriution resulting from tissue dmge (typiclly EGEr > 4.0 considered norml). Lte gdolinium-enhnced MR imges use inversion recovery sequences to null norml myocrdium, highlighting res of retined contrst s high signl res representtive of focl myocrdil firosis. Findings clssiclly include liner, ptchy FIGURE 2: T2-weighted STIR imge t the level of the mid-left ventricle shows n elevted myocrdil skeletl muscle signl intensity rtio (SIR) of 2.5 (norml < 1.9) in keeping with diffuse myocrdil oedem. or nodulr res of enhncement in non-coronry distriution (most commonly the sl inferolterl wlls) with mid-wll or su-epicrdil pttern 17 (see Figure 3). Lstly, while more commonly mrker of diffuse myocrdil firosis, the ECV frction (clculted from ntive nd post-contrst T1 mps) my lso e elevted in myocrditis. 18 Luetkens et l. studied 28 HIV-infected ptients, on HAART with HIV RNA < 200 copies/ml, using CMR nd found elevted prmeters indicting myocrdil inflmmtion (ntive T1 time, reltive T2 signl intensity rtios nd EGEr) s compred with helthy controls. 19 Ntusi et l. looking t 103 HIV-infected individuls, without known CVD, found evidence of suclinicl myocrdil oedem nd n incresed incidence of pericrdil effusions, providing dditionl evidence for chronic myocrdil inflmmtion. 20 Crdiomyopthy Acquired crdiomyopthy in the context of HIV infection represents the finl common pthwy of complex nd multifctoril process resulting in systolic nd distolic dysfunction nd, most often, progression to dilted crdiomyopthy (see Figure 4). In The Hert of Soweto Study the prevlence of HIV-ssocited crdiomyopthy ws reported s 38%, comprising oth ptients with clinicl fetures of hert filure nd those noted to hve suclinicl LV dysfunction on echocrdiogrphy. 21 Although echocrdiogrphy remins the first-line imging modlity for the dignosis of HIV-ssocited crdiomyopthy, CMR llows comprehensive, esily reproducile ssessment of crdic morphology nd function, with dded tissue chrcteristion techniques llowing the detection nd quntifiction of underlying myocrdil firosis through lte gdolinium enhncement (LGE) nd prmetric mpping techniques (see Figure 5). This proves useful in oth

4 Pge 4 of 10 c FIGURE 3: Short-xis (), 2-chmer () nd 4-chmer (c) lte gdolinium phse-sensitive inversion recovery imges show liner mid-wll enhncement in the lterl wll of the LV (white rrows). FIGURE 4: Four-chmer () nd 2-chmer () SSFP imges showing mrkedly dilted left ventricle in ptient with known HIV-ssocited crdiomyopthy. FIGURE 5: T1 mp t the level of the mid-lv () shows mrkedly elevted myocrdil T1 time of 1414 m/s (norml 1052 m/s ± 23 m/s t 3 T) () in keeping with diffuse myocrdil firosis.

5 Pge 5 of 10 prognostiction nd longitudinl follow-up in this suset of ptients s higher levels of myocrdil firosis hve een correlted with n increse in ll-cuse mortlity. Pericrdil disese The spectrum of pericrdil disese ssocited with HIV is rod with isolted pericrdil effusions reported s the commonest mnifesttion. Although non-specific, their presence supports ctive inflmmtion nd my dd weight to the dignosis of suclinicl myocrditis or point to primry pericrdil disese, with Mycocterium tuerculosis eing the most likely pthogen implicted. Historic studies demonstrted tht tuerculous pericrditis ccounted for over 80% of cuses of pericrdil effusion in HIV-infected individuls occurring in su-shrn Afric. 22,23 The underlying pthophysiology implictes retrogrde lymphtic spred from perironchil nd medistinl lymph nodes or hemtogenous dissemintion from primry tuerculous infection. The mnifesttions of tuerculous involvement of the pericrdium my include pericrditis, pericrdil effusions with or without ssocited effusive-constrictive syndromes nd progression to clcified pericrdil constriction. 24,25,26 Crdiovsculr mgnetic resonnce is useful in oth chrcteristion of morphology nd ssessment of hemodynmic sequele ssocited with tuerculous pericrdil disese. Cine SSFP imges demonstrte the size nd loction of effusions, nd lthough not specificlly T2 weighted, they frequently llow visulistion of orgnised firin strnds within the pericrdil sc (see Figure 6). Furthermore, s progressive inflmmtion results in decresing pericrdil complince nd the development of constriction, right ventriculr filling pressures rise with susequent flttening of the interventriculr septum producing chrcteristic D shped LV or even trnsient septl inversion to the left side (distolic septl ounce) in erly distole 5,27 (see Figure 7). Pre- nd post-contrst T1-weighted ntomic imges llow ccurte mesurement of pericrdil thickness nd my show high signl res of enhncement in keeping with ctive inflmmtion or firosis (see Figure 8). The detection of morphologicl normlities of the pericrdium coupled with evidence of constrictive physiology is helpful in identifying ptients who would enefit from surgicl pericrdiectomy nd in guiding susequent stripping procedures. Coronry rtery disese The ssocition etween HIV nd ccelerted coronry rtery disese (CAD) is well descried nd hs een the focus of extensive study in recent yers. 28 Despite overll decline in ll-cuse mortlity relted to the introduction of ART, ptients with HIV hve n incresed risk of cute myocrdil infrction s compred with the generl popultion. 29 The reson for this is oth complex nd multifctoril, with HIV-medited endothelin dysfunction nd ART-relted dyslipidemi (prticulrly ssocited with protese inhiitor use) plying role. 29 Endothelil cells re thought to lter procogulnt, nticogulnt nd firinolytic pthwys in vivo, while underlying HIV-ssocited pltelet dysfunction nd ckground vsculitis likely contriutes to the development of CAD. 30,31 Furthermore, the chronic inflmmtory stte imposed y HIV infection is ssocited with n incresed risk of spontneous coronry rtery dissection (see Figure 9). In ddition to trditionl Frminghm risk fctors, durtion of HIV infection nd lower CD4 CD8 rtios correlte with incresed coronry rteril plque urden. 32 Despite the known reltionship etween HIV infection nd ccelerted therosclerosis, the nticipted pndemic of CVD relted to CAD hs not mterilised in su-shrn Afric. The Hert of Soweto Study showed tht, of the FIGURE 6: CMR SSFP imges ( nd ) show mrked pericrdil thickening (white rrows) nd lrge pericrdil effusion contining orgnised firin strnds (white sterisk). A lrge left-sided pleurl effusion is lso evident (lck sterisk).

6 Pge 6 of 10 FIGURE 7: Short-xis SSFP sequences t end-distole (left) nd end-systole (right) show systolic flttening of the interventriculr septum (white rrow) indictive of right ventriculr pressure overlod. de novo mnifesttions of hert disese within the HIVpositive suset of the cohort (518 of 5328 cses), CAD ws the primry dignosis in only 14 ptients (2.7%). 21 In cohort of HIV-infected ptients, Zhng et l. concluded tht incresing ge ws ssocited with non- AIDS defining illnesses, including CVD. 33 The widespred ccessiility to ART my, in prt, e responsile for the chnging spectrum of diseses relted to HIV, with n overll shift from AIDS-relted illnesses to long-term gerelted complictions. 28 Coronry ngiogrphy hs een the gold stndrd for the ssessment of the coronry rteries for severl decdes, offering high sptil nd temporl resolution of coronry flow. A significnt limittion hs een its inility to provide informtion out the ffected vessel wlls themselves, preventing further study of plque chrcteristics nd vsculr remodelling ssocited with ongoing or suclinicl disese. Computed tomogrphy is more recently recognised s roust tool for the ssessment of coronry ntomy nd quntifiction of overll clcified nd non-clcified plque urden, ut hs limittions in its ility to offer further insights into the underlying properties of tissues eing imged. Ongoing dvncements in high field strength coronry MR hve shown gret promise in ccurtely guging the degree of coronry stenosis, llowing coronry vessel wll imging, mesurement of coronry lood flow velocities nd further chrcteristion of non-clcified plques using delyed enhncement imging techniques. 32 In study of 35 HIV-positive ptients, significnt increse in right coronry rtery vessel wll thickness ws found s compred with helthy controls. 34 Another puliction showed tht the extent of locl coronry epicrdil dipose tissue ws significntly relted to coronry endothelil dysfunction s mesured on coronry CMR. 35 With the ongoing dvnces in the tretment for HIV nd stedily incresing life expectncy in infected individuls, ccelerted CAD is likely to ply more significnt role in HIV-relted CVD over time, nd novel CMR techniques offer insights tht my roden our understnding of this condition nd inform future tretment strtegies. Peripherl vsculr disese Humn immunodeficiency virus-ssocited vsculopthy encompsses wide spectrum of conditions including cererovsculr disese, peripherl rteril thromosis, rteril neurysms nd deep venous thromosis. Its epidemiology remins incompletely chrcterised, with severl descried histologicl sutypes nd multifctoril etiology. 36 CMR techniques used to study this entity include mesurement of reduced ortic distensiility, s demonstrted y cine cquisitions through vrious ortic plnes nd incresed pulse wve velocity s clculted from phse contrst velocity encoded sequences. Both mesures hve een shown to e sensitive mrkers of reduced ortic elstic function, predictive of oth future dverse crdiovsculr events nd mortlity in severl popultion-sed studies. A study y Rider et l. found tht treted HIV infection in ptients without concurrent metolic syndrome ws ssocited with n 11% increse in pulse wve velocity nd 14% regionl reduction in ortic distensiility s compred with helthy controls. 37 This effect ws similr in HIV-negtive ptients with metolic syndrome nd dditive in the suset of ptients with oth illnesses occurring concurrently. 37

7 Pge 7 of 10 c d FIGURE 8: Short-xis SSFP () nd T1-weighted () imges demonstrte the presence of lrge pericrdil effusion (white rrow) nd mrked thickening of the viscerl nd prietl pericrdium. Four-chmer (c) nd short-xis (d) lte gdolinium imges show intense enhncement of the thickened viscerl nd prietl pericrdium (white rrows) nd the lrge hypointense pericrdil effusion (white sterisk). The effects of chronic inflmmtion nd ART-ssocited lipodystrophy exert similr effects on the entire vsculr system, with incresed crotid rtery intim-medi thickness (C-IMT) on B-mode ultrsound shown to e predictive of future stroke nd myocrdil infrction. C-IMT, s mesured y crotid CMR, hs een shown to correlte well with sonogrphic mesurements, with the dded dvntge of preserved resolution long the entire length of the exmined rteries nd ility to derive novel whole vessel prmeters including plque volume quntifiction, which my e useful s surrogte mrkers for longitudinl follow-up of crdiovsculr risk in this suset of ptients.38 Humn immunodeficiency virusssocited pulmonry rteril hypertension The estimted prevlence of pulmonry rteril hypertension (PAH) in the HIV popultion is 0.5%, up to 2500-fold greter thn tht of the generl popultion.39 The precise mechnism is uncertin, with oth host nd virl fctors thought to contriute to the underlying pthogenesis. Furthermore, n incresed propensity for thromoemolic disese or recurrent pulmonry infections with resulting pulmonry firosis likely contriutes to the development of PAH nd the high mortlity ssocited with this condition.

8 Pge 8 of 10 c FIGURE 9: Four-chmer (), short-xis () nd 2-chmer (c) lte gdolinium-enhnced imges show high signl trnsmurl infrction of the LV pex (rrow heds) in n HIV-positive ptient with spontneous coronry rtery dissection. The presence of low signl intensity picl thromus is lso noted (white rrow). c d FIGURE 10: Four-chmer () nd 3-chmer () SSFP sequences in ptient with known lymphom show n isointense left tril mss (rrows) rising from the intertril septum. Corresponding lte gdolinium-enhnced imges (c nd d) show heterogeneous enhncement of the mss. The imging findings of HIV-ssocited PAH re indistinguishle from those of primry PAH, with morphologic normlities oserved including, dilttion of the pulmonry trunk, min pulmonry rteries nd eventully the right ventricle (RV) nd right trium. Cine imging is used for the quntifiction of RV indices (end systolic nd

9 Pge 9 of 10 distolic volumes, EF nd myocrdil mss) nd ssessment of tricuspid regurgittion, following nnulr distortion relted to RV dilttion. 40 LGE hs een noted t the superior nd inferior LV or RV hinge-points in ptients with PAH. 40 The degree of enhncement hs een shown to relte to RV volume nd mss, rising suspicion tht incresed mechnicl strin excertes structurl deformtion t the insertion points of the interventriculr septum, resulting in rchitecturl distortion nd firosis of the myocrdium in this region. 41 Myocrdil stetosis 1 H-MR spectroscopy ( 1 H-MRS) is rodly ccepted s fst, ccurte nd reproducile mens for the quntifiction of intrcellulr triglyceride content in the cytosol of non-dipose cells. 42 Most commonly, single volume of interest (voxel) is positioned over the interventriculr septum, nd myocrdil spectr (with nd without wter suppression) re cquired t end-systole in severl crdic plnes using either point-resolved spectroscopy (PRESS) or stimulted echo cquisition mode (STEAM) sequences. Susequent nlysis llows the expression of severl myocrdil lipid constituents (including triglycerides, sturted nd unsturted ftty cids) s percentge of the overll tissue wter content. Two recent studies using 1 H-MRS hve demonstrted incresed myocrdil lipid content in ptients with HIV, dding weight to the hypothesis tht morphologic ltertions in myocrdil tissue nd possile lipotoxicity my underlie suclinicl LV dysfunction. 11,43 Crdic tumours nd tumour mimics Thromi represent the most common crdic mss, with stgnnt lood flow in the setting of LV systolic dysfunction, myocrdil infrction or neurysms, nd dilted crdiomyopthy coupled with chronic inflmmtory stte predisposing to their formtion. When lrge, these my e redily pprent on trnsthorcic echocrdiogrphy; however, suoptiml visulistion of the left tril ppendge nd LV pex my compromise their detection with potentilly disstrous clinicl consequences. Additionlly, despite good sonogrphic visulistion of the LV pex, lyered murl thromi my e difficult to differentite from underlying myocrdium. In contrst, thromi re redily detected on CMR, lrgely ppering s low intensity mss lesions tht re incomptile with the norml myocrdil contour or commonly noted intrcrdic ntomicl structures (e.g. crist terminlis, ppillry muscles, modertor nd nd Eustchin vlve) on stndrd cine SSFP sequences. The cquisition of erly post-gdolinium inversion recovery sequences, typiclly 1 2 min following intrvenous contrst dministrtion, fcilittes detection s the vsculr thromi pper hypointense in contrst to the enhncing lood pool nd perfused myocrdium. There is sustntil increse in the risk of developing non-hodgkin s lymphom in HIV-infected ptients, with secondry involvement of the hert found frequently t post-mortem, thought to result from lymphtic, hemtogenous or direct extension. Clinicl presenttion is often heterogeneous with ptients remining symptomtic until the tumour produces significnt mss effect or ostruction of crdic chmers or gret vessels, 44 resulting in pulmonry or systemic emolistion 45 or conduction normlities. 46 Most cses re of the diffuse lrge B-cell sutype, presenting s solid, ill-defined mss typiclly centred in the right trium with infiltrtion long the epicrdium nd tricuspid nnulus, with ssocited encsement, rther thn invsion, of the coronry rteries. 47 The reltively low likelihood of concurrent intrtumourl hemorrhge or necrosis results in homogenously hypoor isointense mss on T1-weighted imges, with vrile LGE (see Figure 10). Crdiovsculr mgnetic resonnce thus enles comprehensive chrcteristion of crdic msses, with cine imging llowing chrcteristion of the size, shpe nd loction of these lesions while llowing review of potentil complictions, including mss effect on djcent coronry rteries nd infiltrtion of surrounding structures, tht my explin co-existing conduction defects nd hemodynmic sequele relted to vlvulr dysfunction. Conclusion Humn immunodeficiency virus infection ffects the entire crdiovsculr xis through complex interply of multiple host, virl nd tretment relted fctors. The vilility of nd ccess to ART hve hd significnt impct on improving the survivl in ptients with HIV or AIDS, nd it is likely tht over time, dverse crdiovsculr events re likely to ply n incresed role in contriuting to cuses of moridity nd mortlity in this suset of ptients. CMR offers n opportunity to comprehensively ssess the crdiovsculr system, llowing detection of suclinicl disese or detiled chrcteristion of known pthologies nd informing susequent clinicl prctice with the hopes of improving outcomes in ffected individuls. Furthermore, the non-invsive nd non-ionising nture of CMR mke it roust, flexile reserch tool well suited to longitudinl follow-up of ptients nd the development of novel imging iomrkers tht will serve to improve our understnding of disese processes, tretment effects nd overll crdiovsculr outcomes in HIV-infected individuls over time. Acknowledgements This mnuscript is not funded. Prof. N. Ntusi grtefully cknowledges support from the Ntionl Reserch Foundtion nd the Medicl Reserch Council of South Afric, s well s the Hrry Crossley Foundtion. Competing interests The uthors declre tht they hve no finncil or personl reltionships tht my hve inppropritely influenced them in writing this rticle.

10 Pge 10 of 10 Authors contriutions V.S. ws responsile for the initil drft of the puliction, nd selection nd processing of figures. P.S. ws responsile for cquisition of CMR cses. S.J., H.S., S.M. nd N.N. were responsile for the criticl review nd finl pprovl of the mnuscript, nd selection nd processing of figures. References 1. UNAIDS Fct sheet 2016 [homepge on the Internet]. UNAIDS [cited 2017 My]. Aville from: 2. Hogg RS, Heth KV, Yip B, et l. Improved survivl mong HIV-infected individuls following initition of ntiretrovirl therpy. JAMA. 1998;279(6): doi.org/ /jm Evns D. Ten yers on ART Where to now? S Afr Med J. 2013;103(4): Ntusi NAB, Ntsekhe M. Humn immunodeficiency virus-ssocited hert filure in su-shrn Afric: Evolution in the epidemiology, pthophysiology, nd clinicl mnifesttions in the ntiretrovirl er. ESC Her Fil. 2016;3(3): doi.org/ /ehf Hundley WG, Bluemke DA, Finn JP, et l. ACCF/ACR/AHA/NASCI/SCMR 2010 expert consensus document on crdiovsculr mgnetic resonnce. A report of the Americn College of Crdiology Foundtion Tsk Force on Expert Consensus Documents. J Am Coll Crdiol. 2010;55(23): Ferreir VM, Piechnik SK, Dll Armellin E, et l. Ntive T1-mpping detects the loction, extent nd ptterns of cute myocrditis without the need for gdolinium contrst gents. J Crdiovsc Mgn Reson. 2014;16(1): / X Hf P, Grg P, Messroghli DR, Brodent DA, Greenwood JP, Plein S. Crdic T1 mpping nd extrcellulr volume (ECV) in clinicl prctice: A comprehensive review. J Crdiovsc Mgn Reson. 2017;18(1):89. s Aggrwl P, Shrm A, Bhrdwj R, Rin R. Myocrdil dysfunction in humn immunodeficiency virus infection: An echocrdiogrphic study. J Assoc Physicins Indi. 2009;57: Hkim JG, Mteng JA, Siziy S. Myocrdil dysfunction in humn immunodeficiency virus infection: An echocrdiogrphic study of 157 ptients in hospitl in Zimwe. Hert. 1996;76(2): Li H, Redheuil A, Tong W, Bluemke DA, Lim JAC, Ren S, et l. HIV infection nd norml regionl ventriculr function. Int J Crdiovsc Imging. 2009;25(8): Hollowy CJ, Ntusi N, Suttie J, et l. Comprehensive crdic mgnetic resonnce imging nd spectroscopy revel high urden of myocrdil disese in HIV ptients. Circultion. 2013;128(8): CIRCULATIONAHA Thir DK, Liu CY, Rmn F, Mngt S, Purdy JB, Durte HA, et l. Anorml myocrdil function is relted to myocrdil stetosis nd diffuse myocrdil firosis in HIV-infected dults. J Infect Dis. 2015;212(10): org/ /infdis/jiv Reinsch N, Neuhus K, Esser S, Potthoff A, Hower M, Brockmeyer NH, et l. Prevlence of crdic distolic dysfunction in HIV-infected ptients: Results of the HIV-HEART study. HIV Clin Trils. 2010;11(3): Hsue PY, Twkol A. Inflmmtion nd firosis in HIV: Getting to the hert of the mtter. Circ Crdiovsc Imging. 2016;9(3): CIRCIMAGING Bárro G, Lorenzo GDI, Grisorio B, Brrini G, Gruppo THE, Per I, et l. Crdic involvement in the cquired immunodeficiency syndrome: A multicenter cliniclpthologicl study. AIDS Res Hum Retroviruses. 1998;14(12): doi.org/ /id Herskowitz A, Wu TC, Willoughy SB, et l. Myocrditis nd crdiotropic virl infection ssocited with severe left ventriculr dysfunction in lte-stge infection with humn immunodeficiency virus. J Am Coll Crdiol. 1994;24(4): Rj V, Joshi S, Pennell DJ. Crdic mgnetic resonnce of cute myocrditis in n humn immunodeficiency virus ptient presenting with cute chest pin syndrome. Circultion. 2010;121(25): CIRCULATIONAHA Rdunski UK, Lund GK, Stehning C, et l. CMR in ptients with severe myocrditis: Dignostic vlue of quntittive tissue mrkers including extrcellulr volume imging. JACC Crdiovsc Imging. 2014;7(7): jcmg Luetkens JA, Doerner J, Schwrze-Znder C, et l. Crdic mgnetic resonnce revels signs of suclinicl myocrdil inflmmtion in symptomtic HIV-infected ptients. Circ Crdiovsc Imging. 2016;9(3): CIRCIMAGING Ntusi N, O Dwyer E, Dorrell L, et l. HIV-1-relted crdiovsculr disese is ssocited with chronic inflmmtion, frequent pericrdil effusions, nd prole myocrdil edem. Circ Crdiovsc Imging. 2016;9(3): org/ /circimaging Sliw K, Crrington MJ, Becker A, Thienemnn F, Ntsekhe M, Stewrt S. Contriution of the humn immunodeficiency virus/cquired immunodeficiency syndrome epidemic to de novo presenttions of hert disese in the hert of Soweto study cohort. Eur Hert J. 2012;33(7): eurhertj/ehr Cegielski JP, Lwktre J, Dukes CS, et l. Tuerculous pericrditis in Tnznin ptients with nd without HIV infection. Tuer Lung Dis. 1994;75(6): Longo-Menz B, Tondungu K, Seghers KV, Mugw D. HIV infection nd pericrdil disese invsion in Afric. Arch Ml Coeur Viss. 1997;90(10): Russell JBW, Syed FF, Ntsekhe M, et l. Cse report tuerculous effusiveconstrictive pericrditis. 2008;19(4): Tse G, Ali A, Alpendurd F, Prsd S, Rphel CE, Vssiliou V. Tuerculous constrictive pericrditis. Res Crdiovsc Med. 2015;4(4): /crdiovscmed Ntusi NA, Plkowski G, Smuels P, Moos S, Ntsekhe M, Myosi B. Crdiovsculr mgnetic resonnce chrcteristion of pericrdil nd myocrdil involvement in ptients with tuerculous pericrdil constriction with nd without HIV coinfection. J Crdiovsc Mgn Reson. 2016;18(Suppl 1):Q / X-18-S1-Q Spottiswoode B, Russell JB, Moos S, Meintjes EM, Epstein FH, Myosi BM. Anorml distolic nd systolic septl motion following pericrdiectomy demonstrted y ciné DENSE MRI. Crdiovsc J Afr. 2008;19(4): Boccr F, Lng S, Meulemn C, Ederhy S, Mry-Kruse M, Costgliol D, et l. HIV nd coronry hert disese: Time for etter understnding. J Am Coll Crdiol. 2013;61(5): Bozzette SA, Ake CF, Tm HK, et l. Long-term survivl nd serious crdiovsculr events in HIV-infected ptients treted with highly ctive ntiretrovirl therpy. J Acquir Immune Defic Syndr. 2008;47(3): Meht NJ, Khn IA. HIV-ssocited coronry rtery disese. Angiology. 2003;54(3): Lewis W. Atherosclerosis in AIDS: Potentil pthogenetic roles of ntiretrovirl therpy nd HIV. J Mol Cell Crdiol. 2000;32(12): /jmcc Ghri AM, Ad-elmoniem KZ, Pettigrew RI, Hdign C. Non-invsive coronry imging for therosclerosis in HIV infection. Curr Prol Dign Rdiol. 2011; 40(6): Zhng S, Vn Sighem A, Kesselring A, et l. Risk of non-aids-defining events mong HIV-infected ptients not yet on ntiretrovirl therpy. HIV Med. 2015;16(5): Ad-Elmoniem KZ, Unsl AB, Esher S, et l. Incresed coronry vessel wll thickness in HIV-infected young dults. Clin Infect Dis. 2014;59(12): Hys A, Intorno M, Schär M, et l. Regionl coronry endothelil dysfunction is relted to locl epicrdil ft in HIV+ ptients. J Crdiovsc Mgn Reson. 2016; 18(Suppl 1): Ntusi NAB, Tylor D, Nidoo N, Mendelson M. Progressive humn immunodeficiency virus-ssocited vsculopthy: Time to revise ntiretrovirl therpy guidelines? Crdiovsc J Afr. 2011;22(4): /CVJA Rider OJ, Asd M, Ntusi N, Winwright E, Clutton G, Hncock G, et l. HIV is n independent predictor of ortic stiffness. J Crdiovsc Mgn Reson. 2014;16(1): Rose KAM, Ver JH, Drivs P, et l. Atherosclerosis is evident in treted HIVinfected sujects with low crdiovsculr risk y crotid crdiovsculr mgnetic resonnce. J Acquir Immune Defic Syndr. 2016;71(5): /QAI Speich R, Jenni R, Oprvil M, Pf M, Russi EW. Primry pulmonry hypertension in HIV infection. Chest. 1991;100(5): Brdlow WM, Simon J, Gis R, Mohiddin RH. Crdiovsculr mgnetic resonnce in pulmonry hypertension. J Crdiovsc Mgn Reson. 2012;14(1): Sheht ML, Lossnitzer D, Skrok J, et l. Myocrdil delyed enhncement in pulmonry hypertension: Pulmonry hemodynmics, right ventriculr function, nd remodeling. Am J Roentgenol. 2011;196(1): AJR Wei J, Nelson MD, Szczepnik EW, et l. Mechnisms of distolic dysfunction in crdiovsculr disese: Myocrdil stetosis s possile mechnistic link etween distolic dysfunction nd coronry microvsculr dysfunction in women. Am J Physiol Hert Circ Physiol. 2016;310:H14 H19. jphert Nelson MD, Victor RG, Szczepnik EW, Simh V, Grg A, Szczepnik LS. Crdic stetosis nd left ventriculr hypertrophy in ptients with generlized lipodystrophy s determined y mgnetic resonnce spectroscopy nd imging. Am J Crdiol. 2013;112(7): Mtsuo S, Sto Y, Miymoto A, et l. Primry mlignnt lymphom of the right trium resulting in superior ven cvl syndrome in n HIV-positive ptient: Depiction t multislice computed tomogrphy nd mgnetic resonnce imging. Crdiovsc Revsc Med. 2006;7(4): Sklidis EI, Prthenkis FI, Zchris EA, Dtseris GE, Vrds PE. Pulmonry tumor emolism from primry crdic B-cell lymphom. Chest. 1999;116(5): Llitjos JF, Redheuil A, Puymirt E, Vedrenne G, Dnchin N. AIDS-relted primry crdic lymphom with right-sided hert filure nd high-grde AV lock: Insights from mgnetic resonnce imging. Ann Crdiol Angeiol (Pris). 2014;63(2): Jeudy J, Kirsch J, Tvor F, et l. From the rdiologic pthology rchives: Crdic lymphom: Rdiologic-pthologic correltion. RdioGrphics. 2012;32(5):