《MRI在系统性淀粉样变性心脏受累的患者中的预后的评估.pdf》由会员分享，可在线阅读，更多相关《MRI在系统性淀粉样变性心脏受累的患者中的预后的评估.pdf（5页珍藏版）》请在taowenge.com淘文阁网|工程机械CAD图纸|机械工程制图|CAD装配图下载|SolidWorks_CaTia_CAD_UG_PROE_设计图分享下载上搜索。
1、BRIEF OBSERVATIONPrognosis Assessment of Cardiac Involvement in SystemicAL Amyloidosis by Magnetic Resonance ImagingArsene Mekinian,MD,aChristophe Lions,MD,bXavier Leleu,MD,cAlain Duhamel,MPHD,dNicolas Lamblin,MD,eValerie Coiteux,MD,cPascal De Groote,MD,ePierre-Yves Hatron,MD,PhD,aThierry Facon,MD,P
2、hD,cJean-Paul Beregi,MD,PhD,bEric Hachulla,MD,PhD,aDavid Launay,MD,PhDafor the Lille Amyloidosis Study GroupaService de Mdecine Interne,Hpital Claude Huriez,Centre Hospitalier Rgional Universitaire(CHRU),Lille,France;bService deRadiologie,Hpital Cardiologique,CHRU,Lille,France;cService des Maladies
3、du Sang,Hpital Claude Huriez,CHRU,Lille,France;dCentre detudes et de recherch en informatique mdicale(CERIM),Laboratoire de Statistiques Mdicales,Facult deMdecine,Lille,France;andeService de Cardiologie,Hpital Cardiologique,CHRU,Lille,France.ABSTRACTBACKGROUND:Cardiac involvement is one of the most
4、important prognostic factors in systemic ALamyloidosis.The aim of our study was to assess the role of cardiovascular magnetic resonance(CMR)imaging in prognosis evaluation in AL amyloidosis.METHODS:We retrospectively analyzed 29 consecutive patients with AL amyloidosis who had undergoneCMR.Clinical,
5、laboratory,echocardiographic,and CMR characteristics were compared between CMR-positive(ie,with CMR signs of cardiac localization of AL amyloidosis)and CMR-negative patients.Univariate and multivariate analyses were performed to assess the prognostic value of positive CMR incomparison with other pro
6、gnostic factors.RESULTS:CMR was positive in 11 patients(38%).The overall survival rates for CMR-positive patients were28%,14%,and 14%versus 84%,77%,and 45%at 1,2,and 5 years,respectively,for CMR-negative patients(P?.002).Late gadolinium enhancement patterns,biventricular hypertrophy,and pericardial
7、effusion on CMRwere more frequent in nonsurvivors.Congestive heart failure,abnormal echocardiography,Eastern CooperativeOncology Group grade?1,brain natriuretic peptide,and left ventricular ejection fraction?55%also wereassociated with a decreased survival.The presence of congestive heart failure wa
8、s the only significant variableassociated with survival on multivariate analysis.CONCLUSION:We found that the presence of a positive CMR in AL amyloidosis was associated with asignificantly increased risk of death,in particular of cardiac origin,but was not independent of clinicalcongestive heart fa
9、ilure.2010 Elsevier Inc.All rights reserved.The American Journal of Medicine(2010)123,864-868KEYWORDS:AL amyloidosis;Cardiovascular magnetic resonance imaging;Prognosis;SurvivalThe heart is affected in near 50%of cases in AL amy-loidosis and is a major determinant of prognosis.1Somestudies have trie
10、d to establish prognosis tools,especiallybased on cardiac biomarkers like troponin or natriureticpeptides in AL amyloidosis.2Recently,cardiovascularmagnetic resonance imaging(CMR)with late gadoliniumenhancement sequences was shown to be useful for thediagnosis of cardiac involvement in AL amyloidosi
11、s.3-7However,data about the prognostic value of an abnormalCMR are scarce,8,9and a comparison of CMR with otherprognostic tools such as echocardiography or biomarkersis lacking.2The aims of this study were to assess the prognosticvalue of CMR in AL amyloidosis and to compare theprognostic performanc
12、e of CMR with that of other knownprognostic factors.Funding:None.Conflict of Interest:The authors have no potential conflicts of interestto declare.Authorship:All authors had access to the data and a role in writing themanuscript.Requests for reprints should be addressed to David Launay,MD,PhD,Servi
13、ce de Mdecine Interne,Hpital Claude Huriez,CHRU,Lille,France.E-mail address:d-launaychru-lille.fr0002-9343/$-see front matter 2010 Elsevier Inc.All rights reserved.doi:10.1016/j.amjmed.2010.03.022PATIENTS AND METHODSPatientsWe retrospectively studied 29 patients with AL amyloidosis whohadundergoneCM
14、Rbetween2003and2008andfollowedbytheAmyloidosis Study Group of LilleHospital,France.In all cases,the diagnosis ofamyloidosis was ascertained bya tissue biopsy(fat aspirationn?4,accessory salivary glandn?7,rectum n?5,bone mar-row n?3,kidney n?7,heartn?1,or muscle n?2).Thetype of amyloidosis,the presen
15、ceof monoclonal light chain protein,and the organ involvement weredeterminedasrecommended.10AL cardiac involvement in echo-cardiography was defined as leftventricular(LV)mean wall thick-ness?12 mm,in the absence of hypertension or otherpotential causes of left ventricular hypertrophy.10CMR was perfo
16、rmed on a 1.5 Tesla MR scan(Intera,Philips Medical Systems,Best,The Netherlands).After asecond dose of 0.1 mmol/kg meglumine gadoterate,thedelayed contrast enhancement sequence was performed inthree cardiac axes(short axis,long axis,4 chambers)usinginversion recovery gradient echo with a Look-Locker
17、 se-quence.CMR was considered as positive,that is,revealingcardiac amyloidosis,when it was impossible to obtain anormal myocardial signal on a late gadolinium enhancementLook-Locker sequence with inversion time?300 ms.11Clinical,CMR,echocardiographic,and laboratory datawere collected at diagnosis,be
18、fore any treatment.Clinicaland laboratory data also were collected after a completecourse of treatment.Survival was considered from the date of the diagnosis ofamyloidosis until July 2008(cut-off date).Statistical AnalysisSurvival was analyzed using the variables that could affectsurvival in amyloid
19、osis:age,age?65 years,Eastern Coop-erative Oncology Group grade(ECOG)?1,congestiveheart failure,type of amyloidosis,weight loss at diagnosis,number of involved organs,time between diagnosis andtreatment,CMR,echocardiography,LV ejection fraction?55%(in echocardiography),LV mean wall thickness.Theseru
20、m?2 microglobulin,albumin,creatinine,troponin,brain natriuretic peptide(BNP),serum free light chain(sFLC)levels,and the bone marrow plasma cell percentagewere analyzed.Univariate survival analysis(Cox proportional hazardregression models or Kaplan Meier)and a multivariateanalysis by Cox regression m
21、odel with stepwise selectionwere carried out to identify significant death predictorswithin variables linked to survival(P?.05)and CMR(P?.5).Statistical analysis was performed using SAS soft-ware(SAS Institute Inc.,Cary,NC).A value of P?.05 wasconsidered significant.RESULTSBaseline CharacteristicsTh
22、e baseline characteristics of the29 AL amyloidosis patients aresummarized in Table 1.Mean du-ration of follow-up was 32?5months.On echocardiography,LV mean wall thickness?12 mmwas present in 15 cases(54%).Nopatients with LV mean wall thick-ness?12 mm had a restrictive di-astolic pattern or diffuse“g
23、ranularsparkling.”Specific treatment wasmelphalan-dexamethasone in 21cases,bortezomib-dexamethasonein 4 cases,lenalidomide-dexa-methasone in 2 cases,and high-dose melphalan plus stemcell transplantation in 2 cases.Cardiovascular Magnetic ResonanceCMR was positive in 11 cases(38%).CMR characteristics
24、 ofpatients are summarized in Table 2.There was no difference inbaseline characteristics or laboratory findings between CMR-CLINICAL SIGNIFICANCEPositive cardiovascular magnetic reso-nance is associated with a significantlyincreased risk of death,especially ofcardiac origin,in AL amyloidosis.In the
25、presence of congestive heart fail-ure,cardiovascular magnetic resonancedoes not have to be performed,as it doesnot modify prognosis determination.Table 1Patients Baseline CharacteristicsCharacteristics(n?29)Age(years)63?11Sex(M/F)19/10ECOG 2/3/4,n(%)8(28)/3(10)/1(3)Involved organs(n)Heart14Kidney13L
26、iver3Nerve10Gastrointestinal tract6Soft tissue10Lung2HeartCongestive heart failure,n(%)17(59)BNP(pg/mL)(n?27)316?411Troponin(ng/mL)(n?26)0.11?0.14Monoclonal immunoglobulin?type,n(%)21(73)sFLC(mg/L)543?673sFLC(?/?ratio)20.0?88Creatinine(mg/L)1.8?1.8Albumin(g/L)32?7?2 microglubin(mg/L)5.59?7.40ECOG?Ea
27、stern Cooperative Oncology Group grade;BNP?brain na-triuretic peptide;sFLC?serum free light chain assay.865Mekinian et alCardiovascular Magnetic Resonance Imaging in AL Amyloidosispositive and CMR-negative patients.sFLC levels were590?700 mg/L in CMR-positive patients versus 520?670mg/L,with ratios
28、of 8?20 and 26?100,respectively(P?.4).Conversely,cardiaccharacteristicsweresignificantlydifferent between these 2 groups(Table 2).SurvivalMean survival was 32?5 months.Death had occurred in 15cases(52%),and in 10 cases(83%)was considered to be ofcardiac origin.Deaths(P?.01),in particular those of ca
29、r-diac origin(P?.002),were statistically more frequent inpatients with a positive CMR.The mean survival of theCMR-positive patients was 10?3 months,versus 44?6months for CMR-negative patients(P?.002).The overallsurvival rates for CMR-positive patients were 28%,14%,and 14%at 1,2,and 5 years,respectiv
30、ely,versus 84%,77%,and 45%at 1,2,and 5 years,respectively,for CMR-negative patients(P?.01)(Figure).The positive CMR,the presence of congestive heartfailure,the BNP levels,the LV ejection fraction?55%,ECOG?1,and the positive echocardiography were thesignificant variables associated with survival in u
31、nivariateanalysis(P?.05)(Table 3).In multivariate analysis,congestive heart failure was theonly factor significantly and independently associated withsurvival,with a hazard ratio of 5.5(P?.002;95%confi-dence interval,1.3-23.0)(Table 3).In multivariate analysiscomparing CMR and echocardiography(posit
32、ive echocar-diography defined as LV mean wall thickness?12 mm)after exclusion of the other cardiologic parameters,onlypositive CMR(as previously defined)was significantly andindependently associated with survival,with a hazard ratioof 4.8(P?.01;95%confidence interval,1.4-16.5).DISCUSSIONThe main res
33、ult of this study is that patients with a positiveCMR had a worse prognosis than patients with a negativeCMR.However,in multivariate analysis,only the presenceof congestive heart failure was an independent prognosisfactor.Positive CMR was defined in this study as the impossi-bility of obtaining a no
34、rmal myocardial signal on the Look-Locker late-enhancement sequences.11Unlike the majorityof CMR studies,we did not consider the presence of lategadolinium enhancement as a sufficient positive CMR cri-Table 2Patients Clinical,Laboratory,Echocardiographic and CMR CharacteristicsPositive CMR(n?11)Nega
35、tive CMR(n?18)P-ValueBaseline clinical dataAge(years)59(37-81)63(46-79).3ECOG?1,n(%)7(64)5(28).12Cardiac characteristicsCongestive heart failure,n(%)11(100)1(6).0001Positive echocardiography,n(%)11(100)3(17).001LV ejection fraction?55%,n(%)6(55)1(6).005LV mean wall thickness(mm)16(12-19)11(8-17).004
36、Electrocardiogram low voltage,n(%)4(36)1(6).3BNP(pg/mL)400(86-1874)87(3-1065).03Troponin level(ng/mL)0.1(0.01-0.51)0.03(0-0.51).14CMR characteristicsInterventricular septum thickness(mm)19?510?3.0002LV posterior wall(mm)13?410?3.28LV ejection fraction(%)55?1565?12.10LV end-diastolic volume(mL)133?21
37、121?42.34LV end-systolic volume(mL)64?2751?33.22LV mass(g)181?70102?32.004RV ejection fraction(%)52?1554?12.70RV end-diastolic volume(mL)100?33113?50.4.61Pericardial effusion,n(%)6(55)1(6).03Biventricular hypertrophy,n(%)10(91)1.0001Late gadolinium enhancement pattern,n(%)8(73)0.0001OutcomeSurvival(
38、months)6(1-29)59(2-107).02Death,n(%)9(82)6(33).01Cardiac death,n(%)9(82)1(6).002Values are mean?SD or medians with ranges.CMR?cardiovascular magnetic resonance;ECOG?Eastern Cooperative Oncology Group grade;LV?left ventricle;BNP?brain natriuretic peptide;RV?right ventricle.866The American Journal of
39、Medicine,Vol 123,No 9,September 2010terion.Indeed,even if it is highly characteristic of cardiacamyloidosis,the diffuse late gadolinium enhancement pat-tern is present in only 64%-80%of AL amyloidosis patientswith cardiac involvement.A limited late gadolinium en-hancement pattern is not specific.4-7
40、Moreover,in cardiacamyloidosis,the late gadolinium pattern may be difficult toobtain,as the optimal inversion time that will null normalmyocardium could be difficult to determine.In amyloidosis,the Look-Locker sequence shows that myocardial nulling isearlier than the blood nulling,and that normal my
41、ocardialsignal with an inversion time?300 ms is impossible toobtain.This pattern is the inverse of the normal pattern andis the best diagnosis feature in amyloidosis.11,12As anillustration,all patients with cardiac involvement had posi-tive CMR as defined in our study,whereas diffuse lategadolinium
42、enhancement pattern was present in only 73%of our patients.In another study of 29 AL and transthyretin amyloidosis,gadolinium kinetics showed higher blood T1 in nonsurvi-vors,whereas the intramyocardial T1 difference after gad-olinium injection(subepicardium-subendocardium)wassignificantly higher in
43、 survivors.8The presence of late gad-olinium enhancement pattern did not correlate significantlywith survival in that study,but survival in transthyretinamyloidosis is very different from survival in AL amyloid-osis.In a study of 21 cases of cardiac amyloidosis,lategadolinium enhancement pattern did
44、 not predict mortality,but only CMR variables were analyzed to predict survival.9In contrast,another study has shown that the late gadolin-ium enhancement was associated with poorer survival,butthey could not assess its independent value,as multivariablemodeling was not possible because of the absen
45、ce of mor-tality in subjects with normal CMR.13Moreover,echocar-diographic characteristics,as well as BNP and sFLC,werenot analyzed in that study.No study has compared the prognosis performance ofCMR with that of all other known prognostic factors,asdone in our study.In multivariate analysis,congest
46、ive heartfailure was the only independent prognostic factor in ourstudy.One explanation could be that all patients with pos-itive CMR had congestive heart failure.In our study,CMRwas positive only in patients with advanced cardiomyopa-thy.These results suggest that in the presence of congestiveheart
47、 failure,CMR does not add any additional informationon the assessment of amyloidosis prognosis.In conclusion,the presence of a positive CMR was as-sociated with a significantly increased risk of death,inparticular of cardiac origin,in AL amyloidosis.CMR doesnot appear to be mandatory in assessing th
48、e prognosis ofpatients with overt congestive heart failure.The role ofthe CMR in the evaluation of cardiac involvement andprognosis in the early stages of AL amyloidosis and theFigureKaplan-Meier survival curves according to the positivity or negativity of cardio-vascular magnetic resonance(CMR).Tab
49、le 3Significant Prognosis VariablesUnivariate AnalysisMultivariate AnalysisVariablesP-ValueHazard Ratio(95%CI)P-ValueCongestive heartfailure.00035.5(1.3-22.98).018CMR.00181.05(0-36).9BNP.00461.1(1-1.004).033LV ejection fraction?55%.0160.9(0.2-5).9ECOG?1.0322(0.5-7).3Echocardiography.0341(0.2-7).9CI?
50、confidence interval;CMR?cardiovascular magnetic resonance;BNP?brain natriuretic peptide;LV?left ventricular;ECOG?EasternCooperative Oncology Group grade.867Mekinian et alCardiovascular Magnetic Resonance Imaging in AL Amyloidosisevaluation of the cardiac response remains to be deter-mined prospectiv