Prognostic Significance of Cardiac Magnetic Resonance Imaging Late Gadolinium Enhancement in Fabry Disease
2018; Lippincott Williams & Wilkins; Volume: 138; Issue: 22 Linguagem: Inglês
10.1161/circulationaha.118.037103
ISSN1524-4539
AutoresKate Hanneman, Gauri R. Karur, Syed Wasim, Chantal F. Morel, Robert M. Iwanochko,
Tópico(s)Protein Tyrosine Phosphatases
ResumoHomeCirculationVol. 138, No. 22Prognostic Significance of Cardiac Magnetic Resonance Imaging Late Gadolinium Enhancement in Fabry Disease Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBPrognostic Significance of Cardiac Magnetic Resonance Imaging Late Gadolinium Enhancement in Fabry Disease Kate Hanneman, MD, MPH, Gauri R. Karur, MBBS, MD, Syed Wasim, BSc, Chantal F. Morel, MD and Robert M. Iwanochko, MD Kate HannemanKate Hanneman Kate Hanneman, MD, MPH, Toronto General Hospital, University Health Network, 585 University Ave, 1 PMB-298, Toronto, ON, Canada M5G 2N2. Email E-mail Address: [email protected] Toronto Joint Department of Medical Imaging, Toronto General Hospital, University Health Network (K.H., G.R.K.) , Gauri R. KarurGauri R. Karur Toronto Joint Department of Medical Imaging, Toronto General Hospital, University Health Network (K.H., G.R.K.) , Syed WasimSyed Wasim Fred A. Litwin Centre in Genetic Medicine, University Health Network & Mount Sinai Hospital (S.W., C.F.M) , Chantal F. MorelChantal F. Morel Fred A. Litwin Centre in Genetic Medicine, University Health Network & Mount Sinai Hospital (S.W., C.F.M) and Robert M. IwanochkoRobert M. Iwanochko Division of Cardiology, Peter Munk Cardiac Centre, University Health Network (R.M.I.), University of Toronto, Toronto, Canada. Originally published26 Nov 2018https://doi.org/10.1161/CIRCULATIONAHA.118.037103Circulation. 2018;138:2579–2581Cardiac involvement is the leading cause of mortality in Fabry disease (FD). Late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging predicts adverse cardiac events in other cardiomyopathies. However, it is unclear whether LGE is a significant predictor of adverse cardiac events in FD. The purpose of this study was to evaluate the prognostic significance of the presence and extent of LGE in FD.This retrospective cohort study was approved by the institutional research ethics board. The requirement for written informed consent was waived. All patients with gene-positive FD who had undergone cardiac magnetic resonance imaging with LGE between March 2008 and March 2018 and had clinical follow-up at our institution were included. Magnetic resonance imaging studies were performed with 1.5- or 3-T scanners (MAGNETOM Avanto or Skyra; Siemens Healthcare, Erlangen, Germany). Multiplane LGE images were acquired 12 to 15 minutes after intravenous contrast administration and were visually evaluated for the presence of LGE. Left ventricular endocardial and epicardial borders were contoured on short-axis LGE images to assess the extent of LGE using a signal intensity threshold of 4 SDs, expressed as a percentage of myocardial mass (Circle cmr42; Circle Cardiovascular Imaging, Calgary, Canada).The primary end point was defined as the composite of ventricular tachycardia (VT), bradycardia, heart failure, and cardiac death. Nonsustained VT and sustained VT were defined as ≥3 consecutive beats arising below the atrioventricular node with an inter-beat (RR) interval of >100 bpm lasting <30 and ≥30 seconds, respectively. Bradycardia was defined as a heart rate <60 bpm requiring device implantation for pacing. Heart failure was defined as the development of New York Heart Association functional class III/IV symptoms. Cardiac death was classified as sudden or heart failure–related death. Individual adverse cardiac events were evaluated as secondary end points. Patients without events were censored at the time of their last clinical follow-up.Statistical analysis was performed with STATA version 14.1 (StataCorp, College Station, TX). A 2-tailed value of P<0.05 was considered statistically significant. Time-to-event survival analysis using univariable Cox proportional hazard models were used to estimate the hazard ratio (HR) for the presence and extent of LGE.Eighty-two patients were included in the study with 3.8±2.8 years of follow-up (mean age, 44.7±14.8 years; 32.9% male). LGE was present in 34 patients (41.5%) with a mean LGE extent of 4.4±7.8%.Overall, 16 patients (19.5%) reached the primary end point with an incidence rate of 6.1%/y: 13 of 34 patients (38.2%) with LGE compared with 3 of 48 patients (6.3%) without LGE (HR, 7.35; 95% CI, 2.09–25.89; P=0.002; Table). The risk of the primary end point increased with the extent of LGE (HR, 1.26/5% increase in LGE; 95% CI, 1.06–1.50; P=0.008).Table. Number of Events and Univariable Survival Analyses for Primary and Secondary End PointsEvents, n (%)LGE PresenceLGE Extent*Total (n=82), n (%)LGE-Negative (n=48), n (%)LGE-Positive (n=34), n (%)HR (95% CI)PValueHR (95% CI)PValuePrimary end point Composite end point†16 (19.5)3 (6.3)13 (38.2)7.35 (2.09–25.89)0.0021.26 (1.06–1.50)0.008Secondary end points NSVT15 (18.3)3 (6.3)12 (35.3)6.75 (1.90–24.02)0.0031.15 (0.94–1.41)0.17 Sustained VT‡1 (1.2)0 (0)1 (2.9)———— Bradycardia2 (2.4)1 (2.1)1 (2.9)1.28 (0.08–20.47)0.860.75 (0.16–3.42)0.71 Heart failure‡2 (2.4)0 (0)2 (5.9)——2.18 (0.91–5.19)0.08 Cardiac death‡1 (1.2)0 (0)1 (2.9)————HR indicates hazard ratio; LGE, late gadolinium enhancement; NSVT, nonsustained ventricular tachycardia; and VT, ventricular tachycardia.*HRs are for a 5% increase in quantitative LGE extent.†The primary end point is defined as the composite of NSVT and sustained VT, bradycardia, heart failure, and cardiac death (nonmutually exclusive events).‡Analysis of secondary end points is limited by the number of events observed.Secondary end points were nonsustained VT in 15 patients (18.3%), sustained VT in 1 patient (1.2%), bradycardia in 2 patients (2.4%), heart failure in 2 patients (2.4%), and heart failure–related cardiac death in 1 patient (1.2%). The risk of nonsustained VT increased with the presence of LGE (HR, 6.75; 95% CI, 1.90–24.02; P=0.003) but did not increase significantly with the extent of LGE (HR, 1.15/5% increase in LGE; 95% CI, 0.94–1.41; P=0.17). The risk of sustained VT, bradycardia, heart failure, and cardiac death did not increase significantly with the presence or extent of LGE, although analysis was limited by low numbers of individual events.The main findings of this study are that the presence and extent of LGE are associated with a greater risk of adverse cardiac events in FD. LGE has been shown to represent replacement fibrosis in FD and is an accepted substrate for arrhythmia, supporting the biological plausibility of these findings.1 Identification of patients at elevated risk of adverse events is important given the availability of treatment.Only a few prior studies have reported the association between LGE and adverse events in FD. Krämer et al2 reported that the annual increase in LGE was an independent predictor of ventricular arrhythmia in FD. However, 2 other studies reported no significant association between LGE and adverse events in patients with FD, possibly related to differences in the end points evaluated.3,4A potential limitation of LGE as an imaging biomarker is that LGE may not identify reversible interstitial changes. T1 mapping is a newer magnetic resonance imaging technique that can identify diffuse myocardial changes and may add incremental diagnostic value in FD.5A limitation of this study is that FD is a relatively rare condition. The modest number of events observed makes statistical modeling prone to overfitting and limits the analysis of individual events and the ability to control for potential confounders.In conclusion, LGE is relatively common in patients with FD and is a significant predictor of adverse cardiac events. These findings support the necessity for larger, prospectively designed studies to definitively establish LGE as causally related to major adverse cardiac events in FD.Sources of FundingDr Hanneman received funding from the Radiological Society of North America Research Scholar Grant RSCH1608.DisclosuresS. Wasim has received honoraria and other research support from Shire Pharma Canada ULC and Sanofi Genzyme (modest). Dr Morel has received honoraria and research grants from Shire Pharma Canada ULC and Sanofi Genzyme (modest). Dr Iwanochko has received honoraria from Shire Pharma Canada ULC and Sanofi Genzyme (modest). The other authors report no conflicts.FootnotesData sharing: The data, analytical methods, and study materials will not be made available to other researchers for purposes of reproducing the results or replicating the procedure.https://www.ahajournals.org/journal/circKate Hanneman, MD, MPH, Toronto General Hospital, University Health Network, 585 University Ave, 1 PMB-298, Toronto, ON, Canada M5G 2N2. Email kate.[email protected]caReferences1. Moon JC, Sheppard M, Reed E, Lee P, Elliott PM, Pennell DJ. The histological basis of late gadolinium enhancement cardiovascular magnetic resonance in a patient with Anderson-Fabry disease.J Cardiovasc Magn Reson. 2006; 8:479–482.CrossrefMedlineGoogle Scholar2. Krämer J, Niemann M, Störk S, Frantz S, Beer M, Ertl G, Wanner C, Weidemann F. Relation of burden of myocardial fibrosis to malignant ventricular arrhythmias and outcomes in Fabry disease.Am J Cardiol. 2014; 114:895–900. doi: 10.1016/j.amjcard.2014.06.019CrossrefMedlineGoogle Scholar3. 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Use of myocardial T1 mapping at 3.0 T to differentiate Anderson-Fabry disease from hypertrophic cardiomyopathy.Radiology. 2018; 288:398–406. doi: 10.1148/radiol.2018172613CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Fadl S, Revels J, Rezai Gharai L, Hanneman K, Dana F, Proffitt E and Grizzard J (2022) Cardiac MRI of Hereditary Cardiomyopathy, RadioGraphics, 10.1148/rg.210147, 42:3, (625-643), Online publication date: 1-May-2022. Al-Arnawoot A, O'Brien C, Karur G, Nguyen E, Wasim S, Iwanochko R, Morel C and Hanneman K (2020) Clinical Significance of Papillary Muscles on Left Ventricular Mass Quantification Using Cardiac Magnetic Resonance Imaging, Journal of Thoracic Imaging, 10.1097/RTI.0000000000000556, 36:4, (242-247), Online publication date: 1-Jul-2021. Menacho Medina K, Seraphim A, Katekaru D, Abdel-Gadir A, Han Y, Westwood M, Walker J, Moon J and Herrey A (2021) Noninvasive rapid cardiac magnetic resonance for the assessment of cardiomyopathies in low-middle income countries, Expert Review of Cardiovascular Therapy, 10.1080/14779072.2021.1915130, 19:5, (387-398), Online publication date: 4-May-2021. Cho K and Holloway C (2021) Wearable device notification as first presentation of sinus node dysfunction, Internal Medicine Journal, 10.1111/imj.15277, 51:4, (608-609), Online publication date: 1-Apr-2021. Karur G, Mathur S, Morel C, Iwanochko R, Wald R and Hanneman K (2021) Increased Spread of Native T1 Values Assessed With MRI as a Marker of Cardiac Involvement in Fabry Disease, American Journal of Roentgenology, 10.2214/AJR.20.23102, 216:2, (355-361), Online publication date: 1-Feb-2021. O'Brien C, Britton I, Karur G, Iwanochko R, Morel C, Nguyen E, Thavendiranathan P, Woo A and Hanneman K (2020) Left Ventricular Mass and Wall Thickness Measurements Using Echocardiography and Cardiac MRI in Patients with Fabry Disease: Clinical Significance of Discrepant Findings, Radiology: Cardiothoracic Imaging, 10.1148/ryct.2020190149, 2:3, (e190149), Online publication date: 1-Jun-2020. Felis A, Whitlow M, Kraus A, Warnock D and Wallace E (2020) Current and Investigational Therapeutics for Fabry Disease, Kidney International Reports, 10.1016/j.ekir.2019.11.013, 5:4, (407-413), Online publication date: 1-Apr-2020. Hanneman K, Karur G, Wasim S, Wald R, Iwanochko R and Morel C (2020) Left Ventricular Hypertrophy and Late Gadolinium Enhancement at Cardiac MRI Are Associated with Adverse Cardiac Events in Fabry Disease, Radiology, 10.1148/radiol.2019191385, 294:1, (42-49), Online publication date: 1-Jan-2020. Mathur S, Dreisbach J, Karur G, Iwanochko R, Morel C, Wasim S, Nguyen E, Wintersperger B and Hanneman K (2019) Loss of base-to-apex circumferential strain gradient assessed by cardiovascular magnetic resonance in Fabry disease: relationship to T1 mapping, late gadolinium enhancement and hypertrophy, Journal of Cardiovascular Magnetic Resonance, 10.1186/s12968-019-0557-0, 21:1, Online publication date: 1-Dec-2019. Tower-Rader A and Jaber W (2019) Multimodality Imaging Assessment of Fabry Disease, Circulation: Cardiovascular Imaging, 12:11, Online publication date: 1-Nov-2019. Vajapey R, Eck B, Tang W and Kwon D (2019) Advances in MRI Applications to Diagnose and Manage Cardiomyopathies, Current Treatment Options in Cardiovascular Medicine, 10.1007/s11936-019-0762-z, 21:11, Online publication date: 1-Nov-2019. Valbuena-López S, Eiros R, Dalmau R and Guzmán G (2019) Contemporary View of Magnetic Resonance Imaging in Fabry Disease, Current Cardiovascular Imaging Reports, 10.1007/s12410-019-9498-0, 12:6, Online publication date: 1-Jun-2019. November 27, 2018Vol 138, Issue 22 Advertisement Article InformationMetrics © 2018 American Heart Association, Inc.https://doi.org/10.1161/CIRCULATIONAHA.118.037103PMID: 30571357 Originally publishedNovember 26, 2018 Keywordsmagnetic resonance imagingFabry diseasePDF download Advertisement SubjectsCardiomyopathyMagnetic Resonance Imaging (MRI)Prognosis
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