Prognostic Implications of Diffuse Interstitial Fibrosis in Asymptomatic Primary Mitral Regurgitation
2019; Lippincott Williams & Wilkins; Volume: 140; Issue: 25 Linguagem: Inglês
10.1161/circulationaha.119.043250
ISSN1524-4539
AutoresDanai Kitkungvan, Eric Yang, Kinan Carlos El Tallawi, Sherif F. Nagueh, Faisal Nabi, Mohammad A. Khan, Duc T. Nguyen, Edward A. Graviss, Gerald M. Lawrie, William A. Zoghbi, Robert O. Bonow, Miguel A. Quiñones, Dipan J. Shah,
Tópico(s)Infective Endocarditis Diagnosis and Management
ResumoHomeCirculationVol. 140, No. 25Prognostic Implications of Diffuse Interstitial Fibrosis in Asymptomatic Primary Mitral Regurgitation Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBPrognostic Implications of Diffuse Interstitial Fibrosis in Asymptomatic Primary Mitral Regurgitation Danai Kitkungvan, MD, Eric Y. Yang, MD, PhD, Kinan C. El Tallawi, MD, Sherif F. Nagueh, MD, Faisal Nabi, MD, Mohammad A. Khan, MD, Duc T. Nguyen, MD, PhD, Edward A. Graviss, PhD, Gerald M. Lawrie, MD, William A. Zoghbi, MD, Robert O. Bonow, MD, MS, Miguel A. Quinones, MD and Dipan J. Shah, MD Danai KitkungvanDanai Kitkungvan Houston Methodist DeBakey Heart & Vascular Center, TX (D.K., E.Y.Y., K.C.E.T., S.F.N., F.N., M.A.K., G.M.L., W.A.Z., M.A.Q., D.J.S.). Division of Cardiovascular Medicine, McGovern Medical School, University of Texas Health and Science Center at Houston (D.K.). Search for more papers by this author , Eric Y. YangEric Y. Yang Houston Methodist DeBakey Heart & Vascular Center, TX (D.K., E.Y.Y., K.C.E.T., S.F.N., F.N., M.A.K., G.M.L., W.A.Z., M.A.Q., D.J.S.). Search for more papers by this author , Kinan C. El TallawiKinan C. El Tallawi Houston Methodist DeBakey Heart & Vascular Center, TX (D.K., E.Y.Y., K.C.E.T., S.F.N., F.N., M.A.K., G.M.L., W.A.Z., M.A.Q., D.J.S.). Search for more papers by this author , Sherif F. NaguehSherif F. Nagueh Houston Methodist DeBakey Heart & Vascular Center, TX (D.K., E.Y.Y., K.C.E.T., S.F.N., F.N., M.A.K., G.M.L., W.A.Z., M.A.Q., D.J.S.). Search for more papers by this author , Faisal NabiFaisal Nabi Houston Methodist DeBakey Heart & Vascular Center, TX (D.K., E.Y.Y., K.C.E.T., S.F.N., F.N., M.A.K., G.M.L., W.A.Z., M.A.Q., D.J.S.). Search for more papers by this author , Mohammad A. KhanMohammad A. Khan Houston Methodist DeBakey Heart & Vascular Center, TX (D.K., E.Y.Y., K.C.E.T., S.F.N., F.N., M.A.K., G.M.L., W.A.Z., M.A.Q., D.J.S.). Search for more papers by this author , Duc T. NguyenDuc T. Nguyen Department of Pathology and Genomic Medicine, Houston Methodist Research Institute, TX (D.T.N., E.A.G.). Search for more papers by this author , Edward A. GravissEdward A. Graviss Department of Pathology and Genomic Medicine, Houston Methodist Research Institute, TX (D.T.N., E.A.G.). Search for more papers by this author , Gerald M. LawrieGerald M. Lawrie Houston Methodist DeBakey Heart & Vascular Center, TX (D.K., E.Y.Y., K.C.E.T., S.F.N., F.N., M.A.K., G.M.L., W.A.Z., M.A.Q., D.J.S.). Search for more papers by this author , William A. ZoghbiWilliam A. Zoghbi Houston Methodist DeBakey Heart & Vascular Center, TX (D.K., E.Y.Y., K.C.E.T., S.F.N., F.N., M.A.K., G.M.L., W.A.Z., M.A.Q., D.J.S.). Search for more papers by this author , Robert O. BonowRobert O. Bonow Division of Cardiology, Northwestern Memorial Hospital and Northwestern University Feinberg School of Medicine, Chicago, IL (R.O.B.). Search for more papers by this author , Miguel A. QuinonesMiguel A. Quinones Houston Methodist DeBakey Heart & Vascular Center, TX (D.K., E.Y.Y., K.C.E.T., S.F.N., F.N., M.A.K., G.M.L., W.A.Z., M.A.Q., D.J.S.). Search for more papers by this author and Dipan J. ShahDipan J. Shah Dipan J. Shah, MD, Houston Methodist DeBakey Heart & Vascular Center, 6550 Fannin, Suite 1801, Houston, TX 77030. Email E-mail Address: [email protected] Houston Methodist DeBakey Heart & Vascular Center, TX (D.K., E.Y.Y., K.C.E.T., S.F.N., F.N., M.A.K., G.M.L., W.A.Z., M.A.Q., D.J.S.). Search for more papers by this author Originally published16 Dec 2019https://doi.org/10.1161/CIRCULATIONAHA.119.043250Circulation. 2019;140:2122–2124Chronic volume overload in primary mitral regurgitation (MR) leads to progressive left ventricular (LV) remodeling with extracellular matrix expansion (diffuse interstitial fibrosis).1 Cardiac magnetic resonance imaging (CMR) allows for the noninvasive quantification of this via extracellular volume (ECV) mapping, which has demonstrated good correlation with histologic findings of interstitial myocardial fibrosis in several conditions including valvular heart disease.2 There has been no study reporting a prognostic link between elevated ECV and outcomes in primary MR. We used ECV, as a surrogate for diffuse interstitial fibrosis, to evaluate whether elevated ECV represents a prognostic biomarker in asymptomatic patients with primary MR.Patients undergoing contrast-enhanced CMR for assessment of chronic MR at Houston Methodist Hospital (Houston, TX) from 2012 to 2017 were enrolled into a prospective observational registry. To avoid confounding pathogeneses of fibrosis, we excluded patients with history of (1) coronary artery disease, (2) cardiomyopathy, (3) infiltrative disease (ie, amyloidosis/sarcoidosis), (4) previous cardiac surgery, or (5) congenital heart disease, and CMR findings of (1) LV ejection fraction 1.3 cm and relative wall thickness >0.42). These aforementioned criteria also excluded patients with secondary MR. Only asymptomatic patients with at least moderate primary MR (regurgitant fraction ≥30%) and no American College of Cardiology/American Heart Association class I indications for mitral correction were included for longitudinal follow up.3 Patients were followed until they developed (1) referral for mitral valve surgery attributable to symptoms or other class I indications3 or (2) cardiovascular death. The study was approved by the institutional review board at the Houston Methodist Research Institute.CMR images were acquired using 1.5-T or 3.0-T scanners (Siemens Avanto, Aera, or Verio). Our protocol and image analysis have been described previously.4 In brief, cine-CMR was performed for anatomic and functional assessment using a steady-state free-precession sequence. Flow across the aortic valve was ascertained using phase-contrast imaging. An ECG-gated modified Look-Locker inversion recovery sequence was performed at a mid-LV short axis in a matching position before and after gadolinium (≈15 min after 0.15 mmol/kg of extracellular agent).2 The pre- and postcontrast modified Look-Locker inversion recovery sequence acquisitions used a 5(3)3 and a 4(1)3(1)2 sampling scheme, respectively. Quantitative parametric images of myocardial T1 were generated in the mid-LV septum (excluding areas with replacement fibrosis) at the same location for pre- and postcontrast. ECV was calculated per Society for Cardiovascular Magnetic Resonance Guidelines.2Of 144 asymptomatic patients included, 62 (decompensated cohort) had clinical events (59 referred for mitral surgery, successful repair in 95%, and 3 experienced cardiovascular deaths), whereas 82 remained asymptomatic (compensated cohort). The indication for surgical referral was development of symptoms in 90% of patients. The mean time to clinical event in the decompensated cohort was 12.6±16.8 months, and the mean follow-up time in the compensated cohort was 33.8±23.9 months.Clinical and most imaging variables were similar among cohorts (decompensated vs compensated: age 64.1 vs 60.6 years, LV ejection fraction 66% vs 67%, LV end-diastolic volume 100.1 vs 92.1 mL/m2, prevalence of replacement fibrosis 34% vs 31%). Patients in the decompensated cohort had more severe MR (regurgitant fraction 47% vs 38%; P<0.001), larger left atrial size (83.4 vs 67.9 ml/m2; P<0.001), and higher ECV (median ECV 28.1% vs 27.1%; P<0.001). Prevalence of elevated ECV (ECV ≥30%, threshold selected a priori based upon normal volunteers and confirmed optimal by ROC curve analysis) was higher in the decompensated group (32% vs 6%; P<0.001). On multivariate Cox modeling, only MR severity (HR 2.69 [95% CI, 1.75–4.14] for 10% increment of regurgitant fraction) and elevated ECV (HR 2.25 [95% CI, 1.24–4.11]) remain independent predictors of decompensation. For any given MR severity, patients with elevated ECV had worse outcomes than those without (Figure).Download figureDownload PowerPointFigure. Kaplan-Meier curves for survival without mitral valve surgery stratified by mitral regurgitant fraction (RF) and extracellular volume (ECV).Symptoms related to MR are considered a definitive indication for mitral valve surgery.3 However, once they have occurred, the prognosis of patients become unfavorable because operative mortality is higher and postoperative survival is lower, even with normal LV size and systolic function.5 Imaging biomarkers that can detect subclinical changes before symptoms or development of LV systolic dysfunction/dilatation may have an important role in management of patient with MR. In our study, the severity of MR and elevated ECV were the only factors that remained independently predictive with adverse events, whereas traditional parameters such as LV ejection fraction and LV size did not. Incorporating ECV with quantitative MR severity assessment by CMR may aid in further stratifying patients who were likely to develop future indications for mitral valve surgery. It is possible that less compliant ventricles from greater interstitial fibrosis burden (as measured by elevated ECV) may lead to development of symptoms despite lesser degrees of LV dilation, whereas ventricles with lesser interstitial fibrosis may remain compliant and able to accommodate excessive volume without development of symptoms. Future studies with a larger sample size will be required to confirm our findings, validate the ECV threshold for patient selection, and ultimately demonstrate a potential clinical benefit of early mitral valve surgery.Sources of FundingDr Shah receives salary support from the National Science Foundation (Grant CNS-1646566) and the National Institutes of Health (1R01HL137763-01).DisclosuresNone.Footnoteshttps://www.ahajournals.org/journal/circBecause of confidentiality issues, data sets and study materials are safeguarded by the Houston Methodist Research Institute and cannot be made available to outside parties.Dipan J. Shah, MD, Houston Methodist DeBakey Heart & Vascular Center, 6550 Fannin, Suite 1801, Houston, TX 77030. Email [email protected]orgReferences1. Edwards NC, Moody WE, Yuan M, Weale P, Neal D, Townend JN, Steeds RP. Quantification of left ventricular interstitial fibrosis in asymptomatic chronic primary degenerative mitral regurgitation.Circ Cardiovasc Imaging. 2014; 7:946–953. doi: 10.1161/CIRCIMAGING.114.002397LinkGoogle Scholar2. Messroghli DR, Moon JC, Ferreira VM, Grosse-Wortmann L, He T, Kellman P, Mascherbauer J, Nezafat R, Salerno M, Schelbert EB, et al. Clinical recommendations for cardiovascular magnetic resonance mapping of T1, T2, T2* and extracellular volume: a consensus statement by the Society for Cardiovascular Magnetic Resonance (SCMR) endorsed by the European Association for Cardiovascular Imaging (EACVI).J Cardiovasc Magn Reson. 2017; 19:75. doi: 10.1186/s12968-017-0389-8CrossrefMedlineGoogle Scholar3. Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP, Fleisher LA, Jneid H, Mack MJ, McLeod CJ, O’Gara PT, et al. 2017 AHA/ACC Focused Update of the 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.Circulation. 2017; 135:e1159–e1195. doi: 10.1161/CIR.0000000000000503LinkGoogle Scholar4. Kitkungvan D, Nabi F, Kim RJ, Bonow RO, Khan MA, Xu J, Little SH, Quinones MA, Lawrie GM, Zoghbi WA, et al. Myocardial fibrosis in patients with primary mitral regurgitation with and without prolapse.J Am Coll Cardiol. 2018; 72:823–834. doi: 10.1016/j.jacc.2018.06.048CrossrefMedlineGoogle Scholar5. Enriquez-Sarano M, Suri RM, Clavel MA, Mantovani F, Michelena HI, Pislaru S, Mahoney DW, Schaff HV. Is there an outcome penalty linked to guideline-based indications for valvular surgery? Early and long-term analysis of patients with organic mitral regurgitation.J Thorac Cardiovasc Surg. 2015; 150:50–58. doi: 10.1016/j.jtcvs2015.04.009CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Marwick T and Chandrashekhar Y (2022) Quantification and Selective Use of Multimodality Imaging in the Assessment of Valvular Regurgitation, JACC: Cardiovascular Imaging, 10.1016/j.jcmg.2022.04.001, 15:5, (957-959), Online publication date: 1-May-2022. Liu B, Neil D, Bhabra M, Patel R, Barker T, Nikolaidis N, Billing J, Hayer M, Baig S, Price A, Vijapurapu R, Treibel T, Edwards N and Steeds R (2022) Reverse Myocardial Remodeling Following Valve Repair in Patients With Chronic Severe Primary Degenerative Mitral Regurgitation, JACC: Cardiovascular Imaging, 10.1016/j.jcmg.2021.07.007, 15:2, (224-236), Online publication date: 1-Feb-2022. 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Kitkungvan D, Yang E, El Tallawi K, Nagueh S, Nabi F, Khan M, Nguyen D, Graviss E, Lawrie G, Zoghbi W, Bonow R, Quinones M and Shah D (2021) Extracellular Volume in Primary Mitral Regurgitation, JACC: Cardiovascular Imaging, 10.1016/j.jcmg.2020.10.010, 14:6, (1146-1160), Online publication date: 1-Jun-2021. Lawrie G (2020) Surgical treatment of mitral regurgitation, Current Opinion in Cardiology, 10.1097/HCO.0000000000000772, 35:5, (491-499), Online publication date: 1-Sep-2020. Salvatore T, Ricci F, Dangas G, Rana B, Ceriello L, Testa L, Khanji M, Caterino A, Fiore C, Popolo Rubbio A, Appignani M, Di Fulvio M, Bedogni F, Gallina S and Zimarino M (2021) Selection of the Optimal Candidate to MitraClip for Secondary Mitral Regurgitation: Beyond Mitral Valve Morphology, Frontiers in Cardiovascular Medicine, 10.3389/fcvm.2021.585415, 8 December 17, 2019Vol 140, Issue 25 Advertisement Article InformationMetrics © 2019 American Heart Association, Inc.https://doi.org/10.1161/CIRCULATIONAHA.119.043250PMID: 31841370 Originally publishedDecember 16, 2019 Keywordsfibrosismitral valve insufficiencymagnetic resonance imagingPDF download Advertisement SubjectsMagnetic Resonance Imaging (MRI)Valvular Heart Disease
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