The Clinical Significance of Cardiac MRI Late Gadolinium Enhancement in Hypertrophic Cardiomyopathy

HomeRadiologyVol. 302, No. 2 PreviousNext Reviews and CommentaryFree AccessEditorialThe Clinical Significance of Cardiac MRI Late Gadolinium Enhancement in Hypertrophic CardiomyopathyKate Hanneman Kate Hanneman Author AffiliationsFrom the Department of Medical Imaging, Toronto General Hospital Research Institute, University Health Network, University of Toronto, 585 University Ave, 1PMB-298, Toronto, ON, Canada M5G 2N2.Address correspondence to the author (e-mail: [email protected]).Kate Hanneman Published Online:Nov 2 2021https://doi.org/10.1148/radiol.2021212214MoreSectionsPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In See also the article by Liu and Zhao et al in this issue.Dr Hanneman is an associate professor at the University of Toronto, director of cardiac imaging research at the Joint Department of Medical Imaging, and a clinician scientist at the Toronto General Hospital Research Institute. She is the recipient of Canadian Institute of Health Research grant funding and leads an active research program focused on improving health outcomes for patients with cardiomyopathies using cardiac imaging.Download as PowerPointOpen in Image Viewer Hypertrophic cardiomyopathy (HCM) is a common genetic heart disease characterized by left ventricular hypertrophy in the absence of another systemic or cardiac disease capable of producing a similar magnitude of hypertrophy in each patient. The diagnosis of HCM is established with cardiac imaging based on maximum end-diastolic wall thickness of 15 mm or greater in adults, in the absence of another cause of hypertrophy, or 13 mm or greater if there is a family history of HCM or in conjunction with a positive genetic test (1). Although some patients with HCM are asymptomatic, up to 40% will experience an adverse event, including sudden cardiac death, heart failure symptoms, and atrial fibrillation with risk of thromboembolic stroke.Cardiac imaging plays an essential role in patients with HCM beyond establishing the diagnosis, including evaluating the severity of the phenotype, characterizing structural and functional cardiac abnormalities, and assessment of risk factors for sudden cardiac death. Risk stratification in HCM is based on noninvasive risk markers. These markers can identify patients with HCM at greatest risk of sudden cardiac death who may then be candidates for preventative therapy, including implantable cardioverter-defibrillator placement. Implantable cardioverter-defibrillators are effective at successfully aborting life-threatening arrythmias in patients with HCM and at saving lives. However, careful selection of patients at high risk is needed given the potential risks associated with implantation and impaired quality of life associated with implantable cardioverter-defibrillator shocks.Although echocardiography is the primary imaging modality in HCM, cardiac MRI is an important complementary imaging technique that provides unique information regarding myocardial tissue characterization. Late gadolinium enhancement (LGE) at cardiac MRI is the reference standard for noninvasive assessment of myocardial replacement fibrosis, and it is strongly associated with adverse cardiac events (2,3). A key update in the most recent American Heart Association and American College of Cardiology guidelines for the diagnosis and treatment of patients with HCM published in 2020 was the inclusion of extensive LGE (defined as LGE extent ≥15% of left ventricular mass) as a risk factor for HCM sudden cardiac death risk stratification and as a criterion that could be used to guide patient selection for implantable cardioverter-defibrillator placement (1). This recent change in management guidelines highlights the important role of cardiac imaging in patients with HCM.In this issue of Radiology, Liu and colleagues (4) characterize patterns of LGE at cardiac MRI in 798 participants with HCM in relation to disease phenotype and clinical outcomes. Their results demonstrated that LGE was inhomogeneous and asymmetric and had prognostic significance regardless of location. The most common location for LGE was at the basal to mid interventricular septum and anterior wall. The location was unrelated to hypertrophic phenotype, mutation status, and genotype. Besides location, the overall distribution of LGE is important to characterize particularly in patients with unexplained left ventricular hypertrophy. The pattern of LGE could be an important clue regarding alternative causes of left ventricular hypertrophy. For example, LGE is most commonly located at the basal inferolateral wall in patients with Fabry disease, whereas LGE is typically extensive with characteristic septal sparing in patients with Danon disease (5,6).Most cardiac MRI studies in patients with HCM to date have focused on the prognostic value of the global extent of LGE in the entire left ventricular myocardium. However, in this study, the authors quantified regional LGE in specific myocardial segments and evaluated the relationship between regional extent of LGE and prognosis. Their study showed that the overall extent of LGE was strongly associated with adverse clinical events, with a 1.8 times higher risk of sudden cardiac death for every 10% increase in LGE extent even after adjusting for age, sex, maximal left ventricular wall thickness, and maximal left ventricular outflow tract gradient as potential confounders. Participants with extensive LGE (≥15% of LV mass) had a higher incidence of all-cause death (P = .03) and cardiovascular death (P = .02). The relationship between LGE and adverse events was robust even when evaluated with a segmental analysis, with a higher extent of LGE in multiple regions associated with a greater risk of all-cause death. The strength of this relationship reinforces that LGE extent is a powerful predictor of sudden cardiac death in HCM. Replacement fibrosis is a substrate for life-threatening ventricular arrythmias, which supports the biologic plausibility of these findings.Participants in the study included a spectrum of phenotypic expressions and most had undergone genetic testing with whole-genome sequencing (202 of 588 participants [34%] were identified to be sarcomeric mutation carriers). LGE was more extensive in participants positive for mutation versus participants negative for mutation (5.7% vs 2.8%), concordant with recent results from 2755 patients in the Hypertrophic Cardiomyopathy Registry (7). Interestingly, despite this difference in LGE extent between mutation groups, there was no evidence of effect modification by mutation type on the relationship between LGE extent and adverse events. This means that there is no evidence that the magnitude of the effect of LGE extent on adverse cardiac events differs between patients who are positive or negative for mutation. These results may be interpreted to mean that patients with HCM with extensive LGE are at a higher risk of sudden cardiac death regardless of their genotype status. Effect modification requires a much larger sample size to evaluate than main effects. Therefore, the large, well-characterized cohort included in this study was ideally suited to evaluate this relationship.The authors also reported that LGE extent was only weakly correlated with maximal wall thickness (r = 0.35; P < .001). This is an interesting and potentially important finding as it suggests that echocardiographic assessment of maximum wall thickness may not be adequate for phenotypic characterization and risk assessment in all patients with HCM, and it highlights the importance of the incremental tissue characterization afforded with MRI. Of note, a recent previous study reported that maximum native T1 and extracellular volume correlated strongly with LV mass indexed to body surface area in patients with HCM without LGE or left ventricular outflow tract obstruction (r = 0.86; P < .001) (8). Higher native T1 and extracellular volume were associated with interstitial fibrosis in patients with HCM, and these findings suggest that the relationship between fibrosis and left ventricular hypertrophy severity might differ at different stages of the disease and between different fibrosis types (replacement vs interstitial).Limitations of this study included the fact that parametric mapping sequences were not included. Native T1 values and extracellular volume could provide incremental information to LGE, such as the ability to differentiate between HCM and other left ventricular hypertrophy phenotypes (9). Large multicenter MRI studies with protocols, including T1 mapping and extracellular volume, will be crucial to determine the incremental value of these techniques beyond LGE and to establish their prognostic value. Routine implementation of LGE quantification in clinical practice was previously hindered by the additional postprocessing time required. However, artificial intelligence convolutional neural network–based methods for myocardial segmentation now allow for fast and accurate quantification of LGE in patients with HCM (10).The strengths of this study include a very large cohort and characterization of regional and segmental LGE findings in relation to maximum wall thickness and clinical outcomes. The relatively modest number of events over a median 2.9-year follow-up despite the very large sample size is consistent with the recent literature (8). The detailed and segmental analysis in this large cohort provides unique insights into the underlying disease process in HCM. Liu et al (4) have made an important contribution to the body of literature supporting the clinical significance of quantitative cardiac MRI assessment of myocardial tissue changes in patients with HCM.Disclosures of Conflicts of Interest: K.H. Honoraria for Sanofi Genzyme, Amicus, and Medscape; associate editor for Radiology: Cardiothoracic Imaging.References1. Ommen SR, Mital S, Burke MA, et al. 2020 AHA/ACC Guideline for the Diagnosis and Treatment of Patients With Hypertrophic Cardiomyopathy: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol 2020;76(25):e159–e240. Crossref, Medline, Google Scholar2. Hanneman K, Karur GR, Wasim S, Wald RM, Iwanochko RM, Morel CF. Left Ventricular Hypertrophy and Late Gadolinium Enhancement at Cardiac MRI Are Associated with Adverse Cardiac Events in Fabry Disease. Radiology 2020;294(1):42–49. Link, Google Scholar3. Kuruvilla S, Adenaw N, Katwal AB, Lipinski MJ, Kramer CM, Salerno M. Late gadolinium enhancement on cardiac magnetic resonance predicts adverse cardiovascular outcomes in nonischemic cardiomyopathy: a systematic review and meta-analysis. Circ Cardiovasc Imaging 2014;7(2):250–258. Crossref, Medline, Google Scholar4. Liu J, Zhao S, Yu S, et al. Patterns of Replacement Fibrosis in Hypertrophic Cardiomyopathy. Radiology 2021.https://doi.org/10.1148/radiol.2021210914. Published online November 2, 2021. Link, Google Scholar5. Deva DP, Hanneman K, Li Q, et al. Cardiovascular magnetic resonance demonstration of the spectrum of morphological phenotypes and patterns of myocardial scarring in Anderson-Fabry disease. J Cardiovasc Magn Reson 2016;18(1):14. Crossref, Medline, Google Scholar6. Wei X, Zhao L, Xie J, et al. Cardiac Phenotype Characterization at MRI in Patients with Danon Disease: A Retrospective Multicenter Case Series. Radiology 2021;299(2):303–310. Link, Google Scholar7. Neubauer S, Kolm P, Ho CY, et al. HCMR Investigators. Distinct Subgroups in Hypertrophic Cardiomyopathy in the NHLBI HCM Registry. J Am Coll Cardiol 2019;74(19):2333–2345. Crossref, Medline, Google Scholar8. Xu J, Zhuang B, Sirajuddin A, et al. MRI T1 Mapping in Hypertrophic Cardiomyopathy: Evaluation in Patients Without Late Gadolinium Enhancement and Hemodynamic Obstruction. Radiology 2020;294(2):275–286. Link, Google Scholar9. Karur GR, Robison S, Iwanochko RM, et al. Use of Myocardial T1 Mapping at 3.0 T to Differentiate Anderson-Fabry Disease from Hypertrophic Cardiomyopathy. Radiology 2018;288(2):398–406. Link, Google Scholar10. Fahmy AS, Neisius U, Chan RH, et al. Three-dimensional Deep Convolutional Neural Networks for Automated Myocardial Scar Quantification in Hypertrophic Cardiomyopathy: A Multicenter Multivendor Study. Radiology 2020;294(1):52–60. Link, Google ScholarArticle HistoryReceived: Aug 30 2021Revision requested: Sept 2 2021Revision received: Sept 3 2021Accepted: Sept 7 2021Published online: Nov 02 2021Published in print: Feb 2022 FiguresReferencesRelatedDetailsAccompanying This ArticlePatterns of Replacement Fibrosis in Hypertrophic CardiomyopathyNov 2 2021RadiologyRecommended Articles Patterns of Replacement Fibrosis in Hypertrophic CardiomyopathyRadiology2021Volume: 302Issue: 2pp. 298-306Cardiac MRI of Hereditary CardiomyopathyRadioGraphics2022Volume: 42Issue: 3pp. 625-643Hypertrophic Cardiomyopathy from A to Z: Genetics, Pathophysiology, Imaging, and ManagementRadioGraphics2016Volume: 36Issue: 2pp. 335-354MRI T1 Mapping in Hypertrophic Cardiomyopathy: Evaluation in Patients Without Late Gadolinium Enhancement and Hemodynamic ObstructionRadiology2019Volume: 294Issue: 2pp. 275-286MRI Characteristics, Prevalence, and Outcomes of Hypertrophic Cardiomyopathy with Restrictive PhenotypeRadiology: Cardiothoracic Imaging2020Volume: 2Issue: 4See More RSNA Education Exhibits MRI Mapping in the study of Myocardial DiseaseDigital Posters2022Secondary Findings of Hypertrophic Cardiomyopathy: A Diagnosis to Be MadeDigital Posters2020MRI of Hereditary CardiomyopathyDigital Posters2020 RSNA Case Collection Hypertrophic cardiomyopathyRSNA Case Collection2020Cardiac fibromaRSNA Case Collection2020Primary LymphedemaRSNA Case Collection2022 Vol. 302, No. 2 Metrics Altmetric Score PDF download