Myocardial Fibrosis in Hypertrophic Cardiomyopathy

Moravsky, Gil; Ofek, Efrat; Rakowski, Harry; Butany, Jagdish; Williams, Lynne; Ralph-Edwards, Anthony; Wintersperger, Bernd J.; Crean, Andrew M.

doi:10.1016/j.jcmg.2012.09.018

Cited by 189 publications

(60 citation statements)

References 30 publications

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“…Depending on different clinical and imaging applications, quantification of myocardial fibrosis in LGE CMR images has been performed with SI thresholding that differs among studies [39–42]. We presented a comparative assessment for the amount of fibrosis using various levels of threshold and showed all thresholds achieved a high accuracy separating the two groups.…”

Section: Discussionmentioning

confidence: 99%

Quantitative assessment of myocardial fibrosis in an age-related rat model by ex vivo late gadolinium enhancement magnetic resonance imaging with histopathological correlation

Beliveau

Cheriet

Anderson

et al. 2015

Computers in Biology and Medicine

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Late gadolinium enhanced (LGE) cardiac magnetic resonance (CMR) imaging can detect the presence of myocardial infarction from ischemic cardiomyopathies (ICM). However, it is more challenging to detect diffuse myocardial fibrosis from non-ischemic cardiomyopathy (NICM) with this technique due to more subtle and heterogeneous enhancement of the myocardium. This study investigates whether high-resolution LGE CMR can detect age-related myocardial fibrosis using quantitative texture analysis with histological validation. LGE CMR of twenty-four rat hearts (twelve 6-week-old and twelve 2-year-old) was performed using a 7 Tesla MRI scanner. Picrosirius red was used as the histopathology reference for collagen staining. Fibrosis in the myocardium was quantified with standard deviation (SD) threshold methods from the LGE CMR images and 3D contrast texture maps that were computed from grey level co-occurrence matrix of the CMR images. There was a significant increase of collagen fibers in the aged compared to the young rat histology slices (2.60±0.27 %LV vs. 1.24±0.29 %LV, p<0.01). Both LGE CMR and texture images showed a significant increase of myocardial fibrosis in the elderly compared to the young rats. Fibrosis in the LGE CMR images correlated strongly with histology with the 3 SD threshold (r=0.84, y=0.99x+0.00). Similarly, fibrosis in the contrast texture maps correlated with the histology using the 4 SD threshold (r=0.89, y=1.01x+0.00). High resolution ex-vivo LGE CMR can detect the presence of diffuse fibrosis that naturally developed in elderly rat hearts. Our results suggest that texture analysis may improve the assessment of myocardial fibrosis in LGE CMR images.

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Section: Discussionmentioning

confidence: 99%

Quantitative assessment of myocardial fibrosis in an age-related rat model by ex vivo late gadolinium enhancement magnetic resonance imaging with histopathological correlation

Beliveau

Cheriet

Anderson

et al. 2015

Computers in Biology and Medicine

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“…Additionally, LGE has the unique ability to identify areas of fibrosis. 23,24 Scarce data exist on the genotype-phenotype association in patients with HCM as assessed by CMR. 25 We sought to compare CMR phenotype between patients harboring mutations in the 2 most common genes, MYH7 and MYBPC3.…”

Section: Weissler-snir Et Al Phenotypic-genotypic Correlation By Cmr mentioning

confidence: 99%

Lack of Phenotypic Differences by Cardiovascular Magnetic Resonance Imaging in MYH7 (β-Myosin Heavy Chain)- Versus MYBPC3 (Myosin-Binding Protein C)-Related Hypertrophic Cardiomyopathy

Weissler‐Snir

Hindieh

Gruner

et al. 2017

Circ: Cardiovascular Imaging

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H ypertrophic cardiomyopathy (HCM) is the most commonly inherited monogenic cardiac disease with an estimated prevalence of 1:500.1 HCM is inherited as an autosomal dominant trait with a variable expression and age-related penetrance.2,3 In ≈35% to 60% of cases, HCM is caused by mutations in genes encoding sarcomere proteins. 4,5 To date, >1400 mutations in >13 genes have been identified, with the MYH7 (β-myosin heavy chain) and MYBPC3 (myosin-binding protein C) most commonly affected, accounting for >70% of genotyped families. 2,6See Editorial by Tower-Rader and Desai See Clinical PerspectiveAlthough thin-filament disease seems to have distinct phenotypic features in terms of left ventricular (LV) hypertrophy (LVH), cardiac magnetic resonance (CMR) late gadolinium enhancement (LGE) distribution, and diastolic abnormalities, 7 findings on the phenotypic differences between patients with MYH7 and MYBPC3 gene mutations have been inconsistent.Background-The 2 most commonly affected genes in hypertrophic cardiomyopathy (HCM) are MYH7 (β-myosin heavy chain) and MYBPC3 (β-myosin-binding protein C). Phenotypic differences between patients with mutations in these 2 genes have been inconsistent. Scarce data exist on the genotype-phenotype association as assessed by tomographic imaging using cardiac magnetic resonance imaging. Methods and Results-Cardiac magnetic resonance imaging was performed on 358 consecutive genotyped hypertrophic cardiomyopathy probands at 5 tertiary hypertrophic cardiomyopathy centers. Genetic testing revealed a pathogenic mutation in 159 patients (44.4%). The most common genes identified were MYH7 (n=53) and MYBPC3 (n=75); 33.1% and 47% of genopositive patients, respectively. Phenotypic characteristics by cardiac magnetic resonance imaging of these 2 groups were similar, including left ventricular volumes, mass, maximal wall thickness, morphology, left atrial volume, and mitral valve leaflet lengths (all P=non-significant). The presence of late gadolinium enhancement (65% versus 64%; P=0.99) and the proportion of total left ventricular mass (%late gadolinium enhancement; 10.4±13.2% versus 8.5±8.5%; P=0.44) were also similar. Conclusions-This multicenter multinational study shows lack of phenotypic differences between MYH7-and MYBPC3-associated hypertrophic cardiomyopathy when assessed by cardiac magnetic resonance imaging. Postmutational mechanisms appear more relevant to thick-filament disease expression and outcome than the disease-causing variant per se. (Circ Cardiovasc Imaging. 2017;10:e005311.

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“…A retrospective study of 1293 patients demonstrated that LGE>15% of LV mass was associated with a 2-fold increase in SCD risk (8), suggesting that the amount of LGE rather than just its presence may be an important risk marker. LGE identifies replacement and interstitial fibrosis(9), but post-mortem analysis indicates that diffuse fibrosis is also present in other regions not identified by LGE. Recent advances in T1 mapping with CMR (10) have enabled validation of diffuse interstitial fibrosis measurements in HCM (11) and demonstration of increases, even in genotype (+), phenotype (−) patients(12).…”

Section: Introductionmentioning

confidence: 99%

Hypertrophic Cardiomyopathy Registry: The rationale and design of an international, observational study of hypertrophic cardiomyopathy

Kramer

Appelbaum

Desai

et al. 2015

American Heart Journal

128

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Hypertrophic cardiomyopathy (HCM) is the most common monogenic heart disease with a frequency as high as 1 in 200. In many cases, HCM is caused by mutations in genes encoding the different components of the sarcomere apparatus. HCM is characterized by unexplained left ventricular hypertrophy (LVH), myofibrillar disarray, and myocardial fibrosis. The phenotypic expression is quite variable. While the majority of patients with HCM are asymptomatic, serious consequences are experienced in a subset of affected individuals who present initially with sudden cardiac death (SCD) or progress to refractory heart failure (HF). The HCMR study is a National Heart Lung and Blood Institute (NHLBI)-sponsored 2750 patient, 41 site, international registry and natural history study designed to address limitations in extant evidence to improve prognostication in HCM (NCT01915615). In addition to collection of standard demographic, clinical, and echocardiographic variables, patients will undergo state-of-the-art cardiac magnetic resonance (CMR) for assessment of left ventricular (LV) mass and volumes as well as replacement scarring and interstitial fibrosis. In addition, genetic and biomarker analysis will be performed. HCMR has the potential to change the paradigm of risk stratification in HCM, using novel markers to identify those at higher risk.

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Myocardial Fibrosis in Hypertrophic Cardiomyopathy

Cited by 189 publications

References 30 publications

Quantitative assessment of myocardial fibrosis in an age-related rat model by ex vivo late gadolinium enhancement magnetic resonance imaging with histopathological correlation

Quantitative assessment of myocardial fibrosis in an age-related rat model by ex vivo late gadolinium enhancement magnetic resonance imaging with histopathological correlation

Lack of Phenotypic Differences by Cardiovascular Magnetic Resonance Imaging in MYH7 (β-Myosin Heavy Chain)- Versus MYBPC3 (Myosin-Binding Protein C)-Related Hypertrophic Cardiomyopathy

Hypertrophic Cardiomyopathy Registry: The rationale and design of an international, observational study of hypertrophic cardiomyopathy

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