Non-invasive measurement of myocardial extracellular volume using T1 mapping as a novel biomarker of diffuse fibrosis in dilated cardiomyopathy

The increasing use of cardiovascular magnetic resonance (CMR) is based on its capability to perform biventricular function assessment and tissue characterization without radiation and with high reproducibility. The use of late gadolinium enhancement (LGE) gave the potential of non-invasive biopsy for fibrosis quantification. However, LGE is unable to detect diffuse myocardial disease. Native T1 mapping and extracellular volume fraction (ECV) provide knowledge about pathologies affecting both the myocardium and interstitium that is otherwise difficult to identify. Changes of myocardial native T1 reflect cardiac diseases (acute coronary syndromes, infarction, myocarditis, and diffuse fibrosis, all with high T1) and systemic diseases such as cardiac amyloid (high T1), Anderson-Fabry disease (low T1), and siderosis (low T1). The ECV, an index generated by native and post-contrast T1 mapping, measures the cellular and extracellular interstitial matrix (ECM) compartments. This myocyte-ECM dichotomy has important implications for identifying specific therapeutic targets of great value for heart failure treatment. On the other hand, T2 mapping is superior compared with myocardial T1 and ECM for assessing the activity of myocarditis in recent-onset heart failure. Although these indices can significantly affect the clinical decision making, multicentre studies and a community-wide approach (including MRI vendors, funding, software, contrast agent manufacturers, and clinicians) are still missing.

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Relationship between cardiac magnetic resonance derived extracellular volume fraction and myocardial strain in patients with non-ischemic dilated cardiomyopathy

European Heart Journal ◽

10.1093/ehjci/ehaa946.0239 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

M Azuma ◽

S Kato ◽

S Kodama ◽

K Hayakawa ◽

M Kagimoto ◽

...

Keyword(s):

Magnetic Resonance ◽

Dilated Cardiomyopathy ◽

Myocardial Fibrosis ◽

Negative Correlation ◽

T1 Mapping ◽

Myocardial Strain ◽

Extracellular Volume ◽

P Values ◽

Chamber View ◽

Non Ischemic Dilated Cardiomyopathy

Abstract Background The feature tracking (FT) technique has been proposed as a robust method to evaluate the myocardial strain using conventional cine magnetic resonance imaging (MRI) of the left ventricle. Data is limited regarding the relationship between FT-derived myocardial strain and diffuse myocardial fibrosis evaluated by T1 mapping in patients with non-ischemic dilated cardiomyopathy (NIDCM). Purpose The aim of this study was to evaluate the correlation between extracellular volume (ECV) by T1 mapping and myocardial strain by FT in patients with NIDCM. Methods A total of sixty-four patients with NIDCM (62±12 years) and 15 controls (62±11 years) were studied. Using a 1.5T MR scanner, pre- and post- T1 mapping images of LV wall at mid-ventricular level was acquired to calculate ECV by modified Look-Locker inversion recovery (MOLLI) sequence. Radial strain (RS), circumferential strain (CS) and longitudinal strain (LS) was assessed by FT technique. ECV and myocardial strain were compared using a 6-segment model at mid-ventricular level. Results Compared to the controls, the NIDCM patients had a significantly higher ECV (0.30±0.02 vs. 0.24±0.01, p<0.001) and impaired myocardial strain (RS, 24.2±3.0 vs. 52.2±6.2, p<0.001; CS, −7.5±2.1 vs. −15.3±2.2, p<0.001; LS −10.4±3.5 vs. −20.2±4.7, p<0.001, respectively). Similar results were obtained when comparing all 6 myocardial segments (segment 7–12) (all p values <0.001). In a segment-based analysis, a significant positive correlation was found between the ECV and CS (r=0.26 to 0.41; all p values <0.05), a negative correlation was found between the ECV and RS (r=−0.31 to −0.41; all p values <0.05). In a patient-based analysis, there were significant positive correlations between the ECV and CS (r=0.45, p<0.001), ECV and LS from 2-chamber view (r=0.30, p=0.006), ECV and LS from 4-chamber view (r=0.37, p<0.001). There was a significant negative correlation between the ECV and RS (r=−0.43, p<0.001) (FIGURE) Conclusions In NIDCM patients, severity of myocardial fibrosis evaluated by T1 mapping is associated with impaired myocardial strain by FT technique. Correlation between the ECV and strain Funding Acknowledgement Type of funding source: None

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P1585 Cardiac magnetic resonance estimated extracellular volume fraction, but not native T1 mapping, detects scar in patients referred for cardiac resynchronization therapy

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jez319.1005 ◽

2020 ◽

Vol 21 (Supplement_1) ◽

Author(s):

C Kjellstad Larsen ◽

J Duchenne ◽

E Galli ◽

J M Aalen ◽

E Kongsgaard ◽

...

Keyword(s):

T1 Mapping ◽

Volume Fraction ◽

Extracellular Volume ◽

Extracellular Volume Fraction ◽

Cardiac Resynchronization ◽

Diffuse Fibrosis ◽

Resynchronization Therapy ◽

Native T1 ◽

T1 Relaxation ◽

Contrast Agent Injection

Abstract Funding Acknowledgements The study was supported by Center for Cardiological Innovation Background Myocardial scar burden (focal fibrosis) is associated with poor response to cardiac resynchronization therapy (CRT), and should preferably be detected prior to device implantation. Late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) is considered reference standard for scar detection, but is not available in renal failure. Diffuse fibrosis is assessed by T1 mapping CMR with or without calculation of extracellular volume fraction (ECV). The method is vulnerable to partial volume effects, thus subendocardial tissue is most often not included in mapping analyses. Whether the contrast-free native T1mapping could replace LGE in the preoperative evaluation of patients referred for CRT is unknown. Purpose To investigate if native T1 mapping and calculation of ECV can adequately detect scar in patients referred for CRT. Methods Scar was quantified as percentage segmental LGE in 45 patients (age 65 ± 10 years, 71% male, QRS-width 165 ± 17ms) referred for CRT. In total 720 segments were analyzed, and LGE≥50% was considered transmural scar. T1-mapping before and after contrast agent injection was performed in all patients. ECV was calculated based on the ratio between tissue T1 relaxation change and blood T1 relaxation change after contrast agent injection, corrected for the haematocrit level. The agreement between native T1/ECV and scar was evaluated with receiver operating characteristic (ROC) curves with calculation of area under the curve (AUC) and 95% confidence interval (CI). Results LGE was present in 255 segments, 465 segments were without LGE. Average native T1 in segments with LGE was 1028 ± 88 ms, and 1040 ± 60 ms in segments without LGE (p = 0.16). The corresponding numbers for ECV were 38.7 ± 10.9% and 30.0 ± 4.7%, p < 0.001. Native T1 showed poor agreement to scar independent of scar size (AUC = 0.532, 95% CI 0.485-0.578 for scars of all sizes, and AUC = 0.572, 95% CI 0.495-0.650 for transmural scars). ECV, on the other hand, showed reasonable agreement with scar of all sizes (AUC = 0.777, 95% CI 0.739-0.815), and good agreement with transmural scars (AUC = 0.856, 95% CI 0.811-0.902). (Figure) Conclusion The contrast-free CMR technique T1 mapping does not adequately detect scars in patients referred for CRT. Adding post contrast T1 measurements and calculating ECV improves accuracy, especially for transmural scars. Future studies should investigate if diffuse fibrosis could be predictive of CRT response. Abstract P1585 Figure. Detection of transmural scars

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Extracellular volume assessed by CMR T1-mapping correlates with histologically determined amount of diffuse fibrosis in DCM

Journal of Cardiovascular Magnetic Resonance ◽

10.1186/1532-429x-16-s1-m8 ◽

2014 ◽

Vol 16 (S1) ◽

Cited By ~ 1

Author(s):

Fabian aus dem Siepen ◽

Sebastian Buss ◽

Florian Andre ◽

Marius Keller ◽

Sebastian A Seitz ◽

...

Keyword(s):

T1 Mapping ◽

Extracellular Volume ◽

Diffuse Fibrosis

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Abstract 14783: Relationship Between Native Papillary Muscle T1 Time and Severity of Functional Mitral Regurgitation in Patients With Non-ischemic Dilated Cardiomyopathy

Circulation ◽

10.1161/circ.132.suppl_3.14783 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Shingo Kato ◽

Sébastien Roujol ◽

Francesca Delling ◽

Shadi Akhtari ◽

Jihye Jang ◽

...

Keyword(s):

Mitral Regurgitation ◽

Dilated Cardiomyopathy ◽

Papillary Muscle ◽

T1 Mapping ◽

Functional Mitral Regurgitation ◽

Diffuse Fibrosis ◽

Regurgitant Fraction ◽

Native T1 ◽

Non Ischemic Dilated Cardiomyopathy ◽

Native T1 Time

Introduction: Functional mitral regurgitation is one of the severe complications of non-ischemic dilated cardiomyopathy (DCM). Non-contrast native T1 mapping has emerged as a non-invasive method to evaluate myocardial fibrosis. Hypothesis: We hypothesized that papillary muscle native T1 time is correlated with severity of functional mitral regurgitation in DCM patients. Methods: Forty DCM patients (55±13 years) and 20 healthy adult control subjects (54±13 years) were studied. Native T1 mapping was performed using a slice interleaved T1 mapping sequence (STONE) which enables acquisition of 5 slices in the short-axis plane within a 90 sec free-breathing scan. We measured papillary muscle diameter, length and shortening. DCM patients were allocated into 2 groups based on the presence or absence of functional mitral regurgitation. Results: Papillary muscle T1 time was significantly elevated in DCM patients with mitral regurgitation (n=22) in comparison to those without mitral regurgitation (n=18) (anterior papillary muscle: 1127±36 msec vs 1063±16 msec, p<0.001; posterior papillary muscle: 1124±30 msec vs 1062±19 msec, p<0.001), but LV T1 time was similar (1129±38 msec vs 1134±58 msec, p=0.93). Multivariate linear regression analysis showed that papillary muscle native T1 time (β=0.109, 95%CI: 0.048-0.170, p=0.001) and tenting height (β=1.334, 95%CI: 0.434-2.234, p=0.005) are significantly correlated with mitral regurgitant fraction. Elevated papillary muscle T1 time was associated with larger diameter, longer length and decreased papillary muscle shortening (all p values <0.05). Conclusions: In DCM, papillary muscle native T1 time is significantly elevated and related to mitral regurgitant fraction. These results suggest that papillary muscle diffuse fibrosis might be associated with severity of mitral regurgitation in this population.

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Towards cardiac MRI based risk stratification in idiopathic dilated cardiomyopathy

Heart ◽

10.1136/heartjnl-2018-313767 ◽

2018 ◽

Vol 105 (4) ◽

pp. 270-275 ◽

Cited By ~ 7

Author(s):

Pamela Frances Brown ◽

Chris Miller ◽

Andrea Di Marco ◽

Matthias Schmitt

Keyword(s):

Risk Stratification ◽

Dilated Cardiomyopathy ◽

Cardiac Mri ◽

Randomised Trial ◽

Extracellular Volume ◽

Idiopathic Dilated Cardiomyopathy ◽

Diffuse Fibrosis ◽

Resource Utilisation ◽

Selection Strategy ◽

Gadolinium Contrast

Sudden cardiac death (SCD) secondary to arrhythmia remains a risk in those with dilated cardiomyopathy (DCM), an implantable cardiac defibrillator (ICD) is an effective strategy to prevent SCD. Current guidelines recommend selection for ICD based on ejection fraction (EF) less than 35%, however, most SCD occurs in those with EF>35%. Although meta-analysis has demonstrated a survival benefit for primary prevention ICD in DCM, no randomised trial has shown a significant reduction in overall mortality including the most recent ‘Danish Study to Assess the Efficacy of ICDs in Patients With Non-Ischemic Systolic Heat Failure on Mortality’ study. Clearly, a more sophisticated selection strategy is required. Cardiac MRI (CMR) is an ideal non-invasive imaging technique which allows calculation of EF as well as tissue characterisation with gadolinium contrast, parametric mapping and feature tracking. Late gadolinium enhancement detects mid-wall fibrosis in approximately 30% of those with DCM, three meta-analyses have demonstrated an association between fibrosis in DCM and SCD, and those without fibrosis are at low risk of SCD. T1 mapping and extracellular volume (ECV) calculation are methods of demonstrating diffuse fibrosis in the myocardium. Raised ECV and native T1 have been associated with worse outcomes but the relationship to SCD has not been well studied. Undoubtedly, more research is required but CMR has several tools which offer incremental value above EF to improve risk stratification and consequent outcomes and resource utilisation in those with DCM.

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FRI0236 FIRST PILOT STUDY OF T1 MAPPING MRI WITH ECV MEASUREMENT OF PERIPHERAL MUSCLE IN SYSTEMIC SCLEROSIS PATIENTS SHOWS DIFFUSE FIBROSIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.5724 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 702.2-702

Author(s):

R. B. Dumitru ◽

A. Goodall ◽

D. Broadbent ◽

A. Kidambi ◽

S. Plein ◽

...

Keyword(s):

Skeletal Muscle ◽

Systemic Sclerosis ◽

Pilot Study ◽

T1 Mapping ◽

Inflammatory Myopathy ◽

Extracellular Volume ◽

Diffuse Fibrosis ◽

Muscle Involvement ◽

Native T1 ◽

Peripheral Muscle

Background:Peripheral myositis in systemic sclerosis (SSc) is associated with poor prognosis and myocarditis1but non-inflammatory myopathy, which also represents a significant cause of disability in SSc remains poorly understood. Cardiovascular magnetic resonance (CMR) T1 mapping studies in asymptomatic SSc patients show increased extracellular volume (ECV), suggestive of diffuse fibrosis in both the myocardium and thoracic muscle2.Objectives:To evaluate the feasibility of T1 mapping MRI and determine ECV in peripheral muscle of SSc patients with and without myopathy and explore the association between cardiac and peripheral muscle T1 mapping in SSc.Methods:This was a hypothesis-generating pilot and feasibility study. SSc patients, fulfilling the 2013 ACR/EULAR criteria, with no cardiovascular disease or myositis but either minimal muscle symptoms (non-inflammatory myopathy) or no muscle involvement and healthy volunteers (HV) underwent peripheral muscle T1 mapping-MRI for native T1 and extracellular volume (ECV) quantification of the dominant thigh. Patients also had T1 mapping CMR, and creatine-kinase (CK) measured. Non-inflammatory myopathy was defined as current/history of minimally raised CK (<600 IU/l) +/- presence of clinical signs-symptoms (including proximal myasthenia and/or myalgia) +/- a Manual Muscle Testing (MMT) score <5 in the thighs.Results:12 SSc patients and 10 HV were recruited. SSc patients had a median (IQR) age of 52 (41,65) years, 9/12 had limited cutaneous SSc, 4/12 interstitial lung disease, 7/12 non-inflammatory myopathy. Higher skeletal muscle ECV was recorded in SSc patients compared to HV [mean (SD) 23(11)%, vs 11(4)% p=0.04]. Skeletal muscle native T1 values were comparable between the 2 groups although modestly higher in SSc patients [mean (SD) 1396ms (56) vs 1387ms (42)] (Figure 1A).Peripheral muscle ECV associated with CK (R2=0.307, rho=0.554, p=0.061) and was higher in SSc patients with evidence of myopathy compared to those with no myopathy [28 (10)% vs 15 (5)%, p=0.023] (Figure 1B). An ECV of 22% was determined to best identify myopathy with a sensitivity of 71% and a specificity of 80%.SSc patients had raised myocardial ECV and native T1 with means (SD) of 31 (3) % and 1287 (54) ms respectively (normal reference range ECV ≤29%, native T1 ≤1240ms). No clear association between myocardial and peripheral muscle ECV (rho=-0.485) or between myocardial ECV and peripheral muscle native T1 (rho=0.470) of SSc patients was observed.Conclusion:This pilot study to determine ECV-MRI of the peripheral muscle showed higher ECV in SSc patients compared to HV, suggesting the presence of diffuse fibrosis in the peripheral muscle of SSc patients. These data support further investigation to understand the pathophysiological involvement and relationship of peripheral and cardiac muscle in SSc.References:[1]Follansbee WP et al, Am Heart J. 1993[2]Barison A et al, Eur Heart J Cardiovasc Imaging. 2015Disclosure of Interests:Raluca-Bianca Dumitru: None declared, Alex Goodall: None declared, David Broadbent: None declared, Ananth Kidambi: None declared, Sven Plein: None declared, Francesco Del Galdo: None declared, Ai Lyn Tan: None declared, John Biglands: None declared, Maya H Buch Grant/research support from: Pfizer, Roche, and UCB, Consultant of: Pfizer; AbbVie; Eli Lilly; Gilead Sciences, Inc.; Merck-Serono; Sandoz; and Sanofi

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