MR extracellular volume mapping and non-contrast T1ρ mapping allow early detection of myocardial fibrosis in diabetic monkeys

Abstract Introduction Heart failure with preserved ejection fraction (HFpEF) represents a major challenge in modern cardiology. As described previously, in HFpEF comorbidities promote a systemic inflammatory state, leading to diffuse myocardial fibrosis resulting in myocardial stiffening. Gut dysbiosis which is considered as the novel source of chronic systemic inflammation has been actively investigated as the risk factor for the development and aggravation of cardiovascular diseases including heart failure. Cardiac magnetic resonance T1-mapping is a novel tool, which allows noninvasive quantification of the extracellular space and diffuse myocardial fibrosis. Moreover, the extracellular volume (ECV) fraction can be calculated, providing information on the relative expansion of the extracellular matrix, thus being a noninvasive alternative to myocardial biopsy studies. Purpose The research was aimed at investigating the correlation between the left ventricular ECV and gut microbial genera in patients with HFpEF. Methods 42 patients with confirmed HF-pEF (mediana and interquartile range of age 67 [64; 72] years, 47% men, body mass index <35 kg/m2 with no history of myocardial infarction or diabetes mellitus) were enrolled in the study. The patients underwent transthoracic echocardiography with Doppler study, HF-pEF was confirmed according to the recent ESC guidelines (based on E/e' ratio, N-terminal pro-B type natriuretic peptide >125 pg/ml and symptoms of heart failure). The intestinal microbiome was investigated using high-throughput sequencing of bacterial 16S rRNA gene. As the last step of research T1-myocardial mapping with the modified look-locker inversion-recovery protocol (MOLLI) sequence at 1.5 Tesla was performed to assess left ventricular extracellular volume fraction. Results The mean±std in ECV was 31.02±4.4%. The relative abundance (%) of the most prevalent phyla in gut microbiota was 48±22.5 for Firmicutes, 47.4±22.8 for Bacteroidetes and 1.5 [1.5; 2.5] for Proteobacteria. The analysis showed significant negative correlations between ECV and the following bacterial genera: Faecalibacterium (r=−0.35), Blautia (r=−0.43), Lachnoclostridium (r=−0.32). Moreover ECV positively correlated with Holdemania (r=0.4), Victivallis (r=0.38), Dehalobacterium (r=0.38), Enterococcus (r=0.33) and Catabacter (r=0.32). All correlation values with p<0.05. Conclusion We discovered both negative and positive significant correlations between ECV – the non-invasive marker of myocardial fibrosis and several bacterial genera, which may have negative impact on myocardial remodeling in HF-pEF. Funding Acknowledgement Type of funding source: None

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Proteoglycan remodeling is accelerated in women with angina pectoris and diffuse myocardial fibrosis: the iPOWER Study

European Heart Journal ◽

10.1093/ehjci/ehaa946.1280 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

N.D Mygind ◽

S Holm Nielsen ◽

M Mide Michelsen ◽

A Pena ◽

D Bechsgaard Frestad ◽

...

Keyword(s):

Cardiac Magnetic Resonance ◽

Magnetic Resonance ◽

Angina Pectoris ◽

Myocardial Fibrosis ◽

T1 Mapping ◽

Obstructive Coronary Artery Disease ◽

Extracellular Volume ◽

Diffuse Myocardial Fibrosis ◽

Public Institution ◽

Funding Source

Abstract Background Women with angina and no obstructive coronary artery disease (CAD) have an unfavourable prognosis, possibly due to coronary microvascular disease and diffuse myocardial fibrosis (DMF). In DMF myocardial extracellular matrix (ECM) proteins are actively remodeled by matrix metalloproteinase (MMP). Purpose We investigated MMP-mediated degradation of the protegoglycans biglycan and versican in women with angina pectoris and possible DMF assessed by cardiac magnetic resonance T1 mapping. Methods Seventy-one women with angina pectoris and no obstructive CAD were included. Asymptomatic age-matched women served as controls (n=32). Versican and biglycan were measured in serum by specific competitive enzyme-linked immunosorbent assays. T1 mapping was performed by cardiac magnetic resonance with gadolinium measuring T1 and extracellular volume (ECV). Results Both biglycan and versican levels were higher in symptomatic women compared with controls; 31.4 ng/mL vs. 16.4 ng/mL (p<0.001) and 2.1 ng/mL vs. 1.8 ng/mL (p<0.001), respectively (Figure 1) and were moderately correlated to global ECV (r2=0.38, p<0.001 and r2=0.26, p=0.015 respectively). Conclusion Turnover of biglycan and versican was increased in symptomatic compared to asymptomatic women and associated to ECV, supporting a link between angina with no obstructive CAD and fibrotic cardiac remodeling. The examined biomarkers may prove to be suitable for monitoring active ECM remodeling. Figure 1. Levels of BGM and VCANM Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): This work was supported by The Danish Heart Foundation, the Danish Research Fund (Den Danske Forskningsfond) and by University of Copenhagen.

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Abstract 18139: Myocardial Fibrosis Quantified by Cardiovascular Magnetic Resonance is Associated with Histology and Graft Function After Pediatric Heart Transplantation

Circulation ◽

10.1161/circ.130.suppl_2.18139 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Brian Feingold ◽

Cláudia M Salgado ◽

Miguel Reyes-Múgica ◽

Stacey Drant ◽

Susan A Miller ◽

...

Keyword(s):

Cardiovascular Magnetic Resonance ◽

Magnetic Resonance ◽

Heart Transplantation ◽

Myocardial Fibrosis ◽

Graft Failure ◽

Extracellular Volume ◽

Graft Function ◽

Automated Image Analysis ◽

Graft Dysfunction ◽

Pediatric Heart Transplantation

Background: Late survival after pediatric heart transplantation (HTx) remains poor. Many late deaths are due to “graft failure,” typically in the presence of vasculopathy and diffuse myocardial fibrosis (DMF) - a process associated with ventricular remodeling and heart failure (HF). Cardiovascular magnetic resonance (CMR)-derived extracellular volume (ECV) is a validated measure of DMF in the absence of edema or infiltrative disease, and predicts outcomes of HF and mortality in adults. We hypothesize that ECV is a meaningful biomarker of graft dysfunction following pediatric HTx. Objective: To test the association of ECV with histologic myocardial fibrosis after pediatric HTx. We also explored associations of ECV with hemodynamic, echocardiographic, and serum measures of graft function. Methods: We prospectively enrolled consecutive HTx recipients who were ≥13 years old and ≥9 months post HTx for ECV quantification at the time of surveillance endomyocardial biopsy (EMB). Fibrosis was quantified on EMB by automated image analysis after picrosirius staining and digital scanning. CMR measures of blood and myocardial T1 from basal and mid short axis slices, along with contemporaneous hematocrit, quantified ECV. Results: Nineteen pts (12 male) underwent CMR at a mean age of 18.4 ± 2.8 yrs (range 14.9 - 24.4 yrs) and a mean time after HTx of 10.4 ± 6.6 yrs (1.0 - 20.7 yrs). Four pts were excluded from analysis due to acute rejection (ISHLT grade ≥2R) on concurrent EMB (n=2) or poor quality imaging (n=2). Mean ECV was 27.1 ± 3.8 (20.9 - 32.1). Late gadolinium enhancement was observed in 1 pt. ECV showed moderate correlations with histologic myocardial fibrosis (r=0.61; p=0.02) and serum b-type natriuretic peptide (r=0.66; p=0.008). There was a trend to correlation with pulmonary capillary wedge pressure (r=0.51; p=0.06). We found no associations of ECV with systolic or diastolic function, time after HTx, or graft age. Conclusions: We demonstrate a novel association of ECV with histologic myocardial fibrosis and serum and hemodynamic markers of HF after pediatric HTx. Given prior observations of myocardial fibrosis in chronic graft failure, these findings suggest that ECV may be a relevant, noninvasive marker of graft dysfunction and a potential therapeutic target.

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Quantification of diffuse myocardial fibrosis using CMR extracellular volume fraction and serum biomarkers of collagen turnover with histologic quantification as standard of reference

Diagnostic and Interventional Imaging ◽

10.1016/j.diii.2020.07.005 ◽

2020 ◽

Author(s):

C. Foussier ◽

P.A. Barral ◽

M. Jerosh-Herold ◽

V. Gariboldi ◽

S. Rapacchi ◽

...

Keyword(s):

Myocardial Fibrosis ◽

Volume Fraction ◽

Extracellular Volume ◽

Extracellular Volume Fraction ◽

Serum Biomarkers ◽

Diffuse Myocardial Fibrosis ◽

Collagen Turnover

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Erratum

Acta Radiologica ◽

10.1177/0284185117723281 ◽

2017 ◽

Vol 59 (6) ◽

pp. NP11-NP11

Keyword(s):

Systemic Lupus Erythematosus ◽

Diffusion Coefficient ◽

Apparent Diffusion Coefficient ◽

Myocardial Fibrosis ◽

Lupus Erythematosus ◽

Extracellular Volume ◽

Strongly Correlated ◽

Systemic Lupus ◽

Apparent Diffusion

Wu R, An DA, Hu J, et al. The apparent diffusion coefficient is strongly correlated with extracellular volume, a measure of myocardial fibrosis, and subclinical cardiomyopathy in patients with systemic lupus erythematosus. Acta Radiol 2017. DOI: 10.1177/0284185117717763. In the above-referenced article, the corresponding author was wrongly listed as “Lian-Ming Wu” in the initial OnlineFirst version. The online and print versions have been updated to reflect the correct corresponding author, “Jian-Rong Xu.”

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Accelerated collagen turnover in women with angina pectoris without obstructive coronary artery disease: An iPOWER substudy

European Journal of Preventive Cardiology ◽

10.1177/2047487318758750 ◽

2018 ◽

Vol 25 (7) ◽

pp. 719-727 ◽

Cited By ~ 7

Author(s):

Signe H Nielsen ◽

Naja D Mygind ◽

Marie M Michelsen ◽

Daria F Bechsgaard ◽

Hannah E Suhrs ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Angina Pectoris ◽

Myocardial Fibrosis ◽

Volume Fraction ◽

Extracellular Volume ◽

Diffuse Myocardial Fibrosis ◽

Collagen Turnover ◽

Collagen Formation ◽

Artery Disease

Aim Collagens are major cardiac extracellular matrix components, known to be actively remodelled and accumulated during diffuse myocardial fibrosis. We evaluated whether accelerated collagen turnover described by neo-epitope biomarkers reflecting collagen formation and degradation separates patients with diffuse myocardial fibrosis from asymptomatic controls. Methods and results Seventy-one women with angina pectoris without significant coronary artery disease assessed by invasive coronary angiogram were included. Competitive enzyme-linked immunosorbent assays (ELISAs) measuring circulating protein fragments in serum assessed the formation and degradation of collagen type III (Pro-C3, C3M and C3C), IV (P4NP7S and C4M), V (Pro-C5 and C5M) and VI (Pro-C6 and C6M), and degradation of collagen type I (C1M). Serum samples from 32 age-matched asymptomatic women were included as controls. Symptomatic women presented significantly elevated levels of Pro-C6, C3C, C3M, C4M and C8-C ( p < 0.0001–0.0058) and significantly decreased levels of Pro-C3, C5M and C6M ( p < 0.0001–0.041), reflecting accelerated collagen turnover and an imbalanced collagen formation and degradation compared to controls. Cardiac magnetic resonance T1 mapping was performed to determine extracellular volume fraction and thus diffuse myocardial fibrosis. A significant association was identified between C5M and extracellular volume fraction by cardiac magnetic resonance ( p = 0.01). Conclusion Women with angina pectoris, but without significant obstructive coronary artery disease, showed an imbalanced collagen turnover compared to asymptomatic controls. The examined biomarkers are tools to monitor active collagen remodelling in patients with angina pectoris, in risk of developing myocardial fibrosis.

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RETRACTED ARTICLE: Prognostic value of heart failure in hemodialysis-dependent end-stage renal disease patients with myocardial fibrosis quantification by extracellular volume on cardiac magnetic resonance imaging

BMC Cardiovascular Disorders ◽

10.1186/s12872-019-01313-2 ◽

2020 ◽

Vol 20 (1) ◽

Cited By ~ 3

Author(s):

Hua-yan Xu ◽

Zhi-gang Yang ◽

Yi Zhang ◽

Wan-lin Peng ◽

Chun-chao Xia ◽

...

Keyword(s):

Heart Failure ◽

Myocardial Fibrosis ◽

Prognostic Value ◽

T1 Mapping ◽

Extracellular Volume ◽

Cardiac Events ◽

Native T1 ◽

Stage Renal Disease ◽

End Stage ◽

Esrd Patients

Abstract Background End-stage renal disease (ESRD) patients are at high cardiovascular risk, and myocardial fibrosis (MF) accounts for most of their cardiac events. The purpose of this study is to investigate the prognostic value and risk stratification of MF as measured by extracellular volume (ECV) on cardiac magnetic resonance (CMR) for heart failure (HF) in patients with hemodialysis-dependent ESRD. Methods Sixty-six hemodialysis ESRD patients and 25 matched healthy volunteers were prospectively enrolled and underwent CMR to quantify multiple parameters of MF by T1 mapping and late gadolinium enhancement (LGE). All ESRD patients were followed up for 11–30 months, and the end-point met the 2016 ESC guidelines for the definition of HF. Results Over a median follow-up of 18 months (range 11–30 months), there were 26 (39.39%) guideline-diagnosed HF patients in the entire cohort of ESRD subjects. The native T1 value was elongated, and ECV was enlarged in the HF cohort relative to the non-HF cohort and normal controls (native T1, 1360.10 ± 50.14 ms, 1319.39 ± 55.44 ms and 1276.35 ± 56.56 ms; ECV, 35.42 ± 4.42%, 31.85 ± 3.01% and 26.97 ± 1.87%; all p<0.05). In the cardiac strain analysis, ECV was significantly correlated with global radial strain (GRS) (r = − 0.501, p = 0.009), global circumferential strain (GCS) (r = 0.553, p = 0.005) and global longitudinal strain (GLS) (r = 0.507, p = 0.008) in ESRD patients with HF. Cox proportional hazard regression models revealed that ECV (hazard ratio [HR] = 1.160, 95% confidence interval: 1.022 to 1.318, p = 0.022) was the only independent predictor of HF in ESRD patients. It also had a higher diagnostic accuracy for detecting MF (area under the curve [AUC] = 0.936; 95% confidence interval: 0.864 to 0.976) than native T1 and post T1 (all p ≤ 0.002). Kaplan-Meier analysis revealed that the high-ECV group had a shorter median overall survival time than the low-ECV group (18 months vs. 20 months, log-rank p = 0.046) and that ESRD patients with high ECV were more likely to have HF. Conclusions Myocardial fibrosis quantification by ECV on CMR T1 mapping was shown to be an independent risk factor of heart failure, providing incremental prognostic value and risk stratification for cardiac events in ESRD patients. Trial registration Chinese Clinical Trial Registry ChiCTR-DND-17012976, 13/12/2017, Retrospectively registered.

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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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