First pilot study of extracellular volume MRI measurement in peripheral muscle of systemic sclerosis patients suggests diffuse fibrosis.

OBJECTIVES: Peripheral muscle involvement in SSc may comprise myositis or a non-inflammatory myopathy. There is little understanding of the nature of SSc myopathy. This pilot study aimed to evaluate the presence of diffuse fibrosis in the peripheral muscle of patients with SSc by determining extracellular volume (ECV) MRI measurement. METHODS: SSc patients, with either suspected myopathy or no muscle involvement, and healthy controls (HCs) had native T1 and ECV MRI quantification of the thigh and creatine-kinase (CK) measured. Suspected myopathy was defined as current / history of minimally raised CK (>320; <600 IU/l) ± presence of clinical signs/symptoms (including proximal lower-limb muscle weakness and/or myalgia) ± a Manual Muscle Testing (MMT) 8 score of <5 in the thighs. RESULTS: Twelve SSc patients and 10 HCs were recruited. Of the 12 patients, 9 had limited cutaneous SSc, 4 had interstitial lung disease, and 7 had suspected myopathy. The higher skeletal muscle ECV was recorded for SSc patients compared with HCs [mean (s.d.) 23 (11)%, vs 11 (4)%, P = 0.04]. Peripheral muscle ECV was associated with CK (rho = 0.554, P = 0.061) and was higher in SSc patients with myopathy than in those with no myopathy [mean (s.d.) 28 (10) vs 15 (5), P = 0.023]. It was determined that an ECV of 22% best identified myopathy (with a sensitivity of 71% and a specificity of 80%). CONCLUSION: This hypothesis-generating study showed higher ECV in SSc patients compared with HCs, as well as association of ECV with suspected myopathy, suggesting the presence of diffuse fibrosis in the peripheral muscle of SSc patients. Further studies are needed to understand the nature of SSc myopathy.

Arrhythmia in hypertrophic cardiomyopathy: Risk prediction using contrast enhanced MRI, T1 mapping, and personalized virtual heart technology.

BACKGROUND: Hypertrophic cardiomyopathy (HCM), a disease with myocardial fibrosis manifestation, is a common cause of sudden cardiac death (SCD) due to ventricular arrhythmias (VA). Current clinical risk stratification criteria are inadequate in identifying patients who are at risk for VA and in need of an implantable cardioverter defibrillator (ICD) for primary prevention. OBJECTIVE: We aimed to develop a risk prediction approach based on imaging biomarkers from the combination of late gadolinium contrast-enhanced (LGE) MRI and T1 mapping. We then aimed to compare the prediction to a virtual heart computational risk assessment approach based on LGE-T1 virtual heart models. METHODS: The methodology involved combining short-axis LGE-MRI with post-contrast T1 maps to define personalized thresholds for diffuse and dense fibrosis. The combined LGE-T1 maps were used to evaluate imaging biomarkers for VA risk prediction. The risk prediction capability of the biomarkers was compared with that of the LGE-T1 virtual heart arrhythmia inducibility simulation. VA risk prediction performance from both approaches was compared to clinical outcome (presence of clinical VA). RESULTS: Image-based biomarkers, including hypertrophy, signal intensity heterogeneity, and fibrotic border complexity, could not discriminate high vs low VA risk. LGE-T1 virtual heart technology outperformed all the image-based biomarker metrics and was statistically significant in predicting VA risk in HCM. CONCLUSIONS: We combined two MR imaging techniques to analyze imaging biomarkers in HCM. Raw and processed image-based biomarkers cannot discriminate patients with VA from those without VA. Hybrid LGE-T1 virtual heart models could correctly predict VA risk for this cohort and may improve SCD risk stratification to better identify HCM patients for primary preventative ICD implantation.

Comparative study on native T1 value of myocardium between using ConSept and SAX approaches in non-ischemic dilated cardiomyopathy. / ConSept法和SAXæ³•æµ‹é‡éžç¼ºè¡€æ€§æ‰©å¼ åž‹å¿ƒè‚Œç— å¿ƒè‚Œåˆå§‹T1值的对比分析.

OBJECTIVES: T1 mapping can noninvasively quantify the native longitudinal relaxation time (T1 value) of myocardium and provide more information on myocardial fibrosis based on late gadolinium enhancement (LGE). However, the traditional approach of measuring T1 value limits the popularization and application of this technology in clinic because the whole short axis (SAX) of myocardium is required in the regions of interest (ROI). This study aims to evaluate the diagnostic ability of native T1 value obtained by comparison between the midventricular septum (ConSept) and SAX approaches in diffuse myocardial lesions. METHODS: Retrospective analysis was performed on 38 patients with non-ischemic dilated cardiomyopathy (NIDCM) and 27 healthy controls who underwent T1 mapping and gadolinium delayed enhancement (LGE) scanning on a 3.0T cardiac magnetic resonance (CMR) in Xiangya Hospital of Central South University. Patients with NIDCM were divided into a LGE positive group and a LGE negative group according to the presence or absence of LGE. The native T1 value was measured by the ROI placed in the ConSept and SAX, respectively. The ability to distinguish the impaired myocardium from the healthy myocardium and the native T1 values of the myocardium measured by the 2 approaches were compared between the NIDCM group and the control group. RESULTS: The native T1 values of NIDCM group using ConSept or SAX approach were significantly higher than those in the control group (all P<0.001), and the native T1 values in the LGE positive group were greater than those in the LGE negative group (all P<0.05). There was no significant difference in T1 value of middle, basal, and apical layer between the ConSept approach and SAX approach (all P>0.05). ConSept and SAX approaches had a good consistency [concordance correlation coefficient (CCC)=0.954]. CONCLUSIONS: Comparing to the SAX approach, ConSept approach is a simple and equivalent method to measure the native T1 value of myocardium and is suitable for clinical application.

Phenotyping diabetic cardiomyopathy in Europeans and South Asians.

BACKGROUND: The pathogenesis and cardiovascular impact of type 2 diabetes (T2D) may be different in South Asians compared with other ethnic groups. The phenotypic characterization of diabetic cardiomyopathy remains debated and little is known regarding differences in T2D-related cardiovascular remodeling across ethnicities. We aimed to characterize the differences in left ventricular (LV) diastolic and systolic function, LV structure, myocardial tissue characteristics and aortic stiffness between T2D patients and controls and to assess the differences in T2D-related cardiovascular remodeling between South Asians and Europeans. METHODS: T2D patients and controls of South Asian and European descent underwent 3 Tesla cardiovascular magnetic resonance imaging (CMR) and cardiac proton-magnetic resonance spectroscopy (1H-MRS). Differences in cardiovascular parameters between T2D patients and controls were examined using ANCOVA and were reported as mean (95% CI). Ethnic group comparisons in the association of T2D with cardiovascular remodeling were made by adding the interaction term between ethnicity and diabetes status to the model. RESULTS: A total of 131 individuals were included (54 South Asians [50.1 ± 8.7 years, 33% men, 33 patients vs. 21 controls) and 77 Europeans (58.8 ± 7.0 years, 56% men, 48 patients vs. 29 controls)]. The ratio of the transmitral early and late peak filling rate (E/A) was lower in T2D patients compared with controls, in South Asians [- 0.20 (- 0.36; - 0.03), P = 0.021] and Europeans [- 0.20 (- 0.36; - 0.04), P = 0.017], whereas global longitudinal strain and aortic pulse wave velocity were similar. South Asian T2D patients had a higher LV mass [+ 22 g (15; 30), P < 0.001] (P for interaction by ethnicity = 0.005) with a lower extracellular volume fraction [- 1.9% (- 3.4; - 0.4), P = 0.013] (P for interaction = 0.114), whilst European T2D patients had a higher myocardial triglyceride content [+ 0.59% (0.35; 0.84), P = 0.001] (P for interaction = 0.002) than their control group. CONCLUSIONS: Diabetic cardiomyopathy was characterized by impaired LV diastolic function in South Asians and Europeans. Increased LV mass was solely observed among South Asian T2D patients, whereas differences in myocardial triglyceride content between T2D patients and controls were only present in the European cohort. The diabetic cardiomyopathy phenotype may differ between subsets of T2D patients, for example across ethnicities, and tailored strategies for T2D management may be required.

Accurate, precise, simultaneous myocardial T1 and T2 mapping using a radial sequence with inversion recovery and T2 preparation.

We propose a simultaneous myocardial T1 and T2 mapping technique using a radial sequence with inversion recovery and T2 preparation, which achieves high accuracy and precision, with T1 and T2 reproducibility similar to the Modified Look-Locker Inversion recovery (MOLLI) sequence and the conventional bright blood T2 mapping technique, respectively. The sequence was developed by incorporating gold angle radial fast low angle shot (FLASH) readout combined with an inversion pulse and T2prep pulses. The extended Bloch equation simulation with slice profile correction (BLESSPC) algorithm was proposed to reconstruct T1 and T2 maps at the same time in a few seconds, while maintaining good T1 and T2 estimation accuracy. Accuracy and precision were compared among the proposed technique, MOLLI and conventional T2 mapping techniques using phantom studies, 10 healthy volunteers and three patients. In phantom studies, the proposed technique was more accurate than MOLLI (P < 0.05) while achieving similar precision (P = 0.3) in T1 estimation, and was more accurate (P < 0.05) and precise (P < 0.001) than conventional T2 mapping (two-parameter fitting) in T2 estimation. In vivo, the proposed technique achieved significantly higher T1 values (P < 0.001) and similar reproducibility (P = 0.3) compared with MOLLI, with significantly lower T2 values (P < 0.001) and similar reproducibility (P = 0.6) compared with the conventional T2 mapping technique. Thus, the proposed radial T1-T2 mapping technique allows for accurate, precise, simultaneous myocardial T1 and T2 mapping in an 11-heartbeat single breath-hold acquisition.

Late effects of pediatric hematopoietic stem cell transplantation on left ventricular function, aortic stiffness and myocardial tissue characteristics.

BACKGROUND: Pediatric hematopoietic stem cell transplantation (HSCT) recipients are at increased risk of cardiovascular disease later in life. As HSCT survival has significantly improved, with a growing number of HSCT indications, tailored screening strategies for HSCT-related late effects are warranted. Little is known regarding the value of cardiovascular magnetic resonance (CMR) for early identification of high-risk patients after HSCT, before symptomatic cardiovascular disease manifests. This study aimed to assess CMR-derived left ventricular (LV) systolic and diastolic function, aortic stiffness and myocardial tissue characteristics in young adults who received HSCT during childhood. METHODS: Sixteen patients (22.1 ± 1.5 years) treated with HSCT during childhood and 16 healthy controls (22.1 ± 1.8 years) underwent 3 T CMR. LV systolic and diastolic function were measured as LV ejection fraction (LVEF), the ratio of transmitral early and late peak filling rate (E/A), the estimated LV filling pressure (E/Ea) and global longitudinal and circumferential systolic strain and diastolic strain rates, using balanced steady-state free precession cine CMR and 2D velocity-encoded CMR over the mitral valve. Aortic stiffness, myocardial fibrosis and steatosis were assessed with 2D velocity-encoded CMR, native T1 mapping and proton CMR spectroscopy (1H-CMRS), respectively. RESULTS: In the patient compared to the control group, E/Ea (9.92 ± 3.42 vs. 7.24 ± 2.29, P = 0.004) was higher, LVEF (54 ± 6% vs. 58 ± 5%, P = 0.055) and global longitudinal strain (GLS) ( -20.7 ± 3.5% vs. -22.9 ± 3.0%, P = 0.063) tended to be lower, while aortic pulse wave velocity (4.40 ± 0.26 vs. 4.29 ± 0.29 m/s, P = 0.29), native T1 (1211 ± 36 vs. 1227 ± 28 ms, P = 0.16) and myocardial triglyceride content (0.47 ± 0.18 vs. 0.50 ± 0.13%, P = 0.202) were comparable. There were no differences between patients and controls in E/A (2.76 ± 0.92 vs. 2.97 ± 0.91, P = 0.60) and diastolic strain rates. CONCLUSION: In young adults who received HSCT during childhood, LV diastolic function was decreased (higher estimated LV filling pressure) and LV systolic function (LVEF and GLS) tended to be reduced as compared to healthy controls, whereas no concomitant differences were found in aortic stiffness and myocardial tissue characteristics. When using CMR, assessment of LV diastolic function in particular is important for early detection of patients at risk of HSCT-related cardiovascular disease, which may warrant closer surveillance.

Native T1 reference values for nonischemic cardiomyopathies and populations with increased cardiovascular risk: A systematic review and meta-analysis.

BACKGROUND: Although cardiac MR and T1 mapping are increasingly used to diagnose diffuse fibrosis based cardiac diseases, studies reporting T1 values in healthy and diseased myocardium, particular in nonischemic cardiomyopathies (NICM) and populations with increased cardiovascular risk, seem contradictory. PURPOSE: To determine the range of native myocardial T1 value ranges in patients with NICM and populations with increased cardiovascular risk. STUDY TYPE: Systemic review and meta-analysis. POPULATION: Patients with NICM, including hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM), and patients with myocarditis (MC), iron overload, amyloidosis, Fabry disease, and populations with hypertension (HT), diabetes mellitus (DM), and obesity. FIELD STRENGTH/SEQUENCE: (Shortened) modified Look-Locker inversion-recovery MR sequence at 1.5 or 3T. ASSESSMENT: PubMed and Embase were searched following the PRISMA guidelines. STATISTICAL TESTS: The summary of standard mean difference (SMD) between the diseased and a healthy control populations was generated using a random-effects model in combination with meta-regression analysis. RESULTS: The SMD for HCM, DCM, and MC patients were significantly increased (1.41, 1.48, and 1.96, respectively, P < 0.01) compared with healthy controls. The SMD for HT patients with and without left-ventricle hypertrophy (LVH) together was significantly increased (0.19, P = 0.04), while for HT patients without LVH the SMD was zero (0.03, P = 0.52). The number of studies on amyloidosis, iron overload, Fabry disease, and HT patients with LVH did not meet the requirement to perform a meta-analysis. However, most studies reported a significantly increased T1 for amyloidosis and HT patients with LVH and a significant decreased T1 for iron overload and Fabry disease patients. DATA CONCLUSIONS: Native T1 mapping by using an (Sh)MOLLI sequence can potentially assess myocardial changes in HCM, DCM, MC, iron overload, amyloidosis, and Fabry disease compared to controls. In addition, it can help to diagnose left-ventricular remodeling in HT patients. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:891-912.

Cardiac magnetic resonance T1 and extracellular volume mapping with motion correction and co-registration based on fast elastic image registration.

OBJECTIVE: Our aim was to investigate the technical feasibility of a novel motion compensation method for cardiac magntic resonance (MR) T1 and extracellular volume fraction (ECV) mapping. MATERIALS AND METHODS: Native and post-contrast T1 maps were obtained using modified look-locker inversion recovery (MOLLI) pulse sequences with acquisition scheme defined in seconds. A nonrigid, nonparametric, fast elastic registration method was applied to generate motion-corrected T1 maps and subsequently ECV maps. Qualitative rating was performed based on T1 fitting-error maps and overlay images. Local deformation vector fields were produced for quantitative assessment. Intra- and inter-observer reproducibility were compared with and without motion compensation. RESULTS: Eighty-two T1 and 39 ECV maps were obtained in 21 patients with diverse myocardial diseases. Approximately 60% demonstrated clear quality improvement after motion correction for T1 mapping, particularly for the poor-rating cases (23% before vs 2% after). Approximately 67% showed further improvement with co-registration in ECV mapping. Although T1 and ECV values were not clinically significantly different before and after motion compensation, there was improved intra- and inter-observer reproducibility after motion compensation. CONCLUSIONS: Automated motion correction and co-registration improved the qualitative assessment and reproducibility of cardiac MR T1 and ECV measurements, allowing for more reliable ECV mapping.

Joint myocardial T1 and T2 mapping using a combination of saturation recovery and T2 -preparation.

PURPOSE: To develop a heart-rate independent breath-held joint T1 -T2 mapping sequence for accurate simultaneous estimation of coregistered myocardial T1 and T2 maps. METHODS: A novel preparation scheme combining both a saturation pulse and T2 -preparation in a single R-R interval is introduced. The time between these two pulses, as well as the duration of the T2 -preparation is varied in each heartbeat, acquiring images with different T1 and T2 weightings, and no magnetization dependence on previous images. Inherently coregistered T1 and T2 maps are calculated from these images. Phantom imaging is performed to compare the proposed maps with spin echo references. In vivo imaging is performed in ten subjects, comparing the accuracy and precision of the proposed technique to existing myocardial T1 and T2 mapping sequences of the same duration. RESULTS: Phantom experiments show that the proposed technique provides accurate quantification of T1 and T2 values over a wide-range (T1 : 260 ms to 1460 ms, T2 : 40 ms to 200 ms). In vivo imaging shows that the proposed sequence quantifies T1 and T2 values similar to a saturation-based T1 mapping and a conventional breath-hold T2 mapping sequence, respectively. CONCLUSION: The proposed sequence allows joint estimation of accurate and coregistered quantitative myocardial T1 and T2 maps in a single breath-hold. Magn Reson Med 76:888-896, 2016. © 2015 Wiley Periodicals, Inc.

Increased left ventricular myocardial extracellular volume is associated with longer cardiopulmonary bypass times, biventricular enlargement and reduced exercise tolerance in children after repair of Tetralogy of Fallot.

BACKGROUND: Unfavorable left ventricular (LV) remodelling may be associated with adverse outcomes after Tetralogy of Fallot (TOF) repair. We sought to assess T1 cardiovascular magnetic resonance (CMR) markers of diffuse LV myocardial fibrosis in children after TOF repair, and associated factors. METHODS: In this prospective, cross-sectional study, native (=non-contrast) T1 times and extracellular volume fraction (ECV) were quantified in the LV myocardium using CMR. Results were related to ventricular volumes and function, degree of pulmonary regurgitation, as well as surgical characteristics, and exercise capacity. RESULTS: There was no difference in native T1 times or ECV between 31 TOF patients (age at CMR 13.9 ± 2.4 years, 19 male) and 15 controls (age at CMR 13.4 ± 2.6 years, 7 male). Female TOF patients had higher ECVs than males (25.2 ± 2.9 % versus 22.7 ± 3.3 %, p < 0.05). In the patient group, higher native T1 and ECV correlated with higher Z-Scores of right and left ventricular end-diastolic volumes, but not with reduced left and right ventricular ejection fraction or higher pulmonary regurgitation fraction. Longer cardiopulmonary bypass and aortic cross clamp times at surgery correlated with increased native T1 times and ECVs (r = 0.48, p < 0.05 and r = 0.65, p < 0.01, respectively). Maximum workload (percent of predicted for normal) correlated inversely with ECV (r = -0.62, p < 0.05). Higher native T1 times correlated with worse LV longitudinal (r = 0.50, p < 0.05) and mid short axis circumferential strain (r = 0.38, p < 0.05). CONCLUSIONS: As compared to controls, TOF patients did not express higher markers of diffuse fibrosis. Longer cardiopulmonary bypass and aortic cross clamp times at surgery as well as biventricular enlargement and reduced exercise tolerance are associated with markers of diffuse myocardial fibrosis after TOF repair. Female patients have higher markers of diffuse myocardial fibrosis than males.

Coronary microvascular function and myocardial fibrosis in women with angina pectoris and no obstructive coronary artery disease: the iPOWER study.

BACKGROUND: Even in absence of obstructive coronary artery disease women with angina pectoris have a poor prognosis possibly due to coronary microvascular disease. Coronary microvascular disease can be assessed by transthoracic Doppler echocardiography measuring coronary flow velocity reserve (CFVR) and by positron emission tomography measuring myocardial blood flow reserve (MBFR). Diffuse myocardial fibrosis can be assessed by cardiovascular magnetic resonance (CMR) T1 mapping. We hypothesized that coronary microvascular disease is associated with diffuse myocardial fibrosis. METHODS: Women with angina, a clinically indicated coronary angiogram with <50 % stenosis and no diabetes were included. CFVR was measured using dipyridamole (0.84 mg/kg) and MBFR using adenosine (0.84 mg/kg). Focal fibrosis was assessed by 1.5 T CMR late gadolinium enhancement (0.1 mmol/kg) and diffuse myocardial fibrosis by T1 mapping using a modified Look-Locker pulse sequence measuring T1 and extracellular volume fraction (ECV). RESULTS: CFVR and CMR were performed in 64 women, mean (SD) age 62.5 (8.3) years. MBFR was performed in a subgroup of 54 (84 %) of these women. Mean native T1 was 1023 (86) and ECV (%) was 33.7 (3.5); none had focal fibrosis. Median (IQR) CFVR was 2.3 (1.9; 2.7), 23 (36 %) had CFVR < 2 indicating coronary microvascular disease, and median MBFR was 2.7 (2.2; 3.0) and 19 (35 %) had a MBFR value below 2.5. No significant correlations were found between CFVR and ECV or native T1 (R 2 = 0.02; p = 0.27 and R 2 = 0.004; p = 0.61, respectively). There were also no correlations between MBFR and ECV or native T1 (R 2 = 0.1; p = 0.13 and R 2 = 0.004, p = 0.64, respectively). CFVR and MBFR were correlated to hypertension and heart rate. CONCLUSION: In women with angina and no obstructive coronary artery disease we found no association between measures of coronary microvascular disease and myocardial fibrosis, suggesting that myocardial ischemia induced by coronary microvascular disease does not elicit myocardial fibrosis in this population. The examined parameters seem to provide independent information about myocardial and coronary disease.

Characterization of diffuse fibrosis in the failing human heart via diffusion tensor imaging and quantitative histological validation.

Non-invasive imaging techniques are highly desirable as an alternative to conventional biopsy for the characterization of the remodeling of tissues associated with disease progression, including end-stage heart failure. Cardiac diffusion tensor imaging (DTI) has become an established method for the characterization of myocardial microstructure. However, the relationships between diffuse myocardial fibrosis, which is a key biomarker for staging and treatment planning of the failing heart, and measured DTI parameters have yet to be investigated systematically. In this study, DTI was performed on left ventricular specimens collected from patients with chronic end-stage heart failure as a result of idiopathic dilated cardiomyopathy (n = 14) and from normal donors (n = 5). Scalar DTI parameters, including fractional anisotropy (FA) and mean (MD), primary (D1 ), secondary (D2 ) and tertiary (D3 ) diffusivities, were correlated with collagen content measured by digital microscopy. Compared with hearts from normal subjects, the FA in failing hearts decreased by 22%, whereas the MD, D2 and D3 increased by 12%, 14% and 24%, respectively (P < 0.01). No significant change was detected for D1 between the two groups. Furthermore, significant correlation was observed between the DTI scalar indices and quantitative histological measurements of collagen (i.e. fibrosis). Pearson's correlation coefficients (r) between collagen content and FA, MD, D2 and D3 were -0.51, 0.59, 0.56 and 0.62 (P < 0.05), respectively. The correlation between D1 and collagen content was not significant (r = 0.46, P = 0.05). Computational modeling analysis indicated that the behaviors of the DTI parameters as a function of the degree of fibrosis were well explained by compartmental exchange between myocardial and collagenous tissues. Combined, these findings suggest that scalar DTI parameters can be used as metrics for the non-invasive assessment of diffuse fibrosis in failing hearts.

Early detection of myocardial involvement by non-contrast T1ρ mapping of cardiac magnetic resonance in type 2 diabetes mellitus.

Objective: This study aims to determine the effectiveness of T1ρ in detecting myocardial fibrosis in type 2 diabetes mellitus (T2DM) patients by comparing with native T1 and extracellular volume (ECV) fraction. Methods: T2DM patients (n = 35) and healthy controls (n = 30) underwent cardiac magnetic resonance. ECV, T1ρ, native T1, and global longitudinal strain (GLS) values were assessed. Diagnostic performance was analyzed using receiver operating curves. Results: The global ECV and T1ρ of T2DM group (ECV = 32.1 ± 3.2%, T1ρ = 51.6 ± 3.8 msec) were significantly higher than those of controls (ECV = 26.2 ± 1.6%, T1ρ = 46.8 ± 2.0 msec) (all P < 0.001), whether there was no significant difference in native T1 between T2DM and controls (P = 0.264). The GLS decreased significantly in T2DM patients compared with controls (-16.5 ± 2.4% vs. -18.3 ± 2.6%, P = 0.015). The T1ρ and native T1 were associated with ECV (Pearson's r = 0.50 and 0.25, respectively, both P < 0.001); the native T1, T1ρ, and ECV were associated with hemoglobin A1c (Pearson's r = 0.41, 0.52, and 0.61, respectively, all P < 0.05); and the ECV was associated with diabetes duration (Pearson's r = 0.41, P = 0.016). The AUC of ECV, T1ρ, GLS, and native T1 were 0.869, 0.810, 0.659, and 0.524, respectively. Conclusion: In T2DM patients, T1ρ may be a new non-contrast cardiac magnetic resonance technique for identifying myocardial diffuse fibrosis, and T1ρ may be more sensitive than native T1 in the detection of myocardial diffuse fibrosis.

Diffuse Myocardial Fibrosis on Cardiac Magnetic Resonance Imaging Is Related to Galectin-3 and Predicts Outcome in Heart Failure.

AIMS: Ongoing adverse remodeling is a hallmark of heart failure (HF), which might be reflected by either focal or diffuse myocardial fibrosis. Therefore, in (pre)clinical settings, we used immunohistochemistry or cardiac magnetic resonance imaging (CMR) to investigate the association of (focal or diffuse) fibrosis with cardiac biomarkers and adverse events in HF. METHODS AND RESULTS: In C57Bl/6J mice, we determined the presence and extent of myocardial fibrosis 6 weeks post-myocardial infarction (MI). Furthermore, we studied 159 outpatient HF patients who underwent CMR, and determined focal and diffuse fibrosis by late gadolinium enhancement (LGE) and post-contrast T1 time of the non-LGE myocardium, respectively. HF patients were categorized based on the presence of LGE, and by the median post-contrast T1 time. Kaplan-Meier and Cox regression analyses were used to determine the association of fibrosis with HF hospitalization and all-cause mortality. LGE was detected in 61 (38%) patients. Cardiac biomarker levels were comparable between LGE-positive and LGE-negative patients. LGE-positive patients with a short T1 time had elevated levels of both NT-proBNP and galectin-3 (1611 vs. 453 ng/L, p = 0.026 and 20 vs. 15 µg/L, p = 0.004, respectively). This was not observed in LGE-negative patients. Furthermore, a short T1 time in LGE-positive patients was associated with a higher risk of adverse events (log-rank p = 0.01). CONCLUSION: This study implies that cardiac biomarkers reflect active remodeling of the non-infarcted myocardium of patients with focal myocardial scarring. Diffuse fibrosis, in contrast to focal scarring, might have a higher prognostic value regarding adverse outcomes in HF patients.

The Effects of Fibrotic Cell Type and Its Density on Atrial Fibrillation Dynamics: An In Silico Study.

Remodeling in atrial fibrillation (AF) underlines the electrical and structural changes in the atria, where fibrosis is a hallmark of arrhythmogenic structural alterations. Fibrosis is an important feature of the AF substrate and can lead to abnormal conduction and, consequently, mechanical dysfunction. The fibrotic process comprises the presence of fibrotic cells, including fibroblasts, myofibroblasts and fibrocytes, which play an important role during fibrillatory dynamics. This work assesses the effect of the diffuse fibrosis density and the intermingled presence of the three types of fibrotic cells on the dynamics of persistent AF. For this purpose, the three fibrotic cells were electrically coupled to cardiomyocytes in a 3D realistic model of human atria. Low (6.25%) and high (25%) fibrosis densities were implemented in the left atrium according to a diffuse fibrosis representation. We analyze the action potential duration, conduction velocity and fibrillatory conduction patterns. Additionally, frequency analysis was performed in 50 virtual electrograms. The tested fibrosis configurations generated a significant conduction velocity reduction, where the larger effect was observed at high fibrosis density (up to 82% reduction in the fibrocytes configuration). Increasing the fibrosis density intensifies the vulnerability to multiple re-entries, zigzag propagation, and chaotic activity in the fibrillatory conduction. The most complex propagation patterns were observed at high fibrosis densities and the fibrocytes are the cells with the largest proarrhythmic effect. Left-to-right dominant frequency gradients can be observed for all fibrosis configurations, where the fibrocytes configuration at high density generates the most significant gradients (up to 4.5 Hz). These results suggest the important role of different fibrotic cell types and their density in diffuse fibrosis on the chaotic propagation patterns during persistent AF.

Association of Preterm Birth With Myocardial Fibrosis and Diastolic Dysfunction in Young Adulthood.

BACKGROUND: Preterm birth affects about 10% of live births worldwide and is associated with cardiac alterations. Animal models of preterm birth suggest that left ventricular functional impairment may be due to an up-regulation of myocardial fibrosis. OBJECTIVES: The aim of this study was to determine whether diffuse left ventricular fibrosis is evident in young adults born preterm. METHODS: One hundred one normotensive young adults born preterm (n = 47, mean gestational age 32.8 ± 3.2 weeks) and term (n = 54) were included from YACHT (Young Adult Cardiovascular Health sTudy). Left ventricular structure and function were quantified by cardiovascular magnetic resonance and echocardiography. Intravenous administration of a gadolinium-based contrast agent during cardiovascular magnetic resonance was used to quantify focal myocardial fibrosis on the basis of late gadolinium enhancement and, in combination with T1 mapping, to quantify diffuse myocardial fibrosis on the basis of assessment of myocardial extracellular volume fraction. RESULTS: Adults born preterm had smaller left ventricular end-diastolic and stroke volumes, with greater left ventricular mass and wall thickness (P < 0.001). In addition, longitudinal peak systolic strain and diastolic strain rate by both cardiovascular magnetic resonance and echocardiography, and E/A ratio measured by echocardiography, were lower in preterm-born compared to term-born adults (P < 0.05). Extracellular volume fraction was greater in preterm-born compared with term-born adults (27.81% ± 1.69% vs 25.48% ± 1.41%; P < 0.001) and was a significant mediator in the relationship between gestational age and both longitudinal peak diastolic strain rate and E/A ratio. CONCLUSIONS: Preterm-born young adults have greater extracellular volume fraction in the left ventricle that is inversely related with gestational age and may underlie their diastolic functional impairments.

Coal Workers' Pneumoconiosis and Other Mining-Related Lung Disease: New Manifestations of Illness in an Age-Old Occupation.

Coal workers' pneumoconiosis (CWP) and other mining-related lung diseases are entirely preventable, yet continue to occur. While greater attention has been given to CWP and silicosis, mining exposures cause a broad spectrum of respiratory disease, including chronic bronchitis, emphysema, and pulmonary fibrosis. Physicians must obtain a detailed occupational and exposure history from miners in order to make an accurate diagnosis and determine the risk of disease progression. Mining-related lung diseases are incurable and difficult to treat. Therefore, primary prevention by limiting dust exposure and secondary prevention through chest imaging and physiologic screening should be the primary focus of disease control.

Entropy as a Novel Measure of Myocardial Tissue Heterogeneity for Prediction of Ventricular Arrhythmias and Mortality in Post-Infarct Patients.

OBJECTIVES: This study proposed entropy as a new late gadolinium enhanced cardiac magnetic resonance-derived parameter to evaluate tissue inhomogeneity, independent of signal intensity thresholds. This study hypothesized that entropy within the scar is associated with ventricular arrhythmias (VAs), whereas entropy of the entire left ventricular (LV) myocardium is associated with mortality. BACKGROUND: In patients after myocardial infarction, the heterogeneity of fibrosis determines the substrate for VA. Fibrosis in remote areas has been associated with heart failure and mortality. Late gadolinium-enhanced cardiac magnetic resonance has been used to delineate fibrosis, but available methods depend on signal intensity thresholds and results have been inconsistent. METHODS: Consecutive post-myocardial infarction patients undergoing late gadolinium enhanced cardiac magnetic resonance prior to implantable cardioverter-defibrillator implantation were included. From cardiac magnetic resonance imaging, total scar size, scar gray zone, scar transmurality, and tissue entropy were derived. Patients were followed for appropriate implantable cardioverter-defibrillator therapy and mortality. RESULTS: A total of 154 patients (age 64 ± 10 years, 84% male, LV ejection fraction 29 ± 10%, 47% acute revascularization) were included. During a median follow-up of 56 (interquartile range: 40 to 73) months, appropriate implantable cardioverter-defibrillator therapy occurred in 46 patients (30%), and 41 patients (27%) died. From multivariable analysis, higher entropy of the scar (hazard ratio [HR]: 1.9; 95% confidence interval [CI]: 1.0 to 3.5; p = 0.042) was independently associated with VA, after adjusting for multivessel disease, acute revascularization, LV ejection fraction, scar gray zone, and transmurality. Entropy of the entire LV was independently associated with mortality (HR: 3.2; 95% CI: 1.1 to 9.9; p = 0.038). CONCLUSIONS: High entropy within the scar was associated with VA and may indicate an arrhythmogenic scar. High entropy of the entire LV was associated with mortality and may reflect a fibrosis pattern associated with adverse remodeling.

Relationship Between Focal and Diffuse Fibrosis Assessed by CMR and Clinical Outcomes in Heart Failure With Preserved Ejection Fraction.

OBJECTIVES: This study sought to assess the presence and extent of focal and diffuse fibrosis in heart failure in patients with preserved ejection fraction (HFpEF) compared to asymptomatic control subjects, and the relationship of fibrosis to clinical outcome. BACKGROUND: Myocardial fibrosis has been implicated in the pathophysiology of HFpEF. METHODS: In this prospective, observational study, 140 subjects of similar age and sex (HFpEF: n = 96; control subjects: n = 44; 73 ± 8 years of age; 49% males) underwent cardiac magnetic resonance imaging. Late gadolinium-enhanced (LGE) imaging and T1 mapping to calculate myocardial extracellular volume indexed to body surface area (iECV) were used to assess fibrosis. RESULTS: Patients with HFpEF had more concentric remodeling and worse diastolic function. Focal fibrosis was more frequent in HFpEF subjects (overall: n = 49; infarction: n = 17; nonischemic cases: n = 36; mixed patterns: n = 4) than in control subjects (overall: n = 3). Diffuse fibrosis was also greater in HFpEF subjects than control subjects (iECV: 13.7 ± 4.4 ml/m2 versus 10.9 ± 2.8 ml/m2; p < 0.0001). During median follow-up (1,429 days), there were 42 composite events (14 deaths; 28 heart failure hospitalizations) in cases of HFpEF. Myocardial infarction revealed on LGE imaging was a predictor of outcomes on univariate analysis only. With multivariate analysis, iECV (hazard ratio [HR]: 1.689; 95% confidence interval [CI]: 1.141 to 2.501; p = 0.009) was an independent predictor of outcome along with mitral peak velocity of early filling (E)-to-early diastolic mitral annular velocity (E') (E/E') ratio (HR: 1.716; 95% CI: 1.191 to 2.472; p = 0.004) and prior HF hospitalization (HR: 2.537; 95% CI: 1.090 to 5.902; p = 0.031). iECV was also significantly associated with ventricular/left atrial remodeling and renal dysfunction: right ventricular end-diastolic volume indexed (r = 0.456; p < 0.0001), left ventricular mass/volume (r = 0.348; p = 0.001), maximal left atrial volume indexed (r = 0. 269; p = 0.009), and creatinine (r = 0.271; p = 0.009). CONCLUSIONS: Both focal and diffuse myocardial fibrosis are more prevalent in HFpEF subjects than in control subjects of similar age and sex. iECV significantly correlates with indices of ventricular/left atrial remodeling and renal dysfunction and is an independent predictor of adverse outcome in HFpEF. (Developing Imaging And plasMa biOmarkers iN Describing Heart Failure With Preserved Ejection Fraction [DIAMONDHFpEF]; NCT03050593).

Regression of Diffuse Ventricular Fibrosis Following Restoration of Sinus Rhythm With Catheter Ablation in Patients With Atrial Fibrillation and Systolic Dysfunction: A Substudy of the CAMERA MRI Trial.

OBJECTIVES: This study sought to determine if diffuse ventricular fibrosis improves in patients with atrial fibrillation (AF)-mediated cardiomyopathy following the restoration of sinus rhythm. BACKGROUND: AF coexists in 30% of heart failure (HF) patients and may be an underrecognized reversible cause of left ventricular systolic dysfunction. Myocardial fibrosis is the hallmark of adverse cardiac remodeling in HF, yet its reversibility is unclear. METHODS: Patients with persistent AF and an idiopathic cardiomyopathy (left ventricular ejection fraction [LVEF] ≤45%) were randomized to catheter ablation (CA) or ongoing medical rate control as a pre-specified substudy of the CAMERA-MRI (Catheter Ablation versus Medical Rate Control in Atrial Fibrillation and Systolic Dysfunction-an MRI-Guided Multi-centre Randomised Controlled Trial) trial. All patients had cardiac magnetic resonance imaging scans (including myocardial T1 time), serum B-type natriuretic peptide, 6-min walk tests, and Short Form-36 questionnaires performed at baseline and 6 months. Sixteen patients with no history of AF or left ventricular systolic dysfunction were enrolled as normal controls for T1 time. RESULTS: Thirty-six patients (18 in each treatment arm) were included in this substudy. Demographics, comorbidities, and myocardial T1 times were well matched at baseline. At 6 months, patients in the CA group had a significant reduction in myocardial T1 time from baseline compared with the medical rate control group (-124 ms; 95% confidence interval [CI]: -23 to -225 ms; p = 0.0176), although it remained higher than that of normal controls at 6 months (p = 0.0017). Improvements in myocardial T1 time with CA were associated with significant improvements in absolute LVEF (+12.5%; 95% CI: 5.9% to 19.0%; p = 0.0004), left ventricular end-systolic volume (p = 0.0019), and serum B-type natriuretic peptide (-216 ng/l; 95% CI: -23 to -225 ng/l; p = 0.0125). CONCLUSIONS: The improvement in LVEF and reverse ventricular remodeling following successful CA of AF-mediated cardiomyopathy is accompanied by a regression of diffuse fibrosis. This suggests timely treatment of arrhythmia-mediated cardiomyopathy may minimize irreversible ventricular remodeling.