Diffuse Interstitial Myocardial Fibrosis Research Articles

Insights into the effects of Friedreich ataxia on the left ventricle using T1 mapping and late gadolinium enhancement.

The left ventricular (LV) changes which occur in Friedreich ataxia (FRDA) are incompletely understood. Cardiac magnetic resonance (CMR) imaging was performed using a 1.5T scanner in subjects with FRDA who are homozygous for an expansion of an intron 1 GAA repeat in the FXN gene. Standard measurements were performed of LV mass (LVM), LV end-diastolic volume (LVEDV) and LV ejection fraction (LVEF). Native T1 relaxation time and the extracellular volume fraction (ECV) were utilised as markers of left ventricular (LV) diffuse myocardial fibrosis and late gadolinium enhancement (LGE) was utilised as a marker of LV replacement fibrosis. FRDA genetic severity was assessed using the shorter FXN GAA repeat length (GAA1). There were 93 subjects with FRDA (63 adults, 30 children, 54% males), 9 of whom had a reduced LVEF (<55%). A LVEDV below the normal range was present in 39%, a LVM above the normal range in 22%, and an increased LVM/LVEDV ratio in 89% subjects. In adults with a normal LVEF, there was an independent positive correlation of LVM with GAA1, and a negative correlation with age, but no similar relationships were seen in children. GAA1 was positively correlated with native T1 time in both adults and children, and with ECV in adults, all these associations independent of LVM and LVEDV. LGE was present in 21% of subjects, including both adults and children, and subjects with and without a reduced LVEF. None of GAA1, LVM or LVEDV were predictors of LGE. An association between diffuse interstitial LV myocardial fibrosis and genetic severity in FRDA was present independently of FRDA-related LV structural changes. Localised replacement fibrosis was found in a minority of subjects with FRDA and was not associated with LV structural change or FRDA genetic severity in subjects with a normal LVEF.

Sacubitril/valsartan versus valsartan in regressing myocardial fibrosis in hypertension: a prospective, randomized, open-label, blinded endpoint clinical trial protocol.

Diffuse interstitial myocardial fibrosis is a key common pathological manifestation in hypertensive heart disease (HHD) progressing to heart failure (HF). Angiotensin receptor-neprilysin inhibitors (ARNi), now a front-line treatment for HF, confer benefits independent of blood pressure, signifying a multifactorial mode of action beyond hemodynamic regulation. We aim to test the hypothesis that compared with angiotensin II receptor blockade (ARB) alone, ARNi is more effective in regressing diffuse interstitial myocardial fibrosis in HHD. Role of ARNi in Ventricular Remodeling in Hypertensive LVH (REVERSE-LVH) is a prospective, randomized, open-label, blinded endpoint (PROBE) clinical trial. Adults with hypertension and left ventricular hypertrophy (LVH) according to Asian sex- and age-specific thresholds on cardiovascular magnetic resonance (CMR) imaging are randomized to treatment with either sacubitril/valsartan (an ARNi) or valsartan (an ARB) in 1:1 ratio for a duration of 52 weeks, at the end of which a repeat CMR is performed to assess differential changes from baseline between the two groups. The primary endpoint is the change in CMR-derived diffuse interstitial fibrosis volume. Secondary endpoints include changes in CMR-derived left ventricular mass, volumes, and functional parameters. Serum samples are collected and stored to assess the effects of ARNi, compared with ARB, on circulating biomarkers of cardiac remodeling. The endpoints will be analyzed with reference to the corresponding baseline parameters to evaluate the therapeutic effect of sacubitril/valsartan vs. valsartan. REVERSE-LVH will examine the anti-fibrotic potential of sacubitril/valsartan and will offer mechanistic insights into the clinical benefits of sacubitril/valsartan in hypertension in relation to cardiac remodeling. Advancing the knowledge of the pathophysiology of HHD will consolidate effective risk stratification and personalized treatment through a multimodal manner integrating complementary CMR and biomarkers into the conventional care approach.Clinical Trial Registration: ClinicalTrials.gov, identifier, NCT03553810.

Acute and Chronic Cardiopulmonary Effects of High Dose Interleukin-2 Therapy: An Observational Magnetic Resonance Imaging Study.

High dose interleukin-2 (IL-2) is known to be associated with cardiopulmonary toxicity. The goal of this study was to evaluate the effects of high dose IL-2 therapy on cardiopulmonary structure and function. Combined cardiopulmonary magnetic resonance imaging (MRI) was performed in 7 patients in the acute period following IL-2 therapy and repeated in 4 patients in the chronic period. Comparison was made to 10 healthy volunteers. IL-2 therapy was associated with myocardial and pulmonary capillary leak, tissue oedema and cardiomyocyte injury, which resulted in acute significant left ventricular (LV) dilatation, a reduction in LV ejection fraction (EF), an increase in LV mass and a prolongation of QT interval. The acute effects occurred irrespective of symptoms. In the chronic period many of the effects resolved, but LV hypertrophy ensued, driven by focal replacement and diffuse interstitial myocardial fibrosis and increased cardiomyocyte mass. In conclusion, IL-2 therapy is ubiquitously associated with acute cardiopulmonary inflammation, irrespective of symptoms, which leads to acute LV dilatation and dysfunction, increased LV mass and QT interval prolongation. Most of these effects are reversible but IL-2 therapy is associated with chronic LV hypertrophy, driven by interstitial myocardial fibrosis and increased cardiomyocyte mass. The findings have important implications for the monitoring and long term impact of newer immunotherapies. Future studies are needed to improve risk stratification and develop cardiopulmonary-protective strategies.

Advanced cardiovascular multimodal imaging and aortic stenosis.

Aortic valve stenosis has become the most common valvular heart disease on account ofaging population and increasinglife expectancy. Echocardiography is the primary diagnosis tool for this, but it still has many flaws. Therefore, advanced cardiovascular multimodal imaging techniques are continuously being developed in order to overcome these limitations. Cardiac magnetic resonance imaging (CMR) allows a comprehensive morphological and functional evaluation of the aortic valve and provides important data for the diagnosis and risk stratification in patients with aortic stenosis. CMR canfunctionally assessthe aortic flow using two-dimensional and time-resolved three-dimensional velocity-encoded phase-contrast techniques. Furthermore, by late gadolinium enhancement and T1-mapping, CMR can reveal the presence of both irreversible replacement and diffuse interstitial myocardial fibrosis. Moreover, its role in guiding aortic valve replacement procedures is beginning to take shape. Recent studies have rendered the importance of active and passive biomechanics in risk stratification and prognosis prediction in patients with aortic stenosis, but more work is required is just in its infancy, but data are promising. In addition, cardiac computed tomography is particularly useful for the diagnosis of aortic valve stenosis, and in preprocedural evaluation of the aorta, while positron emission tomography can be also used to assess valvular inflammation and active calcification. The purpose of this review is to provide a comprehensive overview of current available data regarding advanced cardiovascular multimodal imaging in aortic stenosis.

Can shear wave imaging distinguish between diffuse interstitial and replacement myocardial fibrosis?

Abstract Funding Acknowledgements Type of funding sources: None. Background Diffuse interstitial or myocardial replacement fibrosis are common features of a large variety of cardiomyopathies. These alterations contribute to functional changes, particularly to an increased myocardial stiffness (MS). Histological examination is the gold standard for myocardial fibrosis quantification, however, it requires endomyocardial biopsy which is invasive and not without risks. Cardiac magnetic resonance (CMR) can characterize the extent of both diffuse and replacement fibrosis and may have prognostic value in various cardiomyopathies. Echocardiographic shear wave (SW) elastography is an emerging approach for measuring MS in vivo. SWs occur after mechanical excitation of the myocardium, e.g. after mitral valve closure (MVC), and their propagation velocity is directly related to MS, thus providing an opportunity to assess stiffness at end-diastole. Purpose The aim was to investigate if velocities of natural SW can distinguish between interstitial and replacement fibrosis. Methods We prospectively enrolled 47 patients (22 patients after heart transplant [54.2 ± 15.8 years, 82.6% male] and 25 patients with established hypertrophic cardiomyopathy [54.0 ± 13.5 years, 80.0% male]) undergoing CMR during their check-up. We performed SW elastography in parasternal long axis views of the LV using a fully programmable experimental scanner (HD-PULSE) equipped with a clinical phased array transducer (Samsung Medison P2-5AC) at 1100 ± 250 frames per second. Tissue acceleration maps were extracted from an anatomical M-mode line along the midline of the LV septum. The SW propagation velocity at MVC was measured as the slope in the M-mode image. All patients underwent T1 mapping as well as late gadolinium enhancement (LGE) cardiac magnetic resonance at 1.5 T to assess the presence of diffuse or replacement fibrosis (Figure A). Therefore, patients were divided in three groups: no fibrosis, diffuse fibrosis and replacement fibrosis. Results Mechanical SW’s were observed in 46 subjects starting immediately after MVC and propagating from the LV base to the apex. SW propagation velocity at MVC correlated well with native myocardial T1 values (r = 0.65, p &amp;lt; 0.0001) and differed significantly among groups (p &amp;lt; 0.0001), with a significant post-test between any pair of groups (Figure B). SW velocities below a cut-off of 6.01 m/s showed the highest accuracy to identify patients without any type of fibrosis (sensitivity 88 %, specificity 89%, area under the curve = 0.93) (Figure C). A cut-off of 8.11 m/s could distinguish replacement fibrosis from diffuse fibrosis with a sensitivity and specificity of 59% and 92 %, respectively (area under the curve = 0.80) (Figure D). Conclusions Shear wave velocities after mitral valve closure can distinguish between normal and pathological myocardium and can detect differences between diffuse and replacement fibrosis. Abstract Figure.

Myocardial involvement in eosinophilic granulomatosis with polyangiitis evaluated with cardiopulmonary magnetic resonance

Patients with eosinophilic granulomatosis with polyangiitis (EGPA) most commonly die from cardiac causes, however, cardiac involvement remains poorly characterised and the relationship between cardiac and pulmonary disease is not known. This study aimed to characterise myocardial and pulmonary manifestations of EGPA, and their relationship. Prospective comprehensive cardiopulmonary investigation, including a novel combined cardiopulmonary magnetic resonance imaging (MRI) technology, was performed in 13 patients with stable EGPA. Comparison was made with 11 prospectively recruited matched healthy volunteers. Stable EGPA was associated with focal replacement and diffuse interstitial myocardial fibrosis (myocardial extracellular volume 26.9% vs. 24.7%; p = 0.034), which drove a borderline increase in left ventricular mass (56 ± 9 g/m2 vs. 49 ± 8 g/m2; p = 0.065). Corrected QT interval was significantly prolonged and was associated with the severity of myocardial fibrosis (r = 0.582, p = 0.037). Stable EGPA was not associated with increased myocardial capillary permeability or myocardial oedema. Pulmonary tissue perfusion and capillary permeability were normal and there was no evidence of pulmonary tissue oedema or fibrosis. Forced expiratory volume in one second showed a strong inverse relationship with myocardial fibrosis (r = −0.783, p = 0.038). In this exploratory study, stable EGPA was associated with focal replacement and diffuse interstitial myocardial fibrosis, but no evidence of myocardial or pulmonary inflammation or pulmonary fibrosis. Myocardial fibrosis was strongly associated with airway obstruction and abnormal cardiac repolarisation. Further investigation is required to determine the mechanisms underlying the association between heart and lung disease in EGPA and whether an immediate immunosuppressive strategy could prevent myocardial fibrosis formation.

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

PurposeTo compare the assessment of diffuse interstitial myocardial fibrosis in valvular diseases using cardiac magnetic resonance (CMR) extracellular volume fraction (ECV) quantification and serum biomarkers of collagen turnover using results of myocardial biopsy as standard of reference. Materials and methodsThis prospective monocentric study included consecutive patients before aortic valvular replacement. All patients underwent: i), 1.5T CMR with pre and post contrast T1 mapping sequence and ECV computation; ii), serum quantification of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) and iii), myocardial biopsies were collected during surgery to assess collagen volume fraction (CVF). Patients with coronary artery disease were excluded. Correlation between native T1, ECV, CVF and serum biomarkers were assessed using Pearson correlation test. Agreement between basal anteroseptal ECV with global ECV was assessed using Bland-Altman test. ResultsTwenty-one patients, 16 with aortic stenosis and 5 with aortic regurgitation were included. There were 12 men and 9 women with a mean age of 74.1±6.8 (SD) years (range: 32–84 years). Mean global ECV value was 26.7±2.7 (SD) % (range: 23.4–32.5%) and mean CVF value was 12.4±9.7% (range: 3.2–25.7%). ECV assessed at the basal anteroseptal segment correlated moderately with CVF (r=0.6; P=0.0026). There was a strong correlation and agreement between basal anteroseptal ECV and global ECV, (r=0.8; P<0.0001; bias 5.4±6.1%) but no correlation between global ECV and CVF (r=0.5; P=0.10). Global ECV poorly correlated with serum TIMP-1 (r=0.4; P=0.037) and MMP-2 (r=0.4; P=0.047). No correlation was found between serum biomarkers and basal anteroseptal- ECV or native T1. ConclusionIn patients with severe aortic valvulopathy, diffuse myocardial fibrosis assessed by anterosepto-basal ECV correlates with histological myocardial fibrosis. Anteroseptobasal ECV strongly correlates with global ECV, which poorly correlates with TIMP-1 and MMP-2, serum biomarkers involved in the progression of heart failure.

No increased extracellular volume fraction or conduction time after childhood septal myectomy.

The aim of this study was to assess the effect of surgical septal myectomy performed during early childhood for severe, drug-refractory hypertrophic cardiomyopathy with left ventricular outflow tract obstruction on the extent of septal myocardial extracellular volume fraction and the potential risk of developing atrioventricular cardiac conduction system disease. In this retrospective study, data from 30 patients with a confirmed diagnosis of childhood-onset hypertrophic cardiomyopathy were reviewed including cardiovascular magnetic resonance (CMR) with myocardial T1 mapping and late gadolinium enhancement, histopathology of myocardial specimens, transthoracic echocardiography, electrocardiography, 24-h Holter and cardiopulmonary exercise testing. Eighteen patients without were compared to 12 patients with prior septal myectomy performed during childhood (non-operated versus myectomy patients). Late gadolinium enhancement on CMR as a correlate for focal myocardial fibrosis was found in 53% of patients, predominantly located in the septal region, with no difference between groups. As compared to non-operated patients, those after myectomy showed a similar amount of total and septal extracellular volume fraction, as calculated from pre- and post-contrast CMR T1 mapping, which is a correlate for diffuse interstitial myocardial fibrosis. PQ-intervals or the occurrence of higher degree conduction system disease were equal between the 2 groups. Data from CMR and electrocardiography suggest that surgical septal myectomy performed during early childhood for severe obstructive hypertrophic cardiomyopathy does not cause an increased septal extracellular volume fraction or delayed atrioventricular conduction time on long-term follow-up.

Early effects of kidney transplantation on the heart - A cardiac magnetic resonance multi-parametric study

Increased native myocardial T1 times in chronic kidney disease (CKD) may be due to diffuse interstitial myocardial fibrosis (DIF) or due to interstitial edema/inflammation. Concerns relating to nephrogenic systemic fibrosis with gadolinium-based contrast agents (GBCA) limit their use in end-stage kidney disease (ESKD) to measure extracellular volume (ECV) and characterise myocardial fibrosis. This study aimed to examine stability of myocardial T1 and T2 times before, and within 2 months after kidney transplantation; a time frame when volume status normalises but myocardial remodelling is unlikely to have occurred, and to compare these with ECV using GBCA after transplantation. Twenty-four patients with ESKD underwent serial cardiovascular magnetic resonance imaging, including T1 and T2 mapping. GBCA was administered on follow-up provided eGFR was >30 ml/min/1.73 m2. Eighteen age- and sex-matched controls were studied at one timepoint. ECV (ECV 28 ± 2% vs. 24 ± 2%, p = 0.001) and T2 times were higher in ESKD compared to controls. After transplantation, septal T1 times increased (MOLLI 985 ms ± 25 vs. 1002 ms ± 30, p = 0.014; ShMOLLI 974 ms ± 39 vs. 992 ms ± 33, p = 0.113), LV volumes reduced (LVEDvol indexed 79 ± 24 vs. 63 ± 20 ml/m2, p = 0.005) but LV mass was unchanged (LV mass index 89 g/m2 ± 38 to 83 g/m2 ± 23, p = 0.141). T2 times did not change after transplantation. Both ECV and myocardial T1 times are elevated in ESKD, supporting the theory that elevated T1 times are due to DIF, although a contribution from myocardial edema cannot be fully excluded. The lack of any fall in T1 or T2 times after transplantation suggests that myocardial T1 times are a stable measure of DIF in CKD.

Protocatechualdehyde reduces myocardial fibrosis by directly targeting conformational dynamics of collagen

Myocardial fibrosis is associated with cardiovascular remodeling, which is characterized by abnormal collagen architecture. However, there are not yet effective strategies targeting this abnormal pathological process. The purpose of our study is to investigate the effect of protocatechualdehyde (PCA) on myocardial fibrosis for exploring the underlying target protein and molecular mechanism. We found PCA significantly suppressed isoprenaline (ISO)-induced fibrosis and collagen deposition in myocardial tissue. Then, the direct pharmacological target of PCA was identified as collagen I using cellular thermal shift assay (CETSA) coupled with stable isotope labeling with amino acids in cell culture (SILAC) technology. Surface plasmon resonance (SPR) analysis further confirmed the specific binding of PCA with collagen I. Moreover, collagen self-assembly assay and atomic force microscope analysis confirmed that PCA directly modulated collagen conformational dynamics. LC-MS/MS analysis was applied to determine lysine residues as the binding sites of PCA on collagen I by covalently cross-linking reaction. Collectively, our study suggests that PCA controls cardiovascular remodeling by mediating diffuse interstitial myocardial fibrosis. Moreover, directly targeting collagen may be a promising strategy for the treatment of heart failure and resultant myocardial fibrosis.

Diffuse myocardial fibrosis in adolescents operated with arterial switch for transposition of the great arteries - A CMR study

Diffuse myocardial fibrosis in adolescents operated with arterial switch for transposition of the great arteries - A CMR study

Abstract 21208: Association Between Serum Collagen and Myocardial Fibrosis Assessed by Magnetic Resonance Imaging: The Multi-Ethnic Study of Atherosclerosis

Introduction: C-terminal telopeptide of procollagen type I (ICTP) and N-terminal propeptide of procollagen type III (PIIINP) are two of the major collagen turnover markers representing collagen degradation and synthesis. Cardiac magnetic resonance (CMR) using delayed enhancement (DE) and T1 mapping, provides a tool for detection and quantification of focal scar and diffuse interstitial myocardial fibrosis. Hypothesis: Levels of the serum biomarkers of ICTP and PIIINP at baseline are associated with the presence of myocardial scar and diffuse interstitial fibrosis at the 10-year follow-up. Methods: Of 3000 participants in a case(CVD)-cohort study that measured PIIINP and ICTP in baseline, 827 subjects with had CMRI at follow-up. Participants were initially aged 45-84 years and free of clinical CVD. Baseline serum PIIINP and ICTP concentrations were assayed using radio-immunoassay. DE-CMRI assessed myocardial scar at 10-year follow-up, with T1 mapping indices of extracellular volume fraction (ECV), pre-contrast T1, and T1 at 25 minutes post-contrast measuring diffuse interstitial fibrosis. Logistic (DE scar vs. absence as a dichotomous outcome) or linear (continuous values of T1 indices as outcomes) multivariable regression analysis with ICTP and PIIINP levels weighted for the design as continuous exposures were performed with adjustment for ACC-AHA ASCVD risk score and glomerular filtration rate at baseline (Model 1) and follow-up (Model 2). Results: Mean (SD) ICTP was 3.1 ± 0.9 μg/L; PIIINP was 5.4 ± 1.3 μg/L; ECV was 27.3 ± 3.1 %; and T1 at 25’ was 517 ± 42 ms. Among 827 participants, 68 had myocardial scar. Increased ICTP and PIIINP levels at baseline were associated with the presence of myocardial scar at follow-up (Table 1). ICTP showed no association with T1 mapping indices. Conclusions: Increased levels of collagen turnover markers were independently associated with the presence of myocardial scar 10 years later, but not with diffuse interstitial fibrosis.

O18-2 - Inflammatory Cardiomyopathy Associated with Rheumatoid Arthritis Treated with Left Ventricular Assist Device

Cardiovascular involvement is common in patients with rheumatoid arthritis (RA), however, advanced heart failure is rare. We report a case of severe heart failure who required the placement of left ventricular assist device (LVAD). A 34-year old woman, who had been diagnosed as RA 8 years before and treated with predonisolone and methotrexate, was admitted to the local hospital due to short of breath. She had severe left ventricular (LV) dysfunction with an ejection fraction (EF) of 15%. Twenty days after the recovery by intensive treatment, she was re-hospitalized due to cardiogenic shock requiring intravenous administration of inotropes and intraaortic balloon pump (IABP). She was referred to our institution as a candidate of heart transplantation because she required the continuous infusions of high-dose inotropes. Fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) revealed increased uptake in LV. Histologic examination from right ventricle showed infiltration of CD3-T lymphocytes and diffuse interstitial or replacement myocardial fibrosis. Based on these finding, she was diagnosed as chronic inflammatory cardiomyopathy with little chance of LV recovery. On the other hand, RA was in a state of remission. She was judged as an indication for heart transplantation and underwent a successful placement of LVAD.

Relation of Myocardial Contrast-Enhanced T1 Mapping by Cardiac Magnetic Resonance to Left Ventricular Reverse Remodeling After Cardiac Resynchronization Therapy in Patients With Nonischemic Cardiomyopathy

Myocardial scar is known to be associated with limited left ventricular (LV) reverse remodeling after cardiac resynchronization therapy (CRT). However, the impact of diffuse myocardial interstitial fibrosis, as assessed with myocardial T1 mapping cardiac magnetic resonance (CMR), has not been studied in patients with CRT. Therefore, we aimed at evaluating the association between diffuse myocardial interstitial fibrosis, in nonischemic cardiomyopathy patients, and LV reverse remodeling after CRT. A total of 40 patients (61± 11years) with nonischemic cardiomyopathy who underwent CMR before CRT implantation were included. Myocardial T1 mapping was performed using an inversion-recovery Look-Locker sequence after gadolinium injection. Myocardial contrast-enhanced T1 time values were assessed from segments without delayed contrast enhancement and normalized for heart rate. At 6-month follow-up, LV reverse remodeling was assessed by the reduction in LV end-systolic volume. Before CRT implantation, mean myocardial contrast-enhanced T1 time was 351 ± 46ms. At 6-month follow-up, LV end-systolic volume decreased by 24 ± 21%. Myocardial contrast-enhanced T1 time showed a significant correlation with LV reverse remodeling (r= 0.5, p= 0.001) together with hemoglobin level, renal function, LV dyssynchrony, and presence of delayed contrast enhancement. Multivariate regression analysis identified myocardial contrast-enhanced T1 time (β-0.160, p= 0.022), LV dyssynchrony (β-0.267, p= 0.002), and renal function (β-0.334, p=0.021) as independent associates of LV reverse remodeling. In conclusion, in nonischemic cardiomyopathy, diffuse interstitial myocardial fibrosis quantified with T1 mapping CMR is independently associated with LV reverse remodeling after CRT and might, therefore, be used to optimize patient selection.

MAGNETIC RESONANCE IMAGING IN THE DIAGNOSIS OF THE HEART LESIONS IN PATIENTS WITH ACROMEGALY

Актуальность. Акромегалия – заболевание, в основе которого лежит патологическая гиперсекреция соматотропного гормона и инсулиноподобных факторов роста. У пациентов с акромегалией независимо от других заболеваний сердечно-сосудистой системы формируется акромегалийная кардиомиопатия, которая, по данным мировой литературы, характеризуется проявлениями триады признаков: гипертрофия, отек и фиброз миокарда. Фиброз миокарда (диффузный интерстициальный) развивается по мере персистирования избытка соматотропного гормона и постепенного нарушения архитектоники сердечной мышцы. Однозначно высказаться о частоте кардиофиброза при акромегалийной кардиомиопатии затруднительно, что объясняется одиночными исследованиями в этой области с участием небольшого количества пациентов.

Focal But Not Diffuse Myocardial Fibrosis Burden Quantification Using Cardiac Magnetic Resonance Imaging Predicts Left Ventricular Reverse Modeling Following Cardiac Resynchronization Therapy.

Many heart failure patients with dyssynchrony do not reverse remodel (RR) in response to cardiac resynchronization therapy (CRT). The presence of focal and diffuse interstitial myocardial fibrosis may explain this high nonresponse rate. T1 mapping is a new cardiac magnetic resonance imaging (CMR) technique that overcomes the limitations of conventional contrast CMR and provides reliable quantitative assessment of diffuse myocardial fibrosis. The study tested the hypothesis that focal and diffuse fibrosis quantification would correlate with a lack of left ventricular (LV) RR to CRT. In a prospective study of 48 consecutive patients (27 ischemic cardiomyopathy, 21 dilated cardiomyopathy) LV scar burdens were quantified (scar core and gray zone using late gadolinium enhancement LGE CMR; interstitial fibrosis using T1 mapping) before CRT implant. LV RR was defined by a ≥ 15% reduction in LV end-systolic volume 6 months postimplant. Twenty-seven (56%) patients were responders with RR. Association between scar quantification and LV RR was assessed using the Poisson regression model. Univariate analysis showed that QRS duration/morphology, scar core, and gray zone volumes expressed as % of LV mass and extracellular volume index (ECV) (a measure of interstitial fibrosis from T1 mapping) to be significant predictors of LV RR. Multivariable-adjusted analyses demonstrated scar core quantification (≥ 13.7% LV mass) to be the only independent predictor of LV RR (prevalence ratio 0.40, P = 0.038). Focal scar burden detected by LGE CMR is associated with a poor response to CRT. Diffuse interstitial fibrosis assessment by T1 mapping, however, is not independently predictive of CRT response.

Quantification of Myocardial Extracellular Volume Fraction with Cardiac MR Imaging in Thalassemia Major.

Purpose To quantify myocardial extracellular volume (ECV) by using cardiac magnetic resonance (MR) imaging in thalassemia major and to investigate the relationship between ECV and myocardial iron overload. Materials and Methods With institutional review board approval and informed consent, 30 patients with thalassemia major (mean age ± standard deviation, 34.6 years ± 9.5) and 10 healthy control subjects (mean age, 31.5 years ± 4.4) were prospectively recruited (clinicaltrials.gov identification number NCT02090699). Nineteen patients (63.3%) had prior myocardial iron overload (defined as midseptal T2* < 20 msec on any prior cardiac MR images). Cardiac MR imaging at 1.5 T included cine steady-state free precession for ventricular function, T2* for myocardial iron quantification, and unenhanced and contrast material-enhanced T1 mapping. ECV was calculated with input of the patient's hematocrit level. Peak systolic global longitudinal strain by means of speckle tracking was assessed with same-day transthoracic echocardiography. Statistical analysis included use of the two-sample t test, Fisher exact test, and Spearman correlation. Results Unenhanced T1 values were significantly lower in patients with prior myocardial iron overload than in control subjects (850.3 ± 115.1 vs 1006.3 ± 35.4, P < .001) and correlated strongly with T2* values (r = 0.874, P < .001). Patients with prior myocardial iron overload had higher ECV than did patients without iron overload (31.3% ± 2.8 vs 28.2% ± 3.4, P = .030) and healthy control subjects (27.0% ± 3.1, P = .003). There was no difference in ECV between patients without iron overload and control subjects (P = .647). ECV correlated with lowest historical T2* (r = -0.469, P = .010) but did not correlate significantly with left ventricular ejection fraction (r = -0.216, P = .252) or global longitudinal strain (r = -0.164, P = .423). Conclusion ECV is significantly increased in thalassemia major and is associated with myocardial iron overload. These abnormalities may potentially reflect diffuse interstitial myocardial fibrosis. (©) RSNA, 2015 Online supplemental material is available for this article.

Diffuse left ventricular interstitial fibrosis is associated with sub-clinical myocardial dysfunction in Alström Syndrome: an observational study.

BackgroundAlström syndrome is a rare inherited ciliopathy with progressive multisystem involvement. Dilated cardiomyopathy is common in infancy and recurs or presents de novo in adults with high rates of premature cardiovascular death. Although Alström syndrome is characterised by fibrosis in solid organs such as the liver, the pathogenesis of related cardiomyopathy are not clear. To date it is not known whether diffuse interstitial myocardial fibrosis is present before the onset of heart failure symptoms or changes in conventional parameters of left ventricular function.MethodsIn this observational study, 26 patients with Alström syndrome (mean age 27 ± 9 years, 65 % male, 24 h ABPM 130 ± 14 / 77 ± 9 mmHg) without symptomatic cardiovascular disease were recruited from a single centre and compared to matched healthy controls. All subjects underwent cardiac MRI (1.5 T) to assess ventricular function, diffuse interstitial myocardial fibrosis by measurement of extracellular volume on T1-mapping (MOLLI) and coarse replacement fibrosis using standard late gadolinium enhancement imaging.ResultsGlobal extracellular volume was increased in Alström syndrome with wider variation compared to controls (0.30 ± 0.05 vs. 0.25 ± 0.01, p < 0.05). Left ventricular long axis function and global longitudinal strain were impaired in Alström syndrome without change in ejection fraction, ventricular size or atrial stress (NT-proBNP) (p < 0.05). Global extracellular volume was associated with reduced peak systolic longitudinal strain (r = −0.73, p < 0.01) and strain rate (r = −0.57, p < 0.01), increased QTc interval (r = 0.49, p < 0.05) and serum triglycerides (r = 0.66, p < 0.01). Nine (35 %) patients had diffuse mid-wall late gadolinium enhancement in a non-coronary artery distribution.ConclusionDiffuse interstitial myocardial fibrosis is common in Alström syndrome and is associated with impaired left ventricular systolic function. Serial studies are required to determine whether global extracellular volume may be an independent imaging biomarker of vulnerability to dilated cardiomyopathy and heart failure.

Myocardial extracellular volume fraction and myocardial fibrosis by cmr in patients with severe aortic stenosis

Background Severe aortic stenosis (AS) induces diffuse interstitial myocardial fibrosis (MF). CMR late gadolinium enhancement (LGE) technique is useful to detect focal MF. The amount of MF is associated with worse long-term prognosis after aortic valve replacement surgery (AVR). Measurements of T1 relaxation times before and after gadolinium administration allow determination of myocardial extracellular volume fraction (ECV) in order to assess diffuse MF. In this study we investigated ECV and LGE prevalence and extent in severe AS, and compare them to left ventricular (LV), aortic valve (AV) function and MF by biopsy.

T1 values by conservative septal postprocessing approach are superior in relating to the interstitial myocardial fibrosis: findings from patients with severe aortic stenosis

Background Accumulation of diffuse interstitial myocardial fibrosis in severe aortic stenosis relates to left ventricular (LV) functional impairment and determines the postoperative outcome in these patients. T1 mapping has been proposed for non-invasive quantification of diffuse interstitial fibrosis. We examined associations between T1 values and collagen volume fraction from endomyocardial biopsies from patients with severe aortic stenosis. We compared whether these relationships differ with respect to the post-processing approach.