Sophie Mavrogeni

A comparison of magnetic resonance imaging and cardiac biopsy in the evaluation of heart iron overload in patients with β‐thalassemia major

Abstract:  Objectives: To apply magnetic resonance imaging (MRI) for the assessment of myocardial iron deposition in patients with β‐thalassemia and compare the results with cardiac biopsy data. Background: Myocardial iron accumulation is the main cause for cardiac complications in β‐thalassemia. Methods: Twenty‐five consecutive thalassemic patients were studied using a 0.5‐T (Tesla) system, ECG‐gated, with echo time (TE) = 17–68 ms. T2 relaxation time of the interventricular septum was calculated assuming simple monoexponential decay. A heart T2 relaxation time value of 32 ms was used for the discrimination between high and low iron deposition. Heart biopsy was performed within a week after the MRI study. Patients with stainable iron in more than 50% of the myofibrils were graded as having severe iron deposition. A serum ferritin level below 2000 ng/mL was considered as an indication of successful chelation. Results: Seven of the 25 patients had heart biopsy indicative of low iron deposition (Group L) and the remaining 18 patients had heart biopsy indicative of high iron deposition (Group H). T2 relaxation time of the heart (T2H) was lower in Group H compared to Group L (31.5 ± 3.9 (range: 28–40) ms vs. 35.7 ± 3.7 (range: 29–40) ms, P = 0.026). The T2H was in agreement with heart biopsy in 86% of the patients in Group L and in 78% of the patients in Group H (overall agreement 80%). Similarly, serum ferritin levels were in agreement with heart biopsy in 28% and 88%, respectively (overall agreement 72%). In Group L, MRI was in better agreement with biopsy compared to serum ferritin (86% vs. 28%, P < 0.05). A receiver operating characteristic curve (ROC) analysis confirmed that a T2 relaxation time of 32 ms had the highest discriminating ability for the corresponding biopsy outcome. Conclusions: Heart T2 relaxation time appears in agreement with cardiac biopsy, both in high and low iron deposition, and may become a useful non‐invasive index in β‐thalassemia.

Detection of Coronary Artery Lesions and Myocardial Necrosis by Magnetic Resonance in Systemic Necrotizing Vasculitides

OBJECTIVE Myocardium and coronary arteries can occasionally be affected in patients with systemic necrotizing vasculitides; however, such involvement has not been systematically assessed using cardiovascular magnetic resonance imaging (MRI). METHODS Magnetic resonance angiography and contrast-enhanced MRI were applied for the assessment of coronary arteries (the left anterior descending [LAD], left circumflex [LCx], and right coronary artery [RCA]) and myocardium, respectively, in 39 patients with vasculitis who were asymptomatic for cardiac disease (16 with microscopic polyangiitis [MPA], 11 with Wegeners granulomatosis [WG], 9 with Churg-Strauss syndrome [CSS], and 3 with polyarteritis nodosa [PAN]). Data were compared with age-matched disease-control patients with rheumatoid arthritis (n = 20) or systemic lupus erythematosus (n = 13), and with healthy control individuals with normal coronaries (n = 40). RESULTS Patients with MPA, WG, and PAN (but not with CSS) were found to display significantly increased maximal diameters of coronary arteries compared with healthy controls (for MPA and WG; P < 0.001 for LAD and RCA, and P < 0.01 for LCx) and with both disease-control groups (for only MPA; P < 0.01 for LAD and RCA, and P < 0.05 for LCx). Fusiform coronary aneurysms were detected in patients with MPA (4/16) and PAN (2/3), whereas coronary ectasias were evident in patients with MPA (14/16) and WG (2/11). The presence of myocardial necrosis (by assessment of late gadolinium-enhanced images) was identified only in patients with MPA (2/16) and CSS (3/8 studied). CONCLUSION Cardiovascular MRI assessment of patients with systemic vasculitis revealed coronary ectatic disease in the majority of patients with MPA and PAN, as well as in several patients with WG. Myocardial necrosis can be detected in MPA and CSS.

Myocarditis as a precipitating factor for heart failure: evaluation and 1‐year follow‐up using cardiovascular magnetic resonance and endomyocardial biopsy

The aim of this study was to evaluate myocarditis as a precipitating factor for heart failure using cardiovascular magnetic resonance (CMR) and endomyocardial biopsy

Magnetic Resonance Angiography, Function and Viability Evaluation in Patients with Kawasaki Disease

OBJECTIVES We evaluated the ability of magnetic resonance imaging to perform a noninvasive assessment of coronary arteries, function and viability in one examination in a population with Kawasaki disease. BACKGROUND Magnetic resonance angiography (MRA) can identify coronary abnormalities in patients with Kawasaki disease (KD). Contrast enhanced cardiovascular magnetic resonance (CeCMR) is the current gold standard for scar detection. Steady-state, free precession (SSFP) cine is a reliable technique to evaluate myocardial function and wall motion. METHODS Twenty patients with KD aged 7-12 yrs, were examined. Coronary MRA was performed using a 1.5 T system with two ECG-triggered pulse sequences. CeCMR images were acquired 15 minutes after the i.v. injection of 0.1 mmol/kg Gd-DTPA using an inversion recovery sequence. SSFP cines were acquired using 6-mm short-axis slices from the atrioventricular ring to the apex. RESULTS Aneurysms of the coronary arteries were identified in 7 patients and coronary ectasia was present in the remaining 12 patients while 1 patient had both. Transmural anterior-apical scar was detected by ceCMR in two cases, while small inferior necrosis was identified in another 2 cases. Left ventricular function was deteriorated only in the two patients with antero-apical infarction. The presence of myocardial infarction was detected in the territory supplied by the involved coronary artery. CONCLUSION In Kawasaki disease MRA, SSFP cine and ceCMR are able to perform noninvasive coronary artery evaluation, function and infarct detection in a single study.

Myocardial Inflammation in Autoimmune Diseases: Investigation by Cardiovascular Magnetic Resonance and Endomyocardial Biopsy

INTRODUCTION Myocardial inflammation often coexists with different types of autoimmune diseases. Our aim was to investigate the presence of myocarditis in these patients by Cardiovascular Magnetic Resonance (CMR) and endomyocardial biopsy. PATIENTS-METHODS Twenty patients, aged 20-55 yrs with autoimmune diseases and cardiac symptoms (3 with Takayasus arteritis, 3 with systemic lupus erythematosus, 5 with rheumatoid arthritis, 7 with autoimmune thyroid disease and 2 with systemic sclerosis) and 20 patients with the same autoimmune diseases but without cardiac symptoms (controls) were studied. The presence of myocarditis and LV function were evaluated by CMR. Myocarditis was documented using T2-weighted (T2-W), T1-weighted (T1-W) before and after contrast media injection and late enhanced images. In 10 patients (positive for myocarditis by CMR with either low LVEF or recent increase in troponin), endomyocardial biopsy was also performed. Myocardial specimens were evaluated by histology and polymerase chain reaction techniques (PCR). RESULTS Myocarditis was identified in 18/20 patients by CMR. In the T2-W images the signal ratio of myocardium to skeletal muscle was 1.89+/-0.25 (control values 1.57+/-0.13, p<0.05). From the T1-W images the relative myocardial enhancement was 11.31+/-11.18 (control values 3.09+/-0.05, p<0.05). Epicardial late gadolinium enhanced areas were identified in 18/20. In myocardial specimens, histology revealed inflammation in 5/10 (50%) and PCR documented viral or microbial genomes in 8/10 (80%). Positive histology and PCR were in agreement with 50% and 80% of positive CMR examinations, respectively. Herpes virus was identified in 3/10, Adeno in 1/10, Coxsackie B6 in 1/10, echo in 1/10, Parvo-B19 in 3/10, CMV in 1/10 and Chlamydia trachomatis in 8/10. CONCLUSIONS Myocardial inflammation is a common finding in patients with autoimmune diseases and cardiac symptoms. The diagnosis can be confirmed by CMR, which is a noninvasive and reliable tool for the investigation of these patients.

Myocardial inflammation in Duchenne Muscular Dystrophy as a precipitating factor for heart failure: a prospective study

BackgroundIn patients with Duchenne Muscular Dystrophy (DMD), the absent or diminished dystrophin leads to progressive skeletal muscle and heart failure. We evaluated the role of myocardial inflammation as a precipitating factor in the development of heart failure in DMD.Methods20 DMD patients (aged 15-18 yrs) and 20 age-matched healthy volunteers were studied and followed-up for 2 years. Evaluation of myocarditis with cardiovascular magnetic resonance imaging (CMR) was performed using STIR T2-weighted (T2W), T1-weighted (T1W) before and after contrast media and late enhanced images (LGE). Left ventricular volumes and ejection fraction were also calculated. Myocardial biopsy was performed in patients with positive CMR and immunohistologic and polymerase chain reaction (PCR) analysis was employed.ResultsIn DMD patients, left ventricular end-diastolic volume (LVEDV) was not different compared to controls. Left ventricular end-systolic volume (LVESV) was higher (45.1 ± 6.6 vs. 37.3 ± 3.8 ml, p < 0.001) and left ventricular ejection fraction (LVEF) was lower (53.9 ± 2.1 vs. 63 ± 2.4%, p < 0.001). T2 heart/skeletal muscle ratio and early T1 ratio values in DMD patients presented no difference compared to controls. LGE areas were identified in six DMD patients. In four of them with CMR evidence of myocarditis, myocardial biopsy was performed. Active myocarditis was identified in one and healing myocarditis in three using immunohistology. All six patients with CMR evidence of myocarditis had a rapid deterioration of left ventricular function during the next year.ConclusionsDMD patients with myocardial inflammation documented by CMR had a rigorous progression to heart failure.

Magnetic resonance evaluation of liver and myocardial iron deposition in thalassemia intermedia and b-thalassemia major

Introduction b-Thalassemia major (TM) and thalassemia intermedia (TI) are forms of inherited hemoglobinopathies. Our aim was to evaluate a population of asymptomatic TM and TI patients using cardiovascular magnetic resonance (CMR). We hypothesized that the TI group could be differentiated from the TM group based on T2*. We also hypothesized that the TI group would demonstrate significantly higher cardiac output compared to the TM group. Patients and methods Twenty-one consecutive TI patients aged 23(19–25) years, 21 TM patients and 21 age and sex matched controls were studied. Evaluation of heart, liver T2* relaxation time and right and left ventricular parameters was performed using a 1.5 T system. Results Myocardial and liver T2* values were significantly higher in TI patients compared to TM (34.35 ± 2.36 vs 15.77 ± 3.53 m, P < 0.001 and 5.12 ± 6.52 vs 1.36 ± 0.53 ms, P < 0.001, respectively). Controls had myocardial T2* 35.07 ± 4.52 ms (similar to TI patients, but significantly increased compared to TM patients, P < 0.001) and liver T2* 26.28 ± 2.37 ms (significantly increased compared to both TI and TM patients, P < 0.001). Left ventricular end-diastolic (LVEDV), end-systolic (LVESV) volumes and left ventricular ejection fraction (LVEF) were higher in TI patients compared to TM (P < 0.001). Stroke volume (LVSV), cardiac output (LVCO) and cardiac index (LVCI) were similarly increased in TI patients compared to TM (P < 0.001). Right ventricular end-diastolic volume (RVEDV), right ventricular end-systolic volume (RVESV) and right ventricular ejection fraction (RVEF) were higher in TI patients compared to TM (P < 0.001). Conclusions Although in TM iron plays a crucial role in the evolution of the disease, in TI the high output cardiac state seems to be the most prominent finding.

The diagnostic role of Cardiac Magnetic Resonance Imaging in detecting myocardial inflammation in systemic lupus erythematosus. Differentiation from viral myocarditis.

Objective The objective of this paper is to evaluate the diagnostic role of cardiac magnetic resonance imaging (CMR) in detecting myocardial inflammation in systemic lupus erythematosus (SLE) and its differentiation from viral myocarditis. Patients and methods Fifty patients with suspected infective myocarditis (IM), with chest pain, dyspnoea or altered ECG, increase in troponin I and/or NT-pro BNP, with or without a history of flu-like syndrome or gastroenteritis and elevated C-reactive protein (CRP) within three to five (median four) weeks before admission, 25 active SLE patients, aged 38 ± 3 years, and 20 age-matched controls were prospectively evaluated by clinical assessment, ECG, echocardiogram and CMR. All patients underwent coronary angiography, and those with significant coronary artery disease (CAD) were excluded. CMR was performed using STIR T2-W (T2W), early T1-W (EGE) and late T1-W (LGE). Endomyocardial biopsies were performed when clinically indicated by current guidelines. Specimens were examined by immunohistological and polymerase chain reaction (PCR) analysis. Results Positive coronary angiography for CAD excluded 10/50 suspected IM and 5/25 active SLE. Positive clinical criteria for acute myocarditis were fulfilled by 28/40 suspected IM and only 5/20 active SLE. CMR was positive for myocarditis in 35/40 suspected IM and in 16/20 active SLE. Endomyocardial biopsy (EMB), performed in 25/35 suspected IM and 7/16 active SLE with positive CMR, showed positive immunohistology in 18/25 suspected IM and 3/7 active SLE. Infectious genomes were identified in 24/25 suspected IM and 1/7 active SLE. Conclusions CMR-positive IM patients were more symptomatic than active SLE. More than half of CMR-positive patients also had positive EMB. PCR was positive in almost all IM, but unusual in SLE. Due to the subclinical presentation of SLE myocarditis and the limitations of EMB, CMR presents the best alternative for the diagnosis of SLE myocarditis.

Imaging modalities for the diagnosis of pulmonary hypertension in systemic sclerosis

Patients with systemic sclerosis (SSc) are at considerable risk of developing pulmonary arterial hypertension (PAH). PAH has a dramatic impact on the natural history of the disease and overall survival of the patient. Despite progress made in elucidating the pathogenesis of PAH and introduction of novel therapies, SSc-related PAH (SScPAH) remains a devastating disease that responds poorly to therapy. Although early diagnosis is of paramount importance, there are no available validated strategies for assessing SScPAH because reliable evaluation of the structure and function of the right ventricle is difficult owing to its complex geometry. Additionally, myocardial fibrosis might affect cardiac contractility and contribute to heart failure. Modern imaging modalities, such as novel echocardiographic techniques and cardiac MRI, are highly sensitive, quantitative and reproducible methods that allow noninvasive assessment of regional and global myocardial performance without relying on geometric assumptions. In this Review, we examine the imaging modalities currently available, focusing on evolving diagnostic imaging methodologies and their possible clinical implications in the SScPAH setting.

Cardiovascular magnetic resonance in rheumatology: Current status and recommendations for use.

Targeted therapies in connective tissue diseases (CTDs) have led to improvements of disease-associated outcomes, but life expectancy remains lower compared to general population due to emerging co-morbidities, particularly due to excess cardiovascular risk. Cardiovascular magnetic resonance (CMR) is a noninvasive imaging technique which can provide detailed information about multiple cardiovascular pathologies without using ionizing radiation. CMR is considered the reference standard for quantitative evaluation of left and right ventricular volumes, mass and function, cardiac tissue characterization and assessment of thoracic vessels; it may also be used for the quantitative assessment of myocardial blood flow with high spatial resolution and for the evaluation of the proximal coronary arteries. These applications are of particular interest in CTDs, because of the potential of serious and variable involvement of the cardiovascular system during their course. The International Consensus Group on CMR in Rheumatology was formed in January 2012 aiming to achieve consensus among CMR and rheumatology experts in developing initial recommendations on the current state-of-the-art use of CMR in CTDs. The present report outlines the recommendations of the participating CMR and rheumatology experts with regards to: (a) indications for use of CMR in rheumatoid arthritis, the spondyloarthropathies, systemic lupus erythematosus, vasculitis of small, medium and large vessels, myositis, sarcoidosis (SRC), and scleroderma (SSc); (b) CMR protocols, terminology for reporting CMR and diagnostic CMR criteria for assessment and quantification of cardiovascular involvement in CTDs; and (c) a research agenda for the further development of this evolving field.