Amlodipine as adjuvant therapy to current chelating agents for reducing iron overload in thalassaemia major: a systematic review, meta-analysis and simulation of future studies.

BACKGROUND AND OBJECTIVES: Iron overload in thalassaemia is a crucial prognostic factor and a major cause of death due to heart failure or arrhythmia. Therefore, previous research has recommended amlodipine as an auxiliary treatment to current chelating agents for reducing iron overload in thalassaemia patients. MATERIALS AND METHODS: A systematic review and meta-analysis of the results of three randomized clinical trials evaluating the use of amlodipine in thalassaemia patients through 12 databases were carried out. RESULTS: Our final cohort included 130 patients. Insignificant difference in decreasing liver iron concentrations was found between amlodipine and control groups {weighted mean difference = -0·2, [95% confidence interval = (-0·55-0·15), P = 0·26]}. As regards serum ferritin, our analysis also showed no significant difference in serum ferritin between amlodipine and control groups {weighted mean difference [95% confidence interval = -0·16 (-0·51-0·19), P = 0·36]}. Similarly, there was insignificant difference in cardiac T2* between amlodipine and control groups {weighted mean difference [95% confidence interval = 0·34 (-0·01-0·69), P = 0·06]}. CONCLUSIONS: Despite the growing evidence supporting the role of amlodipine in reducing iron overload in thalassaemia patients, our meta-analysis did not find that evidence collectively significant. The results of our simulation suggest that when more data are available, a meta-analysis with more randomized clinical trials could provide more conclusive insights.

Cardiovascular magnetic resonance in women with cardiovascular disease: position statement from the Society for Cardiovascular Magnetic Resonance (SCMR).

This document is a position statement from the Society for Cardiovascular Magnetic Resonance (SCMR) on recommendations for clinical utilization of cardiovascular magnetic resonance (CMR) in women with cardiovascular disease. The document was prepared by the SCMR Consensus Group on CMR Imaging for Female Patients with Cardiovascular Disease and endorsed by the SCMR Publications Committee and SCMR Executive Committee. The goals of this document are to (1) guide the informed selection of cardiovascular imaging methods, (2) inform clinical decision-making, (3) educate stakeholders on the advantages of CMR in specific clinical scenarios, and (4) empower patients with clinical evidence to participate in their clinical care. The statements of clinical utility presented in the current document pertain to the following clinical scenarios: acute coronary syndrome, stable ischemic heart disease, peripartum cardiomyopathy, cancer therapy-related cardiac dysfunction, aortic syndrome and congenital heart disease in pregnancy, bicuspid aortic valve and aortopathies, systemic rheumatic diseases and collagen vascular disorders, and cardiomyopathy-causing mutations. The authors cite published evidence when available and provide expert consensus otherwise. Most of the evidence available pertains to translational studies involving subjects of both sexes. However, the authors have prioritized review of data obtained from female patients, and direct comparison of CMR between women and men. This position statement does not consider CMR accessibility or availability of local expertise, but instead highlights the optimal utilization of CMR in women with known or suspected cardiovascular disease. Finally, the ultimate goal of this position statement is to improve the health of female patients with cardiovascular disease by providing specific recommendations on the use of CMR.

A personalized computational model of edema formation in myocarditis based on long-axis biventricular MRI images.

BACKGROUND: Myocarditis is defined as the inflammation of the myocardium, i.e. the cardiac muscle. Among the reasons that lead to this disease, we may include infections caused by a virus, bacteria, protozoa, fungus, and others. One of the signs of the inflammation is the formation of edema, which may be a consequence of the interaction between interstitial fluid dynamics and immune response. This complex physiological process was mathematically modeled using a nonlinear system of partial differential equations (PDE) based on porous media approach. By combing a model based on Biot's poroelasticity theory with a model for the immune response we developed a new hydro-mechanical model for inflammatory edema. To verify this new computational model, T2 parametric mapping obtained by Magnetic Resonance (MR) imaging was used to identify the region of edema in a patient diagnosed with unspecific myocarditis. RESULTS: A patient-specific geometrical model was created using MRI images from the patient with myocarditis. With this model, edema formation was simulated using the proposed hydro-mechanical mathematical model in a two-dimensional domain. The computer simulations allowed us to correlate spatiotemporal dynamics of representative cells of the immune systems, such as leucocytes and the pathogen, with fluid accumulation and cardiac tissue deformation. CONCLUSIONS: This study demonstrates that the proposed mathematical model is a very promising tool to better understand edema formation in myocarditis. Simulations obtained from a patient-specific model reproduced important aspects related to the formation of cardiac edema, its area, position, and shape, and how these features are related to immune response.

A free software for the calculation of T2* values for iron overload assessment.

Background Iron overload assessment with magnetic resonance imaging (MRI) using T2* has become a key diagnostic method in the management of many diseases. Quantitative analysis of the MRI images with a cost-effective tool has been a limitation to increased use of the method. Purpose To provide a free software solution for this purpose comparing the results with a commercial solution. Material and Methods The free tool was developed as a standalone program to be directly downloaded and ran in a common personal computer platform without the need of a dedicated workstation. Liver and cardiac T2* values were calculated using both tools and the values obtained compared between them in a group of 56 patients with suspected iron overload using Bland-Altman plots and concordance correlation coefficients (CCC). Results In the heart, the mean T2* differences between the two methods was 0.46 ms (95% confidence interval [CI], -0.037 -0.965) and in the liver 0.49 ms (95% CI, 0.257-0.722). The CCC for both the heart and the liver were significantly high (0.98 [95% CI, 0.966-0.988] with a Pearson ρ of 0.9811 and 0.991 [95% CI, 0.986-0.994] with a Pearson ρ of 0.996, respectively. No significant differences were observed when analyzing only patients with abnormal concentrations of iron in both organs compared to the whole cohort. Conclusion The proposed free software tool is accurate for calculation of T2* values of the liver and heart and might be a solution for centers that cannot use paid commercial solutions.

Highlights of the 16th annual scientific sessions of the Society for Cardiovascular Magnetic Resonance.

The 16th Annual Scientific Sessions of the Society for Cardiovascular Magnetic Resonance (SCMR) took place in San Francisco, USA at the end of January 2013. With a faculty of experts from across the world, this congress provided a wealth of insight into cutting-edge research and technological development. This review article intends to provide a highlight of what represented the most significant advances in the field of cardiovascular magnetic resonance (CMR) during this year's meeting.

Iron chelation therapy in the management of transfusion-related cardiac iron overload.

Iron overload is one of the major causes of morbidity and death in patients undergoing chronic transfusion therapy. Furthermore, excessive iron accumulation in the heart may result in impaired left ventricular dysfunction. With accurate monitoring techniques and treatment regimens, progression of heart complications can be followed, and their natural history changed. Iron chelation therapy is the mainstay of prevention and reversal of myocardial iron overload. Despite recent appraisals of general chelating strategies, the management of iron chelation in chronically transfused patients with a focus on the heart has not been extensively assessed. New studies published in the past couple of years have provided important new data in this topic and therefore this review summarizes the major studies that examined the removal of iron from the heart with the iron chelators: deferoxamine, deferiprone, and deferasirox. Since chronically transfused patients and their cardiac clinical presentations vary widely, this review tries to identify--with each drug--the precise scenarios evaluated, linking patients' baseline characteristics, clinical setting, and drug intake and dosing. Ultimately, by stratifying patients according to their cardiac iron overload status and ventricular function, this review identifies possible approaches for the initial treatment and follow-up of transfusion-related cardiac iron overload.

Cost-Effectiveness of Using the Coronary Artery Calcium Score in Guiding Therapeutic Decisions in Primary Prevention in the Brazilian Population. / Custo-Efetividade do Emprego do Escore de Cálcio Coronariano na Orientação para a Decisão Terapêutica na Prevenção Primária, na População Brasileira.

BACKGROUND: The use of the coronary artery calcium score to aid cardiovascular risk stratification may be a more cost-effective tool than the conventional strategy. OBJECTIVES: Evaluation of the cost-effectiveness of the use of the calcium score in therapeutic guidance for primary cardiovascular prevention. METHODS: A microsimulation model to assess the clinical and economic consequences of atherosclerotic cardiovascular disease, comparing the prevention strategy using the calcium score and the conventional strategy. RESULTS: The results obtained demonstrated a better cost-effectiveness of the therapeutic strategy guided by the calcium score, by reducing incremental costs and increasing quality-adjusted life years (QALY), which corresponds, in number, to improving the quality of life of the individual. CONCLUSIONS: The use of the coronary artery calcium score proved to be more cost-effective than the conventional strategy, both in terms of cost and QALY, in most of the scenarios studied.

FUNDAMENTO: O emprego do escore de cálcio no auxílio da estratificação de risco cardiovascular pode ser ferramenta com melhor custo-efetividade em comparação à estratégia convencional. OBJETIVOS: Avaliação da custo-efetividade do emprego do escore de cálcio na orientação terapêutica para a prevenção primária cardiovascular. MÉTODOS: Modelo de microssimulação para avaliar as consequências clínicas e econômicas da doença cardiovascular aterosclerótica, comparando-se a estratégia de prevenção pelo uso do escore de cálcio e a estratégia convencional. RESULTADOS: Resultados obtidos demonstram melhor custo-efetividade da estratégia terapêutica guiada pelo escore de cálcio, por meio da redução do custo incremental, e aumento nos anos de vida ajustados por qualidade (QALY), que corresponde, em número, ao benefício incorporado à qualidade de vida do indivíduo. CONCLUSÕES: O emprego do escore de cálcio mostrou-se mais custo-efetivo que a estratégia convencional tanto em custo como em QALY, na maioria dos cenários estudados.

Cost-Minimization Analysis for Cardiac Revascularization in 12 Health Care Systems Based on the EuroCMR/SPINS Registries.

OBJECTIVES: The aim of this study was to compare the costs of a noninvasive cardiac magnetic resonance (CMR)-guided strategy versus 2 invasive strategies with and without fractional flow reserve (FFR). BACKGROUND: Coronary artery disease (CAD) is a major contributor to the public health burden. Stress perfusion CMR has excellent accuracy to detect CAD. International guidelines recommend as a first step noninvasive testing of patients in stable condition with known or suspected CAD. However, nonadherence in routine clinical practice is high. METHODS: In the EuroCMR (European Cardiovascular Magnetic Resonance) registry (n = 3,647, 59 centers, 18 countries) and the U.S.-based SPINS (Stress-CMR Perfusion Imaging in the United States) registry (n = 2,349, 13 centers, 11 states), costs were calculated for 12 health care systems (8 in Europe, the United States, 2 in Latin America, and 1 in Asia). Costs included diagnostic examinations (CMR and x-ray coronary angiography [CXA] with and without FFR), revascularizations, and complications during 1-year follow-up. Seven subgroup analyses covered low- to high-risk cohorts. Patients with ischemia-positive CMR underwent CXA and revascularization at the treating physician's discretion (CMR+CXA strategy). In the hypothetical invasive CXA+FFR strategy, costs were calculated for initial CXA and FFR in vessels with ≥50% stenoses, assuming the same proportion of revascularizations and complications as with the CMR+CXA strategy and FFR-positive rates as given in the published research. In the CXA-only strategy, costs included CXA and revascularizations of ≥50% stenoses. RESULTS: Consistent cost savings were observed for the CMR+CXA strategy compared with the CXA+FFR strategy in all 12 health care systems, ranging from 42% ± 20% and 52% ± 15% in low-risk EuroCMR and SPINS patients with atypical chest pain, respectively, to 31% ± 16% in high-risk SPINS patients with known CAD (P < 0.0001 vs 0 in all groups). Cost savings were even higher compared with CXA only, at 63% ± 11%, 73% ± 6%, and 52% ± 9%, respectively (P < 0.0001 vs 0 in all groups). CONCLUSIONS: In 12 health care systems, a CMR+CXA strategy yielded consistent moderate to high cost savings compared with a hypothetical CXA+FFR strategy over the entire spectrum of risk. Cost savings were consistently high compared with CXA only for all risk groups.

Automated Quantitative Stress Perfusion in a Clinical Routine.

Cardiovascular magnetic resonance (CMR) perfusion imaging is a robust noninvasive technique to evaluate ischemia in patients with coronary artery disease (CAD). Although qualitative and semiquantitative methods have shown that CMR has high accuracy in diagnosing flow-obstructing lesions in CAD, quantitative ischemic burden is an important variable used in clinical practice for treatment decisions. Quantitative CMR perfusion techniques have evolved significantly, with accuracy comparable with both PET and microsphere evaluation. Routine clinical use of these quantitative techniques has been facilitated by the introduction of automated methods that accelerate the work flow and rapidly generate pixel-based myocardial blood flow maps.

T2* Mapping Techniques: Iron Overload Assessment and Other Potential Clinical Applications.

T2* mapping techniques has evolved significantly since their introduction in the early 2000s and a significant amount of evidence has been gathered to support their clinical routine use for iron overload assessment. This article focuses on the most important aspects of how to perform T2* imaging, from acquisition, to postprocessing, to analyzing the data with clinical concentration. Newer techniques have made T2* mapping more robust and accurate, allowing a broader use of this technique for noncontrast ischemia imaging based on blood oxygen levels, in addition to evaluation of intramyocardial hemorrhage and microvascular obstruction.

MRI for Iron Overload in Thalassemia.

MRI is a key tool in the current management of patients with thalassemia. Given its capability of assessing iron overload in different organs noninvasively and without contrast, it has significant advantages over other metrics, including serum ferritin. Liver iron concentration can be measured either with relaxometry methods T2*/T2 or signal intensity ratio techniques. Myocardial iron can be assessed in the same examination through T2* imaging. In this review, we focus on showing how MRI evaluates iron in both organs and the clinical applications as well as practical approaches to using this tool by clinicians taking care of patients with thalassemia.

Custo-Efetividade do Emprego do Escore de Cálcio Coronariano na Orientação para a Decisão Terapêutica na Prevenção Primária, na População Brasileira / Cost-Effectiveness of Using the Coronary Artery Calcium Score in Guiding Therapeutic Decisions in Primary Prevention in the Brazilian Population

Resumo Fundamento: O emprego do escore de cálcio no auxílio da estratificação de risco cardiovascular pode ser ferramenta com melhor custo-efetividade em comparação à estratégia convencional. Objetivos: Avaliação da custo-efetividade do emprego do escore de cálcio na orientação terapêutica para a prevenção primária cardiovascular. Métodos: Modelo de microssimulação para avaliar as consequências clínicas e econômicas da doença cardiovascular aterosclerótica, comparando-se a estratégia de prevenção pelo uso do escore de cálcio e a estratégia convencional. Resultados: Resultados obtidos demonstram melhor custo-efetividade da estratégia terapêutica guiada pelo escore de cálcio, por meio da redução do custo incremental, e aumento nos anos de vida ajustados por qualidade (QALY), que corresponde, em número, ao benefício incorporado à qualidade de vida do indivíduo. Conclusões: O emprego do escore de cálcio mostrou-se mais custo-efetivo que a estratégia convencional tanto em custo como em QALY, na maioria dos cenários estudados.

Abstract Background: The use of the coronary artery calcium score to aid cardiovascular risk stratification may be a more cost-effective tool than the conventional strategy. Objectives: Evaluation of the cost-effectiveness of the use of the calcium score in therapeutic guidance for primary cardiovascular prevention. Methods: A microsimulation model to assess the clinical and economic consequences of atherosclerotic cardiovascular disease, comparing the prevention strategy using the calcium score and the conventional strategy. Results: The results obtained demonstrated a better cost-effectiveness of the therapeutic strategy guided by the calcium score, by reducing incremental costs and increasing quality-adjusted life years (QALY), which corresponds, in number, to improving the quality of life of the individual. Conclusions: The use of the coronary artery calcium score proved to be more cost-effective than the conventional strategy, both in terms of cost and QALY, in most of the scenarios studied.

Regression of coronary artery outward remodeling in patients with non-ST-segment acute coronary syndromes: a longitudinal study using noninvasive magnetic resonance imaging.

BACKGROUND: The association of plaques with outward arterial remodeling and acute coronary syndromes (ACS) has been mostly investigated by cross-sectional intravascular ultrasound studies. Magnetic resonance imaging (MRI) has made it possible to noninvasively assess the coronary vessels of patients with chronic coronary artery disease, but no study has been done in patients with ACS. We sought to serially investigate changes in coronary vessel walls of patients with ACS using noninvasive serial MRI. METHODS: A total of 42 segments of coronary arteries from 22 patients presenting with non-ST-segment elevation ACS were studied at baseline in the acute phase and at 6 months after stabilization and optimization of medical therapy. Patients received routine medical treatment during this period with control of risk factors. Vessel wall area, maximum wall thickness, mean wall thickness, and lumen area were analyzed longitudinally using MRI. RESULTS: Vessel wall area (38.8 +/- 20.0 vs 27.7 +/- 10.4 mm2; P = .001), maximum wall thickness (2.9 +/- 0.7 vs 2.5 +/- 0.6 mm; P < .001), and mean wall thickness (2.0 +/- 0.7 vs 1.6 +/- 0.5 mm; P < .001) were significantly reduced at 6 months compared with baseline, whereas lumen area did not show significant changes (11.5 +/- 4.8 vs 10.9 +/- 5.0 mm2; P = .52). The wall/lumen ratio was significantly reduced from 3.7 +/- 1.7 to 2.9 +/- 1.3 (P = .01), suggesting a regression of outward remodeling. CONCLUSION: Patients with ACS have increased coronary vessel wall thickness and area that can regress with stabilization and medical therapy over the period of 6 months. Magnetic resonance imaging can detect and serially follow these changes, monitoring coronary vascular remodeling from the acute to the chronic phase of the disease.

Coronary artery disease in women: a review on prevention, pathophysiology, diagnosis, and treatment.

Despite numerous studies on women's cardiac health throughout the past decade, the number of female deaths caused by cardiovascular disease still rises and remains the leading cause of death in women in most areas of the world. Novel studies have demonstrated that cardiovascular disease, and more specifically coronary artery disease presentations in women, are different than those in men. In addition, pathology and pathophysiology of the disease present significant gender differences, which leads to difficulties concerning diagnosis, treatment and outcome of the female population. The reason for this disparity is all steps for female cardiovascular disease evaluation, treatment and prevention are not well elucidated; and an area for future research. This review brings together the most recent studies published in the field of coronary artery disease in women and points out new directions for future investigation on some of the important issues.

T1 mapping: technique and applications.

T1 mapping, one form of tissue characterization performed with a parametric approach, has been gaining rapid popularity, as different sequences have been developed to integrate image acquisition into a clinical routine. This technique allows fast progression from the basics of sequence development to its application in normal individuals and distinct diseases, sometimes overriding the more gradual steps taken with other cardiovascular magnetic resonance advances. In this review, the state-of-the-art in T1 mapping is examined, focusing on its techniques, sequences, comparison of native versus extracellular volume fraction measurements, and the current and future clinical applications of the method.