Gadolinium Enhancement Technique Research Articles

Magnetic Resonance Evaluation of Tissue Iron Deposition and Cardiac Function in Adult Regularly Transfused Thalassemia Intermedia Compared with Thalassemia Major Patients.

Objectives: This multicenter, retrospective, population-based, matched-cohort study compared clinical characteristics and magnetic resonance imaging (MRI) findings, including hepatic, pancreatic, and cardiac iron levels and cardiac function, between 135 adult regularly transfused thalassemia intermedia (TI) patients (44.73 ± 12.16 years, 77 females) and 135 age- and sex-matched thalassemia major (TM) patients (43.35 ± 9.83 years, 77 females), enrolled in the Extension-Myocardial Iron Overload in Thalassemia Network. Methods: The MRI protocol included the quantification of hepatic, pancreatic, and cardiac iron levels (R2* technique), the assessment of biventricular function parameters (cine images), and the detection of replacement myocardial fibrosis (late gadolinium enhancement technique). Results: Age, sex, frequency of splenectomy and chelation, and serum ferritin levels were not significantly different (p > 0.05) between the two groups, but TI patients started regular transfusions significantly later (p < 0.0001) and showed significantly lower pre-transfusion hemoglobin levels (p = 0.005). No difference was found in hepatic iron levels (p = 0.853). TI patients exhibited significantly lower pancreatic R2* values (p < 0.0001), also correcting for the duration of regular transfusions, and significantly lower cardiac R2* values (p < 0.0001). In the receiver operating characteristic analysis, pancreatic iron was the strongest discriminator between the two diseases. Left and right ventricular end-diastolic volume indexes were significantly higher in TI than in TM patients (p = 0.003 and p = 0.046, respectively), but the correction for the duration of regular transfusions removed the disease-specific differences (p > 0.05). Left ventricular (LV) mass index was significantly higher in TI (p = 0.049), while no difference (p > 0.05) was found in biventricular ejection fractions and replacement myocardial fibrosis. Conclusions: TI patients showed lower pancreatic and cardiac iron burden and more pronounced LV hypertrophy. These differences could not be explained by the different duration of the transfusional regimen.

Global longitudinal strain by cardiac magnetic resonance is associated with cardiac iron and complications in beta-thalassemia major patients

BackgroundThe aim of this cross-sectional study was to investigate the association of left ventricular (LV) strain parameters with demographics, clinical data, cardiovascular magnetic resonance (CMR) findings, and cardiac complications (heart failure and arrhythmias) in patients with β-thalassemia major (β-TM). MethodWe considered 266 β-TM patients (134 females, 37.08 ± 11.60 years) consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia (E-MIOT) project and 80 healthy controls (50 females, mean age 39.77 ± 11.29 years). The CMR protocol included cine images for the assessment of global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS) using feature tracking (FT) and for the quantification of LV function parameters, the T2* technique for the assessment of myocardial iron overload, and late gadolinium enhancement (LGE) technique. ResultsIn comparison to the healthy control group, β-TM patients showed impaired GLS, GCS, and GRS values.Among β-TM patients, sex was identified as the sole independent determinant of all LV strain parameters. All LV strain parameters displayed a significant correlation with LV end-diastolic volume index, end-systolic volume index, mass index, and ejection fraction, and with the number of segments exhibiting LGE. Only GLS exhibited a significant correlation with global heart T2* values and the number of segments with T2* < 20 ms. Patients with cardiac complications exhibited significantly impaired GLS compared to those without cardiac complications. ConclusionIn patients with β-TM, GLS, GCS, and GRS were impaired in comparison with control subjects. Among LV strain parameters, only GLS demonstrated a significant association with cardiac iron levels and complications.

Imaging of Cardiac Fibrosis: An Update, From the AJR Special Series on Imaging of Fibrosis.

Myocardial fibrosis (MF) is defined as excessive production and deposition of extra-cellular matrix (ECM) proteins that result in pathologic myocardial remodeling. Three types of MF have been identified: replacement fibrosis from tissue necrosis, reactive fibrosis from myocardial stress, and infiltrative interstitial fibrosis from progressive deposition of nondegradable material such as amyloid. Although echocardiography, nuclear medicine, and CT play important roles in the assessment of MF, MRI is pivotal in the evaluation of MF, with the late gadolinium enhancement (LGE) technique used as a primary end point. The LGE technique focuses on the pattern and distribution of gadolinium accumulation in the myocardium and assists in the diagnosis and establishment of the cause of both ischemic and nonischemic cardiomyopathy. LGE MRI also aids prognostication and risk stratification. In addition, LGE MRI is used to guide the management of patients considered for ablation for arrhythmias. Parametric mapping techniques, including T1 mapping and extracellular volume measurement, allow detection and quantification of diffuse fibrosis, which may not be detected by LGE MRI. These techniques also allow monitoring of disease progression and therapy response. This review provides an update on the imaging of MF, including prognostication and risk stratification tools, electrophysiologic considerations, and disease monitoring.

Multiparametric cardiac magnetic resonance in patients with thalassemia intermedia: new insights from the E-MIOT network.

In a relatively large cohort of thalassemia intermedia (TI) patients, we systematically investigated myocardial iron overload (MIO), function, and replacement fibrosis using cardiac magnetic resonance (CMR), we assessed the clinical determinants of global heart T2* values, and we explored the association between multiparametric CMR findings and cardiac complications. We considered 254 beta-TI patients (43.14 ± 13.69years, 138 females) consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia project. MIO was quantified by T2* technique and biventricular function and atrial areas by cine images. Macroscopic myocardial fibrosis was detected by late gadolinium enhancement technique. Compared to never/sporadically transfused patients, regularly transfused (RT)-TI patients exhibited significantly lower global heart T2* values, biventricular end-diastolic volume indexes, left ventricular mass index, and cardiac index. In RT-TI patients, age and serum ferritin levels were the strongest predictors of global heart T2* values. Independently from the transfusional state, cardiac T2* values were not associated with biventricular function. Of the 103 (40.6%) patients in whom the contrast medium was administrated, 27 (26.2%) had replacement myocardial fibrosis. Age, sex distribution, cardiac iron, and biventricular function parameters were comparable between patients without and without replacement myocardial fibrosis. Twenty-five (9.8%) patients had a history of cardiac complications (heart failure and arrhythmias). Increased age and replacement myocardial fibrosis emerged as significant risk markers for cardiac complications. In TI, regular transfusions are associated with less pronounced cardiac remodeling but increase the risk of MIO. Replacement myocardial fibrosis is a frequent finding associated with cardiac complications.

The additive prognostic value of end-systolic pressure-volume relation by stress CMR in patients with known or suspected coronary artery disease.

The difference between rest and peak stress end-systolic pressure-volume relation (ΔESPVR) is an afterload-independent index of left ventricular (LV) contractility. We assessed the independent prognostic value of ΔESPVR index by dipyridamole stress-cardiovascular magnetic resonance (CMR) in patients with known/suspected coronary artery disease (CAD). We considered 196 consecutive patients (62.74 ± 10.66years, 49 females). Wall motion and perfusion abnormalities at rest and peak stress were analysed. Replacement myocardial fibrosis was detected by late gadolinium enhancement(LGE) technique. The ESPVR was evaluated at rest and peak stress from raw measurement of systolic arterial pressure and end-systolic volume by biplane Simpson's method. A reduced ΔESPVR index (≤ 0.02mmHg/mL/m2) was found in 88(44.9%) patients and it was associated with a lower LV ejection fraction(EF) and with a higher frequency of abnormal stress CMR and myocardial fibrosis. During a mean follow-up of 53.17 ± 28.21months, 50(25.5%) cardiac events were recorded: 5 cardiac deaths, 17 revascularizations, one myocardial infarction, 23 hospitalisations for heart failure or unstable angina, and 4 ventricular arrhythmias. According to Cox regression analysis, diabetes, family history, LVEF, abnormal stress CMR, myocardial fibrosis, and reduced ΔESPVR were significant univariate prognosticators. In the multivariate analysis the independent predictors were ΔESPVR index ≤ 0.02mmHg/mL/m2 (hazard ratio-HR = 2.58, P = 0.007), myocardial fibrosis (HR = 2.13, P = 0.036), and diabetes (HR = 2.33, P = 0.012). ΔESPVR index by stress-CMR was independently associated with cardiac outcomes in patients with known/suspected CAD, in addition to replacement myocardial fibrosis and diabetes. Thus, the assessment of ΔESPVR index may be included into the standard stress-CMR exam to further stratify the patients.

Multiparametric Cardiac Magnetic Resonance Assessment in Sickle Beta Thalassemia.

Cardiac involvement in sickle beta thalassemia (Sβ-thal) patients has been poorly investigated. We aimed to evaluate cardiac function and myocardial iron overload by cardiovascular magnetic resonance (CMR) in patients with Sβ-thal. One-hundred and eleven Sβ-thal patients consecutively enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) network were studied and compared with 46 sickle cell anemia (SCA) patients and with 111 gender- and age- matched healthy volunteers. Cine images were acquired to quantify biventricular function. Myocardial iron overload (MIO) was assessed by the T2* technique, while macroscopic myocardial fibrosis was evaluated by the late gadolinium enhancement (LGE) technique. In Sβ-thal and SCA patients, the morphological and functional CMR parameters were not significantly different, except for the left atrial area and left ventricular (LV) stroke volume, indexed by body surface area (p = 0.023 and p = 0.048, respectively), which were significantly higher in SCA patients. No significant differences between the two groups were found in terms of myocardial iron overload and macroscopic myocardial fibrosis. When compared to healthy subjects, Sβ-thal patients showed significantly higher bi-atrial and biventricular parameters, except for LV ejection fraction, which was significantly lower. The CMR analysis confirmed that Sβ-thal and SCA patients are phenotypically similar. Since Sβ-thal patients showed markedly different morphological and functional indices from healthy subjects, it would be useful to identify Sβ-thal/SCA-specific bi-atrial and biventricular reference values.

Left ventricular fibrosis in arrhythmic mitral valve prolapse: quantification and comparison of semi-automated techniques assessed by cardiac magnetic resonance

PurposeLeft ventricular (LV) fibrosis has a key role in arrhythmogenesis in patients with mitral valve prolapse (MVP). Cardiac magnetic resonance identifies LV fibrosis by using late gadolinium enhancement (LGE) technique. LGE assessment and quantification in patients with MVP lacks of standardization protocols.Methods66 MVP patients with normal systolic function and without significant regurgitation were enrolled. Semi-automated gray-scale thresholding techniques using full width at half maximum (FWHM) and 2, 3 and 5 standard deviation (SD) above the remote myocardium were used and compared with the visual assessment, considered as the gold standard.ResultsLGE was identified in 41 MVP patients (62%) and quantified. The mean quantity of LGE visually assessed was 2.40 ± 1.07% or 1.40 ± 0.82 g. With FWHM, LGE resulted 3.56 ± 1.23% or 1.99 ± 1.13 g. Using thresholding, the mean LGE quantity was 9.2 ± 3.1% or 4.82 ± 2.28 g for 2-SD, 5.72 ± 1.75% or 3.06 ± 1.47 g for 3-SD and 2.36 ± 0.99% or 1.29 ± 0.79 g for 5-SD. The 5-SD measurement in percentage demonstrated a good correlation with LGE quantification visually assessed (2.40 ± 1.07 vs. 2.363 ± 0.9909, p = 0.543). When compared with the gold standard, the 5-SD threshold quantification, both in percentage and in grams, revealed the least intra-observer (respectively, ICC: 0.976 and 0.966) and inter-observer variability (respectively ICC: 0.948 and 0.935).ConclusionThe 5-SD gray-scale threshold technique in percentage revealed the best correlation with the visual assessment and an optimal reproducibility in MVP patient.

Low Vitamin D Levels Are Associated with Increased Cardiac Iron Uptake in Beta-Thalassemia Major.

We evaluated the association of vitamin D and parathormone (PTH) levels with cardiac iron and function in beta-thalassemia major (β-TM) patients. Two-hundred and seventy-eight TM patients (39.04 ± 8.58 years, 56.8% females) underwent magnetic resonance imaging for the assessment of iron overload (T2* technique), biventricular function parameters (cine images), and replacement myocardial fibrosis (late gadolinium enhancement technique). Vitamin D levels were deficient (<20 ng/dL) in 107 (38.5%) patients, insufficient (20-30 ng/dL) in 96 (34.5%) patients, and sufficient (≥30 ng/dL) in 75 (27.0%) patients. Deficient vitamin D patients had a significantly higher frequency of myocardial iron overload (MIO; global heart T2* < 20 ms) than patients with sufficient and insufficient vitamin D levels and a significantly higher left ventricular end-diastolic volume index and mass index than patients with sufficient vitamin D levels. PTH was not associated with cardiac iron, function, or fibrosis. In the multivariate regression analysis, vitamin D, serum ferritin, and pancreatic iron levels were the strongest predictors of global heart T2* values. In receiver operating characteristic curve analysis, a vitamin D level ≤ 17.3 ng/dL predicted MIO with a sensitivity of 81.5% and a specificity of 75.3% (p < 0.0001). In TM, the periodic and regular assessment of vitamin D levels can be beneficial for the prevention of cardiac iron accumulation and subsequent overt dysfunction.

Phenotypic Clustering of Beta-Thalassemia Intermedia Patients Using Cardiovascular Magnetic Resonance.

We employed an unsupervised clustering method that integrated demographic, clinical, and cardiac magnetic resonance (CMR) data to identify distinct phenogroups (PGs) of patients with beta-thalassemia intermedia (β-TI). We considered 138 β-TI patients consecutively enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) Network who underwent MR for the quantification of hepatic and cardiac iron overload (T2* technique), the assessment of biventricular size and function and atrial dimensions (cine images), and the detection of replacement myocardial fibrosis (late gadolinium enhancement technique). Three mutually exclusive phenogroups were identified based on unsupervised hierarchical clustering of principal components: PG1, women; PG2, patients with replacement myocardial fibrosis, increased biventricular volumes and masses, and lower left ventricular ejection fraction; and PG3, men without replacement myocardial fibrosis, but with increased biventricular volumes and masses and lower left ventricular ejection fraction. The hematochemical parameters and the hepatic and cardiac iron levels did not contribute to the PG definition. PG2 exhibited a significantly higher risk of future cardiovascular events (heart failure, arrhythmias, and pulmonary hypertension) than PG1 (hazard ratio-HR = 10.5; p = 0.027) and PG3 (HR = 9.0; p = 0.038). Clustering emerged as a useful tool for risk stratification in TI, enabling the identification of three phenogroups with distinct clinical and prognostic characteristics.

Diastology with Cardiac MRI: A Practical Guide.

Diastolic filling of the ventricle is a complex interplay of volume and pressure, contingent on active energy-dependent myocardial relaxation and myocardial stiffness. Abnormal diastolic function is the hallmark of the clinical entity of heart failure with preserved ejection fraction (HFpEF), which is now the dominant type of heart failure and is associated with significant morbidity and mortality. Although echocardiography is the current first-line imaging modality used in evaluation of diastolic function, cardiac MRI (CMR) is emerging as an important technique. The principal role of CMR is to categorize the cause of diastolic dysfunction (DD) and distinguish other entities that manifest similarly to HFpEF, particularly infiltrative and pericardial disorders. CMR also provides prognostic information and risk stratification based on late gadolinium enhancement and parametric mapping techniques. Advances in hardware, sequences, and postprocessing software now enable CMR to diagnose and grade DD accurately, a role traditionally assigned to echocardiography. Two-dimensional or four-dimensional velocity-encoded phase-contrast sequences can measure flow and velocities at the mitral inflow, mitral annulus, and pulmonary veins to provide diastolic functional metrics analogous to those at echocardiography. The commonly used cine steady-state free-precession sequence can provide clues to DD including left ventricular mass, left ventricular filling curves, and left atrial size and function. MR strain imaging provides information on myocardial mechanics that further aids in diagnosis and prognosis of diastolic function. Research sequences such as MR elastography and MR spectroscopy can help evaluate myocardial stiffness and metabolism, respectively, providing additional insights on diastolic function. The authors review the physiology of diastolic function, mechanics of diastolic heart failure, and CMR techniques in the evaluation of diastolic function. ©RSNA, 2023 Quiz questions for this article are available in the supplemental material.

Diagnostic Role of Native T1 Mapping Compared to Conventional Magnetic Resonance Techniques in Cardiac Disease in a Real-Life Cohort.

We sought to compare native T1 mapping to conventional late gadolinium enhancement (LGE) and T2-STIR techniques in a cohort of consecutive patients undergoing cardiac MRI (CMR). CMR was performed in 323 patients, 206 males (64%), mean age 54 ± 8 years, and in 27 age- and sex- matched healthy controls. In T2-STIR images, myocardial hyperintensity suggesting edema was found in 41 patients (27%). LGE images were positive in 206 patients (64%). T1 mapping was abnormal in 171 (49%). In 206 patients (64%), a matching between LGE and native T1 was found. T1 was abnormal in 32 out of 41 (78%) with edema in T2-STIR images. Overall, LGE and/or T2-STIR were abnormal in 209 patients, whereas native T1 was abnormal in 154 (52%). Conventional techniques and T1 mapping were concordant in 208 patients (64%). In 39 patients, T1 mapping was positive despite negative conventional techniques (12%). T1 mapping was able in conditions with diffuse myocardial damage such as cardiac amyloidosis, scleroderma, and Fabry disease (additive role in 42%). In contrast, T1 mapping was less effective in cardiac disease with regional distribution of myocardial damage such as myocardial infarction, HCM, and myocarditis. In conclusion, conventional LGE/T2-STIR and T1 mapping are complementary techniques and should be used together in every CMR examination.

Phenotyping heart failure by cardiac magnetic resonance imaging of cardiac macro- and microscopic structure: state of the art review.

Heart failure demographics have evolved in past decades with the development of improved diagnostics, therapies, and prevention. Cardiac magnetic resonance (CMR) has developed in a similar timeframe to become the gold-standard non-invasive imaging modality for characterizing diseases causing heart failure. CMR techniques to assess cardiac morphology and function have progressed since their first use in the 1980s. Increasingly efficient acquisition protocols generate high spatial and temporal resolution images in less time. This has enabled new methods of characterizing cardiac systolic and diastolic function such as strain analysis, exercise real-time cine imaging and four-dimensional flow. A key strength of CMR is its ability to non-invasively interrogate the myocardial tissue composition. Gadolinium contrast agents revolutionized non-invasive cardiac imaging with the late gadolinium enhancement technique. Further advances enabled quantitative parametric mapping to increase sensitivity at detecting diffuse pathology. Novel methods such as diffusion tensor imaging and artificial intelligence-enhanced image generation are on the horizon. Magnetic resonance spectroscopy (MRS) provides a window into the molecular environment of the myocardium. Phosphorus (31P) spectroscopy can inform the status of cardiac energetics in health and disease. Proton (1H) spectroscopy complements this by measuring creatine and intramyocardial lipids. Hyperpolarized carbon (13C) spectroscopy is a novel method that could further our understanding of dynamic cardiac metabolism. CMR of other organs such as the lungs may add further depth into phenotypes of heart failure. The vast capabilities of CMR should be deployed and interpreted in context of current heart failure challenges.

Pancreatic fatty replacement as risk marker for altered glucose metabolism and cardiac iron and complications in thalassemia major

ObjectivesThis multicenter study assessed the extent of pancreatic fatty replacement and its correlation with demographics, iron overload, glucose metabolism, and cardiac complications in a cohort of well-treated patients with thalassemia major (TM).MethodsWe considered 308 TM patients (median age: 39.79 years; 182 females) consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia Network. Magnetic resonance imaging was used to quantify iron overload (IO) and pancreatic fat fraction (FF) by T2* technique, cardiac function by cine images, and to detect replacement myocardial fibrosis by late gadolinium enhancement technique. The glucose metabolism was assessed by the oral glucose tolerance test.ResultsPancreatic FF was associated with age, body mass index, and history of hepatitis C virus infection. Patients with normal glucose metabolism showed a significantly lower pancreatic FF than patients with impaired fasting glucose (p = 0.030), impaired glucose tolerance (p < 0.0001), and diabetes (p < 0.0001). A normal pancreatic FF (< 6.6%) showed a negative predictive value of 100% for abnormal glucose metabolism. A pancreatic FF > 15.33% predicted the presence of abnormal glucose metabolism. Pancreas FF was inversely correlated with global pancreas and heart T2* values. A normal pancreatic FF showed a negative predictive value of 100% for cardiac iron. Pancreatic FF was significantly higher in patients with myocardial fibrosis (p = 0.002). All patients with cardiac complications had fatty replacement, and they showed a significantly higher pancreatic FF than complications-free patients (p = 0.002).ConclusionPancreatic FF is a risk marker not only for alterations of glucose metabolism, but also for cardiac iron and complications, further supporting the close link between pancreatic and cardiac disease.Key Points• In thalassemia major, pancreatic fatty replacement by MRI is a frequent clinical entity, predicted by a pancreas T2* < 20.81 ms and associated with a higher risk of alterations in glucose metabolism.• In thalassemia major, pancreatic fatty replacement is a strong risk marker for cardiac iron, replacement fibrosis, and complications, highlighting a deep connection between pancreatic and cardiac impairment.

Cardiac MRI: State of the Art.

Cardiac MRI plays an important role in the evaluation of cardiovascular diseases (CVDs), including ischemic heart disease, cardiomyopathy, valvular disease, congenital disease, pericardial disease, and masses. Large multicenter trials have shown the positive impact of MRI-based management on outcomes in several CVDs. These results have made MRI an indispensable technique in the evaluation of these diseases, and cardiac MRI has an important role in multisociety guidelines. MRI is the reference standard for quantification of ventricular volumes and function. Flow imaging enables accurate quantification of flow and velocities through valves, shunts, and surgical conduits or baffles. Late gadolinium enhancement and parametric mapping techniques enable tissue characterization and yield prognostic information. In the past decade, cardiac MRI technology has seen rapid advances in both hardware and sequences. Multiple novel sequences, such as parametric mapping and four-dimensional flow, are increasingly being incorporated into routine clinical practice. Acceleration strategies have matured, allowing faster acquisition of cardiac MRI sequences in patients with arrhythmia and poor breath holding. Challenges of cardiac MRI at high-field-strength magnets and in patients with indwelling cardiac devices or severe renal dysfunction have been mitigated. Artificial intelligence techniques are decreasing the complexity of MRI acquisition and postprocessing. This article reviews the current state of the art and emerging techniques in cardiac MRI.

Additional value of T1 and T2 mapping techniques for early detection of myocardial involvement in scleroderma

BackgroundWe evaluated the prevalence of myocardial involvement by native T1 and T2 mapping, the diagnostic performance of mapping in addition to conventional Lake Louise Criteria (LLC), as well as correlations between mapping findings and clinical or conventional cardiovascular magnetic resonance (CMR) parameters in systemic sclerosis (SSc) patients. MethodsFifty-five SSc patients (52.31 ± 13.24 years, 81.8% female) and 55 age- and sex-matched healthy subjects underwent clinical, bio-humoral assessment, and CMR. The imaging protocol included: T2-weighted, early post-contrast cine sequences, native T1 and T2 mapping by a segmental approach, and late gadolinium enhancement (LGE) technique. ResultsGlobal myocardial T1 and T2 values were significantly higher in SSc patients than in healthy subjects. An increase in native T1 and/or T2 was present in the 62.1% of patients with normal conventional CMR techniques (negative LGE and T2-weighted images). Respectively, 13.5% and 59.6% of patients fulfilled original and updated LLC (overall agreement = 53.9%).Compared with patients with normal native T1, patients with increased T1 (40.0%) featured significantly higher left ventricular end-diastolic volume index and cardiac index, biventricular stroke volume indexes, and global heart T2 values, and more frequently had a history of digital ulcers. Biochemical and functional CMR parameters were comparable between patients with normal and increased T2 (61.8%). ConclusionT1 and T2 mapping are sensitive parameters that should be included in the routine clinical assessment of SSc patients for detecting early/subclinical myocardial involvement.

Cardiac Magnetic Resonance Predicts Heart Failure Mortality in Patients with Thalassemia Major

Iron-induced Heart Failure (HF) still remains the main cause of mortality in patients with thalassemia major (TM), although the introduction of the T2* Cardiovascular Magnetic Resonance (CMR) for the non-invasive assessment of Myocardial Iron Overload (MIO) led to a significant increase in survival rate. However, the pathophysiology of heart failure in TM can be multifactorial. Thanks to its multiparametric potential, CMR represents a unique tool for characterization of myocardial involvement. It is the gold standard for the quantification of biventricular size and function by cine images and for the detection of replacement fibrosis by late gadolinium enhancement (LGE) technique. The aim of this multicenter study was to evaluate the prognostic value of multiparametric CMR in predicting death for HF. We considered 1398 white TM patients who performed a baseline CMR exam within the Myocardial Iron Overload in Thalassemia (MIOT) network. As per inclusion criteria, no patient had a history of HF. Mean age was 30.8±8.9 years and 725 (51.9%) patients were females. During a mean follow-up of 4.83±2.05 years, 49.1% of the patients changed at least once the chelation regimen (i.e.: either switched to a different type of chelator or underwent dose/frequency modification); these patients were more likely to have a global heart T2* value<20ms than patients who maintained the same regimen (33.2% vs 19.7%; P<0.0001) Twelve (1.0%) patients died from heart failure. Table 1 shows the results, presented as hazard ratio (HR) with 95% confidence intervals (CI), of the univariate Cox Regression analysis, performed to test the association between the considered prognostic variables and the outcome. No association was detected between age or gender and HF mortality. Significant MIO (global heart T2*<20 ms), ventricular dysfunction, ventricular dilation, and replacement myocardial fibrosis were identified as significant univariate prognosticators. Due to the low number of deaths for HF, it was not possible to perform a multivariate model. However, based on the presence of the four CMR predictors of HF death, patients were divided into three subgroups: four markers (7 patients; one HF death-14.3%), one to four markers (617 patients, 9 HF deaths-1.5%), and none of the four markers (488 patients; one HF death-0.2%). Patients having all four markers had a significantly higher risk of dying for HF than patients without markers (HR=89.93; 95%CI=5.62-1439.46; P=0.001) or with one to three CMR markers (HR=12.69; 95%CI=1.60-100.36; P=0.016). In our homogeneous white and well-treated Italian/Mediterranean population, we detected a low incidence of deaths for HF, since the T2* report guided the patient-specific adjustment of the chelation regimen. As expected, MIO was a significant predictor of HF death but also other CMR parameters, namely ventricular dilatation, ventricular dysfunction, and replacement myocardial fibrosis emerged as unfavorable prognosis determinant. Importantly, when the four CMR indices were evaluated in combination, they fine-tuned the prognostic stratification of TM patients. Hence, the findings of the present study promote the exploitation of the full potential of CMR, including LGE, for a better risk stratification of TM patients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Clinical implications of cardiac magnetic resonance imaging fibrosis.

Cardiac magnetic resonance (CMR) is a non-invasive imaging method that allows to characterize myocardial tissue. In particular, using the late gadolinium enhancement technique, it is possible to identify areas of focal fibrosis. Specific distribution patterns of this fibrosis allow us to distinguish ischaemic cardiomyopathy (iCMP) from non-ischaemic cardiomyopathy (nCMP) and sometimes to identify the aetiology of the latter. Diffuse fibrosis can also be identified using the parametric T1 mapping sequences. For this purpose, the native T1 of the tissue is measured before the administration of the contrast agent (c.a.) or the extracellular volume is calculated after c.a. Both focal and diffuse fibrosis evaluated with CMR appear to be strong prognostic predictors for the identification of threatening ventricular arrhythmias and sudden cardiac death. These evidence open the doors to a possible role of CMR in the selection of the patient to be sent to a defibrillator implant in primary prevention. In this review, we will briefly review the techniques used in CMR for the evaluation of fibrosis. We will then focus on the clinical role of myocardial tissue fibrosis detection in iCMP and nCMP.

Increased myocardial extracellular volume is associated with myocardial iron overload and heart failure in thalassemia major.

Myocardial extracellular volume (ECV) by cardiovascular magnetic resonance (CMR) is a surrogate marker of diffuse fibrosis. We evaluated the association between ECV and demographics, CMR findings, and cardiac involvement in patients with thalassemia major (TM). A total of 108 β-TM patients (62 females, 40.16 ± 8.83 years), consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia Network, and 16 healthy subjects (6 females, 37.12 ± 16.13 years) underwent CMR. The protocol included assessment of T2*, native T1, and T2 values in all 16 myocardial segments for myocardial iron overload (MIO) quantification, cine images for left ventricular (LV) function quantification, post-contrast T1 mapping for ECV calculation, and late gadolinium enhancement (LGE) technique for replacement myocardial fibrosis detection. Global ECV values were significantly higher in females than in males. Global ECV values were significantly higher in patients with significant MIO (global heart T2* < 20 ms) than in patients without significant MIO, and both groups exhibited higher global ECV values than healthy subjects. No association was detected between native T1 and ECV values, while patients with reduced global heart T2 values showed significantly higher global ECV values than patients with normal and increased global heart T2. Global ECV values were not correlated with LV function/size and were comparable between patients with and without LGE. Compared to patients without heart failure, patients with a history of heart failure (N = 10) showed significantly higher global heart ECV values. In TM, increased myocardial ECV, potentially reflecting diffuse interstitial fibrosis, is associated with MIO and heart failure. • CMR-derived myocardial extracellular volume is increased in thalassemia major patients, irrespective of the presence of late gadolinium enhancement. • In thalassemia major, myocardial iron overload contributes to the increase in myocardial ECV, which potentially reflects diffuse interstitial fibrosis and is significantly associated with a history of heart failure.

Relationship between pancreatic iron overload, glucose metabolism and cardiac complications in sickle cell disease: An Italian multicentre study

Evidence about the cross-talk between iron, glucose metabolism, and cardiac disease is increasing. We aimed to explore the link of pancreatic iron by Magnetic Resonance Imaging (MRI) with glucose metabolism and cardiac complications (CC) in sickle cell disease (SCD) patients. We considered 70 SCD patients consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia Network. Iron overload was quantified by R2* technique and biventricular function by cine images. Macroscopic myocardial fibrosis was evaluated by late gadolinium enhancement technique. Glucose metabolism was assessed by the oral glucose tolerance test. Patients with an altered glucose metabolism showed a significantly higher pancreas R2* than patients with normal glucose metabolism. Pancreatic siderosis emerged as a risk factor for the development of metabolic alterations (OddsRatio 8.25, 95%confidence intervals 1.51-45.1; p=.015). Global pancreas R2* values were directly correlated with mean serum ferritin levels and liver iron concentration. Global pancreas R2* was not significantly associated with global heart R2* and macroscopic myocardial fibrosis. Patients with history of CC showed a significantly higher global pancreas R2* than patients with no CC. Our findings support the evaluation of pancreatic R2* by MRI in SCD patients to prevent the development of metabolic and cardiac disorders.

Link between Genotype and Multi-Organ Iron and Complications in Children with Transfusion-Dependent Thalassemia.

We evaluated the impact of the genotype on hepatic, pancreatic and myocardial iron content, and on hepatic, cardiac and endocrine complications in children with transfusion-dependent β-thalassemia (β-TDT). We considered 68 β-TDT patients (11.98 ± 3.67 years, 51.5% females) consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia network. Iron overload was quantified by T2* technique and biventricular function by cine images. Replacement myocardial fibrosis was evaluated by late gadolinium enhancement technique. Three groups of patients were identified: homozygous β+ (N = 19), compound heterozygous β0β+ (N = 24), and homozygous β0 (N = 25). The homozygous β0 group showed significantly lower global heart and pancreas T2* values than the homozygous β+ group. Compared to patients with homozygous β+ genotype, β0β+ as well as β0β0 patients were more likely to have pancreatic iron overload (odds ratio = 6.53 and 10.08, respectively). No difference was detected in biventricular function parameters and frequency of replacement fibrosis. No patient had cirrhosis/fibrosis, diabetes or heart failure, and the frequency of endocrinopathies was comparable among the groups. In pediatric β-TDT patients, there is an association between genotype and cardiac and pancreatic iron overload. The knowledge of patients’ genotype can be valuable in predicting some patients’ phenotypic features and in helping the clinical management of β-TDT patients.