Real-life experience with liver iron concentration R2 MRI measurement in patients with hemoglobinopathies: baseline data from LICNET.

BACKGROUND: Real-life data on the use of R2 MRI for the assessment of liver iron concentration (LIC) remain limited. METHODS: We conducted a cross-sectional analysis on 363 patients (mean age 35.6 yr, 44.1% men) with hemoglobinopathies (204 ß-thalassemia major [TM], 102 ß-thalassemia intermedia [TI], and 57 sickle cell disease [SCD]) that were evaluated with R2 MRI as part of LICNET, an MRI network of 13 Italian treatment centers. RESULTS: The mean LIC was 7.8 mg/g (median: 4.0), with high LIC (>7 mg/g) noted in both transfused (TM, TI 37%; SCD 38%) and non-transfused (TI 20%) patients. Ferritin levels correlated with LIC in both transfused (TM, TI, SCD) and non-transfused (TI) patients (P < 0.001), although lower values predicted high LIC in non-transfused patients (1900 vs. 650 ng/mL in TM vs. non-transfused TI). A correlation between LIC and ALT levels was only noted in HCV-negative patients (rs = 0.316, P < 0.001). The proportion of patients with high LIC was significantly different between iron chelators used (P = 0.023), with the lowest proportion in deferasirox (30%) and highest in deferiprone (53%)-treated patients. CONCLUSIONS: High LIC values persist in subgroups of patients with hemoglobinopathy, warranting closer monitoring and management optimization, even for non-transfused patients with relatively low ferritin levels.

Extramedullary hematopoiesis is associated with lower cardiac iron loading in chronically transfused thalassemia patients.

The aim of this study was to evaluate, in a large cohort of chronically transfused patients, whether the presence of extramedullary hematopoiesis (EMH) accounts for the typical patterns of cardiac iron distribution and/or cardiac function parameters. We retrospectively selected 1,266 thalassemia major patients who had undergone regular transfusions (611 men and 655 women; mean age: 31.3 ± 8.9 years, range: 4.2-66.6 years) and were consecutively enrolled within the Myocardial Iron Overload in Thalassemia network. The presence of EMH was evaluated based on steady-state free precession sequences; cardiac and liver iron overloads were quantified using a multiecho T2* approach; cardiac function parameters and pulmonary diameter were quantified using the steady-state free precession sequences; and myocardial fibrosis was evaluated using the late gadolinium enhancement technique. EMH was detected in 167 (13.2%) patients. The EMH+ patients had significantly lower cardiac iron overload than that of the EMH- patients (P = 0.003). The patterns of cardiac iron distribution were significantly different in the EMH+ and EMH- patients (P < 0.0001), with a higher prevalence of patients with no myocardial iron overload and heterogeneous myocardial iron overload and no significant global heart iron in the EMH+ group EMH+ patients had a significantly higher left ventricle mass index (P = 0.001) and a significantly higher pulmonary artery diameter (P = 0.002). In conclusion, in regularly transfused thalassemia patients, EMH was common and was associated with a thalassemia intermedia-like pattern of cardiac iron deposition despite regular transfusion therapy.

Myocardial iron overload in thalassaemia major. How early to check?

The age at which it is necessary to start Cardiovascular Magnetic Resonance (CMR) T2* screening in thalassaemia major (TM) is still uncertain. To clarify this point, we evaluated the prevalence of myocardial iron overload (MIO), function and fibrosis by CMR in TM patients younger than 10 years. We retrospectively selected 35 TM patients enrolled in the Myocardial Iron Overload in Thalassaemia network. MIO was measured by T2* multislice multiecho technique. Biventricular function parameters were evaluated by cine images. To detect myocardial fibrosis, late gadolinium enhancement images were acquired. Patients' age ranged from 4·2 to 9·7 years. All scans were performed without sedation. Nine patients showed no MIO, 22 patients had heterogeneous MIO with a T2* global value ≥20 ms; two patients had heterogeneous MIO with a T2* global value <20 ms and two patients showed homogeneous MIO. No patient showed myocardial fibrosis. Among the patients with heart T2*<20 ms, the youngest was 6 years old, none showed heart dysfunction and the iron transfused was <35 g in all cases. Cardiac iron loading can occur much earlier than previously described. The first cardiac T2* assessment should be performed as early as feasible without sedation, especially if chelation is started late or if poor compliance is suspected.

Cardiac complications and diabetes in thalassaemia major: a large historical multicentre study.

The relationship between diabetes mellitus (DM) and cardiac complications has never been systematically studied in thalassaemia major (TM). We evaluated a large retrospective historical cohort of TM to determine whether DM is associated with a higher risk of heart complications. We compared 86 TM patients affected by DM with 709 TM patients without DM consecutively included in the Myocardial Iron Overload in Thalassaemia database where clinical/instrumental data are recorded from birth to the first cardiovascular magnetic resonance (CMR) exam. All of the cardiac events considered were developed after the DM diagnosis. In DM patients versus non-DM patients we found a significantly higher frequency of cardiac complications (46.5% vs. 16.9%, P < 0.0001), heart failure (HF) (30.2% vs. 11.7%, P < 0.0001), hyperkinetic arrhythmias (18.6% vs. 5.5%, P < 0.0001) and myocardial fibrosis assessed by late gadolinium enhancement (29.9% vs. 18.4%, P = 0.008). TM patients with DM had a significantly higher risk of cardiac complications [odds ratio (OR) 2.84, P < 0.0001], HF (OR 2.32, P = 0.003), hyperkinetic arrhythmias (OR 2.21, P = 0.023) and myocardial fibrosis (OR 1.91, P = 0.021), also adjusting for the absence of myocardial iron overload assessed by T2* CMR and for the covariates (age and/or endocrine co-morbidity). In conclusion, DM significantly increases the risk for cardiac complications, HF, hyperkinetic arrhythmias and myocardial fibrosis in TM patients.

Adrenal incidentaloma in thalassemia: a case report and literature review.

In the last 30 years the development and widespread use of modern imaging techniques has caused a 20-time increase in the diagnosis of adrenal incidentaloma (AI). Among AIs myelolipoma (ML) is reported with a frequency up to 10%. In the literature 8 patients with adrenal masses in thalassaemia or chronic haemolytic anaemia have been reported: five cases were shown to have extramedullary haematopoiesis (EH) and 3 ML. We describe here a case of an adult male affected by beta thalassaemia intermedia and large bilateral lipomatous adrenal masses. The patient was referred to our ward at the age of 55 and underwent hormonal testing, MRI, and SPECT/CT scans. Adrenal masses were hormonally inactive, and fat-containing on MRI and CT scans. SPECT/CT examination with 99mTccolloid demonstrated the presence of marrow tissue. ML and EH are the only two tumours with marrow tissue among lipomatous adrenal masses. In our patient a brown nodular mass was resected and histologically classified as ML. In benign adrenal masses, radiological follow-up is indicated; in case of large bilateral masses adrenal function tests are suggested periodically in order to detect possible adrenal hypofunction.

[Role of cardiac imaging in the diagnosis of infective endocarditis]. / Ruolo attuale dell'imaging cardiaco nella diagnosi di endocardite infettiva.

Infective endocarditis is an increasingly common disease in the hospital setting. Although the 2015 guidelines of the European Society of Cardiology deal extensively with many aspects of infective endocarditis, there are still unsolved problems related to diagnosis, in particular to the appropriate use of cardiac imaging methods, that require further study. The aim of this review is to analyze the advantages and limitations of the echocardiographic, radiological and nuclear imaging methods in order to identify diagnostic pathways applicable in clinical practice.

[Imaging in acute aortic syndrome: not just dissection]. / L'imaging nella sindrome aortica acuta: non solo dissezione.

Acute aortic syndrome includes three main pathological conditions: aortic dissection (AD), intramural hematoma (IMH) and penetrating aortic ulcer (PAU). These are life-threatening conditions, therefore early diagnosis and interventional/surgical treatment are fundamental for the survival of affected individuals. While anatomical findings of classical AD provided by imaging techniques are known to all cardiologists, imaging findings of IMH and PAU are less known, as are their prognostic implications and consequences on management and treatment strategies. This review aims to describe and discuss findings and role of imaging techniques in patients with IMH and PAU.

Early Speckle-tracking Echocardiography Predicts Left Ventricle Remodeling after Acute ST-segment Elevation Myocardial Infarction.

BACKGROUND: Prediction of the left ventricular remodeling (LVR) after ST-segment elevation myocardial infarction (STEMI) in patients treated with effective myocardial reperfusion is challenging. METHODS: Forty-one consecutive patients (36 males, age 59 ± 10 years) with STEMI who underwent effective (TIMI III) primary coronary angioplasty were enrolled. All patients had an echocardiography and cardiac magnetic resonance (CMR) study within 72 h from revascularization. Three echocardiographic parameters including LV ejection fraction (EF), global longitudinal strain (GLS) and severe altered longitudinal strain (SAS) area by two-dimensional speckle-tracking echocardiography (2D-STE) and 3 CMR indices including LV global function index (LV-GFI), myocardial salvage index (MSI), and microvascular obstruction (MVO) were calculated. LVR was defined as an increase in CMR LV end-diastolic volume (EDV) >15% after 6 months. RESULTS: Of 41 patients, 10 (24%) had LVR (LV-EDV from 145.1 ± 29.3 to 185.9 ± 49.8 ml, P < 0.001). A significant correlation with LV-EDV variation was found for baseline SAS area (r = 0.81), LV-GFI (r = -0.56), MVO (r = 0.55), EF (r = -0.42), GLS (r = 0.42), not for MSI (r = -0.25). At the multivariable analysis, a significant correlation remained only for the SAS area. The receiver-operating characteristic curve analysis showed that a baseline SAS area ≥15% predicts LVR with a sensitivity of 80.0% and a specificity of 90.3%. CONCLUSIONS: The SAS area evaluated by 2D-STE early in acute STEMI is a valuable predictor of LVR after 6 months. Further investigations are needed to verify its value in predicting patient survival.

Left Ventricle Relative Apical Sparing in Cardiac Amyloidosis.

Amyloidosis is a disease characterized by the extracellular deposition of the protein amyloid. It is a multiorgan disease, and cardiac involvement is not uncommon, generally in the form of a restrictive cardiomyopathy. Typical aspects of cardiac amyloidosis have been described at echocardiography and magnetic resonance imaging (MRI). In particular, the relative apical sparing at two-dimensional speckle-tracking echocardiography has been reported to be specific for cardiac amyloidosis. In our case, we report for the first time that this echocardiographic sign is related to lack of hyperenhancement at late gadolinium enhancement imaging in cardiac MRI.

Left ventricle remodeling in patients with ß-thalassemia major. An emerging differential diagnosis with left ventricle noncompaction disease.

To differentiate left ventricle non-compaction (LVNC) from hypertrabeculated myocardium due to LV remodeling in ß-thalassemia major (ß-TM) patients, cardiac magnetic resonance (CMR) images of 38 ß-TM patients and 10 LVNC patients were compared using 3 diagnostic criteria: ratio of diastolic segmental non-compacted to compacted myocardium (NC/C ratio) >2.5, percentage of non-compacted LV mass (NC-LVM%) >20% and >25% of global LV mass. Specificity of NC/C ratio of >2.5 was the lowest (58%) and of NC-LVM% of >25% the highest (93%). A NC-LVM% >20% showed sensitivity 100% and specificity 87%. Disease differentiation depends on the selected CMR criterion and is better with NC-LVM%.

Polar plot maps by parametric strain echocardiography allow accurate evaluation of non-viable transmural scar tissue in ischaemic heart disease.

AIMS: Assessment of left ventricular (LV) transmural scar tissue in clinical practice is still challenging because magnetic resonance imaging (MRI) and nuclear techniques have limited access and cannot be performed extensively. The aim of this study was to verify whether parametric two-dimensional speckle-tracking echocardiography (2D-STE) can more accurately localize and quantify LV transmural scar tissue in patients with healed myocardial infarct (MI) in comparison with MRI. METHODS AND RESULTS: Thirty-one consecutive patients (age 56 ± 32 years, 29 males) with MRI and echocardiography performed after at least 6 months from an acute MI were studied. Apical LV longitudinal strain images by 2D-STE and short-axis contrast images by MRI were analysed to generate parametric bull's eye maps showing the distribution of the LV transmural scar tissue, whose extension was measured by planimetry and expressed as a percentage of the total myocardial area. Twelve patients also had early 2D-STE and MRI examinations after the acute MI. 2D-STE accurately quantified the extent of transmural scar tissue vs. MRI (r = 0.86; limits of agreement 10.0 and -9.5%). Concordance between 2D-STE and MRI for transmural scar tissue localization was high, with only 3.6% of discordant segments using an LV 16-segment model. Lin coefficients, intra-class correlation coefficients, and Bland-Altman analysis showed very good intra- and inter-observer reproducibility for 2D-STE evaluations. The transmural scar tissue area at 6 months could be predicted by early 2D-STE evaluation. CONCLUSION: 2D-STE polar plots of LV longitudinal strain characterize transmural scar tissue accurately compared with MRI and may facilitate its assessment in clinical practice.

[Paradigm shifts in aortic pathology: clinical and therapeutic implications. Clinical imaging in chronic and acute aortic syndromes. The aorta as a cause of cardiac disease]. / Cambi di paradigma in tema di aorta: implicazioni cliniche e terapeutiche Imaging clinico nelle sindromi croniche ed acute. L'aorta come causa di malattia cardiaca.

Multimodal imaging plays a pivotal role in the assessment of the thoracic aorta, both in chronic and acute settings. Moving from improved knowledge on the structure and function of the aortic wall, as well as on its pathophysiology and histopathology, appropriate utilization of each imaging modality results into a better definition of the patient's need and proper treatment strategy. This review is aimed at highlighting the most critical aspects in this field, providing cardiologists with some novel clues for the imaging approach to patients with thoracic aortic disease.

Italian registry of cardiac magnetic resonance.

OBJECTIVES: Forty sites were involved in this multicenter and multivendor registry, which sought to evaluate indications, spectrum of protocols, impact on clinical decision making and safety profile of cardiac magnetic resonance (CMR). MATERIALS AND METHODS: Data were prospectively collected on a 6-month period and included 3376 patients (47.2 ± 19 years; range 1-92 years). Recruited centers were asked to complete a preliminary general report followed by a single form/patient. Referral physicians were not required to exhibit any specific certificate of competency in CMR imaging. RESULTS: Exams were performed with 1.5T scanners in 96% of cases followed by 3T (3%) and 1T (1%) magnets and contrast was administered in 84% of cases. The majority of cases were performed for the workup of inflammatory heart disease/cardiomyopathies representing overall 55.7% of exams followed by the assessment of myocardial viability and acute infarction (respectively 6.9% and 5.9% of patients). In 49% of cases the final diagnosis provided was considered relevant and with impact on patient's clinical/therapeutic management. Safety evaluation revealed 30 (0.88%) clinical events, most of which due to patient's preexisting conditions. Radiological reporting was recorded in 73% of exams. CONCLUSIONS: CMR is performed in a large number of centers in Italy with relevant impact on clinical decision making and high safety profile.

[Acute cerebral ischemia: an unusual clinical presentation of isolated left ventricular noncompaction in an adult patient]. / Ischemia cerebrale acuta: un'insolita presentazione nell'adulto del ventricolo sinistro non compatto isolato.

Isolated left ventricular noncompaction in adults is uncommon. The most frequent clinical manifestations are heart failure due to left ventricular systolic dysfunction and supraventricular and ventricular arrhythmias, which may be sustained and associated with sudden death. Thromboembolic complications are also possible. We report the case of an adult patient with isolated left ventricular noncompaction who came to our observation because of acute cerebral ischemia, an initial presentation of the disease only rarely described.

Pacing transmural scar tissue reduces left ventricle reverse remodeling after cardiac resynchronization therapy.

BACKGROUND: In patients with ischemic heart failure undergoing cardiac resynchronization therapy (CRT) the underlying myocardial substrate at the left ventricle (LV) pacing site may affect CRT response. However, the effect of delivering the pacing stimulus remote, adjacent to or over LV transmural scar tissue (TST) identified by echocardiography is still unknown. METHODS: First, 35 patients with healed myocardial infarction (57 ± 11 years) were prospectically studied to demonstrate the capability of echocardiographic end-diastolic wall thickness (EDWT) to identify LV-TST as defined by delayed enhancement magnetic resonance imaging (DE-MRI). Subsequently, in 136 patients (65 ± 10 years) who underwent CRT, EDWT was retrospectively evaluated at baseline. The LV catheter placement was defined over, adjacent to and remote from TST if pacing was delivered at a scarred segment, at a site 1 segment adjacent to or remote from scarred segments. CRT response was defined as LV end-systolic volume (ESV) decrease by at least 10% after 6 months. RESULTS: A EDWT ≤ 5mm identified TST at DE-MRI with 92% sensitivity and 96% specificity. In the 76 CRT responders, less overall and posterolateral TST segments and more segments paced remote from TST areas were found. At the multivariate regression analysis, the number of TST segments and scar/pacing relationship showed a significant association with CRT response. CONCLUSIONS: In addition to LV global scar burden, CRT response relates also to the myocardial substrate underlying pacing site as evaluated by standard echocardiography. This information may expand the role of echocardiography to guide pacing site avoiding pacing at TST areas.

[Magnetic resonance imaging for the evaluation of patients undergoing cardiac resynchronization therapy. Advantages, limitations and perspectives]. / La risonanza magnetica nella valutazione del paziente da sottoporre a resincronizzazione cardiaca. Vantaggi, limiti e prospettive.

Cardiac resynchronization therapy (CRT) is a therapeutic option with proven efficacy in improving symptoms and reducing both hospitalization and mortality in patients with refractory heart failure. However, a significant number of patients do not respond to CRT and this may be due to incomplete or inappropriate selection and characterization of patients before pacemaker implant. Cardiac magnetic resonance imaging (CMRI) is an imaging technique that may assist cardiologists in this regard. This technique has the potential to improve the success rate of CRT, due to pre-interventional evaluation of left ventricular function, mechanical dyssynchrony, and characterization and quantification of scar tissue. Recently, venous coronary anatomy has also been successfully evaluated by CMRI. In this review the role of CMRI in patients with heart failure who are candidates for CRT is discussed and potential future developments are indicated.