Homogeneous Myocardial Iron Overload Research Articles

4326Reduction of cardiac outcomes in thalassemia major thanks to a ten-year national Italian networking

Abstract Introduction The MIOT (Myocardial Iron Overload in Thalassemia) Network was a network of thalassemia and CMR centers built in 2006 in order to assure homogeneous and standardized cardiac iron overload assessment for a significant number of patients. Purpose We describe the impact of this ten-year Network on cardiac iron, complications and deaths in patients with thalassemia major (TM). Methods 1746 TM patients (911 F; age 31.17±9.09 yrs) were enrolled in the MIOT Network. Myocardial iron overload (MIO) was quantified by the multislice multiecho T2* technique. Biventricular function was quantified by cine images. Results 1392 TM patients performed an end-of-study CMR. At the last CMR significantly higher global heart T2* values (35.44±10.69 ms vs 29.16±12.02 ms; P<0.0001) and a significant lower number of patients with global heart T2*<20 ms (26.3% vs 12.0%; P<0.0001) were detected. Four patterns of MIO were identified: no MIO (all segments with T2*≥20 ms), heterogeneous MIO and global heart T2*≥20 ms, heterogeneous MIO and global heart T2*<20 ms, and homogeneous MIO (all T2*<20 ms). At the last CMR a significant higher frequency of patients with no MIO and a significant lower frequency for the other three patterns indicating MIO were found (Figure 1). In patients with global heart T2*<20 ms a significant increase in left ventricular ejection fraction (EF) (difference: 3.2±8.5%, P<0.0001) as well as in right ventricular EF (difference: 1.2±8.9%, P=0.002) were detected. Based on CMR results the 75% of the patients changed the chelation therapy. At the last CMR the percentage of patients with an excellent/good compliance was significantly higher (94.8% vs 92.2%%; P<0.0001). The complete history of cardiac complications-CC (heart failure, arrhythmias, pulmonary hypertension, myocardial infarction, angina, myo/pericarditis, peripheral vascular disease) was present for 1062 patients. Out of the 1001 patients with resolved CC or without CC before the enrolment in the project, the 6.6% had a CC before the enrolment in the project. During the study, the frequency of CC was 4.4%, significantly lower (P=0.023). In particular, the frequency of heart failure (HF) was significantly lower (3.5% vs 0.8%, P<0.0001). Forty-six patients died during the study. HF continues to be the leading cause of death (30.4% of all causes), but there was a consistent decline in HF mortality rate, that was 60.2% in an Italian study dated 2004. No patients died for arrhythmias while cancer was the second leading cause of death. Conclusion Over a period of 10 years, the continuous monitoring of cardiac iron levels and a tailored chelation therapy allowed a reduction of MIO in the 70% of patients, with consequent improvement of cardiac function and reduction of cardiac complications and mortality from MIO-related HF. So, a national networking was effective in improving the care and reducing cardiac outcomes of TM patients.

PF786 REDUCTION OF CARDIAC OUTCOMES IN THALASSEMIA MAJOR THANKS TO A TEN‐YEAR NATIONAL ITALIAN NETWORKING

Background:The MIOT (Myocardial Iron Overload in Thalassemia) Network was a network of thalassemia and CMR centers built in 2006 in order to assure homogeneous and standardized cardiac iron overload assessment for a significant number of patients.Aims:We describe the impact of this ten‐year Network on cardiac iron, complications and deaths in patients with thalassemia major (TM).Methods:1746 TM patients (911 females; mean age 31.17 ± 9.09 yrs) were enrolled in the MIOT Network. Myocardial iron overload (MIO) was quantified by the multislice multiecho T2∗ technique. Biventricular function was quantified by cine images.Results:1392 TM patients performed an end‐of‐study CMR. At the last CMR significantly higher global heart T2∗ values (35.44 ± 10.69 ms vs 29.16 ± 12.02 ms; P < 0.0001) and a significant lower number of patients with global heart T2∗<20 ms (26.3% vs 12.0%; P < 0.0001) were detected. Four patterns of MIO were identified: no MIO (all segments with T2∗≥20 ms), heterogeneous MIO and global heart T2∗≥20 ms, heterogeneous MIO and global heart T2∗<20 ms, and homogeneous MIO (all T2∗<20 ms). Figure 1 shows the frequency of the 4 patterns at both scans. At the last CMR a significant higher frequency of patients with no MIO and a significant lower frequency for the other three patterns indicating MIO were detected.In patients with global heart T2∗<20 ms a significant increase in left ventricular ejection fraction (EF) (difference: 3.2 ± 8.5 %, P < 0.0001) as well as in right ventricular EF (difference: 1.2 ± 8.9 %, P = 0.002) were detected.Based on CMR results the 75% of the patients changed the chelation therapy. At the last CMR the percentage of patients with an excellent/good compliance was significantly higher (94.8% vs 92.2%%; P < 0.0001).The complete history of cardiac complications‐CC (heart failure, arrhythmias, pulmonary hypertension, myocardial infarction, angina, myo/pericarditis, peripheral vascular disease) was present for 1062 patients. Out of the 1001 patients with resolved CC or without CC before the enrolment in the project, the 6.6% had a CC before the enrolment in the project. During the study, the frequency of CC was 4.4 %, significantly lower (P = 0.023). In particular, the frequency of heart failure (HF) was significantly lower (3.5% vs 0.8%, P < 0.0001).Forty‐six patients died during the study. HF continues to be the leading cause of death (30.4% of all causes), but there was a consistent decline in HF mortality rate, that was 60.2% in an Italian study dated 2004. No patients died for arrhythmias while cancer was the second leading cause of death.Summary/Conclusion:Over a period of 10 years, the continuous monitoring of cardiac iron levels and a tailored chelation therapy allowed a reduction of MIO in the 70% of patients, with consequent improvement of cardiac function and reduction of cardiac complications and mortality from MIO‐related HF. So, a national networking was effective in improving the care and reducing cardiac outcomes of TM patients.image

Impact of a Ten-Year National Italian Networking on Cardiac Complications in Patients with Thalassemia Major

▪Introduction. The MIOT (Myocardial Iron Overload in Thalassemia) Network was a national Italian network constituted by thalassemia and magnetic resonance imaging (MRI) centers built in 2006. The main aim was to assure available, accessible homogeneous and standardized T2* MRI cardiac and liver iron overload assessments for a significant number of patients with emoglobinopathies. Moreover, the creation of a solid clinical-instrumental web based database allowed data exchange between centers and constituted a means of monitoring health care processes and outcomes. We describe the impact of this ten-year Network on cardiac complications in patients with thalassemia major (TM).Methods. Among the 2497 emoglobinopathies patients consecutively enrolled in the MIOT Network we considered the 1401 TM patients who performed an end-of-study MRI. Per protocol the MRI follow up was scheduled every 18±3 months. Myocardial iron overload (MIO) was quantified by the multislice multiecho T2* technique. Biventricular function was quantified by cine images.Results. At the last MRI significantly higher global heart T2* values (35.5±10.7 ms vs 29.2±12.0 ms; P<0.0001) and a significant lower number of patients with global heart T2*<20 ms (26.3% vs 12.0%; P<0.0001) were detected. Four patterns of MIO were identified: no MIO (all segments with T2*≥20 ms), heterogeneous MIO and global heart T2*≥20 ms, heterogeneous MIO and global heart T2*<20 ms, and homogeneous MIO (all segments with T2*<20 ms). Figure 1 shows the frequency of the 4 patterns at both scans. At the last MRI a significant higher frequency of patients with no MIO and a significant lower frequency for the other three patterns indicating MIO were detected. An improvement in MIO, that is a transition to a better risk class, was detected in the 68.4% of patients showing MIO at the baseline (at least one pathologic segment).In patients with significant baseline MIO (global heart T2*<20 ms) a significant increase in left ventricular ejection fraction (EF) (mean difference: 3.2±8.5 %, P<0.0001) as well as in right ventricular EF (mean difference: 1.2±8.9 %, P=0.002) were detected with a concordant improvement of MIO status.Based on MRI results the 75% of the patients changed the chelation therapy. At the last MRI the percentage of patients with an excellent/good compliance was significantly higher (94.7% vs 92.7%%; P=0.034).The 13.1% of the patients had a cardiac complication (heart failure, arrhythmias, pulmonary hypertension, myocardial infarction, angina, myo/pericarditis, and peripheral vascular disease) before the enrolment in the project. During the study, the frequency of cardiac complications was 7.9 %, significantly lower (P<0.0001). In particular, the frequency of heart failure was significantly lower (5.9% vs 1.7%, P<0.0001).Conclusion. Over a period of 10 years, the continuous monitoring of cardiac iron levels and a tailored chelation therapy allowed a reduction of MIO in the 70% of patients and a consequent improvement of cardiac function and reduction of heart failure. So, a national networking as the MIOT project was effective in improving the care and reducing cardiac outcomes of TM patients. [Display omitted] DisclosuresPepe:Chiesi Farmaceutici S.p.A., ApoPharma Inc., and Bayer: Other: No profit support.

Different patterns of myocardial iron distribution by whole-heart T2* magnetic resonance as risk markers for heart complications in thalassemia major

BackgroundThe multislice multiecho T2* cardiovascular magnetic resonance (CMR) technique allows to detect different patterns of myocardial iron overload (MIO). The aim of this cross-sectional study was to verify the association between cardiac complications (heart failure and arrhythmias), biventricular dysfunction and myocardial fibrosis with different patterns of MIO in thalassemia major (TM) patients. MethodsWe considered 812 TM patients enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) Network. The T2* value in all the 16 cardiac segments was evaluated. ResultsWe identified 4 groups of patients: 138 with homogeneous MIO (all segments with T2*<20ms), 97 with heterogeneous MIO (some segments with T2*<20ms, others with T2*≥20ms) and significant global heart iron (global heart T2*<20ms), 238 with heterogeneous MIO and no significant global heart iron, and 339 with no MIO (all segments with T2*≥20ms).Compared to patients with no MIO, patients with homogeneous MIO were more likely to have cardiac complications (odds ratio—OR=2.67), heart failure (OR=2.54), LV dysfunction (OR=5.59), and RV dysfunction (OR=2.26); patients with heterogeneous MIO and significant global heart iron were more likely to have heart failure (OR=2.38) and LV dysfunction (OR=2.39). ConclusionsCardiac complications, heart failure and dysfunction were correlated with MIO distribution with an increasing risk from the TM patients with no MIO to those with homogeneous MIO. Using a segmental approach, early iron deposit or homogeneous MIO patterns can be characterized to better tailor chelation 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.

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

Summary 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 2t o 97 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.

Prognostic CMR Parameters For Cardiac Complications In Large Cohort Of Well Treated Thalssemia Major Patients

IntroductionCardiac complications are the main cause of death in thalassemia major (TM) patients. Cardiovascular Magnetic Resonance (CMR) plays a key role in their management, assessing myocardial iron overload (MIO), biventricular function, atrial dimensions, and myocardial fibrosis. We evaluated the predictive value of CMR parameters for cardiac complications, including heart failure (HF), arrhythmias and pulmonary hypertension (PH). MethodsWe followed prospectively 537 white TM patients enrolled in the MIOT network. Fifty patients were excluded from the analysis because a cardiac complication was present at the time of the first CMR. All prognostic variables associated with the outcome at the univariate Cox model were placed in the multivariate model and were ruled out if they did not significantly improve the adjustment. ResultsAt baseline the mean age was 29.5±9.0 years and 222 patients were males. The mean follow-up time was 58±18 months. After the first CMR only the 37.8% of the patients did not change the chelation regimen or the frequency/dosage. ConclusionsWe detected few cardiac events thanks to a MR-guided, patient-specific adjustment of the chelation therapy. Severe and homogeneous MIO, myocardial fibrosis and ventricular dysfunction identify patients at high risk of heart failure. Heart T2* doesn't have any power in predicting arrhythmias while male sex and atrial dilation are independent prognosticators. Male sex, severe and homogeneous MIO, myocardial fibrosis and ventricular dysfunction identify patients at high risk of cardiac complications globally considered. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Myocardial Iron overload In Thalassemia Major. how Early To Check?

Introduction It is still controversy in thalassemia major (TM) if Cardiovascular Magnetic Resonance (CMR) T2* screening should be initiated before the 10 years. To answer this question, we studied retrospectively the prevalence of cardiac iron and function and myocardial fibrosis by CMR in a consistent cohort of TM patients younger than 10 years. Methods From the 2171 patients enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) network, we retrospectively selected the 35 TM patients aged less than 10 years who had undergone at least one MRI scan. Myocardial iron overload (MIO) was measured by T2* multislice multiecho technique. Biventricular function parameters were quantitatively evaluated in a standard way by cine images. To detect myocardial fibrosis, late gadolinium enhancement images were acquired. Results Patients’ age ranged from 4.2 to 9.7 years. All MRI scans were performed without sedation. Nine patients (25.7%) showed no myocardial iron overload (MIO),22 patients (62.9%) showed an heterogeneous MIO with a T2* global value ≥ 20 ms; 2 patients (5.7%) showed an heterogeneous MIO and a T2* global value &lt; 20 ms and 2 patients (5.7%) had a homogeneous MIO. No patients showed myocardial fibrosis. Table 1 reports the data of the 4 patients (3 males and 1 female) with significant myocardial iron overload (global heart T2* &lt; 20 ms). The youngest was 6 years old, all showed no heart dysfunction and in all the iron transfused was less than 35 g. Conclusion The first cardiac T2* assessment should be performed as early as possible without sedation and it is mandatory whenever poor compliance is suspected or if chelation has been started late. The use of the contrast medium to detect myocardial fibrosis can be postponed until after 10 years of age. A more sensitive segmental approach to detected heart iron should be considered. Therapy can be modified on the basis of the MRI results and serious organ damage can be prevented. Disclosures: No relevant conflicts of interest to declare.

Regional Myocardial Contractility In Thalassemia Major By Magnetic Resonance Tagging

Introduction Magnetic resonance (MR) tagging analyzed by dedicated tracking algorithms allows very precise measurements of myocardial motion and characterization of regional myocardial function. No extensive data are available in literature. Our aim was to quantitatively assess for the regional myocardial contractility in thalassemia major (TM) patients and to correlate it with heart iron overload and global biventricular function. Methods Seventy-four TM patients (46 F; 31.8 ± 8.5 yrs) enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) network underwent MR (1.5T). Three short-axis (basal, medial and apical) tagged MR images were analyzed off-line using harmonic phase (HARP) methods (Diagnosoft software) and the circumferential shortening (Ecc) was evaluated for all the 16 myocardial segments. Four main circumferential regions (anterior, septal, inferior, and lateral) were defined. The same axes were acquired by a T2* GRE multiecho technique to assess myocardial iron overload (MIO). Biventricular function parameters were quantitatively evaluated by cine images. Results Segmental ECC values ranged from -9.66 ± 4.17 % (basal anteroseptal segment) to 13.36 ± 4.57 % (mid-anterior segment). No significant circumferential variability was detected. Compared with previous studied healthy subjects, TM patients showed strain values significantly lower in all the circumferential regions at each level (mean difference from 4 % to 13 %; P&lt;0.001 for all the comparisons). Segmental Ecc values were not significantly correlated with the correspondent T2* values and no correlation was detected considering the global values, averaged over all segmental values. Three groups identified on the basis of cardiac iron distribution: no MIO, heterogenous MIO and homogeneous MIO. The global ECC was comparable among the three groups (-11.56 ± 1.60 % vs -11.70 ± 2.43 % vs -11.14 ± 1.95 %; P=0.602). Global ECC values were not significantly correlated with age and were comparable between the sexes. Circumferential shortening was not associated to left ventricular (LV) volumes and ejection fraction (with a P&gt;0.5 in all the comparisons). Conclusions TM patients showed a significantly lower cardiac contractility compared with healthy subjects, but this altered contractility was not related to cardiac iron, volumes and function. Disclosures: No relevant conflicts of interest to declare.

Prognostic CMR parameters for heart failure and arrhythmias in large cohort of well treated thalssemia major patients

Purpose: Cardiovascular Magnetic Resonance (CMR) plays a key role in the management of thalassemia major (TM), allowing to assess myocardial iron overload (MIO), biventricular function, atrial dimensions, and myocardial fibrosis. We determined the predictive value of CMR parameters for heart failure (HF) and arrhythmias in TM. Methods: We followed prospectively 537 patients enrolled in the MIOT network. Fifty patients were excluded because a cardiac complication was present at the time of the first CMR. All variables associated with the outcome at the univariate model were placed in the multivariate model and ruled out if they did not significantly improve the model's adjustment. Results: At baseline the mean age was 29.5±9.0 years and 222 were males. The mean follow-up time was 58±18 months. After the first CMR scan only the 37.8% of the patients did not change the chelator or the frequency/dosage. We recorded 19 episodes of HF. In the multivariate analysis the independent predictive factors were an homogeneous pattern of MIO (vs no MIO) (HR=5.81 P=0.014), global heart T2* 20 ms) (HR=6.19 P=0.003), myocardial fibrosis (HR=4.76 P=0.003; Kaplan–Meier curve in Figure) and ventricular dysfunction (HR=3.21 P=0.029). Arrhythmias (all supraventicular hyperhyperkinetic) occurred in 19 patients. In the multivariate analysis the independent predictive factors were male sex (HR=3.17 P=0.047) and atrial dilation (HR=3.07 P=0.026). ![Figure][1] Conclusion: We detected few cardiac events thanks to a CMR-guided, patient-specific adjustment of the chelation therapy. Severe and homogeneous MIO, myocardial fibrosis and ventricular dysfunction identify patients at high risk of HF. Heart T2* doesn't have any power in predicting arrhythmias while male sex and atrial dilation are independent prognosticators. [1]: pending:yes

CMR survey in a large cohort of TI patients categorized in different transfusional regimens

Purpose: We investigated myocardial iron overload (MIO), biventricular parameters and myocardial fibrosis assessed by cardiovascular magnetic resonance (CMR) in a large cohort of thalassemia intermedia (TI) patients categorized in different transfusional regimens. This survey is particularly significant considering the debate on the opportunity to transfuse the TI patients. Methods: We studied retrospectively 252 adult TI patients (119 females, 39±10 yrs) enrolled in the MIOT Network. MIO was assessed by a multislice multiecho T2* approach. Cine sequences were obtained to quantify biventricular function parameters. Myocardial fibrosis was evaluated by late gadolinium enhancement (LGE) acquisitions. Results: 188 patients showed no MIO in any segment, 56 had an heterogeneous MIO (52 with a global heart T2*<20 ms), and 8 showed an homogeneous MIO. Left ventricular (LV) and right ventricular (RV) dilatations were present in the 45% and in the 19% of cases, respectively. LV dysfunction was present in the 18.0% of the cases while RV dysfunction in the 3.63%. LV hypertrophy was found in the 8.7% of cases. Myocardial fibrosis was found in the 22.9% of the patients and was associated with LV dysfunction (P=0.001) and hypertrophy (P=0.038). 48 patients were no transfused, 66 sporadically transfused and 138 regularly transfused. The 3 group were significantly different for the LV volume and mass indexes, the cardiac output and the myocardial fibrosis (Table). View this table: Conclusions: Heart iron was not absent in TI and the majority of the patients showed an heterogeneous distribution. A consistent number of the TI patients had the stigmata of the high cardiac output state cardiomyopathy and myocardial fibrosis seems to be related to the high cardiac output state. The signs of the high cardiac output state were controlled in the regular transfused patients. Conversely, the regular transfusions seem to be started too late for preventing myocardial fibrosis.

Different patterns of myocardial iron overload by T2* Cardiovascular MR as markers of risk for cardiac complication in thalassemia major

Background Cardiac complications mainly related to myocardial iron overload (MIO) remain the main cause of morbidity and mortality in thalassemia major (TM). Thalassemia cardiomyopathy is treatable and partly reversible if appropriate chelation therapy is instituted in time. The validated multislice multiecho T2* Cardiovascular Magnetic Resonance (CMR) technique has permitted to quantify segmental and global myocardial iron burden detecting different patterns of iron overload. Aim of our study was to verify the risk of cardiac complications related to different patterns of MIO in a large cohort of TM patients. Methods We considered 812 TM patients for who CMR and cardiac data were collected in a central data base. Three short-axis views (basal, medium, apical) of the left ventricle were acquired using a multislice multiecho T2* sequence. Using a previously validated software the 16 segmental T2* values and the mean global heart T2* value were provided. A conservative cut off of 20 ms was considered the limit of normal for the segmental and global T2* values. Results We identified 4 groups of patients: group I (17%) with homogeneous MIO (all segments with T2*<20 ms), group II (12%) with heterogeneous MIO (some segments with T2*<20 ms and others with T2*≥20 ms) and global heart T2*<20 ms; group III (29%) with heterogeneous MIO and global heart T2*≥20 ms; group IV (42%) with no MIO (all segments with T2*≥20 ms). The percentage of patients with cardiac complications was significantly different in the 4 groups (group I 24.6%, group II 20.6%, group III 8.4%; group IV 16.4%; P<0.0001). In particular, the percentage of patients with heart failure was significantly different in the 4 groups (group I 17.4%, group II 16.5%, group III 4.2%, group IV 8.3%; P<0.0001). No significant differences were found among groups in the percentage of arrhythmias and pulmonary hypertension. Odds Ratio for cardiac complications was 1.7 (1.0-2.7 OR 95% CI; P=.041) for patients with homogeneous MIO vs patients with no MIO. Odds Ratio for heart failure was 2.3 (1.3-4.2 OR 95% CI; P=0.004) for patients with homogeneous MIO versus patients with no MIO and 2.2 (1.1-4.2 OR 95% CI; P=.020) for patients with heterogeneous MIO and global heart T2*<20 ms versus patients with no MIO. Conclusions

Different Patterns of Myocardial Iron Overload by T2* Cardiovascular MR As Markers of Risk for Cardiac Complication in Thalassemia Major,

Abstract 3190▪▪This icon denotes a clinically relevant abstract Introduction:Cardiac complications mainly related to myocardial iron overload (MIO) remain the main cause of morbidity and mortality in thalassemia major (TM). Thalassemia cardiomyopathy is treatable and partly reversible if appropriate chelation therapy is instituted in time. The validated multislice multiecho T2* Cardiovascular Magnetic Resonance (CMR) technique has permitted to quantify segmental and global myocardial iron burden detecting different patterns of iron overload. The aim of this study was to verify the risk of cardiac complications related to different patterns of MIO in a large cohort of TM patients. Methods:We considered 812 TM patients for who CMR and cardiac data were collected in a central data base. Three short-axis views (basal, medium, apical) of the left ventricle were acquired using a multislice multiecho T2* sequence. Using a previously validated software the 16 segmental T2* values and the mean global heart T2* value were provided. A conservative cut off of 20 ms was considered the limit of normal for the segmental and global T2* values. Results:We identified 4 groups of patients: group I (17%) with homogeneous MIO (all segments with T2*<20 ms), group II (12%) with heterogeneous MIO (some segments with T2*<20 ms and others with T2*≥20 ms) and global heart T2*<20 ms; group III (29%) with heterogeneous MIO and global heart T2*≥20 ms; group IV (42%) with no MIO (all segments with T2*≥20 ms). The clinically relevant findings in the 4 groups are summarized in Table 1. The percentage of patients with cardiac complications was significantly different in the 4 groups (P<0.0001). In particular, the percentage of patients with heart failure was significantly different in the 4 groups (P<0.0001). No significant differences were found among groups in the percentage of arrhythmias and pulmonary hypertension. Odds Ratio for cardiac complications was 1.7 (1.0–2.7 OR 95% CI; P=0.041) for patients with homogeneous MIO versus patients with no MIO. Odds Ratio for heart failure was 2.3 (1.3–4.2 OR 95% CI; P=0.004) for patients with homogeneous MIO versus patients with no MIO and 2.2 (1.1–4.2 OR 95% CI; P=0.020) for patients with heterogeneous MIO and global heart T2*<20 ms versus patients with no MIO.Table 1Homogeneous MIO (N=138)Heterogeneous MIO and global heart T2*<20 ms (N=97)Heterogeneous MIO and global heart T2* ≥20 ms (N=238)No MIO (N=339)PSex (M/F)67/7138/59119/119157/1720.304Age (years)28.9 ± 7.430.8 ± 7.430.4 ± 8.931.1 ± 8.90.069Hemoglobin (g/dl)9.7 ± 0.69.6 ± 0.59.7 ± 0.69.6 ± 0.80.309Serum ferritin (ng/l)2454 ± 19692043 ± 17961328 ± 12771114 ± 1004<0.0001Cardiac disease, n (%)34 (24.6)20 (20.6)20 (8.4)56 (16.5)<0.0001Heart failure, n (%)24 (17.4)16 (16.5)10 (4.2)28 (8.3)<0.0001Arrhythmias, n (%)13 (9.4)6 (6.2)8 (3.4)23 (6.8)0.112Pulm. hypertension, n (%)3 (2.2)1 (1.0)4 (1.7)14 (4.1) Conclusions:Homogeneous MIO predicts a significantly higher risk to develop cardiac complications, especially heart failure, suggesting an intensive chelation therapy in this group of patients. Disclosures:No relevant conflicts of interest to declare.

Different patterns of myocardial iron overload by multislice T2* Cardiovascular MR as markers of risk for cardiac dysfunction in thalassemia major

Background The multislice multiecho T2* CMR technique allows to detect different patterns of myocardial iron overload (MIO). The aim of this study was to verify the risk of biventricular dysfunction related to different patterns of MIO in a large cohort of thalassemia major (TM) patients. Methods 1135 TM patients (538 M, mean age 30 ± 19 years) enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) network underwent CMR (1.5 T). For the assessment of MIO, three short-axis views of the left ventricle (LV) were acquired and the myocardium was segmented into 16-segments standardized LV model. The T2* value on each segment was calculated as well as the global T2* value. A conservative cut off of 20 ms was considered the limit of normal for the segmental and global T2* values. Biventricular function parameters were quantitatively evaluated by SSFP cine images. The lower limit of normal for the LVEF and the RVEF were established from CMR in a large cohort of well-treated TM patients without myocardial iron overload and cardiac diseases. Results Four groups of patients were identified: homogeneous MIO (all segments with T2* values <20 ms) (N=173, 15%), heterogeneous MIO (some segments with T2* values≥20 ms and other segments with T2* values < 20 ms) and global heart T2*<20 ms (N=160, 14%), heterogeneous MIO and global heart T2*≥20 ms (N=337, 30%) and no MIO (all segments with T2* values≥ 20 ms) (N=465, 41%). The LV ejection fraction (EF) was significant different among the groups (P<0.0001) (figure 1A). Odds Ratio for LV dysfunction (LV EF<57%) was 4.8 (3.1-7.3 OR 95% CI; P<0.0001) for patients with homogeneous MIO vs patients with no MIO and 1.9 (1.2-3.2 OR 95% CI; P=0.007) for patients with heterogeneous MIO and global heart T2*<20 vs patients with no MIO. The right ventricular (RV) EF was significant different among the groups (P<0.0001) (figure 1B). Odds Ratio for RV dysfunction (RV EF<55%) was 2.1 (1.4-3.2 OR 95% CI; P=0.001) for patients with homogeneous MIO vs patients with no MIO. Conclusions Biventricular dysfunction is correlated with MIO distribution decreasing from the patients with homogeneous MIO to the patients with no MIO. Homogeneous MIO and heterogeneous MIO with a global heart T2*<20 predicts a significantly higher risk to develop cardiac dysfunction suggesting an intensive chelation therapy in this group of patients.