Background In non transfusion dependent thalassemia (NTDT) the lack of a clear genotype-phenotype relationship complicates the already complex and extensive scenario in clinical practice. Purpose Our aim was to detect if the presence of a β°/β° homozygous genotype was associated to different rate of cardiac findings by Cardiovascular Magnetic Resonance (CMR) and cardiac complications. Methods We considered 81 patients with thalassemia intermedia never transfused o who received occasional transfusions (37.7±11.4 years, 39 females) consecutively enrolled in the Myocardial Iron Overload in Thalassemia project. CMR was used to quantify iron overload (T2* technique), biventricular morphological and functional parameters (cine sequences), and the presence of myocardial fibrosis (late gadolinium enhancement-LGE technique). All cardiac complications were classified according to international guidelines. Results Two groups of patients were identified: non homozygous β°/β° genotype (N=61) and homozygous β°/β° genotype (N=20.) No significant differences for sex and age were found between the groups. Patients with homozygous β°/β° genotype had lower mean haemoglobin levels (8.6±1.1g/dl vs 9.2±1.2 g/dl) but the difference did not reach the statistical significance (P=0.060). No patient showed cardiac iron and global heart T2* values were comparable between the two groups. Left atrial area index, left ventricular (LV) end-diastolic, end-systolic and stroke volume indexes, LV mass index, right ventricular end-diastolic and end-systolic volume indexes were significantly higher in the homozygous β°/β° group (see Table). Frequencies of heart failure and arrhythmias were comparable between the groups. Non-β0/β0 homozygous genotype β0/β0 homozygous genotype P Left Atrial Area (cm2/m2) 13.87±2.59 16.63±2.59 0.001 LV EDVI (ml/m2) 94.88±15.59 112.94±21.52 0.003 LV ESVI (ml/m2) 35.22±9.55 41.88±9.70 0.018 LV SVI (ml/m2) 61.98±12.57 69.81±11.20 0.029 LV mass index (g/m2) 61.26±10.15 68.63±15.89 0.030 RV EDVI (ml/m2) 91.27±23.50 107.53±23.87 0.019 RV ESVI (ml/m2) 33.93±17.55 40.81±15.20 0.043 Conclusions Heart remodelling related to a high cardiac output state cardiomyopathy was more pronounced in patients with homozygous β°/β° genotype. These data can support the knowledge of different phenotypic groups in the management of NTDT patients.
Introduction. Cardiovascular magnetic Resonance (CMR) has dramatically changed the clinical practice and improved the prognosis in thalassemia major (TM). This is the first study evaluating the predictive value of changes in CMR parameters (myocardial iron, function, and fibrosis) for cardiac complications in TM. Methods. We followed prospectively 709 TM patients (374 females; 29.77±8.53 years) consecutively enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) Network who performed a baseline and a 1 st follow up CMR scan after 18 months. Myocardial iron overload (MIO) was measured by multislice multiecho T2* technique and atrial dimensions and biventricular function by cine images. Macroscopic myocardial fibrosis was detected by late gadolinium enhancement technique. Risk classes were defined based on the 4 patterns of MIO from worst to normal. For patients with baseline MIO (at least one segmental T2*<20 ms), improvement was defined as a transition to a better risk class, stabilization as no change in risk class, and worsening as a transition to a worse risk class. For patients without baseline MIO, the worsening was the transition to a worse risk class. The percentage change was used for continuous variables. For biventricular ejection fractions, improvement was a %change>10%, stabilization a %change between -10% and 10%, and worsening a %change<-10%. For biventricular volumes, LV mass index, and atrial areas, improvement was a % change<-10%, stabilization a % change between -10% and 10%, and worsening a % change>10%. Myocardial fibrosis was considered absent if not detected in any of the two CMRs and present if detected in at least one examination . Results. During a mean follow-up of 89.4±33.3 months, cardiac events were recorded in 50 (7.1%) patients: 24 (48%) episodes of heart failure, 24 (48%) arrhythmias (23 supraventricular and 1 hypokinetic), and 2 (4.0%) pulmonary hypertension. Mean time from the 1 st follow up CMR to the development of a cardiac complication was 75.31±35.35 months. In the univariate Cox regression analysis, cardiac iron cleareance and myocardial fibrosis were identified as univariate prognosticators (Table 1). In the multivariate analysis only myocardial fibrosis remained an independent predictor factor. Conclusion. The presence of myocardial fibrosis at the baseline CMR or developed within 18 months emerges as the strongest long-term predictor for cardiac complications in TM. Our data demonstrate the importance in using the contrast medium for CMR scans in thalassemia patients. Figure 1 Figure 1. Disclosures Pepe: Bayer S.p.A.: Other: no profit support; Chiesi Farmaceutici S.p.A: Other: no profit support. Maggio: Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene Corp: Membership on an entity's Board of Directors or advisory committees; Bluebird Bio: Membership on an entity's Board of Directors or advisory committees.
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Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): The MIOT project received “no-profit support” from industrial sponsorships (Chiesi Farmaceutici S.p.A. and ApoPharma Inc.). Background Cardiovascular magnetic Resonance (CMR) has dramatically changed the clinical practice and improved the prognosis in thalassemia major (TM). Aim This is the first study evaluating the predictive value of changes in CMR parameters (myocardial iron, function, and fibrosis) for cardiac complications in TM. Methods We followed prospectively 709 TM patients (374 females; 29.77 ± 8.53 years) consecutively enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) Network who performed a baseline and a 1st follow up CMR scan after 18 months. Myocardial iron overload (MIO) was measured by multislice multiecho T2* technique and atrial dimensions and biventricular function by cine images. Macroscopic myocardial fibrosis was detected by late gadolinium enhancement technique. Risk classes were defined based on the 4 patterns of MIO from worst to normal. For patients with baseline MIO (at least one segmental T2*<20 ms), improvement was defined as a transition to a better risk class, stabilization as no change in risk class, and worsening as a transition to a worse risk class. For patients without baseline MIO, the worsening was the transition to a worse risk class. The percentage change was used for continuous variables. For biventricular ejection fractions, improvement was a %change > 10%, stabilization a %change between -10% and 10%, and worsening a %change<-10%. For biventricular volumes, LV mass index, and atrial areas, improvement was a % change<-10%, stabilization a % change between -10% and 10%, and worsening a % change > 10%. Myocardial fibrosis was considered absent if not detected in any of the two CMRs and present if detected in at least one examination. Results During a mean follow-up of 89.4 ± 33.3 months, cardiac events were recorded in 50 (7.1%) patients: 24 (48%) episodes of heart failure, 24 (48%) arrhythmias (23 supraventricular and 1 hypokinetic), and 2 (4.0%) pulmonary hypertension. Mean time from the 1st follow up CMR to the development of a cardiac complication was 75.31 ± 35.35 months. In the univariate Cox regression analysis, cardiac iron cleareance and myocardial fibrosis were identified as univariate prognosticators (Table 1). In the multivariate analysis only myocardial fibrosis remained an independent predictor factor. Conclusion The presence of myocardial fibrosis at the baseline CMR or developed within 18 months emerges as the strongest long-term predictor for cardiac complications in TM. Our data demonstrate the importance in using the contrast medium for CMR scans in thalassemia patients.
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.
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