title: Prediction of cardiac complications for thalassemia major in the widespread cardiac magnetic resonance era: a prospective multicentre study by a multi-parametric approach.
abstract: Cardiovascular magnetic resonance (CMR) has dramatically changed the clinical practice in thalassemia major (TM), lowering cardiac complications. We prospectively reassessed the predictive value of CMR parameters for heart failure (HF) and arrhythmias in TM.
  
  
  
  We considered 481 white TM patients (29.48 ± 8.93 years, 263 females) enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) network. Myocardial and liver iron overload were measured by T2* multiecho technique. Atrial dimensions and biventricular function were quantified by cine images. Late gadolinium enhancement images were acquired to detect myocardial fibrosis. Mean follow-up was 57.91 ± 18.23 months. After the first CMR scan 69.6% of the patients changed chelation regimen. We recorded 18 episodes of HF. In the multivariate analysis the independent predictive factors were myocardial fibrosis (HR = 10.94, 95% CI = 3.28-36.43, P < 0.0001), homogeneous MIO (compared with no MIO) (HR = 5.56, 95% CI = 1.37-22.51, P  = 0.016), ventricular dysfunction (HR = 4.33, 95% CI = 1.39-13.43, P  = 0.011). Arrhythmias occurred in 16 patients. Among the CMR parameters only the atrial dilation was identified as univariate prognosticator (HR = 4.26 95% CI=1.54-11.75, P  = 0.005).
  
  
  
  CMR guided the change of chelation therapy in nearly 70% of patients, leading to a lower risk of iron-mediated HF and of arrhythmias than previously reported. Homogeneous MIO remained a risk factor for HF but also myocardial fibrosis and ventricular dysfunction identified patients at high risk. Arrhythmias were independent of MIO but increased with atrial dilatation. CMR by a multi-parametric approach dramatically improves cardiac outcomes and provides prognostic information beyond cardiac iron estimation.
authors.affiliation: CMR Unit, Fondazione G. Monasterio CNR-Regione Toscana, Via Moruzzi 1-56124, Pisa, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Pepe
authors.affiliation: CMR Unit, Fondazione G. Monasterio CNR-Regione Toscana, Via Moruzzi 1-56124, Pisa, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Meloni
authors.affiliation: Epidemiology and Biostatistics Unit, Institute of Clinical Physiology, CNR, Pisa, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Rossi
authors.affiliation: Istituto di Radiologia, Policlinico 'Giaccone', Palermo, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Midiri
authors.affiliation: Radiology Department, Catholic University, Campobasso, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Missere
authors.affiliation: Radiology Department, University of Ancona, Ancona, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Valeri
authors.affiliation: U.O. DH Talassemici, Ospedale "Sant'Eugenio, Roma, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Sorrentino
authors.affiliation: U.O. Microcitemie, A. O. 'Bianchi-Melacrino-Morelli', Reggio Calabria, Italy.
authors.forename: Domenico Giuseppe
authors.initials: DG
authors.lastname: D'Ascola
authors.affiliation: UOSD Centro per le Microcitemie, AORN Cardarelli, Napoli, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Spasiano
authors.affiliation: UOSD Centro per le Microcitemie, AORN Cardarelli, Napoli, Italy.
authors.forename: Aldo
authors.initials: A
authors.lastname: Filosa
authors.affiliation: U.O.C. Ematologia con Talassemia, Ospedale Civico, Palermo, Italy.
authors.forename: Liana
authors.initials: L
authors.lastname: Cuccia
authors.affiliation: D.H. Thalassemia, Ospedale Casa Sollievo della Sofferenza IRCCS Opera di Padre Pio, San Giovanni Rotondo, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Dello Iacono
authors.affiliation: Centro della Microcitemia e delle Anemie Congenite, Ospedale Galliera, Genova, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Forni
authors.affiliation: Centro Microcitemia, 'Garibaldi' Hospital, Catania, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Caruso
authors.affiliation: Ematologia II con Talassemia, Ospedali Riuniti 'Villa Sofia-Cervello', Palermo, Italy.
authors.forename: Aurelio
authors.initials: A
authors.lastname: Maggio
authors.affiliation: Ematologia II con Talassemia, Ospedali Riuniti 'Villa Sofia-Cervello', Palermo, Italy.
authors.forename: Lorella
authors.initials: L
authors.lastname: Pitrolo
authors.affiliation: Microcitemia, Azienda Unità Sanitaria Locale TA/1, Taranto, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Peluso
authors.affiliation: CMR Unit, Fondazione G. Monasterio CNR-Regione Toscana, Via Moruzzi 1-56124, Pisa, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: De Marchi
authors.affiliation: CMR Unit, Fondazione G. Monasterio CNR-Regione Toscana, Via Moruzzi 1-56124, Pisa, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Positano
authors.affiliation: Division of Cardiology, Children's Hospital Los Angeles, Los Angeles, CA, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Wood
mesh_terms: D000328:Adult; D001145:Arrhythmias, Cardiac / Q000209:etiology* / Q000503:physiopathology; D009202:Cardiomyopathies / Q000000981:diagnostic imaging* / Q000209:etiology*; D015913:Chelation Therapy / Q000379:methods; D015331:Cohort Studies; D005260:Female; D006801:Humans; D019028:Magnetic Resonance Imaging, Cine / Q000379:methods*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D013997:Time Factors; D055815:Young Adult; D017086:beta-Thalassemia / Q000150:complications* / Q000175:diagnosis* / Q000628:therapy