Multi-parametric Cardiac Magnetic Resonance for Prediction of Cardiac Complications in Thalassemia Intermedia: a Prospective Multicenter Study
Antonella Meloni1, Nicola Giunta2, Pietro Giuliano2, Maria Giovanna Neri1, Stefania Renne3, Antonino Vallone4, Massimiliano Missere5, Emanuele Grassedonio6, Vincenzo Positano1, Daniele De Marchi1, and Alessia Pepe1

1Fondazione G. Monasterio CNR-Regione Toscana, Pisa, Italy, 2"ARNAS" Civico, Palermo, Italy, 3P.O. “Giovanni Paolo II”, Lamezia Terme (CZ), Italy, 4Az. Osp. "Garibaldi" Presidio Ospedaliero Nesima, Catania, Italy, 5P.O. “Giovanni Paolo II”, Campobasso, Italy, 6Policlinico "Paolo Giaccone", Palermo, Italy

Synopsis

We prospectively assessed the predictive value of MRI for cardiac complications in talassemia intermedia (TI). All our patients underwent MRI examination assessing multi-parametric findings (heart and liver iron, myocardial fibrosis, atrial areas, and biventricular function).

Righ ventricular (RV) hypertrophy identified patients at high risk for arrhythmias and pulmonary hypertension. Both RV hypertrophy and fibrosis detected by LGE were independent predictive factor for cardiac complications. So, a widespread program using MRI exploiting its multi-parametric potential, including the measurement of RV mass, can have considerable power for opening the prognosis of TI patients by the early identification and treatment of patients at risk for cardiac complications.

Introduction

Cardiovascular Magnetic Resonance (CMR) has an established role in managing and predicting prognosis of patients with Thalassemia Major (TM) [1]. Thalassemia Intermedia (TI) is a milder variant of thalassemia showing a different clinical and prognostic profile; pulmonary hypertension (PH) is a more common complication in TI patients [2].

We prospectively determined the predictive value of CMR parameters, including measurement of right ventricular mass, for cardiac complications in TI.

Methods

We considered 342 TI patients enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) Network [3]; about half of them (178/302, 58.9%) were transfusion-dependent.

Myocardial and liver iron overload were measured by T2* multiecho technique [4]. Atrial dimensions, left and right ventricular mass and systolic function were quantified by cine images [5]. Late gadolinium enhancement (LGE) images were acquired to detect myocardial fibrosis [6].

Results

Twenty-three patients were excluded because a cardiac complication was present at the time of first CMR, so we prospectively followed 319 patients. All 319 patients were white, with a mean age at time of their first scan of 38.02±11.69 years and 165 (51.7%) of them were females.

Mean follow-up time was 52.24±24.87 months (median 54.64 months). Cardiac events were recorded in 22 patients (6.9%): heart failure (HF) in 1 patient, arrhythmias in 12 patients, pulmonary hypertension (PH) in 7 patients and myocardial infarction (MI) in 2 patients.

Due to the low number of events, only arrhythmias, PH and cardiac complications globally considered were taken as cardiac outcomes for univariate and multivariate analysis.

In the multivariate analysis RV hypertrophy was the only independent predictive factor for arrhythmias (HR=33.83, 95% CI=6.07-188.74, P<0.0001) and PH (HR=73.33, 95% CI=10.00-537.57, P<0.0001). When cardiac complications were considered all together, RV hypertrophy (HR=24.12, 95% CI=5.09-114.12, P<0.0001) and myocardial fibrosis by LGE (HR=6.59, 95% CI=1.33-32.67, P=0.021) were independent prognostic factors in the multivariate analysis. The Figures display the Kaplan–Meier curves showing the impact of the independent predictive factors on each outcome.

Conclusions

For the first time we studied the prognostic value of right ventricular mass as part of multiparametric CMR imaging in a population of TI patients. RV hypertrophy identified patients at high risk for arrhythmias and PH. Both RV hypertrophy and fibrosis detected by LGE were independent predictive factor for cardiac complications. Measurement of RV mass should be part of the multi-parametric CMR study of patient with thalassemia intermedia.

Acknowledgements

We thank all the colleagues of the MIOT Network (https://miot.ftgm.it).

The MIOT project receives “no-profit support” from industrial sponsorships (Chiesi Farmaceutici S.p.A. and ApoPharma Inc.).

References

[1] Meloni A et al. Eur Heart J 2013;34(s1):292.

[2] Aessopos A et al. Chest 2005;127:1523-30.

[3] Meloni A et al. Int J Med Inform 2009;78:503-12.

[4] Pepe A et al. JMRI 2006;23:662-8.

[5] Marsella M et al. Haematologica 2011;96:515–20.

[6] Pepe A et al. Heart 2009;95:1688-93.

Figures

Figure 1. Kaplan–Meier curve showing the impact of each independent predictive factor on the development of arrhythmias.

Figure 2. Kaplan–Meier curve showing the impact of each independent predictive factor on the development of pulmonary hypertension.

Figure 3. Kaplan–Meier curve showing the impact of each independent predictive factor on the development of cardiac complications.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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