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Increased myocardial extracellular volume is associated with myocardial iron overload and heart failure in thalassemia major

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Abstract

Objectives

Myocardial extracellular volume (ECV) by cardiovascular magnetic resonance (CMR) is a surrogate marker of diffuse fibrosis. We evaluated the association between ECV and demographics, CMR findings, and cardiac involvement in patients with thalassemia major (TM).

Methods

A total of 108 β-TM patients (62 females, 40.16 ± 8.83 years), consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia Network, and 16 healthy subjects (6 females, 37.12 ± 16.13 years) underwent CMR. The protocol included assessment of T2*, native T1, and T2 values in all 16 myocardial segments for myocardial iron overload (MIO) quantification, cine images for left ventricular (LV) function quantification, post-contrast T1 mapping for ECV calculation, and late gadolinium enhancement (LGE) technique for replacement myocardial fibrosis detection.

Results

Global ECV values were significantly higher in females than in males. Global ECV values were significantly higher in patients with significant MIO (global heart T2* < 20 ms) than in patients without significant MIO, and both groups exhibited higher global ECV values than healthy subjects. No association was detected between native T1 and ECV values, while patients with reduced global heart T2 values showed significantly higher global ECV values than patients with normal and increased global heart T2. Global ECV values were not correlated with LV function/size and were comparable between patients with and without LGE. Compared to patients without heart failure, patients with a history of heart failure (N = 10) showed significantly higher global heart ECV values.

Conclusion

In TM, increased myocardial ECV, potentially reflecting diffuse interstitial fibrosis, is associated with MIO and heart failure.

Key Points

• CMR-derived myocardial extracellular volume is increased in thalassemia major patients, irrespective of the presence of late gadolinium enhancement.

• In thalassemia major, myocardial iron overload contributes to the increase in myocardial ECV, which potentially reflects diffuse interstitial fibrosis and is significantly associated with a history of heart failure.

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Abbreviations

CMR:

Cardiac magnetic resonance

CoV:

Coefficient of variation

DIF:

Diffuse interstitial fibrosis

ECV:

Extracellular volume fraction

E-MIOT:

Extension-Myocardial Iron Overload in Thalassaemia

GRE:

Gradient-echo

HCV:

Hepatitis C virus

HF:

Heart failure

LGE:

Late gadolinium enhancement

LIC:

Liver iron concentration

LV:

Left ventricle

MEFSE:

Multi-echo fast-spin-echo

MIO:

Myocardial iron overload

MOLLI:

Modified look-locker inversion recovery

NT-proBNP:

N-terminal fragment of B-type natriuretic peptide

SD:

Standard deviations

TM:

Thalassemia major

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Acknowledgements

We would like to thank all the colleagues involved in the E-MIOT project (https://emiot.ftgm.it/). We thank Silvia Miconi for her skillful secretarial work and all patients and the Italian Thalassaemia Foundation “L. Giambrone” for their cooperation.

Funding

The E-MIOT project receives “no-profit support” from industrial sponsorships (Chiesi Farmaceutici S.p.A. and Bayer). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Authors and Affiliations

  1. Department of Radiology, Fondazione G. Monasterio CNR-Regione Toscana, Via Moruzzi, 1 -, 56124, Pisa, Italy

    Antonella Meloni, Laura Pistoia, Vincenzo Positano, Nicola Martini & Filippo Cademartiri

  2. U.O.C. Bioingegneria, Fondazione G. Monasterio CNR-Regione Toscana, Pisa, Italy

    Antonella Meloni, Vincenzo Positano & Nicola Martini

  3. Cardiovascular Department, University of Trieste, Trieste, Italy

    Antonio De Luca & Gianfranco Sinagra

  4. Unità Operativa Semplice Dipartimentale Malattie Rare del Globulo Rosso, Azienda Ospedaliera di Rilievo Nazionale “A. Cardarelli”, Napoli, Italy

    Anna Spasiano

  5. Centro Talassemie ed Emoglobinopatie, Ospedale “Meyer”, Firenze, Italy

    Ilaria Fotzi

  6. Servizio Immunoematologia e Medicina Trasfusionale - Dipartimento dei Servizi, Presidio Ospedaliero “San Francesco” ASL Nuoro, Nuoro, Italy

    Pier Paolo Bitti

  7. Servizio di Immunoematologia e Medicina Trasfusionale, A.S.L. di Bari, Ospedale “Di Venere”, Bari, Italy

    Domenico Visceglie

  8. U.O.C. INFOTEL Translational BioInformatics and eHealth, Fondazione G. Monasterio CNR-Regione Toscana, Pisa, Italy

    Gianna Alberini

  9. Institute of Radiology, Department of Medicine, University of Padua, Padua, Italy

    Alessia Pepe

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  1. Antonella Meloni
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Corresponding author

Correspondence to Filippo Cademartiri.

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Guarantor

The scientific guarantor of this publication is Filippo Cademartiri.

Conflict of interest

The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article.

Statistics and biometry

One of the authors has significant statistical expertise.

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Written informed consent was obtained from all subjects (patients) in this study.

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Institutional Review Board approval was obtained.

Study subjects or cohorts overlap

Some study subjects or cohorts have been previously reported in: Meloni A, Martini N, Positano V, et al. Journal of Cardiovascular Magnetic Resonance; 2021;23(1):70.

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• prospective

• cross sectional study/observational

• performed at one institution

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Meloni, A., Pistoia, L., Positano, V. et al. Increased myocardial extracellular volume is associated with myocardial iron overload and heart failure in thalassemia major. Eur Radiol 33, 1266–1276 (2023). https://doi.org/10.1007/s00330-022-09120-8

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