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Risk factors for heart disease in transfusion-dependent thalassemia: serum ferritin revisited

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Abstract

Heart disease remains a leading cause of morbidity and mortality in transfusion-dependent thalassemia (TDT), which can be attributed to several factors but primarily develops in the setting of iron overload. This was a retrospective cohort study utilizing Webthal® patient data from five major centers across Italy. Patients without heart disease were followed-up for 10 years (2000–2010) and data were collected for demographics, splenectomy status, serum ferritin and hemoglobin levels, and comorbidities associated with heart disease. Among 379 patients analyzed (mean age 22.9 ± 5.1 years, 47.8% men), 44 (cumulative incidence: 11.6%) developed heart disease during the period of observation. Splenectomy (p = 0.002) and serum ferritin level (p < 0.001) were the only risk factors with significant association with heart disease. A serum ferritin threshold of ≥ 3000 ng/mL was the best predictor for the development of heart disease (86.4% sensitivity and 92.8% specificity, AUC: 0.912, 95% CI 0.852–0.971, p < 0.001). On multivariate analysis, only a serum ferritin level ≥ 3000 ng/mL remained significantly and independently associated with increased risk of heart disease (HR: 44.85, 95% CI 18.85–106.74), with a 5- and 10-year heart disease-free survival of 58 and 39%. The association between iron overload and heart disease in patients with TDT is confirmed, yet a new serum ferritin level of 3000 ng/mL to flag increased risk is suggested.

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Acknowledgements

The authors thank Khaled Musallam MD, PhD of EVIDA MEDICAL LTD, London, UK, for medical editorial assistance. Financial support for medical editorial assistance was provided by Novartis Farma SpA.

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Authors and Affiliations

  1. Unità di Cardiologia, Ospedale Galliera, Genoa, Italy

    Giorgio Derchi

  2. Ospedale Regionale per le Microcitemie, ASL8, Cagliari, Italy

    Carlo Dessì & Patrizio Bina

  3. Department of Clinical Sciences and Community, IRCCS Fondazione Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy

    Maria Domenica Cappellini & Marianna Giuditta

  4. Department of Clinical and Biological Sciences, Università di Torino, Turin, Italy

    Antonio Piga & Filomena Longo

  5. Dipartimento della Donna, del Bambino e di Chirurgia Generale e Specialistica, Seconda Università degli Studi di Napoli, Naples, Italy

    Silverio Perrotta & Immacolata Tartaglione

  6. Thalassemia Unit, Department of Public Health, Clinical and Molecular Medicine, Università di Cagliari, Cagliari, Italy

    Raffaella Origa

  7. Ematologia Ospedale “A. Perrino”, Brindisi, Italy

    Antonella Quarta

  8. Ematologia-Centro della Microcitemia e Anemie Congenite, Ospedale Galliera, Via Volta 6, 16128, Genoa, Italy

    Valeria Pinto & Gian Luca Forni

Authors
  1. Giorgio Derchi
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  2. Carlo Dessì
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  3. Patrizio Bina
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  4. Maria Domenica Cappellini
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  5. Antonio Piga
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  6. Silverio Perrotta
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  7. Immacolata Tartaglione
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  8. Marianna Giuditta
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  9. Filomena Longo
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  10. Raffaella Origa
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  11. Antonella Quarta
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  12. Valeria Pinto
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  13. Gian Luca Forni
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Consortia

on behalf of Webthal®

Contributions

Study concept design: GD and GLF. Data collection and assembly: all authors. Data analysis and interpretation: GD and GLF. Manuscript drafting: GD and GLF. Manuscript critical revision for intellectual content: all authors. All authors approved the manuscript prior to submission.

Corresponding author

Correspondence to Gian Luca Forni.

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The authors declare that they have no conflict of interest.

Statement of human and animal rights

At each center, an Ethics Committee approval is obtained.

Informed consent

Written informed consents for data collection and use are retrieved from patients (according to the Italian law, ART. 79 D.Lgs. 196/02).

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Derchi, G., Dessì, C., Bina, P. et al. Risk factors for heart disease in transfusion-dependent thalassemia: serum ferritin revisited. Intern Emerg Med 14, 365–370 (2019). https://doi.org/10.1007/s11739-018-1890-2

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  • DOI: https://doi.org/10.1007/s11739-018-1890-2

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