Systematic Review/Meta-analysis
Long-term Risk of Heart Failure and Myocardial Dysfunction After Thoracic Radiotherapy: A Systematic Review

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Abstract

Background

Chest irradiation is a commonly used treatment for malignancy, with demonstrated symptomatic and survival benefit. The frequency and presentation of cardiovascular complications of radiotherapy remains unclear.

Methods

We performed a systematic review to evaluate the prevalence and manifestations of myocardial dysfunction (asymptomatic and symptomatic) in long-term cancer survivors treated with radiotherapy.

Results

Thoracic radiotherapy is associated with increased risk of heart failure in long-term follow-up, with hazard ratios ranging from 2.7 to 7.4 for Hodgkin lymphoma, and 1.5-2.4 for breast cancer. Although ejection fraction is often normal, systolic dysfunction has been more widely reported with modern techniques including 2-dimensional speckle strain and cardiac magnetic resonance. This might have implications for the selection of patients for cardioprotection. Despite common emphasis, diastolic functional abnormalities were infrequent in the long term. A limited amount of data suggest that right ventricular dysfunction is important in this population.

Conclusions

The reports were heterogeneous, used different treatments, end points, and definitions of myocardial dysfunction, and most studies on the cardiac consequences of radiotherapy involved small numbers of patients and were published decades ago, making it difficult to formulate definitive conclusions for the current era.

Résumé

Introduction

La radiothérapie thoracique constitue un traitement courant contre le cancer qui a montré des bienfaits tant du point de vue de la symptomatologie que de la survie des patients. Le tableau et la fréquence des complications cardiovasculaires liées à ce traitement demeurent toutefois peu connus.

Méthodes

Nous avons procédé à une revue systématique de la prévalence et des manifestations de dysfonction myocardique (asymptomatique et symptomatique) chez des survivants à long terme d’un cancer qui avaient subi une radiothérapie.

Résultats

La radiothérapie thoracique a été associée à une augmentation du risque d’insuffisance cardiaque à long terme, le rapport des risques instantanés allant de 2,7 à 7,4 pour le lymphome hodgkinien et de 1,5 à 2,4 pour le cancer du sein. Même si la fraction d’éjection était souvent normale, une dysfonction systolique a fréquemment été diagnostiquée grâce aux techniques modernes telles que l’échocardiographie bidimensionnelle des marqueurs acoustiques (speckle-tracking) et l’imagerie par résonance magnétique cardiaque. Ceci pourrait avoir une incidence sur le choix des patients nécessitant une cardioprotection. Même si elles sont souvent mentionnées, les anomalies diastoliques fonctionnelles sont peu fréquentes à long terme. Des données limitées indiquent aussi l’importance de la dysfonction ventriculaire droite dans cette population.

Conclusions

Les données recueillies étaient hétérogènes en raison des différences entre les types de traitements administrés, les paramètres d’évaluation fixés et les définitions de la dysfonction myocardique utilisées. De plus, il a été difficile de tirer des conclusions claires à partir de ces données puisque la plupart des études portant sur les effets de la radiothérapie sur la fonction cardiaque ne comptaient qu’un petit nombre de patients et ont été publiées il y a déjà plusieurs décennies.

Section snippets

Methods

We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for reporting the systematic review.12 The search strategy was designed prospectively. PubMed and EMBASE were searched from inception to July 2015. Exact search terms used are listed in Supplemental Appendix S1. Citations and details were stored in a database (EndNote X7.4, Thomson Reuters, New York, NY).

Study selection

From the original screening set of 7329 articles, 768 were deemed suitable for abstract review, to which a further 3 articles were added from bibliographic review of review articles (Fig 1). Of the 768 abstracts reviewed, 176 were selected for full review, of which 38 contributed data to this analysis.

Mediastinal irradiation for HD

Twenty-one studies (1659 patients) were identified as those that fit the inclusion criteria for investigation of long-term ventricular function after mediastinal irradiation for HD. Sixteen

Discussion

The studies selected for this systematic review showed a large degree of heterogeneity, in terms of study characteristics and findings. Notably, a large number of studies (17 of 40) were published > 20 years ago, and many consisted of cohorts with small numbers of patients. It was therefore difficult to reach definitive conclusions regarding the etiology and presentation of radiation-induced myocardial disease, despite that RT has been used as a therapeutic modality for almost a century.

Conclusions

With successful advances in contemporary cancer treatment, clinical challenges are slowly pivoting from increasing 5-year survival to managing chronic health conditions in cancer survivors. This vulnerable population requires further research to identify strategies for identifying patients at high risk for RT-induced myocardial disease and provision of early and effective treatment.

Funding Sources

Funded in part by a Health Professional scholarship from the Heart Foundation Australia.

Disclosures

The authors have no conflicts of interest to disclose.

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