Diastolic Dysfunction is Common in Survivors of Pediatric Differentiated Thyroid Carcinoma

Mariëlle S. Klein Hesselink, Gianni Bocca, Yoran M. Hummel, Adrienne H. Brouwers, Johannes G.M. Burgerhof, Eveline W.C.M. Van Dam, Jourik A. Gietema, Bas Havekes, Marry M. Van Den Heuvel-Eibrink, Eleonora P.M. Corssmit, Leontien C.M. Kremer, Romana T. Netea-Maier, Helena J.H. Van Der Pal, Robin P. Peeters, John T.M. Plukker, Cécile M. Ronckers, Hanneke M. Van Santen, Peter Van Der Meer, Wim J.E. Tissing, Thera P. Links

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Introduction: Whether pediatric patients with differentiated thyroid carcinoma (DTC) are at risk of developing treatment-related adverse effects on cardiac function is unknown. We therefore studied in long-term survivors of pediatric DTC the prevalence of cardiac dysfunction and atrial fibrillation in relation to treatment variables, and the association between cardiac dysfunction and plasma biomarkers. Methods: In this nationwide prospective multicenter study, cardiac assessments were performed in 66 adult survivors of pediatric DTC (age at diagnosis ≤18 years and follow-up ≥5 years after diagnosis) treated in the Netherlands between 1970 and 2009. Assessment included echocardiography, plasma biomarkers (N-terminal pro-brain natriuretic peptide, high-sensitive troponin-T, galectin-3), and 24-hour Holter electrocardiography. Echocardiographic measurements were compared with retrospective data of 66 sex- and age-matched unaffected Dutch controls. Diastolic dysfunction was defined as an early diastolic septal and/or lateral tissue velocity (e′) less than 2 SD of mean age-adjusted reference data. Results: The survivors (86.4% women) had at DTC diagnosis a median age of 16 years. Median follow-up was 17 years. Left ventricular ejection fraction <50% was found in one survivor, and median global longitudinal systolic strain was near normal. Diastolic dysfunction was present in 14 asymptomatic survivors (21.2%). Overall, diastolic function of survivors was lower compared with controls (e′mean 14.5 versus 15.8 cm/s, P = 0.006). Older attained age and higher waist circumference were associated with decreased diastolic function, whereas thyrotropin levels and cumulative administered radioiodine dose were not. In survivors, biomarkers were not associated with diastolic dysfunction; atrial fibrillation was not observed. Conclusion: While systolic function is unaffected, diastolic dysfunction is frequently observed in asymptomatic long-term survivors of pediatric DTC, which may suggest early cardiac aging.

Original languageEnglish
Pages (from-to)1481-1489
Number of pages9
JournalThyroid
Volume27
Issue number12
DOIs
Publication statusPublished - 1 Dec 2017
Externally publishedYes

Cite this

Klein Hesselink, M. S., Bocca, G., Hummel, Y. M., Brouwers, A. H., Burgerhof, J. G. M., Van Dam, E. W. C. M., ... Links, T. P. (2017). Diastolic Dysfunction is Common in Survivors of Pediatric Differentiated Thyroid Carcinoma. Thyroid, 27(12), 1481-1489. https://doi.org/10.1089/thy.2017.0383
Klein Hesselink, Mariëlle S. ; Bocca, Gianni ; Hummel, Yoran M. ; Brouwers, Adrienne H. ; Burgerhof, Johannes G.M. ; Van Dam, Eveline W.C.M. ; Gietema, Jourik A. ; Havekes, Bas ; Van Den Heuvel-Eibrink, Marry M. ; Corssmit, Eleonora P.M. ; Kremer, Leontien C.M. ; Netea-Maier, Romana T. ; Van Der Pal, Helena J.H. ; Peeters, Robin P. ; Plukker, John T.M. ; Ronckers, Cécile M. ; Van Santen, Hanneke M. ; Van Der Meer, Peter ; Tissing, Wim J.E. ; Links, Thera P. / Diastolic Dysfunction is Common in Survivors of Pediatric Differentiated Thyroid Carcinoma. In: Thyroid. 2017 ; Vol. 27, No. 12. pp. 1481-1489.
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title = "Diastolic Dysfunction is Common in Survivors of Pediatric Differentiated Thyroid Carcinoma",
abstract = "Introduction: Whether pediatric patients with differentiated thyroid carcinoma (DTC) are at risk of developing treatment-related adverse effects on cardiac function is unknown. We therefore studied in long-term survivors of pediatric DTC the prevalence of cardiac dysfunction and atrial fibrillation in relation to treatment variables, and the association between cardiac dysfunction and plasma biomarkers. Methods: In this nationwide prospective multicenter study, cardiac assessments were performed in 66 adult survivors of pediatric DTC (age at diagnosis ≤18 years and follow-up ≥5 years after diagnosis) treated in the Netherlands between 1970 and 2009. Assessment included echocardiography, plasma biomarkers (N-terminal pro-brain natriuretic peptide, high-sensitive troponin-T, galectin-3), and 24-hour Holter electrocardiography. Echocardiographic measurements were compared with retrospective data of 66 sex- and age-matched unaffected Dutch controls. Diastolic dysfunction was defined as an early diastolic septal and/or lateral tissue velocity (e′) less than 2 SD of mean age-adjusted reference data. Results: The survivors (86.4{\%} women) had at DTC diagnosis a median age of 16 years. Median follow-up was 17 years. Left ventricular ejection fraction <50{\%} was found in one survivor, and median global longitudinal systolic strain was near normal. Diastolic dysfunction was present in 14 asymptomatic survivors (21.2{\%}). Overall, diastolic function of survivors was lower compared with controls (e′mean 14.5 versus 15.8 cm/s, P = 0.006). Older attained age and higher waist circumference were associated with decreased diastolic function, whereas thyrotropin levels and cumulative administered radioiodine dose were not. In survivors, biomarkers were not associated with diastolic dysfunction; atrial fibrillation was not observed. Conclusion: While systolic function is unaffected, diastolic dysfunction is frequently observed in asymptomatic long-term survivors of pediatric DTC, which may suggest early cardiac aging.",
keywords = "cancer survivors, diastolic dysfunction, differentiated thyroid carcinoma, late effects, pediatric patients",
author = "{Klein Hesselink}, {Mari{\"e}lle S.} and Gianni Bocca and Hummel, {Yoran M.} and Brouwers, {Adrienne H.} and Burgerhof, {Johannes G.M.} and {Van Dam}, {Eveline W.C.M.} and Gietema, {Jourik A.} and Bas Havekes and {Van Den Heuvel-Eibrink}, {Marry M.} and Corssmit, {Eleonora P.M.} and Kremer, {Leontien C.M.} and Netea-Maier, {Romana T.} and {Van Der Pal}, {Helena J.H.} and Peeters, {Robin P.} and Plukker, {John T.M.} and Ronckers, {C{\'e}cile M.} and {Van Santen}, {Hanneke M.} and {Van Der Meer}, Peter and Tissing, {Wim J.E.} and Links, {Thera P.}",
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Klein Hesselink, MS, Bocca, G, Hummel, YM, Brouwers, AH, Burgerhof, JGM, Van Dam, EWCM, Gietema, JA, Havekes, B, Van Den Heuvel-Eibrink, MM, Corssmit, EPM, Kremer, LCM, Netea-Maier, RT, Van Der Pal, HJH, Peeters, RP, Plukker, JTM, Ronckers, CM, Van Santen, HM, Van Der Meer, P, Tissing, WJE & Links, TP 2017, 'Diastolic Dysfunction is Common in Survivors of Pediatric Differentiated Thyroid Carcinoma' Thyroid, vol. 27, no. 12, pp. 1481-1489. https://doi.org/10.1089/thy.2017.0383

Diastolic Dysfunction is Common in Survivors of Pediatric Differentiated Thyroid Carcinoma. / Klein Hesselink, Mariëlle S.; Bocca, Gianni; Hummel, Yoran M.; Brouwers, Adrienne H.; Burgerhof, Johannes G.M.; Van Dam, Eveline W.C.M.; Gietema, Jourik A.; Havekes, Bas; Van Den Heuvel-Eibrink, Marry M.; Corssmit, Eleonora P.M.; Kremer, Leontien C.M.; Netea-Maier, Romana T.; Van Der Pal, Helena J.H.; Peeters, Robin P.; Plukker, John T.M.; Ronckers, Cécile M.; Van Santen, Hanneke M.; Van Der Meer, Peter; Tissing, Wim J.E.; Links, Thera P.

In: Thyroid, Vol. 27, No. 12, 01.12.2017, p. 1481-1489.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Diastolic Dysfunction is Common in Survivors of Pediatric Differentiated Thyroid Carcinoma

AU - Klein Hesselink, Mariëlle S.

AU - Bocca, Gianni

AU - Hummel, Yoran M.

AU - Brouwers, Adrienne H.

AU - Burgerhof, Johannes G.M.

AU - Van Dam, Eveline W.C.M.

AU - Gietema, Jourik A.

AU - Havekes, Bas

AU - Van Den Heuvel-Eibrink, Marry M.

AU - Corssmit, Eleonora P.M.

AU - Kremer, Leontien C.M.

AU - Netea-Maier, Romana T.

AU - Van Der Pal, Helena J.H.

AU - Peeters, Robin P.

AU - Plukker, John T.M.

AU - Ronckers, Cécile M.

AU - Van Santen, Hanneke M.

AU - Van Der Meer, Peter

AU - Tissing, Wim J.E.

AU - Links, Thera P.

PY - 2017/12/1

Y1 - 2017/12/1

N2 - Introduction: Whether pediatric patients with differentiated thyroid carcinoma (DTC) are at risk of developing treatment-related adverse effects on cardiac function is unknown. We therefore studied in long-term survivors of pediatric DTC the prevalence of cardiac dysfunction and atrial fibrillation in relation to treatment variables, and the association between cardiac dysfunction and plasma biomarkers. Methods: In this nationwide prospective multicenter study, cardiac assessments were performed in 66 adult survivors of pediatric DTC (age at diagnosis ≤18 years and follow-up ≥5 years after diagnosis) treated in the Netherlands between 1970 and 2009. Assessment included echocardiography, plasma biomarkers (N-terminal pro-brain natriuretic peptide, high-sensitive troponin-T, galectin-3), and 24-hour Holter electrocardiography. Echocardiographic measurements were compared with retrospective data of 66 sex- and age-matched unaffected Dutch controls. Diastolic dysfunction was defined as an early diastolic septal and/or lateral tissue velocity (e′) less than 2 SD of mean age-adjusted reference data. Results: The survivors (86.4% women) had at DTC diagnosis a median age of 16 years. Median follow-up was 17 years. Left ventricular ejection fraction <50% was found in one survivor, and median global longitudinal systolic strain was near normal. Diastolic dysfunction was present in 14 asymptomatic survivors (21.2%). Overall, diastolic function of survivors was lower compared with controls (e′mean 14.5 versus 15.8 cm/s, P = 0.006). Older attained age and higher waist circumference were associated with decreased diastolic function, whereas thyrotropin levels and cumulative administered radioiodine dose were not. In survivors, biomarkers were not associated with diastolic dysfunction; atrial fibrillation was not observed. Conclusion: While systolic function is unaffected, diastolic dysfunction is frequently observed in asymptomatic long-term survivors of pediatric DTC, which may suggest early cardiac aging.

AB - Introduction: Whether pediatric patients with differentiated thyroid carcinoma (DTC) are at risk of developing treatment-related adverse effects on cardiac function is unknown. We therefore studied in long-term survivors of pediatric DTC the prevalence of cardiac dysfunction and atrial fibrillation in relation to treatment variables, and the association between cardiac dysfunction and plasma biomarkers. Methods: In this nationwide prospective multicenter study, cardiac assessments were performed in 66 adult survivors of pediatric DTC (age at diagnosis ≤18 years and follow-up ≥5 years after diagnosis) treated in the Netherlands between 1970 and 2009. Assessment included echocardiography, plasma biomarkers (N-terminal pro-brain natriuretic peptide, high-sensitive troponin-T, galectin-3), and 24-hour Holter electrocardiography. Echocardiographic measurements were compared with retrospective data of 66 sex- and age-matched unaffected Dutch controls. Diastolic dysfunction was defined as an early diastolic septal and/or lateral tissue velocity (e′) less than 2 SD of mean age-adjusted reference data. Results: The survivors (86.4% women) had at DTC diagnosis a median age of 16 years. Median follow-up was 17 years. Left ventricular ejection fraction <50% was found in one survivor, and median global longitudinal systolic strain was near normal. Diastolic dysfunction was present in 14 asymptomatic survivors (21.2%). Overall, diastolic function of survivors was lower compared with controls (e′mean 14.5 versus 15.8 cm/s, P = 0.006). Older attained age and higher waist circumference were associated with decreased diastolic function, whereas thyrotropin levels and cumulative administered radioiodine dose were not. In survivors, biomarkers were not associated with diastolic dysfunction; atrial fibrillation was not observed. Conclusion: While systolic function is unaffected, diastolic dysfunction is frequently observed in asymptomatic long-term survivors of pediatric DTC, which may suggest early cardiac aging.

KW - cancer survivors

KW - diastolic dysfunction

KW - differentiated thyroid carcinoma

KW - late effects

KW - pediatric patients

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U2 - 10.1089/thy.2017.0383

DO - 10.1089/thy.2017.0383

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JO - Thyroid

JF - Thyroid

SN - 1050-7256

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Klein Hesselink MS, Bocca G, Hummel YM, Brouwers AH, Burgerhof JGM, Van Dam EWCM et al. Diastolic Dysfunction is Common in Survivors of Pediatric Differentiated Thyroid Carcinoma. Thyroid. 2017 Dec 1;27(12):1481-1489. https://doi.org/10.1089/thy.2017.0383