Biomarkers to diagnose ventricular dysfunction in childhood cancer survivors: a systematic review

Leerink, Jan M.; Verkleij, Simone J; Feijen, Elizabeth A M; Mavinkurve‐Groothuis, Annelies M. C.; Pourier, Milanthy S.; Ylänen, Kaisa; Tissing, Wim J. E.; Louwerens, Marloes; Heuvel, Marry M. van den; Broeder, Eline van Dulmen‐den; Vries, Andrica C H de; Ronckers, Cécile M.; Pal, Heleen J H van der; Kapusta, Livia; Loonen, Jacqueline; Bellersen, Louise; Pinto, Yigal M.; Kremer, Leontien C. M.; Kok, Wouter E.

doi:10.1136/heartjnl-2018-313634

Cited by 32 publications

(36 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…NT-proBNP levels did not differ significantly by prior CRT, which is in agreement with an improved ability of novel echocardiographic methods to better detect late subclinical LV dysfunction in asymptomatic childhood cancer survivors than natriuretic peptides assays [32,33,34]. Moreover, the superiority of novel echocardiographic techniques, i.e., global longitudinal strain analysis and tissue Doppler imaging, over conventional parameters to detect systolic [7,8] and diastolic [6,10] LV dysfunction has previously been demonstrated in long-term survivors of childhood cancer, mainly after ALL.…”

Section: Discussionsupporting

confidence: 71%

Cranial Irradiation in Childhood Acute Lymphoblastic Leukemia Is Related to Subclinical Left Ventricular Dysfunction and Reduced Large Artery Compliance in Cancer Survivors

Sulicka-Grodzicka

Chyrchel

Totoń‐Żurańska

et al. 2019

JCM

View full text Add to dashboard Cite

Long-term survivors of acute lymphoblastic leukemia (ALL), the most common childhood malignancy, are at remarkably increased risk of heart failure (HF) in middle age, most likely due anthracycline cardiotoxicity. The role of cranial radiation therapy (CRT) in the development of left ventricular (LV) dysfunction, a predecessor of overt HF, remains unclear. Our aim was to compare LV function and systemic arterial properties according to past CRT in young adult survivors of anthracycline-treated ALL. We studied young adult survivors of childhood ALL at a median of 16 years from diagnosis treated with anthracycline-based chemotherapy, with (n = 12) or without (n = 30) CRT. In addition to fractional shortening (FS) and ejection fraction (EF), LV function was quantified by tissue Doppler imaging of the mitral annulus. Aortic strain/distensibility and arterial compliance were derived from echocardiography and simultaneously recorded pulse pressure. Despite similar FS and EF, peak mitral annular systolic velocity (median (interquartile range): 9.0 (7.5–10.0) vs. 10.0 (8.8–11.5) cm/s, p = 0.05), and early diastolic velocity (13.8 (13.0–14.8) vs. 15.5 (14.0–17.3), p = 0.01) were decreased after chemotherapy combined with CRT compared to chemotherapy without CRT. Systemic arterial compliance was lower in post-CRT subjects (1.0 (0.8–1.2 vs. 1.4 (1.1–1.7) mL/mmHg, p = 0.002). Aortic strain and distensibility were similar regardless of prior CRT. In conclusion, lower arterial compliance and subclinical LV dysfunction may be possible late consequences of past CRT in adult survivors of childhood ALL. Whether arterial stiffening is associated with future HF development in CRT-exposed ALL survivors remains to be investigated.

show abstract

Section: Discussionsupporting

confidence: 71%

Cranial Irradiation in Childhood Acute Lymphoblastic Leukemia Is Related to Subclinical Left Ventricular Dysfunction and Reduced Large Artery Compliance in Cancer Survivors

Sulicka-Grodzicka

Chyrchel

Totoń‐Żurańska

et al. 2019

JCM

View full text Add to dashboard Cite

show abstract

“…Early detection provides opportunities for interventions to preserve systolic function and potentially limit heart failure–associated morbidity and mortality; this is similar to findings observed in the general population 6,7 . However, prior studies have been unsuccessful at identifying early markers of developing cardiac dysfunction in the childhood cancer survivor population 3,8 …”

Section: Introductionmentioning

confidence: 56%

“…Prior cross‐sectional studies focusing on the diagnostic yield of surveillance for cardiomyopathy in asymptomatic childhood cancer survivors have suggested that natriuretic peptides are inadequate as the only method of surveillance because of their low sensitivity and positive predictive value for the detection of current cardiomyopathy 3,8,11,12 . However, associations with future major cardiac events and death have not been systematically assessed in a large cohort of long‐term adult survivors of childhood cancer.…”

Section: Introductionmentioning

confidence: 99%

Cardiac biomarkers and association with subsequent cardiomyopathy and mortality among adult survivors of childhood cancer: A report from the St. Jude Lifetime Cohort

Dixon

Howell

et al. 2020

Cancer

View full text Add to dashboard Cite

BackgroundSurvivors of childhood cancer exposed to cardiotoxic therapies are at significant cardiovascular risk. The utility of cardiac biomarkers for identifying the risk of future cardiomyopathy and mortality is unknown.MethodsN‐terminal pro–B‐type natriuretic peptide (NT‐proBNP) and cardiac troponin T (cTnT) were assessed in 1213 adults 10 or more years from a childhood cancer diagnosis; 786 were exposed to anthracycline chemotherapy and/or chest‐directed radiation therapy (RT). NT‐proBNP values above age‐ and sex‐specific 97.5th percentiles were considered abnormal. Generalized linear models estimated cross‐sectional associations between abnormal NT‐proBNP and anthracycline or chest RT doses as risk ratios with 95% confidence intervals (CIs). A Poisson distribution estimated rates and a Cox proportional hazards model estimated hazard ratios (HRs) for future cardiac events and death.ResultsAt a median age of 35.5 years (interquartile range, 29.8‐42.5 years), NT‐proBNP and cTnT were abnormal in 22.5% and 0.4%, respectively. Exposure to chest RT and exposure to anthracycline chemotherapy were each associated with a dose‐dependent increased risk for abnormal NT‐proBNP (P for trend <.0001). Among exposed survivors with no history of Common Terminology Criteria for Adverse Events–graded cardiomyopathy and with normal systolic function, survivors with abnormal NT‐proBNP had higher rates per 1000 person‐years of cardiac mortality (2.93 vs 0.96; P < .0001) and future cardiomyopathy (32.10 vs 15.98; P < .0001) and an increased risk of future cardiomyopathy (HR, 2.28; 95% CI, 1.28‐4.08) according to a multivariable assessment.ConclusionsAbnormal NT‐proBNP values were prevalent and, among survivors who were exposed to cardiotoxic therapy but did not have a history of cardiomyopathy or current systolic dysfunction, identified those at increased risk for future cardiomyopathy. Further longitudinal studies are needed to confirm this novel finding.

show abstract

“…The strain analysis may benefit the early identification of cardiotoxicity in childhood cancer patients, but only few studies covered myocardial strain for an early diagnosis of LV dysfunction . At present, systematic evidence on the role of biomarkers for cardiotoxicity in childhood cancer patients is limited with one available systematic review that did not assess acute/subacute cardiotoxicity seen within <1 year after the beginning of cancer therapy …”

Section: Discussionmentioning

confidence: 99%

Cardiac biomarkers for the detection of cardiotoxicity in childhood cancer—a meta‐analysis

et al. 2020

View full text Add to dashboard Cite

Aims Childhood cancer therapy is associated with a significant risk of therapy-related cardiotoxicity. This meta-analysis aims to evaluate cardiac biomarkers for the detection of cancer therapy-related left ventricular (LV) dysfunction in childhood cancer patients. Methods and results PubMed, Cochrane Library, Wiley Library, and Web of Science were screened for studies investigating brain natriuretic peptide (BNP)/N-terminal proBNP (NT-proBNP) or cardiac troponin in childhood cancer patients. The odds ratios (OR) for elevation of cardiac biomarkers and association with LV dysfunction were calculated using a random-effects model. Data from 27 studies with 1651 subjects were included. BNP/NT-proBNP levels were higher post-treatment compared with controls or pre-treatment values [standardized mean difference = 1.0; 95% confidence interval (CI) = 0.6-1.4; n = 320; P < 0.001]. LV dysfunction was present in 11.76% of included patients, and risk for LV dysfunction was increased in patients with elevated BNP/NT-proBNP (OR = 7.1; 95% CI = 2.0-25.5; n = 350; P = 0.003). The sensitivity of BNP/NT-proBNP for the detection of LV dysfunction was 33.3%, and the specificity was 91.5%. Sensitivity increased when selecting for studies that assessed patients < 5 years after anthracycline exposure and for studies including high cumulative anthracycline doses. Anthracycline chemotherapy was associated with an increased frequency of elevated troponin (OR = 3.7; 95% CI = 2.1-6.5; n = 348; P < 0.001). The available evidence on the association between elevated troponin and LV dysfunction was insufficient for an adequate analysis. In five included studies, the frequency of LV dysfunction was not increased in patients with elevated troponin (OR = 2.5; 95% CI = 0.5-13.2; n = 179; P = 0.53). Conclusions BNP/NT-proBNP is associated with cardiotoxicity in paediatric cancer patients receiving anthracycline therapy, but owing to low sensitivity, BNP/NT-proBNP has to be evaluated in the context of further parameters including clinical assessment and echocardiography. Future studies are needed to determine whether troponin serves as a marker for cardiotoxicity in children. Standardized recommendations for the application of cardiac biomarkers in children undergoing cardiotoxic cancer therapy may benefit management and clinical outcome.

show abstract

Biomarkers to diagnose ventricular dysfunction in childhood cancer survivors: a systematic review

Cited by 32 publications

References 39 publications

Cranial Irradiation in Childhood Acute Lymphoblastic Leukemia Is Related to Subclinical Left Ventricular Dysfunction and Reduced Large Artery Compliance in Cancer Survivors

Cranial Irradiation in Childhood Acute Lymphoblastic Leukemia Is Related to Subclinical Left Ventricular Dysfunction and Reduced Large Artery Compliance in Cancer Survivors

Cardiac biomarkers and association with subsequent cardiomyopathy and mortality among adult survivors of childhood cancer: A report from the St. Jude Lifetime Cohort

Cardiac biomarkers for the detection of cardiotoxicity in childhood cancer—a meta‐analysis

Contact Info

Product

Resources

About