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Background: Anthracyclines and radiotherapy involving the heart region are cardiotoxic, but the potential cardiotoxicity of vincristine remains unknown. We assessed cardiac function in vincristine-treated >5-year childhood cancer survivors (CCS)., Methods and Results: We cross-sectionally compared echocardiograms of 101 vincristine-treated CCS (median age 35 years [range: 17-53], median vincristine dose 63 mg/m 2 ) from the national Dutch Childhood Cancer Survivor Study, LATER cohort, to 101 age- and sex-matched controls. CCS treated with anthracyclines, radiotherapy involving the heart region, cyclophosphamide or ifosfamide were excluded. Twelve CCS (14%) versus four controls (4%; p 0.034) had a decreased left ventricular ejection fraction (LVEF; men <52%, women <54%). Mean LVEF was 58.4% versus 59.7% (p 0.050). Global longitudinal strain (GLS) was abnormal in nineteen (24%) CCS versus eight controls (9%; p 0.011). Mean GLS was 19.0% versus 20.1% (p 0.001). No ≥grade 2 diastolic dysfunction was detected. In multivariable logistic regression analysis CCS had higher risk of abnormal GLS (OR 3.55, p 0.012), but not abnormal LVEF (OR 3.07, p 0.065), than controls. Blood pressure and smoking history contributed to variation in LVEF, whereas obesity and diastolic blood pressure contributed to variation in GLS. Cumulative vincristine dose was not associated with either abnormal LVEF or abnormal GLS in multivariable models corrected for age and sex (OR per 50 mg/m 2 : 0.88, p 0.85 and 1.14, p 0.82, respectively)., Conclusions: Vincristine-treated long-term CCS showed an abnormal GLS more frequently than controls. Their risk for future clinical cardiac events and the role of risk factor modification should be further elucidated., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Phospholamban (PLN) p.Arg14del mutation carriers are known to develop dilated and/or arrhythmogenic cardiomyopathy, and typical electrocardiographic (ECG) features have been identified for diagnosis. Machine learning is a powerful tool used in ECG analysis and has shown to outperform cardiologists., Objectives: We aimed to develop machine learning and deep learning models to diagnose PLN p.Arg14del cardiomyopathy using ECGs and evaluate their accuracy compared to an expert cardiologist., Methods: We included 155 adult PLN mutation carriers and 155 age- and sex-matched control subjects. Twenty-one PLN mutation carriers (13.4%) were classified as symptomatic (symptoms of heart failure or malignant ventricular arrhythmias). The data set was split into training and testing sets using 4-fold cross-validation. Multiple models were developed to discriminate between PLN mutation carriers and control subjects. For comparison, expert cardiologists classified the same data set. The best performing models were validated using an external PLN p.Arg14del mutation carrier data set from Murcia, Spain (n = 50). We applied occlusion maps to visualize the most contributing ECG regions., Results: In terms of specificity, expert cardiologists (0.99) outperformed all models (range 0.53-0.81). In terms of accuracy and sensitivity, experts (0.28 and 0.64) were outperformed by all models (sensitivity range 0.65-0.81). T-wave morphology was most important for classification of PLN p.Arg14del carriers. External validation showed comparable results, with the best model outperforming experts., Conclusion: This study shows that machine learning can outperform experienced cardiologists in the diagnosis of PLN p.Arg14del cardiomyopathy and suggests that the shape of the T wave is of added importance to this diagnosis., (Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: The Late Effects of Childhood Cancer task force of the Dutch Childhood Oncology Group (DCOG LATER) developed a guideline for follow-up of asymptomatic cardiac dysfunction in childhood cancer survivors (CCS). In this paper, we present the methods, available evidence and final recommendations of our guideline., Materials and Methods: A multidisciplinary working group specified clinical questions that should be answered to get to recommendations for the guideline. We carried out short or extensive evidence summaries and determined methodological quality of studies and levels of evidence in order to answer all clinical questions. When evidence was lacking for CCS, we carefully extrapolated evidence from other populations. Final recommendations were based on evidence and consensus., Results: There was high-level evidence for the increased risk of cardiac dysfunction in CCS and its main risk factors. Evidence was lacking regarding the prognosis, diagnosis and treatment of cardiac dysfunction in CCS. We recommended echocardiographic screening for asymptomatic cardiac dysfunction in CCS treated with cardiotoxic treatments and counseling about potential advantages and disadvantages of our screening recommendations., Conclusion: The DCOG LATER guideline recommends risk-based screening for asymptomatic cardiac dysfunction in CCS, but it should be noted that recommendations are not completely supported by evidence in CCS.