Abstract
BackgroundPediatric cancer survivors are at increased risk of cardiac dysfunction and heart failure. Reduced peak oxygen consumption (peak VO2) is associated with impaired cardiac reserve (defined as the increase in cardiac function from rest to peak exercise) and heart failure risk, but it is unclear whether this relationship exists in pediatric cancer survivors. This study sought to investigate the presence of reduced peak VO2 in pediatric cancer survivors with increased risk of heart failure, and to assess its relationship with resting cardiac function and cardiac haemodynamics and systolic function during exercise.MethodsTwenty pediatric cancer survivors (8–24 years; 10 male) treated with anthracycline chemotherapy ± radiation underwent cardiopulmonary exercise testing to quantify peak VO2, with a value < 85% of predicted defined as impaired peak VO2. Resting cardiac function was assessed using 2- and 3-dimensional echocardiography, with cardiac reserve quantified from resting and peak exercise heart rate, stroke volume index (SVI) and cardiac index (CI) using exercise cardiovascular magnetic resonance (CMR).ResultsTwelve of 20 survivors (60%) had reduced peak VO2 (70 ± 16% vs. 97 ± 14% of age and gender predicted). There were no differences in echocardiographic or CMR measurements of resting cardiac function between survivors with normal or impaired peak VO2. However, those with reduced peak VO2 had diminished cardiac reserve, with a lesser increase in CI and SVI during exercise (Interaction P < 0.01 for both), whilst the heart rate response was similar (P = 0.71).ConclusionsWhilst exercise intolerance is common among pediatric cancer survivors, it is poorly explained by resting measures of cardiac function. In contrast, impaired exercise capacity is associated with impaired haemodynamics and systolic functional reserve measured during exercise. Consequently, measures of cardiopulmonary fitness and cardiac reserve may aid in early identification of survivors with heightened risk of long-term heart failure.
Highlights
Pediatric cancer survivors are at increased risk of cardiac dysfunction and heart failure
The current paradigm for preventing cardiotoxicity relies on the early detection of cardiac dysfunction when it may be more amenable to initiation of heart failure therapy [8]
Participants were classified by normal peak Peak oxygen consumption (VO2) or impaired peak VO2 defined as peak VO2 ≥ 85% agepredicted values
Summary
Pediatric cancer survivors are at increased risk of cardiac dysfunction and heart failure. Cardiovascular disease is the most common morbidity experienced by pediatric cancer survivors with 11% of survivors having a diagnosable cardiac condition prior to 40 years of age, of which heart failure is the predominant cause [5] This has led to a shift in focus, whereby treatment success is determined by the balance between treatment efficacy and the risk of treatmentrelated toxicities [6]. Clinical decision making is complicated by the lack of sensitivity of LVEF and LV FS in explaining treatmentinduced functional limitations, patients’ symptoms and longer-term heart failure events [9, 10] This has resulted in increased interest in alternative surveillance methods for identifying cardiac dysfunction and quantifying heart failure risk [8]. The degree to which these measures are associated with functional impairment and quantifiable heart failure symptoms such as exercise intolerance is unclear
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