Exercise cardiovascular magnetic resonance reveals reduced cardiac reserve in pediatric cancer survivors with impaired cardiopulmonary fitness

Abstract

Background: Pediatric cancer survivors are at increased risk of cardiac dysfunction and heart failure. Reduced peak oxygen consumption (peak VO 2) 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 VO 2 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. Methods: Twenty pediatric cancer survivors (8-24 years; 10 male) treated with anthracycline chemotherapy ± radiation underwent cardiopulmonary exercise testing to quantify peak VO 2 , with a value < 85% of predicted defined as impaired peak VO 2. 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). Results: Twelve of 20 survivors (60%) had reduced peak VO 2 (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 VO 2. However, those with reduced peak VO 2 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). Conclusions: Whilst 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.

Clinical, Echocardiographic, and Biomarker Associations With Impaired Cardiorespiratory Fitness Early After HER2-Targeted Breast Cancer Therapy

“…Our findings confirm the relationship between GLS and VO 2 peak previously reported in survivors of pediatric cancers at long-term follow-up ( 25 ) and in women with HER2+ breast cancer, a median of 7 years after trastuzumab treatment ( 4 ). In the latter study, 22 women with a prior history of CTRCD had persistently reduced LVEF and GLS and a 25% lower VO 2 peak (22.9 ± 4.4 mL O 2 •kg −1 •min −1 ) compared with age-matched healthy control subjects (30.5 ± 3.4 mL O 2 •kg −1 •min −1 ).…”

Rapid cardiovascular aging following allogeneic hematopoietic cell transplantation for hematological malignancy

“…Early detection of cancer treatment-related cardiac dysfunction is critical to facilitate prompt intervention and more effectively prevent irreversible damage and long-term morbidity. Accordingly, the application of exercise stress for the quantification of cardiovascular reserve (defined as the increase in cardiovascular function from rest to peak exercise) has emerged as an efficacious approach in unmasking subclinical cardiovascular pathology ( 22 – 24 ), and predicting all-cause, cardiovascular, and cancer-specific mortality ( 25 – 27 ). Cardiovascular reserve can be evaluated via a specific approach using exercise cardiac magnetic resonance imaging (exercise CMR) to directly quantify cardiac reserve (ability to augment cardiac output during exercise), or an integrative approach using cardiopulmonary exercise testing (CPET) for the assessment of peak oxygen uptake (VO 2 peak).…”

Radiotherapy-Induced Cardiotoxicity: The Role of Multimodality Cardiovascular Imaging

“…Foulkes et al ( 72 ) studied 20 pediatric cancer survivors treated with anthracycline chemotherapy with or without concomitant RT with exercise CMR using a CMR compatible ergometer 4.4 years after diagnosis. Twelve (60%) patients had reduced peak oxygen consumption (VO 2 ; defined as < 85% age-predicted values) and despite having similar resting cardiac function in terms of LVEF and GLS (with feature-tracking) compared to their counterparts with normal peak VO 2 , they demonstrated reduced cardiac reserve on exercise CMR.…”