Over 90,000 North Americans are diagnosed with cancer before the age of 40. Improved cancer therapies have led to an exponential growth in the number of pediatric, adolescent, and young adult cancer survivors (AYA-CS) who are expected to live 50-60 years beyond diagnosis. However, AYA-CS are at increased risk of developing multiple cancer- and treatment-related morbidities including poor fitness (e.g., low VO2peak), hypertension (HTN), diabetes, and poor mental health, which all contribute to premature cardiovascular disease (CVD). The prevalence of CVD events (e.g. heart failure, heart attack, stroke) is up to 23.8% in adult survivors of pediatric cancers with long term follow-up after treatment. The incidence of subclinical CVD, which is a precursor to CVD events, is even higher in AYA-CS; up to 40%, 11%, and 5% experience subclinical cardiomyopathy measured by abnormal global longitudinal strain (GLS), diastolic dysfunction (DD) or mild reduction in left ventricular ejection fraction (LVEF), respectively, and 18% experience reduced aerobic fitness. The treatment of modifiable CVD risk factors must be considered a fundamental target for improving CVD health-related outcomes in AYA-CS. To this end, exercise and best-practices for CVD risk factor modification are integral to a cardiac rehabilitation model. Traditional cardiac rehabilitation models for patients with CVD (consisting of exercise, CVD risk factor treatment, and patient education) are safe and effective in improving HRQoL, morbidity, and mortality risk. However, by virtue of their age and low short-term CVD risk, AYA-CS do not meet traditional criteria for initiating cardiac rehabilitation (CR) and are less likely to receive treatments to reduce CVD risk. AYA-CS with stage B heart failure (SBHF): (1) are at high risk for subsequent HF/CVD death; (2) have lower cardiopulmonary fitness; and (3) are more likely to benefit from CVD risk factor management. Considering that AYA-CS have an estimated 33% prevalence of SBHF, this vulnerable cohort of cancer survivors represent an opportunity for intervention that is highly feasible and potentially impactful. Exercise is a preferred method for optimizing health and survival in PAYA-CS. However, we need models that safely and effectively deliver exercise interventions that meet the unique needs of this population. The cardio-oncology rehabilitation (CORE) model is an intervention that would provide AYA-CS with SBHF a supervised and home-based high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) exercise therapy, CVD risk factor modification, and behavioural support to reduce the risk of CVD. The primary objective of the HIMALAYAS study is to determine whether supervised CORE (Group 1A) improves cardiorespiratory fitness (VO2peak; primary outcome), cardiac function, CVD risk factors and biomarkers, and PROs at 6 months (primary timepoint) as well as 12 and 24 months compared to standard of care group (CON1; Group 1B) in AYA-CS with SBHF. The secondary objective of the study is to assess the independent effects of two passive behavioural support strategies based on the attainment of a weekly PAI score ≥100 [PAI; Group 2A] or the exercise guidelines for cancer survivors (i.e. 90 to 150 minutes of moderate to vigorous PA per week; [ExGL; Group 2B]) on VO2peak, cardiac function, CVD risk factors and biomarkers, and PROs at 24 months compared to standard of care [CON2; Group 2C] in AYA-CS with and without SBHF. Due to the COVID-19 pandemic, CORE intervention will involve a facility-based HIIT session and home-based HIIT session (described as HIIT at Home) per week. The study will include a pre-trial pilot and a substudy within the Primary RCT to develop and validate HIIT at Home methods.
Cardiovascular disease (CVD) is a major contributor to morbidity and mortality in pediatric, adolescent and young adult (AYA) cancer survivors (hereafter referred to as AYA-CS). Exercise is a cornerstone of CVD prevention and treatment; yet, exercise has not been adopted as a standard of care in AYA-CS at high CVD risk. The HIMALAYAS trial is designed to evaluate the impact of an exercise-based cardiac rehabilitation program on cardiovascular (CV) and psychosocial health, as well as CVD risk, in AYA-CS with mild heart dysfunction (stage B heart failure (SBHF)). The primary objective of the HIMALAYAS study is to determine whether supervised Cardio-oncology Rehabilitation [CORE; Group 1A], consisting of moderate to high-intensity aerobic exercise training, CVD risk factor modification and enhanced online behavioural support, improves cardiorespiratory fitness (VO2peak; primary outcome), cardiac function, CVD risk factors and biomarkers, and patient-reported outcomes (PROs) at 6, 12, and 24 months compared to standard of care [CON1; Group 1B] in AYA-CS with SBHF. Additionally, AYA-CS with and without SBHF will participate in a secondary randomized controlled trial (RCT) to assess the independent effects of two passive behavioural support strategies based on the attainment of the personal activity intelligence (PAI) score [PAI; Group 2A] or the exercise guidelines for cancer survivors [ExGL; Group 2B] on cardiorespiratory fitness, cardiac function, CVD risk factors and biomarkers, and PROs at 24 months compared to standard of care [CON2; Group 2C].