8. Is there evidence that exercise increases the risk of deterioration of cardiac systolic function in adult-onset cancer survivors and non- oncology at-risk populations?
First Author Year	Study Design Treatment era Years of follow-up	Participants	Treatment	Main outcomes	Addt’l remarks
Schmitz70 2010	Guideline-expert opinion- American College of Sports Medicine	Only ADULT cancer studies reviewed		Physical activity is strongly recommended with the exception of activities resulting in rapid BP elevation (eg isometric exercise)
Pellicia71 2006	Guideline-expert opinion- European Society of Cardiology			Recommendation is for physical activity in individuals with genetic susceptibility to CHF, but with normal systolic function.
Dickstein63 2008	Guideline – review of published evidence, expert panel; European Society of Cardiology			Recommendations – Weight reduction should be considered in obese persons with heart failure In moderate to severe heart failure, weight reduction should not be recommended routinely	No supporting evidence supplied Level of evidence C
Maron72 2004	Consensus document; expert international panel of clinical cardiovascular specialists and molecular biologists; American Heart Association	Young people (<40 years age) with genetic cardiovascular diseases including hypertrophic cardiomyopathy but not specifically including dilated cardiomyopathy.	Not specifically considered. Considered recommendations for physical activity and recreational sports participation. Childhood cancer survivors (CCS) not included.	Recommendations: Can safely participate in most low or moderate-intensity recreational exercise Some activities should be avoided, eg burst exertion, extremely adverse environmental conditions, exercise programmes with systematic / progressive levels of exertion and aiming at higher levels of conditioning, intense isometric exertion, extreme sports, performance-enhancing substances
Riegel73 2009	Review / scientific statement; expert panel; American Heart Association	Persons with heart failure	Not specifically considered. CCS not mentioned specifically.	Statements In moderate heart failure, exercise improves certain physiological parameters including VO2max, ventilatory response, heart rate variability. Can also reduce depression. Effect on mortality not clear. Cites Pina et al 2003. Individually tailored exercise programme based on results of formal exercise testing may benefit patients with severe symptomatic LV dysfunction. Cites Fletcher et al 2001. Exercise is a beneficial adjunctive treatment in patients with current or prior heart failure symptoms and reduced LVEF. Cites Hunt et al 2005 (states this is level 1B evidence). Modest benefit in HF-Action RCT (Flynn et al, 2009, see below)
Flynn74 2009	HF-Action Randomised controlled trial Randomised 2003-7 Median FU 2.5 years	2331 stable out-patients with heart failure (LVEF ≤35%) 82 centres in USA, Canada, France	Randomised to Usual care + aerobic exercise training (initially supervised, subsequently home-based) vs usual care + recommendation for regular physical activity. Usual care included optimal medical therapy.	At 3 months, usual care + exercise training group showed statistically greater improvement in Kansas City Cardiomyopathy Questionnaire (KCCQ – a 23 item disease-specific questionnaire) score than usual care group. Improvement was maintained. Also modest but significant improvement in quality of life and non-significant reduction in all-cause mortality and hospitalisation in usual care + exercise training group.
Piepoli75 2004	Meta-analysis (individual patient data) 1990–2002 Individual median F/U 5–75mths, overall 23mths	9 studies, total 395 training to 406 control 87% males, 59% with IHD, mean LVEF <28%, 73% on ACE inhibitors	All RCTs, usual care vs addition of exercise training (mostly supervised)	Outcome of mortality in favour of exercise – 0.65 (0.46–0.92) Outcome of death or admission to hospital also in favour of exercise – 0.72 (0.56–0.93)	Intensity generally set at 60–80% peak oxygen consumption. These trials are designed to be “safe” first and foremost. Question of whether differing aetiologies of systolic dysfunction/heart failure have differing responses to physical activity not yet answered.
Davies76 2010	Meta-analysis (publication data) 2001-Jan2008 Individual median F/U 5 mths-60mths., overall 11mths	19 trials, total 3647 patients (HF-ACTION trial contributed 60%) Only one trial 57% femaies, others 72–100% male; age 58	All RCTs, usual care vs addition of exercise training (mostly supervised) Only 4 trials F/U longer than 12 mths.	All cause mortality <12 mth F/U outcome in favour of usual care – 1.03 (0.70–1.53), but >12mth F/U favoured exercise – 0.91 (0.78–1.06) All hospital admissions both < and >12 mths favoured exercise. HRQoL measurements also favoured exercise.	If HF-ACTION trial excluded, significant reduction longer-term mortality seen (0.62 (0.39–0.98). Issues of mix of endurance and resistance training starting to be addressed.