Circulation: Heart Failure Editors’ Picks

Lifelong exercise training maintains a youthful compliance of the left ventricle (LV), whereas a year of exercise training started later in life fails to reverse LV stiffening, possibly because of accumulation of irreversible advanced glycation end products.Alagebrium is a novel drug that breaks advanced glycation end product crosslinks and improves LV stiffness in aged animals.In this study, the authors prescribed alagebrium (200 mg daily) or placebo combined with aerobic exercise training or contact control in healthy, sedentary older individuals for 1 year.The authors evaluated overall cardiac function by the use of several modalities, including invasive pressure-volume measurements, exercise testing, and cardiac MRI before and after the training.To the authors' knowledge, this is the first study to evaluate the effects of alagebrium and exercise training in healthy aged humans.After intervention, exercise training significantly increased exercise capacity, LV mass, and LV end-diastolic volume.Conversely, alagebrium had little effect on exercise capacity or LV geometry.However, alagebrium showed a modest improvement in LV stiffness compared with placebo.This favorable effect of alagebrium on LV stiffness was most prominent in individuals with combined alagebrium and exercise training.Conclusions: Alagebrium had no effect on hemodynamics, LV geometry, or exercise capacity in healthy, previously sedentary seniors.However, it did show a modestly favorable effect on age-associated LV stiffening. 1 Prognostic Value of Exercise Testing During Heart Transplant Evaluation in ChildrenSummary: Maximum oxygen consumption (peak VO2) and efficiency of ventilation (VE) during exercise (VE/VCO2 slope) are known to stratify adults in heart failure for 1-year survival.On the basis of adult data, a recent American Heart Association scientific statement suggested that peak VO2<50% predicted for age and sex should be considered substantial impairment in exercise performance in children with heart disease and therefore a class I indication for heart transplant listing.This single-center study examined the association of peak VO2<50% predicted with risk of death or deterioration in 50 children evaluated for heart transplant during 2002 to 2011 (32 biventricular circulation, 18 palliated single ventricle).Overall, 24 children reached the composite end point (death, urgent transplant, or initiation of mechanical support).Although children with peak VO2<50% predicted and those with peak VO2≥50% predicted were equally likely to be listed, children with peak VO2<50% predicted were at 4.7-fold risk of death or deterioration on follow-up compared with those with peak VO2≥50% predicted among those with a biventricular circulation.VE/ VCO2 slope ≥34 during exercise testing was also associated with poor outcome in children with biventricular circulation.Exercise testing was unable to risk-stratify children with a palliated single ventricle.Conclusions: Exercise testing during HT evaluation in children with biventricular circulation identified those at higher risk of death or deterioration in this small study.Larger studies are needed to assess the role of exercise testing during HT evaluation in children with a palliated single ventricle.2 Effects of Exercise on Left Ventricular Systolic and Diastolic Properties in Patients With Heart Failure and a Preserved Ejection Fraction Versus Heart Failure and a Reduced Ejection FractionSummary: The purpose of the current study was to define exerciseinduced changes in indices of left ventricular systolic and diastolic properties in patients with chronic heart failure (HF), and in particular to compare these changes in patients with HF and a reduced ejection fraction (HFrEF) versus HF and a preserved EF (HFpEF).These results provided new and unique insights into understanding of exercise-induced changes in systolic and diastolic properties.For example, although the increase in cardiac output was blunted in both patients with HFrEF and HFpEF, the mechanisms underlying this limitation were significantly different.In HFrEF, systolic properties fell during exercise, but the recruitment of Frank-Starling mechanisms allowed some increase in stroke volume.By contrast, in patients with HFpEF, there was no recruitment of Frank-Starling mechanisms, but a small increase in left ventricular systolic properties allowed an increase in stroke volume.Left ventricular diastolic pressures rose in both patients with HFrEF and HFpEF; however, this was a volumedependent change in patients with HFrEF but a volume-independent change in patients with HFpEF.These data support the conclusion that although a number of mechanisms limit exercise in HFpEF, 1 dominant mechanism is the abnormalities in diastolic function.By contrast, although a number of mechanisms limit exercise in HFrEF, 1 dominant mechanism is the abnormalities in systolic function.These data may serve to underscore the differences in pathophysiology of the clinical syndrome of HFrEF versus HFpEF.Conclusions: Although exercise limitations were similar between HF and a reduced EF and HF and a preserved EF, there were significant