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Heart failure increases in prevalence with age and is usually associated with various cardiac and non-cardiac comorbidities. For common coexisting conditions such as renal dysfunction, anemia and type 2 diabetes mellitus, important pathophysiologic links have been implicated between cardiac dysfunction and the underlying condition. Indeed, the number and severity of comorbidities in the setting of heart failure is an important driver of prognosis. By targeting the management of coexisting diseases, it may be possible to improve functional capacity, quality of life and perhaps even overall mortality in heart failure patients. Recent clinical trial data has provided insights into cardio-renal interactions in acute heart failure, the impact of iron replacement therapy in iron deficient heart failure patients, and the role of pharmacologic therapies to prevent heart failure related events in high risk patients with type 2 diabetes.