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Heart failure in the elderly population represents a complex clinical situation associated with frequent hospitalizations and numerous comorbidities. The present study aimed to evaluate the impact of a domiciliary-based nurse-led strategy in a group of very elderly patients affected by heart failure who were regularly seen at an outpatient heart failure clinic (HFC).Patients were periodically assessed in their homes by two trained nurses under supervision of the cardiologists of the HFC. During each visit, the nurses examined clinical status and adherence to medication. When necessary, they also gathered venous blood samples for laboratory analysis and recorded an electrocardiogram. In addition, they provided key information regarding disease management to patients as well as to their care givers. During the baseline visit and, subsequently, every 6 months, an echocardiogram was performed at the HFC.Forty-four patients (52.4% male, median age 82 years) were followed up for a mean of 25 ± 12 months. Compared to an equally long time period before randomization, during follow-up, a significant reduction in cardiac hospitalizations (from 1.83 ± 1.54 to 1.07 ± 1.39, P = 0.004), total hospitalizations (from 2.09 ± 1.71 to 1.52 ± 1.68, P = 0.003), HFC visits (from 3.31 ± 2.33 to 2.24 ± 1.38, P = 0.03) and New York Heart Association (NYHA) class (from 2.74 ± 0.70 to 2.49 ± 0.61, P = 0.04) was observed. Total 1-year mortality was 25% and was predicted by several clinical (weight loss, NYHA class), laboratory (hyperuricaemia, anaemia, renal failure, hyposodiemia) and echocardiographic (end-systolic diameter, ejection fraction, systolic pulmonary artery pressure) parameters. Multivariate analysis revealed that hyperuricaemia was as an independent predictor of mortality (odds ratio = 1.53, P = 0.038).The present study demonstrates that a domiciliary-based strategy in elderly patients affected by heart failure guarantees clinical stability and reduces hospitalizations as well as outpatient visits.