Scheduled intermittent inotropes for Ambulatory Advanced Heart Failure. The RELEVANT-HF multicentre collaboration Fabrizio Oliva a,1 , Enrico Perna a,1 , Marco Marini b,1 , Daniele Nassiacos c,1 , Antonio Cirò d,1 , Gabriella Malfatto e,1 , Fabrizio Morandi f,1 , Ivan Caico g,1 , Gianpiero Perna b,1 , Sabina Meloni c,1 , Antonella Vincenzi d,1 , Alessandra Villani e,1 , Andrea Lorenzo Vecchi f,1 , Chiara Minoia g,1 , Alessandro Verde a,1 , Renata De Maria h, ⁎ ,1 , on behalf of the RELEVANT-HF study group a Cardiothoracic and Vascular Department, ASST-Great Metropolitan Hospital Niguarda, Milan, Italy b Department of Cardiovascular Sciences, Ospedali Riuniti, Ancona, Italy c Cardiology Department, ASST Valle Olona, Saronno General Hospital, Saronno, Italy d Cardiology ASST Monza, San Gerardo Hospital, Monza, Italy e Department of Cardiology, San Luca Hospital, Istituto Auxologico Italiano IRCCS, Milan, Italy f Department of Cardiovascular Diseases, Ospedale di Circolo and Macchi Foundation, University of Insubria, Varese, Italy g Cardiology Department, ASST Valle Olona, Gallarate Hospital, Gallarate, Italy h CNR Clinical Physiology Institute, Cardiothoracic and Vascular Department, ASST-Great Metropolitan Hospital Niguarda, Milan, Italy abstract article info Article history: Received 11 July 2018 Accepted 14 August 2018 Available online xxxx Background: Ambulatory Advanced Heart Failure (AAHF) is characterized by recurrent HF hospitalizations, escalating diuretic requirements, intolerance to neurohormonal antagonists, end-organ dysfunction, short- term reduced life expectancy despite optimal medical management (OMM). The role of intermittent inotropes in AAHF is unclear. The RELEVANT-HF registry was designed to obtain insight on the effectiveness and safety of compassionate scheduled repetitive 24-hour levosimendan infusions (LEVO) in AAHF patients. Methods: 185 AAHF NYHA class III–IV patients, with ≥2 HF hospitalizations/emergency visits in the previous 6 months and systolic dysfunction, were treated with LEVO at tailored doses (0.05–0.2 μg/kg/min) without prior bolus every 3–4 weeks. We compared data on HF hospitalizations (percent days spent in hospital, DIH) in the 6 months before and after treatment start. Results: Infusion-related adverse events occurred in 23 (12.4%) patients the commonest being ventricular arrhythmias (16, 8.6%). During follow-up, 37 patients (20%) required for clinical instability treatment adjustments (decreases in infusion dose, rate of infusion or interval). From the 6 months before to the 6 months after treatment start we found lower DIH (9.4 (8.2) % vs 2.8 (6.6) %, p b 0.0001), cumulative number (1.3 (0.6) vs 1.8 (0.8), p = 0.0001) and length of HF admissions (17.4 (15.6) vs 21.6 (13.4) days, p = 0.0001). One-year survival was 86% overall and 78% free from death/LVAD/urgent transplant. Conclusions: In AAHF patients, who remain symptomatic despite OMM, LEVO is well tolerated and associated with lower overall length of hospital stay during six months. This multicentre clinical experience underscores the need for a randomized controlled trial of LEVO impact on outcomes in AAHF patients. © 2018 Published by Elsevier B.V. Keywords: Ambulatory Advanced Heart Failure Levosimendan Hospitalizations Outcome 1. Introduction Advanced refractory (stage D) Ambulant Heart Failure (AAHF) is characterized by recurrent hospital admissions for HF, escalating diuretic requirements, intolerance to neurohormonal antagonists, end-organ dysfunction, cardiac cachexia and arrhythmias, despite maximal optimized drug and device therapy [1,2]. AAHF patients have a short-term reduced life expectancy, severely impaired functional capacity, poor quality of life and generate high health care costs [1]. End-organ dysfunction may ultimately preclude candidacy for advanced life-saving therapies, heart transplantation (HTx) and left ventricular assist device (LVAD). Moreover, heart replacement thera- pies do not represent viable options for most AAHF patients, because of scarce donor supply and contra-indicating comorbidities, leaving a large unmet need for effective symptom palliation. Intermittent or continuous iv inotropes were proposed in the 90's as palliative treatment in AAHF patients, but were suggested to worsen International Journal of Cardiology xxx (2018) xxx–xxx ⁎ Corresponding author at: CNR Clinical Physiology Institute, Cardiothoracic and Vascular Department, ASST-Great Metropolitan Hospital Niguarda, Piazza Ospedale Maggiore 3, 20162 Milan, Italy. E-mail addresses: renata.demaria@ospedaleniguarda.it, rdemaria@ifc.cnr.it (R. De Maria). 1 This author takes responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. IJCA-26864; No of Pages 5 https://doi.org/10.1016/j.ijcard.2018.08.048 0167-5273/© 2018 Published by Elsevier B.V. Contents lists available at ScienceDirect International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard Please cite this article as: F. Oliva, et al., Scheduled intermittent inotropes for Ambulatory Advanced Heart Failure. The RELEVANT-HF multicentre collaboration, Int J Cardiol (2018), https://doi.org/10.1016/j.ijcard.2018.08.048