Risk of heart failure progression in patients with reduced ejection fraction: mechanisms and therapeutic options

  • Edoardo GrondaEmail author
  • Emilio Vanoli
  • Stefania Sacchi
  • Guido Grassi
  • Giuseppe Ambrosio
  • Claudio Napoli


Transition from stage C to stage D of heart failure (HF) represents an irreversible process toward end-stage disease. Crucial interventions to be adopted in the attempt to interfere with this process are represented by the identification of patients at high risk to develop HF progression and by an effective and prompt management. Markers of worse prognosis and disease progression are well established and include recurrence of HF decompensation, intolerance to the neurohormonal standard pharmacological treatment, and resistance to loop diuretics. In addition, both NT-proBNP and sympathetic nervous system (SNS) overdrive are strong predictors of adverse clinical outcome and allow to identify high-risk HF patients even in the presence of mild symptoms. To counteract the deleterious effects of the SNS activation, new strategies such as a new drug combining angiotensin receptor and neprilysin inhibition and baroreceptor stimulation therapy (BAT) have been investigated. Inability to properly counteract the SNS overdrive leads to acute HF decompensation by different mechanisms. The leading ones are represented by the progressive sodium and water retention with fluid overload and by the blood volume redistribution between splanchnic and non-splanchnic regions. The correct understanding of these mechanisms, together with the availability of new therapeutic options such as peritoneal ultrafiltration, represent the rationale but not infrequently overlooked therapeutic options to improve congestion management in HF patients.


Heart failure Reduced ejection fraction Stage D Stage C Risk of progression 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Edoardo Gronda
    • 1
    Email author
  • Emilio Vanoli
    • 1
    • 2
  • Stefania Sacchi
    • 1
    • 3
  • Guido Grassi
    • 4
  • Giuseppe Ambrosio
    • 5
  • Claudio Napoli
    • 6
  1. 1.Fondazione IRCCS Ca’ Granda - Ospedale Maggiore Policlinico di Milano Dipartimento Di Medicina e Specialità Mediche MilanMilanItaly
  2. 2.Department of Molecular MedicineUniversity of PaviaPaviaItaly
  3. 3.Cardiovascular RehabilitationSan Raffaele University HospitalMilanItaly
  4. 4.Clinica MedicaUniversity of Milano-BicoccaMilanItaly
  5. 5.Division of CardiologyUniversity of PerugiaPerugiaItaly
  6. 6.Department of Medical, Surgical, Neurological, Aging and Metabolic SciencesUniversity “L. Vanvitelli”, Naples and Institute of Diagnostic and Nuclear Development (SDN), IRCCSNaplesItaly

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