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Heart Failure: New Approaches to an Old Problem

      This month’s special focus section is devoted to heart failure. Needless to say, a well-functioning and healthy heart is desirable for all people. When this vital organ begins to fail, the treating clinician knows that accurate diagnosis and carefully chosen interventions are essential. In this issue, Professor Peter L. Thompson, our Topic Editor for Cardiovascular, Preventive Medicine, and Primary Care, has assembled a collection of articles discussing heart failure and its treatments, ranging from pharmacotherapy to adjuvant devices.
      • Nanayakkara S.
      • Kaye D.M.
      Management of heart failure with preserved ejection fraction.
      • Macdonald P.S.
      Combined angiotensin receptor and neprilysin antagonists (ARNI): a new paradigm in the management of chronic heart failure.
      • Marangou J.
      • Paul V.
      Current attitudes to cardiac devices in heart failure.
      • Mareev Y.
      • Cleland J.G.
      Should beta-blockers be used in patients with heart failure and atrial fibrillation?.
      • Davidson P.M.
      • Newton P.J.
      • Tankumpuan T.
      • et al.
      Multidisciplinary management of chronic heart failure: principles and future trends.
      • Jabbour A.
      • Macdonald P.S.
      Latest developments in heart transplantation.
      In his accompanying editorial, Professor Thompson summarizes these articles and provides his overview of the current state of the art for therapy of heart failure.
      • Thompson P.L.
      Heart failure: A major management challenge with encouraging recent progress.
      Whenever we read about heart failure, it is almost always described as a complex problem because it encompasses functional and structural impairments involving the ejection of blood from (and the filling of) ventricles. Symptoms and signs are variable. Some patients may be asymptomatic for a time; others may present with any combination of fatigue, shortness of breath, exercise limitations, or fluid retention appearing as edema.
      In 2013, the American Heart Association and the American College of Cardiology Foundation issued guidelines for treating heart failure.
      • Yancy C.W.
      • Jessup M.
      • Bozkurt B.
      • et al.
      2013 ACCF/AHA guideline for the management of heart failure: a report of the american college of cardiology foundation/american heart association task force on practice guidelines.
      Unless interventions are successful, heart failure progresses through stages ranging from stage A, in which patients show no signs of structural damage, to stage D, in which the failure is refractory to standard interventions. The most important intervention is obviously early recognition of any factors that may predispose a patient to heart failure or complicate existing heart failure (eg, hypertension, diabetes mellitus, atrial fibrillation). These guidelines are thoughtful and well documented, but, unfortunately for many clinicians, they may be too lengthy to be readily comprehended and useful.
      In 2015, these guidelines are still valuable with the exception of 1 omission. Although these recommendations discuss the value of inhibition of angiotensin-converting enzymes and angiotensin II receptor antagonists, they do not discuss a newly marketed combination of a receptor antagonist with an agent that inhibits the degradation of important peptides that lower blood pressure by reducing blood volume. The enzyme responsible for this degradation is neprilysin, which raises the concentrations of brain and atrial natriuretic peptides. Sacubitril is a drug that inhibits neprilysin.

      Sacubitril. https://en.wikipedia.org/wiki/Sacubitril. Accessed 2 September 2015.

      Sacubitril is administered as a prodrug that is de-ethylated by esterases to an active intermediary compound that inhibits neprilysin. Valsartan is an angiotensin II type 1 receptor antagonist. In July 2015, the US Food and Drug Administration approved (by granting a Fast Track Designation) a combination of sacubitril and valsartan.
      Trademark: Entresto™ (Novartis AG, Basel, Switzerland).

      FDA approves new drug to treat heart failure. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm453845.htm. Accessed 2 September 2015.

      *Trademark: Entresto™ (Novartis AG, Basel, Switzerland).
      Some clinicians believe that this new drug combination will provide meaningful benefit over currently available treatment choices.
      Sacubitril/Valsartan (Entresto) for Heart failure.

      References

        • Nanayakkara S.
        • Kaye D.M.
        Management of heart failure with preserved ejection fraction.
        Clin Ther. 2015; 37: 2186-2198
        • Macdonald P.S.
        Combined angiotensin receptor and neprilysin antagonists (ARNI): a new paradigm in the management of chronic heart failure.
        Clin Ther. 2015; 37: 2199-2205
        • Marangou J.
        • Paul V.
        Current attitudes to cardiac devices in heart failure.
        Clin Ther. 2015; 37: 2206-2214
        • Mareev Y.
        • Cleland J.G.
        Should beta-blockers be used in patients with heart failure and atrial fibrillation?.
        Clin Ther. 2015; 37: 2215-2224
        • Davidson P.M.
        • Newton P.J.
        • Tankumpuan T.
        • et al.
        Multidisciplinary management of chronic heart failure: principles and future trends.
        Clin Ther. 2015; 37: 2225-2233
        • Jabbour A.
        • Macdonald P.S.
        Latest developments in heart transplantation.
        Clin Ther. 2015; 37: 2234-2241
        • Thompson P.L.
        Heart failure: A major management challenge with encouraging recent progress.
        Clin Ther. 2015; 37: 2182-2185
        • Yancy C.W.
        • Jessup M.
        • Bozkurt B.
        • et al.
        2013 ACCF/AHA guideline for the management of heart failure: a report of the american college of cardiology foundation/american heart association task force on practice guidelines.
        J Am Coll Cardiol. 2013; 62: e147-e239
      1. Sacubitril. https://en.wikipedia.org/wiki/Sacubitril. Accessed 2 September 2015.

      2. FDA approves new drug to treat heart failure. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm453845.htm. Accessed 2 September 2015.

      3. Sacubitril/Valsartan (Entresto) for Heart failure.
        The Med Letter. 2015; 57: 107-109