Loop diuretic resistance complicating acute heart failure

  • Zachary L. CoxEmail author
  • Jeffrey M. Testani


Acute heart failure hospitalizations complicated by diuretic resistance are associated with worse outcomes. Yet, quantification of the frequency and accompanying risk from loop diuretic resistance is limited by the absence of a comprehensive definition with universal clinical application. Herein, we outline limitations of the current metrics used to identify and define diuretic resistance. We discuss the best available methods to identify and prognosticate outcomes in diuretic resistance. We propose a mechanism-based classification system of diuretic resistance by anatomical location as follows: pre-nephron resistance, pre-loop of Henle resistance, loop of Henle resistance, and post-loop of Henle resistance. Within this paradigm, we compare and contrast historical beliefs of resistance mechanisms with current literature specific to patients with heart failure. We recommend a treatment pathway to restore diuretic efficacy with a literature review of the various combination diuretic strategies and ongoing clinical trials that may impact current best practices.


Diuretic resistance Acute heart failure Heart failure Loop diuretic Diuretic Combination nephron blockade Combination diuretic therapy 



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

Authors and Affiliations

  1. 1.Department of Pharmacy Practice, Burton Health Science CenterLipscomb University College of PharmacyNashvilleUSA
  2. 2.Department of PharmacyVanderbilt University Medical CenterNashvilleUSA
  3. 3.Division of Internal Medicine, Section of Cardiovascular MedicineYale University School of MedicineNew HavenUSA

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