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Updated: Dec 26, 2025
Lumped-Parameter and Finite Element Modeling of Heart Failure with Preserved Ejection Fraction
Published on: February 13, 2021
Diuretic Therapy for Patients With Heart Failure: JACC State-of-the-Art Review
G Michael Felker1, David H Ellison2, Wilfried Mullens3
1Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina; Divison of Cardiology, Duke University School of Medicine, Durham, North Carolina.
Insights
Loop diuretics are key for managing heart failure congestion. Understanding renal physiology and diuretic pharmacokinetics is crucial, especially with diuretic resistance, which indicates a poor prognosis.
Area of Science:
- Nephrology
- Cardiology
- Pharmacology
Background:
- Extracellular fluid volume expansion is central to heart failure pathophysiology.
- Increased fluid volume elevates intracardiac filling pressures, causing congestion.
- Loop diuretics are a cornerstone therapy for heart failure, yet evidence guiding their use is limited.
Purpose of the Study:
- To review the fundamental mechanisms and physiological principles of diuretic therapy in heart failure.
- To discuss the available data on the optimal use of diuretics.
- To highlight the clinical challenge of diuretic resistance.
Main Methods:
- Literature review of renal physiology and diuretic pharmacokinetics.
- Analysis of clinical trial data and guidelines for diuretic use in heart failure.
- Discussion of mechanisms underlying diuretic resistance.
Main Results:
- A nuanced understanding of renal physiology and diuretic pharmacokinetics is essential for effective management.
- Diuretic resistance is a significant clinical challenge associated with poor prognosis.
- Optimal use of diuretics requires careful consideration of individual patient factors and potential resistance.
Conclusions:
- Skillful use of diuretics in heart failure management requires a deep understanding of underlying physiology.
- Addressing diuretic resistance is critical for improving patient outcomes.
- Further research is needed to provide robust clinical trial evidence for diuretic therapy.
Abstract:
Expansion of extracellular fluid volume is central to the pathophysiology of heart failure. Increased extracellular fluid leads to elevated intracardiac filling pressures, resulting in a constellation of signs and symptoms of heart failure referred to as congestion. Loop diuretics are one of the cornerstones of treatments for heart failure, but in contrast to other therapies, robust clinical trial evidence to guide the use of diuretics is sparse. A nuanced understanding of renal physiology and diuretic pharmacokinetics is essential for skillful use of diuretics in the management of heart failure in both the inpatient and outpatient settings. Diuretic resistance, defined as an inadequate quantity of natriuresis despite an adequate diuretic regimen, is a major clinical challenge that generally portends a poor prognosis. In this review, the authors discuss the fundamental mechanisms and physiological principles that underlie the use of diuretic therapy and the available data on the optimal use of diuretics.
