ABSTRACT
Diuretics play an essential role in the management of patients with congestive heart
failure. Neurohormonal activation in patients with heart failure results in salt and water
retention that frequently leads to symptoms of dyspnea and edema. By inhibiting the
kidney’s ability to reabsorb sodium, diuretics reduce extracellular fluid volume and are
effective at rapidly reducing symptoms of congestion. The ability to relieve symptoms and
improve functional capacity has made diuretics first line agents in the treatment of heart
failure for the past several decades. Yet despite their universal acceptance, there are data
suggesting that diuretics may have detrimental vascular, hemodynamic, and neurohor-
monal effects, and with the exception of the potassium sparing class, the impact of
diuretics on mortality in patients with heart failure remains unknown. Because diuretics
were introduced prior to the advent of rigorous clinical trials with mortality endpoints,
they have escaped the scrutiny that other heart failure drugs have been subjected to.
Randomized clinical trials involving diuretics in the modern era would be considered by
many to be impractical if not unethical, and most heart failure trials performed today
require that patients already be on a stable dose of diuretic. As a result, the direct influence
of diuretics on cardiac performance, hemodynamic profile, ventricular remodeling,
neurohormonal activation, and long term survival in patients with heart failure remains
controversial and incompletely studied. This chapter will review the limited available
data, highlighting both the beneficial and potentially deleterious effects of diuretics in the
treatment of heart failure. Treatment strategies based on diuretic mechanisms of action and
pharmacokinetic properties will be presented, and therapeutic options for treating patients
with diuretic resistance will be discussed.
