Pathophysiology and Therapy of Cardiac Dysfunction in Duchenne Muscular Dystrophy

Daniel P. Judge; David A. Kass; W. Reid Thompson; Kathryn R. Wagner


Am J Cardiovasc Drugs. 2011;11(5):287-294. 

In This Article

6. Diuretics and Fluid Management in DMD-associated Cardiomyopathy

The use of loop diuretics for symptomatic heart failure is widespread, yet clinical trials supporting their use are lacking. That aside, they are one of the most effective treatments for symptomatic volume overload in the setting of DCM. Because of the constraints of immobility resulting from DMD, many affected individuals limit their oral intake of fluid to diminish urine volume, or they may be simply unable to gain access to fluids when thirsty. This may contribute to hypotension and increased heart rates. ACE inhibitor or ARB treatment can synergistically worsen hypotension in this setting, as angiotensin II-mediated vasoconstriction is one of the principal adaptive mechanisms for maintaining BP in the setting of dehydration.

Aldosterone antagonists (spironolactone and eplerenone) are well established as beneficial treatments for systolic heart failure with moderate to severe symptoms, and for people after acute myocardial infarction complicated by systolic dysfunction and heart failure. The RALES (Randomized Aldactone Evaluation Study) trial randomized 1663 people with severe heart failure and LV EF ≤35% to spironolactone 25 mg daily versus placebo.[28] The trial was stopped early because of a difference in the primary endpoint: death from all causes. After 2 years, there was a 30% reduction in the risk of death among patients treated with spironolactone, attributable to lower rates of both progressive heart failure and sudden cardiac death.[28] The recent EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization And Survival Study in Heart Failure) addressed the use of eplerenone in NYHA class II heart failure.[29] The trial randomized 2737 individuals with age ≥55 years, EF ≤30%, and NYHA class II symptoms to eplerenone 50 mg daily or placebo. The primary outcome was a composite of death from cardiovascular causes or hospitalization for heart failure. The Data Safety and Monitoring Board stopped the study prematurely because of a difference in the primary outcome, which occurred in 18.3% of patients who received eplerenone versus 25.9% of those who received placebo (p = 0.008).[29]

Before considering the use of aldosterone antagonists for DMD-associated DCM, one should consider several points. Shortly after RALES trial data were made public, a retrospective review of prescribing practices showed a marked increase in the use of this drug for heart failure.[30] This was followed by increased rates of both hospitalization and death from hyperkalemia.[30] Although the recent EMPHASIS-HF trial enrolled individuals with milder heart failure, 85% were using a diuretic at the time of enrollment.[29] And while only 0.3% of participants were hospitalized for hyperkalemia, the trial excluded individuals with an estimated glomerular filtration rate (GFR) of less than 30mL/min/1.73m2. Because of reduced muscle mass, GFR can be difficult to determine in people with DMD.[31]


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