CARDIOVASCULAR MEDICINE

Increasing plasma potassium with amiloride shortens the QT interval and reduces ventricular extrasystoles but does not change endothelial function or heart rate variability in chronic heart failure

C A J Farquharson, A D Struthers

University Department of Clinical Pharmacology and Therapeutics, Ninewells Hospital and Medical School, Dundee, UK

Correspondence to:
Correspondence to:
Professor A D Struthers, University Department of Clinical Pharmacology and Therapeutics, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK;
a.d.struthers{at}dundee.ac.uk

Objectives: To test whether simply increasing plasma potassium with amiloride would exert any of the same beneficial effects on "surrogate outcome measures" that are seen with spironolactone. The latter has been shown to improve mortality in chronic heart failure, possibly as a result of improvements in endothelial dysfunction, vascular angiotensin converting enzyme (ACE), autonomic function, myocardial fibrosis, ventricular arrhythmias, and QT interval indices.

Design: Randomised, placebo controlled trial.

Setting: Teaching hospital.

Patients and interventions: Double blind crossover study involving 10 patients with New York Heart Association functional class II–III chronic heart failure comparing 5 mg/day amiloride (one month) with placebo.

Main outcome measures: Endothelial function, vascular ACE, collagen markers, 24 hour ECG, and QT interval results.

Results: The amiloride induced increase in serum potassium (0.4 mmol/l) did not significantly change endothelial dysfunction, vascular ACE, collagen markers, or heart rate variability. However, amiloride significantly improved QT interval indices, reducing both QT dispersion (from 65.7 ms to 50.9 ms, p = 0.001) and mean maximal corrected QT (from 445 ms to 435 ms, p = 0.008). Amiloride also reduced ventricular extrasystoles (p < 0.05).

Conclusions: Amiloride shortens QT interval length and reduces ventricular extrasystoles in chronic heart failure, implying that this effect is caused by potassium retention per se. However, unlike spironolactone, amiloride did not improve endothelial dysfunction, vascular ACE, heart rate variability, or myocardial fibrosis, implying that spironolactone improves these latter effects by aldosterone blockade rather than by simply increasing serum potassium. Therefore, amiloride has fewer beneficial mechanistic effects than spironolactone, but it does share with spironolactone the ability to shorten the QT interval and reduce ventricular extrasystoles.

Keywords: aldosterone blockade; potassium; chronic heart failure; endothelial function

Abbreviations: ACE, angiotensin converting enzyme; CHF, chronic heart failure; HOPE, heart outcomes prevention evaluation; HRV, heart rate variability; L-NMMA, N^G-monomethyl-L-arginine; NO, nitric oxide; NYHA, New York Heart Association; PIIINP, procollagen type III amino terminal peptide; QTc, corrected QT interval; QTcd, corrected QT interval dispersion; QTd, QT interval dispersion; RALES, randomized aldactone evaluation study; SOLVD, studies of left ventricular dysfunction; UK-HEART, United Kingdom heart failure evaluation and assessment of risk trial

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