Serum potassium and heart failure: association, causation, and clinical implications

Dyskalemia (hypo- and hyperkalemia) is a common clinical encounter in patients with heart failure (HF), linked to underlying pathophysiologic alterations, pharmacological treatments, and concomitant comorbidities. Both hypo- and hyperkalemia have been associated with a poor outcome in HF. However, it is not known if this association is causal. In order to investigate this relation, we implemented the Bradford Hill criteria for causation examining the available literature. Of note, hypokalemia and low-normal potassium levels (serum potassium < 4.0 mmol/L) appear to be associated with adverse clinical outcomes in HF in a cause-and-effect manner. Conversely, a cause-and-effect relationship between hyperkalemia (serum potassium > 5.0 mmol/L) and adverse clinical outcomes in HF appears unlikely. We also examined the benefits of renin-angiotensin-aldosterone system inhibitors (RAASi) therapy uptitration in patients with HF and reduced ejection fraction. In fact, hyperkalemia often limits RAASi use, thereby negating or mitigating their clinical benefits. Finally, serum potassium levels in HF should be maintained within the range of 4.0-5.0 mmol/L, and although the correction of hyperkalemia does not appear to improve clinical outcomes per se, it may enable the optimal titration of RAASi, offering indirect clinical benefit.