Hyperkalemia in Heart Failure with Reduced Ejection Fraction: Implications and Management

Hyperkalemia is a potentially life-threatening electrolyte imbalance that has traditionally posed significant challenges in the management of heart failure (HF). This review explores the complex interplay between hyperkalemia and the use of guideline-directed medical therapies (GDMT), such as renin-angiotensin-aldosterone system inhibitors (RAASi) and steroidal mineralocorticoid receptor antagonists (sMRAs), including spironolactone and eplerenone, which are currently recommended in guidelines for improving outcomes in heart failure with reduced ejection fraction (HFrEF). While these therapies reduce mortality and hospitalizations in HFrEF, their benefit in patients with heart failure with left ventricular ejection fraction (LVEF) ≥ 40% remains less conclusive. Nevertheless, their use in clinical practice is often limited by the risk of hyperkalemia, potentially leading to dose reduction or discontinuation of life-saving treatments. The prevalence of hyperkalemia in HF patients is notably higher compared to the general population, particularly in those with comorbid chronic kidney disease (CKD) and diabetes mellitus, further complicating management. This review emphasizes the importance of regular potassium monitoring, the potential benefits of combining therapies such as sodium-glucose cotransporter 2 (SGLT2) inhibitors with RAASi to reduce the risk of hyperkalemia, and the emergence of the newer non-steroidal MRA (nsMRA), finerenone, which may have a lower risk of hyperkalemia. Additionally, potassium binders such as patiromer and sodium zirconium cyclosilicate (SZC) are highlighted for their role in managing and preventing hyperkalemia, allowing patients to continue optimal RAASi and MRA therapy without interruption. By synthesizing current evidence on the incidence, risks, and management strategies of hyperkalemia in HF, this review aims to provide a comprehensive guide for clinicians to optimize patient outcomes while mitigating the risks associated with hyperkalemia.