Hyperkalemia in heart failure patients: current challenges and future prospects Raquel López-Vilella, Herminio Morillas-Climent, Diego Plaza-López, Mónica Cebrián-Pinar, Ignacio Sánchez-Lázaro, Luis Almenar-Bonet Heart Failure and Heart Transplant Unit, Cardiology Department, Hospital La Fe, Valencia, Spain Abstract: In heart failure (HF), hyperkalemia is a frequent problem because of several factors, such as neurohormonal mechanisms involved in the disease, renal failure, comorbidities, and drugs with a prognostic benefit. These drugs can block the renin–angiotensin–aldosterone system, and therefore, serum potassium levels can increase, mostly when combined with other drugs as nonsteroidal anti-inflammatories, digitalis, heparin, etc. Hyperkalemia can have severe consequences if not corrected, mostly at the cardiac level (decrease in speed conduction, QRS enlargement, ventricular arrhythmias, and asystole). Therefore, it is important to adequately prescribe these potentially harmful drugs (starting at low doses with close monitoring of renal function and potassium levels), to carefully manage the factors that can interfere with potassium levels, and to early treat hyperkalemia if it develops. There are several investigation lines for the design of new molecules that show a similar efficacy to that of renin–angiotensin–aldosterone system, with a lower risk of hyperkalemia: nonsteroidal mineralocorticoid receptor antagonists like finerenone, which is a more cardioselective drug than traditional mineralocorticoid receptor antagonists, and angiotensin and neprilysin inhibitors such as LCZ696, which have proven to reduce mortality and heart failure hospitalizations. Besides, new drugs are being studied, which are able to reduce levels of serum potassium in a sustained and faster way, like chelating polymers Patiromer and sodium zirconium cyclosilicate. Keywords: hyperkalemia, heart failure, renin–angiotensin–aldosterone system inhibitors