Hyperkalaemia is associated with poor clinical outcomes in patients with Heart Failure (HF). However, monitoring is often suboptimal and hyperkalaemia often inappropriately managed.
Reference ranges may show slight variation but hyperkalaemia as defined by the European Society of Cardiology(ESC) is outlined below:
| Disease Classification | Serum Potassium Level |
|---|---|
| Hypokalaemia | <3.5mmol/L |
| Normal | 3.5-5.0mmol/L |
| Mild hyperkalaemia | 5.0-5.5mmol/L |
| Moderate hyperkalaemia | 5.5-6.0mmol/L |
| Severe hyperkalaemia | >6.0mmol/L |
Incidence
The prevalence of hyperkalaemia in HF at any given time is expected to be less than five percent, although it is much higher in chronic HF (up to 40 percent) and Chronic Kidney Disease (up to 73 percent) over a one-year follow-up period. Recent HF clinical trials showed an occurrence of hyperkalaemia ranging from 5.2 to 13 percent, with a higher incidence when potassium retaining medications are combined.
Causes
Hyperkalaemia in HFrEF can be caused by factors such as impaired potassium elimination, medications, deficiency of aldosterone, high dietary potassium, or excess release of potassium from cells into the blood . HF patients at highest risk of developing hyperkalaemia include patients with renal impairment (up to 50 percent of HFrEF patients) and diabetes mellitus.
Current first-line recommendations for the treatment of patients with HFrEF are illustrated by the Four Pillar approach.
Of these medications, several can cause hyperkalaemia, and using these in combination increases that risk. However, trials with SGLT2-inhibitors in HF have shown a reduced risk of hyperkalaemia compared with placebo in those who received dapagliflozin alongside an MRA, but the mechanism is unclear.
Diagnosis
Those with mild-to-moderate hyperkalaemia may be asymptomatic or experience only mild symptoms such as muscle weakness, palpitations, or a slow weak pulse. Severe hyperkalaemia may result in bradycardia and sudden death. Often, hyperkalaemia is only detected on routine blood tests undertaken as part of the recommended monitoring for medications.
Treatment
Management of hyperkalaemia aims to restore normal levels through intracellular shifting of potassium and/or increasing excretion. Acute hyperkalaemia requires hospital treatment for intravenous therapy, and in severe or life-threatening hyperkalaemia dialysis should be considered.
Treatment options include:
- IV calcium chloride or calcium gluconate: indicated when there are ECG changes associated with hyperkalaemia (such as peaked T waves, widened QRS interval or ventricular arrhythmias) or cardiac arrest. This stabilises the cardiac membrane but does not eliminate potassium and so should be combined with another therapy.
- Insulin (usually with glucose) or nebulised salbutamol (off-label) can be considered; these acutely lower blood potassium through causing the potassium to shift intracellularly.
- Enhancing potassium excretion should be considered: options include loop diuretics if the patient if hypervolaemic (or with adequate ongoing fluid replacement) or potassium binders (resins) to increase intestinal potassium excretion/reduce absorption and reabsorption.
- Sodium bicarbonate can be considered where acidosis is present and respiration adequate, and again causes intracellular shift of potassium.
Ongoing management of chronic hyperkalaemia is limited. Options include:
- Manage RAASi (renin-angiotensin-aldosterone system inhibitor) therapy appropriately, temporarily reducing or discontinuing HF medications which may cause hyperkalaemia. These medications should be re-initiated and titrated to optimal doses after serum potassium stabilises, although often this does not happen and results in potential patient harm.
- Chronic hyperkalaemia often leads to intolerable dietary restrictions which adversely affect patients nutrition and quality of life.
- Consider potassium binders; this may facilitate RAASi dose optimisation but use is restricted and specialist advice should be sought:
- Polystyrene sulfonates (Sodium polystyrene sulfonate – SPS, Resonium® A/Kayexalate®; calcium polystyrene sulfonate – CPS, Calcium Resonium®, Kayexelate® Calcium): must be short-term use only due to severe gastrointestinal side effects. Polystyrenes can lead to worsening HF symptoms due to their mechanism of action and so should not be first line. Of these, calcium resonium is often the preferred choice in HF.
- Patiromer sorbitex calcium (Veltassa®)
- Sodium zirconium cyclosilicate (SZC, Lokelma®)
- Ensure effective diuretic therapy.
- Oral sodium bicarbonate in chronic metabolic acidosis.
Recommendations for RAASi therapy
| European Society for Cardiology | NICE |
| Potassium (mEq/L): 4.5-5.0If not taking maximum tolerated guideline recommended dose, initiate and up-titrate RAASi therapy and closely monitor potassium. >5.0 to ≤6.5If taking maximum tolerated guideline recommended dose of RAASi therapy, initiate potassium-lowering therapy, closely monitor potassium and continue potassium-lowering therapy unless another treatable aetiology for hyperkalaemia is identified.If not taking maximum tolerated guideline recommended dose of RAASi therapy, initiate potassium lowering therapy and titrate RAASi therapy once potassium is <5.0, closely monitor potassium and continue potassium-lowering therapy unless another treatable aetiology for hyperkalaemia is identified. >6.5Temporarily stop or reduce RAASi therapy and manage acute hyperkalaemia. If not already initiated, initiate potassium-lowering therapy, closely monitor potassium and continue potassium-lowering therapy unless another treatable aetiology for hyperkalaemia is identified. | Potassium (mEq/L): >5.0Do not initiate RAASi therapy in patients with CKD ≥6.5Discontinue RAASi therapy once other drugs known to increase the risk of hyperkalaemia have been stoppedPotassium binders should only be used in HF/CKD if there is persistent hyperkalaemia (≥6.0mEq/L) and unable to optimise RASSi therapy. |
NB: It is very rarely necessary to stop RAASi therapy in patients with HF and clinical deterioration is likely if treatment is withdrawn. Specialist advice should be sought before treatment discontinuation. This guidance should be used cautiously in patients with chronic kidney disease. Local guidelines may vary.
Conclusion
Patients with HF are at an increased risk of hyperkalaemia for a variety of reasons and are often inappropriately managed, putting the patient at risk of increased morbidity and mortality. Studies show that the benefits of HF medications outweigh the risks, even if they induce hyperkalaemia, provided there is an appropriate surveillance strategy in place. There is no universally accepted consensus regarding best practice, particularly regarding more recently developed potassium binders.
Further reading:
- Palmer, B., et al. 2021. Clinical Management of Hyperkalemia. Mayo Clinic.
- Comín-Colet,, J., et al., 2022. Spotlight on Hyperkalaemia in Heart Failure. HF Policy Network.
- Ismail, U., Sidhu, K. and Zieroth, S., 2019. Hyperkalaemia in Heart Failure. Cardiac Failure Review, 35(2), pp.150-155.
- Ismail, U., Sidhu, K. and Zieroth, S., 2021. Hyperkalaemia in Heart Failure. [online] Cardiac Failure Review.
- McDonagh, T., et al. 2021. 2021 ESC Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure. European Heart Journal, 42, pp.3599-3726.
- New England Journal of Medicine, 1991. Effect of Enalapril on Survival in Patients with Reduced Left Ventricular Ejection Fractions and Congestive Heart Failure. 325(5), pp.293-302.
- Yusuf, S., Pfeffer, M., Swedberg, K., Granger, C., Held, P., McMurray, J., Michelson, E., Olofsson, B. and Östergren, J., 2003. Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial. The Lancet, 362(9386), pp.777-781.
- McMurray, J., Packer, M., Desai, A., Gong, J., Lefkowitz, M., Rizkala, A., Rouleau, J., Shi, V., Solomon, S., Swedberg, K. and Zile, M., 2014. Angiotensin–Neprilysin Inhibition versus Enalapril in Heart Failure. New England Journal of Medicine, 371(11), pp.993-1004.
- Zannad, F., McMurray, J., Krum, H., van Veldhuisen, D., Swedberg, K., Shi, H., Vincent, J., Pocock, S. and Pitt, B., 2011. Eplerenone in Patients with Systolic Heart Failure and Mild Symptoms. New England Journal of Medicine, 364(1), pp.11-21.
- Pitt, B., Zannad, F., Remme, W., Cody, R., Castaigne, A., Perez, A., Palensky, J. and Wittes, J., 1999. The Effect of Spironolactone on Morbidity and Mortality in Patients with Severe Heart Failure. New England Journal of Medicine, 341(10), pp.709-717.
- Straw, S., McGinlay, M. and Witte, K., 2021. Four pillars of heart failure: contemporary pharmacological therapy for heart failure with reduced ejection fraction. Open Heart, 8(1), pp.1-4.
- Fudim, M., Grodin, J. and Mentz, R., 2018. Hyperkalemia in Heart Failure: Probably Not O“K”. Journal of the American Heart Association, 7(11).
- Kristensen, S., Docherty, K., Jhund, P., Bengtsson, O., Demets, D., Inzucchi, S., Kober, L., Kosiborod, M., Langkilde, A., Martinez, F., Ponikowski, P., Sabatine, M., Sjostrand, M., Solomon, S. and McMurray, J., 2020. Dapagliflozin reduces the risk of hyperkalaemia in patients with heart failure and reduced ejection fraction: a secondary analysis DAPA-HF. European Heart Journal, 41(Supplement_2), p.939.
- Ferreira J, et al. Empagliflozin and serum potassium in heart failure: an analysis from emperor-pooled. J Am Coll Cardiol. 2022 Mar, 79 (9_Supplement) 312.
The opinions expressed in this article are those of the author. They do not purport to reflect the opinions or views of the UKCPA or its members. We encourage readers to follow links and references to primary research papers and guidance.
Competing interest statement:
The author declares: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.
