Hyperkalemia, Heart Failure and Mortality

I recently gave a talk to dietitians in BC about Hyperkalemia in Heart Failure, which I was so happy to be invited to give. It got me reading all I could about hyperkalemia in this patient population – and I learned a lot!

Here is a summary of one of the articles I read to prepare for the talk.

Sfairopoulos, Dimitrios, Angelos Arseniou, and Panagiotis Korantzopoulos. “Serum potassium and heart failure: association, causation, and clinical implications.” Heart Failure Reviews 26.3 (2021): 479-486.

What are the sub-types of Heart Failure?

There are three subtypes of HF:

• Hf with preserved ejection fraction (EF>50%)
• HF with reduced ejection fraction (EF <40%)
• HF with moderately reduced ejection fraction (EF 40-49%)

What is the primary treatment for heart failure?

RAAS inhibition (RAASi) is associated with reduced mortality in HF with reduced ejection fracture.  The evidence is less clear for preserved or moderately reduced ejection fraction, however these medications are still often prescribed for symptom management or to improve quality of life.

Stopping or blocking the Renin-Angiotensin Aldosterone system is good because it stops sodium and water retention and harmful ventricular remodeling.

What medications are considered RAASi?

There are three broad categories:

1. ACEi – Angiotensin Converting Enzyme inhibtors, often ending in pril (e.g. ramipril, lisinopril)
2. ARBs – Angiotensin Receptor Blockers, often ending in sartan (e.g. candesartan, valsartan)
3. MRA – Mineralocorticoid Receptor Antagonists (e.g. spironolactone, eplerenone)

What evidence links potassium and mortality in HF?

Several studies have reported a U-shaped curve between potassium levels and mortality for adults with HF.  This means that if the potassium is either too low or too high, people with these levels of potassium are more likely to die.

The people who are least likely to die tend to have a potassium in the 4.0s.  Different studies have reported slightly different ranges but most fall between 3.9-4.9mmol/L. Notice that this range is more narrow that the range considered normal within the general population.

Additionally, mortality rates from Hyperkalemia appear to be higher among those who have hyperkalemia and heart failure than those who have hyperkalemia and CKD without heart failure.

Is hyperkalemia the cause of mortality in HF?

First and foremost, it is important to note that we do not know that hyperkalemia CAUSES mortality among HF patients, we just know that those two things appear to happen at the same time. It is possible that hyperkalemia is just a MARKER for mortality and not the root cause.

The authors of this paper attempted to try to answer this question using Bradford Hill criteria to use epidemiologic evidence for presumed cause and observed effect.

Author’s conclusion based on this process:

1. Hypokalemia and low normal potassium (K <4.0mmol/L) appear to be associated with adverse clinical outcomes in a cause and effect manner.
2. Hyperkalemia and adverse outcomes appears to be unlikely linked in a cause and effect manner. One of the most challenge confounders is the stopping or reducing of RAAS which in and of itself may increase mortality rates in this population.

The authors can’t conclude this definitively using this criteria, and so conclude by stating that further research is needed.

If someone has hyperkalemia, is it better to reduce the RAASi dose?

There is no doubt that higher doses of RAASi improve outcomes for patients (reduced HF progression and lower hospitalization rates). The author’s explicitly state that it should be stressed that the occurence of hyperkalemia does not diminish the clinical benefits of RAASi. This conclusion is the same for people with CKD (check out more about that here).

Specifically in heart failure, the authors highlight two studies that showed the mortality benefit was found for people on spironolactone or eplerenone up to potassium values of 5.5mmol/L. However above 5.5mmol/L the statistically significant benefit was lost.

What is the ideal serum potassium target for people with HF?

According to the authors of this paper, potassium values should be maintained between 4.1 and 5.0mmol/L. Correcting hyperkalemia doesn’t necessarily improve clinical outcomes, but it may enable RAASi use and up-titration which has well-established benefits for patients. Transient increases up to 5.5mmol/L should not lead to RAASi discontinuation.

The authors do not have a concluding statement for us on what to do if the potassium remains between 5.0-5.5mmol/L.

How can hyperkalemia be corrected?

The authors highlight that two new potassium binder medications are now available:

• Sodium Zirconium
• Patiromer

Patiromer works by exchanging calcium for potassium, while Sodium Zirconium works by exchanging sodium for potassium. This may suggest the patiromer may be better suited for the HF population given the concern with volume overload.

In my clinical practice in Canada, one of the biggest challenges with seeing widespread adoption of these medications is lack of coverage. These medications are expensive and not covered under provincial government drug plans, which makes them cost prohibitive for many patients.

Take Aways

This paper didn’t have much to offer us with regards to diet therapy for hyperkalemia management in heart failure, in fact diet wasn’t mentioned at all! Though, when I read the title and saw “causation” in the it, I thought maybe diet might come up. But it didn’t – so maybe those bananas aren’t to blame?

That being said, I liked the article for giving a nice summary of hyperkalemia and outcomes in the HF population, so here are my biggest take aways:

1. Hyperkalemia does not appear to be the CAUSE of mortality in HF, but rather a marker of mortality risk
2. Whenever possible, our goal is help patients stay safe on RAASi, which has proven benefit in this patient population, which may include using potassium-binding medication.

What role diet plays in this equation, is a post for another day!