Serum potassium levels, cardiac arrhythmias, and mortality following non-ST-elevation myocardial infarction or unstable angina: insights from MERLIN-TIMI 36

Abstract

Background In acute coronary syndrome (ACS), potassium levels <3.5 mEq/L are associated with ventricular arrhythmias. Current guidelines therefore recommend a potassium target >4.0 mEq/L in ACS. Our study evaluated the association between potassium levels, cardiac arrhythmias, and cardiovascular death in patients with non-ST-segment elevation myocardial infarction or unstable angina. Methods Potassium levels were measured in 6515 patients prior to randomization to receive either ranolazine or a placebo in the MERLIN-TIMI 36 trial. A seven-day continuous electrocardiographic assessment was obtained to determine the incidence of non-sustained ventricular tachycardia (NSVT) and ventricular pauses. The association between potassium levels and cardiovascular death was evaluated using a Cox proportional hazards regression model with multivariable adjustment. Results NSVT lasting for at least eight consecutive beats occurred more frequently at potassium levels <3.5 mEq/L than at potassium levels ⩾5 mEq/L (10.1 vs. 4.5%, p=0.03 for trend), whereas the inverse pattern was observed for ventricular pauses >3 s, which occurred more frequently at potassium levels ⩾5 mEq/L than at potassium levels <3.5 mEq/L (5.9 vs. 2.0%, p=0.03 for trend). There was a U-shaped relationship between the potassium level at admission and both early and late risk of cardiovascular death. Compared with patients with potassium levels of 3.5 to <4 mEq/L, a potassium level <3.5 mEq/L was associated with an increased risk of cardiovascular death at day 14 (2.4 vs. 0.8%, HRadj 3.1, p=0.02) and at one year (6.4 vs. 3.0%, HRadj 2.2, p=0.01). The risk of cardiovascular death at one year was also significantly increased at potassium levels ⩾4.5 mEq/L and a similar trend was noted at potassium levels ⩾5 mEq/L. Conclusions The lowest risk of cardiovascular death was observed in patients with admission potassium levels between 3.5 and 4.5 mEq/L. Both lower and higher levels of potassium were associated with tachyarrhythmias and bradyarrhythmias, suggesting a potential mechanistic explanation for the increased risk of cardiovascular death at the extremes of potassium homeostasis.

Race, Serum Potassium, and Associations With ESRD and Mortality

“…Potassium levels outside of the range of normal have been associated with increased risk of all-cause and cardiovascular mortality as well as cardiac arrhythmias and end-stage renal disease (ESRD). 1-6 …”

Evaluation of prognostic role of serum potassium in patients with Acute Myocardial Infarction: A cross-sectional study from a tertiary hospital in northern India

“…A Ushaped relationship between mean serum potassium concentration and mortality rate has been reported in the past literature. 24 As the mortality cases in our study were too small (5 cases), it is not possible to comment on the correlation of mortality and serum potassium levels. However; we observed that percentage of mortality cases increased from normokalemia group (8.57 %) to hypokalemia group (16.6 %).…”

“…6 A U-shaped relationship between the potassium levels at admission and both early and late risk of Cardiovascular death was also observed by Patel RB et al They observed lower risk of cardiovascular death in patients with admission potassium levels between 3.5 and 4.5 mEq/l. 24 Previous studies also show higher mortality in hypokalemic AMI patient in comparison to normokalemic AMI patients. 19,21 Extracellular (serum) potassium concentration is normally maintained within the approximate reference range which is important for normal cardiac function.…”

Serum potassium and acute coronary syndrome: In medio stat virtus

“…It is well known that the high sympathetic activity during ACS stimulates the Na þ /K þ ATPase to pump potassium inside the cell. The intracellular influx increases the resting potential, facilitating the automatic activity of the non-ischaemic myocardium and the triggering of one 4 or even many ventricular events. 5 On the other hand, the mechanism underlying the increased mortality risk in hyperkalemic patients is still a matter of debate, and no hypotheses can be extrapolated from the present meta-analysis.…”

“…In fact, while hyperkalemia leads to reduced cardiac excitability and, therefore, to atrioventricular block, sinus arrest and pulseless electrical activity, these are usually reported for potassium levels that are higher than 5.0 mEq/l, or even more. 4 Mildly increased potassium levels may also indicate renal failure, which constitutes a major risk factor for short-term and long-term survival in ACS. Until more data are available, it is feasible to hypothesise that a mildly increased potassium concentration (4.5-5.0 mEq/l) could be a marker of disease rather than a mortality cause by itself, while higher potassium levels directly expose the ACS patient to an increased risk of asystole and pulseless electrical activity.…”