MyoK+ardial Infarction

Most total body potassium (K) is located in the intracellular space, while extracellular potassium is tightly regulated by intraand extracellular shifts and renal excretion. Changes in intraand extracellular K levels modify the electrophysiological properties of the resting membrane potential in cardiac cells and subsequently influence the generation and conduction of impulses throughout the heart. During the 1950s, hypokalemia was reported to be lower than the fibrillation threshold in isolated rabbit hearts. Subsequently, relatively small observational studies reported an association between hypokalemia and the risk of ventricular arrhythmias in patients with acute myocardial infarction (AMI). Thereafter, practice guidelines, including the American College of Cardiology/American Heart Association guidelines for management of ST-segment elevation MI (STEMI), recommended (Class I) maintaining K levels > 4.0 mEq/L although with the lowest level of evidence (C). Moreover, even higher target levels >4.5 mEq/L were suggested, yet no upper level was set. Concordantly, many hospitals implemented these guidelines by initiating treatment when serum K levels decrease below certain ‘‘goal’’ values. To our knowledge, these recommendations have not been revised, since in formal guidelines and in the most recent guidelines, this issue is not mentioned directly and only the undetermined role or possible deleterious effects of glucose– insulin–potassium (GIK) infusions are discussed. Ma et al, in this issue of Angiology, retrospectively evaluated short-term outcomes of 6613 patients presenting with STEMI, without renal insufficiency, according to K levels at presentation. Following adjustments to potential confounders, the authors found a J-shaped relationship between patient outcomes and K levels, with lowest predefined event rate with K levels of 4 to 4.5 mEq/L. Compared to the latter reference group, multivariate analysis revealed significantly higher 30-day mortality risk in patients with K level of 4.5 to 5.0 (hazard ratio [HR]: 1.52, 95% confidence interval [CI]: 1.17-1.98; P 1⁄4 .002) and even higher risk in patients with K level of 5.0 mEq/L (HR: 1.80, 95% CI: 1.22-2.66; P 1⁄4 .002). This study has some limitations, particularly the relatively low adherence with contemporary guidelines, that is, insufficient use of primary percutaneous coronary intervention (PCI; only *10% of cases) and optimal medical therapy, which might compromise applicability. Nevertheless, the findings are consistent with several recent reports showing that serum K levels, outside a relatively narrow range, are associated with worse outcomes in patients presenting with AMI. The methodology and main findings of the latter studies are summarized in Table 1. These studies, altogether included over 50 000 patients, consistently demonstrated that K levels are significantly associated with short(eg, in hospital) and long-term (up to 10 years) outcomes (eg, mortality and malignant arrhythmias) in patients presenting with AMI. A study that evaluated unstable angina patients and another study evaluating the outcome of target lesion revascularization observed consistent findings. K levels between 3.5 and 4 mEq/L (more frequently) or 4 and 4.5 mEq/L were found to be associated with lowest levels of mortality or other negative outcomes in most studies, while lower levels and even more prominently higher levels (including within normal K range) were significantly associated with worse outcomes. Furthermore, the latter association was similar regardless of K supplementation during hospitalization and seemed to be stepwise in most studies (eg, ‘‘dose response’’) further strengthening its robustness. Hence, best outcomes were reported in patients with K range for which the above-mentioned guidelines might suggest treatment to increase K levels. The exact pathophysiological mechanisms by which decreased or increased K levels are associated with deleterious prognosis in patients with AMI are uncertain. The AMI was reported to be associated with several systemic metabolic changes. These changes include increased plasma concentrations of catecholamines, free fatty acids, glucose, glycerol, cortisol, and cyclic AMP. Sekiyama et al showed a transient decrease in serum K level during the acute phase of acute coronary syndrome (ACS), followed by an increase at the stable phase (discharge). The degree of the K dip was correlated