This study focuses on pre-hospital emergency scenarios and constructs and validates a hypokalemia risk prediction model practical, concise variables, and good predictive performance. Using LASSO and multivariate logistic regression, we identified five key predictors of prehospital hypokalemia: symptom-to-door time, syncope/coma, atrial arrhythmias, PR interval prolongation, and U-wave presence. The significance of these predictive factors lies in their ability to provide early signals of hypokalemia. This is easily overlooked in acute STEMI attacks. For example, the Symptom-to-door time and the presence of syncope or coma reflect the urgency and potential severity of the patient's condition. Atrial arrhythmia, prolonged PR interval, and U-wave are signs of electrophysiological disorders in patients. Based on these factors, we constructed a nomogram. Our prediction model achieved an AUC of 0.735 (95% CI: 0.680–0.791) on ROC analysis, indicating reasonably strong discriminative ability. Notably, manifestations such as muscle weakness, U-wave appearance, and arrhythmias are common to both hypokalemia and acute myocardial infarction, complicating early differentiation[8]. The prediction model, built upon five convenient and easily accessible variables, demonstrated robust performance. This was substantiated by a calibration curve showing strong agreement between predictions and observations. Specifically designed for early hypokalemia detection in STEMI, the model's clinical value was quantified by decision curve analysis, which indicated significant net benefits over a wide spectrum of threshold probabilities. This suggests its potential to guide clinicians in making superior decisions regarding potassium supplementation, with the ultimate goal of lowering arrhythmia-related mortality and enhancing patient outcomes.
Previous retrospective studies consistently demonstrate that STEMI patients frequently develop hypokalemia within 12 hours of onset, with associated increases in malignant arrhythmias and in-hospital mortality [9,10]. This study also found that early onset hypokalemia can occur in STEMI patients. This phenomenon likely reflects acute stress responses characterized by sympathetic nervous system activation, massive catecholamine release, and β2-receptor-mediated potassium shifts into cells. Consequently, prehospital providers must maintain high suspicion for electrolyte disturbances when evaluating patients with suspected acute coronary syndromes, especially for high-risk patients with symptom onset<2 hours, blood potassium assessment and intervention should be prioritized.
Syncope is one of the important atypical manifestations of STEMI patients, and some STEMI patients present with syncope as the initial symptom rather than atypical chest pain, which can be easily misdiagnosed or delayed in treatment [11]. In our cohort, syncope/coma emerged as a robust predictor of hypokalemia (OR=3.57). STEMI itself can cause abnormal blood potassium levels through the release of potassium from necrotic myocardium, stress response, and impaired renal function, which can directly lead to fatal arrhythmias, resulting in syncope/coma. In addition, low potassium itself can also cause a decrease in neuromuscular excitability, which can manifest as muscle weakness, respiratory depression, and even consciousness disorders. Pre-hospital identification of such symptoms should be highly alert to the occurrence of electrolyte imbalances.
Atrial arrhythmias (premature atrial contractions and transient atrial tachycardia) represent both important clinical manifestations of hypokalemia and independent predictors in our analysis (OR=4.18). Hypokalemia can significantly prolong the duration of atrial action potential by inhibiting fast delayed rectifier potassium current (IKr) and fast delayed rectifier potassium current (IKur) on the atrial muscle cell membrane, and ultimately triggering atrial arrhythmia [12]. The pig acute myocardial infarction model constructed by Bikou et al. showed that within 2 hours after myocardial infarction, after using some mechanical devices to replace left ventricular function, and the incidence of atrial arrhythmias also decreased, confirming that "mechanical electrical feedback" is a reversible arrhythmogenic factor [13]. At the clinical level, although the incidence of atrial arrhythmia in STEMI patients is lower than that of ventricular arrhythmia, its value as an early signal of hypokalemia cannot be ignored. A study based on the risk of atherosclerosis in the community found that the incidence of atrial arrhythmias events in the population with coronary heart disease and hypokalemia was as high as 19.84%[14]. We hypothesize a self-perpetuating cycle in STEMI: ischemic-driven catecholamine release lowers serum potassium, which facilitates atrial arrhythmias through altered depolarization/repolarization. These arrhythmias, compounded by ischemia-induced atrial stretch, further impair hemodynamics and coronary perfusion, worsening ischemia and perpetuating hypokalemia. This electromechanical vicious cycle underscores that new atrial arrhythmias warrant prompt potassium evaluation and correction.
The prolongation of PR interval reflects the delay of atrioventricular node conduction. Hypokalemia delays atrioventricular conduction through multiple mechanisms, including sodium-potassium pump inhibition and reduced resting membrane potential. A case report of severe hypokalemia (1.31 mmol/L) confirmed that the prolongation of PR interval after potassium supplementation is reversible [15]. Therefore, detecting prolonged PR interval in STEMI patients can serve as a warning signal for hypokalemia, and the recovery of PR interval after potassium supplementation can also serve as an effective indicator of potassium supplementation. It has strong operability and repeatability in pre-hospital emergency care. Zareei et al. found in 248 patients with acute coronary syndrome that PR interval prolongation can serve as a potential marker of cardiac structure/ischemic load[16]. However, further research is needed to determine whether the PR interval can directly reflect ischemia in the atrioventricular node of STEMI patients.
U-waves represent a hallmark electrocardiographic marker of hypokalemia. When hypokalemia occurs, the outward potassium current (such as IKr, Ito) of myocardial cells weakens, resulting in asynchronous repolarization between ventricular myocardium and conduction system, thus forming U-waves [17]. Ramadurai et al. found that the incidence of U-waves significantly increased with the severity of hypokalemia [18]. It is worth noting that the clinical significance of U-waves seems to be not limited to electrolyte imbalance. Inverted U-waves may represent an early, non-invasive marker of acute myocardial ischemia, even in the absence of canonical ST-T changes, as evidenced by a case study from Girish et al. [19]. In our study, U-waves were confirmed to be an independent predictor of prehospital hypokalemia in STEMI patients (OR=5.2, 95% CI: 2.59-10.46, p<0.001). The appearance of U-waves may not only reflect repolarization abnormalities caused by low potassium, but may also be combined with myocardial electrophysiological disorders caused by ischemia. However, U-waves can also occur in some healthy individuals such as athletes and those with bradycardia, so the quantitative relationship between U-wave morphology (positive/negative, amplitude, duration) and blood potassium levels, as well as the degree of coronary artery disease, still needs further exploration in the future.
A recently published large-scale retrospective cohort study based on the MIMIC-IV database found a significant positive correlation between serum potassium fluctuations and in-hospital mortality [20]. The study by Fax é n et al. demonstrated a positive correlation between hypokalemia upon admission and adverse events during hospitalization [21]. Petnak et al. found that low blood potassium at discharge is significantly associated with one-year mortality [22]. These pieces of evidence all indicate that hypokalemia is an independent risk factor for death in STEMI patients, and its electrophysiological mechanism may be that after myocardial infarction occurs, the expression and function of potassium channels in myocardial cells undergo remodeling downregulation, leading to prolonged action potential duration and increased repolarization dispersion. This electrical remodeling itself puts the myocardium in a vulnerable state, and the presence of hypokalemia can further inhibit potassium channel function, weaken the ischemic preconditioning protective effect mediated by potassium ion channels, aggravate calcium influx and intracellular calcium overload, thereby inducing or exacerbating arrhythmia and increasing mortality [23].
Although the significance of in-hospital potassium management has been well documented, far less attention has been paid to the early, prehospital detection of hypokalemia. Our study bridges this gap by integrating five straightforward clinical and electrocardiographic parameters into a nomogram. This approach facilitates rapid risk assessment at the bedside, significantly enhancing its utility in emergent prehospital settings.
Study limitations
Although this study has made positive explorations in model construction and validation, there are still limitations. First, as a single-center retrospective study, selection and information biases cannot be entirely eliminated. Future multicenter prospective cohort studies are warranted to validate the model's generalizability and stability. Second, our analysis focused on admission potassium levels, limiting insights into temporal potassium dynamics. Future investigations incorporating continuous potassium monitoring through time-to-event models (e.g., Cox regression, Landmark analysis) would better characterize temporal patterns of hypokalemia development. Third, this study still lacks some important predictive variables, such as the Global Acute Coronary Event Registry (GRACE) risk score and Killip classification. In the future, randomized controlled trials can be designed to evaluate whether model guided preventive potassium supplementation strategies can reduce the incidence and mortality of arrhythmias, thus achieving a closed-loop from prediction to intervention.