Hyperkalemia and its outcome implications in patients with heart failure with reduced ejection fraction: results from a single-center cohort

Background Hyperkalemia (HK) is a common complication in patients with HFrEF receiving guideline-directed medical therapy (GDMT), yet real-world data on its determinants, management, and prognostic impact are limited. Purpose To describe the incidence and severity of HK, identify factors associated with its occurrence, characterize physician management strategies, and evaluate the association with major adverse outcomes. Methods HK was defined as a serum potassium level ≥5.0 mEq/L, while at least moderate HK was defined as ≥5.5 mEq/L. Multivariable logistic regression was used to identify factors associated with HK occurrence. Time-dependent Cox regression models were applied to evaluate the association between HK and the primary composite outcome of all-cause death and heart failure hospitalization. All-cause death was assessed as a secondary exploratory outcome. Multivariable models were adjusted for age, sex, estimated glomerular filtration rate, diabetes, and ischemic etiology. Results Among 430 patients (median age 69 [60–76] years; 21.9% female; LVEF 34% [30–35]), 60% of patients were on full GDMT. During a median follow-up of 567 [250–1226] days, 101 HK events (23.5%) were observed, with a median potassium level of 5.3 [5.10–5.40] mEq/L. Nineteen (18.8%) HK events were at least moderate, and no HK ≥6.0 mEq/L. Median time from baseline to first HK event was 623 [204–1112] days (Figure 1). Chronic kidney disease and treatment with ARNi were independently associated with higher odds of HK, while obesity was inversely associated (Figure 2). Regarding HK management strategies, a wait-and-watch approach was adopted in 25 cases (29.8%), mineralocorticoid receptor antagonists were reduced in 35 cases (41.2%) and discontinued in 4 cases (4.7%), ACEi/ARB/ARNi were reduced in 3 patients (3.5%) and discontinued in only 1 case (1.2%). Overall, 17 patients (20.0%) were treated with Patiromer. A wait-and-watch strategy was mainly used for mild HK episodes, whereas increasing potassium levels were associated with a greater use of Patiromer, particularly in moderate HK. Overall, 96 primary outcome events (22.3%) and 50 all-cause deaths (11.6%) occurred. HK was not associated with an increased risk of the primary composite outcome (aHR, 95% CI: 0.87, 0.41–1.85) or all-cause death (0.40, 0.15–1.10). Conclusions In this contemporary real-world cohort of patients with HFrEF, HK was frequent but predominantly mild. Importantly, the target of minimizing GDMT was achieved, also implementing treatment with Patiromer in 20% of patients. With this approach the occurrence of HK in our cohort (corresponding in most cases to mild-moderate HK) was not associated with a higher risk of adverse clinical outcomes. Appropriate management of HK appears to be a priority for long-term maintenance of GDMT in HFrEF and specific patient characteristics associated with higher risk of HK allow a more targeted patient monitoring.Figure 1.Time occurrence of HK.Figure 2.Forest plot.