Predictors of Levosimendan reinitiation in patients with advanced heart failure undergoing intermittent inotropic therapy- is the lung that important?

Abstract Background Levosimendan is a calcium sensitizer and vasodilator used in intermittent infusions for patients with advanced heart failure (HF), aiming to improve hemodynamic function and functional capacity. In some cases, treatment discontinuation occurs due to clinical improvement; however, reinitiation following clinical deterioration is not uncommon. Predictors of levosimendan reinitiation remain poorly defined. Purpose Identify clinical and echocardiographic variables associated with levosimendan reinitiation in patients with advanced HF receiving intermittent inotropic therapy. Methods Retrospective, single-center study including 59 patients with advanced HF undergoing regular (every 2 weeks or monthly) levosimendan infusions. Clinical, laboratory, and echocardiographic data were collected prior to regular treatment initiation, including left ventricular ejection fraction (LVEF), presence of pulmonary hypertension (PH), NT-proBNP, furosemide dose, and the number of HF-related hospitalizations in the preceding six months. A binary logistic regression analysis was performed to identify predictors of levosimendan reinitiation. Results Among 59 patients (73% male), all had HFrEF, with ischemic etiology being the most common (55%), followed by idiopathic dilated cardiomyopathy (16 patients, 27%). Baseline left ventricular ejection fraction was 24.6% (IQR 19.5–29.5), and NT-proBNP was 9,805 pg/mL (IQR 3,292–12,310). The presence of baseline pulmonary hypertension was identified as the only independent predictor of levosimendan reinitiation (OR 1.11; 95% CI 1.01–1.22; p=0.036). A nonsignificant trend toward a lower probability of reinitiation was observed with higher baseline furosemide dose (OR 0.96; p=0.077). Other variables such as LVEF, NT-proBNP, ischemic etiology, sex, and number of prior hospitalizations, were not significantly associated with therapeutic reinitiation(p0.05). Conclusions In this retrospective, single-center cohort of patients with advanced HF receiving regular intermittent levosimendan therapy, baseline pulmonary hypertension was the only independent predictor associated with treatment reinitiation. This finding may reflect greater inotropic dependence in patients with pulmonary congestion and elevated pressures. Larger, prospective, multicenter studies are warranted to confirm these findings and refine risk stratification in this population.