The Effect of Levosimendan on Pulmonary Artery Pressure and Right Ventricular Function in the Perioperative Period in Patients With CTEPH After Pulmonary Thromboendarterectomy (LEVO-CTEPH)

A levosimendan infusion after induction of anesthesia.

Infusion of levosimendan will be initiated after the induction of anesthesia, discontinued at the onset of patient cooling, and resumed at the time of rewarming at 34°C. The drug will be administered using an infusion pump as a continuous infusion at a rate of 0.1 mcg/kg/min. The duration of the drug infusion will be up to 48 hours.

Preoperative management will be conducted according to the patients' primary and concomitant diseases.

A placebo infusion after induction of anesthesia.

Patients in the placebo group will receive an equivalent amount of a colored solution of Soluvit.Soluvit (ATC B05XC; a yellow vitamin mixture indistinguishable from the investigational drug, levosimendan).

Preoperative management will be conducted according to the patients' primary and concomitant diseases.

Mean pulmonary artery pressure (mPAP) measured 24 hours after the end of surgery

Pulmonary vascular resistance

Pulmonary artery pulsatility index. PAPi = (PASP - PADP) / RAP (PASP - PADP): Pulmonary Artery Pulse Pressure. This is the difference between the pressure in the pulmonary artery when the heart contracts (systolic) and relaxes (diastolic).

RAP: Right Atrial Pressure.

Pulmonary artery pressure

Arterial blood pressure

Central venous pressure

Cardiac index

Systemic vascular resistance

Right ventricular stroke work index

Pulmonary capillary wedge pressure

Ejection fraction (EF) of both the right and left ventricles (LVEF and RVEF)

Right ventricular end diastolic volume

Right ventricular systolic pressure

Fractional area change (FAC) of the right ventricle

Tricuspid annular plane systolic excursion

Right ventricular free-wall longitudinal strain

Quantitative concentration of troponin I

In the perioperative period, the Vasoactive-Inotropic Score (VIS) will be calculated using the following formula:

VIS = dobutamine (mcg/kg/min) + dopamine (mcg/kg/min) + (100 × epinephrine (mcg/kg/min) + (100 × norepinephrine (mcg/kg/min)) + (10 × milrinone (mcg/kg/min))

Number of participants with residual pulmonary hypertension, defined as postoperative mean pulmonary artery pressure (mPAP) > 25 mm Hg, measured by right heart catheterization in the postoperative period (up to 72 hours after surgery).

Number of participants who develop pulmonary edema within 24 hours following pulmonary endarterectomy (PEA), confirmed by chest X-ray or chest CT and clinical criteria (including dyspnea, hypoxemia, and bilateral infiltrates), characterized by the presence of frothy secretions in the endotracheal tube (ETT), asymmetric opacities on chest X-ray, and an oxygenation index (PaO₂/FiO₂) < 300 mm Hg in the early postoperative period (up to 72 hours)

Proportion of participants who develop any new-onset cardiac arrhythmia (including atrial fibrillation/flutter, ventricular tachycardia) during the study period, as documented by 12-lead ECG or continuous cardiac monitoring.

Number of participants with cardiovascular events, defined as myocardial infarction (MI) or stroke (cerebrovascular accident, CVA), occurring during the postoperative period.Myocardial infarction is defined according to the Fourth Universal Definition of Myocardial Infarction (elevated cardiac troponin with at least one of the following: ischemic symptoms, new ischemic ECG changes, or imaging evidence of new loss of viable myocardium). Stroke is defined as an acute episode of focal or global neurological dysfunction caused by infarction or hemorrhage in the brain, spinal cord, or retina, confirmed by neuroimaging (CT or MRI).

Number of participants with postoperative pneumothorax, defined as the presence of air in the pleural cavity, confirmed by chest X-ray or chest CT, occurring during the postoperative period.

Number of participants with postoperative seizures, defined as a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain. Diagnosis is based on clinical assessment and, when available, confirmed by electroencephalography (EEG).

Number of participants with postoperative acute kidney injury (AKI), defined and staged according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria, occurring during the early postoperative period (up to 48 hours after surgery). AKI is defined as any of the following: increase in serum creatinine by ≥ 0.3 mg/dL (≥ 26.5 μmol/L) within 48 hours; or increase in serum creatinine to ≥ 1.5 times baseline, which is known or presumed to have occurred within the prior 7 days; or urine output < 0.5 mL/kg/hour for 6 hours. AKI is staged as follows: Stage 1 (serum creatinine 1.5-1.9 times baseline or ≥ 0.3 mg/dL increase, or urine output < 0.5 mL/kg/hour for 6-12 hours), Stage 2 (serum creatinine 2.0-2.9 times baseline, or urine output < 0.5 mL/kg/hour for ≥ 12 hours), and Stage 3 (serum creatinine ≥ 3.0 times baseline, or increase to ≥ 4.0 mg/dL, or initiation of renal replacement therapy, or urine output < 0.3 mL/kg/hour for ≥ 24 hours, or anuria for ≥ 12 hours).

Number of participants who require renal replacement therapy (RRT) in the early postoperative period

Number of participants requiring administration of inhaled nitric oxide (NO) and/or inhaled iloprost in the postoperative period. for the management of residual pulmonary hypertension or right ventricular dysfunction. This includes administration as monotherapy or in combination

Number of participants requiring perioperative blood transfusion, including packed red blood cells (PRBCs), fresh frozen plasma (FFP), platelet concentrates, or cryoprecipitate, in the postoperative period. Transfusion requirements will be recorded as the number of participants receiving any transfusion.

Number of participants requiring postoperative inotropic and/or vasopressor support in the early postoperative period

Total duration of invasive mechanical ventilation (MV) measured in hours (or days) from the time of intubation in the operating room or ICU until successful extubation. This includes the total time on the ventilator, both in the operating room and in the ICU, and includes any episodes of reintubation.

Total length of stay in the intensive care unit (ICU) measured in days from the time of admission to the ICU after surgery until discharge from the ICU to the general ward.

Total length of hospital stay measured in days

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