Enhancing Hemodynamic Parameters in Acute Decompensated Right Heart Failure in Patients With CTD-PAH

Simdax (levosimendan) should be considered as a treatment option for patients with acute decompensated right heart failure (RHF) who have connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH), according to a new report published in Frontiers in Medicine.

The study suggests that levosimendan may be associated with a higher in-hospital survival rate in this high-risk patient category.

The study authors explained that patients with PAH are at risk of developing acute RHF. In some cases, they will develop acute decompensated RHF.

“Acute decompensated RHF is distinguished by a rapid exacerbation of the pathological signs of RHF followed by congestion and systemic circulatory inefficiency, which could result in multisystem organ failure,” they wrote.

For these patients, the prognosis is very poor, they added.

Patients with PAH associated with connective tissue disorders typically prove more complicated to treat than patients with idiopathic PAH, the investigators said. As a result, alternative treatment strategies are warranted.

“Levosimendan, a myocardial calcium sensitizer and vasodilator, which is usually utilized in left heart failure, might be effective in acute pulmonary embolism–induced right ventricular failure treatment, owing to its pharmacological profile with combined pulmonary vasodilation and increased right ventricular contractility,” the authors wrote wrote.

Yet, the authors said data based on left heart failure are not necessarily transferable to RHF, and to date, there is insufficient evidence to evaluate its efficacy in RHF.

They retrospectively analyzed 87 patients who had acute decompensated RHF complicated by CTD-PAH who sought care between November 2015 and April 2021.

Forty-six patients were in the levosimendan cohort, and they received the drug at a dose of 0.05 mcg/kg/min, which was raised to 0.1 mcg/kg/min for 24 hours. If patients’ symptoms were still apparent after 1 week, they could be given another round of levosimendan. The 41 patients in the control cohort received a continuous infusion of 0.5 mcg/kg/min continuous infusion Primacor (milrinone), along with epoprostenol therapy to reduce right ventricle overload.

At follow-up, patients in the levosimendan group had significantly elevated levels of oxygen saturation of mixed venous blood, estimated glomerular filtration rate, 24-hour urine output, and tricuspid annular plane systolic excursion compared with the control group. They also had reduced levels of C-reactive protein, white blood cells, troponin I, creatinine, N-terminal B-type natriuretic peptide, and right ventricular diameter compared with the control group. Patients taking levosimendan also had longer in-hospital survival, although it did not appear to have a significant impact on longer-term outcomes, the authors said.

Taken together, the data suggest levosimendan treatment is practical and helps enhance hemodynamic parameters during hospitalization.

“The increase in the right ventricular stroke index, as well as the leftward shift of the association between the right ventricular preload and cardiac output, illustrated that the surge in the contractility of the right ventricle instead of the reduction of the afterload is the key underlying mechanism,” they wrote.

However, they concluded, larger studies are warranted to validate their hypothesis and the treatment’s impact.

Reference

Qu C, Feng W, Zhao Q, et al. Effect of levosimendan on acute decompensated right heart failure in patients with connective tissue disease-associated pulmonary arterial hypertension. Front Med (Lausanne). Published online March 4, 2022. doi:10.3389/fmed.2022.778620