Heart rate control with landiolol hydrochloride in infants with ventricular dysfunction and pulmonary hypertension

Abstract

Aims Sinus tachycardia potentially leads to a deterioration of cardiac function in critically ill infants. The ultrashort‐acting beta‐blocker landiolol hydrochloride is a new pharmacological option for a selective heart rate (HR) control in patients with sinus tachycardia and heart failure. Methods and results This study was a monocentric retrospective medical chart review study at the University Children's Hospital Bonn (Germany) from 01 January 2018 until 30 June 2020. This study included a cohort of 62 term and preterm infants with a diagnosis of ventricular dysfunction and/or pulmonary hypertension (PH), in combination with preexisting tachycardia and treatment with landiolol hydrochloride. Infants were allocated to subgroups according to weeks of gestational age (GA): born at <35 weeks of GA (Group A) and born at >35 weeks of GA (Group B). Tachycardia was defined depending on GA (<35 weeks of GA: >170 b.p.m.; 35 weeks of GA: >150 b.p.m.). The primary endpoint was defined as percentage of patients achieving HR normalization during the first 24 h of landiolol treatment. Twenty‐nine infants were allocated to Group A and 33 infants to Group B. The overall median GA of the infants was 35.3 (23.3/41.3), with 53% female infants. The primary endpoint was achieved in 57 patients (91.9%). The median time to reach target HR was 1.8 (0.3–24) h. The median starting dose of landiolol was 8.8 (3.9–25.3) μk/kg/min, with a median dosing during the first 24 h of landiolol treatment of 9.9 (2.8–35.4) μk/kg/min. The median landiolol dose while achieving the target HR was 10 (2.4–44.4) μk/kg/min. The right ventricular dysfunction improved significantly in both groups 24 h after onset of landiolol infusion ( P = 0.001 in Group A and P = 0.045 in Group B). The left ventricular and biventricular dysfunction improved significantly 24 h after onset of landiolol infusion in infants of Group B ( P = 0.004 and P = 0.006, respectively). The severity of PH improved significantly after 24 h in infants of Group A ( P < 0.001). During landiolol treatment, no severe drug‐related adverse event was noted. Conclusions The use of landiolol hydrochloride for HR control of non‐arrhythmic tachycardia in critically ill infants is well tolerated. Reduction of HR can be guided quickly and landiolol treatment is associated with an improvement of ventricular dysfunction and PH.

Vasoactive Management of Pulmonary Hypertension and Ventricular Dysfunction in Neonates Following Complicated Monochorionic Twin Pregnancies: A Single-Center Experience

“…Furthermore, a treatment option in neonates with PH and sinus tachycardia as well as MH is selective HR control using beta-blocking agents such as propranolol or landiolol. In a large cohort study, landiolol was shown to effectively and quickly induce HR control in preterm and term neonates with PH and CD [24]. Selective HR control may have manifold beneficial effects in neonates with PH and/or CD: it decreases the myocardial oxygen demand, optimizes ventricular filling in the diastolic phase, optimizes RV-LV coupling, and can improve RV relaxation impairment in terms of PH [35][36][37][38].…”

“…As mentioned above, selective HR control with modern beta-blocking drugs such as landiolol or ivabradine is a treatment option in neonates with diastolic and systolic ventricular dysfunction. A possible target range for HR control which should be aimed for in neonates with sustained sinus tachycardia and CD is 150-170 bpm in preterm neonates born at <35 weeks of GA and 130-150 bpm in late-preterm and term neonates [24].…”

“…Potential candidates for drug treatments for PH management include inhaled nitric oxide (iNO), phosphodiesterase-3 (PDE-3) inhibitors (milrinone), phosphodiesterase-5 (PDE-5) inhibitors (intravenous or oral sildenafil), and endothelin-receptor 1 (ET-1) antagonists (bosentan), as well as new candidates such as the calcium sensitizer levosimendan, along with the possibility of selective heart rate (HR) control using intravenous agents (ivabradine, landiolol). The pharmacological and clinical effects of these drugs have been evaluated in preterm and term infants and described in previous studies [21][22][23][24][25][26][27]. Nevertheless, data regarding PH treatment in complicated MC twin pregnancies are not available.…”

An Overview of the Pharmacokinetics and Pharmacodynamics of Landiolol (an Ultra-Short Acting β1 Selective Antagonist) in Atrial Fibrillation

“…Landiolol may also be used to control HR in pediatric patients with non-arrhythmic sinus tachycardia, heart failure, and pulmonary hypertension. According to Schroeder et al, landiolol administration is well tolerated and safe in pediatric patients, being able to achieve a quick HR control; it is associated with an improvement in ventricular dysfunction and pulmonary hypertension severity in critically ill infants [ 22 ].…”

A developmentally based proposal for neonates with hypoplastic left heart: What a great progress! But please don't stop here! A broad result is emerging

“…Inodilators (milrinone, levosimendan) are the drugs of choice when a failing neonatal myocardium is in real need of support. If catecholamines, especially norepinephrine, are nevertheless administered to maintain sufficient coronary perfusion pressure, this should preferably be done with simultaneous β1-receptor blockade with a highly specific β1-blocker such as landiolol for infusion 9 or oral bisoprolol. 10 Beta1-selective beta-blockers improve hemodynamics by optimizing heart rate, diastolic filling and coronary perfusion time, systemic blood pressure amplitude with additional optimization of the pulmonary/systemic flow ratio and this with almost no side effects, especially without bronchoconstriction due to β2-adrenergic receptor blocking.…”