Administration Of Landiolol Research Articles

Assessing the Risks and Benefits of Hypotensive Anesthesia and Piezosurgical Instruments in Bimaxillary Surgery.

The challenge in bimaxillary surgery lies in significant intraoperative bleeding, prompting various strategies to minimize blood loss. Among the methods considered for controlling intraoperative bleeding, hypotensive anesthesia and the use of piezosurgical instruments (Osada, Tokyo, Japan) have been explored. However, hypotensive anesthesia may have adverse effects on cardiac function, and surgical time is likely to be prolonged when using piezosurgical instruments. This study retrospectively examined whether the combined use of hypotensive anesthesia and piezosurgical instruments reduces intraoperative bleeding and whether the combination impacts cardiac function. The combination of hypotensive anesthesia and piezosurgical instruments significantly reduced intraoperative bleeding. Furthermore, the combination was associated with a significantly higher incidence of tachycardia, particularly with the use of nicardipine. Additionally, the combination significantly lengthened the duration of the surgery and may have increased the burden on cardiac function. Landiolol was effectively employed to manage tachycardia. When selecting hypotensive anesthesia as a means to limit bleeding, proactive preparation and preventive small-dose administration of landiolol could be beneficial in managing the potential occurrence of tachycardia.

Intravenous Landiolol for Rate Control in Supraventricular Tachyarrhythmias in Patients with Left Ventricular Dysfunction: A Systematic Review and Meta-Analysis.

Background: This systematic review explores the effects of landiolol administration in individuals presenting with supraventricular tachyarrhythmia (SVT) and concurrent left ventricular dysfunction, without being septic or in a peri-operative period. Methods: We systematically searched PubMed, Cochrane, Web of Science, and Scopus databases, retrieving a total of 15 eligible studies according to prespecified eligibility criteria. Results: Patients treated with landiolol experienced a substantial reduction in heart rate (HR) (mean HR reduction: 42 bpm, 95% confidence intervals (CIs): 37-47, I2 = 82%) and were more likely to achieve the target HR compared to those receiving alternative antiarrhythmic therapy (pooled odds ratio (OR): 5.37, 95% CIs: 2.87-10.05, I2 = 0%). Adverse events, primarily hypotension, occurred in 14.7% of patients receiving landiolol, but no significant difference was observed between the landiolol and alternative antiarrhythmic receiving groups (pooled OR: 1.02, 95% CI: 0.57-1.83, I2 = 0%). No significant difference was observed between the two groups concerning sinus rhythm restoration (pooled OR: 0.97, 95% CI: 0.25-3.78, I2 = 0%) and drug discontinuation due to adverse events (pooled OR: 5.09, 95% CI: 0.6-43.38, I2 = 0%). Conclusion: While further research is warranted, this systematic review highlights the potential benefits of landiolol administration in the management of SVTs in the context of left ventricular dysfunction.

Landiolol, an intravenous β1-selective blocker, is useful for dissociating a fusion of atrial activation via accessory pathway and atrioventricular node.

During ventricular pacing, a fusion of atrial activation may occur owing to the simultaneous retrograde conduction of the atrioventricular (AV) node and accessory pathway (AP), potentially leading to an inaccurate mapping of the atrial AP insertion site. We tested the hypothesis that landiolol, an ultra-short-acting intravenous β1-blocker, could dissociate a fusion of atrial activation. We conducted a prospective before-and-after study to investigate the effect of landiolol on retrograde conduction via the AV node and AP. We enrolled 21 consecutive patients with orthodromic AV reciprocating tachycardia who underwent electrophysiological studies at our hospital between January 1, 2018, and August 31, 2020. Six patients exhibited a fusion of atrial activation. After landiolol administration (10 μg/kg/min), the effective refractory period was unchanged in AP (280 [240-290] ms vs. 280 [245-295] ms, p = .91), whereas that of the AV node was prolonged (275 [215-380] ms vs. 332 [278-445] ms, p = .03). The Wenckebach pacing rate via retrograde AV node decreased after landiolol administration (180 [140-200] beats per minute [bpm] vs. 140 [120-180] bpm, p = .02). Thus, landiolol decreased the minimum ventricular pacing rate required to dissociate a fusion of atrial activation (180 [160-200] bpm vs. 140 [128-155] bpm, p = .007). Radiofrequency catheter ablation under landiolol administration successfully eliminated AP in all patients during ventricular pacing without complications or recurrence. Landiolol inhibited the AV node without affecting the AP and helped dissociate a fusion of atrial activation at a lower ventricular pacing rate.

300 LITERATURE CASE SERIES REVIEW ON LANDIOLOL IN ACUTE DECOMPENSATED HEART FAILURE SECONDARY TO TACHYARRHYTHMIAS

Abstract Introduction Landiolol is a recently innovated ultra-short-acting beta-blocker. Landiolol is the only beta-blocker with a specific dose recommendation for patients with cardiac dysfunction and acute atrial fibrillation (Class I recommendation according to the ESC guidelines). Landiolol has a shorter elimination half-life than any other beta-blocker, and it can be administered safely to patients with various tachyarrhythmias. The short duration of action and titratability of landiolol makes it ideal for use in critically ill patients. Purpose of the Study Review the case reports in the literature on the administration of landiolol in critically ill patients with acute decompensated heart failure (ADHF) secondary to tachyarrhythmias. Methods 11 case reports of ADHF secondary to tachyarrhythmias were identified. Personal, clinical and humoral data were collected. The heart rate and systolic pressure values in the time before and after the administration of Landiolol were plotted in a summary graph. Results The mean age of the 11 patients was 55 years old with high proBNP values at admission. The etiological diagnosis of heart failure was heterogeneous but tachyarrhythmia was the trigger event in all patients. Patients were critically ill with a mean EF of 26 ± 16% and an initial shock index of 1.4 ±0.5. Landiolol administered together with other antiarrhythmic drugs (amiodarone in 4/11 patients), epinephrine/norepinephrine (9/11) and levosimendan (4/11) favoured heart rate lowering and an increase in systolic blood pressure.At discharge, 4/11 had improved EF, in 10/11 sinus rhythm was restored, and all patients recovered hemodynamic stability without adverse events related to Landiolol (Figure 1). Conclusion In this case series review, Landiolol was a useful strategy in patients with ADHF refractory to conventional therapy by facilitating rate/rhythm control, limiting the toxicity of inotropic drugs and improving the hemodynamic profile. Figure 1

Short acting intravenous beta-blocker as a first line of treatment for atrial fibrillation after cardiac surgery: a prospective observational study.

Post-operative atrial fibrillation (POAF) defined as a new-onset of atrial fibrillation (AF) following surgery occurs frequently after cardiac surgery. For non-symptomatic patients, rate control strategy seems to be as effective as rhythm control one in surgical patients. Landiolol is a new highly cardio-selective beta-blocker agent with interesting pharmacological properties that may have some interest in this clinical situation. This is a prospective, monocentric, observational study. All consecutive adult patients (age >18 years old) admitted in the intensive care unit following cardiac surgery with a diagnosed episode of AF were eligible. Success of landiolol administration was defined by a definitive rate control from the beginning of infusion to the 72th h. We also evaluated rhythm control following landiolol infusion. Safety analysis was focused on haemodynamic, renal and respiratory side effects. From 1 January 2020 to 30 June 2021, we included 54 consecutive patients. A sustainable rate control was obtained for 49 patients (90.7%). Median time until a sustainable rate control was 4 h (1, 22). Median infusion rate of landiolol needed for a sustainable rate control was 10 µg/kg/min (6, 19). Following landiolol infusion, median time until pharmacological cardioversion was 24 h. During landiolol infusion, maintenance of mean arterial pressure target requires a concomitant very low dose of norepinephrine. We did not find any other side effects. Low dose of landiolol used for POAF treatment was effective and safe for a rapid and sustainable rate and rhythm control after cardiac surgery.

Female hormones prevent sepsis-induced cardiac dysfunction: an experimental randomized study

Although epidemiologic research has demonstrated significant differences in incidence and outcomes of sepsis according to sex, their underlying biological mechanisms are poorly understood. Here, we studied the influence of hormonal status by comparing in vivo cardiac performances measured by MRI in non-ovariectomized and ovariectomized septic female rats. Control and ovariectomized rats were randomly allocated to the following groups: sham, sepsis and sepsis plus landiolol. Sepsis was induced by caecum ligation and punction (CLP). Landiolol, a short-acting selective β1-adrenergic blocker improving the in vivo cardiac performance of septic male rats was perfused continuously after sepsis induction. Cardiac MRI was carried out 18 h after induction of sepsis to assess in vivo cardiac function. Capillary permeability was evaluated by Evans Blue administration and measurement of its tissue extravasation. Variation in myocardial gene and protein expression was also assessed by qPCR and western-blot in the left ventricular tissue. Sepsis reduced indexed stroke volume, cardiac index and indexed end-diastolic volume compared to sham group in ovariectomized females whereas it had no effect in control females. This was associated with an overexpression of JAK2 expression and STAT3 phosphorylation on Ser727 site, and an inhibition of the adrenergic pathways in OVR females. Landiolol increased the indexed stroke volume by reversing the indexed end-diastolic volume reduction after sepsis in ovariectomized females, while it decreased indexed stroke volume and cardiac index in control. This was supported by an overexpression of genes involved in calcium influx in OVR females while an inactivation of the β-adrenergic and a calcium efflux pathway was observed in control females. Sepsis decreased in vivo cardiac performances in ovariectomized females but not in control females, presumably associated with a more pronounced inflammation, inhibition of the adrenergic pathway and calcium efflux defects. Administration of landiolol prevents this cardiac dysfunction in ovariectomized females with a probable activation of calcium influx, while it has deleterious effects in control females in which calcium efflux pathways were down-regulated.

Prevention of trigeminocardiac reflex-induced severe bradycardia during cerebral aneurysm clipping surgery by topical anesthesia of the dura surface and atropine administration: a case report

BackgroundTrigeminocardiac reflex (TCR) by stimulation of the sensory branch of the trigeminal nerve induces transient bradycardia and hypotension. We report a case in which light mechanical stimulation to the dura mater during brain surgery induced severe bradycardia.Case presentationA 77-year-old woman with bradycardia-tachycardia syndrome was scheduled for clipping of an unruptured left middle cerebral artery aneurysm. General anesthesia was performed with propofol, remifentanil, and rocuronium. Before starting surgery, the function of the pyramidal tract was examined by motor evoked potential. Transcranial electric stimulation for motor evoked potential induced atrial fibrillation and tachycardia. Continuous administration of landiolol was started and verapamil was used for tachycardia. During detachment of the dura mater from the bone, an electrocardiogram suddenly showed sinus arrest for 6 s. Immediately after the manipulation was interrupted, a junctional rhythm appeared. However, light touch to the dura mater induced severe bradycardia again, and atropine was therefore administered. In addition, the dura surface was anesthetized with topical lidocaine infiltration. After that, light touch-induced bradycardia was prevented.ConclusionsWe experienced a case of severe bradycardia during surgery due to TCR caused by light mechanical stimulation to the dura mater. Topical anesthesia of the dura surface and atropine administration were effective for preventing TCR-induced bradycardia.

Premature atrial contractions with multiple patterns of aberrant conduction followed by torsade de pointes in a patient with polymyalgia rheumatica

Rationale:Recent studies have shown that QT interval prolongation is associated with disease severity and predicts mortality in systemic inflammatory diseases, particularly rheumatoid arthritis. Systemic pro-inflammatory cytokines released from synovial tissues in rheumatoid arthritis, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α, could have direct effects on cardiac electrophysiology, particularly changes in the expression and function of potassium and calcium channels, resulting in QT interval prolongation on surface electrocardiogram (ECG) and an increased predisposition to develop lethal ventricular arrhythmias. However, reports on torsade de pointes (TdP) due to acquired long QT syndrome in patients with polymyalgia rheumatica (PMR) are limited.Patient concerns:An 85-year-old Japanese woman with active PMR developed first syncope.Diagnosis:Frequent premature atrial contractions (PACs) with multiple patterns of aberrant conduction, QT interval prolongation, and morphological T-U wave variability followed by TdP were documented. PACs were the first beat of TdP.Interventions:Amiodarone, together with magnesium and potassium, was intravenously administered. However, TdP resulted in a ventricular arrhythmic storm, for which sedation with mechanical ventilatory support, temporary overdrive cardiac pacing, and intravenous landiolol administration in addition to multiple direct current shocks were effective.Outcomes:Approximately 2 years later, the patient was treated with amiodarone, propranolol, and prednisolone. She did not undergo implantable cardioverter-defibrillator implantation and was quite well, with no recurrence of ventricular tachyarrhythmia.Lessons:IL-6 hyperproduction in inflamed tissues has been widely confirmed in PMR. Frequent PACs with various patterns of aberrant conduction, QT interval prolongation, and morphological T-U wave variability followed by TdP, for which IL-6-mediated enhancement of L-type Ca2+ current and inhibition of the rapid component of the delayed rectifier K+ current are the most likely mechanisms, were documented in an elderly Japanese woman with PMR. ECG may be recorded once in patients with active PMR even when these patients do not complain of palpitation or syncope. If QT interval prolongation or arrhythmia, including even PACs, is observed, follow-up ECG may be warranted, particularly for patients with some risk factors for QT prolongation that could lead to TdP, such as advanced age, female sex, hypopotassemia, and polypharmacy.

Beta-Blocker Landiolol Hydrochloride in Preventing Atrial Fibrillation Following Cardiothoracic Surgery: A Systematic Review and Meta-Analysis.

Objective: The purpose of this article was to assess the benefit of perioperative administration of the intravenous beta-blocker landiolol hydrochloride in preventing atrial fibrillation (AF) after cardiothoracic surgery.Methods: We performed a systematic search in PubMed, Web of Science, CNKI, and OVID to identify randomized controlled trials (RCTs) and cohorts up to January 2021. Data regarding postoperative atrial fibrillation (POAF) and safety outcomes were extracted. Odds ratios (ORs) with 95% confidence intervals (CIs) were determined using the Mantel–Haenszel method. Meanwhile, subgroup analyses were conducted according to surgery type including lung cancer surgery, esophageal cancer surgery, and cardiac surgery.Results: Seventeen eligible articles involving 1349 patients within 13 RCTs and four cohorts were included in our meta-analysis. Compared with control group, landiolol administration was associated with a significant reduction of the occurrence of AF after cardiothoracic surgery (OR = 0.32, 95% CI 0.23–0.43, P <0.00001). In addition, the results demonstrated that perioperative administration of landiolol hydrochloride minimized the occurrence of postoperative complications (OR = 0.48, 95% CI 0.33–0.70, P = 0.0002). Funnel plots indicated no obvious publication bias.Conclusions: Considering this analysis, landiolol was effective in the prevention of AF after cardiothoracic surgery and did not increase the risk of major postoperative complications.

Efficacy and Safety of Early Intravenous Landiolol on Myocardial Salvage in Patients with ST-segment Elevation Myocardial Infarction before Primary Percutaneous Coronary Intervention: A Randomized Study.

Early treatment with an oral β-blocker is recommended in patients with a ST-segment-elevation myocardial infarction (STEMI). In this multicenter study, we evaluated the effects of a continuous administration of landiolol, an ultrashort-acting β-blocker, before primary percutaneous coronary intervention (PCI) on myocardial salvage and its safety in STEMI patients. A total of 47 Japanese patients with anterior or lateral STEMI undergoing a primary PCI within 12 h of symptom onset were randomized to receive intravenous landiolol (started at 3 μg/min/kg dose and continued to a total of 50 mg; n=23) or not (control; n=24). Patients with Killip class III or more were excluded. The primary outcome was the myocardial salvage index on cardiac magnetic resonance imaging (MRI) performed 5-7 days after the PCI. Cardiac MRI was performed in 35 patients (74%). The myocardial salvage index in the landiolol group was significantly greater than that in the control group (44.4±14.6% vs. 31.7±18.9%, respectively; p=0.04). There were no significant differences in adverse events at 24 h between the landiolol and control groups. A continuous administration of landiolol before a primary PCI may increase the degree of myocardial salvage without additional hemodynamic adverse effects within the first 24 h after STEMI.

Postoperative atrial fibrillation does not impact on overall survival after esophagectomy in patients with thoracic esophageal cancer: results from a randomized, double-blind, placebo-controlled trial.

Background: Administration of landiolol hydrochloride was found to be associated with reduced incidence of atrial fibrillation (AF) after esophagectomy for esophageal cancer in our previous randomized controlled trial (RCT). In addition, reduced incidence of AF was associated with reduction of other complications. Meanwhile, the effects of postoperative AF and other complications on long-term survival following esophagectomy are not well understood.Materials and Methods: Between March 2014 and January 2016, 100 patients with esophageal cancer were registered in an RCT trial and randomly allocated to receive either administration of landiolol or a placebo. We analyzed data from this RCT to better understand the effect of postoperative AF and severe associated complications on overall survival (OS) after esophagectomy for cancer. We also examined whether prophylactic administration of landiolol hydrochloride directly affects prolonged survival in patients with esophageal cancer.Results: The five-year rates of OS in the patients with and without AF were 60%, and 68.6%, respectively, there was no significant difference (P = 0.328). Five-year rates of OS of the patients with and without severe complications were 64.6%, and 67.5%, respectively (P = 0.995). The five-year rates of OS in the placebo and landiolol groups were 65.8% and 68%, respectively (P = 0.809). In multivariate analysis, high stage (stage III/IV) alone was an independent prognostic factor for esophageal cancer patients following esophagectomy.Conclusions: New-onset AF and the other severe complications were not associated with poorer long-term survival following esophagectomy. In addition, administration of landiolol hydrochloride after esophagectomy did not contribute to prolonging the OS.

Randomized controlled trial of landiolol, a short-acting beta-1 adrenergic receptor blocker, illustrating changes in high-molecular weight adiponectin levels after elective percutaneous coronary intervention.

Adiponectin (APN) has cardioprotective properties and bisoprolol has been reported to increase myocardial APN expression and reduce myocardial damage. Administration of landiolol, which has a higher cardio-selectivity and shorter half-life than bisoprolol, during the percutaneous coronary intervention (PCI) may increase serum APN and high-molecular weight (HMW)-APN, an active form of APN, in patients with stable angina pectoris (SAP). We recruited 70 patients with SAP and randomized them to intravenous landiolol during PCI (N = 35) or control group (N = 35). The primary endpoint was serum APN and HMW-APN level 3days after PCI. There was no difference in the primary endpoint between the landiolol and control groups (8.93 ± 5.24 vs. 10.18 ± 5.81μg/mL, p = 0.35 and 3.36 ± 2.75 vs. 4.28 ± 3.13μg/mL, p = 0.20) for APN and HMW-APN levels, respectively. APN and HMW-APN level were significantly decreased 1day after PCI [-0.55 ± 0.92μg/mL (9.87-9.32μg/mL), p < 0.001 and -0.20 ± 0.45μg/mL (3.89-3.69μg/mL), p < 0.001, respectively]. Additionally, the absolute change in HMW-APN was significantly smaller in the landiolol group compared to the control group (-0.08 ± 0.27 vs. -0.31 ± 0.55μg/mL, p = 0.031). Multiple linear regression analysis showed that use of landiolol was an independent predictor of change in HMW-APN (β = 0.276, p = 0.014). Serum APN and HMW-APN level 3days after PCI were similar between patients treated with and without landiolol. APN and HMW-APN decreased 1day after PCI in the SAP and landiolol mitigated decrease in HMW-APN.

Preventive effect of low-dose landiolol on postoperative atrial fibrillation study (PELTA study)

ObjectiveTo investigate the efficacy of prophylactic administration of low-dose landiolol on postoperative atrial fibrillation (POAF) in patients after cardiovascular surgery.MethodsConsecutive 150 patients over 70 years of age who underwent cardiovascular surgery for valvular, ischemic heart, and aortic diseases were enrolled in this single-center prospective randomized control study from 2010 to 2014. They were assigned to three treatment groups: 1γ group (landiolol at 1 μg/kg/min), 2γ group (landiolol at 2 μg/kg/min), or control group (no landiolol). In the two landiolol groups, landiolol hydrochloride was intravenously administered for a period of 4 days postoperatively. Electrocardiography was continuously monitored during the study period, and cardiologists eventually assessed whether POAF occurred or not.ResultsPOAF occurred in 24.4% of patients in the control group, 18.2% in 1γ group, and 11.1% in 2γ group (p = 0.256). Multivariate logistic regression analysis showed that the incidence of POAF tended to decrease depending on the dose of landiolol (trend-p = 0.120; 1γ group: OR = 0.786, 95% CI 0.257–2.404; 2γ group: OR = 0.379, 95% CI 0.112–1.287). Subgroup analysis showed a significant dose-dependent reduction in POAF among categories of female sex, non-use of angiotensin II receptor blockers (ARBs) before surgery, and valve surgery (each trend-p = 0.02, 0.03, and 0.004).ConclusionsThese findings indicate that prophylactic administration of low-dose landiolol may not be effective for preventing the occurrence of POAF in overall patients after cardiovascular surgery, but the administration could be beneficial to female patients, patients not using ARBs preoperatively, and those after valvular surgery.

Effects of \u03b21-adrenergic receptor blockade on the cerebral microcirculation in the normal state and during global brain ischemia/reperfusion injury in rabbits

BackgroundAlthough recent studies using experimental models of ischemic brain injury indicate that systemically-administered β1-blockers have potential protective effects on the cerebrovascular system, the precise mechanisms remain unclear. In addition to their cardiovascular effects, water-soluble β1-blockers can pass the blood–brain barrier and may exert their vascular action on cerebral microvessels. The aim of this study was to investigate the direct effects of β1-blockade on the cerebral microvasculature both in the normal state and ischemia/reperfusion state using the cranial window method.MethodsThe closed cranial window method was used to visualize the cerebral microcirculation and changes in the pial arteriole diameter in adult male rabbits. In the first experiment, various concentrations of the selective β1-blocker landiolol were administered into the cranial window to evaluate the dose-response. In the second experiment, the effect of β1-blockade on the brain during ischemic/reperfusion injury was investigated. Global brain ischemia/reperfusion was induced by clamping the brachiocephalic, left common carotid, and left subclavian arteries for 15 min. Either landiolol or artificial cerebrospinal fluid was infused 5 min after initiation of ischemia through 120 min after reperfusion. Pial arteriole diameter and hemodynamic and physiological parameters were recorded before ischemia, during ischemia, and 5, 10, 20, 40, 60, 80, 100, and 120 min after reperfusion.ResultsIn the first experiment, topical administration of landiolol at higher concentrations produced slight pial arteriole dilation (10− 8 mol/L: 4.3 ± 3.4%, 10− 6 mol/L: 8.0 ± 5.8%, 10− 4 mol/L: 7.3 ± 4.0%). In the second experiment, the topical administration of landiolol significantly dilated the pial arteriole diameters during ischemia/reperfusion injury (ischemia: 30.6 ± 38.6%, 5 min: 47.3 ± 42.2%, 10 min: 47.8 ± 34.2%, 20 min: 38.0 ± 39.0%). There were no statistical differences in hemodynamic and physiological parameters between the landiolol and control groups.ConclusionsThe blockade of β1-adrenergic receptors induced significant vasodilation of pial arterioles during ischemia/reperfusion injury. By contrast, only a slight dilation of the arterioles was observed in the normal state, indicating that ischemic cerebral microvessels are more susceptible to the vasodilatory effect induced by selective blockade of β1-adrenergic receptors than normal microvessels.

Effect of lidocaine with adrenaline and landiolol on hemodynamics in spontaneously hypertensive rats.

Administration of local anesthetics with adrenaline can cause tachycardia and hypertension. This study assessed whether combined administration of landiolol with adrenaline and lidocaine would induce local anesthesia without causing hemodynamic changes. Normal saline (NS), lidocaine with adrenaline (LA), and lidocaine with adrenaline and landiolol (LLA) were injected into Wistar Kyoto (WKY/Izm) or spontaneously hypertensive (SHR/Izm) rats, followed by measurement of the pulse rate (PR), and the systolic, diastolic and mean blood pressures (SBP, DBP and MBP). In the LLA group, the increase in PR was significantly suppressed in both SHR/Izm and WKY/Izm rats relative to those in the LA group. Although SBP was significantly reduced in WKY/Izm rats given LLA, relative to those given NS or LA, it was elevated in SHR/Izm rats given LLA. Landiolol-induced changes in PR may be due to blockade of adrenaline-induced β1 receptor stimulation, which suppresses cardiac hyperactivity, whereas the early surge of blood pressure in SHR/Izm rats given LLA may be due to the dominant alpha-adrenergic effects of β1 receptor inhibition. The anti-adrenergic effects of LLA were safe and effective in WKY/Izm rats, although the unexpected early hypertensive surge in SHR/Izm rats indicates the need for caution.

Landiolol, an ultra-short acting beta-1 blocker, for preventing postoperative lung cancer recurrence: study protocol for a phase III, multicenter randomized trial with two parallel groups of patients

BackgroundRecurrence of cancer after curative surgery is a major problem after most cancer treatments. Increased sympathetic activity during the perioperative period could promote cancer cell invasion to blood vessels and angiogenesis, resulting in cancer metastasis. Recent studies showed that use of beta blockers can be associated with the prolonged survival of patients with cancer. The objective of this study is to evaluate the preventive effects of landiolol hydrochloride, which is an ultra-short-acting beta-1-selective blocker that has been developed in Japan, on reducing recurrence of cancer after curative surgery for patients with lung cancer.MethodsThe present study is a phase III, multicenter, randomized trial with two parallel groups of patients with lung cancer, comparing surgery alone and surgery with landiolol administration for three days during the perioperative period. A total of 400 patients will be enrolled from 12 Japanese institutions. The primary endpoint is two-year relapse-free survival and overall survival after curative surgery for lung cancer. The secondary endpoints are additional treatment after recurrence of cancer, safety events, and the incidence of postoperative complications.DiscussionThe principal question addressed in this trial is whether landiolol can reduce recurrence of cancer after curative surgery for lung cancer.Trial registrationJapan Registry of Clinical Trials, jRCT2011180004. Registered 17 January 2019.

Pilot study of bisoprolol 8 mg transdermal patch at bedtime before coronary computed tomography angiography

BackgroundCoronary computed tomography angiography (CCTA) is recommended for first-line evaluation of stable coronary artery disease, and there is a standard protocol to control heart rate (HR) in guidelines. However, time is required to decrease HR to the recommended ≤60 beats per minute (bpm). We investigated whether the bisoprolol 8mg transdermal patch at bedtime on the day before CCTA can achieve a target HR and simplify the CCTA process. MethodsWe randomly assigned 63 patients with an HR of ≥70 bpm and systolic blood pressure ≥120mmHg to a standard protocol group (n=33) or a group (n=30) that applied a bisoprolol 8mg transdermal patch (Bis) at bedtime on the day before CCTA evaluation. The primary endpoint was a change in HR between enrollment in the study and the time of CCTA evaluation. The secondary endpoints were elapsed time from arrival at the CCTA suite to starting CCTA image acquisition, and the rates of oral metoprolol and intravenous landiolol administration (UMIN00035246). ResultsBaseline characteristics did not significantly differ between two groups. HR was significantly lower upon arrival at the CCTA suite in Bis, than standard protocol group (67.5±7.8 bpm vs. 75.0±10.6 bpm; p=0.00002), and the amount of elapsed time from arrival to the start of CCTA evaluation was also significantly decreased in Bis group (76.9±34.9min vs. 94.8±29.2min; p=0.0356). Rates of oral metoprolol and intravenous landiolol administration did not significantly differ between two groups (63.3% vs. 83.3%, p=0.143 and 36.7% vs. 60.0%, p=0.12, respectively). ConclusionsThe bisoprolol 8mg transdermal patch lowered HR and decreased the amount of time needed for CCTA, thus streamlining the evaluation process.

4332Benefit of sinus rhythm restoration in acute decompensated heart failure patients with atrial tachyarrhythmia treated with landiolol

Abstract Background Atrial tachyarrhythmias (ATA), such as atrial fibrillation / atrial tachycardia are frequently observed in patients with acute decompensated heart failure (ADHF). Because ATA leads to clinical deterioration and worsen HF, the conversion and prevention of ATA is important of ADHF with ATA. Landiolol, an ultrashort-acting intravenous beta-1 blocker, was developed and has been used for the treatment of ATA. Purpose We evaluated the acute effect of landiolol treatment on heart rate or blood pressure (BP), also the rates and benefits of sinus rhythm (SR) restoration among AHF patients with ATA treated with landiolol. Methods We studied 67 consecutive HF patients with ATA (age: 67±12 years, 36 male) treated with landiolol from 2015 to December 2017 at our University Hospital. They were compared with 50 paired subjects, matched for gender, age and baseline BP who developed HF with ATA from HIJ-HF 2 study (consisted of HF patients hospitalized between 2013 and 2014). Results At the start of landiolol treatment, mean left ventricular ejection fraction (LVEF) was 41±14%. The median maintenance dose of landiolol was 3.0 (1.0–12.0) μ/kg/min and the median treatment duration of landiolol was 5 (1–24) days. After 6 hours from administration of landiolol, mean HR decreased significantly from 140±18 to 100±21 bpm (p&lt;0.05), whereas BP was not difference during landiolol treatment. Sinus rhythm was restored spontaneously in 15 (22%), and by electrical or pharmacological cardioversion in 5 (7%) during a treatment with intravenous landiolol. Furthermore, sinus rhythm was restored in 22 patients using additional rhythm control treatment, such as amiodarone or catheter ablation after intravenous landiolol treatement. Eight patients experienced in-hospital death. Forty-one (69%) of 59 patients discharged alive were in SR. During the follow-up period of 16±12 months, 4 patients died and 12 patients experienced rehospitalization due to worsening HF after hospital discharge. There was a significant higher rate of death or HF rehospitalization in patients without SR restoration than patients with SR restoration (44% vs. 20%, p&lt;0.05) (Figure A). Compared with 50 paired subjects from HIJ-HF 2 study, those who treated with landiolol developed a significant higher rate of SR restoration (68% vs. 20%, p&lt;0.05) (Figure B). Figure 1 Conclusion This study demonstrated that landiolol treatment was effective for both rate control and conversion to sinus rhythm in ADHF patient with ATA. We should consider that the benefits of rhythm control in ADHF patients with ATA during and after landiolol treatment.

Use of low-dose \u03b21-blocker for sinus tachycardia in patients with catecholamine support following cardiovascular surgery: a retrospective study

BackgroundSinus tachycardia coupled with high-dose catecholamine is common after cardiopulmonary bypass (CPB). The present study assessed the hemodynamic efficacy and safety of combination therapy using low-dose β1-selective adrenergic blocker (landiolol) and inotropes.MethodsThis was a retrospective, single center, self-comparison study at post-anesthesia care unit within a tertiary care center. The study included adults who underwent cardiac surgery with CPB and received landiolol between April 2007 and November 2011. We assessed hemodynamic data prior to and 1 h after initiation of landiolol therapy.ResultsWe evaluated 11 patients who were administered 2.6 ± 1.3 μg/kg/min (mean ± SD) landiolol with sinus tachycardia and received catecholamine therapy after on-pump cardiovascular surgery. Landiolol administration led to a significant reduction in heart rate (HR; 112.4 ± 5.8 vs 126.0 ± 7.6 beats/min, p < 0.001), and a significant increase in stroke volume index (SVI) assessed by pulmonary artery catheterization (22.4 ± 5.4 vs. 18.9 ± 4.2 mL/m2, p = 0.04). Only one patient showed no HR reduction, whereas seven patients showed decreased HR and increased SVI (64, 95% confidence interval: 30–98%). Moreover, all five patients who received high-dose catecholamine support showed improved hemodynamics. In terms of safety, no patients required cessation of landiolol therapy.ConclusionsLow-dose landiolol therapy may safely decrease HR and improve hemodynamics among patients with sinus tachycardia receiving catecholamine treatment after cardiovascular surgery.Trial registrationThis study is retrospective. Registration number: 11. Duration of registration: April 2007~November 2011.

Effects of Intravenous Landiolol on Heart Rate and Outcomes in Patients with Atrial Tachyarrhythmias and Acute Decompensated Heart Failure: A Single-Center Experience.

ObjectiveAtrial tachyarrhythmias (ATAs) lead to clinical deterioration and worsening heart failure (HF) in patients with acute decompensated HF (ADHF). We evaluated the effects of the ultrashort-acting intravenous β1-blocker landiolol on the heart rate, hemodynamics, and outcome in patients with ATAs and ADHF.MethodsA total of 67 consecutive hospitalized patients with ATAs and ADHF who were treated with landiolol (36 males, 67 ± 12 years) were included in this single-center retrospective study. The primary endpoints were changes in heart rate and systolic blood pressure from baseline during intravenous landiolol administration. The secondary endpoints included restoration of sinus rhythm and outcomes.ResultsThe median maintenance dose of intravenous landiolol was 3.0 (range 1.0–12.0) μg/kg/min and the median treatment duration was 5 (range 1–24) days. Intravenous landiolol reduced heart rate (141 ± 17 beats/min at baseline to 99 ± 20 beats/min at 6 h, P < 0.001) without a marked reduction in blood pressure or deterioration of HF. During landiolol treatment, 15 (22%) patients had spontaneously restored sinus rhythm. Eight patients experienced in-hospital death, and 41 (69%) were discharged with sinus rhythm. During the follow-up of 16 ± 12 months, patients with sinus rhythm showed a lower frequency of rehospitalization due to worsening HF than patients with ATAs (5/41 vs. 7/18, P = 0.019).ConclusionsOur results showed that intravenous landiolol reduces the heart rate without markedly decreasing blood pressure in patients with ATAs and ADHF. Approximately 70% of the discharged patients were in sinus rhythm, and these patients showed a lower frequency of rehospitalization due to worsening HF (UMIN-CTR no. UMIN000033650).