Cardioprotective effects of p-coumaric acid on tachycardia, inflammation, ion pump dysfunction, and electrolyte imbalance in isoproterenol-induced experimental myocardial infarction.

Cardiovascular diseases cause a large number of deaths throughout the world. No research was conducted earlier on p-coumaric acid's effect on tachycardia, inflammation, ion pump dysfunction, and electrolyte imbalance. Hence, we appraised the above-said parameters in isoproterenol-induced myocardial infarcted rats. This investigation included 24 male albino Wistar rats in 4 groups. Normal control Group 1, p-coumaric acid (8 mg/kg body weight) alone treated Group 2, Isoproterenol (100 mg/kg body weight) induced myocardial infarcted Group 3, p-coumaric acid (8 mg/kg body weight) pretreated isoproterenol (100 mg/kg body weight) induced Group 4. After 1 day of the last dose of isoproterenol injection (day 10), rats were killed and blood and heart were taken and inflammatory markers, lipid peroxidation, nonenzymatic antioxidants, ion pumps, and electrolytes were measured. The heart rate, serum cardiac troponin-T, serum/plasma inflammatory markers, and heart proinflammatory cytokines were raised in isoproterenol-induced rats. Isoproterenol also enhanced plasma lipid peroxidation, lessened plasma nonenzymatic antioxidants, and altered heart ion pumps and serum and heart electrolytes. In this study, p-coumaric acid pretreatment orally for 7 days to isoproterenol-induced myocardial infarcted rats prevented changes in the above-cited parameters. p-Coumaric acid's anti-tachycardial, anti-inflammatory, anti-ion pump dysfunction and anti-electrolyte imbalance properties are the mechanisms for these cardioprotective effects.

Refractory supraventricular fetal tachycardia as a cause of non-immune hydrops: management conundrum.

Supraventricular tachyarrhythmia (SVT) is the most common form of fetal tachyarrhythmias. The presentation can vary from ill-defined, non-sustained episodes of tachyarrhythmia to frank non-immune hydrops. The standard of care is transplacental therapy by treating the mother with oral antiarrhythmic drugs, followed by direct fetal therapy in refractory cases. We report a case of primigravida in her late 20s, who presented at 28.1 weeks of gestation with fetal hydrops and SVT. She was initially managed with oral digoxin and flecainide, but due to worsening hydrops, risk of fetal demise and extreme prematurity, further management by direct fetal therapy was given in terms of intramuscular digoxin and intraperitoneal flecainide. Following which, the fetus had a favourable outcome. This case highlights the possible role of direct fetal therapy in refractory cases of SVT.

Optimal use of intravenous landiolol in acute cardiac care.

INTRODUCTION: B-blockers are regarded as beneficial pharmacologic agents in cardiac care, but their role in the acute setting remains ambiguous. Increasing evidence supports the important role of landiolol in critical care, a highly cardioselective intravenous b-blocker with rapid onset of action and short elimination time. Among its most valuable properties, which may aid to overcome special reservations related to b-blocker therapy in the acute setting, landiolol has a potent negative chronotropic effect while at the same time it exhibits a mild negative inotropic effect. AREAS COVERED: This expert opinion review aims to present basic pharmacologic aspects of landiolol and provide current clinical research focused on its efficacy and safety. EXPERT OPINION: Landiolol is a valuable and safe pharmacologic agent in acute cardiac care. Japanese and European guidelines have incorporated its use for the management of atrial tachyarrhythmia in patients with cardiac dysfunction. Although emerging clinical trials have experimented its use in patients with sustained ventricular tachycardia/fibrillation, acute myocardial infarction undergoing primary percutaneous intervention and in patients with septic cardiomyopathy, more studies are needed in order to establish its value in such cardiac conditions.

[Clinical characteristics of 42 children with focal atrial tachycardia originated from the right atrial appendage].

Objective: To investigate the feature and treatment of atrial tachycardia (AT) originated from right atrial appendage (RAA) in children. Methods: The data of 42 children with AT originated from RAA, who were admitted the First Hospital of Tsinghua University from January 2010 to September 2022 were analyzed retrospectively.The clinical characteristics, treatment and efficacy were analyzed. The children were divided into tachycardia cardiomyopathy group and normal cardiac function group. The differences in the ablation age and the heart rate during AT between two groups were compared by independent sample t-test. Results: Among 42 children, there were 20 males and 22 females. The age of onset was 2.7 (0.6, 5.1) years. Their age at radiofrequency ablation was (6.5±3.6) years, and the weight was (23.4±10.0) kg. Thirty-two children (76%) had sustained AT. The incidence of tachycardia cardiomyopathy was 43% (18/42). Compared to that of the normal cardiac function group, the ablation age and the heart rate at atrial tachycardia of the tachycardia cardiomyopathy group were higher ((8.1±3.8) vs. (5.3±3.1) years, t=-2.63, P=0.012; (173±41) vs. (150±30) beats per minute, t=-2.05, P=0.047. Thirty-eight children (90%) responded poorly to two or more antiarrhythmic drugs. The immediate success rate of radiofrequency ablation (RFCA) was 57% (24/42), and the AT recurrence rate was 17% (4/24). Twenty-two children underwent RAA resection, and their AT were all converted to sinus rhythm after the surgery. During the RAA resection, 10 cases of right atrial appendage aneurysm were found, 9/18 of which failed the RFCA. Conclusions: The AT originated from the RAA in children tend to present with sustained AT, respond poorly to antiarrhythmic drugs, and has a low success rate of RFCA as well as high recurrence rate. Resection of the RAA is a safe and effective complementary treatment.

LCZ696 Ameliorates Tachycardia-Induced Cardiac Calcium Dyshomeostasis in the SERCA2α-Dependent Pathway.

The incidence, prevalence, and economic burden of heart failure have continued to increase worldwide. It remains unclear whether LCZ696 can ameliorate calcium reuptake in the sarcoplasmic reticulum via the sarcoplasmic endoplasmic reticulum calcium ion-ATPase 2α (SERCA2α)-dependent pathway during cardiac diastole. We investigated whether LCZ696 could ameliorate tachycardia-induced myocardial injury by modulating cardiac SERCA2α levels. A tachycardia-induced myocardial injury model was established by daily intraperitoneal administration of 60 mg/kg isoprenaline (ISO) for 2 weeks. LCZ696 was orally administered for the following 4 weeks. SERCA2α and calcium ion (Ca2+)-related protein expression was assessed by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting. For additional in vitro studies, HL-1 cardiomyocytes were used. A SERCA2α overexpression vector was constructed and transfected into HL-1 cells. The expression of SERCA2α and Ca2+-related proteins were also measured using qRT-PCR and western blotting. Our in vivo results demonstrated that myocardial injury was successfully induced by intraperitoneal administration of ISO. The expression of both SERCA2α- and Ca2+-related proteins was impaired. Oral administration of LCZ696 increased the expression of SERCA2α, alleviated Ca2+-related protein impairment and cardiac Ca2+ dyshomeostasis, and ameliorated myocardial injury. These results were compared with our in vitro findings. Ca2+-related proteins are affected by the overexpression of SERCA2α. LCZ696 improved tachycardia-induced myocardial injury by increasing SERCA2α expression, which reversed the development of heart failure in ISO-induced mice. These results provide new insights into how sustained LCZ696 treatment in heart failure improves cardiac function through intracellular Ca2+-regulatory mechanisms.

Acute Cardiovascular and Cardiorespiratory Effects of JWH-018 in Awake and Freely Moving Mice: Mechanism of Action and Possible Antidotal Interventions?

JWH-018 is the most known compound among synthetic cannabinoids (SCs) used for their psychoactive effects. SCs-based products are responsible for several intoxications in humans. Cardiac toxicity is among the main side effects observed in emergency departments: SCs intake induces harmful effects such as hypertension, tachycardia, chest pain, arrhythmias, myocardial infarction, breathing impairment, and dyspnea. This study aims to investigate how cardio-respiratory and vascular JWH-018 (6 mg/kg) responses can be modulated by antidotes already in clinical use. The tested antidotes are amiodarone (5 mg/kg), atropine (5 mg/kg), nifedipine (1 mg/kg), and propranolol (2 mg/kg). The detection of heart rate, breath rate, arterial oxygen saturation (SpO2), and pulse distention are provided by a non-invasive apparatus (Mouse Ox Plus) in awake and freely moving CD-1 male mice. Tachyarrhythmia events are also evaluated. Results show that while all tested antidotes reduce tachycardia and tachyarrhythmic events and improve breathing functions, only atropine completely reverts the heart rate and pulse distension. These data may suggest that cardiorespiratory mechanisms of JWH-018-induced tachyarrhythmia involve sympathetic, cholinergic, and ion channel modulation. Current findings also provide valuable impetus to identify potential antidotal intervention to support physicians in the treatment of intoxicated patients in emergency clinical settings.

Ivabradine monotherapy in pediatric patients with focal atrial tachycardia: a single-center study.

This study investigated the efficacy of ivabradine monotherapy in pediatric patients with focal atrial tachycardia (FAT). We prospectively enrolled 12 pediatric patients (7.5 ± 4.5 years; six girls) with FAT who were resistant to conventional antiarrhythmics and received ivabradine as monotherapy. Patients were classified as having tachycardia-induced cardiomyopathy (TIC) if they had a left ventricular ejection fraction (LVEF) of < 50% and a left ventricular end-diastolic dimension (LVDD) z-score of > 2 due to tachycardia. Oral ivabradine was initiated at 0.1 mg/kg every 12 h, increased to 0.2 mg/kg every 12 h if no restoration of stable sinus rhythm was observed after two doses, and discontinued after 48 h if neither rhythm nor heart rate control was observed. Of these patients, six (50%) had incessant atrial tachycardia, and 6 had frequent short episodes of FAT. Six patients were diagnosed with TIC, and their mean LVEF and mean LVDD z-score were 36.2 ± 8.7% (range, 27-48%) and 4.2 ± 1.7 (range, 2.2-7.3), respectively. Finally, six patients achieved either rhythm (n = 3) or heart rate control (n = 3) within 48 h of ivabradine monotherapy. One patient achieved rhythm/heart rate control with ivabradine at a dose of 0.1 mg/kg every 12 h, while the others achieved rhythm/heart rate control at a dose of 0.2 mg/kg every 12 h. Five patients received ivabradine monotherapy for chronic therapy, one (20%) of whom had FAT breakthrough 1 month after discharge, and metoprolol was added. Neither FAT recurrence nor adverse effect (with or without beta-blocker) was observed during a median follow-up of 5 months. CONCLUSION: Ivabradine is well-tolerated and may provide early heart rate control in pediatric FAT and can be considered early, especially in the presence of left ventricular dysfunction. Further investigations are deserved to confirm the optimal dose and long-term efficacy in this population. WHAT IS KNOWN: • Focal atrial tachycardia (FAT) is the most common arrhythmia associated with tachycardia-induced cardiomyopathy (TIC) in children, and the efficacy of conventional antiarrhythmic medications in the treatment of FAT is poor. • Ivabradine is currently the only selective hyperpolarization-activated cyclic nucleotide-gated (HCN) inhibitor, which can effectively low HR without negative effect on blood pressure or inotropy. WHAT IS NEW: • Ivabradine (0.1-0.2 mg/kg every 12 h) can effectively suppress focal atrial tachycardia in 50% of pediatric patients. • Ivabradine provides early control of heart rate and hemodynamic stabilization in children with severe left ventricular dysfunction due to atrial tachycardia within 48 h.

Irritant-evoked reflex tachyarrhythmia in spontaneously hypertensive rats is reduced by inhalation of TRPM8 agonists l-menthol and WS-12.

Inhalation of noxious irritants activates nociceptive sensory afferent nerves innervating the airways, inducing reflex regulation of autonomic networks and the modulation of respiratory drive and cardiovascular (CV) parameters such as heart rate and blood pressure. In healthy mammals, irritant-evoked pulmonary-cardiac reflexes cause parasympathetic-mediated bradycardia. However, in spontaneously hypertensive (SH) rats, irritant inhalation also increases sympathetic drive to the heart. This remodeled pulmonary-cardiac reflex may contribute to cardiovascular risk caused by inhalation of air pollutants/irritants in susceptible individuals with cardiovascular disease (CVD). Previous studies have shown that the cooling mimic l-menthol, an agonist for the cold-sensitive transient receptor potential melastatin 8 (TRPM8), can alleviate nasal inflammatory symptoms and respiratory reflexes evoked by irritants. Here, we investigated the impact of inhalation of TRPM8 agonists l-menthol and WS-12 on pulmonary-cardiac reflexes evoked by inhalation of the irritant allyl isothiocyanate (AITC) using radiotelemetry. l-Menthol, but not its inactive analog d-menthol, significantly reduced the AITC-evoked reflex tachycardia and premature ventricular contractions (PVCs) in SH rats but had no effect on the AITC-evoked bradycardia in either SH or normotensive Wistar-Kyoto (WKY) rats. WS-12 reduced AITC-evoked tachycardia and PVCs in SH rats, but this more potent TRPM8 agonist also reduced AITC-evoked bradycardia. l-Menthol had no effect on heart rate when given alone, whereas WS-12 evoked a minor bradycardia in WKY rats. We conclude that stimulation of TRPM8-expressing afferents within the airways reduces irritant-evoked pulmonary-cardiac reflexes, especially the aberrant reflex tachyarrhythmia in SH rats. Airway menthol treatment may be an effective therapy for reducing pollution-associated CV exacerbations.NEW & NOTEWORTHY Irritant-evoked pulmonary-cardiac reflexes are remodeled in spontaneously hypertensive (SH) rats-causing de novo sympathetic reflexes that drive tachyarrhythmia. This remodeling may contribute to air pollution-associated risk in susceptible individuals with cardiovascular disease. We found that inhalation of TRPM8 agonists, l-menthol and WS-12, but not the inactive analog d-menthol, selectively reduces the reflex tachyarrhythmia evoked by allyl isothiocyanate (AITC) inhalation in SH rats. Use of menthol may protect susceptible individuals from pollution-associated CV exacerbations.

Wide QRS Complex Tachycardia Change to Narrow QRS Complex Tachycardia After ß-Blocker Administration.

This case report describes a patient in their 80s with a history of paroxysmal atrial fibrillation who presented with palpitation, dizziness, nausea, and vomiting.

Hemodynamic profile effects of PM101 amiodarone formulation in patients with post-operative tachyarrhythmias.

Amiodarone may be considered for patients with junctional ectopic tachycardia refractory to treatment with sedation, analgesia, cooling, and electrolyte replacements. There are currently no published pediatric data regarding the hemodynamic effects of the newer amiodarone formulation, PM101, devoid of hypotensive agents used in the original amiodarone formulation. We performed a single-center, retrospective, descriptive study from January 2012 to December 2020 in a pediatric ICU. Thirty-three patients were included (22 male and 11 female) between the ages of 1.1 and 1,460 days who developed post-operative junctional ectopic tachycardia or other tachyarrhythmias requiring PM101. Data analysis was performed on hemodynamic parameters (mean arterial pressures and heart rate) and total PM101 (mg/kg) from hour 0 of amiodarone administration to hour 72. Adverse outcomes were defined as Vasoactive-Inotropic Score >20, patients requiring ECMO or CPR, or patient death. There was no statistically significant decrease in mean arterial pressures within the 6 hours of PM101 administration (p > 0.05), but there was a statistically significant therapeutic decrease in heart rate for resolution of tachyarrhythmia (p < 0.05). Patients received up to 25 mg/kg in an 8-hour time for rate control. Average rate control was achieved within 11.91 hours and average rhythm control within 62 hours. There were four adverse events around the time of PM101 administration, with three determined to not be associated with the medication. PM101 is safe and effective in the pediatric cardiac surgical population. Our study demonstrated that PM101 can be used in a more aggressive dosing regimen than previously reported in pediatric literature with the prior formulation.

Efficacy of a single dose of esmolol to prevent extubation-related complications during emergence from anesthesia: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Few trials have examined the efficacy of esmolol to attenuate hemodynamic and respiratory responses during extubation. However, the most appropriate dose of esmolol and an optimal protocol for administering this beta-blocker are uncertain. METHODS: Ninety patients ASA physical status I, II, and III (aged 18...60 years) scheduled to procedures with general anesthesia and tracheal extubation were selected. Patients were randomized into esmolol and placebo group to evaluate the efficacy and safety of a single bolus dose of esmolol (2...mg.kg-1) on cardiorespiratory responses during the peri-extubation period. The primary outcome was the rate of tachycardia during extubation. RESULTS: The rate of tachycardia was significantly lower in esmolol-treated patients compared to placebo-treated patients (2.2% vs. 48.9%, relative risk (RR): 0.04, 95% confidence interval (95% CI)...=...0.01 to 0.32, p...=...0.002). The rate of hypertension was also significantly lower in the esmolol group (4.4% vs. 31.1%, RR: 0.14, 95% CI 0.03 to 0.6, p...=...0.004). Esmolol-treated patients were associated with higher extubation quality compared to patients who received placebo (p...<...0.001), with an approximately two-fold increase in the rate of patients without cough (91.1%) in the esmolol group compared to the placebo group (46.7%). The rate of bucking was approximately 5-fold lower in the esmolol group (8.9% vs. 44.5%, respectively, RR: 0.20 (95% CI, 0.1 to 0.5, p...=...0.002, with an NNT of 2.8). CONCLUSION: A single bolus dose of esmolol is an effective and safe therapeutic strategy to attenuate cardiorespiratory responses during the peri-extubation period.

Case series: propranolol liquid in the treatment of tachyarrhythmias in neonates and infants: potential for errors.

Oral propranolol therapy is commonly used for the prevention of tachyarrhythmias in infancy and childhood. Propranolol is commercially produced in four concentrations allowing varying volumes to be administered. However, quite often an alternative strength of propranolol liquid is issued without clear change in instructions or warning. This may lead to parents inadvertently administering the wrong dose.

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

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.

Fingers on the Wrist and Taming the Funny Current, Rejuvenate the Wounded Heart: Ivabradine-Responsive Atrial Tachycardia.

A 19-year-old male presented with dyspnea on exertion (New York Heart Association [NYHA] class II) and occasional palpitations for six months. He had initially been evaluated at another facility and diagnosed with dilated cardiomyopathy. Despite treatment, there was no improvement in his symptoms. On evaluation at our centre, his previous electrocardiograms appeared normal. However, palpation of his radial pulse for one minute revealed runs of regular tachycardia, interspersed with a normal pulse rate. A 30-second rhythm strip electrocardiogram (ECG) showed multiple runs of ectopic tachycardia originating from the right atrial appendage, interspersed with ectopic atrial rhythms. Echocardiography showed severe left ventricle (LV) dysfunction with an ejection fraction of 20-25%. Radio-frequency ablation was recommended, but the patient declined. Instead, he was started on Ivabradine. After a month, his symptoms fully resolved. The ECG displayed a normal sinus rhythm with no tachycardia, and his left ventricular ejection function improved.

Efficacy of a single dose of esmolol to prevent extubation-related complications during emergence from anesthesia: a randomized, double-blind, placebo-controlled trial

Abstract Background Few trials have examined the efficacy of esmolol to attenuate hemodynamic and respiratory responses during extubation. However, the most appropriate dose of esmolol and an optimal protocol for administering this beta-blocker are uncertain. Methods Ninety patients ASA physical status I, II, and III (aged 18-60 years) scheduled to procedures with general anesthesia and tracheal extubation were selected. Patients were randomized into esmolol and placebo group to evaluate the efficacy and safety of a single bolus dose of esmolol (2 mg.kg-1) on cardiorespiratory responses during the peri-extubation period. The primary outcome was the rate of tachycardia during extubation. Results The rate of tachycardia was significantly lower in esmolol-treated patients compared to placebo-treated patients (2.2% vs. 48.9%, relative risk (RR): 0.04, 95% confidence interval (95% CI) = 0.01 to 0.32, p= 0.002). The rate of hypertension was also significantly lower in the esmolol group (4.4% vs. 31.1%, RR: 0.14, 95% CI 0.03 to 0.6, p= 0.004). Esmolol-treated patients were associated with higher extubation quality compared to patients who received placebo (p< 0.001), with an approximately two-fold increase in the rate of patients without cough (91.1%) in the esmolol group compared to the placebo group (46.7%). The rate of bucking was approximately 5-fold lower in the esmolol group (8.9% vs. 44.5%, respectively, RR: 0.20 (95% CI, 0.1 to 0.5, p= 0.002, with an NNT of 2.8). Conclusion A single bolus dose of esmolol is an effective and safe therapeutic strategy to attenuate cardiorespiratory responses during the peri-extubation period.

Cryoablation as a first-line therapy for atrial fibrillation: current status and future prospects.

INTRODUCTION: Atrial fibrillation (AF) is a common chronic and progressive heart rhythm disorder. For those in whom sinus rhythm is desired, contemporary clinical practice guidelines recommend antiarrhythmic drugs (AADs) as the initial therapy. However, these medications have modest efficacy and are associated with significant adverse effects. AREAS COVERED: The current article reviews the evidence surrounding first-line catheter ablation, particularly the emerging evidence surrounding the use of cryoballoon ablation as a first-line therapy. The focus of the review is on the outcomes of arrhythmia freedom, quality of life, health-care utilization, and safety. In addition, the article will review novel cryoablation systems. EXPERT OPINION: Recent evidence suggests that cryoballoon ablation significantly improves arrhythmia outcomes (e.g. freedom from any atrial tachyarrhythmia or symptomatic atrial tachyarrhythmia, reduction in arrhythmia burden), patient-reported outcomes (e.g. symptoms and quality of life), and health-care resource utilization (e.g. hospitalization), without increasing the risk of adverse events. These findings are relevant to patients, providers, and health-care systems, as they help inform the decision-making regarding the initial choice of rhythm-control therapy in patients with treatment-naive AF.

Control of Heart Rate in Infant and Child Tachyarrhythmia With Reduced Cardiac Function Using Landiolol (HEARTFUL)　- Results of a Prospective, Multicenter, Uncontrolled Clinical Study.

BACKGROUND: The prospective Control of HEART rate in inFant and child tachyarrhythmia with reduced cardiac function Using Landiolol (HEARTFUL) study investigated the effectiveness and safety of landiolol, a short-acting ß1 selective blocker, in children.Methods and Results: Twenty-five inpatients aged ≥3 months to <15 years who developed supraventricular tachyarrhythmias (atrial fibrillation, atrial flutter, supraventricular tachycardia, and inappropriate sinus tachycardia) were treated with landiolol. The primary endpoint, the percent of patients with a reduction in heart rate ≥20% from the initial rate of tachycardia, or termination of tachycardia at 2 h after starting landiolol, was achieved in 12/25 patients (48.0%; 95% CI 28.4-67.6), which exceeded the predetermined threshold (38.0%). At 2 h after starting landiolol administration, heart rate had decreased by ≥20% in 45.8% (11/24) and recovery to sinus rhythm was achieved in 40.0% (6/15) of the patients. Adverse reactions (ARs) occurred in 24.0% (6/25) of patients, and the study was discontinued in 4.0% (1/25) of the patients; however, none of these ARs were considered serious. The most common AR was hypotension (20.0% [5/25] of patients). CONCLUSIONS: The HEARTFUL study has demonstrated the efficacy of landiolol, by reducing heart rate or terminating tachycardia, in pediatric patients with supraventricular tachyarrhythmias. Although serious ARs and concerns were not identified in this study, physicians should be always cautious of circulatory collapse due to hypotension.