Potential use of ivabradine in postoperative junctional ectopic tachycardia: a systematic review and single-arm meta-analysis

Abstract

Background

Postoperative junctional ectopic tachycardia (JET) is a frequent, hemodynamically consequential arrhythmia after congenital heart surgery. Ivabradine is increasingly used off-label, but its effectiveness and safety in pediatric postoperative JET remain uncertain.

Methods

We conducted a systematic review and single‑arm meta‑analysis of studies enrolling children (< 18 years) with postoperative JET treated with oral or nasogastric ivabradine. Outcomes included conversion to sinus rhythm, time to conversion, recurrence, use of concomitant antiarrhythmic drugs (AADs), adverse events (AEs) (bradycardia, hypotension, QT prolongation, atrioventricular block), and all‑cause mortality. Study‑level event rates were pooled as proportions using random‑effects models.

Results

Five studies (1 randomized trial arm, 3 cohorts, 1 case series; N = 87) met the inclusion criteria. Ivabradine dosing ranged from 0.05 to 0.1 mg/kg every 12 h. Across ivabradine‑based regimens, the pooled conversion proportion was 98.8% (95% CI 93.8–100), with reported mean times to stable sinus rhythm between 7.1 and 55.5 h. The pooled JET recurrence proportion was 3% (95% CI 0–12.1). Concomitant intravenous or oral AADs were used in 48.3% of patients (95% CI 10.4–87.2). No ivabradine-attributed bradycardia, hypotension, QT-interval prolongation, or new/worsening atrioventricular block was reported; all‑cause mortality was 2.1% (95% CI 0–10.1), attributed in the primary reports to postoperative complications rather than directly to ivabradine. In a sensitivity analysis restricted to two studies with ≤ 25% concomitant antiarrhythmic drug use, the conversion proportion remained high (98%), but confidence intervals for recurrence and mortality were wide.

Conclusions

In the small, predominantly observational studies available, ivabradine-based regimens were associated with high conversion to sinus rhythm and low short-term recurrence of postoperative JET, with no hemodynamic or conduction AEs reported among 87 patients. Interpretation is limited by nonrandomized designs, frequent cotreatment with other AADs, short follow‑up, and regional concentration of data; the pooled proportions should be viewed as exploratory summaries rather than estimates of ivabradine’s independent effect. Multicentre randomized trials are needed to define causal efficacy, optimal dosing, and longer‑term safety.

Trial Registration

This systematic review and single-arm meta-analysis was prospectively registered with PROSPERO (CRD420251080412).

Supplementary Information

The online version contains supplementary material available at 10.1186/s12872-026-05741-9.

Background

Postoperative junctional ectopic tachycardia (JET) is a well-recognized arrhythmia in children following congenital heart surgery, representing the most common hemodynamically significant tachyarrhythmia in this setting [1]. It originates from the atrioventricular (AV) junction due to abnormal automaticity rather than reentrant mechanisms, often precipitated by surgical trauma, ischemia, or catecholamine stress to the conduction tissue [2]. Clinically, JET manifests as a rapid junctional rhythm with AV dissociation or retrograde 1:1 conduction, leading to loss of AV synchrony. This results in significant hemodynamic compromise. The tachycardia reduces diastolic filling time and cardiac output, which can precipitate low cardiac output syndrome, prolong intensive care, and in severe cases lead to life-threatening instability [3]. Managing JET is inherently challenging because its onset is often rapid and refractory, demanding prompt intervention in an already fragile postoperative patient.

Conventional treatment strategies for postoperative JET have important limitations. Standard care typically includes general supportive measures (sedation, ventilation, correction of fever and electrolyte imbalances) and antiarrhythmic interventions such as cooling (therapeutic hypothermia) and intravenous antiarrhythmic drugs (AADs). Amiodarone is widely used as a first-line antiarrhythmic drug (AAD) for JET, sometimes in conjunction with overdrive atrial pacing to restore AV synchrony; however, these approaches carry substantial risks [4]. Intravenous amiodarone often causes bradycardia, vasodilation, and hypotension, compounding hemodynamic instability in postoperative infants [5]. Likewise, aggressive measures like atrial pacing require invasive procedures and deep sedation, while systemic hypothermia can impair coagulation and metabolic function [6]. In essence, currently available therapies must strike an uneasy balance between arrhythmia control and hemodynamic compromise. This underscores the need for a more targeted, hemodynamically neutral antiarrhythmic option for JET – one that can slow the ectopic junctional rhythm without further depressing cardiac output or blood pressure in vulnerable pediatric patients [4].

Ivabradine has emerged as a promising candidate in this context. This selective inhibitor of the cardiac pacemaker selective funny (I_f) current (hyperpolarization-activated cyclic nucleotide-gated [HCN] channels) was originally developed to slow sinus rates in chronic angina and heart failure [7]. Unlike nonselective AADs, ivabradine acts specifically on automaticity: it substantially slows pacemaker firing by inhibiting the I_f current, while exerting minimal effects on myocardial contractility or vascular tone. Ivabradine is generally considered hemodynamically neutral, producing heart rate reduction with minimal hypotension or negative inotropy compared with AADs like amiodarone [8]. This unique mechanism makes it an attractive therapy for automatic junctional tachyarrhythmias such as JET. Early clinical reports have accordingly documented successful use of ivabradine in pediatric JET after cardiac surgery, with conversion to sinus rhythm or effective rate control achieved even in refractory cases [7]. Notably, published case series and small studies generally describe few drug-related adverse events (AEs) with ivabradine. However, the evidence to date remains limited to single-center reports, small cohorts, and off-label experiences. However, the evidence to date remains limited to single-center reports, small cohorts, and off-label experiences [9]. No focused quantitative synthesis has yet evaluated ivabradine specifically for postoperative JET (in contrast to broader reviews that have combined congenital JET) to rigorously appraise its efficacy and safety in this setting.

In light of the above, we conducted a systematic review and meta-analysis to critically evaluate ivabradine for postoperative JET in children. By consolidating the available evidence across heterogeneous study designs, this work aims to provide the first comprehensive, evidence-based assessment of the therapeutic role of ivabradine in postoperative JET. Through this focused synthesis, our goal is to clarify whether ivabradine offers a real advance as a hemodynamically favorable antiarrhythmic in the management of JET after congenital heart surgery, and to inform both current practice and future research directions in pediatric cardiac electrophysiology.

Methods

This systematic review and single-arm meta-analysis was prospectively registered with PROSPERO (CRD420251080412) and conducted under the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement (Table S1) [10]. No protocol deviations occurred.

Database and literature search

We conducted a literature search in ScienceDirect, Europe PMC, ProQuest, Wiley Online Library, SAGE Journals, PubMed, EBSCOhost, Google Scholar, and the Cochrane Library from inception to 30 April 2025 without language restrictions. The PubMed strategy combined MeSH terms and free-text keywords for ivabradine and supraventricular tachycardias driven by automaticity (including JET). Postoperative status was applied at the screening stage (full strategies in Table S2). Reference lists of all eligible articles and relevant reviews were manually searched to identify additional studies. No previous publications on this specific topic were found.

Eligibility criteria

Studies were eligible when they (i) enrolled ≥ 5 children (< 18 years old) with postoperative JET uncomplicated by heart failure or cardiomyopathy; (ii) treated all participants with oral or nasogastric ivabradine, whether as monotherapy or in combination with other antiarrhythmic drugs; (iii) reported at least one prespecified outcome (conversion to sinus rhythm, time to conversion, bradycardia, hypotension, prolonged QT, any conduction block, need for concomitant antiarrhythmics, post-conversion arrhythmia recurrence, or all-cause mortality); and (iv) provided raw numerators/denominators or percentages from which exact event counts could be derived. Case reports, narrative reviews, editorials, commentaries, animal or in-vitro studies, and publications with overlapping patient cohorts were excluded.

Study selection and data extraction

Three reviewers (S.S.I., C.C., and J.E.G.) independently screened titles, abstracts, and full texts, removing duplicates with EndNote X9 (Clarivate Analytics, Philadelphia, USA). Disagreements were reconciled through discussion with senior authors (H.B., N.A.T., and A.H.). From each included study, reviewers uniformly captured the study design, setting, enrolment period, sample size, patient age and sex, tachycardia subtype, ivabradine dosage/regimen, concomitant therapy, follow-up duration, and all outcomes of interest. Continuous variables reported as medians with interquartile ranges were transformed to means and standard deviations using the Wan and Luo algorithms; authors were contacted once for clarification of ambiguous data [11, 12].

Risk of bias assessment

Risk of bias was assessed using study design–specific instruments, given the anticipated heterogeneity. RCTs were evaluated with Cochrane Risk of Bias 2.0, cohort and comparative non-randomized studies with ROBINS-I V2, and case series with the Methodological Quality and Synthesis of Case Series and Case Reports tool [13–15]. Three reviewers (S.S.I., J.B., and C.C.) assessed the risk of bias independently; unresolved discrepancies were adjudicated by senior authors (H.B., N.A.T., and A.H.).

Data synthesis and statistical analysis

All statistical work was computed in R v4.4.2 (R Foundation for Statistical Computing, Vienna, Austria) using the meta package (version 8.1–0) [16, 17]. A proportional meta-analysis was run for every binary endpoint. Study-level event rates (events/total) were first stabilized with the arcsine transformation and then combined with the inverse-variance method, as recommended by Schwarzer et al. [18]. Pooled proportions and their 95% confidence intervals were derived with the DerSimonian–Laird random-effects model, reflecting expected clinical and methodological diversity across studies. Statistical heterogeneity was examined with Cochran’s Q test (significance threshold p < 0.1) and quantified via the I² statistic; I² values exceeding 75% were taken to represent a high degree of heterogeneity [19]. Results are displayed in forest plots, showing individual study estimates, weights, and the overall pooled effect. Because all included data for ivabradine in postoperative JET were single‑arm or observational, the pooled proportions are intended as descriptive summaries of outcomes under ivabradine‑based management rather than as causal estimates of drug effect. In particular, the pooled conversion and recurrence proportions reflect regimens that frequently included concomitant AADs and supportive therapies. All inferential interpretation therefore considers these results to be hypothesis‑generating and primarily useful for informing the design and expected event rates of future controlled trials.

Sensitivity analysis and publication bias

We prespecified two sensitivity analyses: (i) excluding studies at serious/critical risk of bias; and (ii) restricting to studies in which ≤ 25% of participants received concomitant anti-arrhythmic drugs (proxy for predominantly ivabradine monotherapy). For outcomes with ≥ 10 studies, we planned meta-regression and small-study effects assessment (funnel plot and Egger’s test), with exploratory trim-and-fill if indicated [20, 21].

Results

Study selection and baseline characteristics

A total of 1089 records were identified through database searching: 280 from Science Direct, 206 from Europe PMC, 178 from ProQuest, 122 from Wiley, 104 from Sage Journals, 74 from PubMed, 66 from EBSCOHost, 56 from Google Scholar, and 3 from the Cochrane Library. Following the removal of 348 duplicate entries, the remaining 741 articles were screened by reviewing titles and abstracts. From initial screening, 64 articles were shortlisted for full-text evaluation. Following a detailed review, 5 studies met the eligibility criteria and were included in the final analysis, as illustrated in the PRISMA flowchart (Fig. 1) [7, 22–25].

Fig. 1.

PRISMA flow diagram of study selection [10]. Licensed under CC BY 4.0

The studies included in this analysis included 1 RCT, 2 retrospective cohorts, 1 prospective cohort, and 1 case series. Collectively, these studies involved a total of 87 patients diagnosed with postoperative JET. In Khan et al., the original series included 7 postoperative tachyarrhythmia cases (6 JET, 1 multifocal atrial tachycardia); only the 6 postoperative JET patients were included in this study [24]. As part of the therapeutic approach, the dose ranges from 0.05 mg/kg/dose to 0.1 mg/kg/dose given twice daily. Baseline characteristics are summarized in Table 1.

Table 1.

Characteristics of included studies

	Study	Year	Database	Follow up (months)†	N	Population	Age (months)†	Male (%)	ECG	Baseline HR (bpm)†	Ivabradine Dose (mg/kg per dose, schedule)	Time to Conversion (hours)†	Duration (days)	Previous Medication
1	Kamali	Oct 2024	Two pediatric cardiac surgery centers in Istanbul, Turkey (2022–2023	0.38 (0.1–3)	26	CHD: 100%	8 (0.2–36)	74	Postoperative JET	185 ± 12.62	0.1, q12 h	55.5 (6–168)	0.5–7	Dexmedetomidine
2	Arvind	Aug 2021	All India Institute of Medical Sciences, New Delhi, India (Aug 2018–Feb 2020)	0.36 (0.26–0.48)	48	CHD: 100%	33.5 (22.5–71)	75	Postoperative JET	185 ± 14.52	0.1, q12 h	24.8 ± 19.2	2.5–12	NA
3	Khan	Sep 2020	Wockhardt Hospital, Mumbai, India (Jun 2018–Aug 2019)	1	6*	CHD: 100%	19.2 ± 16.8	66.67	Postoperative JET	168–202	0.05, q12 h	8 ± 5.46	1–2	Amiodarone
4	Kumar	Nov 2019	Army Hospital Research and Referral, New Delhi, India (2017)	NA	5	CHD: 100%	8.8 ± 2.1	60	Postoperative JET	NA	0.05, q12 h	31.6 ± 13.6	NA	Amiodarone, esmolol
5	Krishna	Aug 2019	Amrita Institute of Medical Sciences, Kochi, India (Jun 2018 – May 2019)	NA	8	CHD: 100%	0.1–60	50	Postoperative JET	185 ± 12.46	0.05, q12 h	7.11 ± 4.34	2	Adrenaline, Milrinone, Dopamine, Amiodarone
	Summary¶				87			65.13

CHD Congenital Heart Disease, ECG Electrocardiogram, JET Junctional Ectopic Tachycardia, HR Heart Rate, NA Not Available

† Plus-minus values are means ± standard deviations; parentheses values are median (interquartile range: Q1–Q3)

* n = 7 (6 postoperative JET, 1 MAT); analysis restricted to the 6 postoperative JET patients

¶ Accounting for only the available data

Across the included studies, the pooled patient population had a mean age of 0.1–33.5 months, with males comprising 65.1% of the studies. Reported follow-up was short: medians 0.36–0.38 months in the two largest studies (74/87 participants) and 1 month in one study (6/87), with interquartile range (IQR) extending to 3 months in one cohort; two small cohorts (13/87) did not report duration. Geographically, the included studies were distributed across two countries: Turkey contributed 26 patients (28%) from 1 study, while the majority of patients were enrolled from studies conducted in India, comprising 67 patients (72%) across 4 studies. This distribution reflects a significant representation from South Asia in the current evidence base on ivabradine use for pediatric postoperative JET.

Risk of bias assessment

Using the Cochrane Risk of Bias 2.0 tool, the RCT by Arvind et al. was judged to be at low risk of bias across all five domains (Figure S1) [23]. The included non-randomized studies were assessed using the ROBINS-I V2 tool and generally showed moderate overall risk of bias (Figure S2). All three studies demonstrated consistent risk patterns across the seven domains. Kamali et al., Kumar et al., and Krishna et al. showed moderate risk of bias in domains related to confounding, deviations from intended interventions, and selection of reported results, primarily due to the observational nature of these studies and lack of adjustment for key confounders [7, 22, 25]. The consistent moderate risk in confounding domains across all studies reflects the inherent limitations of observational designs, where control for confounding variables and pre‑specified protocols are typically absent. However, all studies demonstrated low risk of bias in participant selection, classification of interventions, missing data, and measurement of outcomes, indicating well-defined interventions, complete outcome data, and objective ECG-based outcome measurements [7, 22–25].

The case series by Khan et al. demonstrated overall good methodological quality (Table S3). The case series appeared to represent the full experience at the reporting center, with clear selection and adequate ascertainment of both exposure and outcome. Alternative causes were ruled out, and follow-up was sufficient for outcomes to occur. However, the report did not include a challenge–rechallenge phenomenon, and the presence of a dose–response relationship was unclear. Despite these limitations, the case was described in sufficient detail to enable replication or application in clinical practice [24].

Pooled efficacy

Across five studies, the pooled conversion to sinus rhythm proportion with ivabradine-based therapy was 98.8% (95% CI 93.8–100; I² = 0%) (Fig. 2A). The mean time from initiation to stable sinus rhythm ranged from 7.1 to 55.5 h across studies. JET recurrence was uncommon: the pooled incidence was 3% (95% CI 0–12.1; I² = 34.9%) (Fig. 2B). Concomitant AAD use was reported in a pooled 48.3% of cases (95% CI 10.4–87.2; I² = 91.4%), reflecting practice variability (Fig. 2C). Thus, the pooled conversion and recurrence proportions describe outcomes under ivabradine-based multimodal regimens, in which almost half of patients also received concomitant AADs. No significant subgroup differences were observed between starting doses of 0.05 vs. 0.1 mg/kg every 12 h.

Fig. 2.

A Forest plot of conversion to sinus rhythm. B Forest plot of JET recurrence; C Forest plot of concomitant AADs

Pooled safety

Across all five studies, no ivabradine-attributed episodes of bradycardia, hypotension, QT-interval prolongation, or new/worsening AV block were reported. In Kamali et al., one patient presented with postoperative complete AV block alongside JET (not described as an ivabradine-related AEs) [22]. All-cause mortality was 2.1% (95% CI 0–10.1; I² = 30.5%) (Fig. 3) and was attributed to postoperative complications rather than to ivabradine. No significant subgroup differences were observed between 0.05 vs. 0.1 mg/kg every 12 h.

Fig. 3.

Forest plot of all-cause mortality

Sensitivity analysis

No study was rated at serious or critical risk of bias; therefore, only the prespecified sensitivity analysis restricting to studies in which ≤ 25% of participants received concomitant anti‑arrhythmic drugs (proxy for predominantly ivabradine monotherapy) was applicable (Table S4). Two studies met this criterion—Arvind et al. (4.2% with concomitant therapy) and Krishna et al. (25%)—yielding a pooled concomitant-therapy proportion of 9.4% (95% CI 0–37.2; I² = 67.6%) [23, 25]. Within this subset, sinus-rhythm conversion occurred in 98% of patients (95% CI 90.9–100; I² = 0%), the recurrence rate was 11.23% (95% CI 3.4–21.9; I² = 0%), and all-cause mortality was 10.5% (95% CI 0–34; I² = 56.9%). Consistent with the primary analysis, no ivabradine-attributed bradycardia (Figure S3), hypotension (Figure S4), QT-interval prolongation (Figure S5), or AV block were reported (Figure S6). Given only five studies were available, we did not assess publication bias or conduct meta-regression, as these procedures are underpowered and potentially misleading.

Discussion

This systematic review and single‑arm meta‑analysis indicates that ivabradine, used as part of multimodal postoperative management, was associated with a conversion to sinus rhythm proportion of 98.8% (95% CI 93.8–100) and a recurrence proportion of 3% (95% CI 0–12.1) after congenital heart surgery, with no ivabradine-attributed bradycardia, hypotension, QT prolongation, or new/worsening AV block reported across 5 studies (N = 87). These findings suggest that ivabradine may be a feasible and hemodynamically acceptable component of postoperative JET management, but they do not establish the independent efficacy of ivabradine given the observational designs and frequent cotreatment with other AADs.

Contemporary pediatric reviews describe postoperative JET care as multimodal—supportive measures (analgesia/sedation, correction of fever and electrolytes), cooling, temporary atrial pacing to restore AV synchrony, and intravenous AADs, most commonly amiodarone—with recognized risks (notably hypotension and conduction slowing) [4]. Against this backdrop, the only RCT to date showed oral ivabradine to be noninferior to intravenous amiodarone for conversion to sinus rhythm, with comparable time to conversion, more rapid early rate control with amiodarone, and no ivabradine-related AEs—findings consistent with our pooled estimates and safety profile [23]. The nonrandomized studies yielded high conversion proportions aligning with the pooled estimate (98.8%) and did not report hemodynamic AEs. A single-center cohort reported rate slowing with ivabradine that enabled overdrive atrial pacing and sustained control during the monitored postoperative course [25]. A small series of refractory cases reported conversion when ivabradine was added to amiodarone, without observed hemodynamic compromise [7]. A two-centre experience reported use of ivabradine as primary therapy in hemodynamically stable children and as an adjunct when instability was present [22]. Across these reports, the clinical profile aligns with our synthesis: ivabradine was associated with a high observed conversion to sinus rhythm, with no ivabradine-attributed hemodynamic compromise reported in the pooled sample (n = 87; all included patients).

In a postoperative JET cohort, intravenous sotalol and amiodarone achieved similar overall success, but sotalol lowered heart rate more rapidly within the first 90 min, which may be advantageous when early rate control is critical [26]. Beyond JET, a multicenter registry supports the feasibility and safety of intravenous sotalol for pediatric and congenital patients with tachyarrhythmias, further contextualizing practice choices when intravenous therapy is needed [27]. Evidence from congenital (non-postoperative) JET—a mechanistically related automatic tachycardia—also supports ivabradine’s efficacy and tolerability, either as adjunct to amiodarone or, in select reports, as monotherapy, which lends external coherence but does not substitute for postoperative-specific data.

The therapeutic effect of ivabradine in postoperative JET is mechanistically plausible given its unique action. JET arises from enhanced automaticity within the AV node or bundle of His, triggered by surgical trauma, mechanical stretch, ischemia–reperfusion injury, and circulating catecholamines [28]. This pathological automaticity involves dysregulated activation of HCN channels, particularly the HCN4 subtype, which generates the I_f channel responsible for pacemaker activity. Ivabradine’s profile aligns with this mechanism: selective inhibition of HCN-mediated I_f slows diastolic depolarization and pacemaker firing with limited effects on contractility or AV refractoriness relative to nonselective AADs [29, 30]. In children recovering from congenital heart surgery, often involving cardiopulmonary bypass, β-blockers or calcium-channel blockers can precipitate hypotension or heart block; this pharmacology is clinically relevant and consistent with the absence of reported hypotension in the included studies. Rate slowing may also facilitate atrial overdrive pacing once rates are reduced [31]. These mechanistic considerations are inferential and based on experimental and translational data on HCN channels and I_f channels; none of the included postoperative JET studies measured ion-channel expression directly.

Between-study variability likely reflected clinical heterogeneity in baseline patient and perioperative characteristics (age ranging from neonates to early childhood, varied surgical substrates, and concomitant inotrope/inodilator use), as well as methodological differences (study design and dosing regimens of 0.05–0.1 mg/kg per dose, twice daily). However, available data do not allow attribution of heterogeneity to pharmacologic inconsistency [7, 22–25]. Despite this, conversion proportions were consistently high, with time to conversion ranging from 7.1 to 55.5 h across studies; differences probably reflect illness severity, timing of initiation (early versus rescue), enteral administration, and use as monotherapy versus add-on. We prespecified tests for small-study effects only when ≥ 10 studies informed an outcome; thus, formal funnel-plot or Egger testing was not performed [20, 21]. In the subset with ≤ 25% concomitant therapy, point estimates for recurrence (11.23%) and mortality (10.5%) were higher with wide confidence intervals, consistent with sparse events and small denominators; qualitative conclusions were unchanged.

For infants and young children immediately post–congenital heart surgery, these exploratory data are consistent with ivabradine being a potentially hemodynamically favorable option that could be considered, alongside established measures such as cooling, pacing, and amiodarone, in centres with appropriate experience. Definitive positioning of ivabradine will require comparative trials to determine whether it should be used as first-line therapy in hemodynamically stable patients or as an adjunct when hypotension limits intravenous AADs. In the interim, practical, hypothesis-generating implications are that clinicians might: (i) consider weight-based enteral ivabradine after general measures when blood pressure limits intravenous AADs; (ii) use the initial rate-slowing to facilitate atrial overdrive pacing and restore AV synchrony, as reported in clinical series; and (iii) when very rapid early control is essential, use intravenous agents (amiodarone or sotalol) initially, with ivabradine added to sustain control while limiting further hemodynamic load [23, 25, 26]. Given that ivabradine is administered enterally, absorption may become unreliable once postoperative low cardiac output develops. Early initiation before hemodynamic compromise may therefore improve the likelihood of adequate absorption and timely rate control [4].

Generalizability is strongest to high-volume congenital programs similar to those represented (predominantly South Asia), where early postoperative JET is common and pacing access is routine. Most patients were infants/toddlers without overt ventricular dysfunction; extrapolation to older children, advanced HF, or prolonged postoperative courses should be cautious. Findings pertain to postoperative JET; while congenital JET shares an automaticity substrate, it is a distinct context with different natural history and treatment goals.

Key limitations of this review include the small number of studies and modest total sample size, which limit power to detect rare serious AEs. The analysis relied on aggregated study-level data without individual participant data, precluding uniform adjustment for important confounders such as vasoactive–inotropic scores and bypass times. Continuous outcomes were reported inconsistently (e.g., time to conversion), and follow-up was generally short, limiting inferences regarding relapse and late harms. Finally, the single-arm, aggregated design precludes isolating the independent effect of ivabradine from concomitant AADs, supportive measures, and the natural postoperative course of JET resolution. Given the small number of centres involved and the novelty of ivabradine use in this setting, it is also likely that successful or uncomplicated experiences are more frequently published than non-responses or AEs; our pooled estimates may therefore overestimate benefit and underestimate risk. Strengths include adherence to a prespecified protocol, a comprehensive search, use of design-appropriate risk-of-bias tools, and a focused clinical question restricted to postoperative JET—avoiding dilution with congenital JET cohorts.

Future research should therefore prioritize: (1) a pragmatic, multicenter RCT comparing ivabradine with amiodarone and intravenous sotalol under standardized co-interventions (cooling, pacing) and powered for clinically meaningful outcomes (time to sustained AV-synchronous rhythm, intensive care unit length-of-stay) to define independent efficacy and speed of control; (2) pediatric pharmacokinetic/pharmacodynamic studies to clarify optimal dosing (including loading strategies), enteral absorption in low-output states, and interactions with inotropes; (3) longer follow-up cohorts to quantify recurrence, late conduction effects, and rare AEs; (4) collaborative individual participant data meta-analyses to test effect modification by age, surgical substrate, inotropic exposure, and early use versus add-on, thereby informing patient selection and timing; and (5) mechanism-driven studies of ivabradine in other automaticity-mediated supraventricular tachyarrhythmias (e.g., focal atrial tachycardia, multifocal atrial tachycardia, [non-postoperative] congenital JET), including dose-finding and comparative-effectiveness work, to assess generalizability across automatic substrates.

Conclusion

In children with postoperative JET, ivabradine‑based regimens were associated with high observed conversion to sinus rhythm (98.8%, 95% CI 93.8–100) and low short‑term recurrence (3%, 95% CI 0–12.1), with time to conversion ranging from 7.1 to 55.5 h and no bradycardia, hypotension, QT‑interval prolongation, or AV block reported across five small studies (N = 87). Interpretation of these pooled proportions is constrained by predominantly nonrandomized designs, frequent concomitant AAD use (~ 48%), short follow‑up, and regional clustering of data, which prevent causal attribution to ivabradine alone and may inflate apparent success rates. In the sensitivity subset with ≤ 25% concomitant AADs use, point estimates for recurrence (11.2%) and mortality (10.5%) were higher and imprecise. Overall, ivabradine appears to be a promising candidate for further study as part of multimodal management of pediatric postoperative JET, particularly when hypotension limits intravenous antiarrhythmics; adequately powered multicentre randomized trials are needed to define its independent efficacy, optimal dosing, and longer‑term safety.

Abbreviations

AAD

Antiarrhythmic Drug

AADs

Antiarrhythmic Drugs

AEs

Adverse Events

AV

Atrioventricular

CHD

Congenital Heart Disease

ECG

Electrocardiogram

HCN

Hyperpolarization-activated Cyclic Nucleotide-gated

HR

Heart Rate

I_f

Funny Current (pacemaker current)

IQR

Interquartile range

JET

Junctional Ectopic Tachycardia

PRISMA

Preferred Reporting Items for Systematic Reviews and Meta-Analyses

RCT

Randomized controlled trial

Authors’ contributions

HB and SSI conceived the study idea and developed the research questions and protocol. SSI coordinated the project and was responsible for data curation, formal analysis, visualization, and overall methodology. JB, CC, and JEG performed the literature search, study selection, and data extraction. SSI, JB, CC, and JEG drafted the original version of the manuscript. HB, NAT, and AH provided supervision and revision of the manuscript. All authors contributed to manuscript review and editing, approved the final version, and agree to be accountable for all aspects of the work.

Funding

This research received no specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Data availability

The data that supports the findings of this study are available in the article and the supplementary material of this article.

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.