Authors: Allon Raphael, Hazar Asad, Moshe Rav-Acha, Oholi Tovia-Brodie, Yoav Michowitz, Ziv Dadon, Yechiel Schlesinger, Amiram Nir
Categories: Original Article, arrhythmia, bradycardia, bronchiolitis, RSV, sinus arrest
Source: Journal of Pediatrics: Clinical Practice
Authors: Allon Raphael, Hazar Asad, Moshe Rav-Acha, Oholi Tovia-Brodie, Yoav Michowitz, Ziv Dadon, Yechiel Schlesinger, Amiram Nir
Bronchiolitis is a major cause of respiratory illness in infants. Few studies have demonstrated arrhythmias during bronchiolitis, including bradycardia and atrioventricular block, some requiring pacemaker implantation. However, the association between bronchiolitis and cardiac arrhythmias remains unclear. In this work we sought to investigate the incidence and characteristics of arrhythmias during bronchiolitis in infants younger than 1 year of age.
A single-center, prospective cohort study was conducted on infants hospitalized with a clinical diagnosis of bronchiolitis. Demographic and clinical data were collected via questionnaire. All infants underwent overnight Holter monitoring during hospitalization.
Among 100 enrolled infants (79% positive for respiratory syncytial virus), 18 (18%) demonstrated sinus arrest (2-13 seconds) in 8 infants, bradycardia <60 bpm in 7 infants, and frequent atrial premature complexes (3%-18% of beats) in 3 infants. Follow-up Holter recordings in 7 patients (38%) showed resolution of arrhythmias within 1-4 months. No significant demographic or clinical predictors were identified. None of the infants exhibited symptoms (eg, cyanosis, unresponsiveness) associated with arrhythmia severity.
Our study shows that bronchiolitis is associated with significant arrhythmias in infants, particularly sinus arrest, bradycardia, and atrial premature complexes. In our cohort, none of the infants with significant arrhythmia required arrhythmia intervention. Clinicians should be aware of this association and consider delaying decisions regarding pacemaker implantation until after the resolution of bronchiolitis even in cases of infants with severe bradycardia. Future investigations should explore the pathophysiology and prognostic implications of this phenomenon.
What is KnownBronchiolitis is the leading cause of respiratory illness and hospitalization in infants under one year of age. While it is often associated with apnea, some studies and case reports have also documented cardiac arrhythmias during the acute phase of the illness.What is NewThis study identifies a significant association between bronchiolitis and significant arrhythmias, including sinus arrest, sinus bradycardia, and atrial premature complexes.Bronchiolitis is a leading cause of respiratory illness in infants and may be complicated by aрոeа, with respiratory syncytial virus (RSV) as the primary etiologic agent. Bronchiolitis is a major cause of respiratory illness in infants. RSV is the most common cause of bronchiolitis in children younger than 1 year of age^1^ and is estimated to contribute to mortality in up to 2% ոеоոаtеs younger than 28 days of age and 7% of infants aged 28-364 days.^2^ Canadian data suggest that 20% of RSV-related deaths occur in infants without known risk factors.^3^ Apnea is a recognized complication, particularly in infants born premature and those younger than 2 months of age.^4^ Although no direct causal link has been established between bronchiolitis and sudden infant death syndrome (SIDS), overlapping features such as seasonality and RSV detection in SIDS cases have been reported.^5^^,^^6^
Although several case reports and small studies have documented cardiac manifestations during bronchiolitis, the association between bronchiolitis and cardiac arrhythmia remains poorly understood. The first report of RSV-associated complete atrioventricular block in a child was published in 1974.^7^ Several subsequent reports describing atrioventricular block, with or without evidence of myocardial damage, have appeared in the medical literature,7, 8, 9, 10, 11, 12 as summarized by Oulego-Erroz et al.^13^ Of these cases, 4 underwent pacemaker implantation7, 8, 9, 10 and 2 were treated with medications.11, 12, 13 We previously reported 2 healthy infants diagnosed with several episodes of symptomatic sinus arrest at the time of bronchiolitis. All episodes, except one, resolved spontaneously. On one occasion, chest compressions were necessary. For both infants, the rhythm pathology disappeared with resolution of the viral infection.^14^
A 1995 prospective study reported bradycardia as the main presenting sign in 75% of 47 infants who tested positive for RSV (<80 bpm in infants born preterm, <60 bpm in infants born at term).^15^ Another prospective study, in 2010, found sinoatrial (SA) block in 76.5% of infants who tested positive for RSV, with 14.7% of cases lasting longer than 2 seconds.^16^
Despite these findings, the pathophysiology and risk factors for arrhythmia during bronchiolitis remain unclear. We therefore conducted a prospective study to characterize arrhythmia in infants younger than 1 year hospitalized with bronchiolitis.
A single-center, prospective cohort study was conducted in infants younger than 1 year of age who were hospitalized with clinical diagnosis of bronchiolitis and who required oxygen therapy. The diagnosis of bronchiolitis was made clinically by a certified pediatrician on the basis of history and physical examination.^17^ Infants were enrolled over 2 consecutive winter seasons (2022-2023 and 2023-2024). During this period, 629 infants were hospitalized with bronchiolitis. Although parental consent rates were high, enrollment was limited to 100 infants because of the availability of Holter monitors and staffing, which was restricted to regular workdays. Infants with known congenital heart disease were excluded. This study was approved by the institutional review board of Sa'are Zedek Medical center in Jerusalem (SZMC-0228-22). Waivers were obtained from the SZMC Helsinki Committee regarding consent to participate and consent for publication.
After we obtained informed consent, caregivers completed a demographic and clinical questionnaire. Clinical data, including treatments and oxygen requirements, were extracted from medical records.
All enrolled infants underwent 24-hour Holter monitoring (Lifecard CF; Spacelabs Healthcare) during hospitalization. All Holter recordings were reviewed by a pediatric cardiac electrophysiologist, and all findings were subsequently verified by a second, independent pediatric electrophysiologist to ensure diagnostic accuracy. We interpreted our Holter data using the reference limits for healthy pediatric populations for the relevant age group.^18^^,^^19^ Significant arrhythmias were defined as bradycardia down to a heart rate <60 bpm,^18^^,^^19^ sinus arrest of 2 seconds or longer, or atrial premature beats (APBs) of more than 3%.^19^ Sinus arrythmia was not defined as significant arrhythmia. Sinus pause (longer than 3 seconds) and sinus arrest were defined as sinus arrest.^20^ SA block, including sinus arrest, was defined by the 2018 guidelines as evidence that blocked conduction between the sinus node and adjacent atrial tissue.^20^ All infants with significant arrhythmias were called for a second 24-hour Holter monitoring, and a follow-up telephone call was conducted more than 2 years after discharge to assess for the presence of subsequent cardiac symptoms or related clinical events.
Continuous variables are presented as mean and 95% CIs. Categorical variables are reported as frequencies and percentages. Between-group comparisons were conducted using the Student t test, Mann-Whitney U test, or χ^2^ test as appropriate. A P value ≤ .05 was considered statistically significant. Analyses were performed using IBM SPSS Statistics for Windows, Version 23.0 (IBM Corp).
A total of 100 infants were enrolled in the study. Remarkable arrhythmia was observed in 18 (18%) infants. The cohort was divided into 2 those with normal Holter findings and those with remarkable arrhythmia. Demographic characteristics are presented in Table I.Table IDemographic, prenatal, and family medical history of study populationCharacteristicsArrythmias, n = 18No arrythmias, n = 82All patients, n = 100 (%)P valueAge, months, mean [SD]2.5 [3.2]3.6 [3.6]3.4 [3.5].29∗Gender, No. (%) Male10 (56)46 (56)56 (56).96† Female8 (47)36 (44)44 (44)Pregnancy and birth, No. (%) Prenatal US screening12 (70)58 (67)70 (70).73† Fetal echo4 (22)17 (21)21 (21).87† Birth week [IQR]38.1 [37.1-39.2]38.4 [37.8-38.9]38.3 [37-38].85∗ AGA15 (83)60 (72)76 (76).78† SGA2 (11)16 (20)17 (17) LGA1 (5)7 (8)7 (7)Oxygen treatment after birth2 (11)14 (17)16 (16).53† Phototherapy3 (16)8 (9)11 (11).39† RSV vaccine0 (0)5 (6)5 (5).28†Family history, No. (%) Number of siblings2.5 (1.7-5.2)3 (2-5)3 [2-5].35‡ SIDS0 (0)2 (2.4)2 (2).5† Cardiac history2 (11)6 (7)8 (8).59† AD or asthma4 (22)30 (36)34 (34).24†AD, atopic dermatitis; AGA, appropriate for gestational age; LGA, large for gestational age; SGA, small for gestational age.Demographic, prenatal, and family medical history of study population are shown. Patients are grouped by Holter findings (normal vs significant arrhythmia). P < .05 considered significant.∗Independent t test.†χ^2^ test.‡Mann-Whitney U test.
The mean age of the cohort was 3.4 months, with no significant age difference between groups (P = .29). Male patients comprised 56% of the cohort. Pre- and postnatal history, including prenatal ultrasound, echocardiogram, gestational age, and birth weight, are presented in Table I, with no significant differences found between the arrhythmia and nonarrhythmia groups.
Five infants received the RSV vaccine before their diagnosis. None of these infants developed cardiac arrhythmia, although this finding was not statistically significant (P = .28). Eight infants had a family history of cardiac disease, and 2 had a family history of SIDS; neither variable was significantly associated with arrhythmia (P = .50 and P = .59, respectively).
Virological testing, clinical symptoms, and treatment details are summarized in Table II. RSV was detected in 79% of infants, adenovirus in 18%, and both viruses in 10%. None of the infants with remarkable arrhythmia tested positive for both viruses, although the difference was not statistically significant (P = .11).Table IIVirologic and clinical characteristics of current illnessCharacteristicsArrythmias, n = 18No arrythmias, n = 82All patients, n = 100P valuePositive virus PCR panel, No. (%)15 (83)72 (87)87 (87) RSV13 (72)65 (79)78 (78).57 Adenovirus2 (11)16 (19)18 (18).51∗ RSV and Adenovirus0 (0)10 (12.8)10 (10).4∗ Influenza A0 (0)1 (1)1 (1).11∗Clinical characteristics Fever10 (55)59 (72)69 (69).17∗ Day of fever [IQR]3.5 [1.7-5.7]3 [2-5]3 [2-5].61† Day of cough5 [4-7]4 [3-6]4.6 [3-6].07†Symptoms Cyanosis3 (16)18 (22)21 (21).17∗ Unresponsive4 (22)13 (16)17 (17).61† Apathy8 (44)30 (36)38 (38).07†Treatment Ventolin5 (28)36 (44)41 (41).2∗ Systemic steroids5 (28)29 (35)34 (34).5∗ Caffeine3 (16)3 (4)6 (6).03∗Maximum oxygen treatment NC <1 L2 (11)23 (28)25 (25).13∗ NC >1 L4 (22)23 (28)27 (27).61∗ HFNC <40%5 (27)15 (18)20 (20).36∗ HFNC >40%7 (39)21 (25)28 (28).25∗HFNC, high-flow nasal canula; NC, nasal canula; PCR, polymerase chain reaction.Comparison between infants with and without significant arrhythmias.P < .05 considered significant.∗χ^2^ test.†Mann-Whitney U test.
Holter monitoring was performed at a similar interval from fever onset in both groups (mean 3 days, P = .61) but occurred 1 day later on average from the onset of cough in the arrhythmia group (5 vs 4 days, P = .007). Symptoms such as cyanosis, unresponsiveness, and apathy occurred in both groups without statistically significant differences (P = .61, .51, and .53, respectively). Before Holter monitoring, 41% of infants received salbutamol, and 34% received systemic steroids, with no significant association with arrhythmia (P = .20 and P = .50). No significant differences in illness severity, as assessed by maximal oxygen requirement, were observed between groups.
Table III summarizes the arrhythmias observed in the 18 infants with abnormal Holter findings. Sinus arrest ranging from 2 to 13 seconds were recorded in 8 infants. Of these, 5 had 4-5 episodes, 1 had 10 episodes, and 2 had 24 episodes during Holter monitoring. Three infants underwent follow-up Holter in one case, sinus arrest resolved after 3 months; in the other 2, they resolved after 1 month. At telephone follow-up, all infants except one were reported to be healthy and asymptomatic. One infant, who presented on the initial Holter with sinus arrest of 3.5 seconds followed by subsequent normal Holer, experienced a single cyanotic episode triggered by crying, which was clinically diagnosed as a breath-holding spell.Table IIISummary of Holter-detected arrhythmias and follow-up in affected infants (n = 18)PatientsGenderAge, monthVirusHolter summaryFollow-upType1F10Adeno5 episodes of sinus arrest 3.1-13 secondsIn 1 and 2 months with pauses. third Holter normalSinus pauses2M1RSV5 episodes of sinus arrest max 3.5 secondsOne month later normal BHS after 18 mo3F2RSV5 episodes of sinus arrest max 3.23 seconds4F1RSV4 episodes of sinus arrest from 1.9 to 2.36 secondsOne month later normal5F2RSV24 arrest max 2.4 and sinus bradycardia to 35 (13 beats) junctional rhythm (5 beats up to 40 bpm)6M1RSV4 episodes of sinus arrest max 2.4 seconds7M5Neg24 episodes of sinus arrest max 2.3 seconds8M0.5RSV10 episodes of sinus arrest with junctional escape max 1.92 seconds9M1RSVOccasional junctional rhythmOne month normalBradycardia10M2RSVOccasional sinus bradycardia11F5NegTwo episodes of sinus bradycardia12M1RSV17 episodes of junctional rhythmOne month normal13F1RSVOne episode of sinus bradycardia14F3RSVFrequent sinus bradycardia, occasional APBs (some with aberrant conduction)15F1RSVTwo episodes of ventricular escape16F0.5AdenoFrequent APBs (18%) with aberrant conductionIn 1 month with improvement and 4 months normalFrequent APBs17M11NegFrequent APBs (3%) and blocked APBsIn 1 and 6 months normal18M0.5RSVFrequent APBs (3%)BHS, breath-holding spell; F, female; M, male.
Seven infants experienced episodes of bradycardia with heart rates less than 60 bpm. Two of these had normal follow-up Holter recordings after 1 month and all were reported to be asymptomatic at the 2 years’ follow-up. Three infants exhibited frequent APBs, accounting of 3%-18% of all beats. In 2 of these cases, follow-up Holter testing showed resolution within 1-4 months and all remained symptom-free at the 2 years’ telephone follow-up.
In this prospective study, 18% of infants hospitalized with bronchiolitis requiring oxygen therapy demonstrated remarkable arrhythmias. These included sinuses arrest in 8, sinus bradycardia in 7%, and frequent APBs in 3%. Notably, none of the infants with identified significant arrhythmias by Holter required pacemaker implantation or other arrhythmia interventions.
Although bronchiolitis is a well-known condition in infancy, its cardiac manifestations are less commonly described. Our findings are consistent with previous literature. Esposito et al reported sinoatrial block lasting more than 2 seconds in 14.7% of infants with RSV bronchiolitis.^16^ Similarly, Forster and Schumacher identified bradycardia as a presenting symptom in 75% of infants in a neonatal intensive care unit who tested positive for RSV.^15^ Case reports have also described symptomatic arrhythmias, including high-grade AV block, sinus arrest during bronchiolitis,12, 13, 14 and even in association with SIDS,^6^ possibly representing the severe end of a broader phenomenon.
In our own previous report, 2 otherwise-healthy infants developed sinus arrest during bronchiolitis, one of whom required chest compressions. In both cases, the arrhythmias resolved as the illness subsided.
The present study expands upon these findings by providing systematic Holter monitoring data. As in the study by Esposito et al, where most infants had multiple episodes of SA block that resolved within a month, we observed spontaneous resolution of arrhythmias in infants with follow-up (38% with follow-up Holter) and confirmed long-term clinical stability up to 2 years by telephone follow-up for the remaining patients, with no reported cardiac symptoms except one breath-holding spell.^16^ These findings are clinically although some infants met theoretical criteria for pacemaker implantation, expectant management seems to be safe.
Although earlier reports linked arrhythmias specifically to RSV, we observed similar phenomena with non-RSV viruses as well. This suggests that the arrhythmogenic potential may not be virus specific. One possible mechanism of the bradyarrhythmia is heightened vagal tone during bronchiolitis, which may contribute to both bradyarrhythmia and apnea. This hypothesis aligns with the work of Schroeder et al, who reported apnea in 5% of infants with bronchiolitis, although heart rate data during these episodes were not available and the direct efferent vagal response causing sinus node dysfunction is still an unproven hypothesis that requires further mechanistic study.^4^
Despite comprehensive data collection, we did not identify any clinical or demographic predictors of arrhythmia. Variables such as age, sex, family history, clinical symptoms, and viral etiology were not associated with arrhythmia. This underscores the need for future research to identify the underlying mechanisms and improve risk stratification.
This study has several limitations. Although this is the largest prospective Holter study to date on the topic, the sample size was restricted by logistical constraints, including a limited number of Holter machines and the inability to initiate monitoring on weekends or holidays, and as a result, the number of arrhythmia cases was modest (n = 18) and Holter monitoring was only 24 hours; therefore, the time courses of both occurrence and resolution are unknown. In addition, our cohort was limited to hospitalized infants requiring oxygen and may not reflect the broader outpatient population. The rate of follow-up Holter studies was low and completed in only 38% of affected infants; however, none of the others reported clinical events in the 2 years that followed.
Cardiac arrhythmias, including sinus arrest and bradycardia, were observed in 18% of infants hospitalized with bronchiolitis. In all cases with follow-up, the arrhythmias resolved spontaneously without the need for pacemaker implantation or long-term therapy. No demographic or clinical predictors were identified. These findings support a cautious, observational approach when managing arrhythmias in the context of bronchiolitis and argue against premature interventions in the absence of persistent symptoms. Further studies including larger studies and longer monitoring are warranted to clarify the underlying mechanisms, prognosis, and optimal monitoring strategies for affected infants.
Allon Raphael: Writing – original draft, Visualization, Validation, Resources, Project administration, Methodology, Investigation, Funding acquisition, Formal analysis, Data curation, Conceptualization. Hazar Asad: Methodology, Investigation, Data curation, Conceptualization. Moshe Rav-Acha: Validation, Supervision. Oholi Tovia-Brodie: Validation. Yoav Michowitz: Validation. Ziv Dadon: Writing – review & editing, Validation. Yechiel Schlesinger: Validation, Supervision, Resources. Amiram Nir: Writing – review & editing, Validation, Supervision, Conceptualization.
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.