Expert Review of Cardiovascular Therapy
ISSN: 1477-9072 (Print) 1744-8344 (Online) Journal homepage: http://www.tandfonline.com/loi/ierk20
Atrial fibrillation in young patients
Jean-Baptiste Gourraud, Paul Khairy, Sylvia Abadir, Rafik Tadros, Julia
Cadrin-Tourigny, Laurent Macle, Katia Dyrda, Blandine Mondesert, Marc
Dubuc, Peter G. Guerra, Bernard Thibault, Denis Roy, Mario Talajic & Lena
Rivard
To cite this article: Jean-Baptiste Gourraud, Paul Khairy, Sylvia Abadir, Rafik Tadros, Julia CadrinTourigny, Laurent Macle, Katia Dyrda, Blandine Mondesert, Marc Dubuc, Peter G. Guerra, Bernard
Thibault, Denis Roy, Mario Talajic & Lena Rivard (2018): Atrial fibrillation in young patients, Expert
Review of Cardiovascular Therapy, DOI: 10.1080/14779072.2018.1490644
To link to this article: https://doi.org/10.1080/14779072.2018.1490644
Accepted author version posted online: 18
Jun 2018.
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Publisher: Taylor & Francis
Journal: Expert Review of Cardiovascular Therapy
DOI: 10.1080/14779072.2018.1490644
Review
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Atrial fibrillation in young patients
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Jean-Baptiste Gourraud1, Paul Khairy1, 2, Sylvia Abadir2, Rafik Tadros1, Julia Cadrin-Tourigny1,
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Thibault1, Denis Roy1, Mario Talajic1 & Lena Rivard1
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Laurent Macle1, Katia Dyrda, Blandine Mondesert1, Marc Dubuc1, Peter G. Guerra1, Bernard
1 Electrophysiology Service, Montreal Heart Institute, Université de Montréal, Montreal
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Canada
Montreal Canada
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2 Department of Pediatric Cardiology, Sainte-Justine Hospital, Université de Montréal,
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Corresponding author:
Lena Rivard MD, MSc.
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Electrophysiology Service, Montreal Heart Institute, Université de Montréal, Montreal
Canada
Abstract
Introduction: Atrial fibrillation (AF) is the most frequent arrhythmia worldwide. While
mostly seen in elderly, it can also affect young adults (≤45 years of age), older adolescent
and children.
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Areas covered: The aim of this review is to provide an overview of the current management
of AF in young patients. Specific issues arise over diagnostic workup as well as
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antiarrhythmic and anticoagulation therapies. The future management and diagnostic
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strategies are also discussed.
Expert commentary: Management of AF in the young adult is largely extrapolated from
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adult studies and guidelines. In this population, AF could reveal a genetic pathology (e.g.
Brugada or Long QT syndrome) or be the initial presentation of a cardiomyopathy.
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pathology
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Therefore, thorough workup in the young population to eliminate potential malignant
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Key words: atrial fibrillation, children, pediatrics, genetics, management
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1. Introduction
Atrial fibrillation (AF) is the most common cardiac arrhythmia in the adult population,
with a projected number of affected patients in the United States exceeding 10 million by
2050 (1, 2). AF is associated with increased cardiovascular morbidity and mortality and
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appears to be associated with a worse prognostic outcome in patients diagnosed before 30
years of age (3, 4). Although AF predominantly afflicts elderly patients with structural heart
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disease (prevalence >10% after age 80), it can also occur in younger individuals (prevalence
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0.05% before age 30 (3–5). In this population, AF is frequently associated with congenital or
structural heart disease. Lone AF (i.e., without underlying cardiomyopathy) is rare (1–4) and
guided by studies performed in adults.
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its management remains unclear. In the absence of specific guidelines, its management is
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In this context, we discuss the current literature on clinical presentation, management
options and prognosis of lone AF in young patients. We also explore particular circumstances
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of diagnosis including genetic components, association with inherited ventricular arrhythmia
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and supraventricular tachycardia (SVT).
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2. Diagnosis
Presentation of AF is dependent on age and comorbidities. Beyond the variation in
prevalence, age has a strong influence on the type of the first AF episode. While paroxysmal
AF is the usual initial presentation in young patients, persistent AF (episodes lasting more
than 7 days or requiring cardioversion) and permanent AF (without restoration of sinus
rhythm) become predominant after 60 years of age (2, 6, 7). Mills et al. described 42
subjects below age 18 (median age 15.5 years, 83% male) with lone AF in the absence of
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congenital heart disease, perioperative state, thyroid disease or ventricular preexcitation.
The initial episode of AF was considered paroxysmal in >90%, with a median duration of 12
(IQR, 7-24) hours (8).
While 21% of the overall population and 40% of patients older than 80 years are
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asymptomatic, more than 95% of young patients present with symptoms (mostly
palpitations and atypical chest pain) at the time of diagnosis (7–9). In the study by Mills et
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al., palpitations and atypical chest pain were described in 85% and 26%, respectively of
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with a median duration of 6 (IQR, 1-12) months.
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symptomatic patients (8). Previous cardiac symptoms were described in 36% of patients,
3. Etiology and risk factors
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Lone AF in young patients remains a diagnosis of exclusion and should be preceded by
careful evaluation to rule out an early stage of cardiomyopathy. Workup should evaluate the
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presence of triggers, predisposing factors and inherited ventricular arrhythmia (Table 1).
3.1 Risk factors
Table 2 summarizes main known parameters associated with AF. Ceresnak et al.
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reported a 61% prevalence of obesity in 18 patients affected with lone AF (mean age 17.9
years, 83% male) (10). This association has been long described in studies of older adults,
with a 41% excess risk of AF that increases with body mass index (BMI) (11–13). Smith et al.
studied a population-based 36-year cohort study of 12,850 young men who had their BMI
measured at their examination for fitness for military service. After a median follow-up of 29
years, the adjusted HR of AF was 2.08 (95% CI 1.48 to 2.92) for overweight men (BMI 25.0 to
29.9 kg/m2) and 2.87 (95% CI 1.07 to 1.16) for obese men (BMI ≥30 kg/m2) compared to
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normal weight men (18.9 to 24.9 kg/m2) (14). In an animal model, sustained obesity results
in left atrial dilatation, interstitial atrial fibrosis and atrial electrical remodeling increasing the
vulnerability to AF (15). In the Framingham Heart Study, pericardial fat, intra thoracic fat and
abdominal visceral fat (assessed by computed tomography) were associated with AF (16).
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Furthermore, obesity has also been linked to systemic hypertension and obstructive sleep
apnea, two additional predisposing factors of AF (11). Although a direct relationship
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between these factors and AF has not been demonstrated, similar cardiovascular effects of
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hypertension, obstructive sleep apnea and obesity have been noted in children (below the
age of 18), suggesting a potential role in lone AF (17–19). Mah et al. studied 48 patients
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(aged ≤22 years) with lone AF and did not find any association between risk of AF recurrence
and left atrial dilatation (20).
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Excessive participation in endurance sports is a suspected predisposing factor for AF
(21, 22). Association with AF seems to increase after 1500 to 2000 lifetime hours of sports
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practice, suggesting a potential threshold effect (23, 24). Indeed, Andersen et al. described a
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U shaped association between exercise and AF in young patients (mean age 18.2 years) (24).
This reflects the increased risk of AF with a sedentary lifestyle associated with obesity as well
as with excess sports.
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Alcohol intoxication has long been associated with the occurrence of AF, particularly
with the practice of binge drinking (25). Several classes of drugs and stimulants could also
induce AF (26). In the same report, two additional patients had a history of bronchodilator
(albuterol) use at the onset of their AF episodes (8).
Identification of predisposing factors for AF could alter management and potentially
decrease recurrences (27). However, a recent study in the Framingham cohort concluded
that secondary AF also recurs after identification of predisposing factors, with similar long-
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term AF-related stroke and mortality risks (28). Careful follow-up is essential in young
patients given the long-term potential for recurrences and ramifications.
3.2 Familial atrial fibrillation
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Family history of AF has been reported in 5 to 30% of patients, especially in young
patients with lone AF (8). Relatives of an affected family member present with a 40%
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increased risk of arrhythmia occurrence (29, 30).
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Contribution of genetic testing has been disappointing since only rare genetic
variants were identified in a small number of patients (31–33). Few familial studies using
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linkage analysis have succeeded in identifying a genetic variant. Incomplete penetrance,
phenotype variability and a complex mode of inheritance could explain this complex
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heritability. Finally, rare genetic variations in 36 genes have been associated with AF (34).
Some mutations affect sodium and potassium currents (Ikr, Iks, Ik1, Ikur, IkATP, IkAch, Ikur, IAHP,
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If and INa), known to be involved in other inherited arrhythmias. Other mutations affect
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cellular electrical coupling, sodium homeostasis, transcription factors and the nuclear
envelope (35). However, rare variants in AF concern only a small fraction of patients. In
contrast, to account for the missing inheritability of rare variants, genome-wide association
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studies have identified a total of 15 common genetic variants (single nucleotide
polymorphism, SNP) linked to AF that could modify the phenotype and identify loci that have
been previously linked to cardiac conduction (34, 36). Considering this complex genetic
inheritance and the limited diagnostic and prognostic value, routine genetic testing is not
currently indicated for lone AF (27).
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3.2.1
3.2.2 J wave syndromes (Brugada and early repolarization syndrome)
In Brugada syndrome (BrS), supraventricular arrhythmias, predominantly AF, are
prevalent in 9 to 20% of patients (37–39). Andorin et al. identified a similar rate, 10%, of
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supraventricular arrhythmias in 106 children (median age 11 years) with BrS (40).
particular aspect of BrS in children is that AF can precede appearance of a BrS pattern on
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ECG (41). The association between AF and an early repolarization pattern has been
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demonstrated in several studies, particularly in young athletes (before age 30), but never in
children (42).
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The link between J wave syndromes and AF is not well understood. A proposed
pathophysiological mechanism postulates atrial vulnerability and increased dispersion of
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repolarization and refractoriness (43, 44). This hypothesis is supported by the KCNJ8-S422L
mutation that has been associated with lone AF, BrS and early repolarization syndrome (45–
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47). This mutation induces gain of function in ATP-sensitive potassium channel current
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leading to shortening of the atrial action potential duration and increased atrial vulnerability
(48).
As prognosis is poor in untreated patients, it is important to promptly identify BrS
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underlying apparently lone AF (Figure 1) (40, 49, 50). The use of sodium channel blocker
tests remain a matter of debate in children and a baseline ECG should be first performed
after cardioversion to rule out underlying BrS (51–54). With appropriate management, the
prognosis of BrS has improved in children (40, 49). While quinidine therapy may be of
interest in preventing ventricular and supraventricular arrhythmias, implantation of a
cardioverter-defibrillator should be considered in high-risk patients (40, 50, 55).
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3.2.3 Long QT syndrome
Atrial Fibrillation has been reported in 2 to 33% of patients with LQTS (56, 57). In a
study of 457 patients (mean age 23) with LQTS (predominantly LQT1), Johnson et al.
described that over 60% of patients experience their first episode of AF before the age of 18
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year, and before the occurrence of symptoms related to ventricular arrhythmias (56).
Further investigations demonstrated that the main genes (KCNQ1, KCNH2, SCN5A)
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associated with LQTS increase the risk of developing AF (58–62). Genetic modifiers in
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healthy patients and those with prolonged QT intervals have been associated with an
increased risk of early onset of initially presumed lone AF (63, 64). Thus, the same cardiac
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ion channel mutations can predispose to both lethal arrhythmias and atrial arrhythmias (65,
66).
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Because of an increased risk of lethal arrhythmias, antiarrhythmic drugs that prolong
action potential duration should be avoided (55). Kirchhof et al. demonstrated that LQT1
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patients presented with a prolonged atrial action potential and atrial effective refractory
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period (61). This prolongation of atrial action potential could lead to polymorphic atrial
tachyarrhythmias (“atrial torsade de pointes”) which appear on ECGs as AF with a longer
cycle length (61, 67, 68, Figure 2 ). In contrast, mexiletine may be effective in preventing AF
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recurrences without increasing the risk of torsade de pointes in LQT1 (69).
Once a diagnosis is established and treatment is initiated, life-threatening cardiac
events are uncommon in pediatric patients with LQTS (68). Baseline ECGs appear to be a
sufficient screening tool to detect LQTS in the pediatric population (70) and careful
examination of ECGs using the Bazett formula should be performed after initial detection of
AF (71).
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3.2.4 Short QT syndrome
In 2000, Gussak et al. reported the case of a 17 year-old girl with a QTc of 248 ms and
AF requiring repeated cardioversion (72) (Figure 3). The authors demonstrated similar ECG
changes in a 37- year-old patient who also experienced sudden cardiac death. In a recent
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report of children with SQTS (25 patients, mean age 15 years), Villafane et al. described
previous diagnoses of AF in 4 patients (73). The youngest patient with AF was 4 days old. In
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arrhythmias (2) during a median 5.9 years follow-up.
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this population, 8 patients initially experienced sudden cardiac death (6) or life-threatening
Both patients had mutations in KCNH2, KCNQ1 and KCNJ2, leading to a gain of
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function in potassium channel current that shortened the atrial action potential duration
death, and early-onset AF.
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and refractoriness (74–77). Patients with SQTS may present with syncope, sudden cardiac
Although no medical therapy appears effective and a cardioverter-defibrillator
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implantation is associated with a high incidence of inappropriate shocks, early identification
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of SQTS is required because of the high risk of sudden cardiac death (73, 78).
3.3 Cardiomyopathy
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Rheumatic fever and congenital heart disease are the leading causes of structural
heart disease and of AF in the young (79–82). Although heart failure is strongly associated
with AF, AF can also occur in the early stages of disease (83, 84).
Isolated diastolic
dysfunction is associated with an increased occurrence of AF, which could explain the 20%
prevalence of AF observed early in the course of hypertrophic cardiomyopathy (85–87).
However, structural abnormalities can be delayed with respect to occurrence of
arrhythmias. Supraventricular arrhythmias are prevalent in 36% of LMNA mutation carriers
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between the ages of 10-20 years (88). Genetic variants in the SCN5A gene have also been
associated with early onset AF (89–91). The association of both AF and conduction system
disease suggests the presence of either LMNA or SCN5A mutations even in the absence of
dilated cardiomyopathy (92, 93)(Figure 4). Although the clinical impact of these mutations
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remains controversial, an increased risk of sudden cardiac death has been reported (94, 95).
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3.4 Supraventricular tachycardia
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Several studies have emphasized the association between SVT and AF in young
patients(8, 10, 37, 96, 97). Rapid atrial activation during SVT may induce AF. Elimination of
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SVT, such as atrioventricular nodal re-entrant tachycardia (AVNRT) or atrioventricular reentrant tachycardia (AVRT), may prevent AF recurrence(98, 99).
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Wutzler et al. recently described a series of 124 patients (mean age 29 years) with AF
in whom a 57% prevalence of SVT was observed(97). Supraventricular tachycardia was
seen
in
patients
without
comorbidities.
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mostly
In
children
undergoing
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electrophysiological study after AF occurrence, the prevalence of SVT has been estimated to
be 30-39%(8, 10).
Atrial Fibrillation is of specific concern in Wolff-Parkinson-White (WPW) syndrome
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that manifests as ventricular preexcitation with palpitations suggestive of AVRT. Because of
the risk of ventricular fibrillation related to rapidly conducting anterograde accessory
pathways (Figure 5), patients with AF or short anterograde refractory periods (<250 ms)
should be offered catheter ablation (100, 101). Ventricular fibrillation is rare in patients with
WPW syndrome occurring in only 1.5 per 1000 patient/years of follow up whereas AF occurs
in more than one third of patients (102, 103).
In addition to SVT, other proposed
pathophysiological mechanisms to account for the high prevalence of AF in patients with
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WPW syndrome include atrial vulnerability, increased dispersion of repolarization and
refractoriness, and eccentric atrial activation due to retrograde conduction across the
accessory pathway (104–106).
Slow-pathway or accessory-pathway ablation has an impact on recurrent AF, with
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Sciarra et al. demonstrating a 7.7% recurrence rate in 257 patients (mean age 29 years) after
a 21-month follow-up, consistent with findings from Haïssaguerre et al. (98, 107). Pediatric
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cases reports further corroborate these findings and suggests that ablating SVT could reduce
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the need for pharmacological therapy and more extensive AF ablation procedures (8, 10, 96,
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97).
4 Management issues
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Management of AF involves two main aspects: symptoms and prevention of
thromboembolism. Although no specific data addressing this in the young are available,
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issues specific to a young population should be considered (27).
4.1 Acute management
The patient’s initial clinical status should determine the initial management.
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Hemodynamically unstable patients should receive prompt cardioversion (1–2 J/kg) (27).
Acute non-cardiac conditions associated with AF (e.g., hypertension, hyperthyroidism,
pulmonary embolism, viral infections, and sepsis) should be identified and treated. For
other patients, the decision to restore sinus rhythm or slow ventricular rate should be
individualized.
In hemodynamically stable patients, a rate control strategy can be initiated
depending on ventricular rate response and symptoms. When rapid rate control is required,
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intravenous administration of a beta-blocker (e.g., esmolol, propranolol, and metoprolol)
should be considered over a nondihydropyridine calcium channel blocker, amiodarone or
digoxin given the shorter time to effect.(108, 109). Intravenous amiodarone is generally
reserved for critically ill infants since it is associated with an increased rate of adverse events
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in this population (110). Because of a negative inotropic effect, intravenous
nondihydropyridine calcium channel blockers should not be used as first-line therapy for
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rate control (111).
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In patients with pre-excitation, intravenous medication (preferably class I AAD) or
electrical cardioversion should be considered in emergency situations. Because of the
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increased risk of ventricular fibrillation, amiodarone, beta blockers, calcium channel blockers
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and digoxin should be avoided in these cases (27).
4.2 Rate and rhythm control
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For rhythm control, preferential pharmacological agents are class IA (e.g.,
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procainamide), class IC drugs (e.g., flecainide and propafenone), and some class III
antiarrhythmic drugs (e.g., ibutilide and dofetilide) (27). There is a paucity of data regarding
safety and efficacy of class III AADs, such that their use in children should be limited. While
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amiodarone is the most effective AAD for the maintenance of sinus rhythm, it is less
effective for acute cardioversion (112).
Following the acute management phase, the objective of rhythm control is to prevent
symptomatic recurrences of AF. Large clinical studies have not revealed superiority of
rhythm control over a rate control strategy (113). However some evidence shows improved
quality of life when sinus rhythm can be maintained (114, 115). Benefits of AADs appear to
be offset by their adverse effects which include proarrhythmia for all but amiodarone,
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flecainide, propafenone and dronedarone, and increased mortality for quinidine,
disopyramide and sotalol (116). Current guidelines recommend beta blockers, propafenone
or flecainide as first-line therapy for lone AF (27).
In recent years, catheter ablation targeting pulmonary vein triggers is increasingly
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used for rhythm control (117,118) . In a recent study, Saguner et al. reported 85 young
adults (mean age 31±4 years; 69% men) who underwent pulmonary vein isolation for
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paroxysmal (N=52) or persistent AF (N=33). After a median follow-up of 4.6 years (IQR: 2.6-
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6.6) and a mean of 1.50±0.6 procedures, 84% patients remained in sinus rhythm. Structural
heart disease and obesity independently predict AF recurrence (119). In children, pulmonary
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vein ablation procedures have been successfully achieved with cryothermal and
radiofrequency energy (8, 120–123). There is no clear evidence of one approach being
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superior to the other (8, 120–123). In general, the efficacy of catheter ablations appears to
be higher in young patients, at the early stage of AF disease (124, 125). In 1548 consecutive
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patients who underwent 2038 AF ablation procedures. Leong Sit et al. compared major
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procedure complications and efficacy according to age in four groups : <45 years (group 1),
45 to 54 years (group 2), 55 to 64 years (group 3), and ≥65 years (group 4).
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antiarrhythmic drugs, 76% patients in group 1 were free of AF after a mean follow-up of 36
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months compared to 68 % (mean FU of 28 months), 65 % (mean FU 28 months) and 55%
(mean FU of 28 months) of patients in groups 2, 3 and 4, respectively (P<0.001) (125).
However, considering the risks involved, it appears reasonable to limit catheter ablations to
symptomatic children and young adults with recurrent AF (126). Additionally, while catheter
ablations may be appropriate in older adolescents, such procedures should be carefully
discussed in children because of the marked enlargement of lesions over time in immature
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hearts (127). Minimally invasive epicardial ablation has also been reported in a child with
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lone AF (128).
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4.3 Prevention of thromboembolism
Increased risk of stroke, morbidity and mortality associated with AF is well
established in adults (4, 27, 129, 130). Strokes resulting from AF are associated with
increased mortality and worse functional outcomes (131). Although age appears to be
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associated with more extensive AF-related strokes, young patients are also subject to poor
clinical outcomes (6, 132). In the pediatric multicenter Canadian study on lone AF,
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intracradiac thrombi were present in 5% of the population in whom one presented with a
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cerebral ischemic event (8).
Cardioversion for AF <48 hours in duration may be performed without prior
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anticoagulation in patients with a low risk of stroke (i.e., no valvular heart disease, no risk
factors for thromboembolism, rheumatic heart disease, or mechanical valves). If duration is
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>48 hours or unknown, or if risk factors for thromboembolism are present, anticoagulation
should be pursued for 3 weeks prior to cardioversion or, alternatively, transesophageal
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echography can be performed to rule out intracardiac thrombi (27). Whatever the context
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(i.e. low/high risk of thromboembolism, emergency/delayed cardioversion) and the
technique used (i.e. pharmacological or electrical cardioversion), at least 4 weeks of
anticoagulation is recommended following cardioversion (27). Although these guidelines
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address adults, the high prevalence of thrombus observed in children with lone AF is similar
to adults, suggesting that similar considerations are applicable to children in preventing
thromboembolic complications (8, 133, 134). Nuotio et al. showed that in patients with a
CHA2DS2-VASc [Congestive Heart failure, Hypertension, Age ≥75 (double), Diabetes, and prior
Stroke or TIA (double), Vascular disease, Age 65–74, and Sex (female ) < 2, stroke or TIA after
cardioversion occurred in up to 0.9% within 30 days after cardioversion if no anticoagulation
was administered after the procedure (135).
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The CHADS2 [Congestive Heart failure, Hypertension, Age ≥75, Diabetes, and prior
Stroke or TIA (double)] or CHA2DS2-VASc risk scores)] is recommended to guide long-term
anticoagulation decisions (27, 136). Based on large observational studies, the threshold to
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initiate OAC has been lowered in patients older than 65 years of age and men with a
CHA2DS2-VASc score of 1 and a score of 2 for women (27, 137). This threshold could even be
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reduced further with the safer profile of NOACs. While no such score has been validated in
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children, studies in populations with congenital heart disease suggest that these scores are
low in young populations and insensitive to guide thromboprophylactic therapy (8, 138).
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Subclinical stroke appears to occur early in the clinical course of AF, even with a CHADS2
score of 0-1 (139). The benefits of anticoagulant therapy for subclinical stroke and silent
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cerebral ischemia have yet to be assessed. Pending the results of studies such as the BRAINAF trial (ClinicalTrials.gov NCT02387229), no thromboprophylaxis is recommended for young
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patients without risk factors for stroke.
5. Conclusion
Despite its scarcity, diagnosis of lone AF in young patients is essential considering
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that associated morbidity and mortality may be substantially reduced with appropriate
therapy. As symptoms are usually non-specific, diagnosis remains a challenge and often
requires repeat or long-term ECG monitoring.
Lone AF typically presents in association with SVT during adolescence. However,
inherited arrhythmias and cardiomyopathy should always be investigated. Lone AF remains
a diagnosis of exclusion. Identification of associated diseases considerably alters prognosis
and therapy. The management of lone AF is largely individualized and guided by the adult
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literature. While rhythm control with AADs appears reasonable in patients with growing
myocardium, catheter ablation may be an alternative for symptomatic older adolescents.
Many questions remain unresolved, including accurate estimations of thromboembolic risk
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in children.
6. Expert commentary
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Atrial fibrillation (AF) is a common arrhythmia in older adults but, in the absence of
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structural heart disease is rare in pediatric, teenagers and young adult patients. Prevalence
of AF has been estimated to 0.05% in patients younger than 30 years of age compared to
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10% in patients older than 80. A family history of AF is more often present in young patients.
Genetic testing has been disappointing and is not done in clinical practice. Management of
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AF in this younger population is largely extrapolated from adult studies and guidelines but is
associated with the need of a specific workup. Indeed, the workup should rule out the
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presence of a genetic pathology, a re-entrant tachycardia (atrioventricular nodal reentrant
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tachycardia or atrioventricular reentrant tachycardia) or predisposing factors such as
obesity, alcohol or drug use or strenuous exercise. Obesity has also been linked to sleep
apnea, diabetes and hypertension in this young population. Long-term practice of strenuous
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endurance exercise (cycling, cross country skiing or marathon running) has been associated
with an increased risk of paroxysmal AF in otherwise healthy young adults. Sport reduction
or abstinence have shown a reduction in AF episodes.
Furthermore, in this young population, AF could reveal a genetic disease with direct
consequences on AF management and medication since the use of antiarrhythmic class I in
Brugada syndrome and the use of antiarrhythmic class III in Long QT syndrome could trigger
malignant ventricular arrhythmias. Other genetic diseases like short QT and anterior
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repolarization syndrome have also been associated with an increased risk of AF (present in
up to 30% of patients). Atrial fibrillation could also be the initial presentation of a
cardiomyopathy, in particular laminopathy. A long-term follow-up is recommended.
However, younger patients tend to be more symptomatic and less-willing to take
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long-term medication. An electrophysiological study could be useful to rule-out a reentrant
tachycardia which can trigger AF and for which ablation could reduce the risk of AF
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recurrence. In young adults, AF catheter ablation is associated with a lower complication
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rate, shorter hospitalizations and a higher success rate when compared to older patients. As
in the older patients, the CHA2DS2-VASc [Congestive Heart failure, Hypertension, Age ≥75
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(double), Diabetes, and prior Stroke or TIA (double), Vascular disease, Age 65–74, and Sex
(female) and stroke or TIA(double)] is used to stratify stroke risk and in the absence of other
factor
(i.e.,
hypertension,
diabetes,
stroke
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risk
or
TIA
or
vascular
disease)
thromboprophylaxis is not recommended for young patients with lone AF. But in children,
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teenager and young adults, stroke is associated to a poorer clinical outcome when compared
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to older patients. If AF lasts longer than 48 hours, transoesophageal echography or 4-weeks
of anticoagulation therapy is recommended prior to cardioversion with anticoagulation
continuing for 4 weeks following the cardioversion.
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AF remains rare in young patients and lone AF remains a diagnosis of exclusion.
Usual AF guidelines apply. In the future, controlled randomized trials and large registry data
are much needed to develop specific guidelines in this young AF population.
7. Five-year view
Genetic testing should be done in clinical practice to help differentiate lone AF,
channelopathy or cardiomyopathy. Antiarrhythmic therapy should be personalized. Atrial
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ablation should be done as first-line therapy and anticoagulation therapy should be initiated
at a younger age.
Key issues
Lone atrial fibrillation is rare in subjects younger than 30 years and an
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•
underlying cause should be ruled out.
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Patients with Long QT, Short QT and Brugada syndrome are at a higher risk of
developing AF.
•
Ablation of atrial fibrillation appears to be effective in this population with a
an
one-year success rate > 70%.
Atrial fibrillation could be induced by SVT. SVT ablation decreases the risk of
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AF recurrence.
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Funding
This paper was not funded.
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Declaration of interest
L Rivard is the principal Investigator of the BRAIN AF trial (ClinicalTrials.gov NCT02387229)
cr
and received salary support from the Fonds de Santé en recherche du Québec (FRSQ). This
us
research did not receive any specific grant. The authors have no other relevant affiliations
an
or financial involvement with any organization or entity with a financial interest in or
financial conflict with the subject matter or materials discussed in the manuscript apart from
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relationships to disclose.
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those disclosed. Peer reviewers on this manuscript have no relevant financial or other
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123. Balaji S, Kron J, Stecker EC. Catheter ablation of recurrent lone atrial fibrillation in
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2016;39:60–4
124. Leong-Sit P, Zado E, Callans DJ, et al. Efficacy and risk of atrial fibrillation ablation before
45 years of age. Circ Arrhythm Electrophysiol 2010;3:452–457.* This study shows that, in
patients younger than 45 years, catheter ablation is associated with a lower major
complication rate and a comparable efficacy rate of AF .
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126. Wasmer K, Breithardt G, Eckardt L. The young patient with asymptomatic atrial
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29
Table 1 Initial specific evaluation in young adults presenting with AF
Evaluation:
To identify:
•
•
•
ECG
•
TTE
ip
t
To rule out cardiomyopathy
Left atrial size
Pre-excitation syndrome
LQT: QTc during recovery phase ≥
460 ms
ed
Exercise testing
•
•
•
•
•
Reeentrant tachycardia
Electrophysiological
study
Blood test
•
To identify a predisposing
arrhythmia such as AVNRT or AVRT
Thyroid, renal and hepatic function
ce
pt
Holter monitoring
•
(29, 34)
cr
Family history
us
•
•
•
(11-16, 25)
(43, 55-57)
an
•
Symptoms
Precipitating factors: alcohol use,
drugs
Predisposing factors resumed in
Table 2 (obesity, exercise ..)
Familial atrial fibrillation
Genetic disease
Familial history of syncope,
drowning, sudden cardiac death
Pre-excitation syndrome
Long QT, Short QT
Repolarization anomalies (anterior
repolarization syndrome, Brugada
syndrome or others)
Response to antiarrhythmic therapy
M
History and physical
exam
•
•
References
(140)
(101)
(101)
Ac
TTE for transthoracic echography, AVNRT for atrioventricular nodal reentrant tachycardia
and AVRT for atrioventricular reentrant tachycardia.
30
Table 2 Known predisposing factors for AF
2.1
2.2
Hypertension
1.5
1.4
Diabetes mellitus
1.4
1.6
1.07
Obstructive sleep apnea
3.29
1.1
Exercise
3.1
1.6
ed
Alcohol use
1.4
M
Smoking
an
Obesity (per kg/m2)
1.6
1.2
ce
pt
Hyperthyroidism
Increased pulse pressure
Myocardial infarction
1.4
1.2
Valvular heart disease
1.8
3.4
Heart failure
4.5
5.9
European ancestry
Family history
Ac
Ventricular diastolic
dysfunction, left atrial
dilatation
Ventricular diastolic
dysfunction, left atrial
dilatation
Atrial and cellular
remodelling
Left atrial dilatation,
hypertension
Hypoxemia, hypertension,
ventricular diastolic
dysfunction
Left atrial and cellular
remodelling
Left atrial dilatation,
increasing vagal tone
Ventricular diastolic
dysfunction, vagal tone
Cellular remodelling
Atrial remodelling
Ventricular diastolic
dysfunction, atrial
remodelling
Atrial remodelling
Atrial remodelling and
overload
Genetic variant
Genetic variant
us
Increasing age (per 10
years)
Supposed mechanisms
1.13
1.4
References
(141)
ip
t
Relative risk
men
women
(141)
cr
Clinical Risk Factors
(141)
(11)
(11)
(142)
(23)
(25)
(143)
(144)
(141)
(141)
(141)
(145)
(29, 146)
31
Figure legends:
Figure 1: ECG of patient affected with BrS and AF
(25 mm/s; 10 mm/mV)
Figure 2: Polymorphic atrial tachyarrhythmia associated with LQTS.
ip
t
ECG (25 mm/s; 10 mm/mV) was recorded in a 21-year-old man previously diagnosed with
LQT1 after syncope. Note the particular aspect of AF which appears quite organised. It is
permission (67).
us
cr
also known as a polymorphic atrial tachyarrhythmia. Modified from Kirchof et al. with
Figure 3: ECG of a 17-year-old man presenting both paroxysmal AF and SQTS.
an
Modified from Villafane et al. with permission (73)
(25 mm/s; 10 mm/mV)
M
Figure 4: ECG of a 19-year-old man presenting with LMNA mutation.
He presented with AF at 11 years of age and suffered aborted sudden cardiac death at the
ed
age of 19 years. Conduction disturbance associated with AF led to detection of mutations in
ce
pt
SCN5A and LMNA genes.
(25 mm/s; 10 mm/mV)
Figure 5: ECG of a patient presenting with WPW syndrome and AF
Ac
(25 mm/s; 10 mm/mV)
32
ip
t
cr
Ac
ce
pt
ed
M
an
us
Figure 1
Figure 2
33
ed
ce
pt
Ac
ip
t
cr
us
an
M
Figure 3
34
ed
ce
pt
Ac
Figure 4
35
ip
t
cr
us
an
M
ed
ce
pt
Ac
ip
t
cr
us
an
M
Figure 5
36