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Arrhythmias and sudden death
Original article
Incidence and prognostic significance of new onset atrial fibrillation/flutter in acute pericarditis
  1. Massimo Imazio1,
  2. George Lazaros2,
  3. Elisa Picardi3,
  4. Panagiotis Vasileiou2,
  5. Fabrizio Orlando1,
  6. Mara Carraro1,
  7. Dimitris Tsiachris2,
  8. Charalambos Vlachopoulos2,
  9. George Georgiopoulos2,
  10. Dimitrios Tousoulis2,
  11. Riccardo Belli1,
  12. Fiorenzo Gaita3
  1. 1Cardiology Department, Maria Vittoria Hospital, and Department of Public Health and Pediatrics, University of Torino, Torino, Italy
  2. 21st Department of Cardiology, University of Athens Medical School, Hippokration General Hospital, Athens, Greece
  3. 3University Division of Cardiology, Department of Medical Sciences, Città della Salute e della Scienza, University of Torino, Torino, Italy
  1. Correspondence to Massimo Imazio, MD, FESC, Cardiology Department, Maria Vittoria Hospital and Department of Public Health and Pediatrics, University of Torino, Torino, Italy. Via Luigi Cibrario 72, 10141 Torino, Italy, massimo_imazio{at}yahoo.it, massimo.imazio{at}unito.it

Abstract

Objective Data on the incidence of new onset atrial fibrillation and flutter (AF/f) in patients with acute pericarditis are limited. We sought to determine the incidence and prognostic significance of AF/f in this setting.

Methods Between January 2006 and June 2014, consecutive new cases of acute pericarditis were included in two urban referral centres for pericardial diseases. All new cases of AF/f defined as episodes lasting ≥30 s were recorded. Events considered during follow-up consisted of AF/f and pericarditis recurrence, cardiac tamponade, pericardial constriction and death.

Results 822 consecutive new cases of acute pericarditis (mean age 53±15 years, 444 men) were analysed. AF/f was detected in 35 patients (4.3%, mean age 66.5±11.3 years, 18 men). Patients with AF/f were significantly older (p=0.017) and presented more frequently with pericardial effusion (p<0.001). Arrhythmias developed within 24 h of pericarditis onset in 91.4% of cases, lasted >24 h in 25.7% and spontaneously converted in 74.3% of patients. Underlying structural heart disease was present in 17% of AF/f cases. In a 30-month follow-up, patients with history of AF/f at the initial episode had a higher rate of arrhythmia occurrence (34.3% vs 0.9%, p<0.001), mostly (75%) within 3 months. No other differences were detected in additional clinical events including haemorrhagic complications in patients receiving oral anticoagulation.

Conclusions The occurrence of AF/f in acute pericarditis identifies a predisposed population to AF/f with a high recurrence risk (about 35%): in these patients, pericarditis may act as an arrhythmic trigger and oral anticoagulation should be seriously considered according to guidelines.

https://doi.org/10.1136/heartjnl-2014-307398

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    Introduction

    Acute pericarditis is a common disorder with a reported incidence between 3.3 and 27.7 per 100 000 of the population per year, at least in the Western world.1 ,2 It accounts for approximately 0.1% of all hospital admissions and 0.2% of the cardiovascular ones in developed countries with a low prevalence of tuberculosis.2–5 The in-hospital mortality rate of acute pericarditis is estimated at 1.1% and prognosis is essentially determined by the underlying cause.2 ,4 ,6–8 Although arrhythmias are not exceptional in the setting of acute pericarditis, limited contemporary data is available on their incidence and prognostic impact both, in the short- and long-term.9 Among them, atrial fibrillation (AF) appears as the most frequently reported rhythm disturbance in the context of acute pericarditis.9–12 In a more recent paper, data on the prevalence, correlates and natural history of AF in patients with tuberculous pericarditis were reported from five hospitals in Cape Town (South Africa). AF was common (25% of cases at presentation) with most cases resolving in the first 2 weeks and no additional cases after 6 months of follow-up. LV dysfunction was associated with an increased risk of AF.9

    Thus, the aim of this investigation was to assess prospectively the incidence and prognostic role of AF/flutter (AF/f) in the specific context of acute pericarditis in European countries with a low prevalence of tuberculosis, with particular emphasis on the appearance of AF/f recurrences and embolic events during follow-up.

    Materials and methods

    Between January 2006 and June 2014, all consecutive cases with new onset acute pericarditis were recorded and studied prospectively in two referral centres for pericardial diseases (Maria Vittoria Hospital, Torino, Italy and, Hippokration General Hospital, University of Athens Medical School, Athens, Greece). Informed consent was obtained from each patient and the study protocol conforms to the ethical principles of the 2008 Declaration of Helsinki.

    A detailed medical history was obtained from all patients. All patients enrolled were inquired for a history of heart disease of any type (including coronary heart disease, heart failure, severe heart valve disease, cardiomyopathy, history of AF/f and other sustained arrhythmias) and stroke. Baseline features registered included: age, gender, C-reactive protein (CRP), troponin I, chronic kidney disease, thyroid dysfunction, ECG changes with emphasis on the presence of ST-segment elevation, presence and magnitude of pericardial effusion (the size was labelled as small if <10 mm, moderate if between 10 and 20 mm and large if >10 mm),4 fever, pericardial rubs, chest pain with features compatible with pericarditis, EF and left atrial dimensions. The inclusion of the above-mentioned features was based on their possible or established association with AF.13 The presence of arterial hypertension and diabetes mellitus was also evaluated in order to calculate the CHA2DS2-VASc score for each patient.13 We excluded patients with chronic AF defined as long-standing persistent (lasted for ≥1 year with a decision to adopt a rhythm control strategy) or permanent.14 Medications administered for acute pericarditis and management of AF were at the discretion of the attending physician according to international guidelines.14 ,15

    The diagnosis of acute pericarditis (new onset) was established in the presence of at least two of the following four criteria: pleuritic/pericarditic chest pain (typically worse on lying down and improved by leaning forward), pericardial friction rub, ECG changes (namely diffuse ST-segment elevation and/or PR depression) and new or worsening pericardial effusion.16–18 CRP elevation was considered a confirmatory parameter.19

    Pericarditis-related AF/f was defined as first diagnosed AF/f13 lasting ≥30 s either documented by electrocardiography or continuous ECG monitoring.13 ,20

    The clinical events considered during follow-up consisted of all-cause mortality, transient ischaemic attack (TIA)/stroke or any embolic event, recurrence of AF/f and recurrence of pericarditis. The criteria applied for the diagnosis of recurrent pericarditis relied on the presence of chest pain compatible with pericarditis along with one of the following: fever, pericardial rub, ECG changes and pericardial effusion similar to those described above for acute pericarditis, and an increase of CRP, erythrocyte sedimentation rate or white blood cell count.17

    Statistical analysis

    Data were expressed as mean±SD for continuous variables and as percentages for categorical variables. Comparisons between patient groups (patients with or without AF/f) were performed with the Mann–Whitney test for continuous variables and a χ2 analysis or Fisher exact test (as appropriate) for categorical variables. We performed a multivariable analysis to assess possible risk factors for AF/f in the setting of pericarditis including underlying possible risk factors for AF (such as age, gender, hypertension, presence of structural heart disease and LV dysfunction) or factors associated with the severity of pericarditis (fever, presence of effusion).

    Time-to-AF distribution was estimated by the Kaplan–Meier method. A probability value of <0.05 was considered to show statistical significance. Analyses were performed with the software package MedCalc Software V.14.8.1 (Acacialaan 22, 8400 Ostend, Belgium).

    Results

    During the study period, 822 new cases of acute pericarditis (mean age 53±15 years, 444 men) were recorded. Among them, 700 patients (85.2%) were diagnosed with viral or idiopathic pericarditis. Specific aetiologies were connective tissue diseases or pericardial injury syndrome in 58 cases (7.1%), neoplastic pericarditis in 41 cases (5.0%) and tuberculous pericarditis in 23 patients (2.8%).

    AF/f was detected in 35/822 patients (4.3%, mean age 66.5±11.3 years, 18 men). Among the latter arrhythmic events, 32 patients had AF (91.4%) and three patients had atrial flutter (8.6%). All patients were symptomatic.

    Baseline characteristics of the studied population with or without AF/f are reported in table 1. Patients with AF/f were significantly older as compared with their counterparts without arrhythmias (p=0.017). In addition, systemic arterial hypertension (p=0.002), dilated left atrium on echocardiography (p=0.019) and pericardial effusion (p<0.001) were more often present in the subgroup with arrhythmic events without, however, differences in the rates of large effusions. Apart from a trend for a higher incidence of fever (>38°C) in patients who developed AF (p=0.06), no difference was detected in other baseline features.

    View this table:
    Table 1

    Comparison of baseline characteristics of the studied population between patients with or without atrial fibrillation/flutter

    Concerning the specific characteristics of the 35 patients who developed AF/f in further details, only 3 (8.6%) had LV systolic dysfunction (defined as EF <55%), 6 had structural heart disease (17%), 20 had a history of arterial hypertension (57.1%), 2 had a past history of AF (5.7%) and 1 patient had a past history of stroke (2.9%). By definition, the two patients with a previous history of AF should not be considered as having a ‘new onset AF’. They have been included in the analysis as patients with a new episode of AF. The CHA2DS2-VASc score was 0 in 9 (25.7%) patients, 1 in 5 (14.3%), 2 in 4 (11.4%), 3 in 10 (28.6%), 4 in 3 (8.6%) and 5 in 4 (11.4%). The left atrial dimension was 39.1±5.2 mm. The great majority of patients had idiopathic pericarditis (33 out 35, 94.3%). On multivariable analysis no clinical factors were associated with the onset of AF/f including underlying risk factors for AF (such as age, gender, hypertension, presence of structural heart disease and LV dysfunction) or factors associated with the severity of pericarditis (eg, fever, presence of effusion).

    AF/f appeared within 24 h of symptoms onset in 32 patients (91.4%), lasted more than 24 h in nine of them (25.7%) and was transient in all cases. Spontaneous conversion to sinus rhythm was observed in 26 patients (74.3%), whereas pharmacological conversion was performed in 8 patients (22.8%) and electrical in 1 (2.8%). No other supraventricular arrhythmias were recorded in the studied population.

    Antiarrhythmic therapy was administered in 13 patients (37.1%) and anticoagulants in 13 (37.1%) according to current European Society of Cardiology (ESC) guidelines.14 ,15 These patients received a β-blocker and an ACE-inhibitor or sartan (if the ACE-inhibitor was contraindicated) as anti-hypertensive treatment. No haemorrhagic complications (either intrapericardial or systemic) were detected in patients receiving chronic anticoagulation. The treatment of pericarditis included aspirin or non-steroidal anti-inflammatory drugs in 15 patients (42.9%), corticosteroids in 11 patients (31.4%) and colchicine in 11 cases (31.4%). The therapeutic regimen for tuberculous pericarditis consisted of a four-drug regimen including: (1) isoniazid (300 mg orally once daily), (2) rifampicin (600 mg orally once daily; 10 mg/kg/day), (3) pyrazinamide (15–30 mg/kg/day up to 2 g/day given as a single dose and (4) ethambutol (15–25 mg/kg orally once daily). After daily therapy for 8 weeks, patients were switched to a daily two-drug regimen with isoniazid and rifampicin to complete a 6-month course of therapy.21

    After a mean follow-up of 30 months, patients with AF/f onset in the setting of acute pericarditis, had a greater risk of AF/f recurrence (34.3% vs 8.9%, p<0.001, table 2 and figure 1). The mean time to arrhythmia recurrence was 7.7±14.7 months and 9 out of 12 cases of recurrences (75%) occurred within 3 months. The possibility of recurrence according to pre-specified time intervals is reported in figure 2. In 9 out of 12 patients (75%) who exhibited an arrhythmic recurrence, the latter occurred in the setting of pericarditis recurrence. No difference was detected concerning the occurrence of recurrent pericarditis, cardiac tamponade or constrictive pericarditis in the long term (between patients with AF/f at first presentation and those without). Moreover, we did not record significant differences in the occurrence of further AF/f recurrences between patients with spontaneous sinus rhythm restoration or no spontaneous sinus rhythm restoration. Most importantly, no cases of TIA/stroke, peripheral embolism or deaths were recorded during follow-up.

    View this table:
    Table 2

    Adverse events after a mean follow-up of mean follow-up of 30 months

    Figure 1
    Figure 1

    AF/f recurrence free-survival. AF/f, atrial fibrillation/flutter.

    Figure 2
    Figure 2

    The time to recurrence of AF/f displayed as a box-and-whiskers plot with median and IQR (2.25 months, IQR 3 months). AF/f, atrial fibrillation/flutter.

    Discussion

    In this prospective cohort study, the incidence of AF/f in patients with a first episode of acute pericarditis and the long-term outcome was assessed. To the best of our knowledge this is the largest series published so far in this specific context and the first one to evaluate the long-term prognosis.

    The incidence to AF/f during a first episode of acute pericarditis was 4.3%, with AF being the most common arrhythmia. Patients with AF/f were older, and more commonly had a presentation with pericardial effusion. We also recorded a trend for higher temperature at presentation in such patients. AF/f was recorded within 24 h from symptoms onset in the great majority (>90%); it was transient in all cases and converted spontaneously to sinus rhythm within 24 in ∼75% of cases. No differences in the outcomes (eg, first or additional recurrences of AF/f) were recorded between those with spontaneous or pharmacological/electrical conversion.

    Structural heart disease was present in ∼17% of cases and a history of relevant arrhythmic events in the past was uncommon.

    Cardiac arrhythmias have been reported to occur during the acute phase of pericarditis.8 ,10 ,12 Although data relevant to their nature and incidence are sparse, AF appears as the most common sustained rhythm disturbance in this specific context.8 ,10–12 In relevant series the incidence of AF in acute pericarditis ranges between 6% and 25%.9–12 ,22–24 In the present study, the incidence of AF/f is lower than previously reported. The main reason for this divergence probably mainly lies on the adopted definitions of AF and also on the different aetiologies of pericarditis. For instance, in the study by Syed et al9 a higher incidence was reported (namely 25%) in the setting of tuberculous pericarditis. Actually, Spodick in his pioneering works on this topic defined AF as ‘six ectopic beats per minute or anything worse’.8 ,10 ,25 Moreover, adoption of general terms such as ‘supraventricular arrhythmias’ and their inclusion may interfere with the interpretation of the true incidence of AF/f in acute pericarditis. Interestingly, all arrhythmic events occurred exclusively in the presence of a concomitant underlying heart disease as in the experience of Spodick et al.25 In our study population, a substrate of structural heart disease was observed in 17% of AF/f cases.

    A potential link between AF/f and acute pericarditis may be ascribed to the vicinity of sinus node to the atrial surface, namely 1 mm. Thus, it is supposed that epicardial inflammation may extend to the sinus node. The above hypothesis has been supported by a necropsy study on 38 patients with pericarditis, where sinus node involvement has been confirmed in all cases.26 Accordingly, sinus node involvement in the inflammatory process of pericarditis may account for AF/f onset.11 Nevertheless, available data in this setting are not unanimous since sinus node was not clearly affected in another postmortem investigation and the relationship between sinus node involvement and AF/f is not well established.27

    Regarding the long-term impact of AF/f in acute pericarditis in a follow-up of 30 months, no differences were recorded concerning recurrent pericarditis, cardiac tamponade constrictive pericarditis and, most importantly, thromboembolic phenomena in patients with or without AF/f. On the contrary, a higher incidence of AF/f was observed in the group with AF/f during the episode of acute pericarditis. Recurrences in two-thirds of patients occurred simultaneously with pericarditis recurrences, mostly within 3 months.

    Generally the management strategy of patients exhibiting AF/f during acute pericarditis is empirical. Anticoagulation has been administered in approximately one-third of patients in this study according to available guidelines. It is reasonable that current recommendations on the use of anticoagulation should be applied also to this group of patients, since AF/f recurs in a high proportion of patients (ie, 34.3%) during follow-up, mostly but not exclusively during pericarditis recurrence. In this setting pericardial inflammation may be a trigger for the occurrence of the arrhythmia in predisposed individuals. In this study anticoagulated patients had no additional risk of intrapericardial haemorrhage.

    Limitations

    This study has potential limitations. Silent episodes of AF could have been missed. However, patients were encouraged to report cardiac rhythm abnormalities and/or palpitations. In the latter circumstance, Holter monitoring was scheduled to unveil subclinical AF/f episodes.

    Although widely applied, the selected cut-off of ≥30 s of AF duration is not based on solid data and in addition, to date it is uncertain whether shorter runs of AF are harmless. Moreover, a mean follow-up of 30 months may be too short to draw definitive conclusions and a longer follow-up would be desirable in order to understand the eventual arrhythmia progression and the risk of further arrhythmic events beyond the acute phase. Due to the limited number of patients with AF/f, the study may be underpowered to assess embolic events during the follow-up.

    Conclusions

    In this large-scale study the incidence of AF/f in the setting of acute pericarditis was 4.3%. The latter arrhythmias developed more frequently in older patients with pericardial effusion and fever. The management strategy of patients exhibiting AF/f during acute pericarditis is rather empirical. In our view, this study contributes to clarify the following points: (1) the occurrence of AF/f in acute pericarditis identifies a predisposed population to AF/f with a high recurrence risk (approximately 35%) and in these patients pericarditis seems an arrhythmic trigger and oral anticoagulation should be seriously considered according to guidelines recommendation; (2) anticoagulation is not associated with an increased risk of cardiac tamponade in the acute phase (anticoagulation has been administered in approximately one-third of patients, without complications); (3) an efficacious treatment of the first episode may prevent AF/f reappearance taking into consideration that most of AF/f recurrences coincided with pericarditis recurrences.

    Key messages

    • What is already known on this subject?

    • Limited data are available on the incidence and prognostic meaning of atrial fibrillation/flutter (AF/f) in the setting of acute pericarditis.

    • What might this study add?

    • In this large-scale study the incidence of AF/f in the setting of acute pericarditis was 4.3% and involved especially older patients with pericardial effusion and fever. In this study the occurrence of AF/f in acute pericarditis identified a predisposed population to AF/f with a high recurrence risk (about 35%), where pericarditis was an arrhythmic trigger. Anticoagulation was not associated with an increased risk of cardiac tamponade during follow-up.

    • How might this impact on clinical practice?

    • The occurrence of AF/f during pericarditis identified patients at higher risk of further recurrences. In this setting pericardial inflammation may be a trigger for the occurrence of the arrhythmia and oral anticoagulation should be seriously considered according to guidelines, taking into account that anticoagulated patients had no additional risk of intrapericardial haemorrhage.

    Acknowledgments

    The authors are grateful to Arcangela Pane for her technical assistance.

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    Footnotes

    • MI and GL contributed equally to this manuscript.

    • Contributors All authors contributed to the planning, conduct and reporting of the work. MI and GL drafted the manuscript that was revised and approved by all authors.

    • Funding The work was supported by institutional funding.

    • Competing interests None declared.

    • Patient consent Obtained.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data sharing statement All relevant data have been included in the paper.

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