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First published online on March 30, 2007
Chest, doi:10.1378/chest.06-2733
doi:10.1378/chest.06-2733
(Chest. 2007; 132:44-49)
© 2007 American College of Chest Physicians
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Transient Atrial Fibrillation Complicating Acute Inferior Myocardial Infarction*

Implications for Future Risk of Ischemic Stroke

Chung-Wah Siu, MBBS, MS; Man-Hong Jim, MBBS; Hee-Hwa Ho, MBBS; Raymond Miu, MBBS; Stephen W.L. Lee, MBBS; Chu-Pak Lau, MD, FCCP and Hung-Fat Tse, MD

* From the Cardiology Division, Department of Medicine, Queen Mary Hospital, Hong Kong, People’s Republic of China.

Correspondence to: Hung-Fat Tse, MD, Cardiology Division, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, People’s Republic of China; e-mail: hftse{at}hkucc.hku.hk

Abstract

Background: Atrial fibrillation (AF) that occurs as a frequent complication of myocardial infarction (MI) is associated with a poor clinical outcome. It nonetheless remains uncertain whether AF that occurs transiently during MI is associated with a subsequent increased risk of the development of AF and ischemic stroke.

Methods: We retrospectively studied the impact of transient AF on the long-term risk of the occurrence of AF, ischemic stroke, and mortality in 431 consecutive patients (mean [± SEM] age, 64 ± 1 years; 75% men). All patients had experienced an acute inferior ST-segment-elevation MI and had preserved left ventricular ejection fraction (LVEF) [> 45%].

Results: All patients were in sinus rhythm on hospital admission, and transient AF was observed in 59 patients (13.7%) during their hospitalization for MI. On hospital discharge, all patients were in sinus rhythm and had been prescribed antiplatelet agents alone as antithrombotic therapy. Patients in whom transient AF developed during MI were older (mean age, 70 ± 1.4 vs 64 ± 0.7 years, respectively; p < 0.01) and more likely to be women (37% vs 23%, respectively; p < 0.02) compared with those without AF. At 1-year follow-up, the incidence of AF (22.0% vs 1.3%, respectively; p < 0.01) and ischemic stroke (10.2% vs 1.8%, respectively; p < 0.01) was higher in patients with transient AF than in those without transient AF. The total mortality rate was nonetheless similar (5.6% vs 6.8%, respectively; p = 0.73); Cox regression analysis demonstrated that age > 65 years and transient AF during MI were independent predictors of the subsequent occurrence of AF and the development of ischemic stroke.

Conclusion: Transient AF complicating acute inferior MI is associated with an increased future risk of AF occurrence and ischemic stroke in patients with preserved LVEF, despite the use of antiplatelet therapy.

Key Words: atrial fibrillation • myocardial infarction • stroke

Transient atrial fibrillation (AF) occurs in up to 20% of patients during acute ST-segment-elevation myocardial infarction (MI), and is associated with an increased risk of early adverse events and in-hospital mortality.123 Data on the clinical outcome of patients in whom AF develops complicating acute MI are nonetheless scarce. Prior studies3 have suggested that patients with acute MI and AF have an increased risk of stroke compared with those without AF. Anticoagulation therapy is established to prevent thromboembolism in patients with AF,45678 but its role in patients with transient AF complicating acute MI remains unclear. In addition, the combination of an oral anticoagulant and antiplatelet agents may result in an excessive bleeding risk.910 Previous studies11 have revealed that only 30% of patients with AF after an acute MI are prescribed oral anticoagulation therapy.

Current clinical guidelines1213 for the use of oral anticoagulation therapy in patients with acute MI are likewise confusing. Oral anticoagulation therapy is recommended for patients with AF and impaired left ventricular ejection fraction (LVEF) following acute MI.1213 Nonetheless, data do not support the routine prescription of oral anticoagulation therapy to prevent thromboembolism in patients with transient AF and preserved LVEF following acute MI. The aim of this study was to investigate the clinical outcome of transient AF in a group of patients who had experienced acute inferior ST-segment-elevation MI and preserved LVEF.

Materials and Methods

Study Population
Clinical characteristics and long-term outcome were recorded in 504 consecutive patients who were admitted with acute inferior ST-segment-elevation MI to Queen Mary Hospital between 1997 and 2005. Demographic characteristics, symptoms, ECG, and functional status at presentation and clinical outcome during follow-up were retrospectively recorded. Clinical data were retrieved from the medical records and subsequently during the most recent clinic visit. Patients with preexisting or persistent AF (n = 5), in whom impaired LVEF of < 45% developed (n = 6), who died (n = 57), or who had missing clinical data (n = 5) were excluded from analysis. A total of 431 patients (324 male and 107 female) were included in this analysis.

Diagnosis and Clinical Outcome
Acute inferior ST-segment-elevation MI was diagnosed in the presence of typical chest pain lasting for ≥ 30 min, ST-segment elevation of ≥ 1 mm in any two of the inferior leads (ie, leads II, III, and aVF), and elevation in serum creatinine kinase or troponin T level of more than twice the upper limit of normal. All patients were monitored by telemetry ECG during the in-hospital period. Transient AF was defined as the occurrence of any new-onset AF that occurred during acute MI with subsequent spontaneous reversion to sinus rhythm prior to hospital discharge. All patients were in sinus rhythm on hospital discharge and were subsequently reviewed in our outpatient clinic every 3 to 4 months. The occurrence of AF, ischemic stroke, and cardiovascular mortality were retrieved from their hospital and outpatient medical records. Occurrence of AF was documented by a standard 12-lead ECG or Holter recording during outpatient follow-up or subsequent hospital admission. The occurrence of ischemic stroke was confirmed by axial CT scanning or MRI of the brain.

Statistical Analysis
Continuous variables are expressed as the mean ± SEM. Statistical comparisons were performed using the Student t test or the Fisher exact test, as appropriate. Hazard ratio (HR) and 95% confidence interval (CI) were calculated by univariate and multivariate Cox proportional hazards regression models. Multivariate analyses were performed with an enter regression model in which each variable with a p value of ≤ 0.1 (based on the univariate analysis) was entered into the model. Calculations were performed using a statistical software package (SPSS, version 12.0; SPSS; Chicago, IL). A p value of < 0.05 was considered to be statistically significant.

Results

Table 1 summarizes the clinical characteristics of the study population. During the acute episode of ST-segment-elevation inferior MI, transient AF developed in 59 patients (13.7%). These patients were significantly older and more likely to be female than those without AF (p < 0.05). There were, nonetheless, no significant differences between the two groups in the prevalence of hypertension, diabetes, hyperlipidemia, and smoking; the site and extent of MI; the use of reperfusion therapies for MI; or LVEF (p > 0.05 for all variables). On hospital discharge, all patients were prescribed aspirin, and none of those with AF were given oral anticoagulation therapy or an antiarrhythmic agent for the treatment of AF. There were no significant differences between patients with or without transient AF in the prescription of other cardiovascular medications such as clopidogrel, ß-adrenergic blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor antagonists, or statins (p > 0.05).


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  		Table 1.. Baseline Clinical Characteristics of Patients With or Without Transient AF*

 
As shown in Figure 1 , despite an increased use of primary coronary intervention after 2001 (2001 to 2005, 13.5%; 1997 to 2000, 0.5%; p < 0.05), there was no significant change in the incidence of transient AF complicating acute MI (2001 to 2005, 13.6%; 1997 to 2001, 13.8%; p > 0.05).


Figure 1
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  		Figure 1.. Secular trends of AF and the use of primary percutaneous coronary intervention in patients with acute inferior ST-segment-elevation MI during the period from 1997 to 2005.

 
Occurrence of AF
After a mean (± SEM) follow-up time of 38.5 ± 1.4 months, AF was diagnosed in 20 patients (34%) with transient AF compared with only 9 patients (2.4%) without transient AF (p < 0.01) [Fig 2 ]. In the majority of patients (93%), the occurrence of AF was paroxysmal in nature, and was observed within the first year following acute MI. The annual incidence of the occurrence of AF within the first year was 22% and 1.3%, respectively, in patients with or without transient AF (p < 0.01). Cox regression analysis revealed the presence of transient AF (HR, 13.4; 95% CI, 6.0 to 30.0; p < 0.01), and age > 65 years (HR, 3.3; 95% CI, 1.1 to 9.9; p < 0.04) to be independent predictors for the occurrence of AF following acute MI.


Figure 2
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  		Figure 2.. Kaplan-Meier curves for the unadjusted rate of occurrence of AF in patients with or without transient AF complicating acute inferior ST-segment-elevation MI.

 
Clinical Outcomes
Despite the use of antiplatelet agents, ischemic stroke developed in 13 patients (22%) with transient AF during follow-up compared with 15 patients (4%) without transient AF (p < 0.01) [Fig 3 ]. The annual incidence of ischemic stroke in patients with transient AF during the first and second year of follow-up was 10.2% and 7.5%, respectively, which are significantly higher than those observed during the first year of follow-up (1.8%) and the second year of follow-up (0.5%) in patients without transient AF (p < 0.01). In patients with transient AF, the majority of ischemic stroke (10 patients; 77%) occurred simultaneously with the recurrence of AF. In contrast, in patients without transient AF, only one ischemic stroke (7%) occurred simultaneously with the occurrence of AF (p < 0.01 [vs patients with transient AF]). In these patients, AF was documented when they presented with ischemic stroke. Cox regression analysis revealed the presence of transient AF (HR, 5.1; 95% CI, 2.4 to 11.2; p < 0.01), and age > 65 years (HR, 3.3; 95% CI, 1.2 to 9.2; p < 0.03) to be independent predictors for the occurrence of ischemic stroke following acute MI. A total of 62 patients died during the follow-up period, although the mortality rate did not differ between patients with transient AF (n = 8; 14%) or without transient AF (n = 54; 15%; p = 0.85) during acute MI.


Figure 3
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  		Figure 3.. Kaplan-Meier curves for the unadjusted rate of occurrence of ischemic stroke in patients with or without transient AF complicating acute ST-segment-elevation MI.

 
Discussion

The results of the present study demonstrate that the presence of transient AF during acute ST-segment-elevation inferior MI was associated with an increased risk for the subsequent development of AF and ischemic stroke. In this study, transient AF developed in approximately 14% of patients who had experienced acute ST-segment-elevation inferior MI. Within the first year of follow-up following an acute MI, there was a 15-fold increase in the risk of the occurrence of AF (approximately 22%) and a fivefold increase in the risk of the development of ischemic stroke (approximately 10%) in patients with transient AF compared with those without AF. More importantly, in those patients with transient AF during acute MI, most cases (77%) of ischemic stroke occurred simultaneously with the occurrence of AF. This finding suggests that the recurrence of AF contributes to the development of ischemic stroke in patients with transient AF during acute MI.

Prior studies123 have shown that new-onset AF after MI is associated with adverse short-term and long-term clinical outcomes. These studies nonetheless included heterogeneous patient populations, and patients in whom AF develops frequently have concomitant poor prognostic factors, such as anterior MI and cardiogenic shock associated with acute MI.2111415 It has been suggested that AF complicating acute MI may simply be an indicator of overall poor clinical status rather than an independent predictor of adverse clinical outcomes. In this study, the clinical implication of transient AF was investigated in a subgroup of patients with acute inferior ST-segment-elevation MI and preserved LVEF who had a favorable long-term prognosis after acute MI. In addition, the use of reperfusion therapy as the primary coronary intervention during acute MI did not appear to affect the incidence of transient AF. The acute hemodynamic changes related to acute MI are thus less likely to be the primary cause of transient AF in the present patient cohort compared with patients with impaired LVEF after MI. In this study, the high recurrence rate (34%) of AF during long-term follow-up in patients with transient AF after acute inferior MI was comparable with that observed in patients with paroxysmal AF.16 One plausible explanation is that there may be an underlying propensity for the development of AF in these patients that is triggered during acute MI.

During a mean follow-up period of 39 months, ischemic stroke developed in approximately 6% of patients while they were receiving therapy with antiplatelet agents. Furthermore, the annual risk of ischemic stroke was even higher (8 to 10%) in patients with transient AF during MI. This incidence is twofold to threefold higher than that seen in patients with AF and comparable risk factors,17 but is lower than the previous observed incidence of ischemic stroke (approximately 14%) in patients with persistent AF after ST-segment-elevation MI who were treated with antiplatelet agents alone.18 Although the latest American College of Cardiology/American Heart Association/European Society of Cardiology guidelines19 on AF consider coronary artery disease to be a "less validated or weaker" risk factor for stroke in patients with AF, patients with age > 75 years together with concomitant coronary artery disease are considered to be at "high risk" for stroke, according to UK National Institute for Health and Clinical Excellence guidelines.20 In this study, the presence of transient AF and age > 65 years in patients with acute MI were identified as independent predictors of ischemic stroke. This suggests that the presence of MI should be considered a moderate risk factor for stroke in patients with AF, and the use of antiplatelet agents alone may not provide adequate protection against thromboembolism.

Previous studies921 have shown that moderate-to-high-intensity anticoagulation therapy with warfarin to achieve an international normalized ratio (INR) of 3 to 4 provides vascular protection in patients with MI that is equivalent to that achieved with aspirin, and the concomitant use of aspirin is associated with an increased risk of bleeding. No conclusive data are available on the efficacy of moderate-intensity anticoagulation therapy (INR, 2 to 3), which is commonly used in patients with AF as a secondary prevention of MI.21 Thus, in patients with MI and AF, aspirin combined with moderate-intensity anticoagulation therapy (INR, 2 to 3) may be a preferable antithrombotic regimen, provided there are no contraindications.

The situation is more complicated in patients with AF who have undergone percutaneous coronary intervention during acute MI. Anticoagulation therapy with warfarin alone is associated with a high rate of adverse cardiac events in patients who undergo percutaneous coronary intervention with coronary stenting.22 There are very limited data on the optimal antithrombotic regimen for these patients. As a result, a wide variation in antithrombotic regimens has been observed in AF patients after percutaneous coronary intervention.23 The recent American College of Cardiology/American Heart Association/European Society of Cardiology guidelines19 on the management of AF state that low-dose aspirin and/or clopidogrel may be administered concurrently with anticoagulation therapy immediately after a coronary intervention. Such triple therapy appears to be safe and effective in the short term, provided that there is careful monitoring of the INR.10232425 Unfortunately, the prolonged use of triple therapy is associated with an increased risk of major bleeding.10 As a result, the combined use of warfarin and clopidogrel has been suggested as a long-term maintenance regimen, depending on the type of stent used, and the risk of recurrent myocardial ischemia and bleeding.1922 This strategy is nonetheless based on expert consensus rather than clinical evaluation. The clinical efficacy and risk of bleeding with warfarin and clopidogrel combination therapy remain unclear. Further studies are needed to determine the optimal use of oral anticoagulation therapy in combination with antiplatelet therapy in patients with AF complicating acute MI.

Footnotes

Abbreviations: AF = atrial fibrillation; CI = confidence interval; HR = hazard ratio; INR = international normalized ratio; LVEF = left ventricular ejection fraction; MI = myocardial infarction

Drs. Siu and Jim contributed equally to this study.

The authors have no real or perceived conflicts of interest or disclosures of any personal or financial support.

Received for publication November 17, 2006. Accepted for publication January 15, 2007.

References

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Coronary Artery Disease and Ischemic Stroke in Atrial Fibrillation
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Chest 2007 132: 8-10. [Full Text] [PDF]



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