Downloaded from http://heart.bmj.com/ on July 11, 2017 - Published by group.bmj.com
Coronary artery disease
ORIGINAL ARTICLE
All types of atrial fibrillation in the setting of myocardial infarction are associated with impaired outcome Gorav Batra,1 Bodil Svennblad,1 Claes Held,1 Tomas Jernberg,2 Per Johanson,3 Lars Wallentin,1 Jonas Oldgren1 ▸ Additional material is published online only. To view please visit the journal online (http://dx.doi.org/10.1136/ heartjnl-2015-308678). 1
Uppsala Clinical Research Center and Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden 2 Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden 3 Sahlgrenska Academy, University of Gothenburg and AstraZeneca, Gothenburg, Sweden Correspondence to Dr Gorav Batra, Uppsala Clinical Research Center and Department of Medical Sciences, Cardiology, Uppsala University, Uppsala Science Park, MTC, Dag Hammarskjölds väg 14B, Uppsala 752 37, Sweden; [email protected] Received 15 September 2015 Revised 6 January 2016 Accepted 18 January 2016 Published Online First 29 February 2016
ABSTRACT Objectives To evaluate 90-day cardiovascular outcome in patients after myocardial infarction (MI) in relation to different subtypes of atrial fibrillation (AF) and MI. Methods We studied 155 071 hospital survivors of MI between 2000 and 2009 in Swedish registries. AF subtypes were defined according to history of AF and inhospital ECG recordings. Clinical outcomes were evaluated with multivariable Cox models. Results AF was documented in 24 023 (15.5%) cases. The AF subtypes were new-onset AF with sinus rhythm at discharge (3.7%), new-onset AF with AF at discharge (3.9%), paroxysmal AF (4.9%) and chronic AF (3.0%). The event rate per 100 person-years for the composite cardiovascular outcome (all-cause mortality, MI or ischaemic stroke) was 90.9 in patients with any type of AF versus 45.2 in patients with sinus rhythm, adjusted hazard ratio with 95% CI (HR) 1.28 (1.19 to 1.37). There were no significant differences in the composite cardiovascular outcome between AF subtypes. AF was associated with higher risk of mortality, HR 1.59 (1.41 to 1.80), reinfarction, HR 1.14 (1.05 to 1.24), and ischaemic stroke, HR 2.29 (1.92 to 2.74), respectively. In subgroup analysis, AF was associated with a higher risk of composite cardiovascular outcome in the non-STelevation myocardial infarction (NSTEMI) and STelevation myocardial infarction (STEMI) cohort, HR 1.24 (1.13 to 1.36) and HR 1.34 (1.21 to 1.48), respectively, with p value for interaction=0.23. Conclusions AF is common in the setting of MI and is associated with a higher risk of composite cardiovascular outcome and the individual components; mortality, reinfarction and ischaemic stroke, respectively. No major difference in outcome was observed between AF subtypes. No difference in outcome for AF was observed between the NSTEMI and STEMI cohort.
INTRODUCTION
To cite: Batra G, Svennblad B, Held C, et al. Heart 2016;102:926–933. 926
Atrial fibrillation (AF) is the most frequently sustained arrhythmia with an increasing incidence due to ageing population.1 AF is a common finding in the setting of myocardial infarction (MI) with the incidence reported to vary between 6% and 21%.2 Previous studies have shown that the occurrence of AF in the setting of MI is associated with an increased risk of mortality and ischaemic stroke.3–7 However, there is limited knowledge on the occurrence and the outcome associated with different subtypes of AF in the setting of MI, which is of importance when estimating prognosis of
individual patients. In addition, there is limited knowledge regarding the association between AF and the subtype classification of MI into non-ST-elevation myocardial infarction (NSTEMI) and ST-elevation myocardial infarction (STEMI). We aimed to study the occurrence of different subtypes of AF in the setting of MI and the association with 90-day all-cause mortality, MI or ischaemic stroke. We also evaluated outcome in AF patients with NSTEMI and STEMI.
METHODS This is a retrospective observational study including all consecutive Swedish patients admitted due to MI in all 72 coronary care units between January 2000 and December 2009. All patients admitted to coronary care units in Sweden are reported in the Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies register (SWEDEHEART). Key patient characteristics on admission and variables registered during the hospital stay and at discharge are recorded. The quality of data has been monitored yearly with results showing a 96.1% agreement between the data entered in the registry and the patient records.8 Data about mortality were obtained by data linking the SWEDEHEART registry with the Swedish Cause of Death Registry. Information about readmission and history of diabetes mellitus, hypertension, ischaemic stroke, chronic obstructive pulmonary disease, congestive heart failure, MI, peripheral vascular disease, renal disease, liver disease, bleeding events, dementia and cancer, based on the International Classification of Diseases, 10th revision, were obtained by data linking SWEDEHEART with the National Patient Registry (NPR); see online supplementary tables S1–S4. The Swedish Cause of Death Registry includes data on mortality in Sweden from 1961 and the NPR includes diagnoses on all patients hospitalised in Sweden from 1987 and forward. These registries are part of the Swedish National Board of Health and have been shown to have high validity.9 10 Data linkage of these registries with SWEDEHEART was approved and performed by the National Board of Health and Welfare using the unique civic registration number of each Swedish citizen. Diagnosis of AF was based on physician interpretation of ECG on arrival and at discharge.
Batra G, et al. Heart 2016;102:926–933. doi:10.1136/heartjnl-2015-308678
Downloaded from http://heart.bmj.com/ on July 11, 2017 - Published by group.bmj.com
Coronary artery disease Data on previous diagnosis of AF, preceding the current hospital admission, were collected in the NPR. Patients were categorised into four groups: new-onset AF with sinus rhythm at discharge; new-onset AF with AF at discharge; paroxysmal AF and chronic AF. New-onset AF with sinus rhythm at discharge was defined as no medical history of AF according to NPR with AF on arrival ECG but sinus rhythm on discharge ECG. New-onset AF with AF at discharge was defined as no medical history of AF in NPR with AF on the discharge ECG, regardless of arrival ECG. Paroxysmal AF was recorded in cases with a known medical history of AF, but with sinus rhythm on either the arrival or discharge ECG. Chronic AF was documented in patients with a history of AF and with AF on both the arrival and discharge ECG. The primary end point was a composite cardiovascular outcome including all-cause mortality, MI or ischaemic stroke within 90 days from discharge. Results were also analysed for the following individual outcomes within 90 days from discharge; all-cause mortality, MI and ischaemic stroke, respectively. Patients were censored for death when analysing the individual outcomes; MI or ischaemic stroke. No other censoring scheme was applied. Outcome definitions are presented in online supplementary table S4.
Statistics Descriptive statistics for baseline characteristics are presented in a tabular format with continuous variables as a median with interquartile range (IQR) and categorical variables as percentages. Kaplan–Meier estimates were reported to illustrate outcome according to subtype classification of AF. Unadjusted and adjusted Cox regression analyses were calculated to identify the relation between occurrence of AF and outcome. In the adjusted Cox-regression analysis, clinical relevant variables included in the CHA2DS2-VASc scoring system11 were individually accounted for and included the following: congestive heart failure, hypertension, age, diabetes mellitus, prior ischaemic stroke, transient ischaemic attack and systemic embolism, vascular disease, gender, and also admission year, hospital (as a γ distributed random frailty effect), in-hospital revascularisation, anticoagulants and antiplatelets at discharge. Continuous variables entered the models as cubic splines to allow for violation of the linearity assumption. Due to enrichment of data from the NPR, no data were missing when adjusting for differences in baseline characteristics. Diagnostics for the proportional hazards assumption was done using Schoenfeld residuals with no significant violations of the assumption observed. Finally, a subgroup analysis was performed on the 69 919 patients undergoing percutaneous coronary intervention (PCI) to assess the association between different subtypes of AF and outcomes in this population. Results were stated statistically significant for a two-sided p value
Coronary artery disease
ORIGINAL ARTICLE
All types of atrial fibrillation in the setting of myocardial infarction are associated with impaired outcome Gorav Batra,1 Bodil Svennblad,1 Claes Held,1 Tomas Jernberg,2 Per Johanson,3 Lars Wallentin,1 Jonas Oldgren1 ▸ Additional material is published online only. To view please visit the journal online (http://dx.doi.org/10.1136/ heartjnl-2015-308678). 1
Uppsala Clinical Research Center and Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden 2 Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden 3 Sahlgrenska Academy, University of Gothenburg and AstraZeneca, Gothenburg, Sweden Correspondence to Dr Gorav Batra, Uppsala Clinical Research Center and Department of Medical Sciences, Cardiology, Uppsala University, Uppsala Science Park, MTC, Dag Hammarskjölds väg 14B, Uppsala 752 37, Sweden; [email protected] Received 15 September 2015 Revised 6 January 2016 Accepted 18 January 2016 Published Online First 29 February 2016
ABSTRACT Objectives To evaluate 90-day cardiovascular outcome in patients after myocardial infarction (MI) in relation to different subtypes of atrial fibrillation (AF) and MI. Methods We studied 155 071 hospital survivors of MI between 2000 and 2009 in Swedish registries. AF subtypes were defined according to history of AF and inhospital ECG recordings. Clinical outcomes were evaluated with multivariable Cox models. Results AF was documented in 24 023 (15.5%) cases. The AF subtypes were new-onset AF with sinus rhythm at discharge (3.7%), new-onset AF with AF at discharge (3.9%), paroxysmal AF (4.9%) and chronic AF (3.0%). The event rate per 100 person-years for the composite cardiovascular outcome (all-cause mortality, MI or ischaemic stroke) was 90.9 in patients with any type of AF versus 45.2 in patients with sinus rhythm, adjusted hazard ratio with 95% CI (HR) 1.28 (1.19 to 1.37). There were no significant differences in the composite cardiovascular outcome between AF subtypes. AF was associated with higher risk of mortality, HR 1.59 (1.41 to 1.80), reinfarction, HR 1.14 (1.05 to 1.24), and ischaemic stroke, HR 2.29 (1.92 to 2.74), respectively. In subgroup analysis, AF was associated with a higher risk of composite cardiovascular outcome in the non-STelevation myocardial infarction (NSTEMI) and STelevation myocardial infarction (STEMI) cohort, HR 1.24 (1.13 to 1.36) and HR 1.34 (1.21 to 1.48), respectively, with p value for interaction=0.23. Conclusions AF is common in the setting of MI and is associated with a higher risk of composite cardiovascular outcome and the individual components; mortality, reinfarction and ischaemic stroke, respectively. No major difference in outcome was observed between AF subtypes. No difference in outcome for AF was observed between the NSTEMI and STEMI cohort.
INTRODUCTION
To cite: Batra G, Svennblad B, Held C, et al. Heart 2016;102:926–933. 926
Atrial fibrillation (AF) is the most frequently sustained arrhythmia with an increasing incidence due to ageing population.1 AF is a common finding in the setting of myocardial infarction (MI) with the incidence reported to vary between 6% and 21%.2 Previous studies have shown that the occurrence of AF in the setting of MI is associated with an increased risk of mortality and ischaemic stroke.3–7 However, there is limited knowledge on the occurrence and the outcome associated with different subtypes of AF in the setting of MI, which is of importance when estimating prognosis of
individual patients. In addition, there is limited knowledge regarding the association between AF and the subtype classification of MI into non-ST-elevation myocardial infarction (NSTEMI) and ST-elevation myocardial infarction (STEMI). We aimed to study the occurrence of different subtypes of AF in the setting of MI and the association with 90-day all-cause mortality, MI or ischaemic stroke. We also evaluated outcome in AF patients with NSTEMI and STEMI.
METHODS This is a retrospective observational study including all consecutive Swedish patients admitted due to MI in all 72 coronary care units between January 2000 and December 2009. All patients admitted to coronary care units in Sweden are reported in the Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies register (SWEDEHEART). Key patient characteristics on admission and variables registered during the hospital stay and at discharge are recorded. The quality of data has been monitored yearly with results showing a 96.1% agreement between the data entered in the registry and the patient records.8 Data about mortality were obtained by data linking the SWEDEHEART registry with the Swedish Cause of Death Registry. Information about readmission and history of diabetes mellitus, hypertension, ischaemic stroke, chronic obstructive pulmonary disease, congestive heart failure, MI, peripheral vascular disease, renal disease, liver disease, bleeding events, dementia and cancer, based on the International Classification of Diseases, 10th revision, were obtained by data linking SWEDEHEART with the National Patient Registry (NPR); see online supplementary tables S1–S4. The Swedish Cause of Death Registry includes data on mortality in Sweden from 1961 and the NPR includes diagnoses on all patients hospitalised in Sweden from 1987 and forward. These registries are part of the Swedish National Board of Health and have been shown to have high validity.9 10 Data linkage of these registries with SWEDEHEART was approved and performed by the National Board of Health and Welfare using the unique civic registration number of each Swedish citizen. Diagnosis of AF was based on physician interpretation of ECG on arrival and at discharge.
Batra G, et al. Heart 2016;102:926–933. doi:10.1136/heartjnl-2015-308678
Downloaded from http://heart.bmj.com/ on July 11, 2017 - Published by group.bmj.com
Coronary artery disease Data on previous diagnosis of AF, preceding the current hospital admission, were collected in the NPR. Patients were categorised into four groups: new-onset AF with sinus rhythm at discharge; new-onset AF with AF at discharge; paroxysmal AF and chronic AF. New-onset AF with sinus rhythm at discharge was defined as no medical history of AF according to NPR with AF on arrival ECG but sinus rhythm on discharge ECG. New-onset AF with AF at discharge was defined as no medical history of AF in NPR with AF on the discharge ECG, regardless of arrival ECG. Paroxysmal AF was recorded in cases with a known medical history of AF, but with sinus rhythm on either the arrival or discharge ECG. Chronic AF was documented in patients with a history of AF and with AF on both the arrival and discharge ECG. The primary end point was a composite cardiovascular outcome including all-cause mortality, MI or ischaemic stroke within 90 days from discharge. Results were also analysed for the following individual outcomes within 90 days from discharge; all-cause mortality, MI and ischaemic stroke, respectively. Patients were censored for death when analysing the individual outcomes; MI or ischaemic stroke. No other censoring scheme was applied. Outcome definitions are presented in online supplementary table S4.
Statistics Descriptive statistics for baseline characteristics are presented in a tabular format with continuous variables as a median with interquartile range (IQR) and categorical variables as percentages. Kaplan–Meier estimates were reported to illustrate outcome according to subtype classification of AF. Unadjusted and adjusted Cox regression analyses were calculated to identify the relation between occurrence of AF and outcome. In the adjusted Cox-regression analysis, clinical relevant variables included in the CHA2DS2-VASc scoring system11 were individually accounted for and included the following: congestive heart failure, hypertension, age, diabetes mellitus, prior ischaemic stroke, transient ischaemic attack and systemic embolism, vascular disease, gender, and also admission year, hospital (as a γ distributed random frailty effect), in-hospital revascularisation, anticoagulants and antiplatelets at discharge. Continuous variables entered the models as cubic splines to allow for violation of the linearity assumption. Due to enrichment of data from the NPR, no data were missing when adjusting for differences in baseline characteristics. Diagnostics for the proportional hazards assumption was done using Schoenfeld residuals with no significant violations of the assumption observed. Finally, a subgroup analysis was performed on the 69 919 patients undergoing percutaneous coronary intervention (PCI) to assess the association between different subtypes of AF and outcomes in this population. Results were stated statistically significant for a two-sided p value
