Discussion
In the current study investigating the prevalence and demographic and clinical characteristics of AF in patients with de novo myocardial infarction, we found a lower prevalence rate of 3.1%, in contrast to previous studies in the literature.1,2 The exclusion of patients with a previous history of revascularization and diagnosis of stable coronary artery disease (SCAD) as well as the relatively younger age of the enrolled population is thought to play a main role in the lower than expected prevalence of AF in our study. SCAD and AF share common risk factors and patients with a long history of SCAD and its risk factors also show increased risk of incident AF.5In addition, coronary revascularization procedures, particularly CABG, have been found to create a predisposition to incident AF.6 For this reason, the authors are of the opinion that the exclusion of patients with SCAD and revascularization history were the main factors behind the low percentage of AF patients in the study population. Furthermore, a positive correlation between age and AF has been confirmed in many registries.7 The relatively young mean age (approximately 60 years old) of patients enrolled in our study may also have resulted in the lower prevalence of AF in our study population. Theoretically, patients without previous diagnosis of SCAD and/or without history of revascularization may be younger and have fewer AF risk factors. Although ethnicity may play a role for differences in the prevalence of AF, no evidence has been reported showing different rates of AF between Turkey and the rest of the world.8 However, acute coronary syndrome registries conducted in Turkey report younger average ages in patients admitted with acute MI than in European countries and the United States.9,10 We believe that the younger age pattern may have an effect on lower AF prevalence in our study than that of other global registries.
Our study also found that non-ST-elevation myocardial infarction (NSTEMI) presentation was higher in the AF population than in patients without AF, with approximately 70% of AF patients presenting with NSTEMI. Age is a common risk factor of both AF and NSTEMI. The current literature shows a positive correlation between increasing age and the rate of NSTEMI in the MI population and a higher prevalence of AF in patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS).11 On the other hand, AF with fast ventricular response can precipitate Type 2 MI that commonly presents with ST segment changes rather than elevation on admission ECG.1 However, while this study did not find any differences in the prevalence of MINOCA between the AF and non-AF groups, possible type II error cannot be ignored.
Advanced age, female gender, lower LV ejection fraction (LVEF), higher Killip class, obesity, presence of multiple comorbidities, and hemodynamic instability are associated with AF.2Similar to previous studies, patients in the AF group were older than in the non-AF group and the proportion of women to men in the AF group was higher than that in the non-AF group. Previous registries revealed that with advanced age, gender difference in MI patients lessens and the female/male ratio increases.12 AF patients were an average of twelve years older than non-AF patients in our study, which may explain the gender difference between the AF and non-AF groups. Additionally, smoking is more common in men than in women in the Turkish population.13 The authors believe that the observed difference in smoking between the groups may be due to the female dominance in the AF group. Hypertension is an essential predictor of AF development14 and higher hypertension prevalence in the AF group can play a role in the development of AF in advanced age (64.7% vs. 48.5%, p=0.023). In addition, we should pay attention to type I statistical error in evaluations of differences of gender, smoking, and prevalence of hypertension in this context. Lower LVEF in the AF group (45.0% [30.0-50.0] vs. 50.0% [35.0-55.0], p=0.008) can be explained by the higher burden of comorbidities such as advanced age and hypertension in AF patients. Loss of atrial kick and possible tachycardiomyopathy are other factors that may result in lower EF and have been found to be responsible for worse hemodynamic status and increased mortality.15 Accordingly, the ratio of Killip class 3 and 4 patients at admission was higher in the AF group in our study.
An interesting finding in our study was the relatively low percentage of patients who were initially treated by the thrombolytic therapy. ST-elevation myocardial infarction (STEMI) patients made up nearly half of the study population (46.0%) but only 3.0% of all patients received thrombolytic treatment before coronary angiography. Even in the AF group, while 31.3% of patients presented with STEMI, none received thrombolytic therapy. It is possible that the lower preference for thrombolytic therapy as an initial reperfusion choice may be related to the well-organized ambulance system and sufficient number of invasive cardiology centers which are capable of performing 7/24 primary PCI around the country.
Oral P2Y12 inhibitor loading was common in both AF and non-AF patients. Although the AF group was found to have a higher oral P2Y12 inhibitor loading rate (96.0% vs. 91.8%, p=0.027) than the non-AF group, this can be an incidental finding and accepted as an example of type I statistical error. The study also found the use of oral P2Y12 inhibitors other than clopidogrel to be relatively common in the AF group, with approximately one third of patients in the AF group loaded with an oral P2Y12inhibitor other than clopidogrel. We believe that the relatively common use of more potent P2Y12 inhibitors in AF population was due to the lower percentage of AF patients who had been already taken OAC therapy. It can be argued that with common OAC usage, potent P2Y12 inhibitor loading ratios would be lower.
Ischemic stroke is a devastating complication of AF and MI patients with AF carry a significant risk of stroke. Previously, it has been reported that dual/triple therapy by adding an OAC decreases the risk of stroke.16 Despite this stroke risk, most AF patients admitted with MI were discharged without any OAC therapy. Many trials have focused on finding the sweet spot between stroke, stent thrombosis, and major bleeding risk and compared triple and dual therapy strategies with different duration and different regimens. Almost all of reported greater safety with dual therapy with OAC plus clopidogrel than triple therapy.17 Current guidelines advise personalized management of these patients according to bleeding and thrombosis risk.18,19 It is also important to emphasize the low percentage of oral anticoagulant usage in patients with AF before emergency admission.
Underdiagnosed/overlooked AF, particularly in asymptomatic patients, undertreatment, and compliance issues with OAC therapy may be the main reasons for the lower percentage of OAC use in the study population. These results show the importance of successful and timely diagnosis of AF, patient education on OAC therapy, and transparent performance metrics and guideline adaptation for health providers.
In conclusion, the study reports a lower percentage of AF prevalence in the de novo MI population than previous studies of enrolled unselected MI and ACS cohorts. It also demonstrated the underuse of OAC in AF patients, emphasizing the vital role of opportunistic diagnostic strategies, patient education, and implementations for guideline adaptation.
Study limitations: The study had several limitations discussed below. Regarding the cross-sectional design of the study, it was not possible to obtain short and long-term prognostic metrics of the patient population. Due to the relatively small sample size of the AF population, possible type II statistical errors may have affected the comparative data. Some demographic and clinical characteristics of the study population may be specific to the Turkish population and thus not reflect a global perspective. MI was defined in line with the Third Universal Definition of Myocardial Infarction. However, the current Fourth Universal Definition of Myocardial Infarction was published after the starting date of study and protocol revisions were not made due to possible risks of harmonization between pre- and post-revision data. AF diagnosis was based on a12 lead ECG performed at admission, meaning that incident AF could not be captured and differentiated from existing chronic patterns. For this reason, the organizing committee required the completion of a form from the investigators in case with suspicion of incident AF. Similarly, we did not receive any data about the patterns of AF (ie first diagnosed, paroxysmal, persistent, etc). A higher rate of first diagnosed AF patterns may explain the dramatic percentages of OAC use in the study population.
Author contributions: Concept: A.C, U.O.T.; Design: U.O.T., A.C.; Supervision: U.O.T., M.Z., O.E.; Materials: A.C., C.E., G.A., Y.D., O.A.O., S.K., Y.C., I.U., M.B.T., R.D., V.P., H.O., M.O., K.T., D.K., N.C., M.G., S.I., F.Y.C., H.A., A.A., M.Z., O.E., U.O.T.; Data: A.C., S.K.; Analysis: A.C., S.K., U.O.T.; Literature search: A.C., U.O.T; Writing: A.C., U.O.T; Critical revision: U.O.T., M.Z., O.E.
Funding: This work was supported by the Cardiovascular Academy Society of Turkey [grant number: KVAK 2018/01].
Acknowledgements: The study was presented at European Society of Cardiology Congress, Paris 2019.
Conflict of interest: none declared.