Characteristics of the patients
The present investigation was designated to verify statistical methods of our previous observations. Our experience tended us to suggest that patients admitted to the hospital with AF and those developing AF while already staying in a medical department due to other acute conditions, substantially differ with respect to their clinical profile and prognosis. Thus far, this issue has been poorly investigated. Our present results reveal that such difference does exist, implicating that these two patient groups require distinction in their bedside management.
The present study design differed from that of a single similar publication available in the literature in which patients who were hospitalized for acute medical illness and developed AF during hospitalization were compared with those hospitalized for acute medical condition but did not develop AF during hospitalization, or with patients referred to the emergency room with the new-onset AF being their sole complaint.13 Unlike the retrospective data collection in the mentioned publication, the majority of our data were collected prospectively. Our patient populations were much larger and included both genders, unlike the above mentioned study comprising only 24 patients of male sex in each group. Selection of the analyzed clinical variables was more extensive and the follow-up period was longer.
In the present investigation, the two study groups substantially differed with respect to their comorbidities as well as their clinical characteristics and laboratory analyses. Thus, patients from the in-hospital group were statistically more likely to have DM , RD, chronic lung disease or history of stroke, compared to the out-of-hospital group, confirming the previous observation that patients developing AF during hospital stay are more severely ill.13 Patients of the in-hospital AF group had higher body temperature as well as higher heart and respiratory rates when compared to the out-hospital AF population. Furthermore, these patients demonstrated lower levels of serum albumin and blood hemoglobin. Inflammatory markers, such as serum CRP, erythrocyte sedimentation rate and white blood cell count, were significantly elevated in the in-hospital AF population.
Some aspects regarding the AF characteristics of the in-hospital group patients from our study are novel and as such might be of clinical importance. Thus, contrary to our out-of- hospital group, the in-hospital group had higher frequency of episodes of AF occurring during hospitalization, despite the fact that higher proportion of these patients returned to sinus rhythm on discharge. This would tend to suggest that the trigger for AF remained active up to amelioration of those clinical conditions which had been the reason for the patient’s admittance in the first place. It is plausible that, in addition to routine anti-arrhythmic treatment, any effective treatment of concurrent acute illness also had a positive impact on successful cardioversion. We are not aware of any data regarding the recurrence rates of AF during hospitalization in patients similar to those comprised in our study. As stated before, elevation of various inflammatory markers in the in-hospital group indicates a significant association between inflammation and development of AF, as well as between successful treatment of inflammation and conversion of AF to normal rhythm. According to the literature, high levels of CRP are associated with increased risk of AF recurrence.16–18
The additional interesting finding is the observed longer mean time elapsing from the AF onset up to conversion to sinus rhythm in the in-hospital compared to the out-of-hospital group (59 h and 26 h, respectively). We also have demonstrated that patients with AF onset during hospitalization needed a significantly prolonged hospital stay, compared to patients from the out-of-hospital group. Lengthening of hospital stay has been previously reported in AF patients with HF,11 acute myocardial infarction9 and after surgery.7,8 There is no data regarding the length of hospital stay for patient populations similar to ours. The data provided herein allow us to conclude that patients with the in-hospital onset AF developed the latter at the later stages of their hospital stay. Consequently, their hospital stay was prolonged as a result of such complication. However, it is also possible that in a given patient severity of the clinical profile was predictive both of the prolongation of hospital stay and conversion of AF to normal rhythm.
We also observed that longer time period was needed for cardioversion in our entire study group, as compared to drug-oriented trials.19–21 Nevertheless, it was comparable with study performed on unselected patient population.22 Time of pharmacologically achieved conversion to sinus rhythm appears to vary depending on the anti-arrhythmic drug choice.19–21 Among the prescribed anti-arrhythmic drugs used in our study, amiodarone was the one most frequently applied both during hospitalization and on discharge. We applied amiodarone so extensively since it is one of the most effective anti-arrhythmic agents which is also commonly used in clinical practice as a drug of choice for treatment of patients with AF in the presence of coronary artery disease and/or HF,3,5,19–21,23,24 the latter conditions being common in our patients. However, amiodarone is known to exert its effects more slowly than other anti-arrhythmic drugs19–21 Thus, despite the fact that amiodarone administration was associated with relative prolongation of time elapsing from the AF onset to conversion to normal rhythm, successful cardioversion was achieved in the majority of our patients.
We conducted a long-term follow-up on ourstudy groups, including survival and the variables associated with the latter. In accordance with previously published data,11,12,22,25 the following variables were found to be significantly associated with poor prognosis: older age, DM, RD, reduced LVEF and first episode of AF. Moreover, we observed decreased long-term survival in patients with the onset of AF during hospitalization, compared to those admitted to the hospital with AF. Furthermore, significant predictors of death were found to be different for the two study groups: in the in-hospital group - older age and male gender, whereas in the out-of-hospital group - older age, RD, DM, reduced LVEF and new-onset AF. Treatment with statins was associated with prolonged survival only in the out-of-hospital group.
Of interest, the first episode of AF (compared with diagnosed paroxysms of AF prior to admission) was significantly associated with lower survival. Similar observations have been reported in other studies performed on AF patients hospitalized with acute coronary syndromes and HF or admitted for cardioversion.11,12,22 Our results support the hypothesis that first episode of AF should always be considered a risk factor for the presence of previously unknown and, most probably, severe underlying disease.22 It is possible that increased mortality after the acute event of AF is due to these adverse consequences of new-onset AF on cardiac function. The intrinsic mechanisms leading to increased mortality shortly after the new-onset AF are probably of hemodynamic origin, whereas in the recurrent forms of arrhythmia mortality most probably results from stroke, progressive electrical remodeling, etc.11,12 Noteworthy, since patients with recurrent episodes of AF are likely to be already pharmacologically treated after their previous cardiovascular evaluations, this alone might be predictive of a better long-term prognosis.11,22
As already mentioned, in the present study treatment with statins was associated with prolonged survival of both the entire patient population and the out-of-hospital group. Beneficial effects of statins on AF have been previously reported in several studies. Data from different observational trials have shown that statins may decrease the incidence of different types of AF, including the new-onset AF after electrical cardioversion, cardiac surgery, acute coronary syndrome and/or left ventricular dysfunction.26–30 The anti-arrhythmic mechanisms of statin-induced AF prevention in HF patients are not fully understood. Positive effects of statins on AF appear to be independent of their cholesterol-reducing properties, but might be related to their pleiotropic anti-inflammatory and antioxidant effects, as well as to atrial remodeling attenuation and ion channel stabilization.28 Inflammation, documented by higher levels of CRP, which may be a pathogenic component of AF, appears to be involved in the early phase of electrical remodeling (as early as within 24 h after AF initiation) and to promote the persistence of AF.4,27,28
The main limitation of the present study was the relatively small number of patients within the in-hospital group, which might have compromised our ability to define any other variables predictive of lower survival. In addition, it was difficult to accurately estimate the onset, and therefore the total duration of AF in the out-of hospital group. With respect to the period preceding the hospitalization, we could only rely on the clinical records of the patient, if available, or on the complaints and symptom descriptions provided by the patient. It is also possible that our results were limited by inclusion of patients from only one internal medicine department from a single medical center as well as by the specificity of local medical services.