New‐onset atrial fibrillation incidence and associated outcomes in the medical intensive care unit

In patients with critical medical illness, data regarding new‐onset atrial fibrillation (NOAF) is relatively sparse. This study examines the incidence, associated risk factors, and associated outcomes of NOAF in patients in the medical intensive care unit (MICU).


INTRODUCTION
Atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting one in four patients over the age of 65, and is associated with significant morbidity and mortality. 1 Patients with AF are at increased risk for complications including rapid ventricular response, decreased cardiac output, cardiogenic shock, and death. MICU patients who develop NOAF are a particularly susceptible population with increased risk for developing life-threatening sequelae. [2][3][4][5] However, NOAF in specifically MICU patients has been understudied relative to NOAF in surgical patients. [6][7][8] The risk of stroke associated with AF is well established, with AF patients at a 4 to 5-fold greater risk of ischemic stroke. 9 Annual stroke risk in patients with AF is most commonly estimated using the CHA 2 DS 2 -VASc score to identify patients who will benefit from oral anticoagulation. 10 However, data regarding the optimal long-term anticoagulation strategy for NOAF in MICU patients, especially those with only one or more brief episodes of AF, is relatively limited. 8 Given the associated negative consequences, an improved way to stratify MICU patients based on their risk for developing NOAF may be helpful from a monitoring and prevention standpoint. The predictive value of previously existing risk scores (such as CHA 2 DS 2 -VASc, C 2 HEST, ESCARVAL and CHARGE-AF scores) for NOAF in various settings has previously been assessed. [11][12][13][14][15] In one study of post-coronary artery bypass graft (CABG) patients, CHARGE-AF was found to outperform CHA 2 DS 2 -VASc and age alone for prediction of NOAF. 16  including stroke and mortality within 1 year. Patients who died before discharge were censored. We also assessed associations of AF recurrence and medications prescribed at discharge with the primary outcomes of stroke and mortality. Statistical significance was defined as p < .05 for all analyses. All data was analyzed using R 3.6.1 statistical software.

RESULTS
A total of 241 patients of the 2234 total cohort developed NOAF during their MICU stay, a NOAF incidence of 11 Table 3, the only significant finding was that NOAF patients who were prescribed rate control medications were more likely to experience a stroke outcome (p = .034). However, this association was not significant after adjusting for age and sex (p = .062). *not significant after adjusting for age and sex (p = .062).

DISCUSSION
We retrospectively analyzed a cohort of non-postoperative MICU patients diagnosed with NOAF to examine the incidence, predictive factors, and outcomes associated with this common condition. in the published literature. 8 Potential sources of this variability may include study bias, variation in detection and diagnosis, and variable pathology between different ICUs. Our reported incidence may be towards the lower end of the spectrum in part due to the exclusion of all postoperative patients from the study. Nonetheless, we find that NOAF is a common and serious condition among critically ill patients in the MICU setting.
Our finding that patients with NOAF had a longer hospital LOS is supported by previous literature. 2,3,5,17,18,19 This relationship between NOAF and LOS is not surprising given that NOAF appears to be a marker for more severe illness in the ICU setting. 20 We found a strong association between NOAF and in-hospital mortality as well as 1-year mortality. Previous studies have largely shown a similar positive relationship between NOAF and mortality. 2,4,22 However, fewer studies have assessed mortality after discharge, and one prior large study did not find any significant difference in postdischarge survival among patients with NOAF. 2 The present body of evidence regarding NOAF among MICU patients is heterogeneous, and we suspect measurable outcomes are highly variable in this population due to inter-study differences in exclusion criteria, patient age, and other demographic variables. 8 Perhaps, with early detection and interventions for NOAF, mortality associated with AF-related complications (e.g., cerebrovascular accident) can be effectively mitigated among the critically ill.
We also examined AF recurrence and its effect on the primary outcomes of stroke and mortality. Prior research has demonstrated an association increased AF burden and these outcomes. 23 A positive relationship existed between AF recurrence and both these clinical outcomes, but neither was significant. While our study has a large total population, there is a relatively small number (241) of patients with NOAF. Furthermore, this critically ill study population inherently leads to suboptimal follow-up, most commonly due to the high rates of mortality, including during the MICU stay itself. This relatively small sample size limited our statistical power. Likely for similar reasons, we did not observe any significant differences in treatments strategies used for NOAF and clinical outcomes. This is consistently an area in the literature that has been difficult to study. 8 Regarding the association of beta blockers and stroke, while ultimately not a significant finding, perhaps this represents a reverse causation bias. Patients with higher AF burden, and therefore at higher risk of stroke, may have been more likely to be prescribed beta blockers.
In our cohort, we found that the CHARGE-AF score had the greatest predictive value for NOAF. Similar differences in predictive validity have been demonstrated in post-CABG patients 16  There were several limitations we encountered in our study. While we controlled for demographics in our measured outcomes, it is possible that either group had different degrees of illness severity that confounded our results. Due to limitations in the data available for automated extraction, we were unable to obtain useful information regarding the reason for MICU admissions. Furthermore, the Acute Physiology and Chronic Health Evaluation II score or a similar prognostic scoring system could have helped us control for this, however, automating retrieval of the values necessary to calculate such a score was limited by the data readily available in the EHR. Additionally, our automated data extraction was unable to pull all the data points required to calculate CHARGE-AF scores in 29% of the control and 45% of the NOAF cohorts, almost completely due to missing ambulatory weight and blood pressure data. The inclusion of data only prior to hospital stays likely led to the majority of this missingness. However, we felt this limitation was acceptable because the alternative of including data after hospital encounters would introduce a confounding factor of increased data missingness stemming from subjects who expired. Furthermore, the data was intended for the calculation of a predictive risk score and therefore should ideally employ data prior to the event of interest. To address this issue and include all available data from our cohort, we imputed a median value to supply the missing ambulatory data for each group. The AUC for this imputed CHARGE-AF score was quite close to the original CHARGE-AF score AUC.

CONCLUSION
NOAF was common in this cohort of non-postoperative critical care patients, with an incidence of 11.4%. Compared to the control group, NOAF was associated with longer MICU and hospital LOS as well as greater risk of mortality. CHARGE-AF scores had the greatest predictive value for NOAF in our cohort. Future directions of research may focus on risk stratification of this patient population to potentially optimize prevention of NOAF, possibly with empiric antiarrhythmic drug use. There is also a need for stronger evidence to guide the treatment strategies for these patients. With such advancements, we can hope to mitigate both the negative patient outcomes and large healthcare costs associated with NOAF.