First-time atrial fibrillation (AF) in otherwise medically ill patients without a history of AF has a variable incidence of 1%–44% in hospitalized patients [1,2]. However, it is unclear whether the arrhythmia is transient in this setting, or rather the harbinger of persistent AF in years to come [1]. Here we will refer to this phenomenon as AF of new onset during acute illness (AFNOAI). Risk factors for the long-term persistence of AFNOAI are unknown. Identification of these factors might help guide decisions around initiation of anticoagulation for higher risk individuals. This study assesses the risk factors for persistence of AFNOAI in the 5 years after hospital discharge for critically ill patients.

Two-hundred and fifty-one (1.8%) of 13,983 unique MICU admissions had AFNOAI. One-hundred and twenty-six (50%) were excluded due to in-hospital death and 17 (7%) were excluded due to absence of clinical documentation after discharge. One-hundred and eight patients were included. Median follow-up time was 26.0 months (interquartile range [IQR], 6.1–60.0 months).

Table 1 compares characteristics of patients with and without persistence of AFNOAI in the 5 years after discharge. The mean age overall was 65 years (IQR, 52–78 years); 69% were male. Thirty (28%) were admitted for sepsis, 31 (29%) for pulmonary disease, 10 (9%) for gastrointestinal bleed, 6 (6%) for cardiac arrest, 7 (6%) for renal failure, and 24 (22%) for other causes. Eighty percent had AF with rapid ventricular response.

Forty-one patients (38%) had persistence of AFNOAI, with a median time to first documented recurrent AF episode of 6.6 months (IQR, 1.0–29.5 months) after hospital discharge. Five patients (4.6%) had a stroke, of whom 4 had persistent AFNOAI. Fifty-nine (55%) patients died in the 5 years after discharge; median time to death was 9.6 months (IQR, 1.6–24.6 months).

Table 2 shows the results of the Cox’s proportional hazards model, using select predictors. Age, hyperlipidemia and immunosuppression were associated with AFNOAI persistence. Diastolic dysfunction and mitral regurgitation (MR) also showed a trend towards association with AFNOAI persistence. Eight patients had no echocardiogram available within a year of admission and seven had incomplete echocardiogram data. Missing data was imputed.

Our study describes risk factors associated with the persistence of AFNOAI after critical illness. We found that age, hyperlipidemia and immunosuppression were linked with AFNOAI persistence in our cohort of patients. Diastolic dysfunction and MR may also predispose to persistence. By contrast, disease-associated variables, such as admission diagnosis and organ failure, bore no influence.

The importance of cardiac factors demonstrated in our study reinforces prior data in patients who had undergone non-cardiac surgery, which showed that hypertension and left atrial enlargement were associated with persistence of new onset AF [3]. The association with age likely mirrors the increasing prevalence of AF in the older population [4]. MR and diastolic dysfunction may increase the likelihood of AFNOAI persistence by creating a more arrhythmogenic atrial substrate [4,5]. However, the relationship with hyperlipidemia is ambiguous—other studies have demonstrated both increased and decreased AF risk with respect to hyperlipidemia [6]. Immunosuppression may increase susceptibility to intercurrent illness, including arrhythmias.

Of the five patients who had a stroke, four had persistence of AFNOAI, implying a causal link therein. Indeed, other studies have demonstrated an increased stroke risk in patients with AFNOAI and up to 47.5% of patients did not receive another AF diagnosis before their stroke, highlighting the importance of initiating anticoagulation in a timely fashion [3,7].

The epidemiology of AFNOAI in our study is consistent with previous data, lending credence to the generalizability of our results. AFNOAI was rare in our study (1.8%), but the AFNOAI persistence rate was high (38%), similar to prior research [1,3,7]. Half of patients with AFNOAI expired in hospital, and over half of hospital survivors died in the 5 years after discharge, again consistent with existing evidence of a high mortality rate in this cohort [7-10].

Our study is the first of its kind to look at a vast array of risk factors for persistence of AFNOAI. A limitation is the small sample size. Additionally, some episodes of AFNOAI may have been missed by our screening algorithm, while others may have been clinically silent—in one study only 16.4% of cases were clinically detected [9]. Due to the lack of timely EKGs in patient charts, it was not possible to determine the cardiac rhythm at the time of discharge for each patient— there is potentially a difference in AFNOAI persistence rates between those with sinus rhythm restored at the time of discharge versus those with AF on discharge. Moreover, since patients did not have continuous cardiac monitoring after discharge, it was impossible to tell precisely if and when they first reverted to AF during the 5-year follow-up period. The true AFNOAI persistence rate may be even higher, if we consider that only symptomatic AF, and AF recorded on EKG, was counted in our study during the follow-up period. Larger prospective studies with continuous cardiac monitoring on discharge are needed to confirm the risk factors for persistent AFNOAI, and whether anticoagulation confers benefit.

Our study showed that AFNOAI has a high persistence rate after discharge and that certain comorbid and cardiac factors may increase the risk of persistence. Stroke prophylaxis should be considered, based on a patient’s individual AFNOAI persistence risk, though ultimately such discussion must be framed in the context of the guarded prognosis in this cohort.