Patients with severe sepsis and new-onset atrial fibrillation at increased risk of in-hospital stroke, death

Atrial fibrillation (AF) is one of the most common arrhythmias among critically ill patients. "Previous studies have demonstrated that 6 percent to 20 percent of patients with severe sepsis develop new-onset AF, suggesting that severe sepsis may be a predisposing factor for new-onset AF," according to background information in the article. "Chronic AF is a known risk factor for stroke and death, but the clinical significance of new-onset AF in the setting of severe sepsis is uncertain."

To examine the association of new-onset AF during severe sepsis with adverse outcomes of in-hospital mortality and ischemic stroke, Allan J. Walkey, M.D., M.Sc., of the Boston University School of Medicine, and colleagues conducted a study that included administrative claims data from the California State Inpatient Database from nonfederal acute care hospitals for January 1 through December 31, 2007. Data were available for 3,144,787 hospitalized adults. The researchers identified 49,082 cases of severe sepsis that met qualifying criteria for the study. New-onset AF was defined as AF that occurred during the hospital stay, after excluding AF cases present at admission.

New-onset AF occurred during 20,608 hospitalizations (0.65 percent; including sepsis and nonsepsis) and during 2,896 hospitalizations (5.9 percent) of patients with severe sepsis, with analysis indicating that 14 percent of all hospital-associated new-onset AF occurred in the context of severe sepsis. Compared with hospitalized patients without severe sepsis, patients with severe sepsis had a nearly 7 times the odds of having new-onset AF. Factors associated with increased risk of new-onset AF during severe sepsis included demographics (increasing age, male sex, and white race), comorbidities (history of heart failure, obesity, malignancy, and stroke), and various acute factors (such as increasing number of organ failures, respiratory failure and renal failure).

Among individuals with severe sepsis, new-onset AF was associated with increased adjusted risks of in-hospital ischemic stroke. In contrast, patients with severe sepsis and preexisting AF did not have an increased risk of in-hospital ischemic stroke compared with those with severe sepsis and no AF. In patients with severe sepsis, in-hospital ischemic stroke occurred in 75 of 2,896 individuals (2.6 percent) with new-onset AF compared with 57 of 9,986 (0.57 percent) with preexisting AF and 249 of 36,200 (0.69 percent) without AF.

Compared with severe sepsis patients without new-onset AF, patients with new-onset AF had a greater risk of in-hospital mortality (1,629 [56 percent] vs. 18,027 [39 percent] deaths).

The researchers speculate that several potential mechanisms might explain the increased ischemic stroke risk in patients with severe sepsis and new-onset AF. "Severe sepsis alone may be associated with an increased risk of stroke through hemodynamic [blood circulation] collapse, increased systemic inflammation, and coagulopathy [clotting/bleeding disorder]. New-onset AF may simply be a marker for greater severity of illness and, thus, greater stroke risk."

"Given projected estimates of severe sepsis incidence in 1 million Americans in 2011, it is likely that new-onset AF occurs in more than 60,000 patients with severe sepsis in the United States each year," the authors write. "Current guidelines do not address AF that occurs in the setting of severe sepsis or acute infection, suggesting that new-onset AF that occurs during severe sepsis is an underrecognized public health problem. If our findings of increased stroke and death in the setting of AF and severe sepsis are replicated in other data sets, then it will be important to examine management strategies that might diminish the risk of adverse outcomes associated with AF during severe sepsis."

Editorial: Is Severe Sepsis Associated With New-Onset Atrial Fibrillation and Stroke?

In an accompanying editorial, Christopher H. Goss, M.D., M.Sc., of the University of Washington, and Shannon S. Carson, M.D., of the University of North Carolina. Chapel Hill, write that an important question is whether the findings of this study should lead clinicians to intervene with stroke prevention therapy, such as with acute cardioversion (a method to restore an abnormal heart rhythm back to normal), anticoagulation, or both.

"It is difficult to maintain successful cardioversion as long as severe sepsis persists, perhaps because acute risk factors such as high catecholamine [any of several compounds occurring naturally in the body that serve as hormones or as neurotransmitters in the sympathetic nervous system] states have not yet resolved. Anticoagulation presents additional risks for patients with severe sepsis due to coagulation abnormalities and frequent invasive procedures. Given the limitations of these observational data, current practice should not change in favor of interventions that could involve additional risk. Given the small event rate, a randomized trial of anticoagulation for new-onset atrial fibrillation in severe sepsis would be logically difficult. However, further observational studies with large databases assessing how interventions might modify the risk of stroke could provide more useful information."