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Atrial Fibrillation During SepsisAtrial Fibrillation During Sepsis: A Determinant of Long-term Outcomes? FREE TO VIEW

Yee C. Lau, MBChB; Gregory Y. H. Lip, MD
Author and Funding Information

From the University of Birmingham Centre for Cardiovascular Sciences, City Hospital.

CORRESPONDENCE TO: Gregory Y. H. Lip, MD, University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Dudley Rd, Birmingham, B18 7QH, England; e-mail: g.y.h.lip@bham.ac.uk


FINANCIAL/NONFINANCIAL DISCLOSURES: The authors have reported to CHEST the following conflicts of interest: Dr Lip has served as a consultant for Bayer AG, Astellas Pharma Inc, Merck & Co, Sanofi SA, Bristol-Myers Squibb Co/Pfizer Inc, Daiichi-Sankyo Co Ltd, Biotronik, Medtronic Inc, Portola Pharmaceuticals Inc, and Boehringer Ingelheim GmbH, and has been on the speakers bureau for Bayer AG, Bristol-Myers Squibb Co/Pfizer Inc, Boehringer Ingelheim GmbH, Daiichi-Sankyo Co Ltd, Medtronic Inc, and Sanofi Aventis US LLC. Dr Lau has reported no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2014;146(5):1138-1140. doi:10.1378/chest.14-0986
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Published online

Despite the advancement of antimicrobial agents, sepsis remains a major global health issue and leading cause of death in low-income countries. In the United States, severe sepsis affects up to 750,000 Americans and is associated with a high mortality rate.1 In severe sepsis, atrial fibrillation (AF) also commonly occurs.2 Sepsis may precipitate AF per se, perhaps unmasking a propensity to develop the arrhythmia, or the association could reflect greater clinical vigilance or monitoring during treatment (or hospitalization) for severe sepsis. Nonetheless, the prognostic effects of sepsis-associated new-onset AF on the subsequent occurrence of AF and long-term outcomes remained uncertain until, in the present issue of CHEST, the article by Walkey et al3 (see page 1187) sheds some light on these questions.

Using data extracted from Medicare claims between 1999 and 2010, Walkey et al3 report an observational study showing patients with sepsis and associated new-onset AF have a higher rate of AF occurrence following hospitalization compared with those without AF during sepsis (54.9% vs 15.5%). This finding is potentially of significant importance, as contemporary perception is that with the treatment of sepsis, sustained atrial arrhythmia will be eliminated.

Nevertheless, a possible explanation for this finding may be that the more elderly population in the new-onset AF group possessed higher incidence of asymptomatic, chronic silent AF, which was brought to light by hospitalization secondary to acute sepsis, than the no-AF group (age 80.7 years vs 79.5 years). Sepsis and subsequent inflammatory response also may have unmasked those with higher propensity for development and maintenance of AF, as illustrated by the higher incidence of comorbidities classically associated with AF, among the new-onset AF group compared with the no-AF group, such as heart failure, ischemic heart disease, and valvular heart disease.

What are the clinical implications? This finding further emphasizes the need for clinicians to look harder and longer for AF among the at-risk population, for example, the sepsis survivor, through regular review of symptoms, opportunistic screening via pulse palpation, and/or ambulatory ECG monitoring.4 The need for diligent AF detection can be demonstrated by the high pick-up rate of previously undiagnosed AF by continuous monitoring, via implantable loop recorder, of patients with prior ischemic stroke or thromboembolism.5

Equally important, Walkey et al3 also uncovered that new-onset AF during sepsis leads to poorer long-term outcomes, with higher rate of hospitalization for heart failure, ischemic stroke, and death. This relationship remains, even after adjustment for several patient and sepsis factors. The article demonstrates a relatively low, cumulative, 5-year ischemic stroke event rate in new-onset AF group (5.3%) vs no AF group (4.7%), but this perhaps reflects survivor bias, as the 5-year mortality rate in all patient groups far exceeded 70%.

With the combination of increased AF occurrence and worse outcomes (hospitalization of heart failure, ischemic stroke, and death) among those sepsis survivors with new-onset AF, proactive vigilance for AF and its management, particularly stroke prevention, is important. An intimate relationship between sepsis and a propensity for thrombosis is evident, which may be ameliorated by antibiotics used to treat sepsis.6

In some patients, the use of oral anticoagulation therapy may not be recommended during the acute phase of severe sepsis, due to potential coagulopathy secondary to sepsis per se or corresponding sepsis-induced organ failure or difficulties achieving therapeutic anticoagulation with vitamin K antagonists (VKAs) (eg, warfarin) during an acute illness.7 The risk of bleeding is further increased by the need for frequent, invasive, therapeutic, or surgical procedures for resuscitation or resolution of the initial cause of sepsis. The availability of the non-VKA oral anticoagulants offer efficacy, safety, and convenience over the VKAs, and allows easier initiation of thromboprophylaxis and a potentially greater net clinical benefit.8

Current guidelines recommend use of the CHA2DS2-VASc (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, previous stroke/transient ischemic attack, vascular disease, age 65 to 74 years, and sex category) score to identify those with lowest risk for stroke or morbidity, following which effective stroke prevention with oral anticoagulation therapy can be offered to those with one or more risk factors. Prestroke risk assessment is simple and feasible, being supported by recent publications validating that the high prestroke CHA2DS2-VASc score predicts worse long-term outcome even in patients with sepsis but without AF.9,10

Finally, Walkey et al3 also highlight the potential of upstream therapy to tackle sepsis-associated new-onset AF. Sepsis triggers an inflammatory response, and this may directly increase the risk of AF via increased catecholamine release. Previous work has demonstrated the significant rise in C-reactive protein level prior to the onset of sepsis-induced AF.2 Thus, potential suppression of overwhelming inflammation may have a role in reducing the incidence of, or even preventing, subsequent arrhythmia. For example, the potential of perioperative use of corticosteroids in cardiac surgery to prevent AF has been promising.11 In sepsis, systemic steroids, however, may be counterproductive, so other options need to be found. Given the high prevalence of AF, the challenge is to accurately identify those patients who have an increased propensity for developing AF and those at particular risk of complications. Indeed, sepsis may simply be the catalyst to expose the vulnerability of developing this arrhythmia (and its complications).

In conclusion, Walkey et al3 demonstrate a high incidence of occurrence of further AF in sepsis survivors who had previously experienced acute sepsis-associated AF. These patients also exhibited higher rates of mortality and stroke, and heart failure risk. As survival of sepsis improves, there is the need to diligently identify those at risk for AF recurrence and its complications.

References

Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001;29(7):1303-1310. [CrossRef] [PubMed]
 
Meierhenrich R, Steinhilber E, Eggermann C, et al. Incidence and prognostic impact of new-onset atrial fibrillation in patients with septic shock: a prospective observational study. Crit Care. 2010;14(3):R108. [CrossRef] [PubMed]
 
Walkey AJ, Hammill BG, Curtis LH, Benjamin EJ. Long-term outcomes following development of new-onset atrial fibrillation during sepsis. Chest. 2014;146(5):1187-1195.
 
Lowres N, Neubeck L, Redfern J, Freedman SB. Screening to identify unknown atrial fibrillation. A systematic review. Thromb Haemost. 2013;110(2):213-222. [CrossRef] [PubMed]
 
Cotter PE, Martin PJ, Ring L, Warburton EA, Belham M, Pugh PJ. Incidence of atrial fibrillation detected by implantable loop recorders in unexplained stroke. Neurology. 2013;80(17):1546-1550. [CrossRef] [PubMed]
 
Franks Z, Campbell RA, Vieira de Abreu A, et al. Methicillin-resistantStaphylococcus aureus-induced thrombo-inflammatory response is reduced with timely antibiotic administration. Thromb Haemost. 2013;109(4):684-695. [CrossRef] [PubMed]
 
De Caterina R, Husted S, Wallentin L, et al. Vitamin K antagonists in heart disease: current status and perspectives (Section III). Position paper of the ESC Working Group on Thrombosis—Task Force on Anticoagulants in Heart Disease. Thromb Haemost. 2013;110(6):1087-1107. [CrossRef] [PubMed]
 
Pisters R, Nieuwlaat R, Lane DA, Crijns HJ, Lip GY. Potential net clinical benefit of population-wide implementation of apixaban and dabigatran among European patients with atrial fibrillation. A modelling analysis from the Euro Heart Survey. Thromb Haemost. 2013;109(2):328-336. [CrossRef] [PubMed]
 
Ntaios G, Lip GY, Makaritsis K, et al. CHADS2, CHA2S2DS2-VASc, and long-term stroke outcome in patients without atrial fibrillation. Neurology. 2013;80(11):1009-1017. [CrossRef] [PubMed]
 
Tu HT, Campbell BC, Meretoja A, et al. Pre-stroke CHADS2 and CHA2DS2-VASc scores are useful in stratifying three-month outcomes in patients with and without atrial fibrillation. Cerebrovasc Dis. 2013;36(4):273-280. [CrossRef] [PubMed]
 
Dieleman JM, van Paassen J, van Dijk D, et al. Prophylactic corticosteroids for cardiopulmonary bypass in adults. Cochrane Database Syst Rev. 2011;;(5):CD005566.
 

Figures

Tables

References

Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001;29(7):1303-1310. [CrossRef] [PubMed]
 
Meierhenrich R, Steinhilber E, Eggermann C, et al. Incidence and prognostic impact of new-onset atrial fibrillation in patients with septic shock: a prospective observational study. Crit Care. 2010;14(3):R108. [CrossRef] [PubMed]
 
Walkey AJ, Hammill BG, Curtis LH, Benjamin EJ. Long-term outcomes following development of new-onset atrial fibrillation during sepsis. Chest. 2014;146(5):1187-1195.
 
Lowres N, Neubeck L, Redfern J, Freedman SB. Screening to identify unknown atrial fibrillation. A systematic review. Thromb Haemost. 2013;110(2):213-222. [CrossRef] [PubMed]
 
Cotter PE, Martin PJ, Ring L, Warburton EA, Belham M, Pugh PJ. Incidence of atrial fibrillation detected by implantable loop recorders in unexplained stroke. Neurology. 2013;80(17):1546-1550. [CrossRef] [PubMed]
 
Franks Z, Campbell RA, Vieira de Abreu A, et al. Methicillin-resistantStaphylococcus aureus-induced thrombo-inflammatory response is reduced with timely antibiotic administration. Thromb Haemost. 2013;109(4):684-695. [CrossRef] [PubMed]
 
De Caterina R, Husted S, Wallentin L, et al. Vitamin K antagonists in heart disease: current status and perspectives (Section III). Position paper of the ESC Working Group on Thrombosis—Task Force on Anticoagulants in Heart Disease. Thromb Haemost. 2013;110(6):1087-1107. [CrossRef] [PubMed]
 
Pisters R, Nieuwlaat R, Lane DA, Crijns HJ, Lip GY. Potential net clinical benefit of population-wide implementation of apixaban and dabigatran among European patients with atrial fibrillation. A modelling analysis from the Euro Heart Survey. Thromb Haemost. 2013;109(2):328-336. [CrossRef] [PubMed]
 
Ntaios G, Lip GY, Makaritsis K, et al. CHADS2, CHA2S2DS2-VASc, and long-term stroke outcome in patients without atrial fibrillation. Neurology. 2013;80(11):1009-1017. [CrossRef] [PubMed]
 
Tu HT, Campbell BC, Meretoja A, et al. Pre-stroke CHADS2 and CHA2DS2-VASc scores are useful in stratifying three-month outcomes in patients with and without atrial fibrillation. Cerebrovasc Dis. 2013;36(4):273-280. [CrossRef] [PubMed]
 
Dieleman JM, van Paassen J, van Dijk D, et al. Prophylactic corticosteroids for cardiopulmonary bypass in adults. Cochrane Database Syst Rev. 2011;;(5):CD005566.
 
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