Cardiol Res

Cardiology Research, ISSN 1923-2829 print, 1923-2837 online, Open Access

Article copyright, the authors; Journal compilation copyright, Cardiol Res and Elmer Press Inc

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Review

Volume 16, Number 1, February 2025, pages 1-14

Beyond the Beat: A Multifaceted Review of Atrial Fibrillation in Sepsis: Risk Factors, Management Strategies, and Economic Impact

**Table 1.** Study Characteristics, Risk Factors, and Outcomes for NOAF in Critical Illness
Author, year of study	Study design	Number of patients	NOAF, n (%)	Risk factor for NOAF	Outcomes
NOAF: new-onset atrial fibrillation; AF: atrial fibrillation; HTN: hypertension; CHF: congestive heart failure; CAD: coronary artery disease; MI: myocardial infarction; DM: diabetes mellitus; SAPS: simplified acute physiology score; PAD: peripheral artery disease; HLD: hyperlipidemia; MODS: multiple organ dysfunction score; CKD: chronic kidney disease; SIRS: systemic inflammatory response syndrome; LVEF: left ventricle ejection fraction; APACHE: acute physiology and chronic health evaluation; MAP: mean arterial pressure; SOFA: sequential organ failure assessment; ICU: intensive care unit; SR: sinus rhythm; RR: relative risk; OR: odds ratio; HR: hazard ratio; HLD: hyperlipidemia; PAD: peripheral arterial disease; MICU: medical intensive care unit; BP: blood pressure.
Liu et al, 2024 [13]	Retrospective	1,425,055 patients with sepsis	21,327 (1.49% (95% CI: 1.47 - 1.51))	Older age, male sex, HTN, CHF, CAD, valvular disease, mechanical ventilation, renal replacement therapy, pericarditis, myocarditis, MI, ischemic stroke, septic shock, cerebrovascular disease	In-hospital mortality: adjusted RR = 1.03 (95% CI: 1.01 - 1.06)
Paula et al, 2024 [14]	Retrospective	1,357 noncardiac ICU patients	73 (5.38)	Older age, HTN, DM, renal failure, CHF, SAPS II	Hospital mortality of chronic vs. NOAF: 31% vs. 28.8%, P = 0.779; hospital mortality AF vs. non-AF: 30.2% vs. 22.9%, P = 0.024
Wetterslev et al, 2023 [27]	Prospective	1,415 ICU patients	13.3% (11.5 - 15.1)	HTN, paroxysmal AF, sepsis, or high disease severity at ICU admission	Adjusted cause-specific HR for 90-day mortality by AF was 1.38 (95% CI: 0.95 - 1.99)
Savaie et al, 2023 [29]	Retrospective	340 noncardiac ICU patients	44 (12.9)	Pneumonia, thyroid disease	The mortality rate of patients with NOAF was 21%. OR of the presence of NOAF and mortality (P < 0.05; OR: 2.378, CI: 1.104 - 5.16)
Wang et al, 2023 [15]	Retrospective	21,538 sepsis patients	78 (0.53), 6,759 total AF patients (31.4)	Older age, MI, CHF, HTN, HLD, PAD, cerebrovascular disease, dementia, chronic pulmonary disease, renal disease, diabetes	28-day mortality (HR: 1.07, 95% CI: 0.99 - 1.15)
Fernando et al, 2020 [16]	Retrospective	15,014 ICU patients, 1,944 sepsis patients	1,541 (10.3), 208 sepsis patients (10.7)	Older age, higher MODS, higher comorbidities burden (CHF, PAD, HTN, COPD, DM, CKD, liver disease, malignancy, psychosis, depression)	In-hospital mortality for sepsis patients: adjusted OR = 1.28 (95% CI: 1.09 - 1.36))
Steinberg et al, 2019 [28]	Prospective	27 septic shock patients	9 (33.3)	High SOFA score	Overall mortality AF vs. SR: 66.7% vs. 11.1%, P = 0.024
Desai et al, 2019 [17]	Retrospective	5,808,166 sepsis patients	1,126,433 (19.4)	Older age, White race, male sex, cardiovascular disease, pulmonary disease, diabetes, hypothyroidism, cerebrovascular disease, renal failure, fluid and electrolyte disorders	All-cause mortality rate for AF vs. non-AF with sepsis: 18.4% and 11.9%, P = 0.001
Makrygiannis et al, 2018 [18]	Prospective	133 noncardiac ICU patients	20 (15)	Age > 65, arterial HTN, SIRS, sepsis, left atrial dilatation, diastolic dysfunction	NOAF is not an independent predictor of ICU mortality. Sepsis and age > 65 years were statistically significant an independent predictor of ICU mortality.
Launey et al, 2019 [30]	Prospective	261 patients with septic shock	57 (22)	Lower risk with low dose hydrocortisone	ICU mortality in hydrocortisone group vs. non-hydrocortisone group: 37% vs. 24% (P = 0.018). 28-day mortality in hydrocortisone group vs. non-hydrocortisone group: 38% vs. 26% (P = 0.036)
Moss et al, 2017 [19]	Retrospective	8,356 ICU patients	749 (8.96)	Older age, acute respiratory failure, sepsis	Hospital mortality: OR = 1.63, 95% CI: 1.01 - 2.63
Liu et al, 2016 [31]	Retrospective	503 sepsis patients	240 (47.7)	Older age, LVEF < 45%, HTN, CHF, CAD, cerebrovascular disease	Failure of restored SR was independently associated with increased in-hospital mortality in patients with sepsis and NOAF.
Guenancia et al, 2015 [20]	Prospective	66 patients with septic shock	29 (43.9)	Older age, LVEF < 45%	ICU mortality rate in septic shock patients with and without new-onset AF was 24% vs. 19%, P = 0.61. Mortality did not differ between these two groups at 28 days (22% vs. 28%, NOAF vs. SR respectively, P = 0.58) and at 90 days (41% vs. 43% respectively, P = 0.88).
Shaver et al, 2015 [10]	Prospective	1,770 ICU patients	123 (7), 13% of sepsis patients, 10% of patients without sepsis	Older age, shock, hypotension, advanced organ failure, positive fluid balance, antecedent vasopressor use, increased left atrial dimension, more diastolic dysfunction, mitral regurgitation	OR for death in sepsis patients with any AF: 1.29 (0.85 - 1.94), P = 0.228
Wells et al, 2011 [21]	Retrospective	465 MICU patients with sepsis/septic shock	132	Older age, CAD, White race	Sepsis + NOAF is 5.7 times more likely to die compared to the Neither group.
Chen et al, 2015 [22]	Retrospective	741 MICU patients	53 (7.15)	Older age, APACHE II score, systolic BP, MAP, heart rate	In-hospital mortality: adjusted OR = 2.21, 95% CI: 1.07 - 4.54, P = 0.032
Walkey et al, 2014 [23]	Retrospective	138,722 sepsis patients	9,540 (6.9)	Older age, male sex, White race, comorbid conditions (chronic lung disease, heart failure, ischemic heart disease, valvular heart disease), acute organ failure	Greater 5-year risks of hospitalization for heart failure compared NOAF vs. control group (11.2% vs 8.2%). Multivariable-adjusted HR: 1.25, 95% CI: 1.16 - 1.34. Ischemic stroke (5.3% vs. 4.7%; HR: 1.22, 95% CI: 1.10 - 1.36). Death (74.8% vs. 72.1%; HR: 1.04, 95% CI: 1.01 - 1.07).
Walkey et al, 2013 [24]	Retrospective	60,209 sepsis patients	4,320 (7.2)	Older age, White race, acute organ dysfunction, ICU admission, mechanical ventilation, right heart catheterization, diagnosis of endocarditis, and coronary artery bypass graft surgery.
Walkey et al, 2011 [25]	Retrospective	49,082 sepsis patients	2,896 (5.9)	Older age, obesity, CHF, metastatic/hematologic malignancy, prior stroke, organ dysfunction, respiratory, abdominal, skin or soft tissue infection, bacteremia	In-hospital mortality: RR = 1.13 (95% CI: 1.08 - 1.19)
Meierhenrich et al, 2010 [26]	Prospective	629 noncardiac ICU patients → 64 septic shock patients	49 in ICU patients → 23 in septic shock patients	Older age, arterial HTN, higher SOFA	ICU mortality in septic shock patients with new-onset AF was 10/23 (44%) compared with patient that had SR: 6/27 (22%) (P = 0.14). The median length of ICU stay among surviving patients was longer in patients with new-onset AF compared to those with maintained SR (30 vs. 17 days, P = 0.017). Failure to restore SR was associated with increased ICU mortality (71.4% vs. 21.4%, P = 0.015).

Table 1. Study Characteristics, Risk Factors, and Outcomes for NOAF in Critical Illness

Author, year of study

Study design

Number of patients

NOAF, n (%)

Risk factor for NOAF

Outcomes

NOAF: new-onset atrial fibrillation; AF: atrial fibrillation; HTN: hypertension; CHF: congestive heart failure; CAD: coronary artery disease; MI: myocardial infarction; DM: diabetes mellitus; SAPS: simplified acute physiology score; PAD: peripheral artery disease; HLD: hyperlipidemia; MODS: multiple organ dysfunction score; CKD: chronic kidney disease; SIRS: systemic inflammatory response syndrome; LVEF: left ventricle ejection fraction; APACHE: acute physiology and chronic health evaluation; MAP: mean arterial pressure; SOFA: sequential organ failure assessment; ICU: intensive care unit; SR: sinus rhythm; RR: relative risk; OR: odds ratio; HR: hazard ratio; HLD: hyperlipidemia; PAD: peripheral arterial disease; MICU: medical intensive care unit; BP: blood pressure.

Liu et al, 2024 [13]

Retrospective

1,425,055 patients with sepsis

21,327 (1.49% (95% CI: 1.47 - 1.51))

Older age, male sex, HTN, CHF, CAD, valvular disease, mechanical ventilation, renal replacement therapy, pericarditis, myocarditis, MI, ischemic stroke, septic shock, cerebrovascular disease

In-hospital mortality: adjusted RR = 1.03 (95% CI: 1.01 - 1.06)

Paula et al, 2024 [14]

Retrospective

1,357 noncardiac ICU patients

73 (5.38)

Older age, HTN, DM, renal failure, CHF, SAPS II

Hospital mortality of chronic vs. NOAF: 31% vs. 28.8%, P = 0.779; hospital mortality AF vs. non-AF: 30.2% vs. 22.9%, P = 0.024

Wetterslev et al, 2023 [27]

Prospective

1,415 ICU patients

13.3% (11.5 - 15.1)

HTN, paroxysmal AF, sepsis, or high disease severity at ICU admission

Adjusted cause-specific HR for 90-day mortality by AF was 1.38 (95% CI: 0.95 - 1.99)

Savaie et al, 2023 [29]

Retrospective

340 noncardiac ICU patients

44 (12.9)

Pneumonia, thyroid disease

The mortality rate of patients with NOAF was 21%. OR of the presence of NOAF and mortality (P < 0.05; OR: 2.378, CI: 1.104 - 5.16)

Wang et al, 2023 [15]

Retrospective

21,538 sepsis patients

78 (0.53), 6,759 total AF patients (31.4)

Older age, MI, CHF, HTN, HLD, PAD, cerebrovascular disease, dementia, chronic pulmonary disease, renal disease, diabetes

28-day mortality (HR: 1.07, 95% CI: 0.99 - 1.15)

Fernando et al, 2020 [16]

Retrospective

15,014 ICU patients, 1,944 sepsis patients

1,541 (10.3), 208 sepsis patients (10.7)

Older age, higher MODS, higher comorbidities burden (CHF, PAD, HTN, COPD, DM, CKD, liver disease, malignancy, psychosis, depression)

In-hospital mortality for sepsis patients: adjusted OR = 1.28 (95% CI: 1.09 - 1.36))

Steinberg et al, 2019 [28]

Prospective

27 septic shock patients

9 (33.3)

High SOFA score

Overall mortality AF vs. SR: 66.7% vs. 11.1%, P = 0.024

Desai et al, 2019 [17]

Retrospective

5,808,166 sepsis patients

1,126,433 (19.4)

Older age, White race, male sex, cardiovascular disease, pulmonary disease, diabetes, hypothyroidism, cerebrovascular disease, renal failure, fluid and electrolyte disorders

All-cause mortality rate for AF vs. non-AF with sepsis: 18.4% and 11.9%, P = 0.001

Makrygiannis et al, 2018 [18]

Prospective

133 noncardiac ICU patients

20 (15)

Age > 65, arterial HTN, SIRS, sepsis, left atrial dilatation, diastolic dysfunction

NOAF is not an independent predictor of ICU mortality. Sepsis and age > 65 years were statistically significant an independent predictor of ICU mortality.

Launey et al, 2019 [30]

Prospective

261 patients with septic shock

57 (22)

Lower risk with low dose hydrocortisone

ICU mortality in hydrocortisone group vs. non-hydrocortisone group: 37% vs. 24% (P = 0.018). 28-day mortality in hydrocortisone group vs. non-hydrocortisone group: 38% vs. 26% (P = 0.036)

Moss et al, 2017 [19]

Retrospective

8,356 ICU patients

749 (8.96)

Older age, acute respiratory failure, sepsis

Hospital mortality: OR = 1.63, 95% CI: 1.01 - 2.63

Liu et al, 2016 [31]

Retrospective

503 sepsis patients

240 (47.7)

Older age, LVEF < 45%, HTN, CHF, CAD, cerebrovascular disease

Failure of restored SR was independently associated with increased in-hospital mortality in patients with sepsis and NOAF.

Guenancia et al, 2015 [20]

Prospective

66 patients with septic shock

29 (43.9)

Older age, LVEF < 45%

ICU mortality rate in septic shock patients with and without new-onset AF was 24% vs. 19%, P = 0.61. Mortality did not differ between these two groups at 28 days (22% vs. 28%, NOAF vs. SR respectively, P = 0.58) and at 90 days (41% vs. 43% respectively, P = 0.88).

Shaver et al, 2015 [10]

Prospective

1,770 ICU patients

123 (7), 13% of sepsis patients, 10% of patients without sepsis

Older age, shock, hypotension, advanced organ failure, positive fluid balance, antecedent vasopressor use, increased left atrial dimension, more diastolic dysfunction, mitral regurgitation

OR for death in sepsis patients with any AF: 1.29 (0.85 - 1.94), P = 0.228

Wells et al, 2011 [21]

Retrospective

465 MICU patients with sepsis/septic shock

132

Older age, CAD, White race

Sepsis + NOAF is 5.7 times more likely to die compared to the Neither group.

Chen et al, 2015 [22]

Retrospective

741 MICU patients

53 (7.15)

Older age, APACHE II score, systolic BP, MAP, heart rate

In-hospital mortality: adjusted OR = 2.21, 95% CI: 1.07 - 4.54, P = 0.032

Walkey et al, 2014 [23]

Retrospective

138,722 sepsis patients

9,540 (6.9)

Older age, male sex, White race, comorbid conditions (chronic lung disease, heart failure, ischemic heart disease, valvular heart disease), acute organ failure

Greater 5-year risks of hospitalization for heart failure compared NOAF vs. control group (11.2% vs 8.2%). Multivariable-adjusted HR: 1.25, 95% CI: 1.16 - 1.34. Ischemic stroke (5.3% vs. 4.7%; HR: 1.22, 95% CI: 1.10 - 1.36). Death (74.8% vs. 72.1%; HR: 1.04, 95% CI: 1.01 - 1.07).

Walkey et al, 2013 [24]

Retrospective

60,209 sepsis patients

4,320 (7.2)

Older age, White race, acute organ dysfunction, ICU admission, mechanical ventilation, right heart catheterization, diagnosis of endocarditis, and coronary artery bypass graft surgery.

Walkey et al, 2011 [25]

Retrospective

49,082 sepsis patients

2,896 (5.9)

Older age, obesity, CHF, metastatic/hematologic malignancy, prior stroke, organ dysfunction, respiratory, abdominal, skin or soft tissue infection, bacteremia

In-hospital mortality: RR = 1.13 (95% CI: 1.08 - 1.19)

Meierhenrich et al, 2010 [26]

Prospective

629 noncardiac ICU patients → 64 septic shock patients

49 in ICU patients → 23 in septic shock patients

Older age, arterial HTN, higher SOFA

ICU mortality in septic shock patients with new-onset AF was 10/23 (44%) compared with patient that had SR: 6/27 (22%) (P = 0.14). The median length of ICU stay among surviving patients was longer in patients with new-onset AF compared to those with maintained SR (30 vs. 17 days, P = 0.017). Failure to restore SR was associated with increased ICU mortality (71.4% vs. 21.4%, P = 0.015).